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Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule activator

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the Canton mutant and several other common G6PD mutants. AG1 reduces oxidative stress in cells and zebrafish. Furthermore, AG1 decreases chloroquine- or diamide-induced oxidative stress in human erythrocytes. Our study suggests that a pharmacological agent, of which AG1 may be a lead, will likely alleviate the challenges associated with G6PD deficiency.

Introduction

Reduced glutathione (GSH) provides the cellular first line of defense against oxidative stress-induced injury, which can be maintained by NADPH generated mainly via the pentose phosphate pathway and its rate-limiting enzyme, glucose-6-phosphate dehydrogenase (G6PD; Fig. 1a). Accordingly, missense DNA mutations that impair G6PD activity or stability result in increased oxidative stress and a spectrum of disease phenotypes featuring, most commonly, hemolytic anemia, and collectively called G6PD deficiency1. In particular, G6PD is essential in preserving the integrity of erythrocytes because, lacking mitochondria, they have no other NADPH-generating enzymes to protect against oxidative stress2.

Canton G6PD (R459L) variant is biochemically different from WT G6PD. a Enzymatic scheme of G6PD activity. b A linear map of G6PD domain structure with most common variants indicated. c Catalytic activity of recombinant WT G6PD and Canton G6PD enzymes with kinetic parameters (n = 5, ****p < 0.0001). d Thermostability of WT G6PD and Canton G6PD enzyme (n = 3, **p = 0.003). e G6PD protein levels and residual G6PD activity (normalized to NT (no treatment) of each enzyme) after incubation with chymotrypsin for 1 h (n = 3 for protein level assay, **p = 0.0046; n = 2 for enzyme assay, *p = 0.024). f Protein stability assessment with cycloheximide treatment (50 μg mL−1), blocking de novo protein biosynthesis, in lymphocytes derived from corresponding subjects (n = 3, *p = 0.013). Protein levels were normalized to the level of each enzyme at 0 h (no treatment). g G6PD activity was lower in cell lysates with Canton variant (n = 4, ****p < 0.0001). h, i, j Lymphocytes with Canton variant generated less GSH and more reactive oxygen species (ROS) and were less viable (n = 4, (n = 3 for Fig. 1i), *p < 0.05, **p < 0.01). Error bars represent mean ± SEM. Statistical differences were calculated by two-tailed unpaired Student’s t-test. NT: no treatment, WT: wild-type, Chy: chymotrypsin

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G6PD deficiency represents one of the most common inherited and sex-linked enzymopathies. The G6PD gene maps to the X-chromosome; thus, the phenotype is manifest fully in males whereas female heterozygotes display varying degrees of G6PD deficiency, due to alternate X-chromosome inactivation3,4. G6PD deficiency afflicts more than an estimated 400 million individuals worldwide, many of whom live in malaria endemic regions. Impaired anti-oxidant defense in G6PD-deficient erythrocytes makes them vulnerable to early membrane damage and ultimately phagocytosis when infected with malaria5. This mechanism that results in limiting the propagation of the parasite in the bloodstream explains how G6PD deficiency provides resistance against malaria4,5,6.

Symptoms of G6PD deficiency are triggered by exposure to certain foods, medications, infection and/or environmental factors2,4. For example, consumption of fava beans causes oxidative stress to erythrocytes possibly by two main toxins, vicine or convicine, thus triggering acute hemolytic episode (favism) in affected subjects7. G6PD-deficient individuals are also at a high risk of severe hemolysis when given anti-malarial drugs, such as quinine, primaquine or chloroquine, through irreversible oxidative activity of their metabolites on erythrocytes8,9. G6PD deficiency can be life-threatening, especially in newborns, leading to bilirubin-induced neurological injury and bilirubin encephalopathy (kernicterus) and even to death10,11,12,13,14,15. In a recent study, a systematic analysis of 2253 articles discussing G6PD revealed that dysregulation of G6PD is also associated with autoimmune diseases and metabolic disorders, indicating that clinical risks associated with G6PD deficiency are likely underestimated16. As there are currently no means to correct G6PD deficiency, there is no treatment for the disease; management mainly consists of supportive care and discontinuation of triggers. The use of anti-oxidants such as vitamin E or selenium has proven to be ineffective in treating G6PD deficiency17,18,19.

On the other hand, based on studies performed in Sardinia, G6PD deficiency has some beneficial effect on longevity20. In studies using dehydroepiandrosterone (DHEA), an inhibitor of G6PD (that is also an adrenal steroid), loss of G6PD function has been suggested to prevent cancer progression20,21. Despite all the beneficial effects, the detrimental effect of G6PD deficiency are still clear in hemolytic anemia and kernicterus of infancy. Given the risk of hemolytic crisis and related sequelae from various triggers in affected subjects in both malaria endemic and non-endemic regions, we believe that developing a pharmacological agent that corrects G6PD deficiency may benefit affected individuals.

G6PD is functionally active as a dimer or a tetramer22. Each monomer has a catalytic nicotinamide adenine dinucleotide phosphate (NADP+)-binding domain and β+α domain, containing an additional binding site for NADP+ that structurally stabilizes the enzyme (Fig. 1b)23,24. The glucose 6-phosphate (G6P)-binding site is located between these two domains (Fig. 1b). Using different informatics tools, we recently demonstrated that the majority of the variants that cause severe (<10% of normal G6PD activity, class I and class II) or mild (10–60% of normal G6PD activity, class III) deficiency are primarily located in those functional regions of the enzyme, disturbing the enzyme’s activity and stability25.

Here we present a comprehensive report describing the molecular basis for G6PD deficiency with Canton variant (R459L) and our efforts to restore its decreased function using a small molecule, AG1. Our study provides the first step in identifying a potential therapeutic approach to correct G6PD deficiency.

Results

Canton G6PD variant has reduced activity and stability

We first began our efforts focusing on the Canton variant, with the mutation R459L, located in the β+α domain (Fig. 1b). Canton G6PD is prevalent in China and Southeast Asia (50–60% of the variants26,27), causing severe deficiency (class II). Recombinant Canton G6PD enzyme showed only 18% of normal G6PD activity with lower KM for both NADP+ and G6P (Fig. 1c), which is consistent with the biochemical characteristics analyzed using blood samples derived from subjects carrying the Canton variant28. Relative to the wild-type (WT) enzyme, Canton G6PD also displayed impaired ability to form tetramers in the presence of increased concentrations of the cofactors that facilitate tetramer formation, NADP+ or MgCl229,30, when cross-linked by glutaraldehyde (Supplementary Fig. 1a). This reduced oligomerization state of the Canton G6PD may contribute to its reduced enzymatic activity. Furthermore, the Canton variant was less thermostable; its T1/2, the temperature at which the enzyme retains half of its catalytic activity, was 42.6 °C, which is 4.6 °C lower than T1/2 of WT enzyme (Fig. 1d). Canton G6PD was more susceptible to degradation by chymotrypsin relative to the WT enzyme, which corresponded with a significantly decreased enzymatic activity (Fig. 1e). This suggests that Canton G6PD may undergo higher conformational fluctuation, leading to a greater accessibility to proteases and its reduced thermostability31.

We also show that the Canton variant was less stable than WT G6PD in lymphocytes derived from a male subject carrier with a Canton mutation in G6PD; 24 h after cycloheximide treatment (50 μg mL−1) to inhibit de novo protein biosynthesis, the level of the Canton variant protein was ~33% lower than the WT enzyme (Fig. 1f and Supplementary Fig. 1b). G6PD activity in lysates of lymphocytes of the Canton variant carrier was ~90% lower than G6PD activity in normal lymphocytes (Fig. 1g), which coincided with low levels of total GSH and increased levels of reactive oxygen species (ROS) (Fig. 1h, i). Moreover, the viability of the lymphocytes of the Canton variant carrier was ~50% lower relative to normal lymphocytes when cultured under the stress condition induced by serum starvation (Fig. 1j).

The same results were observed in SH-SY5Y neuronal cells transiently expressing WT G6PD or the Canton variant (His-tagged); Canton G6PD protein levels dropped by 50% within 24 h of cycloheximide treatment, as compared to 20% decrease of WT G6PD (Supplementary Fig. 1c). SH-SY5Y cells expressing the Canton variant also showed lower G6PD enzymatic activity in the lysates, and a lower level of GSH, a higher level of ROS, and lower cell viability in culture (Supplementary Fig. 1d, e, f, g) and knockdown of G6PD by siRNA reduced cell viability, recapitulating the phenotype of G6PD deficiency (Supplementary Fig. 1h).

Canton mutation loses essential inter-helical interactions

To elucidate the molecular basis of the reduced stability and activity of Canton G6PD, we examined the crystal structures of WT and Canton G6PD at 1.9 Å and 2.6 Å resolution, respectively (Table 1). Although no NADP+ was added to protein solution prior to the crystallization, both crystal structures contained NADP+ at the second NADP+-binding site (structural NADP+-binding site) in the β+α domain (Supplementary Fig. 2a). (The stability of the enzyme with NADP+ association at this site has been previously reported and NADP+ can be removed by incubating the enzyme with G6P24,30.) The overall conformations of WT and Canton G6PD were very similar, as indicated by a root-mean-square deviation of 0.6 Å for the superimposition of Cα atoms (Fig. 2a). However, we noticed a loose helical interaction between the helix (αn), containing the Canton variant-R459L, and an adjacent helix (αe) (Fig. 2b, left panel), which was not described in previously reported structures24. In WT G6PD, R459 forms electrostatic and hydrogen bond interactions with D181 and N185 on the adjacent helix (αe), whereas Canton mutation does not, resulting in loosened inter-helical interactions and displacements of the helix (αe) and a proceeding loop consisting of K171, P172, F173, G174, and R175, several amino acids away from R459-interacting residues on the helix (αe) (Fig. 2b, right panel). In particular, K171 and P172 are the key residues involved in positioning of G6P and NADP+ in their binding pockets23,24. Thus, the loose inter-helical interaction in the Canton variant is likely to be a major driving force for positioning the loop and thus changing the orientations of these residues. In 7 out of 8 molecules in the asymmetric unit of the Canton variant structure, P172 was observed in the trans conformation, consistent with previous data23,24 and accordingly, the side chain of K171 was oriented away from catalytic NADP+ and G6P binding pockets (Fig. 2b, right panel, and Supplementary Fig. 2b, c). K171A and P172G mutations in WT G6PD completely abolished the enzyme’s catalytic activity, indicating the importance of these residues in catalysis (Supplementary Fig. 2d).

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Canton mutation (R459L) loses essential inter–helical interactions. a Structural overlay of WT G6PD (green) and Canton variant (orange). Structural NADP+ is shown as spheres, and arrows and circles indicate G6P and catalytic NADP+-binding sites (G6P and catalytic NADP+ were not observed in our structures). b (Left) Inter-helical interactions through R459 on the αn helix in WT G6PD and side chains of D181 and N185 on the adjacent helix (αe). (Right) Canton mutation loses such interactions, leading to displacements of the helix (αe) and a loop containing K171, P172, F173, G174 and R175 that precedes the helix. c, d Mutations of R459-interacting residues on the αe helix showed Canton mutation-like activity and thermostability (n = 3, ****p < 0.0001, one-way ANOVA) and were also susceptible to chymotrypsin treatment (n = 4 for D181A, ****p < 0.0001; n = 3 for N185A, *p = 0.026, two-tailed unpaired Student’s t-test). Error bars represent mean ± SEM. NT no treatment; WT: wild-type; Chy: chymotrypsin

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We further mutated the R459-interacting residues, D181 and N185, to alanine in WT G6PD to determine the importance of the inter-helical interactions and found that these point-mutated enzymes are biochemically similar to the Canton variant; they exhibited about 20% of the normal activity, with lower KM values for both NADP+ and G6P and lower T1/2 values (Fig. 2c and Supplementary Fig. 2e). These mutants were also more susceptible to proteolytic digestion, relative to WT G6PD (compare Fig. 2d to Fig. 1e). Taken together, these data support the importance of the inter-helical interaction between R459 and D181 and N185 for catalytic activity and stability of the enzyme and provides a structural insight into the biochemical defects of the Canton variant. Indeed, other human mutations located around this helical interaction site, such as P172S (<10% enzyme activity), F173L (<10% enzyme activity), and D181V (10–60% enzyme activity), cause moderate to severe G6PD deficiency32,33,34, likely because they are predicted to undergo similar conformational changes based on our observation.

AG1 activates and stabilizes G6PD mutants

Our biochemical and structural studies led us to determine whether improving the activity of G6PD variants with a pharmacological agent can provide a new therapeutic approach to reduce the risk of pathologies implicated in patients with G6PD deficiency. To this end, we screened for agonists of G6PD (AGs) using the recombinant Canton G6PD enzyme by a high-throughput screen (HTS) and identified one agonist, 2,2’-disulfanediylbis(N-(2-(1H-indol-3-yl)ethyl)ethan-1-amine) (AG1, Mr = 438.1912) (Supplementary Fig. 3a). We confirmed that the active species in the HTS sample is a product resulting from thiol oxidation under ambient conditions35, which was validated by mass spectrometry and nuclear magnetic resonance spectroscopy (Supplementary Fig. 3a and Supplementary Note 1). AG1 increases the activity of Canton G6PD up to 1.7-fold with EC50≈3 μM and WT G6PD by about 20% over basal activity (Fig. 3a, b and Supplementary Fig. 3b). Although AG1 was a mild activator, it changed the kinetic parameters of Canton G6PD, indicating that AG1 may facilitate improved binding of NADP+ and/or G6P to the enzyme (Fig. 3c). We found that AG1 also promoted formation of dimers, as determined by partial native gel electrophoresis (Fig. 3d). The small increase observed in molecular weight of the monomeric G6PD might be due to either some modification of the enzyme by AG1 or an equilibrium shift toward dimeric states. When the recombinant Canton G6PD enzyme was incubated with G6P to remove the structural NADP+, the dimeric G6PD was destabilized, dissociating into a monomer (Fig. 3e). In the presence of AG1, however, the equilibrium shifted toward a dimer (Fig. 3e), further indicating that AG1 stabilizes a dimeric form of the enzyme. AG1 had no effect on the dimerization or activity of several other NAD- or NADP+-dependent dimeric or tetrameric enzymes, including 6-phosphogluconate dehydrogenase (6PGD), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), aldehyde dehydrogenase 2 (ALDH2), and aldehyde dehydrogenase 3A1 (ALDH3A1) (Supplementary Fig. 3c). Whereas 1 μM of AG1 increased the viability of SH-SY5Y cells by 20%, it had no effect when G6PD was knocked down by siRNA, supporting the specificity of AG1 toward G6PD (Supplementary Fig. 3d). Note also that the decrease in viability by the knockdown of G6PD implies the critical role of G6PD for cell survival. AG1 also reduced the susceptibility of Canton G6PD to proteolysis (Fig. 3f) and mildly improved its stability in lymphocytes (Fig. 3g and Supplementary Fig. 3e). The enzymatic activity in lymphocyte lysates with the Canton variant (~10% of normal activity) was enhanced by 78% in the presence of AG1 (Fig. 3h). The levels of GSH were slightly higher after treatment with AG1 for 24 h, which coincided with decreased ROS levels and improved cell viability (Fig. 3i–k) in the lymphocytes cultured under the serum starvation stress. AG1 treatment also increased the proteolytic stability of Canton G6PD in SH-SY5Y cells (Supplementary Fig. 3f). There was also a mild increase in G6PD activity, GSH levels, and viability of these cells together with a decrease in ROS levels (Supplementary Fig. 3g, h, i, j). Finally, as predicted, the activity of Canton variant-mimicking mutations that we generated (Fig. 2c, d), D181A and N185A, were similarly affected by AG1, as measured by increased activity and proteolytic stability (Supplementary Fig. 4a, b, c), suggesting that AG1 may correct a structural defect common to mutations that disturb that helical structure (Fig. 2b).

AG1 (activator of G6PD) induces biochemical changes in the Canton variant. a Increased activity of Canton G6PD enzyme by AG1 (n = 5, ***p = 0.0002, two-tailed unpaired Student’s t-test) and b a dose response curve of AG1. c AG1 changed kinetic parameters of Canton G6PD. d AG1 promoted dimerization of Canton G6PD (n = 3). e Size-exclusion FPLC (calibrated Superdex 75 10/300 GL column) profile of purified Canton G6PD in the presence of G6P or AG1. f AG1 reduced proteolytic susceptibility of Canton G6PD (n = 3, ***p < 0.001, *p < 0.05, one-way ANOVA). The protein levels were normalized to the non-treated (NT) enzyme level. g Cycloheximide-chase assay using lymphocytes carrying the Canton variant (n = 3). Protein levels were normalized to the level of each enzyme at time 0 h. h, i, j AG1 increased G6PD activity in cell lysates with the Canton variant (n = 4, **p = 0.0032, two-tailed unpaired Student’s t-test), mildly enhanced a GSH level (n = 7, *p = 0.0282, two-tailed unpaired Student’s t-test) and reduced a ROS level in culture (n = 6, *p = 0.0452, two-tailed unpaired Student’s t-test). k AG1 increased viability of lymphocytes carrying the Canton variant (n = 6, **p = 0.003, two-tailed unpaired Student’s t-test). l, m AG1 activated other major G6PD variants, including A (V68M, N126D; blue spheres), Mediterranean (S188F, orange spheres), and Kaiping (R463H, yellow spheres) variants, respectively (n = 4, ****p < 0.0001, **p < 0.01, *p = 0.011, one-way ANOVA), and promoted their dimerization (n = 3). Purple spheres in the structure represent the side chain of R459. n Cycloheximide-chase assay using fibroblasts carrying the Mediterranean variant (n = 4, *p = 0.0437, two-tailed unpaired Student’s t-test). o, p AG1 significantly decreased a ROS level (n = 6, ***p = 0.0001, ****p < 0.0001, one-way ANOVA) and increased a GSH level in those cultures (n = 3, *p = 0.0214, ****p < 0.0001, one-way ANOVA). 100 μM and 1 μM of AG1 were used for in vitro assays and cell-based assays, respectively. 5% DMSO (stock) was used as vehicle. For FPLC assay, 500 μM AG1, 200 μg of Canton G6PD recombinant enzyme and 10 mM G6P were used. Cells were subjected to serum starvation for 48 h. Error bars represent mean ± SEM. MW: molecular weight, FPLC: fast protein liquid chromatography, NT: no treatment, Veh: vehicle, WT: wild-type, Med: Mediterranean fibroblast

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Because G6PD exhibits cooperative folding36 and AG1 increased and/or stabilized G6PD dimer levels, we next examined the possibility that binding of AG1 to the enzyme could correct other point mutation-containing G6PD variants outside the αe-αn inter-helical interaction sites. We focused on A (V68M & N126D), Mediterranean (S188F), and Kaiping (R463H) G6PD (Fig. 1b), the three most common human variants in non-overlapping regions of the world causing mild to severe deficiency (Africa, Mediterranean and Southeast Asia, respectively). AG1 activated all these variants by up to 2-fold and increased the levels of the dimeric state (Fig. 3l, m). AG1 also stabilized G6PD in fibroblasts derived from a subject who carries Mediterranean mutation following cycloheximide treatment (Fig. 3n and Supplementary Fig. 5a). The lysate of human fibroblasts with the Mediterranean variant had only 22% activity of control human fibroblasts, but AG1 increased that activity by 50% (Supplementary Fig. 5b). Fibroblasts carrying the Mediterranean variant generated more ROS and less GSH under stress induced by serum starvation relative to fibroblasts from control subject, which was significantly blunted by AG1 treatment (Fig. 3o, p). Lower cell viability under the same condition was also improved by 22% in the presence of AG1 (Supplementary Fig. 5c). When Mediterranean G6PD expression was knocked down by siRNA, the viability was further dropped by 23%, and AG1 did not rescue it (Supplementary Fig. 5c), indicating the selective effect of AG1 for G6PD. Taken together, these data raise the possibility that by increasing (or stabilizing) the levels of dimeric G6PD and/or increasing the enzyme activity, AG1 may represent a lead compound for a drug to treat not only Canton-like mutations, but also some of the other most common G6PD deficiencies in humans.

AG1 reduces oxidative stress in zebrafish

Capitalizing on a recent report describing a morpholino-generated G6PD-deficient zebrafish model, in which exposure to pro-oxidants resulted in cardiac edema and a brisk hemolysis37, we next set out to determine the effect of AG1 in vivo. Using zebrafish embryos, we first confirmed that embryos develop normally at concentrations <10 μM of AG1 (Fig. 4a and Supplementary Fig. 6a), indicating that AG1 is not toxic to developing zebrafish embryos. We next used the anti-malarial drug, chloroquine, a common trigger for hemolytic crisis in G6PD-deficient humans4,37, to induce an oxidative challenge in the zebrafish embryos and found that chloroquine (100 μg mL−1) treatment at 24 h post fertilization (hpf) led to pericardial edema and increased ROS levels (Fig. 4a, b), which was consistent with the primaquine-induced phenotypes observed in a morpholino-based G6PD-deficient zebrafish model37. Upon chloroquine treatment, hemoglobin staining was also slightly reduced (Supplementary Fig. 6b). Under the same condition, AG1 significantly reduced ROS levels, resulting in less embryos exhibiting pericardial edema (Fig. 4a, b and Supplementary Fig. 6a; scores were determined by an observer blinded to the treatment group) and mildly increased hemoglobin staining (Supplementary Fig. 6b). Although a slight increase in G6PD activity was observed in lysates of pooled AG1-treated embryos, there was a significant increase in total NADPH levels possibly due to the increase in the product of G6PD downstream, 6-phosphogluconate, which serves as a substrate for the downstream enzyme, 6-phosphogluconate dehydrogenase (6PGD), another NADPH-producing enzyme in the pathway (Fig. 4c). As expected, the attenuation of pericardial edema was specific to G6PD deficiency, as pericardial edema due to mesoderm defects in tbx16 mutants was not corrected by AG1 treatment (Supplementary Fig. 6c, d)38,39. To further confirm the specificity of AG1 in vivo, we used CRISPR-Cas9 to generate loss-of-function F0 embryos (crispants). g6pd crispants had a lower G6PD level (Supplementary Fig. 6e), a 51% higher level of ROS, a 67% lower level of G6PD activity and a 58% lower NADPH level, and increased pericardial edema (Fig. 4d–f; scores were determined by an observer blinded to the treatment group). Treatment with 1 μM AG1 did not significantly affect these parameters in the g6pd crispants (Fig. 4d–f). Note also that there was a slight (albeit not statistically significant) increase in the number of crispant embryos exhibiting reduced hemoglobin staining (Supplementary Fig. 6f).

AG1 attenuates ROS-induced pericardial edema in a G6PD-dependent manner. a Embryos were treated at 24 hpf with 1 μM AG1 with and without chloroquine (CQ; 100 μg mL−1) and scored at 32 hpf. Representative phenotypic images of pericardial edema and pooling (magenta arrows) are provided on the left (scale bar: 300 μm). Embryo orientation is lateral view, anterior left. Raw counts used for chi-square analysis and calculated p value are included in table below. b ROS levels in individual WT embryos from three independent clutches. Embryos were treated at 24 hpf for 5 h before ROS measurement. Error bars represent mean ± SD (***p < 0.001, ns = not statistically significant, p > 0.99, Kruskal–Wallis multiple comparison test, adjusted p value using Dunn’s test). c G6PD activity and NADPH levels were measured using the lysates of pooled embryos (from two independent clutches). Error bars represent mean ± SEM (***p = 0.0003, two-tailed unpaired Student’s t-test). d Embryos were injected with either sgRNA targeting exon 10 of g6pd (Guide alone) or sgRNA + Cas9 protein (Guide + Cas9, G6PD KO (knockout)) to generate G6PD F0 crispants. Representative phenotypic images of pericardial edema and pooling (magenta arrows) are provided on the left (scale bar: 300 μm). Treatment conditions are the same as in a. Raw counts used for chi-square analysis and calculated p value are included in table below. e ROS levels in individual embryos with sgRNA or sgRNA + Cas9 (G6PD KO) protein injection. Treatment conditions and the statistics are the same as in b (*p = 0.0267, **p < 0.01, ****p < 0.0001, ns = not statistically significant). f G6PD activity and NADPH levels were measured with lysates of pooled embryos from three independent experiments. Error bars represent mean ± SEM of the replicate measurements (*p < 0.05, **p < 0.01, one-way ANOVA for G6PD activity measurement and two-tailed unpaired Student’s t-test for NADPH measurement). Veh: vehicle, KO: knockout, CQ: chloroquine

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AG1 reduces hemolysis of human erythrocytes

We next determined whether AG1 protects erythrocytes from oxidative stress. Our preliminary study using human erythrocytes from seven healthy subjects showed that AG1 (5 μM) reduces the extent of hemolysis, when erythrocyte suspension (5%) was exposed to either 1 mM chloroquine (CQ) or diamide (a GSH oxidant), suggesting anti-hemolytic potential of AG1 (Fig. 5a). In support of this, AG1 increased GSH levels and reduced ROS levels together with increased G6PD activity under these drug-induced oxidative stress (Fig. 5b–d). Oxidative stress impairs erythrocyte membrane integrity through initial oxidation of hemoglobin, leading to the precipitation of Heinz bodies and band 3 (a major erythrocyte membrane protein) clustering; thus, band 3 clustering serves as an essential molecular marker of erythrocyte removal40. Using erythrocytes isolated from 9 to 11 individual whole blood samples, we confirmed that band 3 protein is aggregated with either chloroquine (CQ) or diamide treatment, which was alleviated by AG1 treatment (Fig. 5e and Supplementary Fig. 7a). This suggests that AG1 contributes to stabilizing erythrocyte membranes. Red blood cell transfusion is commonly used clinical therapy, but structural and functional changes in erythrocytes during storage, collectively referred to as storage lesion, remain concerned in transfusion practice41. Storage under conventional conditions is considered as oxidative stress for erythrocytes, as evidenced by increase in ROS over time and accumulation of oxidative biomarkers42,43. Thus, we determined that whether AG1 can improve preservation during refrigerated storage by monitoring the degree of hemolysis over 28 days. We found that AG1 (1 μM) reduces hemolysis over time by an average of 12% at day 28 (Fig. 5f and Supplementary Fig. 7b). Accordingly, the protein leakage from the treated erythrocytes was decreased as well (Fig. 5g and Supplementary Fig. 7c), which corresponded with increased G6PD activity (Fig. 5h). These data suggest that AG1-like compounds can serve as a novel preservative for prolonged storage of erythrocytes and impact to a broader population as well as G6PD-deficient patients.

AG1 reduces hemolysis upon exposure to oxidative stressors. a AG1 reduced the extent of hemolysis of 5% erythrocyte suspension treated with either 1 mM chloroquine (CQ) for 4 h under light or 1 mM diamide for 4 h at 37 °C (n = 7 independent blood samples, *p = 0.0372, **p = 0.0019, ****p < 0.0001, one-way ANOVA). bd AG1 significantly increased GSH levels and reduced ROS levels, when 5% erythrocyte suspension was exposed to either 1 mM chloroquine or diamide for 3 h at 37 °C, which was consistent with increased G6PD activity (n = 9–11, *p < 0.05, **p < 0.01, ****p < 0.0001, one-way ANOVA). e Band 3 protein was clustered (cBand3) when 5% erythrocyte suspension was treated with chloroquine, which was alleviated by AG1 treatment. Each lane represents one individual sample, and quantification is provided in Supplementary Fig. 7a. fh AG1 (1 μM) improved storage of erythrocytes (5% suspension) at refrigerated temperature by reducing hemolysis and concomitant protein leakage for 28 days (n = 13 independent blood samples, *p < 0.05, two-tailed unpaired Student’s t-test), which corresponded with increased G6PD activity (n = 4, *p = 0.0323, ***p = 0.0003, one-way ANOVA). Each sample was re-treated with AG1 every week. Representative hemolysis phenotypic images are provided below f. Error bars represent mean ± SD. NT: no treatment, CQ: chloroquine, cBand3: clustered band 3 protein

Full size image

Discussion

In humans, in addition to the role of G6PD in preventing hemolysis (erythrocyte lysis), the anti-oxidant property of G6PD may relate to development of a variety of other pathologies, including kidney injury, heart failure, psychiatric disorder, diabetes, cholelithiasis, and cataract44,45,46,47,48,49,50,51,52, suggesting that G6PD deficiency can be an underestimated risk factor for multiple human pathologies. Because AG1 increased the impaired activity of several common G6PD variants, our study suggests that a single pharmacological agent may provide treatment for several major G6PD enzymopathies, affecting many millions of people worldwide. Such a drug may also help prevent or reduce the sequelae of G6PD deficiency and/or synergize with other palliative treatments such as illumination for kernicterus53,54. We expect many other pathologies associated with G6PD deficiency, as aforementioned, to be affected by such treatment as well. Treatment with AGs may also be beneficial to G6PD-deficienct populations in developing countries, in which the use of hemolytic crisis-triggering drugs, like anti-malarial drugs (primaquine and chloroquine), are still common. We believe that AG1-like drugs may also be useful for preservation of blood for transfusion, as evidenced in Fig. 5 and for subjects with WT G6PD with other diseases associated with increased oxidative stress.

Human studies demonstrate that clinical pathology related to G6PD deficiency, at least as reflected by hemolytic crisis, occurs in subjects who carry a variant with <60% activity relative to the subjects with WT G6PD55. Therefore, although AG1 is safe, an optimal AG should be improved, to increase the catalytic activity in G6PD-deficient subjects to at least 60% of normal. Nonetheless, based on our initial studies, AG1 should be viewed as a lead compound to correct G6PD deficiency and also to treat subjects with WT G6PD at risk of oxidative stress. Our current effort focuses on improving the biochemical and pharmacological features of AG1 through further medicinal chemistry efforts and structural studies. Finally, identifying small-molecule enzyme activators is still considered a challenging task in the field of drug discovery and development56, and even less common is the ability to identify a small molecule that corrects functional defect due to different mutations; AG1 represents a compound that does both.

Methods

Materials

Antibodies used in this study were principally purchased from Santa Cruz Biotechnology (G6PD (G-12): SC-373886 (dilution 1:1000), 6PGD (G-2): SC-398977 (dilution 1:1000), His (HIS.H8): SC-57598 (dilution 1:1000), Enolase (H-300): SC-15343 (dilution 1:1000)), Cell Signaling Technology (beta actin (8H10D10): 3700 S (dilution 1:1000)), Everest Biotech (G6PD: EB07841 (dilution 1:1000)), Advance Immunochemical (GAPDH (6C5): 6C5 (dilution 1:2000)), and Abcam (G6PD: AB87230 (dilution 1:1000), band 3 (EPR1426): AB108414 (dilution 1:1000)). TALON Superflow (28-9575-02) and bovine thrombin (91-030) were purchased from GE Healthcare and BioPharma for protein purification. Pfu Turbo polymerase (600252) used for site-directed mutagenesis was purchased from Agilent Technologies. Chymotrypsin was purchased from Promega (V1061). Cell counting kit-8 (CK04) and glutathione quantification kit (T419) were purchased from Dojindo. Cycloheximide (C7698) and chloromethyl-2’,7’-dichlorodihydrofluorescein diacetate (CM-H2DCFDA, C6827) were purchased from Sigma and Thermo Fisher Scientific, respectively. Glutathione assay kit (703002) used for blood assays was purchased from Cayman Chemical.

Cell culture

Lymphocytes derived from a normal subject (HG 00866) and a G6PD-deficient subject carrying the Canton variant (HG 02367) were purchased from Coriell Institute and cultured in RPMI 1640 supplemented with 15% fetal bovine serum (FBS), 100 U mL−1 penicillin, and 100 μg mL−1 streptomycin. An SH-SY5Y neuroblastoma cell line (ATCC CRL-2266) was cultured in Dulbecco’s Modification of Eagle’s Medium/Ham’s F-12 50/50 Mix supplemented with 10% FBS, 100 U mL−1 penicillin, and 100 μg mL−1 streptomycin. A fibroblast cell line derived from a G6PD-deficient subject carrying the Mediterranean variant and normal fibroblast cell line as control were purchased from Coriell Institute (GM 01152) and Thermo Fisher Scientific (C0135C), respectively, and cultured in minimum essential medium supplemented with 15% FBS, 100 U mL−1 penicillin, and 100 μg mL−1 streptomycin. All the cell lines were maintained at 37 °C in a humidified incubator with an atmosphere of 5% of CO2 and 95% air.

Plasmid construction and site-directed mutagenesis

The gene encoding WT G6PD was inserted into the pET-28a vector, using NdeI and SalI restriction enzyme sites. Site-directed mutagenesis was performed to generate G6PD variants using appropriate primer sets (Supplementary Table 1) according to the manufacturer’s guidelines (Agilent-Quikchange site-directed mutagenesis). Briefly, the PCR reaction of 50 μL contained 10–50 ng of template, 125 ng of primers, 200 μM dNTPs, and 2.5 units of Pfu Turbo DNA polymerase. The reaction was initiated at 95 °C for 30 s to denature the template DNA, followed by 18 amplification cycles (95 °C for 30 s, 55 °C for 1 min and 68 °C for 7 min). All constructs were verified by sequencing.

Protein expression and purification

G6PD and its variants were expressed in E. coli C43 (DE3). When the culture density reached an OD600 of 0.5–0.6, 0.5 mM IPTG was added to induce the protein expression. After culturing at 28 °C overnight, the bacteria were centrifuged, and the pellets were lysed by sonication in buffer containing 50 mM Tris (pH 7.4), 300 mM NaCl, 5% glycerol, 0.4 mM PMSF, 1 mg mL−1 lysozyme, 0.1% Triton X-100 and protease inhibitor cocktail (Sigma P8340). G6PD was then purified by incubating the supernatant with TALON Superflow resin equilibrated with 1 bed volume of equilibration buffer (50 mM Tris (pH 7.4), 300 mM NaCl and 5 mM imidazole) at 4 °C for 1 h. The resin was washed with 5 bed volumes of wash buffer (50 mM Tris (pH 7.4), 300 mM NaCl and 20 mM imidazole) in a gravity-flow column and resuspended in 5 mL of equilibration buffer for size exclusion chromatography (50 mM Tris (pH 7.4) and 150 mM NaCl). Bovine thrombin (100 units) was added to the resin, which was followed by overnight incubation at 4 °C with gentle shaking. Tag-less G6PD was eluted and applied onto HiLoad 16/600 Superdex 75 pg size exclusion chromatography. Fractions containing G6PD were pooled and concentrated using 10 kDa MWCO membrane. The final concentration of G6PD was determined by Bradford method, and the protein was stored in 40% glycerol at −80 °C.

Enzyme assay and kinetic measurements

Enzyme activity was measured by monitoring NADPH production, which was coupled with diaphorase converting resazurin to fluorescent resorufin (excitation at 565 nm and emission at 590 nm) (Supplementary Fig. 3a); fluorescent signal was thus proportional to G6PD activity. All the assays were performed at 25 °C and run for 5 min in buffer containing 50 mM Tris (pH 7.4), 0.5 mM EDTA, 3.3 mM MgCl2, 1 U mL−1 diaphorase and 0.1 mM resazurin. 10 ng of recombinant enzymes or 10 μg of cell lysates was used for the assay with 10 μM NADP+ (Sigma) as cofactor and 100 μM G6P (Sigma) as substrate. Steady-state kinetic parameters were obtained by varying concentrations of NADP+ (0–10 μM) with a constant concentration of G6P (100 μM) and similarly for G6P (0–100 μM) with a constant concentration of NADP+ (10 μM) with 10 ng of recombinant enzymes. Data analysis was performed using GraphPad Prism software v.6 (GraphPad Software, La Jolla, CA USA). Kinetic parameters were obtained by fitting the data to the Michaelis–Menten equation.

High-throughput screening assay

The diaphorase-coupled enzyme assay as described above was used to screen for small-molecule activators. All the compounds purchased from SPECS, Chembridge, ChemDiv Kinase, LOPAC, Microsource Spectrum, Biomol FDA, Biomol ICCB, and NIH Clinical Collection were added to Canton G6PD enzyme reaction mixture at a final concentration of 16.67 μM using Caliper Life Sciences Staccato system with a Twister II robot and a Sciclone ALH3000 (Caliper Life Sciences, Alameda, CA USA) integrated with a V&P Scientific pin tool, which was followed by the incubation for 3 h. Then addition of G6P initiated the reaction, which was run for 2.5 min. The fluorescent signals were recorded 4 times during the run using Molecular Devices AnalystGT (Molecular Devices, Sunnyvale, CA USA). Any compounds showing 30% activation of the enzyme were rescreened in a dose-dependent manner (0–30 μM, duplicate) to identify potential hits. The screening and data analysis were carried out by Stanford University High-Throughput Bioscience Centers (HTBC).

Thermostability assay

10 ng of recombinant enzymes was incubated at various temperatures ranging from 25 to 65 °C for 20 min, and the activity was measured as described above. After normalization of the data between 0 and 100, Boltzmann sigmoidal equation was used to calculate the T1/2 value, the temperature at which the enzyme retains half of original activity.

In vitro proteolysis assay

200 ng of recombinant enzymes was incubated with 10 ng of chymotrypsin for 1 h at room temperature. 100 μM of the compound was added to some reaction conditions. The following protein level was examined by Western blot (original blot data are available in the Supplementary Information).

Overexpression of WT G6PD and Canton variant in SH-SY5Y cells

Prior to the cellular-based assays using SH-SH5Y cells, the duration of overexpression of WT G6PD and Canton variant was examined by transfecting the cells seeded in a 12-well plate. The genes encoding human WT G6PD and Canton variant were first PCR-amplified, which was then inserted into pcDNA 3.1/myc-His C (ThermoFisher Scientific) using HindIII and XhoI restriction enzyme sites. 0.5 μg of cDNA and 1.5 μg of lipofectamine (Invitrogen) were diluted in 50 μL of Opti-MEM medium, respectively and incubated for 5 min. The diluted DNA was combined with diluted lipofectamine, which was followed by incubation for 20 min prior to the addition to cells. The transfected cells were collected at different time points (up to 72 h), and the overexpressed G6PD levels were examined by Western blot. The transfection was carried out in 50% serum-starved cells. Once the duration of expression was confirmed, other cellular-based assays were performed.

Cycloheximide chase assay

50,000 cells (SH-SH5Y cells or fibroblast cells) or 100,000 cells (lymphocytes) were seeded in a 12-well plate and incubated overnight. The cells were subjected to serum starvation (50–75%) for 48 h and treated with 50 μg mL−1 of cycloheximide at different time points (0–48 h). The cells were treated with the compound (1 μM) for 48 h together with cycloheximide. Then the cells were collected in PBS containing protease inhibitor cocktail and 1% Triton X-100 and centrifuged at 18,800 × g at 4 °C for 10 min. 10 μg of total protein was loaded onto SDS–PAGE gels, and the protein levels were examined by Western blot (original blot data are available in Supplementary Information).

Glutathione (GSH) measurement

Total glutathione level was measured using a Total Glutathione Quantification Kit (Dojindo), according to the manufacturer’s instructions. Cells were subjected to serum starvation (50–75%) for 48 h to induce oxidative stress and treated with the compound for 24 h before measurement. The absorbance was read at 412 nm.

Cell viability assay

Cell viability was measured using a Cell-Counting Kit-8 (CCK-8, Dojindo), utilizing WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt, according to the manufacturer’s instructions. Cells were subjected to serum starvation (50–75%) for 48 h before measurement. Cells in 100 μL of medium per well were treated with 10 μL of CCK-8 solution and incubated for 2 h at 37 °C. The absorbance was read at 450 nm. Viability of lymphocytes was measured by staining with a 0.4% solution of trypan blue in buffered isotonic salt solution (pH 7.2). The viability was calculated as the number of viable cells (non-stained by the dye) divided by the total number of cells within the grids on the hemacytometer. Cells were treated with 1 μM of the compound 24 h before the measurement.

Cellular reactive oxygen species (ROS) measurement

Cells in a 96-well plate were incubated with chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate (CM-H2DCFDA) at a final concentration of 5 μM in HBSS (Hank’s balanced salt solution) for 30 min at 37 °C. After wash, cells were treated with Hoechst 33342 (Molecular Probes) to stain nuclei and incubated for another 10 min at 37 °C. Cells were washed in HBSS, and the florescence was analyzed with excitation/emission at 485/525 nm. Cells were subjected to serum starvation (50–75%) for 48 h to induce oxidative stress and treated with the compound for 24 h before measurement. The signal was normalized to nuclei staining (excitation/emission at 350/470 nm).

Native gel electrophoresis

200–300 ng of recombinant enzymes was incubated with the compound (varying in assays) for 10 min at room temperature. To prevent streaking and artifacts in native PAGE gel, the samples in a native state (no boiling of sample and no reducing agent in sample buffer) were electrophoresed by SDS–PAGE. Cross-linking assay was initiated by incubating 200 ng of recombinant enzymes in PBS with 0.1% of glutaraldehyde and different concentrations of NADP+ (0, 10, 100, 1000 μM) or MgCl2 (0, 1, 10, 100 mM). The mixture was incubated for 10 min at room temperature, which was followed by the addition of 100 mM Tris (pH 8.0) at a final concentration to terminate the reaction. The samples were electrophoresed as described above.

G6PD siRNA-knockdown assay

Endogenous G6PD was knocked down in each cell line as follows; 2 pmol of siRNA G6PD (Santa Cruz Biotechnology, sc-60667) and 0.5 μg lipofectamine (Invitrogen) were diluted in 10 μL of Opti-MEM medium, respectively and incubated for 5 min. The diluted siRNA was combined with diluted lipofectamine, which was followed by additional incubation for 20 min prior to the addition to cells in a 96-well plate.

Crystallization, data collection, structure determination and refinement

Crystals of WT G6PD recombinant enzyme grew in sitting drops containing 20% w/v PEG 3350, 0.2 M potassium formate, pH 7.3. Suramin (G6PD inhibitor) was added to the protein solution (the final concentration in the drop was 0.5 mM) prior to the crystallization. Canton G6PD recombinant enzyme was crystallized in sitting drops containing 20% w/v PEG 3350, 0.2 M ammonium citrate tribasic, pH 7.0. AG1 dissolved in 30% DMSO was added to the protein prior to the crystallization to reach final concentration of 0.5 mM in the drop. None of the Suramin or AG1 compound was visible in the electron density map of WT G6PD and Canton G6PD; however, they significantly improved diffracting quality of the crystals. Note that our inability to observe AG1 in the crystal structure may reflect instability or flexibility of the ligand bound to G6PD. Additional crystallographic studies and further medicinal chemistry efforts will help determine the binding site of AG1 in the enzyme and the mechanism by which it activates G6PD. X-ray diffraction data of WT G6PD and Canton G6PD were collected at 100 K at beamline 12–2 of Stanford Synchrotron Radiation Light Source (SSRL) and beamline 5.0.2 of Advanced Light Source (ALS), respectively. A solution of 20% glycerol was used as cryo-protectant. Crystals of WT and Canton G6PD diffracted to 1.9 Å and 2.6 Å resolution, respectively. The data were processed using iMOSFLM57, and further analysis of the data by POINTLESS58,59 indicated the space group of F222 and P212121 for WT G6PD and Canton G6PD crystals, respectively. WT G6PD structure was solved using molecular replacement with a monomeric G6PD structure from PDB: 2BHL used as a search model in MOLREP. Canton G6PD structure was solved using the WT G6PD structure that was already solved in this study. Molecular models were further built in Coot60. Both structures were refined using the restrained isotropic refinement in REFMAC61,62. TLS parameters were not used for the refinement in both cases. Each refinement was done using 10 cycles of maximum likelihood restrained refinement, with geometry weight adjusted to 0.05. Data collection and refinement statistics are summarized in Table 1. The atomic coordinates and structure factors are deposited in the PDB database under accession codes PDB: 6E08 for WT G6PD and PDB: 6E07 for Canton G6PD. All structure figures were prepared using PyMOL (PyMOL Molecular Graphics System, Version 1.5.0.5; Schrödinger).

Zebrafish husbandry

Adult zebrafish (AB strain; 3–18 months old) were raised according to standard protocols, and embryos were obtained through natural mating and staged63. Adult tbx16b104/+ was a generous gift from S. Amacher (Ohio State University). All animal procedures were performed according to NIH guidelines and approved by the Committee on Administrative Panel on Laboratory Animal Care (APLAC) at Stanford University. Embryos were raised in E3 medium at 28.5 °C.

Zebrafish crispants

sgRNA against exon 10 of g6pd was designed using CHOPCHOP and in vitro transcribed using the T7 quick high yield RNA synthesis kit (New England Biolabs, E2050S)64,65. The gene-specific oligo sequence was: 5′-TAATACGACTCACTATAGAGAAGGGGAGGCAAAACTGGTTTTAGAGCTAGAAATAGCAAG-3’. sgRNA and Cas9 protein (New England Biolabs, M0386T) were mixed and microinjected into one-cell-stage embryos. For each injected clutch, 10 individual embryos were isolated at 24 hpf for sequencing to confirm introduction of a CRISPR-mediated indel in exon 10.

Zebrafish compound treatment

Embryos were dechorinated with pronase at 24 hpf and treated with 100 μg mL−1 of chloroquine and/or AG1 (1 μM) by directly adding the compounds to the well. For ROS measurements, the embryos were incubated with compounds for 5 h and then the ROS-detecting reagent (CM-H2DCFDA) was added at a final concentration of 500 ng mL−1 to the well and incubated for 3 h. One embryo was placed to each well of a black, opaque 96-well plate. The florescence was analyzed with excitation/emission at 485/525 nm. After ROS assays, embryos at about 32 hpf were pooled and lysed in buffer containing 50 mM Tris (pH 7.4), 150 mM NaCl, 1 mM EDTA, 0.1% NP-40 and protease inhibitor cocktail, which was followed by three cycles of freeze and thawing in liquid nitrogen. The lysate was centrifuged at 18,800 × g at 4 °C for 15 min. Total protein concentration in the supernatants (total lysate) was determined by the Bradford method. 10 μg of total lysate was used for enzymatic assay. 50 μg of total lysate was used to measure NADPH levels using a NADPH quantification kit (Biovision), according to the manufacturer’s instructions. 50 μg of total lysate was loaded onto 10% SDS–PAGE gels, and the protein levels were examined by Western blot using anti-G6PD antibody (Abcam (G6PD: AB87230)).

Zebrafish imaging

Live embryos were anesthetized and mounted in 3% methylcellulose. Embryos were imaged with a Leica M205FA microscope equipped with a 1.0x Plan Apochromatic objective and a SPOT Flex camera or a Leica DM4500B compound microscope equipped with a QImaging Retiga-SRV camera. For hemoglobin staining, live embryos were stained in 0.6 mg mL−1o-dianisidine solution containing 10 mM sodium acetate (pH 4.5), 0.65% H2O2 and 40% ethanol in the dark for 15 min and cleared in glycerol37. Embryos were then mounted in 100% glycerol and imaged with a Leica M205FA microscope equipped with a 1.0x Plan Apochromatic objective and a SPOT Flex camera. All images were captured using SPOT or MetaMorph imaging software (Diagnostic Imaging Inc.) and processed in Photoshop (Adobe). Adjustments were limited to brightness levels and cropping. Analysis was carried out by an observer blinded to the experimental conditions.

Blood sample assay

De-identified blood samples were obtained from the Stanford Blood Center. Erythrocytes were collected by filtering the samples through a cellulose slurry to remove platelets and leukocytes and then washed with saline. G6PD activity was measured spectrophotometrically by the Beutler method66. The activity of all the samples used in this study was in a normal range (5–9 U g−1 Hb), suggesting that the subjects have WT G6PD. 5% erythrocyte suspension was pre-incubated with 1–5 μΜ AG1 at 4 °C overnight, which was followed by treatment with (or without) either 1 mΜ chloroquine (CQ) or 1 mM diamide for 3–4 h at 37 °C (for hemolysis assay with chloroquine, the mixture was incubated under light). Then centrifugation at 100 × g for 5 min was followed. Hemoglobin release in the supernatant was monitored by measuring absorbance at 540 nm. Saline was used as a negative control (0% hemolysis) and a sample treated with 0.1% Triton X-100 was used as a positive control (100% hemolysis). For ROS measurement, erythrocyte mixture was washed with saline by centrifugation after treatment and incubated with chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate (CM-H2DCFDA) at a final concentration of 5 μM in saline at 37 °C for 15 min. After wash, the samples were lysed with 0.1% Triton X-100 (final concentration), and the florescence was analyzed with excitation/emission at 485/525 nm. GSH measurement was determined using a Cayman glutathione assay kit (Cayman Chemicals, 703002). Briefly, 50 μL of diluted erythrocyte lysate samples were mixed with 150 μL of assay reagents including glutathione reductase, 5′,5-dithiobis-(2-nitrobenzoic acid) (DTNB) and NADPH, which was followed by incubation for 25 min at room temperature. The absorbance was read at 412 nm. For storage assay, 5% erythrocyte suspension was stored at 4 °C with and without 1 μM AG1, and hemolysis and G6PD activity were monitored every week for 28 days to examine whether AG1 improves preservation of erythrocytes over time. Protein leakage was also examined by measuring the absorbance of the supernatant of samples at 280 nm. The samples were re-treated with AG1 every week.

Statistical analyses

Most assays were repeated at least in three independent experiments. The data from in vitro and cell-based assays are presented as mean ± standard error of the mean (SEM), and the data from the human erythrocyte study are presented as mean ± standard deviation (SD). Statistical differences were calculated by either Student’s t-test (two-tailed, unpaired), one-way ANOVA, or two-way ANOVA using GraphPad Prism software. In assays with human erythrocytes, each sample was utilized as its own control, and assay parameters were compared before and after treatment; thus, randomization was not needed. For all zebrafish experiments, at least two breeding tanks, each containing 3–4 males and 3–5 females from separate stocks, were set up to generate embryos. Embryos from each tank were randomly distributed across tested conditions. Unfertilized and developmentally abnormal embryos were removed prior to compound treatment. No statistical methods were used to determine sample size per condition. For phenotypic analysis, raw counts for each condition were used for chi-square analysis or Fisher’s exact test based on expected values. For all phenotypic analysis, the scorer was blinded to treatment conditions. For ROS assays, the normality of each distribution was assessed using the Shapiro–Wilk test and determined to be non-normal. A Kruskal–Wallis test with a Dunn’s secondary test was used to determine differences between all conditions. p values were corrected for multiple comparisons testing. p values and number of samples or experiments replicated are indicated within the figure legends, and p < 0.05 was considered statistically significant.

Data availability

The data that support the findings of this study are available from the corresponding author upon request. Protein structures have been deposited in the Protein Data Bank (PDB) with accession codes of 6E07 and 6E08 for Canton G6PD and WT G6PD, respectively.

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    FRESH STUDENTS RETURNING STUDENTS DETAILS SCIENCE NON-SCIENCE SCIENCE NON-SCIENCE Tuition Examination Fees 7,000.00 5,000.00 7,000.00 5,000.00 Labouratory Fees 3,000.00 1,500.00 3,000.00 1,000.00 Library / MTN Lib. 2,000.00 2,000.00 2,000.00 2,000.00 Admission Brochure 1,500.00 1,500.00 Orientation Brochure 1,500.00 1,500.00 Sport 1,000.00 1,000.00 1,000.00 1,000.00 Student Comm Service 1,000.00 1,000.00 Student Handbook Brochure 1,500.00 1,500.00 Utility 7,000.00 7,000.00 7,000.00 7,000.00 Med. Char / TSHIP /NHIS / Life Ins 7,400.00 7,400.00 3,400.00 3,400.00 Verification of Resul 5,000.00 5,000.00 Medical Exam / Eye Test /td> 5,500.00 5,500.00 Academic Gown (Rental) 5,000.00 5,000.00 Forensic ID Card 2,000.00 2,000.00 Bank Charges / Portal Charges 2,000.00 2,000.00 1,000.00 1,000.00 Development Levy 20,000.00 20,000.00 20,000.00 20,000.00 Student Union Dues 1,000.00 1,000.00 1,000.00 1,000.00 TOTAL 73,400.00 69,900.00 45,400.00 41,400.00

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    THEY ARE ALSO EXPECTED TO UPDATE THEIR PERSONAL DATA FORMS WITH INFORMATION SUCH AS PERMANENT ADDRESS;NEXT OF KIN; ETC.
    NOTE THAT THEY ARE TO THEN VISIT THEIR COURSE ADVISERS FOR VALIDATION OF REGISTERED COURSES.
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    Knox Together: COVID-19 Plans & Policies

    Latest Updates

    November 8

    Dear Knox Community,

    As we approach the end of fall term and students prepare to return home for winter break, we would like to remind faculty, staff, and students that COVID-19 PCR saliva testing through Shield IL is available Monday through Friday from 8:30 a.m. until 12:30 p.m. at the T. Fleming Fieldhouse. 

    We strongly encourage students to utilize this testing prior to departure. If you are in need of testing as a requirement for a flight, you should also plan to test at the fieldhouse during the normally-scheduled times listed in this email. Shield IL test results have been coming back within 24 hours. Please do not forget to schedule an appointment through your Shield IL portal at Portal Shield illinois login or the SHIELDIL app. 

    Monday through Friday COVID-19 Saliva Testing Ends Friday November 19

    Beginning Monday November 22, saliva testing availability will be limited. The test site hours will continue to be 8:30 a.m. until 12:30 p.m. on the days that testing is open. Please consult the following list of dates for winter break COVID-19 testing availability.

    Monday 11/22 and Tuesday 11/23
    Monday 11/29, Wednesday 12/1, and Friday 12/3
    Monday 12/6, Wednesday 12/8, and Friday 12/10
    Monday 12/13, Wednesday 12/15, and Friday 12/17
    Monday 12/20 and Wednesday 12/22
    Wednesday 12/29 and Thursday 12/30

    Monday through Friday Testing Resumes Monday, January 3, 2022 

    We will announce our specific plans for winter arrival testing in December, as we continue to monitor evolving public health conditions and guidance from the CDC and our medical consultants.

    Thank you for all you have done during fall term to keep our campus safe and healthy. 

    Regards,

    Mike Schneider

    Abby Putnam

    October 11

    Dear Knox Campus Community,

    We are encouraged by the results from our first round of required COVID-19 testing during the week of September 20. As you may know, we identified just five COVID-19 cases, a strong indicator that our three-pronged approach of vaccinations, testing, and masking is currently working to keep infection rates low on our campus. 

    While an optimistic start to the academic year, we need to remain vigilant, and make sure we build the best testing capacity on campus that we can. This step will ensure we can quickly respond to the unpredictable nature of the COVID-19 pandemic.

    Switching COVID-19 Testing Provider to SHIELD Illinois; Please Register Now

    With this in mind, we are switching our testing provider to SHIELD Illinois, and are requiring all members of our campus community to take a few minutes to register with SHIELD Illinois by Monday, October 18. You may recall that we utilized Shield IL last year during winter and spring terms, and many campus members already have SHIELD Illinois accounts. 

    SHIELD Illinois will be our testing provider for the remainder of this academic year, as it provides a more streamlined experience for you -- a fast and efficient registration process, a simple and rapid on-site testing experience, and you will receive your results quickly and reliably.

    SHIELD Illinois will be new to many; registration is simple and takes just a few minutes.

    How to Register for SHIELD Illinois 

    We understand that most returning students, and some faculty and staff, are already registered with SHIELD Illinois. At this time, we are asking all students, faculty and staff to visit Portal.shieldillinois.com, and if you find that you are already registered, please ensure your information is accurate. 

    To create your new SHIELD Illinois portal account, please visit Portal.shieldillinois.com and click Sign up for an account. Using the student or employee agency code below, create your new portal account. Once you submit your information, you will be sent a verification code to enter and confirm your identity. You can also create your portal by going to the Apple Store or Google Play Store and downloading the SHIELDIL app (Point and Click Solutions, Inc.) and using the appropriate code below. We recommend that you copy and paste this code in order to avoid errors.

    Student Agency Code: antfzz8i-stu

    Employee Agency Code:  antfzz8i-empl 

    If you have trouble creating an account, please call the patient support line at 217-265-6059, 24 hours a day, 7 days a week.

    Registering now will ensure everyone is prepared to use SHIELD IL whether we announce another all-campus testing event in the future, whether you have an exemption and need to test twice weekly, or whether you are symptomatic and need to be tested.

    Thank you for your support and your ongoing dedication to keeping our campus safe.

    Regards,

    Michael Schneider

    Abby Putnam

    September 14

    Dear Knox Community,

    This email details two important announcements regarding COVID-19 testing. Please read the information below carefully.

    REQUIRED COVID-19 TESTING FOR ALL DURING WEEK OF SEPTEMBER 20-24

    We are requiring all faculty, staff and students to complete campus-wide COVID-19 testing during the week of September 20-24. This campus-wide testing will help us assess the presence of the virus in our campus community, which will in turn inform the strategies needed to continue to safely hold in-person classes, gatherings, and activities. 

    Testing will be conducted Monday through Friday, September 20-24, at the T. Fleming Fieldhouse from 8:30 a.m. to 4:00 p.m. No appointment is needed. The state of Illinois requires certain demographic information for test registration. In order to shorten wait times and make the testing process as quick as possible for you, please complete this form prior to arriving for your test.

    Also, please note that if you have tested positive for COVID-19 in the last 90 days, according to the CDC, you do not need to test. If you have tested positive in the last 90 days, please report this information to Health Services at health@knox.edu by Monday, September 20.

    In order to avoid long wait times at the end of the week, please plan your test as early in the week as possible. Prior to arriving for a test, avoid drinks, food, smoking, nasal sprays, teeth cleaning, and chewing gum for at least 60 minutes before sample collection. Test results will be sent to you by email in one to two days. Health Services will also receive a confidential test result report.

    Employees will receive release time to get tested during that week. Please coordinate with your supervisor to schedule the release time for your test.

    COVID-19 TESTING AVAILABLE EVERY WEEK ON CAMPUS UNTIL FURTHER NOTICE

    In addition to the required testing outlined above, COVID-19 testing is available to all students, faculty, and staff regardless of vaccination status, Monday through Friday from 8:30 a.m. until 12:30 p.m. at the T. Fleming Fieldhouse at no cost. All community members are welcome and encouraged to test if they have any symptoms of COVID-19, or if they have had a concerning exposure, whether they are vaccinated or not. No appointment is needed. 

    Faculty and staff can visit the Knox Together Workplace for Faculty and Staff web page for more information and answers to any questions regarding when a COVID-19 test is appropriate. Students can visit the Health and Wellness web page for information and answers to questions about COVID-19 testing.

    If you have any questions, please email together@knox.edu. 

    Thank you for your continued commitment to doing all you can to keep everyone in our community safe and healthy.

    Regards,
    Michael A. Schneider
    Provost and Dean of the College
    Interim Vice President of Student Development

    Paul Eisenmenger
    Vice President for Finance and Administrative Services

    August 12

    Dear Knox Community,

    Opening our campus, bringing our community back together, and providing an in-person student experience that is as close to normal as possible are our priorities that are guiding our planning and preparation for the upcoming academic year. We know we are at our best when we are living and learning together on campus, and we are committed to doing all we can to provide a healthy and safe environment for all members of our community. 

    The protocols outlined below are informed by CDC and WHO guidelines and we continue to monitor the COVID-19 conditions nationally, locally, and in our community. We will adjust these health and safety policies as needed to create the safest possible environment for our community. 

    Vaccinations are required for students, faculty, and staff for the upcoming academic year. In May, we announced that all students are required to be fully vaccinated against COVID-19 for the 2021-22 academic year except for those with an approved medical or religious exemption. On August 1, we announced that all faculty and staff are required to be fully vaccinated against COVID-19 by Monday, September 13, except for those with an approved medical or religious exemption. Students requesting an exemption should reach out to Health Services; faculty and staff requesting an exemption should reach out to Human Resources. If you have not yet reported your vaccination information, please do so as soon as possible using the appropriate link below.

    Returning students: Upload Your COVID-19 Vaccine Record

    New incoming students: Pre-arrival Tracker

    Faculty and staff: Confidential Vaccination Verification Form 

    Masks are now required indoors, regardless of vaccination status. 

    This includes all Knox College buildings and spaces. There are several instances where it is not required or practical to remain masked at all times including: 

    The NCAA and Midwest Conference have protocols in place to allow athletic competition to resume this fall. Knox athletic teams and visiting teams are subject to those protocols. In some cases, student-athletes and/or coaches may not be masked during particular practice and competition activities.  

    Masks are not required outdoors, but are recommended in crowded outdoor settings, and when interacting with campus visitors. 

    All students will be tested for COVID-19 upon arrival; those who have approved medical and religious exemptions will be tested twice weekly on an ongoing basis. New and returning students will be tested upon arrival, and those students and faculty and staff who have approved medical and religious exemptions will be tested twice weekly. We will share details of the testing process soon.

    In addition, a small number of new and returning international students are unable to complete the full vaccination process prior to arrival due to the limited availability of the vaccine in their area. If you are an international student and do not have access to a vaccine in your home country, please contact Health Services immediately to make arrangements to be vaccinated upon arrival if you have not done so already. Testing for those who arrive without being fully vaccinated will be twice weekly until they are fully vaccinated. 

    Visitor and guest policy 

    Residence hall visitors:Visitors and guests (anyone other than a Knox student, faculty, or staff member) are NOT allowed in residence halls. A one-time exception is being made for families on move-in day. Family members assisting with move-in must wear masks at all times, limit the time inside the residence hall, and limit the number of family members in the residence hall to only those essential for move-in.

    The policy regarding residence hall visitors will be revisited near the end of September.

    Day visitors to non-residential buildings: Speakers, performers, and alumni visitors fall into this category. These visitors are subject to the indoor mask policy. Prior to entering a non-residential campus building, visitors for the day must check in with campus safety and complete a form providing vaccination status. If a visitor is vaccinated, or unvaccinated and provides proof of a negative COVID test within 72 hours of arrival on campus, they will receive a Knox wristband, and will be able to enter non-residential campus buildings. 

    Prospective students and their families: Prospective students and their families are required to wear masks indoors and outdoors when physical distancing is not possible. They will be required to check in with admission. They are also encouraged to limit the number of family members who join them for their visit. Prospective students and their families will not visit residence halls, observe classes, or participate in overnight visits. 

    Repeat visitors to non-residential buildings: These visitors include ensemble members, community groups that regularly use our indoor facilities, or other members of the community who do ongoing research in our library. Members of this visitor category are subject to the indoor mask policy, and must be vaccinated. They will be required to check in with campus safety, complete a form and provide proof of vaccination and will be issued a lanyard and visitor pass which will include their name and date approved.

    15 minutes or under visitors to non-residential buildings: These visitors include those delivering supplies, mail, or other items to campus. These visitors are subject to the indoor mask policy and must limit their time indoors to 15 minutes or under. Any time over 15 minutes will require following the day visitor policy. 

    Athletics spectator policies (with guidance from the NCAA and Midwest Conference) are being developed and will be available on the Prairie Fire and Knox Together website. Please check the policies frequently as they are subject to change.

    We will also update our Knox Together website to ensure any information provided there is current. We understand that you may have questions; please email them to health@knox.edu. 

    Following these policies will ensure that we can safely bring our community back together, and provide an in-person student experience that is as close to normal as possible. Thank you for doing your part to keep us all safe and healthy.

    C. Andrew McGadney
    President

    July 30

    Dear Knox Faculty and Staff,

    I’m looking forward to having nearly all Knox staff be back on campus next week for the first time in well over a year, with faculty and students arriving soon after. The next few weeks are critical to our success in creating a safe environment for our students and colleagues as we begin the 2021-2022 academic year.  

    You may recall that in May, we announced our students are required to be vaccinated for the upcoming academic year. After consultation with the Board of Trustees, FASCom, Staff Council, and members of the senior staff, we are now requiring that all faculty and staff members be fully vaccinated against COVID-19 by September 13, 2021. As is necessary for unionized employees, Knox will engage with leaders of the Collective Bargaining Unit to discuss and formalize the obligations of union-represented employees. Employees requesting a medical or religious exemption may contact Human Resources. 

    The decision to require students, faculty, and staff to be vaccinated is based on scientific fact, our responsibility to each other as members of the Knox community, and our ability to carry out our mission. Please keep in mind that infection (including the more contagious Delta variant), hospitalizations, and death rates are rising among those who are not vaccinated. 

    We join countless for-profit, state, and federal organizations and hundreds of colleges and universities throughout the country making this difficult but necessary decision. The Chronicle of Higher Education is tracking vaccination policies here. 

    For those who have not yet received a vaccination, free vaccinations are available at the following locations:

    Knox County Health Department
    Walgreens
    Hy-Vee 

    All faculty and staff are required to provide vaccination status here by August 6. And, as stated above, all faculty and staff must be fully vaccinated by September 13. 

    Finally, we are in the process of updating health and wellness guidelines for fall as well as a FAQ document which will be available soon. We will hold an open forum on Thursday, August 5 at 12 p.m. in Kresge Recital Hall for any staff and faculty members who would like to ask questions. Thank you for doing all you can to ensure that we can provide a healthy, happy, and productive learning and work environment for everyone this fall.

    C. Andrew McGadney
    President

    The policies above are for the 2021-2022 academic year.

    July 8

    Dear Knox Community,

    We hope you are having an enjoyable and productive summer. 

    As we move through this season and continue to monitor Illinois Phase 5 guidelines and Knox County metrics, we wanted to provide you with an important update to our summer campus COVID-19 health and wellness protocols. 

    Updated Summer Health and Wellness Protocols

    Starting tomorrow, Friday, July 9, we are transitioning to protocols that are in line with Illinois Phase 5 guidelines. These protocols are in place to protect the health and safety of our entire community and we trust that everyone will follow the protocols out of respect for our colleagues and students.

    At this time, we are not mandating the COVID-19 vaccine for faculty and staff, but continue to strongly encourage anyone who has not yet received  a vaccination to get one as soon as possible. If you need assistance in obtaining a vaccine, please reach out to Abby Putnam in Health Services at 309-341-7559 or email health@knox.edu.

    Returning to Campus

    While many staff have been on campus throughout the pandemic, we look forward to welcoming everyone back to campus by Monday, August 2.

    Should you have any questions about the updated summer COVID-19 health and wellness policies, please contact Abby Putnam in Health Services at 309-341-7559 or email health@knox.edu. If you have any questions about returning to campus or telecommuting arrangements, please contact your supervisor or me at 309-341-7200 or email hr@knox.edu.

    The last 18 months have been extremely challenging for many of us both personally and professionally. We are grateful for your flexibility and perseverance throughout this difficult time and look forward to bringing our community back together on the campus. I’ll see you in August, if not before.

    Regards,

    Amy Chambers
    Assistant Vice President
    Human Resources

    June 17

    Dear Knox Community,

    Going forward, Knox Together emails will be sent on an as-needed basis. During the pandemic, these notes primarily shared information on health and wellbeing. Now that we have the vaccine and positivity rates are declining, we no longer need weekly updates. With our new president starting on July 1, there may be new updates about campus news and events. 

    Illinois Restored Plan Phase 5 

    As of last Friday, June 11, Illinois is now in the Illinois Restored Plan  Phase 5 (fully reopened). Please read the guidelines carefully since not all restrictions have been lifted. Face coverings are recommended for unvaccinated persons and all individuals on public transportation, in transportation hubs, and congregate facilities (healthcare facilities and long-term care homes, for instance). Also, businesses and venues should continue to allow for social distancing to the greatest extent possible, especially indoors, and they can continue to put in place additional public health mitigations as they deem appropriate (wearing masks, for example).

    Summer COVID-19 Policies

    Please check here for any updates to our summer COVID-19 policies, including our visitor policy, which you will find at the bottom of the linked web page. As we near the start of the academic year, we will update the website, and campus leadership will advise you of any changes.

    Thank you for your attention to this weekly email during the past months and for your questions, feedback, patience and support. Enjoy your summer, and best of luck in the coming academic year as you return to your “new normal.”

    TERESA L. AMOTT
    President

    June 10

    Dear Knox Community,

    Commencement was an especially joyous occasion this year, as we celebrated our 2021 graduates during two in-person ceremonies this past Saturday. When I rose to welcome the assembled students, faculty, staff, family and friends, I was overcome by the size and presence of the audience. After such a long and unprecedented period in the history of the College, at long last, we were truly together. Congratulations once again to all of our graduates. Thank you to our faculty and staff for everything you did this year to enable their success and to support the health and well being of our campus during the last 15 months. 

    This past Monday, Illinois Governor Pritzker announced that the state is moving into Phase 5 (full reopening) tomorrow. This is wonderful news, and a very encouraging sign for a fully reopened Knox College campus in the fall. Please note that not all restrictions will be lifted, as we continue to battle COVID-19. 

    PLEASE GET VACCINATED

    Even though Illinois is moving to full reopening, vaccinations are lagging in the state and across the country. We are strongly encouraging everyone in the Knox community to get vaccinated. According to responses from those members of our community who used the Healthcheck 360 tracker, we estimate that 88% of our students are fully vaccinated, and according to the most recent information, a comparable number of faculty and staff have had at least one dose of the vaccine. Vaccines are widely available; for local vaccine sites, or more information about getting vaccinated, please contact the Knox County Health Department. 

    REMINDER: SUMMER COVID 19 POLICIES

    Summer health and wellness policies took effect on Monday. As we move into Phase 5, we have relaxed many of our restrictions while maintaining safety as our priority. Please visit the Knox Together website for updated information about mask requirements, physical distancing, gathering size restrictions, COVID testing, and more. Also, please stay tuned for updates to these policies throughout the summer. 

    UPDATED VISITOR POLICY

    Starting immediately, visitors to campus do not need to be temperature and symptom checked upon arrival to campus. Visitors who will be inside campus buildings for more than 15 minutes do still need to be preapproved by a senior staff member, and do still need to check in upon arrival. Please review our updated visitor policy for more information.

    COMMENCEMENT AND AWARDS LINKS

    If you would like to watch the two Commencement ceremonies that took place last Saturday, you can find the videos here. Our honorary degree recipients recorded special messages for our graduates. Please watch the messages on this page. More than 30 of our students received academic honors awards. You can view our faculty announcing the awards and recipients here. 

    While we do not have video from The First Generation Reception, I want to acknowledge the inspiring remarks from student speaker Matrice Young and faculty speaker Prof. Mary Crawford. Both shared their personal stories of being the first in their families to graduate from college and their recognitions of all those who helped them achieve their dreams.

    Ray and I send our heartfelt thanks to all of you who were able to attend our campus farewell event, either virtually or in person, and to all those who planned yet one more event in a busy season. It was wonderful to see you and talk with you before our last drive back from Galesburg to Laporte, Pennsylvania -- a drive we made many times during the past ten years, but one made more poignant by knowing that we were starting a new chapter in our lives. More about that in a later message.

    Please enjoy your summer with family and friends, and stay safe and well.

    TERESA L. AMOTT
    President

    May 27

    Dear Knox Community,

    We have quite a few important items to share with you this week; we have published our Summer 2021 COVID Health and Wellness policies and continue to share important vaccine and Commencement information. 

    Please Read: Summer 2021 COVID Health and Wellness Policies

    Summer Health and Wellness Policies will take effect June 7. In alignment with state and federal guidelines, and thanks to low positivity rates on campus, we are pleased to be able to relax some of our restrictions while maintaining safety as our priority. Please visit the Knox Together website for updated information about mask requirements, physical distancing, gathering sizes, COVID testing, and more. Also, please stay tuned for updates to these policies throughout the summer. 

    We have had many questions about visitors to campus. A visitor is defined as any individual coming to campus who is not a Knox College student, faculty, or staff member. Please be sure to check the details of our summer visitor policy at the bottom of this page. There are policies that apply to outdoor and indoor spaces, as well as approval processes for different categories of visitors, such as individuals visiting students on campus and contractors, vendors, and admission visitors.

    Important Hy-Vee Vaccine Clinic Follow-Up Information

    People who received their first dose at the Hy-Vee on-campus clinic this past Tuesday or those who missed their second dose should go to a Hy-Vee pharmacy or find a location close to home that can give the second dose. 

    We have received inquiries about vaccines for international students arriving on campus in the fall. We are aware that campus-approved COVID-19 vaccines (Pfizer, Moderna, or Johnson & Johnson) are not widely available in all countries. We will facilitate vaccinations for students who are unable to be immunized prior to arriving on campus in the fall. Although fall policies have not been fully drafted, at this time, we do not anticipate that unvaccinated students will be required to arrive early to campus or quarantine upon arrival. 

    Commencement - Those Not Working or Not a Ticketed Guest

    Anyone who is not working Commencement or who is not a ticketed guest will be asked to maintain a reasonable distance from the Commencement perimeters for safety and to allow for the flow of graduates and guests in and out of the area. Anyone in the area outside of the perimeter will be expected to follow current campus COVID-19 protocols and guidelines for gathering. Please contact commencement@knox.edu if you have any questions about Commencement.

    As we continue through the Bridge Phase in Illinois and summer and Phase 5 (full reopening) approaches, hope for a healthy and peaceful future is well within our reach. As we have done for the past year, let’s continue to do our part to end this academic year on a high note and celebrate our resilience, innovation, and deep care for one another.

    TERESA L. AMOTT
    President

    May 20

    Dear Knox Community,

    As we near the end of the academic year and prepare to celebrate our graduating class, please accept my heartfelt gratitude for everything you have all done to ensure our campus community emerges from the past year as healthy and hopeful as humanly possible. It has been a long year, and yet together, we are getting much closer to the light at the end of the pandemic tunnel. 

    COVID Vaccination Policy for Fall Announced

    Students will be required to be vaccinated for the 2021-22 academic year, subject to medical or religious exemptions. Students returning for the 2021-22 academic year should submit their vaccine record to health@knox.edu once fully vaccinated. Health Services will work with students who are unable to access one of the FDA-approved COVID vaccines prior to returning to campus.  

    At this time, faculty and staff are strongly urged to receive the vaccine, but for now, it is not required.   

    May 25 HyVee Vaccination Clinic - First and Second Doses

    Hy-Vee Pharmacy will return to campus on Tuesday, May 25 for the second dose Moderna vaccine clinic. This event will take place in the T. Fleming Fieldhouse from 10:00 a.m. to 2:00 p.m. You can sign up here. 

    Students, faculty, and staff who have not received their first dose of the vaccine are also welcome to sign up with this link. People who receive their first dose at this clinic will need to go to the Hy-Vee pharmacy for their second dose, or find a location close to home that can give the second dose. 

    Reminder - Please Continue to Wear Your Mask on Campus

    We understand that the recent CDC guidance regarding wearing a mask may be confusing for many individuals and organizations. To avoid any confusion at Knox with the short time remaining in the term, we will not change our policies on wearing masks on campus at this time. 

    Even if you are fully vaccinated, please continue to wear your masks according to the Knox Together guidelines through the end of the academic year.

    Important Commencement Reminders for Graduates

    This is a gentle reminder that we are asking graduates who do not plan to use their tickets to please log into the system to release their tickets by this Sunday, May 23. After this deadline, if there are any unused guest tickets, they will be made available to other graduates. If available, groups of tickets will be released and can be claimed on a first come, first served basis on Tuesday, May 25 at 8:00 a.m. and 8:00 p.m. 

    Also, please mark your calendar for Commencement rehearsal on Thursday, June 3 on the South Lawn. All students walking in the ceremonies are required to attend. Morning graduates will rehearse at 10:30 a.m., and afternoon graduates will rehearse at 1:00 p.m. Graduates will pick up their cap and gown at rehearsal. Please contact commencement@knox.edu if you are unable to attend rehearsal.

    Please accept my wishes for a peaceful, healthy, and successful conclusion to this academic year.

    TERESA L. AMOTT
    President

    May 14

    Dear Knox Community,

    Yesterday, Governor Pritzker announced that the state has made sufficient progress in mitigating COVID-19 to enter the next phase of our state’s reopening plan, a bridge phase that starts today. This phase offers slightly relaxed capacity restrictions before reaching Phase 5, the full reopening phase. In his announcement, he also said that Illinois is expected to fully reopen and enter Phase 5 of its COVID reopening plan on Friday, June 11, barring any significant reversals in our key COVID-19 statewide indicators.

    Campus Health and Wellness Policies through End of Academic Term
    While the bridge phase expands gathering capacity restriction, given that we have only two weeks left in the academic year and seek to maintain our low COVID positivity rates, we will continue to cap indoor and outdoor gathering limits at 50 people. There may be exceptions to this 50-person limit, particularly for outdoor activities. Exceptions may be requested through the appropriate senior staff member.

    Additionally, we have all heard the news about the CDC issuing updated guidance for fully vaccinated people; the guidance says that if you are fully vaccinated, you can resume activities without wearing a mask or physically distancing, except where required by federal, state, local, tribal, or territorial laws, rules, and regulations, including local business and workplace guidance.

    With the short time remaining in the term, we want to avoid any confusion and will not be changing our policies on wearing masks on campus at this time. Even if you are fully vaccinated, please continue to follow the Knox Together guidelines through the end of the academic year.

    We will communicate summer campus health and wellness policies later this month.

    Graduates Can Bring An Additional Guest to Commencement
    Given this heartening news, we have good news for our 2021 graduates: With capacity limits slightly increased in the bridge phase, and keeping in mind that the six foot social distance requirement is still in place, we have been able to plan for each graduate to invite an additional guest to the Commencement exercises on June 5. This raises the number of guests per graduate from two to three.

    Graduates will receive an email tomorrow, Saturday, May 15 with a link to the electronic ticketing system, along with instructions for how to claim guest tickets. We are asking graduates who do not plan to use their tickets to please log into the system as soon as possible to release their tickets so that others who would like to invite additional guests can claim them. We ask that tickets be released by May 23. After this deadline, if there are any unused guest tickets, they will be made available to other graduates. If available, groups of tickets will be released and can be claimed on a first come, first served basis on May 25 at 8:00 a.m. and 8:00 p.m.

    Finally, I want to thank the faculty and staff who quickly volunteered to assist with Commencement. The volunteer slots are full! We appreciate your enthusiasm and willingness to help make the day extra special for our graduates and their guests.

    If you have any questions about Commencement, please email commencement@knox.edu. You can also visit the Commencement FAQs on our website.

    Thank you for your patience during these unpredictable times as we continue to do our best to provide a joyful Commencement to our graduates while abiding with public health guidelines.

    Best,
    Teresa

    May 6

    Dear Knox Community,

    On Tuesday, Illinois Governor J.B. Pritzker announced that the state of Illinois is on track to enter Phase 5 of its reopening plan in July. This would mark a full reopening with no capacity limits. He also reiterated that we are very likely to enter the next phase of our state’s reopening plan soon -- a transition phase with slightly relaxed capacity restrictions -- before reaching a full reopening this summer. What wonderful news! I am confident that the Knox community will contribute to this positive momentum by continuing to practice our Knox Together Pledge protocols and ensuring that all eligible individuals get vaccinated.

    Important 2021 Commencement Updates

    With one month remaining until our 2021 Commencement exercises, I wanted to share important news with you about the event. We have created a 2021 Commencement site on our Knox College website and are providing answers to frequently asked questions as well, for your convenience.

    As a reminder, we will hold two Commencement events on Saturday, June 5, 2021. The first is scheduled for 10:00 a.m.; the second is scheduled for 3:00 p.m. We anticipate that each ceremony will last one to 1.5 hours. 

    Students were provided the opportunity to indicate a preference for the morning or afternoon ceremony, and they were sent an email on May 1 with their assigned ceremony time to enable their guests to plan travel. By splitting the number of graduates in half, we have the space to safely accommodate graduates and their guests for each ceremony. 

    We  have confirmed the location for our 2021 Commencement; both ceremonies will be held on South Lawn. To ensure we abide by state capacity restrictions, we will be fencing off the stage and seating areas and taking tickets at entrances. Entrance to the Commencement event area is restricted to ticketed guests and those participating in the formal ceremony. 

    A limited number of faculty will participate in the ceremonies formally in light of space limitations on the commencement stage. Faculty and staff can also participate by volunteering to help with the ceremonies. We will need more volunteers than ever before to welcome guests to campus and assist with seating.  If you are interested in volunteering, please sign up here or email kridlon@knox.edu. 

    We hope that this information is helpful to you, and I look forward to seeing many of you on June 5. And, if you have any questions that our communications, website or FAQs about commencement do not answer, please email commencement@knox.edu. Thank you, and see you soon.

    TERESA L. AMOTT
    President

    April 30

    Dear Knox Community,

    We delayed this email for a day since yesterday was Knox Proud Day. A huge thank you to those of you who volunteered, gave, and supported our efforts on this annual day of giving. You can view our thank you video, which shares current donor and dollar amounts, here.

    On Wednesday, Illinois Governor J.B. Pritzker announced that the state is "making progress" in its coronavirus metrics and that we could soon enter the next phase of our state’s reopening plan, a transition phase with slightly relaxed capacity restrictions before reaching a full reopening. This is hopeful news and along with spring weather, should help us all restore and rebalance.

    In order for us to contribute to these positive metrics and keep our campus healthy, we are providing information and reminders below. Please read the information carefully. 

    On-Campus Vaccine Clinic

    Kudos to the 137 students, faculty and staff who received their first Moderna COVID-19 vaccine at the on-campus Hy-Vee clinic on Wednesday! We so appreciate your efforts to keep yourself and your community healthy and safe. Regarding the second dose of the vaccine, Hy-Vee is committed to providing the second dose vaccine clinic, but has not yet set the date and time. This information will come at a later date.

    Students: Email Photo of Your Proof of Vaccination to Health Services 

    As you are aware, in the fall we may require proof of vaccination for students, faculty and staff. To ensure that we have proof of vaccination should anyone misplace their vaccination cards, Health Services is asking students who have completed their COVID vaccination series to send a picture of their proof of vaccination record cards to Health@knox.edu. 

    Fully Vaccinated? Please Continue to Wear Your Mask on Campus

    On Tuesday, the CDC issued updated guidance for fully vaccinated people regarding wearing masks. Given that we have only one month left in the academic year, we want to avoid any confusion and will not change our policies on wearing masks on campus. If you are fully vaccinated, please continue to follow the Knox Together guidelines through the end of the academic year.

    Please Continue to Complete Your Daily Symptom Tracker

    As a reminder, all members of the Knox campus community are required to complete their daily symptom tracker through the end of the academic year. Doing so supports our commitment to following the Knox Together Pledge. The information in the tracker is critical for us as we monitor the overall health status of the community, so If you are not completing your daily symptom tracker, you are putting your fellow community members at risk. If you have any questions about the daily symptom tracker, please contact Health Services.

    Local Vaccination Clinics Scheduled for May 1 - May 4

    If you were unable to receive a vaccination at the on-campus Hy-Vee clinic on Wednesday, the Knox County Unified Command, a coalition of health, safety and education agencies and organizations, is holding four consecutive days of large scale vaccine clinics in Galesburg at 1150 W Carl Sandburg Drive (the old Bergner’s building) from Saturday, May 1 through Tuesday, May 4.

    Please register for the clinics here. To register, you will need to choose a time slot and follow the prompts to submit your registration. Please note that all the green time slots have openings. If a time slot turns red, all time slots at that time are filled. You will receive an email confirmation with a QR code when your registration is finalized; to make sign-in easier, please do your best to take the QR Code with you to your vaccine appointment. 

    Please also consider using these other available vaccination sites.

    Thank you so much for your continued support of one another as we near the end of this challenging academic year.

    TERESA L. AMOTT
    President

    April 22

    KNOX TOGETHER EMAIL - Week of April 19, 2021

    Dear Knox Community,

    We have received a number of questions about end of the year COVID testing and pre-graduation testing for seniors. This email will provide you with answers to those questions and also a reminder about upcoming vaccine clinics, both on campus and in Galesburg.

    All Students: End of the Year Testing

    COVID testing with Shield Illinois will continue through the week of 5/26 on Mondays, Wednesdays, and Thursdays from 8 a.m. to 1 p.m. in the Fieldhouse. Students should continue to schedule their weekly tests by last name in their MyShield portal. Additional testing related to air travel can be scheduled through Health Services by emailing Health@knox.edu. 

    Seniors: Pre-Commencement Testing

    All seniors participating in Commencement must test the week prior to Saturday’s event. Testing will take place during the following dates and times at the Fieldhouse:

    Monday May 31-- 9 a.m. to 1 p.m.
    Tuesday June 1-- 9 a.m. to 1 p.m.
    Wednesday June 2 -- 9 a.m. to 4 p.m.

    These tests can also be scheduled in your MyShield portal. 

    Please note, this is a change from our normal weekly schedule to allow for all test results to be back prior to Commencement. In addition, to allow for a busy senior week schedule, the hours have been extended on Wednesday to 4 p.m. 

    Reminder - Vaccine Clinic Scheduled for April 28

    If you are eligible for a vaccination, please consider signing up for the vaccine clinic for students, faculty, and staff in the Fieldhouse next Wednesday, April 28 from 10:00 a.m. to 2:00 p.m. The clinic is a partnership with Hy-Vee, and the Moderna vaccine will be administered at that time.  

    Please note that you do not need health insurance to get a COVID-19 vaccine with Hy-Vee. The vaccination is free. Pharmacies might collect insurance information, but they cannot charge you for the vaccine or for any fees, copays or coinsurance. In addition, if you do not have insurance, they will not bill you anything nor will they turn you away.

    You can sign up for a vaccine here; slots are on a first come, first served basis. It takes about five to 10 minutes to sign up. There are a total of 208 slots available for the clinic, and when a slot fills, it will no longer appear on the list of available times.

    Regarding the second dose of the vaccine, Hy-Vee has not yet set the second dose vaccine date and time. This information will come at a later date. Please go ahead and schedule your first dose; we will update you as soon as we know the second date and time. 

    Another Option: Local Vaccination Clinics, May 1 - May 4

    We were recently notified that the Knox County Unified Command, a coalition of health, safety and education agencies and organizations, will hold four consecutive days of large scale vaccine clinics in Galesburg at 1150 W Carl Sandburg Drive (the old Bergner’s building) from Saturday, May 1 through Tuesday, May 4.

    Please register for the clinics here. To register, you will need to choose a time slot and follow the prompts to submit your registration. Please note that all the green time slots have openings. If a time slot turns red, all time slots are filled. You will receive an email confirmation with a QR code when your registration is finalized; to make sign-in easier, please do your best to bring the QR Code with you to your vaccine appointment. 

    Please also consider using these other available vaccination sites.

    As more and more of our campus community gets vaccinated, we need to remember that we must stay vigilant and continue to abide by the Knox Together Pledge to keep one another safe and healthy. The pandemic is still with us, as reported this week.

    TERESA L. AMOTT
    President

    April 15

    More info on the Knox Together Email - Week of April 12, 2021

    Dear Knox Community,

    I'm writing to follow up on my earlier Knox Together message. Since then, we have learned that there may be some confusion surrounding the need to have proof of health insurance in order to schedule a vaccine appointment. You do not need health insurance in order to get a covid vaccine or to schedule an appointment with Hy Vee. The vaccination is free. Pharmacies might collect insurance information but they cannot charge you for the vaccine or for any fees, copays or coinsurance. In addition, if you do not have insurance, they will not bill you anything nor will they turn you away.

    Questions have also been asked about the second dose. At this time, Hy-Vee has not set the second dose vaccine date and time. This information will come at a later date. Please go ahead and schedule  your first dose and watch for more information to come. 

    Thanks for those who wrote to me with their questions,

    Teresa

    April 15

    Knox Together Email - Week of April 12, 2021

    Dear Knox Community,

    I am keeping this week’s Knox Together email brief, because I have two very important reminders to share with you today.

    First, COVID-19 cases are on the rise in Knox County, and the State of Illinois is also experiencing a resurgence of the pandemic.  Yesterday, the Illinois Department of Health reported that approximately 24% of the population is fully vaccinated. Although the number of people getting vaccinated continues to rise, the availability of ICU beds is decreasing -- an indicator that the pandemic is still very much with us. You can see how we’re doing at Knox College by visiting our COVID-19 Testing Dashboard, which is updated every Friday afternoon.

    In light of this news, I want to remind our community to stay vigilant and continue to follow the protocols outlined in the Knox Together Pledge. It is essential that everyone on our campus follow safety protocols, including social distancing, masking, and adhering to guidelines for campus events.

    Vaccine Clinic Scheduled for April 28

    I am pleased to announce that we are partnering with Hy-Vee to hold a vaccine clinic for students, faculty, and staff on our campus on Wednesday, April 28 from 10:00 a.m. to 2:00 p.m. in the Fieldhouse. The Moderna vaccine will be administered at that time.  

    You can sign up for a vaccine here; slots are on a first come, first served basis. It takes about five to 10 minutes to sign up. There are 13 openings for every 15 minute time slot -- a total of 208 slots available for the clinic. When a slot fills, it will not show up anymore. I encourage you to sign up quickly if you are interested in getting a vaccine at the onsite clinic.

    Please also consider using these other available vaccination sites if you prefer not to wait until April 28:

    Knox County Health Department
    Hy-Vee 
    CVS (Target) 
    A list of statewide mass vaccination clinic locations.
    Walgreens requires a personalized account. Once you have created your account, you can check vaccine availability by zip code.    

    Finally, I ask all supervisors to remain as flexible as possible in accommodating employee requests to get vaccinated. Hourly employees will receive up to one hour of paid time off to visit the clinic of their choice for each vaccine dose during work hours, coordinated in advance with their supervisors.  Employees should record this time by using the pay code “COVID” on their time cards, with supervisor approval.

    If you have any questions about Knox Together safety protocols or vaccines, please email Health Services at health@knox.edu.

    TERESA L. AMOTT
    President

    April 8

    Knox Together Email - Week of April 5, 2021

    Dear Knox Community,

    Today, we want to address the trial of Derek Chauvin, the former Minneapolis police officer charged with the murder of George Floyd, and its impact. People are making choices daily on how to engage with the trial, whether that is watching it in full or reading news reports. We want to acknowledge that the information being presented and shared is difficult to hear, and may be amplified by racial battle fatigue for our Black community members.  

    This trial acts as another mirror to the history of racial violence in the United States as much as it is about Derek Chauvin's actions. George Floyd’s murder follows an all-too-familiar pattern that our country must commit to undoing -- the systemic racism and violence communities of color have faced for hundreds of years. This offers an opportunity for each of us to ask ourselves how we can take action in our lives to address racial injustice.  Intercultural Life has provided a set of resources to help us learn more about anti-racism efforts and direct actions that can be taken.

    As the trial continues, we also wanted to share a number of resources with all of you that may be of help during the next few weeks. The HOPE Center will be hosting a racial healing circle for Black students, faculty and staff in the coming weeks, more details to come. The Center is also open for students, faculty and staff who want a space to talk or be in community with others. Staff are available to meet one on one with students as well. Counseling Services continues to provide remote sessions, and can be reached simply by emailing counseling@knox.edu to request an appointment. You can find a number of mental health resources related to the Chauvin trial on the NAMI Minnesota website. There are also many racial justice resources that provide ideas for actions you can take now to educate yourself and hold police accountable, including Campaign Zero, Black Lives Matter, the NAACP, and Color of Change. 

    Last Fall during Opening Convocation, our speaker, Randall Strickland ‘90, challenged us to fight for the oppressed, saying “it is so vital to understand that as justice touches everyone, so does injustice.” He encouraged us to “say their names” at every opportunity. So we remember George Floyd. Rayshard Brooks. Breonna Taylor. Atatianna Jefferson. Stephon Clark. Botham Jean. Jamar Clark. Philando Castile. Michael Brown. Eric Garner, and many others. We must continue our work together to fight racism in the United States in all its forms and create a more just world. Today, especially, we ask that you join us in supporting our Black students and colleagues, and in remembering that each of us is obligated to stand up to injustice whenever and wherever it occurs.

    Teresa Amott, President
    Tianna Cervantez, Executive Director for Diversity, Equity and Inclusion

    April 1

    KNOX TOGETHER EMAIL - Week of March 29, 2021

    Dear Knox Community,

    Earlier this week, we announced our current Commencement plan for the class of 2021, and we also shared with the class of 2020 that we are planning a Commencement celebration for them during Homecoming on the afternoon of Sunday, October 10. While both celebrations are contingent upon public health guidance, we are hopeful that we will be able to deliver the joyful, celebratory experience our graduates deserve.

    COVID-19 Update

    This week, the Illinois Department of Public Health reported that an increase in COVID-19 cases, positivity rates, and hospitalizations will keep the state from entering the next phase of Governor Pritzker’s reopening plan. Currently, the Illinois Department of Public health is monitoring key indicators in all 11 health regions of the state that potentially signify a resurgence. The state will continue to monitor for 14 days to determine if current mitigations should remain in place. 

    Since the beginning of Spring term, we have seen three positive student cases, which came with a significant number of close contacts who are currently in quarantine. While our campus positivity rate remains low at 0.53% for the term so far, it is more important than ever for us all to abide by the Knox Together Pledge. We must continue to commit to keeping our campus community healthy.

    Vaccine Update

    The Galesburg Register-Mail has also reported that eligibility for the COVID-19 vaccine in Knox County is expanding to all adults in the county. The Illinois Department of Health advised local health departments to expand eligibility if they have available vaccines. Adults 18 years and over must contact the Knox County Health Department to schedule an appointment.

    We just learned that Cottage Hospital Clinics has COVID vaccine availability this Friday, April 2nd, from 8 am to 4 pm for anyone age 18 and older. You can call 309-343-7130 during normal business hours to ask for an appointment time. 

    There is no shuttle planned for this event. However, Cottage Hospital is within walking distance of the College and the city bus is free to students. Please reach out to Health Services if you have further questions. 

    This expansion is yet another positive step toward our return to the “human-powered” experience that is so special at Knox. We strongly encourage all eligible Knox community members 18 years and over to make an appointment if you have not done so already. 

    We certainly understand that it has been more than a year since the pandemic began its deadly spread across our country, and with the warmer weather and the start of spring term, we are all getting restless to spend time with others. Now, more than ever, we need every member of our community to commit to keeping one another safe and continuing to follow necessary safety protocols. Thank you in advance for your cooperation at this critical time.

    TERESA L. AMOTT
    President

    March 25

    KNOX TOGETHER EMAIL - Week of March 22, 2021

    Dear Knox Community,

    Following a brief Spring Break, classes have resumed and Spring Term, our final term of this academic year, is underway. The white tents used for outdoor classrooms and gatherings in the fall are going up again on our campus (tent reservations are available through the Room Reservations App on MyKnox; login required).

    I do want to remind our community to stay vigilant and continue to follow the protocols outlined in The Knox Together Pledge. Yesterday, Illinois Governor Pritzker indicated concern over very recent reversals in several positive trends, stating public health officials are monitoring to see whether the data indicate spreading COVID-19 variants or just a temporary situation. 

    Vaccine Update

    The Governor has now included higher education employees as a priority group for vaccination, starting this week. This expansion is another step toward returning to the face-to-face residential community that is so special at Knox. We strongly encourage any Knox community members who are eligible for a vaccine to make an appointment

    Also, we want to remind you that last week, the Governor announced that COVID-19 vaccinations will be expanded to all residents 16 and older outside of Chicago beginning Monday, April 12. We recommend that students take something with their College address on it just in case they are asked about a local address prior to receiving a vaccine.  

    For your reference, here are links to those offering vaccines in the area:

    Last week, the Governor announced a phased approach to reopening that will offer us more opportunities over time to gather in groups both inside and outside. We all eagerly anticipate these next stages, as long as the reversals reported yesterday are temporary, and we return to positive trends. 

    Parents and students have asked about COVID-19 vaccination requirements for Knox students. As long as public health guidance continues to support that it is safe and effective, as evidenced by FDA approval beyond emergency use, we anticipate that we will require our students to be vaccinated unless they have a medical, physical, or philosophical objection. We will follow legal and public health guidance. We do not anticipate implementing this requirement until the 2021-2022 academic year.

    Limited Spectator Capacity at Knox Athletic Outdoor Contests

    Beginning March 28, a limited number of spectators will be allowed to attend Knox College athletic outdoor contests for baseball, football, men’s and women’s golf, men’s and women’s soccer, softball, and track and field. Designated seating areas will be assigned for the Knox community (students, faculty and staff) and Prairie Fire student-athletes’ family members. No members of the general public will be admitted to athletics events at this time, and no visiting team spectators are allowed. Our spectator policies are contingent upon COVID-19 guidance and information provided by state and county public health officials. 

    Many Prairie Fire competitions on the Knox campus will be livestreamed to give our fans, families, and friends an opportunity to remain engaged and see our student-athletes in action. All competitions that are planned for livestreaming are already designated as such on the schedules on the Prairie Fire website. 

    For more details on spectator seating areas and expectations at Knox College sports events, please visit our Fan Zone. Check back frequently, as changes may occur at the NCAA, MWC, federal, state, and local levels. Please check for updates on game-day.

    Hope remains on the horizon if we all continue to do our part! Please stay safe and well, and continue to send your questions and ideas to together@knox.edu.

    TERESA L. AMOTT
    President

    March 18

    KNOX TOGETHER EMAIL - Week of March 15, 2021

    Dear Knox Community,

    As we finish our winter term and look forward to the spring, we want to provide a few brief but important updates to you. 

    Spectators at Spring Athletics Events

    The Midwest Conference (MWC) announced its redefined spectator policy on Thursday, March 10th. Each campus will be allowed to make spectator decisions based on its campus conditions and the state and local restrictions in effect. The MWC granted member schools the discretion to make these decisions due to the varying venue and facility situations on each campus and each institution’s ability to control access to its facilities and address the entire campus community’s overall safety. 

    We are hopeful that by early April, we will have the opportunity to open up our athletic events in a safe, limited manner. We are in constant touch with the local public health authorities and medical professionals and are confident that we will be able to accommodate limited spectators in the near future. 

    There are many moving parts to consider as we develop manageable options based on NCAA, Midwest Conference, state, and local requirements, as well as our facility configurations, capacity, and staff size, so please stay tuned for announcements about spectators.

    Vaccinations

    Illinois Governor Pritzker announced earlier today a plan for gradually reopening the state, and stated COVID-19 vaccinations will be expanded to all residents 16 and older outside of Chicago beginning April 12. Illinois is receiving increasing shipments of doses from the federal government. When 70% of Illinois residents 65 and over are vaccinated, capacity limits will be relaxed, (unless the downward trend in COVID-19 metrics reverses during a 28-day monitoring period). As of this morning, 58% of those 65 and  older had been vaccinated. As Knox has been guided by the Illinois capacity limits, these changes will offer us opportunities to gather -- masked and distanced in groups in groups larger than are currently permitted. 

    As vaccines become more available, we strongly encourage any Knox community members who are eligible for a vaccine to make an appointment. Depending upon the location, you may be asked to show proof that you are living in the area. We recommend that students take something with their College address on it just in case they are asked prior to receiving a vaccine.  

    Right now the vaccine clinics continue to be offered by pharmacies, hospitals, and the Knox County Health Department. Additionally, the state of Illinois is adding new statewide mass vaccine clinics every week. It is strongly advised that individuals register themselves, as there are questions specific to the registrant, such as potential for allergic reactions and use of blood thinners.

    We are providing you with a number of links to ensure you have the resources you need to determine eligibility and find a vaccination site.

    State and County Resource Links:

    Pharmacies:

    Students - Spring Break

    The three-day spring break is scheduled for Sunday, March 21 through Tuesday, March 23.  We recognize that this is a very short period of time between two intensive academic terms, and that many members of our community are feeling stress and burnout. We wish there were an opportunity for a longer break, but the short break allows us to complete the year on time while also protecting the community from transmission of the new variants which are circulating across the country. So, we ask you to stay focused on health and safety, and to please use this time to rest, recover and relax. Practice self-care and if you are feeling stressed, reach out to someone who can assist you.

    Thank you for all you have done during the past year to keep our campus safe. I am confident that together, we can all successfully complete this academic year. I hope you all take pride in knowing we all did our part to take care of our community during these unprecedented times.

    TERESA L. AMOTT
    President

    March 12

    Dear Knox Community,

    There has been some confusion and several questions on COVID testing times. Please view the information below for times and dates of testing. 

    Faculty and staff: 

    Knox College employees are able to access saliva testing through MySHIELDIllinois at Knox College. As a courtesy, the College is allowing any employee that feels ill, has been exposed, or would like to take part in COVID-19 testing to do so at no charge. 

    Please do not schedule a test outside of these time frames. The Shield Illinois website will allow you to schedule for any day and time of the week, even days that Knox College is not conducting testing. 

    You should refrain from eating, drinking, tooth brushing, mouth washing, and tobacco use for 1 hour before submitting your saliva sample. 

    Please feel free to contact Human Resources at hr@knox.edu or Health Services at health@knox.edu with any questions you may have.

    Students: 

    Students are required to test every other week, based on the first letter of their last name. Students should also test if they have symptoms of COVID-19 or have been exposed. Testing occurs in the T. Fleming Fieldhouse and the schedule is as follows: 

    Please do not schedule a test outside of these time frames. The Shield Illinois website will allow you to schedule for any day and time of the week, even days that Knox College is not conducting testing.

    Students should visit their MyShield portal to schedule their bi-weekly COVID test.  

    You should refrain from eating, drinking, tooth brushing, mouth washing, and tobacco use for 1 hour before submitting your saliva sample.

    March 11

    KNOX TOGETHER EMAIL - Week of March 8, 2021

    Dear Knox Community,

    This week marks one year of the world taking extraordinary measures to stem the spread of COVID-19. Reaching this significant milestone, we are all feeling hopeful as more and more vaccines are distributed and administered across the globe. This week’s email addresses questions about whether we plan to resume in-person learning and operations in the fall. It also includes some important reminders about ensuring we all do our part to preserve the health and safety of our campus community.

    Plans for Fall Term 2021 

    Many of you have asked whether we will resume normal operations starting Fall 2021. I want to let you know that it is our intention to fully return to our regular, in-person classroom and intercollegiate athletics environment starting with the Fall Term. 

    The residential character of our College, coupled with our human-powered educational delivery model, are our institution’s greatest strengths. We are committed to bringing both fully back for our students’ benefit as soon as conditions permit. 

    When we move back to normal operations, remote learning requests will be evaluated on a case-by-case basis, as they were in pre-pandemic times.  

    Students Returning to Campus for Spring Term

    Those of you who are not currently living on campus but are returning to campus housing for Spring Term should have received an email from Campus Life yesterday. The email covers the following important items: 

    If you did not receive this email, please contact Assistant Dean for Campus Life Jacob McLean at jrmclean@knox.edu. 

    Please Don’t Travel During Spring Break

    The three-day spring break is scheduled for March 21-23, and we are advising you to please refrain from traveling during this brief, three-day period. This will help to preserve the safety and wellbeing of our community, and it will prevent the potential spread of COVID-19, including its newer and more transmissible variants. If you have an essential reason to travel outside of Knox County during this period, please consult with Health Services in advance of your travel.

    If You’ve Been Vaccinated, You Still Must Wear a Mask on Campus

    Health officials are reporting that after you get vaccinated against COVID-19, you still need to practice the usual pandemic precautions, including continuing to wear a mask and maintaining six feet or more of distance from people outside your household. Here’s why:

    Vaccinated Employees - Use HealthCheck Through Remainder of Year

    We have received questions about whether employees who have been fully vaccinated and are past the two-week waiting period after their second shot should continue to use the HealthCheck app. Health Services has advised that everyone must continue to use HealthCheck through the remainder of the academic year. As research into the vaccines and immunity progresses and everyone has been offered the vaccine, we may be able to relax our precautions. 

    This pandemic year has upset our sense of the passage of time in so many ways, and we are only now starting to understand how much has changed and how much has been lost. Some of you have said that you are sorry that I had to spend the last year of my presidency coping with the pandemic, but I want you to know that I have never been more proud of Knox  because of all that we have done as a community to preserve one another’s health and safety. Thank you for your continued support and vigilance. 

    TERESA L. AMOTT
    President

    March 4

    KNOX TOGETHER EMAIL - Week of March 1, 2021

    Dear Knox Community,

    We have heard feedback from many of you that these emails are helpful -- but too long. Going forward, we will make every effort to keep them brief and informative. We are providing reminders about spring return and vaccines in this email.

    I want to again recognize the dedication of our students in keeping our campus healthy. You can see how we’re doing on our COVID-19 Testing Dashboard. 

    Spring Term Return and Protocols - Students and Parents

    Vaccine News for All

    Some key points to keep in mind:

    While the news continues to be hopeful and our future is indeed bright, we still have new COVID-19 variants out there to worry about. Please continue to follow safety protocols and the principles in the Knox Together Pledge.

    Thank you for reading and for your continued support for our efforts to keep the Knox community safe.

    TERESA L. AMOTT
    President

    February 25

    Dear Knox Community,

    Unlike some of the emails we have sent in recent months, this email shares some heartening and hopeful news with you. 

    As of last Friday, we wrapped up the second round of COVID-19 baseline testing with our students. During the two weeks of baseline testing, we conducted 1,589 tests and had 1 positive result, which means we had a 0.06% test positivity rate. Amazing! The low number of positive tests we had throughout our two rounds of baseline testing is a clear indication that all of our students remain committed to our Knox Together Pledge. I am so proud of the dedication our students have exhibited to ensure that our campus remains safe and healthy. 

    COVID Testing Changes for Students

    As a result of this impressive positivity rate, this past Monday, we started testing one half of the campus each week. Students have been assigned alternating weeks based on their last names (A through K during the week of February 22, L through Z during the week of March 1, and so on). Students should visit their MyShield portal and schedule a testing time that is convenient for them each week they are to test.

    Spring Term Return and Protocols

    Students not currently residing on campus but who plan to live on campus for the spring term should return on Sunday, March 21. Students will receive their first COVID test upon arrival and a second one approximately five days later. Students must quarantine in their rooms until they receive notice that their first test result is negative, and may not attend in-person classes or other group activities until receiving a second negative result. Returning students must be in close communication with their spring course instructors to make arrangements to participate in course activities during their quarantine.

    If you have not yet contacted Campus Life about your plans to return to campus housing for the spring term, please do so immediately by emailing campuslife@knox.edu. Additionally, if the March 21 return date is not feasible for you given your finals schedule, please notify Campus Life of this as well, and they will make arrangements to accommodate you.

    Finally, on February 7 you should have received an email from NO-REPLY@UILLINOIS.EDU to create an account to participate in our SHIELD Illinois COVID saliva testing. This email gave you instructions and an activation code to help you set up your account. Once you have done this, you will be directed to schedule a COVID test appointment. Please schedule your appointment for March 21 or for the alternative date Campus Life assigned you to arrive on campus if March 21 does not work for you. Please create your account now; the activation code expires in early March. If you cannot locate your email or if your activation code expires, please call SHIELD at 217-265-6059 to get a new one. 

    MWC Resuming Competition for Spring Sports

    The Midwest Conference (MWC) announced last Friday that it will resume competition for the spring sports of baseball, softball, men’s tennis, women’s tennis, men’s outdoor track & field and women’s outdoor track & field. Member institutions, based upon campus and local realities of the pandemic, retain ultimate authority over the decision whether or not to participate in intercollegiate athletics this spring. At this time, Knox College is optimistic that Prairie Fire student-athletes will participate in competition this spring under the MWC umbrella.

    Vaccine Update

    Vaccine information changes daily as the new administration seeks to ramp up the pace of vaccination ahead of greater transmission of the new variants. This week, the Associated Press is reporting that COVID-19 vaccine makers told the U.S. Congress to expect a big jump in the delivery of doses over the coming month, assuring that they will provide enough shots for most Americans to get vaccinated by summer. 

    In Illinois, vaccines continue to be distributed to county health departments, pharmacies and hospitals, and the state is currently deeming as eligible individuals who are 65+ and certain frontline workers. As of February 25, eligibility was expanded to include individuals under 65 with health conditions that put them at risk of severe COVID illness. From an education sector standpoint, the state continues to restrict eligibility to the K-12 education sector. We continue to monitor eligibility requirements and will notify our campus as soon as anything changes.

    The Knox County Health Department appointment links go live at 2:00 pm every Friday on their Facebook page and their website. You can also check out the Hy-Vee Pharmacy and Walgreens sites for vaccine availability. We know that some Knox retirees and employees who are 65+ have received  vaccinations through those sites, so keep checking. 

    Please continue to ask questions and send ideas and suggestions to together@knox.edu. Your feedback has been incredibly helpful in ensuring we are thorough in our planning and decision making. I continue to be so grateful and impressed by our students, faculty and staff, and their commitment to one another’s safety. And while this week brings us hopeful news, we must remain vigilant in ensuring our community of care stays as strong as it can be for the foreseeable future.

    TERESA L. AMOTT
    President

    February 20

    With a happy heart, I share with you the Midwest Conference (MWC) has opted to move forward with competition for spring sports under the MWC umbrella!

    The Midwest Conference (MWC) announced today that it will resume competition for the spring sports of baseball, softball, men’s tennis, women’s tennis, men’s outdoor track & field and women’s outdoor track & field. Member institutions, based upon campus and local realities of the pandemic, retain ultimate authority over the decision as to whether or not to participate in intercollegiate athletics this spring. 

    At this time, Knox College is optimistic that Prairie Fire student-athletes will be able to participate this spring under the MWC umbrella. 

    “We are thrilled that we have this opportunity to get our student-athletes back into MWC competition,” said Knox College Director of Athletics Daniella Irle. “This is a great day for our Fire family. While the seasons will not be normal, I know that our spring sport student-athletes are looking forward to championship competition after losing that opportunity last spring. As always, Knox College and the Midwest Conference are moving forward with COVID-19 protocols and the health of our student-athletes and staff in mind.”

    “Our student-athletes have been through so much in the last year and have had to adapt, improvise, and overcome,” said Knox College Head Baseball Coach Jami Isaacson. “This is a great day for Prairie Fire and MWC student-athletes because it means that all the work they have been putting in over the last year will come to fruition in MWC competition.”

    “It will feel good to get back on the field after only playing four games in the last 22 months,” added Knox College Head Softball Coach Erin Rutledge. “The team is very excited to show what they can do on the field of play. It is critical that our student-athletes are able to compete against someone outside of our own team.”

    MWC schools are allowed to engage in spring competition against non-league opponents as long as they adhere to the league’s COVID-19 return-to-play protocol and end competition against non-MWC institutions 15 days prior to the start of league play in each respective sport. MWC competition in most spring sports is expected to start between late March and mid-April and will conclude by mid-May. Conference schedules will be posted online in the coming weeks but are subject to change due to the current health circumstances.

    “It’s been nearly eleven months since our student-athletes have played against each other due to COVID-19,” said Ripon College President Zach Messitte, the MWC Executive Committee Chair. “While we are excited to resume league play later this spring, the Conference will continue to adhere to best practices in order to maximize the safety and health of our students, coaches, officials and spectators.”

    The MWC will closely monitor the COVID-19 environment on MWC campuses, local communities and at the regional and national levels as the ten member schools prepare for the upcoming spring season. At this time, no decision about spectators has been made so current guidance (no spectators at MWC events) remains in place and will be reviewed at a later date.

    The Prairie Fire men’s and women’s golf teams compete in the St. Louis Intercollegiate Athletic Conference (SLIAC). At this time, the SLIAC is committed to pursuing competition in the spring.

    DANIELLA J. IRLE
    Director of Athletics

    February 20

    Welcome back to winter term.

    As we return to in-person instruction on February 22, campus buildings will return to regular opening hours with a few additional requirements. 

    Please remember that classroom use follows comparatively strict Knox Together protocol during regular class times to allow for air recirculation in rooms between class meetings. Please use the Library, Science Commons, lounges, and other unscheduled spaces if you are looking for a study space during class times. Meeting spaces can be reserved through the online calendar.

    Departments and program offices may set policies to manage use of spaces, such as labs and studios, in their areas. Please pay attention to locally posted occupancy limits and usage guidelines, and don’t hesitate to seek clarification from the department chairs or office managers.

    CFA Music Practice Rooms are open, but students must reserve a time and room through the room reservation system (available on your my.knox portal, or by emailing Andy Crawford at acrawfor@knox.edu).

    Seymour Library and the Amott Science Commons will be open initially according to the following schedule. Updates will be posted.

    Seymour Library
    Sunday - Thursday: noon - 10:00 pm 
    Friday: noon - 6:00 pm
    Saturday: noon - 5:00 pm

    Amott Science Commons
    Sunday: noon - 10:00 pm
    Monday - Thursday: noon - 8:00 pm
    Friday: noon - 6:00 pm
    Saturday: noon - 5:00 pm

    Help Desk and Computer Lab Hours will be open and adhering to the schedule below.

    Help Desk
    Monday - Thursday 7:30 am - Midnight
    Friday 7:30 am - Midnight
    Saturday Noon - 6:00 pm
    Sunday Noon - 6:00 pm

    Cat/Stellyes Lab
    Monday - Thursday 8:00 am - Midnight
    Friday 8:00 am - 6:00 pm
    Saturday Noon - 6:00 pm
    Sunday Noon - Midnight

    Founders Lab
    Everyday 7:30 am - 2:00 am

    WAC Lab
    Monday - Thursday 8:00 am - Midnight
    Friday 8:00 am - 6:00 pm
    Saturday Noon - 6:00 pm
    Sunday Noon - Midnight

    GDH (Burkhardt) Lab
    Monday - Friday 8:00 am - 4:00 pm

    Your commitment to the Knox Together plan during the fall term allowed us to successfully complete the term. We are optimistic that, with your help, conditions will permit us to keep these spaces open for the remainder of the academic year.

    Michael A. Schneider
    Provost and Dean of the College

    February 18

    KNOX TOGETHER Email for February 18, 2021 - Commencement Updates for Knox Classes of 2021 and 2020

    Dear Knox Community,

    For this week’s email update, we are sharing two emails we sent this afternoon to the Knox Classes of 2021 and 2020 regarding Commencement planning. We wanted to be sure you were aware of these emails in the event that you receive or have any questions about the status of both Commencements.

    Email to the Knox Class of 2021

    Email to the Knox Class of 2020 

    As you can see, we are committed to providing both classes with meaningful celebrations, while balancing the need for campus and personal safety and wellbeing. We will continue to update you as our plans develop. In the meantime, if you have any questions or concerns, please email together@knox.edu. 

    TERESA L. AMOTT
    President

    February 11

    KNOX TOGETHER EMAIL - Week of February 8, 2021

    Dear Knox Community,

    It is wonderful to have our students coming back to campus this week. Their return -- even in the dead of winter -- is a glimmer of hope for the new normal. Thank you to our students and parents for following all arrival protocols, including testing and quarantine, and to our staff and faculty for ensuring our students have the support needed for a smooth transition back to campus. 

    While arriving back to campus is a joyous time for all, please continue to stay vigilant and adhere to the Knox Together Pledge; the safety and wellness of our campus depends upon you. 

    Commencement Decision Announcement Next Week

    In a previous email, we committed to February 15 as the date we would announce our decision regarding the Class of 2021 Commencement. There will be a slight delay in timing, so look for that commencement information arriving by Thursday, February 18.

    Vaccine Distribution Update

    Last week I shared an update on vaccine distribution in Illinois and locally. I’m sure that you will be as pleased as I am to hear that the federal government is stepping up distribution to the states. We anticipate that there will finally be more vaccination opportunities in Illinois in the coming weeks.

    Reminder - Sign up for SHIELD and HEALTHCHECK360

    By now, students, faculty, and staff should have received an emailed invitation to sign up for an account to participate in saliva testing. The email is from NO-REPLY@UILLINOIS.EDU. On February 15, students will receive an email from HEALTHCHECK360. This is the same symptom tracker program that the College used during fall term. You must re-register for the program, and please be sure to choose the time that the email or text comes to you (based on your schedule). 

    On-Campus Event Planning Policy 

    The Campus Meeting and Event Planning Guidelines remain the same as those from fall term. Anyone who is considering hosting a meeting or event must abide by the policy and guidelines, designed to build community while keeping us as safe as possible during the pandemic. Please be sure to review these guidelines before you begin your event planning. 

    Elective S/U Grading Due Date Changed 

    For the remainder of the academic year, the due date for electing S/U grading for a course has been changed to match the course withdrawal date in winter, spring, and summer terms. In winter, the due date for elective S/U grading is March 5.

    Students considering elective S/U grading for a course should consult their academic advisors during the upcoming advising and pre-enrollment period. All other rules and regulations for S/U grading remain unchanged. Elective S/U grading aims to encourage students to take courses outside of their major. We hope that this change for additional time to consider elective S/U grading will support students during this unusual year. 

    For any questions about this change, please contact the Registrar’s Office at registrar@knox.edu. 

    Alumni Achievement Awards

    I encourage you to tune in tomorrow, February 12, at 5:00 p.m. CT when Knox honors our six alumni achievement award winners who are meeting the moment in true Knox ways. From careers in medicine to international  economics, funding for the arts, popular television drama, and life-long learning, this year’s recipients, including two young alumni recipients, truly epitomize the value of a liberal arts education. 

    Looking Ahead

    I am heartened by the focus on vaccine production and distribution, the downward daily trends in the number of COVID-19 cases in our country as reported by the CDC, and the corresponding downward trend in Illinois. 

    However, we must continue to be mindful of the risks of spreading and contracting COVID-19, particularly with the CDC reporting on three emerging variants of the virus (with potential for more severe disease, spreading more easily, requiring different treatments, and/or a change in effectiveness of current vaccines). 

    To help prevent the spread of COVID-19 and its variants, infectious disease experts are recommending double masking -- a cloth mask over a surgical mask. A recent CDC study found that double masking offers substantially improved protection against transmission of and exposure to infectious aerosols, so please layer up!

    Let’s continue to work together to ensure we are keeping each other safe as we move forward to when we can put these trying pandemic times behind us. Thank you for your continued support.

    TERESA L. AMOTT
    President

    February 5

    Dear Colleagues,

    I know many of you are eager to receive the COVID-19 vaccinations and like many of us have found it difficult, and frustrating, to sort through the decentralized information that is out there. Here is what we know at this moment, but we also know that the information is changing daily as the new administration seeks to ramp up the pace of vaccination ahead of greater transmission of the new variants.

    At present, vaccines are being distributed by the federal government to states, which determine who is eligible, where vaccines can be administered, and how many vaccine doses are distributed week by week. 

    In Illinois, vaccines are currently being distributed to county health departments, pharmacies and hospitals, and the state is currently deeming as eligible individuals 65+ and certain frontline workers. We had hoped that higher education would be considered eligible frontline workers, but the state is restricting eligibility to the K-12 education sector. 

    Starting February 5, these sites in Galesburg are receiving vaccines on a weekly basis: Hy-Vee Pharmacy, Walgreens, OSF, Cottage Hospital, along with the Knox County Health Department which is setting up vaccine sites. OSF is prioritizing vaccines for their patients, and they are reaching out to patients on an individual basis. The volume of available vaccines is very sparse at this point, so we all have to be patient and check the websites for the participating sites often. The good news is that we do believe that more vaccines will become available each week.

    The Knox County Health Department appointment links will go live at 2 pm every Friday starting February 5th on their Facebook page and at their website. You can also check out the Hy-Vee Pharmacy and Walgreens sites for availability. We know that some Knox retirees and employees 65+ have been able to get vaccinations through those sites, so keep checking.

    If any of this information changes, we will try to provide links to the new info. I have also found that checking the Register-Mail and WGIL websites has been helpful.

    TERESA L. AMOTT
    President

    February 4

    KNOX TOGETHER UPDATE - Week of February 1, 2021

    Dear Knox Community,

    We are all eagerly awaiting the arrival of students on campus next week.

    Following the required student quarantine period, I’m looking forward to seeing all of you -- masked, physically distanced, and ready to continue your winter term studies -- bringing our campus to life. Today, I am sharing some important reminders with you as you begin your return to Knox. 

    Student COVID Testing and HealthCheck 360 

    All students will be tested twice upon their return to campus and will also be tested every other week for the remainder of the academic year. The test is free and is required for all students taking courses on the Knox campus. 

    Please watch your email for two important items. This week, you will receive an email from NO-REPLY@UILLINOIS.EDU to create an account to participate in saliva testing. This email will give you very specific instructions and an activation code to help you set up your account. Once you have set up your account, you will be directed to schedule a COVID test appointment. Please schedule your appointment on the day you were assigned by Campus Life to arrive on campus. The only testing times available for initial testing are Monday-Thursday 2/8-2/11, 9:00 am to 6:45 pm. 

    On February 15, you will receive an email from HEALTHCHECK360. This is the same symptom tracker program that the College used during fall term. You must re-register for the program, and please be sure to choose the time that the email or text comes to you (based on your schedule). 

    Move-in and Quarantine Safety Protocols 

    If you need assistance moving back into campus housing, you are limited to one move-in helper. Move-in helpers should enter the fieldhouse with you and will be screened for COVID symptoms. Additional guests are permitted to come to campus, but they cannot enter the residence halls. You and your guests must wear masks at all times when on campus except when in your private room or when outside and able to maintain at least six feet of physical distance. 

    Upon your return to campus, it is important that you quarantine in your room until you have received a negative test result. While we anticipate getting results within 24 hours, you should anticipate that your initial quarantine could last for up to 48 hours. Initial quarantine means that you are required to remain in your assigned room, except to use the restroom and pick up meals up to three times a day from dining services. You must wear a mask and maintain at least six feet of physical distance whenever you are outside of your own room (both indoors and outdoors). 

    After you receive a negative test result, you will participate in modified quarantine until Sunday, February 21. During this time, you can hang out in your own suite/house’s common area as long as you wear a mask and maintain at least six feet of physical distance. You can also get fresh air, walk around campus, engage in recreational activities, and visit with friends outdoors, while continuing to follow our safety protocols, including wearing a mask and maintaining six feet of physical distance. 

    You cannot travel during initial quarantine. However, you can travel within Knox County during modified quarantine as long as you wear a mask and practice appropriate physical distancing.

    All students are asked to participate in modified quarantine, even if they have been on campus for the first part of winter term. 

    Winter Term Classes 

    From midnight Friday, February 5 until midnight Saturday, February 13 is our “hard pause” in all courses. Academic work, including preparation for class meetings, resumes on Sunday, February 14. Class meetings resume remotely on Monday, February 15. Students will not have access to academic buildings, including the library, until the academic buildings formally reopen for in-person instruction on Monday, February 22. The only exception to this rule is a small number of cases for maintenance of labs and equipment. The Dean of the College will communicate directly with students who have received approval to access academic buildings in the first half of the winter term about access during the modified quarantine.

    Until the modified quarantine is complete, no group activities will be permitted in academic buildings. 

    Spring Term Advising and Pre-Enrollment Begins

    Advising and pre-enrollment for spring term courses begins on Monday, February 15 and continues until Friday, February 26. All students must meet with their academic advisors during this time to select courses for next term.

    Also, please contact Campus Life if your plans for living on campus for the spring term have changed. 

    Dining During Move-In and Testing/Quarantine Periods

    Knox Dining Services will offer modified service during the move in and testing period. All meals will be provided through the Hard Knox Café. Once the quarantine period has concluded, the Gizmo, Outpost, and Grab n’ Go will resume regular service hours.

    Mealtime hours during quarantine are below. Enter Hard Knox through the doors on the side with the gallery, and exit through the Campus Card office. Dine-in seating will not be available during this time.

    Monday through Sunday:

    Breakfast         7:30 am – 9:30 am

    Lunch               11:00 am – 2:00 pm

    Dinner              4:30 pm – 7:30 pm

    Menu choices will be posted in the following locations: on the dining services webpage, through an optional daily menu mail, on digital screens in the gallery, and at the service counters. To reduce wait times, two counters in Hard Knox will offer take-away food items, including two packaged hot entree choices, rice or potato, vegetables, sides, desserts, and canned or bottled beverages. A vegan meal option will also be available. 

    As with last Spring and Fall terms, any dietary or spiritual food needs can be communicated directly with Chef Joe; arrangements for requested accommodations will gladly be made on an individual basis. Dining inquiries can be directed to Doug Stenfeldt, Dining Services General Manager, at djstenfeldt@knox.edu, or Joseph Peterson, Executive Chef, at jdpeterson@knox.edu.  

    Postal Services During Move-In and Testing/Quarantine Periods

    Knox Postal Services will modify operations during the move-in and testing periods. Hours of operation from Monday, February 8 through Saturday, February 21 are:

    Monday through Friday:  10:00am to 4:00pm
    Saturday:                         10:00am to 11:00am

    You may pick up and drop off your packages and mail by proceeding to the service windows in the lower level of Seymour Union. Please do not access your PO box to retrieve mail. The staff at the service window will retrieve it for you. 

    There will be a postal services employee stationed in the hallway to monitor and limit the number of individuals queued to the service windows. We ask that you follow the instructions of this employee before proceeding to a service window. Also, please use the stairs to proceed to the lower level if possible, so that we may preserve use of the elevator for those who are unable to use the stairs. Once you have concluded your business, exit the area promptly.

    Sherrill Zaric, long time Director of Postal Services, retired from the College on January 25. Please direct any postal services queries to Russell Frakes, Interim Manager of Postal Services ( rffrakes@knox.edu).

    The Knox Together Pledge

    Please remember that adherence to the testing and quarantine protocols are core expectations of the Knox Together Pledge. Please take a moment to review and sign the Pledge if you have not already done so. And if you have already signed the pledge, please revisit it before returning to campus so you fully understand what we are requiring of you to support our campus safety and wellness. 

    Looking forward to seeing you very soon. Safe travels.

    TERESA L. AMOTT
    President

    January 28

    KNOX TOGETHER UPDATE - Week of January 25, 2021

    Dear Knox Community,

    Thank you to those of you who participated in our virtual forum yesterday. We appreciate your questions and ideas; they help us ensure we are keeping our campus as healthy and safe as possible. We are so looking forward to students returning to campus for winter term starting February 8! Our faculty and staff are working tirelessly to prepare an engaging educational experience. We are also looking forward to the next few months, when we hope to carefully ramp up our in-person learning as it becomes safer to do so.

    Important Health and Wellness Policies Update

    As we anticipate returning to campus, I encourage everyone to spend some time reviewing the Knox Together Pledge that we committed to at the start of the academic year. If you are new to Knox and have not yet signed the Pledge, you may do so here. 

    Additionally, I encourage you to refamiliarize yourself with Knox's COVID Health and Wellness Policies. We must take these policies seriously to keep ourselves and each other as safe as possible. The choices you make will impact not only your own health and safety, but also the health and safety of your friends, colleagues, and those who clean our suites and classrooms. 

    Because it is so important that we each do our part to minimize  the spread of COVID-19, the consequences for violating our community’s health and wellness policies are serious. Students who willfully disregard campus protocols regarding wearing masks, physical distancing, participating in large gatherings, and other critical public health restrictions will lose the privilege of living on campus and taking on-campus classes. Student organizations will lose College recognition and funding opportunities. Details about potential sanctions can be found here. All members of the campus community are empowered to remind each other about and request adherence to our COVID-19 health and wellness policies, and may report alleged violations here.

    I am proud that we were able to maintain low positivity rates on campus throughout the fall term and am truly optimistic that we will be able to continue that trend throughout the winter and spring. Let's all do our part to ensure a successful remainder of the academic year.

    CARES 2.0 Funding Update

    Knox is expected to receive $1,982,465 in federal funds from the Coronavirus Relief and Response Supplemental Appropriations Act (CRRSAA) within the next three to six weeks. The funds will again be allocated in two separate portions: One for students, and one for institutional relief. Our student portion will be the same amount as it was in the first CARES Act round of funding -- $664,035. We will again distribute the funds to students with the highest levels of demonstrated financial need. 

    We continue to review the guidance provided by the Department of Education so that we understand the restrictions regarding how we can spend the two funding allocations, and we will keep you informed.

    Faculty and Staff  - Phase 3 of Knox Together Plan on February 1

    Last week, we sent an email to faculty and staff about moving to our Knox Together Plan Phase 3 on February 1. The guidelines for Phase 3 are: 

    We realize departments may have different work arrangements and needs and will require different workplace modifications. Please work with your supervisor to address departmental and individual arrangements.

    Academic Building Opening Schedule Now Through February 22

    We have received a number of questions regarding access to academic buildings in the coming weeks. Most academic buildings will be open during the week of February 1-5 during regular work hours. During the “hard pause” break, students will not have any access to academic buildings, except for the few exceptional cases for maintenance of labs and equipment. 

    Until the modified quarantine is complete, no group activities will be permitted in academic buildings. 

    The Dean of the College will communicate directly with students who have received approval to access academic buildings in the first half of the winter term about access during the modified quarantine. Academic buildings will formally reopen at the end of the modified quarantine on Monday, February 22. 

    Common Topics from Yesterday’s Forum

    We have summarized our answers to some of the most common topics discussed at yesterday’s forum, below. We have also provided you with a link to the student and parent virtual forum for your reference, should you have missed the forum and want to view it.

    Vaccinations: We are doing all we can to facilitate vaccine distribution. We are in touch with the local health officials, who are in charge of allocating vaccine doses to entities authorized to distribute them. Locally, Hy-Vee Pharmacy, Cottage Hospital, OSF, and Walgreen’s are vaccinating those who qualify. Right now, those who are employed by the K-12 schools and those over 65 years of age are able to get vaccinated. There will be more information in the coming months, but as of now, we must wait.

    Regarding COVID-19 vaccination requirements for Knox students, as long as public health guidance continues to support that it is safe and effective, we anticipate that we will require our students to be vaccinated unless they have a medical, physical, or philosophical objection. We will follow legal and public health guidance. We do not anticipate implementing this requirement until the 2021-2022 academic year. 

    When students, faculty and staff will be back on campus: We all recognize that we are on a long arc that stretches incrementally in steps over the months ahead. We will slowly gain new comfort levels and learn more about the new vaccine and vaccination progress. There is no single milestone that will drive a full return to campus for all. Over time, we anticipate that the balance will shift to more and more in-person courses.  We are designing courses to be responsive to public health context and will continue to use social distancing and classroom capacities as we did in the fall. As we get into warmer weather, we will begin using our tents for classes, and will have more outdoor instruction.

    Commencement: We understand that commencement is a critical milestone in the lives of our students and their families, and members of our campus community. And we know that you are eager to hear how we are planning to celebrate that milestone.

    It is very difficult for us to look as far ahead as June, because we don’t know what public health conditions will be by that time. Many colleges are planning hybrid commencements and are offering a combination of live and virtual events. We are reviewing all options for both the Class of 2021 and the Class of 2020, and we will have an announcement about our preliminary plans in mid-February; we hope to have more guidance from public health authorities about travel and gathering size by that time. We currently have a team actively working on commencement planning and options, so please stay tuned.

    Protocols for student return for spring term: From an academic perspective, students need to be in communication with their instructors for spring term so that they know what is expected of them. We know there are a number of students who want to finish out the winter term remotely and return to campus for the spring term. 

    The return date for spring is March 24, 2021. Please contact Campus Life ( campuslife@knox.edu or 309-341-7527) to ensure that you have a housing assignment that meets your needs for the spring term.

    During the forum, we answered nearly 50 questions from participants. I encourage all of you to view the recording to learn more about our plans for the remainder of winter term. This will help ensure that you are apprised of our plans to keep our community safe while offering an engaging Knox experience. 

    Personally, I have appreciated the expressions of support and suggestions for improvement that I have received from you over the past months. I have been so impressed by our students, faculty and staff and their commitment to one another’s safety. I am confident that we will emerge stronger and wiser because of your commitment to our Knox community of care.

    TERESA L. AMOTT
    President

    January 22

    KNOX TOGETHER: Moving to Phase 3 on February 1

    Dear Knox Faculty and Staff,

    As you already know, Governor Pritzker announced on Monday, January 18 that our region (Region 2) will be moving to Tier 1 mitigation rules, further lifting restrictions because our region met the state’s COVID-19 metrics. With this development and through close consultation with public health experts, on February 1 we will move to our Knox Together Plan Phase 3. As a reminder, the guidelines for Phase 3 are:

    We realize departments may have different work arrangements and needs and will require different workplace modifications. Please work with your supervisor to address departmental and individual arrangements.

    As a reminder, during the week of January 4, we began implementation of our updated plan for testing faculty and staff. Everyone must be tested for COVID-19 prior to returning to campus. Please refer to the email dated December 17, 2020 for employee testing dates/times and location. 

    If you have recently traveled via public transportation or participated in a gathering with individuals outside of your household, you should not return to campus until you have received a negative COVID-19 test result. The ideal testing window is five to eight days after possible exposure. Please feel free to reach out to Human Resources or Health Services with any questions about testing options. 

    Please be assured that we will continue to keep you informed as we work together to navigate the continued uncertainties of this time, and will also closely monitor guidance from public health authorities, as we have done since the start of the pandemic. We appreciate your support as our plans to ensure our campus community remains healthy and safe continue to evolve with the pandemic. If you have any questions, send them to together@knox.edu.

    TERESA L. AMOTT
    President

    January 21

    KNOX TOGETHER UPDATE - Week of January 18, 2021

    Dear Knox Community,

    As you may have already heard, Governor Pritzker announced over the weekend that our region in Illinois (Region 2) has moved to Tier 1 mitigation rules, further lifting restrictions because our region met the state’s C OVID-19 metrics. While this is promising news, we need to continue to abide by our Knox Together Pledge to ensure our campus remains safe until the pandemic is under control.

    CARES 2.0 Funding Confirmed

    Last week, Knox received notification from the US Department of Education that we would be receiving a total of $1,982,465 from the Coronavirus Relief and Response Supplemental Appropriations Act (CRRSAA). This funding is a supplement to the CARES Act funding that we received last year. At this point, we know that the funds will again be allocated in two separate portions: one for students and one for institutional relief. Our student portion will be the same amount as it was in the first CARES Act round of funding -- $664,035. 

    We do not yet know when we can draw down the funding, but we anticipate that this will occur sometime in the next three to six weeks. We are continuing to review the guidance provided by the Department of Education so that we understand the restrictions regarding how we can spend the two funding allocations, and we will keep you informed.

    Answering Your Questions

    Following our announcement last week about students returning to campus starting on February 8, we received a few questions. A few of the most common ones are posted below, and we hope that our answers are helpful to you. Should you have further questions, please email together@knox.edu.

    Also, please remember that we are holding two virtual forums to answer any questions you may have about the return to campus, testing and safety protocols, and other issues related to our Knox Together plan. They will both be held on Wednesday, January 27. A faculty and staff forum will take place at 12:00 PM Central Time, and a forum for family and students will be held at 7:00 PM Central Time.  An email will be sent early next week with further details and links to the virtual forums.

    All students will again be tested twice upon their return to campus, and  all students will be tested every other week for the remainder of the academic year. The test administered will be the Shield Illinois Saliva Test, a PCR test created and used by the University of Illinois system, and also used by many other educational institutions in Illinois and other states. The test is free, and it is required for all students who are taking courses on the Knox campus. 

    Knox College Health Services is in constant communication with local officials to determine when the vaccine will be available for the Knox College community, and we will continue to share updates with you.

    At the present time, vaccine allotments are being distributed to county health departments. Each county in Illinois is prioritizing available vaccines according to the guidance of local health experts. At this time we don’t have any additional information, but we will keep you informed. 

    Yes, organizations will be allowed to meet. We understand that these meetings and events play a key role in creating a welcoming, vibrant campus community. All meetings and events must follow our COVID protocols for masks and physical distancing as detailed in the updated guidelines on the Knox Together site.

    All in-person and remote student organization events, with the exception of regular meetings, must be registered with the Campus Life Office. In addition, all in-person event registrations must include a formal safety plan that outlines how the event organizers will ensure compliance with the College’s COVID protocols. 

    We are requiring the same protocols as fall term. We are continuing the rigorous cleaning and sanitation processes for all classrooms and other academic spaces, residence halls and meeting spaces.

    All participants attending in-person classes must wear masks or face coverings at all times. Physical distancing will require that classes meet in smaller subgroups, interactions with faculty and peers will occur both in virtual and in-person settings. Classroom meeting schedules are set to support student engagement while ensuring classrooms have adequate time for air recirculation between meetings. Classroom occupancies are clearly marked. Courses that rely heavily on classroom, lab and studio spaces have been reenvisioned so that physical distancing and cleaning protocols can be observed. 

    Most courses will operate in hybrid modes, with a combination of in-person and remote components to serve students who are on campus as well as those learning from home. We will slowly and intentionally add more in-person components consistent with our data from testing and in response to the availability of vaccinations for our community. In the interests of health and wellness of the entire community, we will follow a careful and deliberate process. 

    If you were planning to live in the dorm, please contact campuslife@knox.edu, or 309-341-7527. Please also notify Tim Foster, Associate Dean of the College: tfoster@knox.edu or 309-341-7214. Share this information with your instructors and academic advisor. Some courses have significant on-campus components in the second half of the term, which you should clarify with your instructors.

    Contact the Campus Life office at campuslife@knox.edu / 309-341-7527. 

    I hope that like me, you are seeing progress and hope on the horizon. While we continue to manage through these uncertain times, we are doing all we can to provide certainty to our Knox College community. Faculty and staff are working very hard to deliver the quality education our students want and deserve, and as we update any processes or protocols, we will let you know as soon as possible. 

    Thank you for your questions; keep them coming. I’m looking forward to seeing you soon.

    Take care,

    TERESA L. AMOTT
    President

    January 14

    KNOX TOGETHER UPDATE - Week of January 11, 2021

    Dear Knox Community,

    Following a significant amount of research and consultation with public health authorities, we have determined that students can begin returning to campus starting Monday, February 8. Students received a  communication from the Campus Life Office in November with their assigned return to campus/testing date and time. Campus Life will also resend this email for your convenience by the end of next week. If you have any questions about your return to campus, please contact campuslife@knox.edu.

    Why we made this decision

    Governor Pritzker announced that Friday, our region (Region 2) will be moving to Tier 2 mitigation rules, relaxing restrictions from Tier 3. The governor indicated in a statement that Illinois did not experience the post-Thanksgiving uptick in COVID cases that plagued most of the rest of the country. While closely watching the post-holiday positivity rates, his administration is cautiously optimistic. 

    We are ever mindful of the consequences of the pandemic for our educational mission. Numerous studies and news articles -- and our own experiences and internal data -- have shown that prolonged isolation is stressful for all of us. This impact is especially profound for our students, who have selected a residential college experience as the best place for their learning. The remote instructional environment has allowed us to keep moving forward while protecting the health of the community during this stage of the pandemic. At the same time, we know that a return to campus is necessary to provide the full range of human-powered, engaging experiences that our students have come to expect from Knox College.

    We also learned a great deal about mitigating the virus on our campus during the fall term and have developed an even stronger plan to keep our campus healthy. Our plan includes a new more comprehensive and less-invasive testing regimen combined with an updated quarantine strategy. Many colleges in our peer group are implementing similar plans, and when we look at ours in comparison to others, we are confident that our enhanced Knox Together plan is the right one for our community. 

    Virtual forums to answer your questions

    We will host two virtual forums to answer any questions you may have about the return to campus, testing and safety protocols, and other questions related to our Knox Together plan. They will both be held on Wednesday, January 27. A faculty and staff forum will take place at 12:00 PM Central Time, and a forum for family and students will be held at 7:00 PM Central Time. 

    Stay tuned for further details and links to the virtual forums.

    Vaccine rollout and information

    There is hope on the horizon for a faster vaccine rollout. This week, the CDC communicated new vaccine priorities for people 65 years of age and older and those with preexisting conditions that enhance their vulnerability to severe COVID-19 disease. More pharmacies and community centers around the country are being authorized to administer vaccines. Governor Pritzker is also expected to soon announce a timeline for the next phase of the vaccine rollout. 

    Knox College Health Services is in constant communication with local officials to determine when vaccines will be available for the Knox College community, and we will continue to share any updates or changes with you. Each county in Illinois is going to prioritize available vaccines to residents, according to the guidance of local health experts.

    Important improvements to testing protocols 

    We tested all students for COVID-19 twice upon arrival to campus in the fall term, with ongoing surveillance testing throughout the term. While this was successful, we are implementing a much more comprehensive testing program with a less-invasive and equally accurate test for winter and spring terms -- one that delivers results faster and only requires saliva from those being tested. All students will again be tested twice upon their return to campus. Additionally, all students will be tested every other week during both terms. 

    The test administered will be the Shield Illinois Saliva Test, created and used by the University of Illinois system, and also used by many other educational institutions in Illinois and other states. 

    The Shield Illinois Saliva Test will also be available to faculty and staff, who may test for symptoms or concern of exposure.

    An employee or student who develops symptoms or has a concerning exposure will be asked to test as soon as possible. Faster testing and quarantine will help us preserve the health and well-being of our campus community.

    Stay tuned for emails with further details regarding the upcoming terms’ testing days and times.  

    What students need to do upon returning to campus

    Upon your return to campus, please remember that you can transmit the disease to others even if you are exhibiting no symptoms, so for the health of our community, it is important that you quarantine in your room until you have received a negative test result. While we anticipate getting results within 24 hours, you should anticipate that your initial quarantine could last for up to 48 hours. Initial quarantine means that you are required to remain in your assigned room, except to use the restroom and pick up meals three times a day from dining services. You must wear a mask and maintain at least six feet of physical distance whenever you are outside of your own room (both indoors and outdoors). 

    After you receive a negative test result, you will participate in modified quarantine until Sunday, February 21. Modified quarantine means that you can hang out in your own suite/house’s common area as long as you wear a mask and maintain at least six feet of physical distance. You can also get fresh air, walk around campus, engage in recreational activities, and visit with friends outdoors, while continuing to follow our safety protocols, including wearing a mask and maintaining six feet of physical distance. All students are asked to participate in modified quarantine, even if they have been on campus for the first part of winter term. 

    Questions and Answers

    Here are answers to some questions we expect you might have right away; please also remember to visit the Knox Together website for answers to other questions. You can also email together@knox.edu and attend one of the virtual forums we are holding on Wednesday, January 27 if you have additional questions.

    How does this impact quarantine protocols for those arriving from abroad?

    Students arriving from abroad will follow the same quarantine plan as those arriving from within the United States. If a student shows any COVID-related symptoms, their quarantine period may be extended.

    Does this quarantine plan apply to students who stayed on campus during winter break?

    Students who lived on campus during winter break will have a COVID-19 test but do not need to quarantine in their rooms while awaiting test results. However, they must participate in modified quarantine until February 21.

    When will staff be returning to campus?

    Essential employees providing direct services to students, such as dining services, will need to be on campus when students return. Those not providing direct services will continue to work remotely until a vaccine becomes widely available to members of our community.

    What if my roommate and I have different arrival dates, so our initial quarantines end on different days?

    If Roommate A’s initial quarantine ends before Roommate B’s, Roommate A may move into the modified quarantine phase, moving about campus while adhering to mask and physical distance policies. However, no in-person classes or student activities will be allowed until all students have received their first test results.

    What types of meals will be available during quarantine?

    Knox Dining Services will offer modified service during the move in and testing period. All meals will be provided through the Hard Knox Café.  Once the testing and quarantine period has concluded, The Gizmo, The Outpost, and Grab n’ Go will resume regular service hours.

    Mealtime hours during the move in and testing period are below. Enter Hard Knox through the doors on the side with the gallery, and exit through the Campus Card office. Dine-in seating will not be available during this time.

    Monday through Sunday:

    Breakfast         7:30 – 9:30

    Lunch               11:00 – 2:00

    Dinner              4:30 – 7:30

    Menu choices will be posted in the following locations: On the dining services webpage, through an optional daily menu mail, on digital screens in the gallery, and at the service counters. To reduce wait times, two counters in Hard Knox will offer take away food items, including two packaged hot entrée choices, rice or potato, vegetables, sides, desserts, and canned or bottled beverages, as well as a vegan meal option. 

    As with last Spring and Fall terms, any dietary or spiritual food needs can be communicated directly with Chef Joe, and we will make arrangements for accommodations on an individual basis.

    Dining inquiries can be directed to Doug Stenfeldt, Dining Services General Manager, at djstenfeldt@knox.edu, or Joseph Peterson, Executive Chef, at jdpeterson@knox.edu.  

    How will I get my mail/packages/textbooks during quarantine?

    We are working on the details of how this will happen, but we will make sure you can access essential textbooks and mail when you return to campus.

    Can I work in my on-campus job during quarantine?

    You can work in your on-campus job during initial quarantine if you can do so remotely. Exceptions may be made for students who lived on campus during the first part of winter term.

    Can I go off campus during quarantine?

    Not during initial quarantine. You can travel within Knox County during modified quarantine, as long as you wear a mask and practice appropriate physical distancing.

    We know this is asking a lot of you, and we encourage you and your family to regard this as a short-term sacrifice—a collective community effort that will give us the very best chance at continuing in-person instruction for the duration of the term.  

    Please remember that adherence to the quarantine protocol is a core expectation of the Knox Together Pledge. I hope you will take a moment to review and sign the Pledge if you have not already done so. You will need to be logged in to your Google account with your Knox email address and password to access the Pledge.

    Fifth Year Guarantee reminder

    We also want to remind you of our “Fifth Year for Free Guarantee.” If you are enrolled at Knox full-time for the entire 2020-21 academic year, you can return to campus for up to one additional year of study, tuition-free—and take part in more of the opportunities you’ve been looking forward to. If you’re interested in pursuing this option, please work with your academic advisor to determine appropriate course selections. Student-athletes will need to consult with the athletics department about eligibility requirements.

    Hope on the horizon

    The health and wellness of our campus community continues to be our top priority. Faculty and staff are working very hard to deliver the quality education our students want and deserve. There continue to be many aspects of our environment that we cannot control, but we have learned from the fall term, and there is hope on the horizon for the warmer weather months. In the meantime, we need to remain as flexible, nimble, and resourceful as ever, as our country continues its efforts to mitigate the pandemic. 

    Looking forward to seeing you next month!

    TERESA L. AMOTT
    President

    January 7

    KNOX TOGETHER UPDATE - Week of January 4, 2021

    Dear Knox Community,

    Happy New Year! I hope you all had a peaceful, restful and safe holiday season. I also want to extend a warm welcome back to our faculty, staff, and students as we start our winter term virtually. 

    The rollout of the vaccines in Illinois has begun with frontline health workers. We are in touch with the public health authorities and are awaiting information on the sequence of vaccinations. At present, we do not know where higher education will fall in the priorities, but we will share any information we receive as soon as possible.

    We will continue our safety protocols for the foreseeable future, however, as it may take more time than expected for us all to receive the vaccines. Illinois Governor Pritzker’s mitigation plans for our health region (we’re currently at Tier 3) remain in effect, as well.

    Parents and Students - What to do now

    Students will need to complete an online check-in by this Friday, January 8 by logging in to my.knox.edu. Online check-in is very important to the Registrar, Student Financial Services, and other offices needing to know who is enrolled this term. Students will not be able to access any Knox apps or student schedules until the Online Check-in process is completed.

    Our current plan is still to have students return to campus the week of February 8. We have identified next Friday, January 15 as the date by which we will advise you of any necessary modifications to this timeline. If we need to consider alternative options, we will look to guidance from national, state and local public health authorities.

    Faculty and Staff - What to do now

    Please continue to plan for students returning to campus starting February 8. Dean Schneider’s separate report to faculty on December 11 addresses details of the calendar and contingency plans for winter term.

    This week, we began implementation of our updated plan for testing faculty and staff. As you know, everyone must be tested for COVID-19 prior to returning to campus, just as we did in the fall. Please refer to this email from Health Services about return to work testing processes. If you have questions about testing, please contact Health Services.

    If you traveled via public transportation or participated in a gathering with individuals outside of your household during the holiday break, you should not return to campus until you have quarantined at home for 14 days or received a negative COVID-19 test result. You can access testing beyond what Health Services is offering by contacting the Knox County Health Department at (309) 344-2225, or by contacting your primary care provider. The ideal testing window is five to eight days after possible exposure. Please feel free to reach out to Human Resources or Health Services with any questions about testing options. 

    Similarly, students engaging in on-campus work or research activities in your areas must contact Health Services to arrange for a COVID-19 test immediately following any travel or holiday gatherings, and quarantine until they receive a negative test result. 

    Coronavirus Response and Relief, Supplemental Appropriations Act 

    Recently, we were gratified to learn that institutions of higher education will receive some funding from the new Supplemental Appropriations Act recently signed by President Trump. At this time, we do not know how much we will receive, whether there will be restrictions on the use of the funds, or how soon we will receive funds. We will communicate any updates to you when we receive additional information.

    We encourage you to visit the Knox Together website, and follow our social media channels for campus updates. Thank you for your support and care for our campus community as we navigate these uncharted waters together.

    TERESA L. AMOTT
    President

    December 17

    KNOX TOGETHER UPDATE - Week of December 14

    Dear Knox Community,

    I know we are all happy to see some hope on the horizon with the first deliveries of a highly effective COVID-19 vaccine this week. We will still need to practice our safety protocols for the foreseeable future, however, as it will be some time before we can all receive the vaccines. 

    You will likely find some of the content in this email to be similar to the content in last week’s communication, but it is important information that will keep our community updated and safe; that is why we are sending it yet again this week.

    Return to Work Testing for Faculty and Staff

    We have updated our plan for testing faculty and staff starting on Monday, January 4.  Everyone will need to be tested for COVID-19 prior to returning to campus after the holidays, just as we did in the fall. You recently received an email from Health Services about return to work testing processes. If you have any questions about testing, please contact Health Services.

    Travel Guidance

    Additionally, we ask that you be especially vigilant about your safety and health over the coming holidays. If your holiday break plans include traveling via public transportation or participating in a gathering with individuals outside of your household, you should not return to campus until you have quarantined at home for 14 days or received a negative COVID-19 test result. You can access testing by contacting the Knox County Health Department at (309) 344-2225 or by contacting your primary care provider. The ideal testing window is five to eight days after possible exposure. Please feel free to reach out to Human Resources or Health Services with any questions about testing options. 

    Similarly, students engaging in on-campus work or research activities in your areas must contact Health Services to arrange for a COVID-19 test immediately following any travel or holiday gatherings, and quarantine until they receive a negative test result. 

    Plan for Students Return to Campus

    Our current plan is still to have students return to campus the week of February 8. We have identified Friday, January 15 as the date by which we will advise you of any necessary modifications to this timeline. If we need to consider modification options, we will look to guidance from national, state and local public health authorities.

    Stay in the Know About Knox Together 

    Visit the Knox Together website, and follow our social media channels for campus updates and news about Knox students and our extended Knox community. Check your email for these Knox Together Updates.

    Parents and Students - What to do now

    Students will need to prepare for the remote start of the winter term on Monday, January 4, continue to plan for a return to campus the week of February 8, and remember that we will make and communicate a firm decision on January 15 about any plan modifications.

    Faculty and Staff - What to do now

    Please continue to plan for students returning to campus starting February 8. Dean Schneider’s separate report to faculty on December 11 addresses details of the calendar and contingency plans for winter term.

    We also ask that you follow Illinois Governor Pritzker’s mitigation plans for our health region (we’re currently at Tier 3). Watch for the email on January 15 announcing any change in plans for the winter term.  

    We wish you all a happy holiday season and ask that you also stay safe and practice appropriate safety protocols. The safety of our campus community depends on how each one of us celebrates the holidays. Thank you for your support and care for our campus community as we continue to adjust to the unpredictable nature of the pandemic.

    TERESA L. AMOTT
    President

    December 17

    Dear Knox Community:

    As we look ahead to returning safely after the break, we are asking that each faculty and staff member be tested for COVID prior to resuming work on campus. Health Services will be administering COVID-19 testing to all faculty and staff. There is no cost to you for this testing. 

    Testing will be offered at the T. Fleming Fieldhouse on the following dates and times:

    You may choose the date and time of your testing. Please select the date closest to when you plan to return to work on campus, keeping in mind that test results take 2-4 days. In order to assist Health Services to plan staffing and supplies, please indicate your preferred test date by clicking here. Test results will be sent to you via email from Health Services. 

    We realize that some of you are essential workers on campus and, therefore, will be returning on or before January 4 (or maybe you never stopped working). In this case, you should plan to test on January 4 or as soon as your schedule allows. There is no quarantine required of employees during the time that they are awaiting test results. We do ask that you follow all usual hand hygiene, physical distancing, and masking protocols. In addition, stay home if you are sick. 

    We look forward to seeing you in January. Best wishes from Health Services!

    Abby A. Putnam MS, NP-C
    Knox College Health Services

    December 10

    KNOX TOGETHER UPDATE - Week of December 7

    Dear Knox Community,

    As we get closer to the holidays, we want to remind you of a few items from last week’s email.

    Plan for Returning to Campus to be Finalized by January 15

    Our current plan is still to have students return to campus the week of February 8. 

    However, with the potential for increased transmission during the holidays, a vaccine rollout plan that may shift frequently, and changing guidance from health officials about the safety of travel, we have identified Friday, January 15 as the date by which we will advise you of any necessary modifications to this timeline. As we consider modification options, we will look to guidance from national, state and local public health authorities.

    For Students and Parents: What to do now

    Please enjoy your holiday season and stay safe, wearing your masks, practicing physical distancing, and quarantining after travel or gatherings that may put you at risk for exposure. Avoid indoor venues that may attract crowds, and if you celebrate with others, try to do it in groups of 10 or fewer. 

    Visit the Knox Together website, and follow our social media channels for campus updates and news about Knox students and our extended Knox community. Check your email for these Knox Together Updates.

    Prepare for the remote start of the winter term on Monday, January 4, continue to plan for a return to campus the week of February 8, and remember that we will make and communicate a firm decision on January 15 about any plan modifications.

    For Faculty and Staff - What to do now

    We wish you a happy holiday season and ask that you also stay safe and practice appropriate safety protocols. The safety of our campus community depends on how each one of us celebrates the holidays.

    Faculty, please continue to plan for students returning to campus starting February 8. Dean Schneider will share a separate communication regarding winter term preparations.

    Staff, please continue to follow Governor Pritzker’s mitigation plans for our health region (we’re currently at Tier 3). Watch for the email on January 15 announcing any change in plans for the winter term.  

    We thank you for your continued resilience and flexibility as we adjust to the unpredictable nature of the pandemic. The coming winter term will likely require that we continue to observe our COVID-19 practices, and yet, there is certainly hope ahead for all of us in 2021. May your holidays be safe, peaceful, and enjoyable.

    TERESA L. AMOTT
    President

    December 3

    KNOX TOGETHER UPDATE - Week of November 30

    Dear Knox Community,

    As we enter winter break and begin preparing for the remainder of the academic year, we want to share recent news from The Midwest Conference, provide information about a decision date for any potential modifications to the current plan for students to return to campus the week of February 8, and update you on our Knox together communications.

    The Midwest Conference Announces Plan for Fall and Winter Sports

    The Midwest Conference (MWC) Presidents Council announced today that it would not sponsor league competition, including championships, for fall and winter sports during the 2020-2021 academic year. The decision was unanimous and covers men’s and women’s basketball, men’s and women’s cross country, football, men’s and women’s soccer, men’s and women’s swimming & diving, men’s and women’s indoor track & field, and volleyball. The recent surge in positive COVID-19 cases, both regionally and nationally, the resulting impact on academic calendars, and the continued uncertainty surrounding the pandemic were all factors in the decision not to play a winter athletic schedule. 

    We know that this is a very disappointing day for our fall and winter sport student-athletes, but they should not be without hope. As we did in the fall, we will keep moving forward to reimagine athletics seasons to ensure our student-athletes have the most robust experience possible this year. The Prairie Fire Athletics Department will provide athletics-centric training to fall and winter student-athletes when they return to campus. Our Prairie Fire student-athletes and coaches will continue to adapt and adjust as we navigate the COVID-19 landscape together, keeping in mind that the health and well-being of our student-athletes is our number one priority. Fall and winter student-athletes will receive more detailed information from the Director of Athletics and head coaches in the weeks ahead.

    Decision Date for Returning to Campus (or not)

    As you know, there is much uncertainty surrounding the pandemic, including the potential for increased transmission during the holidays, a vaccine rollout that is still in the early planning stages, and guidance from federal, state and local health officials about the safety of travel. Our current plan is still to have students return to campus the week of February 8. Nonetheless, given all of the unknowns, we have identified Friday, January 15 as the date by which we will advise all of you of any necessary modifications to this timeline, including the possibility of completing the entire winter term remotely. As we consider modifications, we will look to guidance from national, state and local public health authorities.

    Regular Communications

    With this email, we will begin a regular weekly cadence of communication to you, every Thursday with the exception of Christmas Eve and New Year’s Eve. 

    We will also send special, singular emails as needed to communicate important and urgent news. 

    Prior to returning to campus, students and their parents will also receive emails regarding health protocols to follow once students are back at Knox.  

    For Students and Parents: What to do now

    Please enjoy your holiday season and stay safe, wearing your masks, practicing physical distancing, and quarantining after travel or gathering that may put you at risk for exposure. Avoid indoor venues that may attract crowds, and if you celebrate with others, try to do it in groups of 10 or less. 

    Check the Knox Together website, and be sure to follow our social media channels for updates on what’s happening on campus, and other news about Knox students and our extended Knox community. Check your email regularly for these Knox Together Updates.

    Be prepared for the remote start of the winter term on Monday, January 4, continue to plan for a return to campus the week of February 8, and remember that we will make a firm decision by January 15 about any changes to the current plan.

    For Faculty and Staff - What to do now

    We wish you a happy holiday season and ask that you also stay safe and practice appropriate safety protocols. 

    For Faculty, please continue to plan for the students’ returning to campus starting February 8. You will also want to develop a contingency plan, should the decision on January 15 be that winter term remains remote

    Staff, please continue to follow Governor Pritzker’s mitigation plans for our health region (we’re currently at Tier 3). Watch for the email on January 15 announcing any change in plans for the winter term.  

    Thank you for your continued support and patience as we navigate the rough waters of these unprecedented times.

    TERESA L. AMOTT
    President

    December 3

    Midwest Conference Announces Plans for Fall and Winter Sports in 2020–2021

    November 12

    Dear Colleagues:

    Many of you have asked about the status of our campus after our fall term ends on November 30. As you may recall, in response to rising COVID-19 numbers in our Health Region, Governor Pritzker recently imposed enhanced mitigation measures across the state. Public health officials nationwide are also expressing great concern about the potential for virus transmission during winter indoor gatherings, especially around the holiday season.

    To ensure the health and safety of our campus community during an especially vulnerable time, we will return to Phase 1 of our three-phase plan for reopening the campus on Monday, November 30. Phase 1 encourages remote work for most employees and allows up to 25% of employees to work on campus, following physical distancing, mask wearing, and additional safety protocols. Please speak with your supervisor about any needs to de-densify your work area to ensure compliance with Phase 1 guidelines.

    If your holiday break plans include traveling via public transportation or participating in a gathering with individuals outside of your household, you should not return to campus until you have quarantined at home for 14 days or received a negative COVID-19 test result. You can access testing by contacting the Knox County Health Department at (309) 344-2225 or by contacting your primary care provider. The ideal testing window is five to eight days after possible exposure. Please feel free to reach out to Human Resources or Health Services with any questions about testing options. 

    Similarly, students engaging in on-campus work or research activities in your areas must contact Health Services to arrange for a COVID-19 test immediately following any travel or holiday gatherings, and quarantine until they receive a negative test result. Students who have applied for on-campus housing should have been notified of their approval to engage in on-campus activities. Any students not living on campus but wishing to engage in on-campus academic activities during the winter break or during the remote portion of winter term must apply to the Dean of the College through this form. 

    For safety purposes, we are also implementing a modified lock-down of campus buildings. The following buildings will remain open to campus community members only during the break, and will follow our normal business hours of 8:00 a.m. to 4:30 p.m.:

    The E&L Andrew Fitness Center and outdoor athletics facilities will be available for current on-campus students, faculty, and staff, and will require following physical distance and mask protocols. The outdoor soccer, basketball, track, and tennis facilities will be open. The Memorial Gym, T. Fleming Fieldhouse, and Frank M. Lay Pool will be closed. The Fitness Center hours (as of November 23) will be Monday through Friday 1:00 to 3:00 p.m. and 4:00 to 6:00 p.m., and Saturday 9:00 a.m. to 12:00 p.m. The Center will be closed on Sundays. 

    We appreciate your support as our plans to ensure our campus community remains healthy and safe continue to evolve with the pandemic. If you have any questions, feel free to send them to together@knox.edu. Thanks to you all for your patience as we stand Together at Knox, and please accept my best wishes for a safe, relaxing, and enjoyable holiday season.

    TERESA L. AMOTT
    President

    November 4

    Dear Knox Community,

    On Sunday, November 1, Illinois Governor Pritzker announced enhanced COVID-19 mitigations for our part of the state because our region, one of 11 healthcare regions established in Illinois, has had a COVID positivity rate of more than 8 percent for three consecutive days. 

    The enhanced mitigations, effective today, include limiting social gatherings to no more than 25 people. Although the mandate states that the mitigations do not apply to schools, Knox College will voluntarily adhere to this limit, both indoors and outdoors. Supervised meetings of classes, athletic teams, etc. will continue to be governed by existing protocols. Please remember that our health and wellness policies apply both on and off campus.

    It has been several months since the pandemic became an unwelcome part of our lives. A colleague recently mentioned his desire to see COVID-19 “in the rearview mirror,” and I certainly share that desire. I want to thank each and every one of you for observing our health protocols—wearing masks, remaining physically distant, washing hands frequently, and, above all, having respect for one another as we work to protect the health of our community. As a result of your efforts, our campus positivity rate remains very low. As the pandemic evolves, we will continue to follow state and local guidance to keep our campus community safe.

    TERESA L. AMOTT
    President

    October 28

    With only a few weeks left in Fall Term, I want to celebrate all of your efforts to adhere to the health and wellness policies regarding masks, physical distancing, and other public health measures. It has not been easy, but we are all learning and adapting together.  Your individual efforts have made a difference in our community. Thank you!

    Some of you have asked for clarification about hosting and attending gatherings off campus at Knox student apartments/houses. I want to remind everyone that health and wellness policies apply both on and off campus. Here are a few specific reminders about life off campus:

    There are serious consequences which are outlined in the accountability rubric  for violations of these policies. Specifically, attending an unauthorized party or gathering on or off campus may result in loss of privilege to live/learn on campus, and hosting an unauthorized party or gathering on or off campus either as an individual or as part of a student organization may result in suspension. 

    I share this information because I know you want to make good choices both on and off campus to help protect the students, faculty and staff you come into contact with.

    Deb Southern
    Assistant Vice President and Dean of Students

    October 2

    Dear Knox Community:

    I write to share with you information on our plans for the remainder of the academic year. As you know, we launched our fall term on September 14 and made the transition to in-person and hybrid instruction on September 21. This was made possible by enormous care and discipline by our entire Knox community—students, faculty and staff—to sustain our educational mission at Knox under highly unusual circumstances. We applaud these efforts to embrace the new ways of working and living together on campus while staying connected with the members of our community learning and working remotely.

    Because of the community response, we remain optimistic that we can complete the current academic term in ways that safeguard health while supporting rich in-person and hybrid educational opportunities. At the same time, we have all been hearing strong words of caution from leading public health experts regarding the future course of the pandemic as we approach the colder months and the typical flu season that accompanies our move indoors. To help to safeguard our community, and especially our most vulnerable members, we believe it is essential that we adapt our academic schedule in response to this guidance. Below we describe the various measures we will take to navigate this complex health landscape with ensuring the delivery of the Knox educational program.

    Schedule for Winter and Spring Terms

    Winter and spring terms will unfold largely according to our traditional academic calendar. winter term courses will begin on January 4, 2021, and Commencement is still slated for June 6, 2021. However, within those bookends, we will make changes to the dates students arrive back on campus after the long winter break.

    We will begin all winter term classes in a remote environment for the first half of the term, and students will not begin returning to campus until the week of February 8, 2021. We will pause instruction during a one-week midterm break (February 8-12) to allow students to transition back to campus and undergo initial COVID testing. This transition will unfold much like the fall term, with one week of remote instruction starting February 15 as students complete their testing and quarantine protocols. We will move fully back to in-person and hybrid instruction beginning February 22 and complete winter term as we are the fall term. Room and board charges will be adjusted accordingly.

    Student-athletes will arrive according to their team schedules. Additional details will be forthcoming on those schedules. In addition, the Midwest Conference is scheduled to make a decision on winter sports competition no later than mid-November, so please stay tuned.

    Students will still have the option of learning remotely for the entirety of winter and/or spring terms if they so choose. Please note that students must remain enrolled continuously in order to take advantage of the "Fifth Year for Free" Guarantee. Additionally, students will be able to petition to remain on campus for winter break and the beginning of winter term if returning home presents significant challenges. More information regarding this process will be forthcoming.

    One of the most significant changes to our academic schedule is that spring break will be quite short and intentionally so. Having completed the work of transitioning students back to campus once, we wish to avoid typical spring break travel and instead move directly into a fully in-person spring term in order to safeguard our campus against any potential outbreaks. Spring term instruction will mostly follow our conventional schedule. We know that this modified schedule will ask more of every member of the community, so we will make some adjustments to the schedule to provide students, faculty, and staff breathing space during the term. We believe this approach offers the best prospects for students to pursue their educational goals, for seniors to complete their work and graduate on time, and for the academic program to be disrupted as little as possible.

    Teaching & Learning

    Many of the changes and adaptations to our new teaching and learning environment will carry over from the fall. All winter term courses will begin in a remote delivery mode and then transition to a combination of in-person and hybrid components. Classroom, studio, lab, and other academic space use will follow the physical distancing and cleaning protocols currently in use on campus. Winter and spring courses, however, will benefit from the full range of technology improvements, classroom modifications, and experimentation, adaptation, and innovation at the core of faculty work since last spring. Faculty have begun the work of making minor modifications to winter and spring course schedules in response to these new guidelines and Winter term pre-enrollment will begin in late October.

    Return to Campus

    In order to facilitate safe and efficient COVID testing, students returning to campus for the second part of winter term will be assigned an arrival date between February 8-11. Students may arrive between 9:00 a.m.–Noon or 2:00p.m.–7:00 p.m. on their assigned date. Campus Life will communicate students’ assigned arrival dates via email in early November.

    As in fall term, all students will receive a COVID test immediately upon their arrival on campus, and then again approximately seven days later. Students will initially quarantine in their room until they have a negative test result. Once a student receives a negative test result, they will participate in modified quarantine until February 22, at which point in-person classes and activities will resume.

    Health and Wellness Policies

    Given current public health guidance, we anticipate that current campus health and wellness policies

    Источник: https://www.knox.edu/

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    • Our address is changing but we ARE NOT moving!

      The City of Houston authorized the change of name for Calhoun Road to Martin Luther King Boulevard effective December 1, 2021.

      You will continue to find us at the same location but don't forget to update our address if you use your GPS.

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      The flu vaccine is now available to UH Students by appointment. Self-Pay cost is $35.00. Students enrolled in the UH-System endorsed Student Health Insurance Plan may obtain the flu vaccine with no out-of-pocket cost.

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      Check us out on the UH Go App. You now have quick access on your mobile device to the Student Health Center website, the patient portal, after hour information, and important announcements. Get the UH Go App

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      The COVID-19 Vaccine is not available at the Student Health Center.

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    COVID-19 News and Updates from the Student Health Center

    Welcome back to campus!

    In-person and telemedicine services are available at the Student Health Center.

    If you are experiencing a medical emergency, call 911 or proceed to the nearest emergency department. The Student Health Center is not an Urgent Care Center or Emergency Department.

    • Primary Care, including Men’s and Women’s Health

      In-person and telemedicine appointments can be scheduled 24/7 through the Healthy Coog Patient Portal or by calling 713-743-5151 during regular business hours.

      For the safety of our patients and staff, patients must complete a COVID-19 Symptom Assessment prior to scheduling an appointment. For those who exhibit symptoms listed on the assessment form, an initial telemedicine consultation/triage can be scheduled in which the provider determines an in-person visit is medically necessary in order to provide treatment or care.

    • The Psychiatry Clinic will continue to offer Telepsychiatry Services.
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    (Includes General Medicine, Men’s Health and Women’s Health)

    At our clinic, you will be cared for by board-certified physicians who are assisted by nurse practitioners, registered nurses, licensed vocational nurses, and certified medical assistants.

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    • Treatment for both short-term and long term medical problems and injures
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    Immunizations

    Immunizations, Tuberculosis Skin Test and Immunological Titers are available by appointment. Titers (including Tuberculosis lab tests) required an office visit with a provider.

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    Our Psychiatry Clinic maintains a reputation for distinction in helping students cope successfully with the challenges and stresses of everyday life to mental health as students work toward their academic goals.

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    Our orthopedic specialist is available to diagnose and treat musculoskeletal conditions.  This includes sports injuries and diseases of the bone and muscle.  Referral for physical therapy may be obtained through this clinic.

    Campus Pharmacy

    Our pharmacists serve as an integral part of the health care team to help provide optimum outcomes and medication management. We believe strongly in educating patients about their medications including proper use, length of therapy, side effect, and potential drug interactions.

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    Источник: https://www.uh.edu/healthcenter/

    Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule activator

    Abstract

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the Canton mutant and several other common G6PD mutants. AG1 reduces oxidative stress in cells and zebrafish. Furthermore, AG1 decreases chloroquine- or diamide-induced oxidative stress in human erythrocytes. Our study suggests that a pharmacological agent, of which AG1 may be a lead, will likely alleviate the challenges associated with G6PD deficiency.

    Introduction

    Reduced glutathione (GSH) provides the cellular first line of defense against oxidative stress-induced injury, which can be maintained by NADPH generated mainly via the pentose phosphate pathway and its rate-limiting enzyme, glucose-6-phosphate dehydrogenase (G6PD; Fig. 1a). Accordingly, missense DNA mutations that impair G6PD activity or stability result in increased oxidative stress and a spectrum of disease phenotypes featuring, most commonly, hemolytic anemia, and collectively called G6PD deficiency1. In particular, G6PD is essential in preserving the integrity of erythrocytes because, lacking mitochondria, they have no other NADPH-generating enzymes to protect against oxidative stress2.

    Canton G6PD (R459L) variant is biochemically different from WT G6PD. a Enzymatic scheme of G6PD activity. b A linear map of G6PD domain structure with most common variants indicated. c Catalytic activity of recombinant WT G6PD and Canton G6PD enzymes with kinetic parameters (n = 5, ****p < 0.0001). d Thermostability of WT G6PD and Canton G6PD enzyme (n = 3, **p = 0.003). e G6PD protein levels and residual G6PD activity (normalized to NT (no treatment) of each enzyme) after incubation with chymotrypsin for 1 h (n = 3 for protein level assay, **p = 0.0046; n = 2 for enzyme assay, *p = 0.024). f Protein stability assessment with cycloheximide treatment (50 μg mL−1), blocking de novo protein biosynthesis, in lymphocytes derived from corresponding subjects (n = 3, *p = 0.013). Protein levels were normalized to the level of each enzyme at 0 h (no treatment). g G6PD activity was lower in cell lysates with Canton variant (n = 4, ****p < 0.0001). h, i, j Lymphocytes with Canton variant generated less GSH and more reactive oxygen species (ROS) and were less viable (n = 4, (n = 3 for Fig. 1i), *p < 0.05, **p < 0.01). Error bars represent mean ± SEM. Statistical differences were calculated by two-tailed unpaired Student’s t-test. NT: no treatment, WT: wild-type, Chy: chymotrypsin

    Full size image

    G6PD deficiency represents one of the most common inherited and sex-linked enzymopathies. The G6PD gene maps to the X-chromosome; thus, the phenotype is manifest fully in males whereas female heterozygotes display varying degrees of G6PD deficiency, due to alternate X-chromosome inactivation3,4. G6PD deficiency afflicts more than an estimated 400 million individuals worldwide, many of whom live in malaria endemic regions. Impaired anti-oxidant defense in G6PD-deficient erythrocytes makes them vulnerable to early membrane damage and ultimately phagocytosis when infected with malaria5. This mechanism that results in limiting the propagation of the parasite in the bloodstream explains how G6PD deficiency provides resistance against malaria4,5,6.

    Symptoms of G6PD deficiency are triggered by exposure to certain foods, medications, infection and/or environmental factors2,4. For example, consumption of fava beans causes oxidative stress to erythrocytes possibly by two main toxins, vicine or convicine, thus triggering acute hemolytic episode (favism) in affected subjects7. G6PD-deficient individuals are also at a high risk of severe hemolysis when given anti-malarial drugs, such as quinine, primaquine or chloroquine, through irreversible oxidative activity of their metabolites on erythrocytes8,9. G6PD deficiency can be life-threatening, especially in newborns, leading to bilirubin-induced neurological injury and bilirubin encephalopathy (kernicterus) and even to death10,11,12,13,14,15. In a recent study, a systematic analysis of 2253 articles discussing G6PD revealed that dysregulation of G6PD is also associated with autoimmune diseases and metabolic disorders, indicating that clinical risks associated with G6PD deficiency are likely underestimated16. As there are currently no means to correct G6PD deficiency, there is no treatment for the disease; management mainly consists of supportive care and discontinuation of triggers. The use of anti-oxidants such as vitamin E or selenium has proven to be ineffective in treating G6PD deficiency17,18,19.

    On the other hand, based on studies performed in Sardinia, G6PD deficiency has some beneficial effect on longevity20. In studies using dehydroepiandrosterone (DHEA), an inhibitor of G6PD (that is also an adrenal steroid), loss of G6PD function has been suggested to prevent cancer progression20,21. Despite all the beneficial effects, the detrimental effect of G6PD deficiency are still clear in hemolytic anemia and kernicterus of infancy. Given the risk of hemolytic crisis and related sequelae from various triggers in affected subjects in both malaria endemic and non-endemic regions, we believe that developing a pharmacological agent that corrects G6PD deficiency may benefit affected individuals.

    G6PD is functionally active as a dimer or a tetramer22. Each monomer has a catalytic nicotinamide adenine dinucleotide phosphate (NADP+)-binding domain and β+α domain, containing an additional binding site for NADP+ that structurally stabilizes the enzyme (Fig. 1b)23,24. The glucose 6-phosphate (G6P)-binding site is located between these two domains (Fig. 1b). Using different informatics tools, we recently demonstrated that the majority of the variants that cause severe (<10% of normal G6PD activity, class I and class II) or mild (10–60% of normal G6PD activity, class III) deficiency are primarily located in those functional regions of the enzyme, disturbing the enzyme’s activity and stability25.

    Here we present a comprehensive report describing the molecular basis for G6PD deficiency with Canton variant (R459L) and our efforts to restore its decreased function using a small molecule, AG1. Our study provides the first step in identifying a potential therapeutic approach to correct G6PD deficiency.

    Results

    Canton G6PD variant has reduced activity and stability

    We first began our efforts focusing on the Canton variant, with the mutation R459L, located in the β+α domain (Fig. 1b). Canton G6PD is prevalent in China and Southeast Asia (50–60% of the variants26,27), causing severe deficiency (class II). Recombinant Canton G6PD enzyme showed only 18% of normal G6PD activity with lower KM for both NADP+ and G6P (Fig. 1c), which is consistent with the biochemical characteristics analyzed using blood samples derived from subjects carrying the Canton variant28. Relative to the wild-type (WT) enzyme, Canton G6PD also displayed impaired ability to form tetramers in the presence of increased concentrations of the cofactors that facilitate tetramer formation, NADP+ or MgCl229,30, when cross-linked by glutaraldehyde (Supplementary Fig. 1a). This reduced oligomerization state of the Canton G6PD may contribute to its reduced enzymatic activity. Furthermore, the Canton variant was less thermostable; its T1/2, the temperature at which the enzyme retains half of its catalytic activity, was 42.6 °C, which is 4.6 °C lower than T1/2 of WT enzyme (Fig. 1d). Canton G6PD was more susceptible to degradation by chymotrypsin relative to the WT enzyme, which corresponded with a significantly decreased enzymatic activity (Fig. 1e). This suggests that Canton G6PD may undergo higher conformational fluctuation, leading to a greater accessibility to proteases and its reduced thermostability31.

    We also show that the Canton variant was less stable than WT G6PD in lymphocytes derived from a male subject carrier with a Canton mutation in G6PD; 24 h after cycloheximide treatment (50 μg mL−1) to inhibit de novo protein biosynthesis, the level of the Canton variant protein was ~33% lower than the WT enzyme (Fig. 1f and Supplementary Fig. 1b). G6PD activity in lysates of lymphocytes of the Canton variant carrier was ~90% lower than G6PD activity in normal lymphocytes (Fig. 1g), which coincided with low levels of total GSH and increased levels of reactive oxygen species (ROS) (Fig. 1h, i). Moreover, the viability of the lymphocytes of the Canton variant carrier was ~50% lower relative to normal lymphocytes when cultured under the stress condition induced by serum starvation (Fig. 1j).

    The same results were observed in SH-SY5Y neuronal cells transiently expressing WT G6PD or the Canton variant (His-tagged); Canton G6PD protein levels dropped by 50% within 24 h of cycloheximide treatment, as compared to 20% decrease of WT G6PD (Supplementary Fig. 1c). SH-SY5Y cells expressing the Canton variant also showed lower G6PD enzymatic activity in the lysates, and a lower level of GSH, a higher level of ROS, and lower cell viability in culture (Supplementary Fig. 1d, e, f, g) and knockdown of G6PD by siRNA reduced cell viability, recapitulating the phenotype of G6PD deficiency (Supplementary Fig. 1h).

    Canton mutation loses essential inter-helical interactions

    To elucidate the molecular basis of the reduced stability and activity of Canton G6PD, we examined the crystal structures of WT and Canton G6PD at 1.9 Å and 2.6 Å resolution, respectively (Table 1). Although no NADP+ was added to protein solution prior to the crystallization, both crystal structures contained NADP+ at the second NADP+-binding site (structural NADP+-binding site) in the β+α domain (Supplementary Fig. 2a). (The stability of the enzyme with NADP+ association at this site has been previously reported and NADP+ can be removed by incubating the enzyme with G6P24,30.) The overall conformations of WT and Canton G6PD were very similar, as indicated by a root-mean-square deviation of 0.6 Å for the superimposition of Cα atoms (Fig. 2a). However, we noticed a loose helical interaction between the helix (αn), containing the Canton variant-R459L, and an adjacent helix (αe) (Fig. 2b, left panel), which was not described in previously reported structures24. In WT G6PD, R459 forms electrostatic and hydrogen bond interactions with D181 and N185 on the adjacent helix (αe), whereas Canton mutation does not, resulting in loosened inter-helical interactions and displacements of the helix (αe) and a proceeding loop consisting of K171, P172, F173, G174, and R175, several amino acids away from R459-interacting residues on the helix (αe) (Fig. 2b, right panel). In particular, K171 and P172 are the key residues involved in positioning of G6P and NADP+ in their binding pockets23,24. Thus, the loose inter-helical interaction in the Canton variant is likely to be a major driving force for positioning the loop and thus changing the orientations of these residues. In 7 out of 8 molecules in the asymmetric unit of the Canton variant structure, P172 was observed in the trans conformation, consistent with previous data23,24 and accordingly, the side chain of K171 was oriented away from catalytic NADP+ and G6P binding pockets (Fig. 2b, right panel, and Supplementary Fig. 2b, c). K171A and P172G mutations in WT G6PD completely abolished the enzyme’s catalytic activity, indicating the importance of these residues in catalysis (Supplementary Fig. 2d).

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    Canton mutation (R459L) loses essential inter–helical interactions. a Structural overlay of WT G6PD (green) and Canton variant (orange). Structural NADP+ is shown as spheres, and arrows and circles indicate G6P and catalytic NADP+-binding sites (G6P and catalytic NADP+ were not observed in our structures). b (Left) Inter-helical interactions through R459 on the αn helix in WT G6PD and side chains of D181 and N185 on the adjacent helix (αe). (Right) Canton mutation loses such interactions, leading to displacements of the helix (αe) and a loop containing K171, P172, F173, G174 and R175 that precedes the helix. c, d Mutations of R459-interacting residues on the αe helix showed Canton mutation-like activity and thermostability (n = 3, ****p < 0.0001, one-way ANOVA) and were also susceptible to chymotrypsin treatment (n = 4 for D181A, ****p < 0.0001; n = 3 for N185A, *p = 0.026, two-tailed unpaired Student’s t-test). Error bars represent mean ± SEM. NT no treatment; WT: wild-type; Chy: chymotrypsin

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    We further mutated the R459-interacting residues, D181 and N185, to alanine in WT G6PD to determine the importance of the inter-helical interactions and found that these point-mutated enzymes are biochemically similar to the Canton variant; they exhibited about 20% of the normal activity, with lower KM values for both NADP+ and G6P and lower T1/2 values (Fig. 2c and Supplementary Fig. 2e). These mutants were also more susceptible to proteolytic digestion, relative to WT G6PD (compare Fig. 2d to Fig. 1e). Taken together, these data support the importance of the inter-helical interaction between R459 and D181 and N185 for catalytic activity and stability of the enzyme and provides a structural insight into the biochemical defects of the Canton variant. Indeed, other human mutations located around this helical interaction site, such as P172S (<10% enzyme activity), F173L (<10% enzyme activity), and D181V (10–60% enzyme activity), cause moderate to severe G6PD deficiency32,33,34, likely because they are predicted to undergo similar conformational changes based on our observation.

    AG1 activates and stabilizes G6PD mutants

    Our biochemical and structural studies led us to determine whether improving the activity of G6PD variants with a pharmacological agent can provide a new therapeutic approach to reduce the risk of pathologies implicated in patients with G6PD deficiency. To this end, we screened for agonists of G6PD (AGs) using the recombinant Canton G6PD enzyme by a high-throughput screen (HTS) and identified one agonist, 2,2’-disulfanediylbis(N-(2-(1H-indol-3-yl)ethyl)ethan-1-amine) (AG1, Mr = 438.1912) (Supplementary Fig. 3a). We confirmed that the active species in the HTS sample is a product resulting from thiol oxidation under ambient conditions35, which was validated by mass spectrometry and nuclear magnetic resonance spectroscopy (Supplementary Fig. 3a and Supplementary Note 1). AG1 increases the activity of Canton G6PD up to 1.7-fold with EC50≈3 μM and WT G6PD by about 20% over basal activity (Fig. 3a, b and Supplementary Fig. 3b). Although AG1 was a mild activator, it changed the kinetic parameters of Canton G6PD, indicating that AG1 may facilitate improved binding of NADP+ and/or G6P to the enzyme (Fig. 3c). We found that AG1 also promoted formation of dimers, as determined by partial native gel electrophoresis (Fig. 3d). The small increase observed in molecular weight of the monomeric G6PD might be due to either some modification of the enzyme by AG1 or an equilibrium shift toward dimeric states. When the recombinant Canton G6PD enzyme was incubated with G6P to remove the structural NADP+, the dimeric G6PD was destabilized, dissociating into a monomer (Fig. 3e). In the presence of AG1, however, the equilibrium shifted toward a dimer (Fig. 3e), further indicating that AG1 stabilizes a dimeric form of the enzyme. AG1 had no effect on the dimerization or activity of several other NAD- or NADP+-dependent dimeric or tetrameric enzymes, including 6-phosphogluconate dehydrogenase (6PGD), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), aldehyde dehydrogenase 2 (ALDH2), and aldehyde dehydrogenase 3A1 (ALDH3A1) (Supplementary Fig. 3c). Whereas 1 μM of AG1 increased the viability of SH-SY5Y cells by 20%, it had no effect when G6PD was knocked down by siRNA, supporting the specificity of AG1 toward G6PD (Supplementary Fig. 3d). Note also that the decrease in viability by the knockdown of G6PD implies the critical role of G6PD for cell survival. AG1 also reduced the susceptibility of Canton G6PD to proteolysis (Fig. 3f) and mildly improved its stability in lymphocytes (Fig. 3g and Supplementary Fig. 3e). The enzymatic activity in lymphocyte lysates with the Canton variant (~10% of normal activity) was enhanced by 78% in the presence of AG1 (Fig. 3h). The levels of GSH were slightly higher after treatment with AG1 for 24 h, which coincided with decreased ROS levels and improved cell viability (Fig. 3i–k) in the lymphocytes cultured under the serum starvation stress. AG1 treatment also increased the proteolytic stability of Canton G6PD in SH-SY5Y cells (Supplementary Fig. 3f). There was also a mild increase in G6PD activity, GSH levels, and viability of these cells together with a decrease in ROS levels (Supplementary Fig. 3g, h, i, j). Finally, as predicted, the activity of Canton variant-mimicking mutations that we generated (Fig. 2c, d), D181A and N185A, were similarly affected by AG1, as measured by increased activity and proteolytic stability (Supplementary Fig. 4a, b, c), suggesting that AG1 may correct a structural defect common to mutations that disturb that helical structure (Fig. 2b).

    AG1 (activator of G6PD) induces biochemical changes in the Canton variant. a Increased activity of Canton G6PD enzyme by AG1 (n = 5, ***p = 0.0002, two-tailed unpaired Student’s t-test) and b a dose response curve of AG1. c AG1 changed kinetic parameters of Canton G6PD. d AG1 promoted dimerization of Canton G6PD (n = 3). e Size-exclusion FPLC (calibrated Superdex 75 10/300 GL column) profile of purified Canton G6PD in the presence of G6P or AG1. f AG1 reduced proteolytic susceptibility of Canton G6PD (n = 3, ***p < 0.001, *p < 0.05, one-way ANOVA). The protein levels were normalized to the non-treated (NT) enzyme level. g Cycloheximide-chase assay using lymphocytes carrying the Canton variant (n = 3). Protein levels were normalized to the level of each enzyme at time 0 h. h, i, j AG1 increased G6PD activity in cell lysates with the Canton variant (n = 4, **p = 0.0032, two-tailed unpaired Student’s t-test), mildly enhanced a GSH level (n = 7, *p = 0.0282, two-tailed unpaired Student’s t-test) and reduced a ROS level in culture (n = 6, *p = 0.0452, two-tailed unpaired Student’s t-test). k AG1 increased viability of lymphocytes carrying the Canton variant (n = 6, **p = 0.003, two-tailed unpaired Student’s t-test). l, m AG1 activated other major G6PD variants, including A (V68M, N126D; blue spheres), Mediterranean (S188F, orange spheres), and Kaiping (R463H, yellow spheres) variants, respectively (n = 4, ****p < 0.0001, **p < 0.01, *p = 0.011, one-way ANOVA), and promoted their dimerization (n = 3). Purple spheres in the structure represent the side chain of R459. n Cycloheximide-chase assay using fibroblasts carrying the Mediterranean variant (n = 4, *p = 0.0437, two-tailed unpaired Student’s t-test). o, p AG1 significantly decreased a ROS level (n = 6, ***p = 0.0001, ****p < 0.0001, one-way ANOVA) and increased a GSH level in those cultures (n = 3, *p = 0.0214, ****p < 0.0001, one-way ANOVA). 100 μM and 1 μM of AG1 were used for in vitro assays and cell-based assays, respectively. 5% DMSO (stock) was used as vehicle. For FPLC assay, 500 μM AG1, 200 μg of Canton G6PD recombinant enzyme and 10 mM G6P were used. Cells were subjected to serum starvation for 48 h. Error bars represent mean ± SEM. MW: molecular weight, FPLC: fast protein liquid chromatography, NT: no treatment, Veh: vehicle, WT: wild-type, Med: Mediterranean fibroblast

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    Because G6PD exhibits cooperative folding36 and AG1 increased and/or stabilized G6PD dimer levels, we next examined the possibility that binding of AG1 to the enzyme could correct other point mutation-containing G6PD variants outside the αe-αn inter-helical interaction sites. We focused on A (V68M & N126D), Mediterranean (S188F), and Kaiping (R463H) G6PD (Fig. 1b), the three most common human variants in non-overlapping regions of the world causing mild to severe deficiency (Africa, Mediterranean and Southeast Asia, respectively). AG1 activated all these variants by up to 2-fold and increased the levels of the dimeric state (Fig. 3l, m). AG1 also stabilized G6PD in fibroblasts derived from a subject who carries Mediterranean mutation following cycloheximide treatment (Fig. 3n and Supplementary Fig. 5a). The lysate of human fibroblasts with the Mediterranean variant had only 22% activity of control human fibroblasts, but AG1 increased that activity by 50% (Supplementary Fig. 5b). Fibroblasts carrying the Mediterranean variant generated more ROS and less GSH under stress induced by serum starvation relative to fibroblasts from control subject, which was significantly blunted by AG1 treatment (Fig. 3o, p). Lower cell viability under the same condition was also improved by 22% in the presence of AG1 (Supplementary Fig. 5c). When Mediterranean G6PD expression was knocked down by siRNA, the viability was further dropped by 23%, and AG1 did not rescue it (Supplementary Fig. 5c), indicating the selective effect of AG1 for G6PD. Taken together, these data raise the possibility that by increasing (or stabilizing) the levels of dimeric G6PD and/or increasing the enzyme activity, AG1 may represent a lead compound for a drug to treat not only Canton-like mutations, but also some of the other most common G6PD deficiencies in humans.

    AG1 reduces oxidative stress in zebrafish

    Capitalizing on a recent report describing a morpholino-generated G6PD-deficient zebrafish model, in which exposure to pro-oxidants resulted in cardiac edema and a brisk hemolysis37, we next set out to determine the effect of AG1 in vivo. Using zebrafish embryos, we first confirmed that embryos develop normally at concentrations <10 μM of AG1 (Fig. 4a and Supplementary Fig. 6a), indicating that AG1 is not toxic to developing zebrafish embryos. We next used the anti-malarial drug, chloroquine, a common trigger for hemolytic crisis in G6PD-deficient humans4,37, to induce an oxidative challenge in the zebrafish embryos and found that chloroquine (100 μg mL−1) treatment at 24 h post fertilization (hpf) led to pericardial edema and increased ROS levels (Fig. 4a, b), which was consistent with the primaquine-induced phenotypes observed in a morpholino-based G6PD-deficient zebrafish model37. Upon chloroquine treatment, hemoglobin staining was also slightly reduced (Supplementary Fig. 6b). Under the same condition, AG1 significantly reduced ROS levels, resulting in less embryos exhibiting pericardial edema (Fig. 4a, b and Supplementary Fig. 6a; scores were determined by an observer blinded to the treatment group) and mildly increased hemoglobin staining (Supplementary Fig. 6b). Although a slight increase in G6PD activity was observed in lysates of pooled AG1-treated embryos, there was a significant increase in total NADPH levels possibly due to the increase in the product of G6PD downstream, 6-phosphogluconate, which serves as a substrate for the downstream enzyme, 6-phosphogluconate dehydrogenase (6PGD), another NADPH-producing enzyme in the pathway (Fig. 4c). As expected, the attenuation of pericardial edema was specific to G6PD deficiency, as pericardial edema due to mesoderm defects in tbx16 mutants was not corrected by AG1 treatment (Supplementary Fig. 6c, d)38,39. To further confirm the specificity of AG1 in vivo, we used CRISPR-Cas9 to generate loss-of-function F0 embryos (crispants). g6pd crispants had a lower G6PD level (Supplementary Fig. 6e), a 51% higher level of ROS, a 67% lower level of G6PD activity and a 58% lower NADPH level, and increased pericardial edema (Fig. 4d–f; scores were determined by an observer blinded to the treatment group). Treatment with 1 μM AG1 did not significantly affect these parameters in the g6pd crispants (Fig. 4d–f). Note also that there was a slight (albeit not statistically significant) increase in the number of crispant embryos exhibiting reduced hemoglobin staining (Supplementary Fig. 6f).

    AG1 attenuates ROS-induced pericardial edema in a G6PD-dependent manner. a Embryos were treated at 24 hpf with 1 μM AG1 with and without chloroquine (CQ; 100 μg mL−1) and scored at 32 hpf. Representative phenotypic images of pericardial edema and pooling (magenta arrows) are provided on the left (scale bar: 300 μm). Embryo orientation is lateral view, anterior left. Raw counts used for chi-square analysis and calculated p value are included in table below. b ROS levels in individual WT embryos from three independent clutches. Embryos were treated at 24 hpf for 5 h before ROS measurement. Error bars represent mean ± SD (***p < 0.001, ns = not statistically significant, p > 0.99, Kruskal–Wallis multiple comparison test, adjusted p value using Dunn’s test). c G6PD activity and NADPH levels were measured using the lysates of pooled embryos (from two independent clutches). Error bars represent mean ± SEM (***p = 0.0003, two-tailed unpaired Student’s t-test). d Embryos were injected with either sgRNA targeting exon 10 of g6pd (Guide alone) or sgRNA + Cas9 protein (Guide + Cas9, G6PD KO (knockout)) to generate G6PD F0 crispants. Representative phenotypic images of pericardial edema and pooling (magenta arrows) are provided on the left (scale bar: 300 μm). Treatment conditions are the same as in a. Raw counts used for chi-square analysis and calculated p value are included in table below. e ROS levels in individual embryos with sgRNA or sgRNA + Cas9 (G6PD KO) protein injection. Treatment conditions and the statistics are the same as in b (*p = 0.0267, **p < 0.01, ****p < 0.0001, ns = not statistically significant). f G6PD activity and NADPH levels were measured with lysates of pooled embryos from three independent experiments. Error bars represent mean ± SEM of the replicate measurements (*p < 0.05, **p < 0.01, one-way ANOVA for G6PD activity measurement and two-tailed unpaired Student’s t-test for NADPH measurement). Veh: vehicle, KO: knockout, CQ: chloroquine

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    AG1 reduces hemolysis of human erythrocytes

    We next determined whether AG1 protects erythrocytes from oxidative stress. Our preliminary study using human erythrocytes from seven healthy subjects showed that AG1 (5 μM) reduces the extent of hemolysis, when erythrocyte suspension (5%) was exposed to either 1 mM chloroquine (CQ) or diamide (a GSH oxidant), suggesting anti-hemolytic potential of AG1 (Fig. 5a). In support of this, AG1 increased GSH levels and reduced ROS levels together with increased G6PD activity under these drug-induced oxidative stress (Fig. 5b–d). Oxidative stress impairs erythrocyte membrane integrity through initial oxidation of hemoglobin, leading to the precipitation of Heinz bodies and band 3 (a major erythrocyte membrane protein) clustering; thus, band 3 clustering serves as an essential molecular marker of erythrocyte removal40. Using erythrocytes isolated from 9 to 11 individual whole blood samples, we confirmed that band 3 protein is aggregated with either chloroquine (CQ) or diamide treatment, which was alleviated by AG1 treatment (Fig. 5e and Supplementary Fig. 7a). This suggests that AG1 contributes to stabilizing erythrocyte membranes. Red blood cell transfusion is commonly used clinical therapy, but structural and functional changes in erythrocytes during storage, collectively referred to as storage lesion, remain concerned in transfusion practice41. Storage under conventional conditions is considered as oxidative stress for erythrocytes, as evidenced by increase in ROS over time and accumulation of oxidative biomarkers42,43. Thus, we determined that whether AG1 can improve preservation during refrigerated storage by monitoring the degree of hemolysis over 28 days. We found that AG1 (1 μM) reduces hemolysis over time by an average of 12% at day 28 (Fig. 5f and Supplementary Fig. 7b). Accordingly, the protein leakage from the treated erythrocytes was decreased as well (Fig. 5g and Supplementary Fig. 7c), which corresponded with increased G6PD activity (Fig. 5h). These data suggest that AG1-like compounds can serve as a novel preservative for prolonged storage of erythrocytes and impact to a broader population as well as G6PD-deficient patients.

    AG1 reduces hemolysis upon exposure to oxidative stressors. a AG1 reduced the extent of hemolysis of 5% erythrocyte suspension treated with either 1 mM chloroquine (CQ) for 4 h under light or 1 mM diamide for 4 h at 37 °C (n = 7 independent blood samples, *p = 0.0372, **p = 0.0019, ****p < 0.0001, one-way ANOVA). bd AG1 significantly increased GSH levels and reduced ROS levels, when 5% erythrocyte suspension was exposed to either 1 mM chloroquine or diamide for 3 h at 37 °C, which was consistent with increased G6PD activity (n = 9–11, *p < 0.05, **p < 0.01, ****p < 0.0001, one-way ANOVA). e Band 3 protein was clustered (cBand3) when 5% erythrocyte suspension was treated with chloroquine, which was alleviated by AG1 treatment. Each lane represents one individual sample, and quantification is provided in Supplementary Fig. 7a. fh AG1 (1 μM) improved storage of erythrocytes (5% suspension) at refrigerated temperature by reducing hemolysis and concomitant protein leakage for 28 days (n = 13 independent blood samples, *p < 0.05, two-tailed unpaired Student’s t-test), which corresponded with increased G6PD activity (n = 4, *p = 0.0323, ***p = 0.0003, one-way ANOVA). Each sample was re-treated with AG1 every week. Representative hemolysis phenotypic images are provided below f. Error bars represent mean ± SD. NT: no treatment, CQ: chloroquine, cBand3: clustered band 3 protein

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    Discussion

    In humans, in addition to the role of G6PD in preventing hemolysis (erythrocyte lysis), the anti-oxidant property of G6PD may relate to development of a variety of other pathologies, including kidney injury, heart failure, psychiatric disorder, diabetes, cholelithiasis, and cataract44,45,46,47,48,49,50,51,52, suggesting that G6PD deficiency can be an underestimated risk factor for multiple human pathologies. Because AG1 increased the impaired activity of several common G6PD variants, our study suggests that a single pharmacological agent may provide treatment for several major G6PD enzymopathies, affecting many millions of people worldwide. Such a drug may also help prevent or reduce the sequelae of G6PD deficiency and/or synergize with other palliative treatments such as illumination for kernicterus53,54. We expect many other pathologies associated with G6PD deficiency, as aforementioned, to be affected by such treatment as well. Treatment with AGs may also be beneficial to G6PD-deficienct populations in developing countries, in which the use of hemolytic crisis-triggering drugs, like anti-malarial drugs (primaquine and chloroquine), are still common. We believe that AG1-like drugs may also be useful for preservation of blood for transfusion, as evidenced in Fig. 5 and for subjects with WT G6PD with other diseases associated with increased oxidative stress.

    Human studies demonstrate that clinical pathology related to G6PD deficiency, at least as reflected by hemolytic crisis, occurs in subjects who carry a variant with <60% activity relative to the subjects with WT G6PD55. Therefore, although AG1 is safe, an optimal AG should be improved, to increase the catalytic activity in G6PD-deficient subjects to at least 60% of normal. Nonetheless, based on our initial studies, AG1 should be viewed as a lead compound to correct G6PD deficiency and also to treat subjects with WT G6PD at risk of oxidative stress. Our current effort focuses on improving the biochemical and pharmacological features of AG1 through further medicinal chemistry efforts and structural studies. Finally, identifying small-molecule enzyme activators is still considered a challenging task in the field of drug discovery and development56, and even less common is the ability to identify a small molecule that corrects functional defect due to different mutations; AG1 represents a compound that does both.

    Methods

    Materials

    Antibodies used in this study were principally purchased from Santa Cruz Biotechnology (G6PD (G-12): SC-373886 (dilution 1:1000), 6PGD (G-2): SC-398977 (dilution 1:1000), His (HIS.H8): SC-57598 (dilution 1:1000), Enolase (H-300): SC-15343 (dilution 1:1000)), Cell Signaling Technology (beta actin (8H10D10): 3700 S (dilution 1:1000)), Everest Biotech (G6PD: EB07841 (dilution 1:1000)), Advance Immunochemical (GAPDH (6C5): 6C5 (dilution 1:2000)), and Abcam (G6PD: AB87230 (dilution 1:1000), band 3 (EPR1426): AB108414 (dilution 1:1000)). TALON Superflow (28-9575-02) and bovine thrombin (91-030) were purchased from GE Healthcare and BioPharma for protein purification. Pfu Turbo polymerase (600252) used for site-directed mutagenesis was purchased from Agilent Technologies. Chymotrypsin was purchased from Promega (V1061). Cell counting kit-8 (CK04) and glutathione quantification kit (T419) were purchased from Dojindo. Cycloheximide (C7698) and chloromethyl-2’,7’-dichlorodihydrofluorescein diacetate (CM-H2DCFDA, C6827) were purchased from Sigma and Thermo Fisher Scientific, respectively. Glutathione assay kit (703002) used for blood assays was purchased from Cayman Chemical.

    Cell culture

    Lymphocytes derived from a normal subject (HG 00866) and a G6PD-deficient subject carrying the Canton variant (HG 02367) were purchased from Coriell Institute and cultured in RPMI 1640 supplemented with 15% fetal bovine serum (FBS), 100 U mL−1 penicillin, and 100 μg mL−1 streptomycin. An SH-SY5Y neuroblastoma cell line (ATCC CRL-2266) was cultured in Dulbecco’s Modification of Eagle’s Medium/Ham’s F-12 50/50 Mix supplemented with 10% FBS, 100 U mL−1 penicillin, and 100 μg mL−1 streptomycin. A fibroblast cell line derived from a G6PD-deficient subject carrying the Mediterranean variant and normal fibroblast cell line as control were purchased from Coriell Institute (GM 01152) and Thermo Fisher Scientific (C0135C), respectively, and cultured in minimum essential medium supplemented with 15% FBS, 100 U mL−1 penicillin, and 100 μg mL−1 streptomycin. All the cell lines were maintained at 37 °C in a humidified incubator with an atmosphere of 5% of CO2 and 95% air.

    Plasmid construction and site-directed mutagenesis

    The gene encoding WT G6PD was inserted into the pET-28a vector, using NdeI and SalI restriction enzyme sites. Site-directed mutagenesis was performed to generate G6PD variants using appropriate primer sets (Supplementary Table 1) according to the manufacturer’s guidelines (Agilent-Quikchange site-directed mutagenesis). Briefly, the PCR reaction of 50 μL contained 10–50 ng of template, 125 ng of primers, 200 μM dNTPs, and 2.5 units of Pfu Turbo DNA polymerase. The reaction was initiated at 95 °C for 30 s to denature the template DNA, followed by 18 amplification cycles (95 °C for 30 s, 55 °C for 1 min and 68 °C for 7 min). All constructs were verified by sequencing.

    Protein expression and purification

    G6PD and its variants were expressed in E. coli C43 (DE3). When the culture density reached an OD600 of 0.5–0.6, 0.5 mM IPTG was added to induce the protein expression. After culturing at 28 °C overnight, the bacteria were centrifuged, and the pellets were lysed by sonication in buffer containing 50 mM Tris (pH 7.4), 300 mM NaCl, 5% glycerol, 0.4 mM PMSF, 1 mg mL−1 lysozyme, 0.1% Triton X-100 and protease inhibitor cocktail (Sigma P8340). G6PD was then purified by incubating the supernatant with TALON Superflow resin equilibrated with 1 bed volume of equilibration buffer (50 mM Tris (pH 7.4), 300 mM NaCl and 5 mM imidazole) at 4 °C for 1 h. The resin was washed with 5 bed volumes of wash buffer (50 mM Tris (pH 7.4), 300 mM NaCl and 20 mM imidazole) in a gravity-flow column and resuspended in 5 mL of equilibration buffer for size exclusion chromatography (50 mM Tris (pH 7.4) and 150 mM NaCl). Bovine thrombin (100 units) was added to the resin, which was followed by overnight incubation at 4 °C with gentle shaking. Tag-less G6PD was eluted and applied onto HiLoad 16/600 Superdex 75 pg size exclusion chromatography. Fractions containing G6PD were pooled and concentrated using 10 kDa MWCO membrane. The final concentration of G6PD was determined by Bradford method, and the protein was stored in 40% glycerol at −80 °C.

    Enzyme assay and kinetic measurements

    Enzyme activity was measured by monitoring NADPH production, which was coupled with diaphorase converting resazurin to fluorescent resorufin (excitation at 565 nm and emission at 590 nm) (Supplementary Fig. 3a); fluorescent signal was thus proportional to G6PD activity. All the assays were performed at 25 °C and run for 5 min in buffer containing 50 mM Tris (pH 7.4), 0.5 mM EDTA, 3.3 mM MgCl2, 1 U mL−1 diaphorase and 0.1 mM resazurin. 10 ng of recombinant enzymes or 10 μg of cell lysates was used for the assay with 10 μM NADP+ (Sigma) as cofactor and 100 μM G6P (Sigma) as substrate. Steady-state kinetic parameters were obtained by varying concentrations of NADP+ (0–10 μM) with a constant concentration of G6P (100 μM) and similarly for G6P (0–100 μM) with a constant concentration of NADP+ (10 μM) with 10 ng of recombinant enzymes. Data analysis was performed using GraphPad Prism software v.6 (GraphPad Software, La Jolla, CA USA). Kinetic parameters were obtained by fitting the data to the Michaelis–Menten equation.

    High-throughput screening assay

    The diaphorase-coupled enzyme assay as described above was used to screen for small-molecule activators. All the compounds purchased from SPECS, Chembridge, ChemDiv Kinase, LOPAC, Microsource Spectrum, Biomol FDA, Biomol ICCB, and NIH Clinical Collection were added to Canton G6PD enzyme reaction mixture at a final concentration of 16.67 μM using Caliper Life Sciences Staccato system with a Twister II robot and a Sciclone ALH3000 (Caliper Life Sciences, Alameda, CA USA) integrated with a V&P Scientific pin tool, which was followed by the incubation for 3 h. Then addition of G6P initiated the reaction, which was run for 2.5 min. The fluorescent signals were recorded 4 times during the run using Molecular Devices AnalystGT (Molecular Devices, Sunnyvale, CA USA). Any compounds showing 30% activation of the enzyme were rescreened in a dose-dependent manner (0–30 μM, duplicate) to identify potential hits. The screening and data analysis were carried out by Stanford University High-Throughput Bioscience Centers (HTBC).

    Thermostability assay

    10 ng of recombinant enzymes was incubated at various temperatures ranging from 25 to 65 °C for 20 min, and the activity was measured as described above. After normalization of the data between 0 and 100, Boltzmann sigmoidal equation was used to calculate the T1/2 value, the temperature at which the enzyme retains half of original activity.

    In vitro proteolysis assay

    200 ng of recombinant enzymes was incubated with 10 ng of chymotrypsin for 1 h at room temperature. 100 μM of the compound was added to some reaction conditions. The following protein level was examined by Western blot (original blot data are available in the Supplementary Information).

    Overexpression of WT G6PD and Canton variant in SH-SY5Y cells

    Prior to the cellular-based assays using SH-SH5Y cells, the duration of overexpression of WT G6PD and Canton variant was examined by transfecting the cells seeded in a 12-well plate. The genes encoding human WT G6PD and Canton variant were first PCR-amplified, which was then inserted into pcDNA 3.1/myc-His C (ThermoFisher Scientific) using HindIII and XhoI restriction enzyme sites. 0.5 μg of cDNA and 1.5 μg of lipofectamine (Invitrogen) were diluted in 50 μL of Opti-MEM medium, respectively and incubated for 5 min. The diluted DNA was combined with diluted lipofectamine, which was followed by incubation for 20 min prior to the addition to cells. The transfected cells were collected at different time points (up to 72 h), and the overexpressed G6PD levels were examined by Western blot. The transfection was carried out in 50% serum-starved cells. Once the duration of expression was confirmed, other cellular-based assays were performed.

    Cycloheximide chase assay

    50,000 cells (SH-SH5Y cells or fibroblast cells) or 100,000 cells (lymphocytes) were seeded in a 12-well plate and incubated overnight. The cells were subjected to serum starvation (50–75%) for 48 h and treated with 50 μg mL−1 of cycloheximide at different time points (0–48 h). The cells were treated with the compound (1 μM) for 48 h together with cycloheximide. Then the cells were collected in PBS containing protease inhibitor cocktail and 1% Triton X-100 and centrifuged at 18,800 × g at 4 °C for 10 min. 10 μg of total protein was loaded onto SDS–PAGE gels, and the protein levels were examined by Western blot (original blot data are available in Supplementary Information).

    Glutathione (GSH) measurement

    Total glutathione level was measured using a Total Glutathione Quantification Kit (Dojindo), according to the manufacturer’s instructions. Cells were subjected to serum starvation (50–75%) for 48 h to induce oxidative stress and treated with the compound for 24 h before measurement. The absorbance was read at 412 nm.

    Cell viability assay

    Cell viability was measured using a Cell-Counting Kit-8 (CCK-8, Dojindo), utilizing WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt, according to the manufacturer’s instructions. Cells were subjected to serum starvation (50–75%) for 48 h before measurement. Cells in 100 μL of medium per well were treated with 10 μL of CCK-8 solution and incubated for 2 h at 37 °C. The absorbance was read at 450 nm. Viability of lymphocytes was measured by staining with a 0.4% solution of trypan blue in buffered isotonic salt solution (pH 7.2). The viability was calculated as the number of viable cells (non-stained by the dye) divided by the total number of cells within the grids on the hemacytometer. Cells were treated with 1 μM of the compound 24 h before the measurement.

    Cellular reactive oxygen species (ROS) measurement

    Cells in a 96-well plate were incubated with chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate (CM-H2DCFDA) at a final concentration of 5 μM in HBSS (Hank’s balanced salt solution) for 30 min at 37 °C. After wash, cells were treated with Hoechst 33342 (Molecular Probes) to stain nuclei and incubated for another 10 min at 37 °C. Cells were washed in HBSS, and the florescence was analyzed with excitation/emission at 485/525 nm. Cells were subjected to serum starvation (50–75%) for 48 h to induce oxidative stress and treated with the compound for 24 h before measurement. The signal was normalized to nuclei staining (excitation/emission at 350/470 nm).

    Native gel electrophoresis

    200–300 ng of recombinant enzymes was incubated with the compound (varying in assays) for 10 min at room temperature. To prevent streaking and artifacts in native PAGE gel, the samples in a native state (no boiling of sample and no reducing agent in sample buffer) were electrophoresed by SDS–PAGE. Cross-linking assay was initiated by incubating 200 ng of recombinant enzymes in PBS with 0.1% of glutaraldehyde and different concentrations of NADP+ (0, 10, 100, 1000 μM) or MgCl2 (0, 1, 10, 100 mM). The mixture was incubated for 10 min at room temperature, which was followed by the addition of 100 mM Tris (pH 8.0) at a final concentration to terminate the reaction. The samples were electrophoresed as described above.

    G6PD siRNA-knockdown assay

    Endogenous G6PD was knocked down in each cell line as follows; 2 pmol of siRNA G6PD (Santa Cruz Biotechnology, sc-60667) and 0.5 μg lipofectamine (Invitrogen) were diluted in 10 μL of Opti-MEM medium, respectively and incubated for 5 min. The diluted siRNA was combined with diluted lipofectamine, which was followed by additional incubation for 20 min prior to the addition to cells in a 96-well plate.

    Crystallization, data collection, structure determination and refinement

    Crystals of WT G6PD recombinant enzyme grew in sitting drops containing 20% w/v PEG 3350, 0.2 M potassium formate, pH 7.3. Suramin (G6PD inhibitor) was added to the protein solution (the final concentration in the drop was 0.5 mM) prior to the crystallization. Canton G6PD recombinant enzyme was crystallized in sitting drops containing 20% w/v PEG 3350, 0.2 M ammonium citrate tribasic, pH 7.0. AG1 dissolved in 30% DMSO was added to the protein prior to the crystallization to reach final concentration of 0.5 mM in the drop. None of the Suramin or AG1 compound was visible in the electron density map of WT G6PD and Canton G6PD; however, they significantly improved diffracting quality of the crystals. Note that our inability to observe AG1 in the crystal structure may reflect instability or flexibility of the ligand bound to G6PD. Additional crystallographic studies and further medicinal chemistry efforts will help determine the binding site of AG1 in the enzyme and the mechanism by which it activates G6PD. X-ray diffraction data of WT G6PD and Canton G6PD were collected at 100 K at beamline 12–2 of Stanford Synchrotron Radiation Light Source (SSRL) and beamline 5.0.2 of Advanced Light Source (ALS), respectively. A solution of 20% glycerol was used as cryo-protectant. Crystals of WT and Canton G6PD diffracted to 1.9 Å and 2.6 Å resolution, respectively. The data were processed using iMOSFLM57, and further analysis of the data by POINTLESS58,59 indicated the space group of F222 and P212121 for WT G6PD and Canton G6PD crystals, respectively. WT G6PD structure was solved using molecular replacement with a monomeric G6PD structure from PDB: 2BHL used as a search model in MOLREP. Canton G6PD structure was solved using the WT G6PD structure that was already solved in this study. Molecular models were further built in Coot60. Both structures were refined using the restrained isotropic refinement in REFMAC61,62. TLS parameters were not used for the refinement in both cases. Each refinement was done using 10 cycles of maximum likelihood restrained refinement, with geometry weight adjusted to 0.05. Data collection and refinement statistics are summarized in Table 1. The atomic coordinates and structure factors are deposited in the PDB database under accession codes PDB: 6E08 for WT G6PD and PDB: 6E07 for Canton G6PD. All structure figures were prepared using PyMOL (PyMOL Molecular Graphics System, Version 1.5.0.5; Schrödinger).

    Zebrafish husbandry

    Adult zebrafish (AB strain; 3–18 months old) were raised according to standard protocols, and embryos were obtained through natural mating and staged63. Adult tbx16b104/+ was a generous gift from S. Amacher (Ohio State University). All animal procedures were performed according to NIH guidelines and approved by the Committee on Administrative Panel on Laboratory Animal Care (APLAC) at Stanford University. Embryos were raised in E3 medium at 28.5 °C.

    Zebrafish crispants

    sgRNA against exon 10 of g6pd was designed using CHOPCHOP and in vitro transcribed using the T7 quick high yield RNA synthesis kit (New England Biolabs, E2050S)64,65. The gene-specific oligo sequence was: 5′-TAATACGACTCACTATAGAGAAGGGGAGGCAAAACTGGTTTTAGAGCTAGAAATAGCAAG-3’. sgRNA and Cas9 protein (New England Biolabs, M0386T) were mixed and microinjected into one-cell-stage embryos. For each injected clutch, 10 individual embryos were isolated at 24 hpf for sequencing to confirm introduction of a CRISPR-mediated indel in exon 10.

    Zebrafish compound treatment

    Embryos were dechorinated with pronase at 24 hpf and treated with 100 μg mL−1 of chloroquine and/or AG1 (1 μM) by directly adding the compounds to the well. For ROS measurements, the embryos were incubated with compounds for 5 h and then the ROS-detecting reagent (CM-H2DCFDA) was added at a final concentration of 500 ng mL−1 to the well and incubated for 3 h. One embryo was placed to each well of a black, opaque 96-well plate. The florescence was analyzed with excitation/emission at 485/525 nm. After ROS assays, embryos at about 32 hpf were pooled and lysed in buffer containing 50 mM Tris (pH 7.4), 150 mM NaCl, 1 mM EDTA, 0.1% NP-40 and protease inhibitor cocktail, which was followed by three cycles of freeze and thawing in liquid nitrogen. The lysate was centrifuged at 18,800 × g at 4 °C for 15 min. Total protein concentration in the supernatants (total lysate) was determined by the Bradford method. 10 μg of total lysate was used for enzymatic assay. 50 μg of total lysate was used to measure NADPH levels using a NADPH quantification kit (Biovision), according to the manufacturer’s instructions. 50 μg of total lysate was loaded onto 10% SDS–PAGE gels, and the protein levels were examined by Western blot using anti-G6PD antibody (Abcam (G6PD: AB87230)).

    Zebrafish imaging

    Live embryos were anesthetized and mounted in 3% methylcellulose. Embryos were imaged with a Leica M205FA microscope equipped with a 1.0x Plan Apochromatic objective and a SPOT Flex camera or a Leica DM4500B compound microscope equipped with a QImaging Retiga-SRV camera. For hemoglobin staining, live embryos were stained in 0.6 mg mL−1o-dianisidine solution containing 10 mM sodium acetate (pH 4.5), 0.65% H2O2 and 40% ethanol in the dark for 15 min and cleared in glycerol37. Embryos were then mounted in 100% glycerol and imaged with a Leica M205FA microscope equipped with a 1.0x Plan Apochromatic objective and a SPOT Flex camera. All images were captured using SPOT or MetaMorph imaging software (Diagnostic Imaging Inc.) and processed in Photoshop (Adobe). Adjustments were limited to brightness levels and cropping. Analysis was carried out by an observer blinded to the experimental conditions.

    Blood sample assay

    De-identified blood samples were obtained from the Stanford Blood Center. Erythrocytes were collected by filtering the samples through a cellulose slurry to remove platelets and leukocytes and then washed with saline. G6PD activity was measured spectrophotometrically by the Beutler method66. The activity of all the samples used in this study was in a normal range (5–9 U g−1 Hb), suggesting that the subjects have WT G6PD. 5% erythrocyte suspension was pre-incubated with 1–5 μΜ AG1 at 4 °C overnight, which was followed by treatment with (or without) either 1 mΜ chloroquine (CQ) or 1 mM diamide for 3–4 h at 37 °C (for hemolysis assay with chloroquine, the mixture was incubated under light). Then centrifugation at 100 × g for 5 min was followed. Hemoglobin release in the supernatant was monitored by measuring absorbance at 540 nm. Saline was used as a negative control (0% hemolysis) and a sample treated with 0.1% Triton X-100 was used as a positive control (100% hemolysis). For ROS measurement, erythrocyte mixture was washed with saline by centrifugation after treatment and incubated with chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate (CM-H2DCFDA) at a final concentration of 5 μM in saline at 37 °C for 15 min. After wash, the samples were lysed with 0.1% Triton X-100 (final concentration), and the florescence was analyzed with excitation/emission at 485/525 nm. GSH measurement was determined using a Cayman glutathione assay kit (Cayman Chemicals, 703002). Briefly, 50 μL of diluted erythrocyte lysate samples were mixed with 150 μL of assay reagents including glutathione reductase, 5′,5-dithiobis-(2-nitrobenzoic acid) (DTNB) and NADPH, which was followed by incubation for 25 min at room temperature. The absorbance was read at 412 nm. For storage assay, 5% erythrocyte suspension was stored at 4 °C with and without 1 μM AG1, and hemolysis and G6PD activity were monitored every week for 28 days to examine whether AG1 improves preservation of erythrocytes over time. Protein leakage was also examined by measuring the absorbance of the supernatant of samples at 280 nm. The samples were re-treated with AG1 every week.

    Statistical analyses

    Most assays were repeated at least in three independent experiments. The data from in vitro and cell-based assays are presented as mean ± standard error of the mean (SEM), and the data from the human erythrocyte study are presented as mean ± standard deviation (SD). Statistical differences were calculated by either Student’s t-test (two-tailed, unpaired), one-way ANOVA, or two-way ANOVA using GraphPad Prism software. In assays with human erythrocytes, each sample was utilized as its own control, and assay parameters were compared before and after treatment; thus, randomization was not needed. For all zebrafish experiments, at least two breeding tanks, each containing 3–4 males and 3–5 females from separate stocks, were set up to generate embryos. Embryos from each tank were randomly distributed across tested conditions. Unfertilized and developmentally abnormal embryos were removed prior to compound treatment. No statistical methods were used to determine sample size per condition. For phenotypic analysis, raw counts for each condition were used for chi-square analysis or Fisher’s exact test based on expected values. For all phenotypic analysis, the scorer was blinded to treatment conditions. For ROS assays, the normality of each distribution was assessed using the Shapiro–Wilk test and determined to be non-normal. A Kruskal–Wallis test with a Dunn’s secondary test was used to determine differences between all conditions. p values were corrected for multiple comparisons testing. p values and number of samples or experiments replicated are indicated within the figure legends, and p < 0.05 was considered statistically significant.

    Data availability

    The data that support the findings of this study are available from the corresponding author upon request. Protein structures have been deposited in the Protein Data Bank (PDB) with accession codes of 6E07 and 6E08 for Canton G6PD and WT G6PD, respectively.

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    Knox Together: COVID-19 Plans & Policies

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    Dear Knox Community,

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    Dear Knox Campus Community,

    We are encouraged by the results from our first round of required COVID-19 testing during the week of September 20. As you may know, we identified just five COVID-19 cases, a strong indicator that our three-pronged approach of vaccinations, testing, and masking is currently working to keep infection rates low on our campus. 

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    This email details two important announcements regarding COVID-19 testing. Please read the information below carefully.

    REQUIRED COVID-19 TESTING FOR ALL DURING WEEK OF SEPTEMBER 20-24

    We are requiring all faculty, staff and students to complete campus-wide COVID-19 testing during the week of September 20-24. This campus-wide testing will help us assess the presence of the virus in our campus community, which will in turn inform the strategies needed to continue to safely hold in-person classes, gatherings, and activities. 

    Testing will be conducted Monday through Friday, September 20-24, at the T. Fleming Fieldhouse from 8:30 a.m. to 4:00 p.m. No appointment is needed. The state of Illinois requires certain demographic information for test registration. In order to shorten wait times and make the testing process as quick as possible for you, please complete this form prior to arriving for your test.

    Also, please note that if you have tested positive for COVID-19 in the last 90 days, according to the CDC, you do not need to test. If you have tested positive in the last 90 days, please report this information to Health Services at health@knox.edu by Monday, September 20.

    In order to avoid long wait times at the end of the week, please plan your test as early in the week as possible. Prior to arriving for a test, avoid drinks, food, smoking, nasal sprays, teeth cleaning, and chewing gum for at least 60 minutes before sample collection. Test results will be sent to you by email in one to two days. Health Services will also receive a confidential test result report.

    Employees will receive release time to get tested during that week. Please coordinate with your supervisor to schedule the release time for your test.

    COVID-19 TESTING AVAILABLE EVERY WEEK ON CAMPUS UNTIL FURTHER NOTICE

    In addition to the required testing outlined above, COVID-19 testing is available to all students, faculty, and staff regardless of vaccination status, Monday through Friday from 8:30 a.m. until 12:30 p.m. at the T. Fleming Fieldhouse at no cost. All community members are welcome and encouraged to test if they have any symptoms of COVID-19, or if they have had a concerning exposure, whether they are vaccinated or not. No appointment is needed. 

    Faculty and staff can visit the Knox Together Workplace for Faculty and Staff web page for more information and answers to any questions regarding when a COVID-19 test is appropriate. Students can visit the Health and Wellness web page for information and answers to questions about COVID-19 testing.

    If you have any questions, please email together@knox.edu. 

    Thank you for your continued commitment to doing all you can to keep everyone in our community safe and healthy.

    Regards,
    Michael A. Schneider
    Provost and Dean of the College
    Interim Vice President of Student Development

    Paul Eisenmenger
    Vice President for Finance and Administrative Services

    August 12

    Dear Knox Community,

    Opening our campus, bringing our community back together, and providing an in-person student experience that is as close to normal as possible are our priorities that are guiding our planning and preparation for the upcoming academic year. We know we are at our best when we are living and learning together on campus, and we are committed to doing all we can to provide a healthy and safe environment for all members of our community. 

    The protocols outlined below are informed by CDC and WHO guidelines and we continue to monitor the COVID-19 conditions nationally, locally, and in our community. We will adjust these health and safety policies as needed to create the safest possible environment for our community. 

    Vaccinations are required for students, faculty, and staff for the upcoming academic year. In May, we announced that all students are required to be fully vaccinated against COVID-19 for the 2021-22 academic year except for those with an approved medical or religious exemption. On August 1, we announced that all faculty and staff are required to be fully vaccinated against COVID-19 by Monday, September 13, except for those with an approved medical or religious exemption. Students requesting an exemption should reach out to Health Services; faculty and staff requesting an exemption should reach out to Human Resources. If you have not yet reported your vaccination information, please do so as soon as possible using the appropriate link below.

    Returning students: Upload Your COVID-19 Vaccine Record

    New incoming students: Pre-arrival Tracker

    Faculty and staff: Confidential Vaccination Verification Form 

    Masks are now required indoors, regardless of vaccination status. 

    This includes all Knox College buildings and spaces. There are several instances where it is not required or practical to remain masked at all times including: 

    The NCAA and Midwest Conference have protocols in place to allow athletic competition to resume this fall. Knox athletic teams and visiting teams are subject to those protocols. In some cases, student-athletes and/or coaches may not be masked during particular practice and competition activities.  

    Masks are not required outdoors, but are recommended in crowded outdoor settings, and when interacting with campus visitors. 

    All students will be tested for COVID-19 upon arrival; those who have approved medical and religious exemptions will be tested twice weekly on an ongoing basis. New and returning students will be tested upon arrival, and those students and faculty and staff who have approved medical and religious exemptions will be tested twice weekly. We will share details of the testing process soon.

    In addition, a small number of new and returning international students are unable to complete the full vaccination process prior to arrival due to the limited availability of the vaccine in their area. If you are an international student and do not have access to a vaccine in your home country, please contact Health Services immediately to make arrangements to be vaccinated upon arrival if you have not done so already. Testing for those who arrive without being fully vaccinated will be twice weekly until they are fully vaccinated. 

    Visitor and guest policy 

    Residence hall visitors:Visitors and guests (anyone other than a Knox student, faculty, or staff member) are NOT allowed in residence halls. A one-time exception is being made for families on move-in day. Family members assisting with move-in must wear masks at all times, limit the time inside the residence hall, and limit the number of family members in the residence hall to only those essential for move-in.

    The policy regarding residence hall visitors will be revisited near the end of September.

    Day visitors to non-residential buildings: Speakers, performers, and alumni visitors fall into this category. These visitors are subject to the indoor mask policy. Prior to entering a non-residential campus building, visitors for the day must check in with campus safety and complete a form providing vaccination status. If a visitor is vaccinated, or unvaccinated and provides proof of a negative COVID test within 72 hours of arrival on campus, they will receive a Knox wristband, and will be able to enter non-residential campus buildings. 

    Prospective students and their families: Prospective students and their families are required to wear masks indoors and outdoors when physical distancing is not possible. They will be required to check in with admission. They are also encouraged to limit the number of family members who join them for their visit. Prospective students and their families will not visit residence halls, observe classes, or participate in overnight visits. 

    Repeat visitors to non-residential buildings: These visitors include ensemble members, community groups that regularly use our indoor facilities, or other members of the community who do ongoing research in our library. Members of this visitor category are subject to the indoor mask policy, and must be vaccinated. They will be required to check in with campus safety, complete a form and provide proof of vaccination and will be issued a lanyard and visitor pass which will include their name and date approved.

    15 minutes or under visitors to non-residential buildings: These visitors include those delivering supplies, mail, or other items to campus. These visitors are subject to the indoor mask policy and must limit their time indoors to 15 minutes or under. Any time over 15 minutes will require following the day visitor policy. 

    Athletics spectator policies (with guidance from the NCAA and Midwest Conference) are being developed and will be available on the Prairie Fire and Knox Together website. Please check the policies frequently as they are subject to change.

    We will also update our Knox Together website to ensure any information provided there is current. We understand that you may have questions; please email them to health@knox.edu. 

    Following these policies will ensure that we can safely bring our community back together, and provide an in-person student experience that is as close to normal as possible. Thank you for doing your part to keep us all safe and healthy.

    C. Andrew McGadney
    President

    July 30

    Dear Knox Faculty and Staff,

    I’m looking forward to having nearly all Knox staff be back on campus next week for the first time in well over a year, with faculty and students arriving soon after. The next few weeks are critical to our success in creating a safe environment for our students and colleagues as we begin the 2021-2022 academic year.  

    You may recall that in May, we announced our students are required to be vaccinated for the upcoming academic year. After consultation with the Board of Trustees, FASCom, Staff Council, and members of the senior staff, we are now requiring that all faculty and staff members be fully vaccinated against COVID-19 by September 13, 2021. As is necessary for unionized employees, Knox will engage with leaders of the Collective Bargaining Unit to discuss and formalize the obligations of union-represented employees. Employees requesting a medical or religious exemption may contact Human Resources. 

    The decision to require students, faculty, and staff to be vaccinated is based on scientific fact, our responsibility to each other as members of the Knox community, and our ability to carry out our mission. Please keep in mind that infection (including the more contagious Delta variant), hospitalizations, and death rates are rising among those who are not vaccinated. 

    We join countless for-profit, state, and federal organizations and hundreds of colleges and universities throughout the country making this difficult but necessary decision. The Chronicle of Higher Education is tracking vaccination policies here. 

    For those who have not yet received a vaccination, free vaccinations are available at the following locations:

    Knox County Health Department
    Walgreens
    Hy-Vee 

    All faculty and staff are required to provide vaccination status here by August 6. And, as stated above, all faculty and staff must be fully vaccinated by September 13. 

    Finally, we are in the process of updating health and wellness guidelines for fall as well as a FAQ document which will be available soon. We will hold an open forum on Thursday, August 5 at 12 p.m. in Kresge Recital Hall for any staff and faculty members who would like to ask questions. Thank you for doing all you can to ensure that we can provide a healthy, happy, and productive learning and work environment for everyone this fall.

    C. Andrew McGadney
    President

    The policies above are for the 2021-2022 academic year.

    July 8

    Dear Knox Community,

    We hope you are having an enjoyable and productive summer. 

    As we move through this season and continue to monitor Illinois Phase 5 guidelines and Knox County metrics, we wanted to provide you with an important update to our summer campus COVID-19 health and wellness protocols. 

    Updated Summer Health and Wellness Protocols

    Starting tomorrow, Friday, July 9, we are transitioning to protocols that are in line with Illinois Phase 5 guidelines. These protocols are in place to protect the health and safety of our entire community and we trust that everyone will follow the protocols out of respect for our colleagues and students.

    At this time, we are not mandating the COVID-19 vaccine for faculty and staff, but continue to strongly encourage anyone who has not yet received  a vaccination to get one as soon as possible. If you need assistance in obtaining a vaccine, please reach out to Abby Putnam in Health Services at 309-341-7559 or email health@knox.edu.

    Returning to Campus

    While many staff have been on campus throughout the pandemic, we look forward to welcoming everyone back to campus by Monday, August 2.

    Should you have any questions about the updated summer COVID-19 health and wellness policies, please contact Abby Putnam in Health Services at 309-341-7559 or email health@knox.edu. If you have any questions about returning to campus or telecommuting arrangements, please contact your supervisor or me at 309-341-7200 or email hr@knox.edu.

    The last 18 months have been extremely challenging for many of us both personally and professionally. We are grateful for your flexibility and perseverance throughout this difficult time and look forward to bringing our community back together on the campus. I’ll see you in August, if not before.

    Regards,

    Amy Chambers
    Assistant Vice President
    Human Resources

    June 17

    Dear Knox Community,

    Going forward, Knox Together emails will be sent on an as-needed basis. During the pandemic, these notes primarily shared information on health and wellbeing. Now that we have the vaccine and positivity rates are declining, we no longer need weekly updates. With our new president starting on July 1, there may be new updates about campus news and events. 

    Illinois Restored Plan Phase 5 

    As of last Friday, June 11, Illinois is now in the Illinois Restored Plan  Phase 5 (fully reopened). Please read the guidelines carefully since not all restrictions have been lifted. Face coverings are recommended for unvaccinated persons and all individuals on public transportation, in transportation hubs, and congregate facilities (healthcare facilities and long-term care homes, for instance). Also, businesses and venues should continue to allow for social distancing to the greatest extent possible, especially indoors, and they can continue to put in place additional public health mitigations as they deem appropriate (wearing masks, for example).

    Summer COVID-19 Policies

    Please check here for any updates to our summer COVID-19 policies, including our visitor policy, which you will find at the bottom of the linked web page. As we near the start of the academic year, we will update the website, and campus leadership will advise you of any changes.

    Thank you for your attention to this weekly email during the past months and for your questions, feedback, patience and support. Enjoy your summer, and best of luck in the coming academic year as you return to your “new normal.”

    TERESA L. AMOTT
    President

    June 10

    Dear Knox Community,

    Commencement was an especially joyous occasion this year, as we celebrated our 2021 graduates during two in-person ceremonies this past Saturday. When I rose to welcome the assembled students, faculty, staff, family and friends, I was overcome by the size and presence of the audience. After such a long and unprecedented period in the history of the College, at long last, we were truly together. Congratulations once again to all of our graduates. Thank you to our faculty and staff for everything you did this year to enable their success and to support the health and well being of our campus during the last 15 months. 

    This past Monday, Illinois Governor Pritzker announced that the state is moving into Phase 5 (full reopening) tomorrow. This is wonderful news, and a very encouraging sign for a fully reopened Knox College campus in the fall. Please note that not all restrictions will be lifted, as we continue to battle COVID-19. 

    PLEASE GET VACCINATED

    Even though Illinois is moving to full reopening, vaccinations are lagging in the state and across the country. We are strongly encouraging everyone in the Knox community to get vaccinated. According to responses from those members of our community who used the Healthcheck 360 tracker, we estimate that 88% of our students are fully vaccinated, and according to the most recent information, a comparable number of faculty and staff have had at least one dose of the vaccine. Vaccines are widely available; for local vaccine sites, or more information about getting vaccinated, please contact the Knox County Health Department. 

    REMINDER: SUMMER COVID 19 POLICIES

    Summer health and wellness policies took effect on Monday. As we move into Phase 5, we have relaxed many of our restrictions while maintaining safety as our priority. Please visit the Knox Together website for updated information about mask requirements, physical distancing, gathering size restrictions, COVID testing, and more. Also, please stay tuned for updates to these policies throughout the summer. 

    UPDATED VISITOR POLICY

    Starting immediately, visitors to campus do not need to be temperature and symptom checked upon arrival to campus. Visitors who will be inside campus buildings for more than 15 minutes do still need to be preapproved by a senior staff member, and do still need to check in upon arrival. Please review our updated visitor policy for more information.

    COMMENCEMENT AND AWARDS LINKS

    If you would like to watch the two Commencement ceremonies that took place last Saturday, you can find the videos here. Our honorary degree recipients recorded special messages for our graduates. Please watch the messages on this page. More than 30 of our students received academic honors awards. You can view our faculty announcing the awards and recipients here. 

    While we do not have video from The First Generation Reception, I want to acknowledge the inspiring remarks from student speaker Matrice Young and faculty speaker Prof. Mary Crawford. Both shared their personal stories of being the first in their families to graduate from college and their recognitions of all those who helped them achieve their dreams.

    Ray and I send our heartfelt thanks to all of you who were able to attend our campus farewell event, either virtually or in person, and to all those who planned yet one more event in a busy season. It was wonderful to see you and talk with you before our last drive back from Galesburg to Laporte, Pennsylvania -- a drive we made many times during the past ten years, but one made more poignant by knowing that we were starting a new chapter in our lives. More about that in a later message.

    Please enjoy your summer with family and friends, and stay safe and well.

    TERESA L. AMOTT
    President

    May 27

    Dear Knox Community,

    We have quite a few important items to share with you this week; we have published our Summer 2021 COVID Health and Wellness policies and continue to share important vaccine and Commencement information. 

    Please Read: Summer 2021 COVID Health and Wellness Policies

    Summer Health and Wellness Policies will take effect June 7. In alignment with state and federal guidelines, and thanks to low positivity rates on campus, we are pleased to be able to relax some of our restrictions while maintaining safety as our priority. Please visit the Knox Together website for updated information about mask requirements, physical distancing, gathering sizes, COVID testing, and more. Also, please stay tuned for updates to these policies throughout the summer. 

    We have had many questions about visitors to campus. A visitor is defined as any individual coming to campus who is not a Knox College student, faculty, or staff member. Please be sure to check the details of our summer visitor policy at the bottom of this page. There are policies that apply to outdoor and indoor spaces, as well as approval processes for different categories of visitors, such as individuals visiting students on campus and contractors, vendors, and admission visitors.

    Important Hy-Vee Vaccine Clinic Follow-Up Information

    People who received their first dose at the Hy-Vee on-campus clinic this past Tuesday or those who missed their second dose should go to a Hy-Vee pharmacy or find a location close to home that can give the second dose. 

    We have received inquiries about vaccines for international students arriving on campus in the fall. We are aware that campus-approved COVID-19 vaccines (Pfizer, Moderna, or Johnson & Johnson) are not widely available in all countries. We will facilitate vaccinations for students who are unable to be immunized prior to arriving on campus in the fall. Although fall policies have not been fully drafted, at this time, we do not anticipate that unvaccinated students will be required to arrive early to campus or quarantine upon arrival. 

    Commencement - Those Not Working or Not a Ticketed Guest

    Anyone who is not working Commencement or who is not a ticketed guest will be asked to maintain a reasonable distance from the Commencement perimeters for safety and to allow for the flow of graduates and guests in and out of the area. Anyone in the area outside of the perimeter will be expected to follow current campus COVID-19 protocols and guidelines for gathering. Please contact commencement@knox.edu if you have any questions about Commencement.

    As we continue through the Bridge Phase in Illinois and summer and Phase 5 (full reopening) approaches, hope for a healthy and peaceful future is well within our reach. As we have done for the past year, let’s continue to do our part to end this academic year on a high note and celebrate our resilience, innovation, and deep care for one another.

    TERESA L. AMOTT
    President

    May 20

    Dear Knox Community,

    As we near the end of the academic year and prepare to celebrate our graduating class, please accept my heartfelt gratitude for everything you have all done to ensure our campus community emerges from the past year as healthy and hopeful as humanly possible. It has been a long year, and yet together, we are getting much closer to the light at the end of the pandemic tunnel. 

    COVID Vaccination Policy for Fall Announced

    Students will be required to be vaccinated for the 2021-22 academic year, subject to medical or religious exemptions. Students returning for the 2021-22 academic year should submit their vaccine record to health@knox.edu once fully vaccinated. Health Services will work with students who are unable to access one of the FDA-approved COVID vaccines prior to returning to campus.  

    At this time, faculty and staff are strongly urged to receive the vaccine, but for now, it is not required.   

    May 25 HyVee Vaccination Clinic - First and Second Doses

    Hy-Vee Pharmacy will return to campus on Tuesday, May 25 for the second dose Moderna vaccine clinic. This event will take place in the T. Fleming Fieldhouse from 10:00 a.m. to 2:00 p.m. You can sign up here. 

    Students, faculty, and staff who have not received their first dose of the vaccine are also welcome to sign up with this link. People who receive their first dose at this clinic will need to go to the Hy-Vee pharmacy for their second dose, or find a location close to home that can give the second dose. 

    Reminder - Please Continue to Wear Your Mask on Campus

    We understand that the recent CDC guidance regarding wearing a mask may be confusing for many individuals and organizations. To avoid any confusion at Knox with the short time remaining in the term, we will not change our policies on wearing masks on campus at this time. 

    Even if you are fully vaccinated, please continue to wear your masks according to the Knox Together guidelines through the end of the academic year.

    Important Commencement Reminders for Graduates

    This is a gentle reminder that we are asking graduates who do not plan to use their tickets to please log into the system to release their tickets by this Sunday, May 23. After this deadline, if there are any unused guest tickets, they will be made available to other graduates. If available, groups of tickets will be released and can be claimed on a first come, first served basis on Tuesday, May 25 at 8:00 a.m. and 8:00 p.m. 

    Also, please mark your calendar for Commencement rehearsal on Thursday, June 3 on the South Lawn. All students walking in the ceremonies are required to attend. Morning graduates will rehearse at 10:30 a.m., and afternoon graduates will rehearse at 1:00 p.m. Graduates will pick up their cap and gown at rehearsal. Please contact commencement@knox.edu if you are unable to attend rehearsal.

    Please accept my wishes for a peaceful, healthy, and successful conclusion to this academic year.

    TERESA L. AMOTT
    President

    May 14

    Dear Knox Community,

    Yesterday, Governor Pritzker announced that the state has made sufficient progress in mitigating COVID-19 to enter the next phase of our state’s reopening plan, a bridge phase that starts today. This phase offers slightly relaxed capacity restrictions before reaching Phase 5, the full reopening phase. In his announcement, he also said that Illinois is expected to fully reopen and enter Phase 5 of its COVID reopening plan on Friday, June 11, barring any significant reversals in our key COVID-19 statewide indicators.

    Campus Health and Wellness Policies through End of Academic Term
    While the bridge phase expands gathering capacity restriction, given that we have only two weeks left in the academic year and seek to maintain our low COVID positivity rates, we will continue to cap indoor and outdoor gathering limits at 50 people. There may be exceptions to this 50-person limit, particularly for outdoor activities. Exceptions may be requested through the appropriate senior staff member.

    Additionally, we have all heard the news about the CDC issuing updated guidance for fully vaccinated people; the guidance says that if you are fully vaccinated, you can resume activities without wearing a mask or physically distancing, except where required by federal, state, local, tribal, or territorial laws, rules, and regulations, including local business and workplace guidance.

    With the short time remaining in the term, we want to avoid any confusion and will not be changing our policies on wearing masks on campus at this time. Even if you are fully vaccinated, please continue to follow the Knox Together guidelines through the end of the academic year.

    We will communicate summer campus health and wellness policies later this month.

    Graduates Can Bring An Additional Guest to Commencement
    Given this heartening news, we have good news for our 2021 graduates: With capacity limits slightly increased in the bridge phase, and keeping in mind that the six foot social distance requirement is still in place, we have been able to plan for each graduate to invite an additional guest to the Commencement exercises on June 5. This raises the number of guests per graduate from two to three.

    Graduates will receive an email tomorrow, Saturday, May 15 with a link to the electronic ticketing system, along with instructions for how to claim guest tickets. We are asking graduates who do not plan to use their tickets to please log into the system as soon as possible to release their tickets so that others who would like to invite additional guests can claim them. We ask that tickets be released by May 23. After this deadline, if there are any unused guest tickets, they will be made available to other graduates. If available, groups of tickets will be released and can be claimed on a first come, first served basis on May 25 at 8:00 a.m. and 8:00 p.m.

    Finally, I want to thank the faculty and staff who quickly volunteered to assist with Commencement. The volunteer slots are full! We appreciate your enthusiasm and willingness to help make the day extra special for our graduates and their guests.

    If you have any questions about Commencement, please email commencement@knox.edu. You can also visit the Commencement FAQs on our website.

    Thank you for your patience during these unpredictable times as we continue to do our best to provide a joyful Commencement to our graduates while abiding with public health guidelines.

    Best,
    Teresa

    May 6

    Dear Knox Community,

    On Tuesday, Illinois Governor J.B. Pritzker announced that the state of Illinois is on track to enter Phase 5 of its reopening plan in July. This would mark a full reopening with no capacity limits. He also reiterated that we are very likely to enter the next phase of our state’s reopening plan soon -- a transition phase with slightly relaxed capacity restrictions -- before reaching a full reopening this summer. What wonderful news! I am confident that the Knox community will contribute to this positive momentum by continuing to practice our Knox Together Pledge protocols and ensuring that all eligible individuals get vaccinated.

    Important 2021 Commencement Updates

    With one month remaining until our 2021 Commencement exercises, I wanted to share important news with you about the event. We have created a 2021 Commencement site on our Knox College website and are providing answers to frequently asked questions as well, for your convenience.

    As a reminder, we will hold two Commencement events on Saturday, June 5, 2021. The first is scheduled for 10:00 a.m.; the second is scheduled for 3:00 p.m. We anticipate that each ceremony will last one to 1.5 hours. 

    Students were provided the opportunity to indicate a preference for the morning or afternoon ceremony, and they were sent an email on May 1 with their assigned ceremony time to enable their guests to plan travel. By splitting the number of graduates in half, we have the space to safely accommodate graduates and their guests for each ceremony. 

    We  have confirmed the location for our 2021 Commencement; both ceremonies will be held on South Lawn. To ensure we abide by state capacity restrictions, we will be fencing off the stage and seating areas and taking tickets at entrances. Entrance to the Commencement event area is restricted to ticketed guests and those participating in the formal ceremony. 

    A limited number of faculty will participate in the ceremonies formally in light of space limitations on the commencement stage. Faculty and staff can also participate by volunteering to help with the ceremonies. We will need more volunteers than ever before to welcome guests to campus and assist with seating.  If you are interested in volunteering, please sign up here or email kridlon@knox.edu. 

    We hope that this information is helpful to you, and I look forward to seeing many of you on June 5. And, if you have any questions that our communications, website or FAQs about commencement do not answer, please email commencement@knox.edu. Thank you, and see you soon.

    TERESA L. AMOTT
    President

    April 30

    Dear Knox Community,

    We delayed this email for a day since yesterday was Knox Proud Day. A huge thank you to those of you who volunteered, gave, and supported our efforts on this annual day of giving. You can view our thank you video, which shares current donor and dollar amounts, here.

    On Wednesday, Illinois Governor J.B. Pritzker announced that the state is "making progress" in its coronavirus metrics and that we could soon enter the next phase of our state’s reopening plan, a transition phase with slightly relaxed capacity restrictions before reaching a full reopening. This is hopeful news and along with spring weather, should help us all restore and rebalance.

    In order for us to contribute to these positive metrics and keep our campus healthy, we are providing information and reminders below. Please read the information carefully. 

    On-Campus Vaccine Clinic

    Kudos to the 137 students, faculty and staff who received their first Moderna COVID-19 vaccine at the on-campus Hy-Vee clinic on Wednesday! We so appreciate your efforts to keep yourself and your community healthy and safe. Regarding the second dose of the vaccine, Hy-Vee is committed to providing the second dose vaccine clinic, but has not yet set the date and time. This information will come at a later date.

    Students: Email Photo of Your Proof of Vaccination to Health Services 

    As you are aware, in the fall we may require proof of vaccination for students, faculty and staff. To ensure that we have proof of vaccination should anyone misplace their vaccination cards, Health Services is asking students who have completed their COVID vaccination series to send a picture of their proof of vaccination record cards to Health@knox.edu. 

    Fully Vaccinated? Please Continue to Wear Your Mask on Campus

    On Tuesday, the CDC issued updated guidance for fully vaccinated people regarding wearing masks. Given that we have only one month left in the academic year, we want to avoid any confusion and will not change our policies on wearing masks on campus. If you are fully vaccinated, please continue to follow the Knox Together guidelines through the end of the academic year.

    Please Continue to Complete Your Daily Symptom Tracker

    As a reminder, all members of the Knox campus community are required to complete their daily symptom tracker through the end of the academic year. Doing so supports our commitment to following the Knox Together Pledge. The information in the tracker is critical for us as we monitor the overall health status of the community, so If you are not completing your daily symptom tracker, you are putting your fellow community members at risk. If you have any questions about the daily symptom tracker, please contact Health Services.

    Local Vaccination Clinics Scheduled for May 1 - May 4

    If you were unable to receive a vaccination at the on-campus Hy-Vee clinic on Wednesday, the Knox County Unified Command, a coalition of health, safety and education agencies and organizations, is holding four consecutive days of large scale vaccine clinics in Galesburg at 1150 W Carl Sandburg Drive (the old Bergner’s building) from Saturday, May 1 through Tuesday, May 4.

    Please register for the clinics here. To register, you will need to choose a time slot and follow the prompts to submit your registration. Please note that all the green time slots have openings. If a time slot turns red, all time slots at that time are filled. You will receive an email confirmation with a QR code when your registration is finalized; to make sign-in easier, please do your best to take the QR Code with you to your vaccine appointment. 

    Please also consider using these other available vaccination sites.

    Thank you so much for your continued support of one another as we near the end of this challenging academic year.

    TERESA L. AMOTT
    President

    April 22

    KNOX TOGETHER EMAIL - Week of April 19, 2021

    Dear Knox Community,

    We have received a number of questions about end of the year COVID testing and pre-graduation testing for seniors. This email will provide you with answers to those questions and also a reminder about upcoming vaccine clinics, both on campus and in Galesburg.

    All Students: End of the Year Testing

    COVID testing with Shield Illinois will continue through the week of 5/26 on Mondays, Wednesdays, and Thursdays from 8 a.m. to 1 p.m. in the Fieldhouse. Students should continue to schedule their weekly tests by last name in their MyShield portal. Additional testing related to air travel can be scheduled through Health Services by emailing Health@knox.edu. 

    Seniors: Pre-Commencement Testing

    All seniors participating in Commencement must test the week prior to Saturday’s event. Testing will take place during the following dates and times at the Fieldhouse:

    Monday May 31-- 9 a.m. to 1 p.m.
    Tuesday June 1-- 9 a.m. to 1 p.m.
    Wednesday June 2 -- 9 a.m. to 4 p.m.

    These tests can also be scheduled in your MyShield portal. 

    Please note, this is a change from our normal weekly schedule to allow for all test results to be back prior to Commencement. In addition, to allow for a busy senior week schedule, the hours have been extended on Wednesday to 4 p.m. 

    Reminder - Vaccine Clinic Scheduled for April 28

    If you are eligible for a vaccination, please consider signing up for the vaccine clinic for students, faculty, and staff in the Fieldhouse next Wednesday, April 28 from 10:00 a.m. to 2:00 p.m. The clinic is a partnership with Hy-Vee, and the Moderna vaccine will be administered at that time.  

    Please note that you do not need health insurance to get a COVID-19 vaccine with Hy-Vee. The vaccination is free. Pharmacies might collect insurance information, but they cannot charge you for the vaccine or for any fees, copays or coinsurance. In addition, if you do not have insurance, they will not bill you anything nor will they turn you away.

    You can sign up for a vaccine here; slots are on a first come, first served basis. It takes about five to 10 minutes to sign up. There are a total of 208 slots available for the clinic, and when a slot fills, it will no longer appear on the list of available times.

    Regarding the second dose of the vaccine, Hy-Vee has not yet set the second dose vaccine date and time. This information will come at a later date. Please go ahead and schedule your first dose; we will update you as soon as we know the second date and time. 

    Another Option: Local Vaccination Clinics, May 1 - May 4

    We were recently notified that the Knox County Unified Command, a coalition of health, safety and education agencies and organizations, will hold four consecutive days of large scale vaccine clinics in Galesburg at 1150 W Carl Sandburg Drive (the old Bergner’s building) from Saturday, May 1 through Tuesday, May 4.

    Please register for the clinics here. To register, you will need to choose a time slot and follow the prompts to submit your registration. Please note that all the green time slots have openings. If a time slot turns red, all time slots are filled. You will receive an email confirmation with a QR code when your registration is finalized; to make sign-in easier, please do your best to bring the QR Code with you to your vaccine appointment. 

    Please also consider using these other available vaccination sites.

    As more and more of our campus community gets vaccinated, we need to remember that we must stay vigilant and continue to abide by the Knox Together Pledge to keep one another safe and healthy. The pandemic is still with us, as reported this week.

    TERESA L. AMOTT
    President

    April 15

    More info on the Knox Together Email - Week of April 12, 2021

    Dear Knox Community,

    I'm writing to follow up on my earlier Knox Together message. Since then, we have learned that there may be some confusion surrounding the need to have proof of health insurance in order to schedule a vaccine appointment. You do not need health insurance in order to get a covid vaccine or to schedule an appointment with Hy Vee. The vaccination is free. Pharmacies might collect insurance information but they cannot charge you for the vaccine or for any fees, copays or coinsurance. In addition, if you do not have insurance, they will not bill you anything nor will they turn you away.

    Questions have also been asked about the second dose. At this time, Hy-Vee has not set the second dose vaccine date and time. This information will come at a later date. Please go ahead and schedule  your first dose and watch for more information to come. 

    Thanks for those who wrote to me with their questions,

    Teresa

    April 15

    Knox Together Email - Week of April 12, 2021

    Dear Knox Community,

    I am keeping this week’s Knox Together email brief, because I have two very important reminders to share with you today.

    First, COVID-19 cases are on the rise in Knox County, and the State of Illinois is also experiencing a resurgence of the pandemic.  Yesterday, the Illinois Department of Health reported that approximately 24% of the population is fully vaccinated. Although the number of people getting vaccinated continues to rise, the availability of ICU beds is decreasing -- an indicator that the pandemic is still very much with us. You can see how we’re doing at Knox College by visiting our COVID-19 Testing Dashboard, which is updated every Friday afternoon.

    In light of this news, I want to remind our community to stay vigilant and continue to follow the protocols outlined in the Knox Together Pledge. It is essential that everyone on our campus follow safety protocols, including social distancing, masking, and adhering to guidelines for campus events.

    Vaccine Clinic Scheduled for April 28

    I am pleased to announce that we are partnering with Hy-Vee to hold a vaccine clinic for students, faculty, and staff on our campus on Wednesday, April 28 from 10:00 a.m. to 2:00 p.m. in the Fieldhouse. The Moderna vaccine will be administered at that time.  

    You can sign up for a vaccine here; slots are on a first come, first served basis. It takes about five to 10 minutes to sign up. There are 13 openings for every 15 minute time slot -- a total of 208 slots available for the clinic. When a slot fills, it will not show up anymore. I encourage you to sign up quickly if you are interested in getting a vaccine at the onsite clinic.

    Please also consider using these other available vaccination sites if you prefer not to wait until April 28:

    Knox County Health Department
    Hy-Vee 
    CVS (Target) 
    A list of statewide mass vaccination clinic locations.
    Walgreens requires a personalized account. Once you have created your account, you can check vaccine availability by zip code.    

    Finally, I ask all supervisors to remain as flexible as possible in accommodating employee requests to get vaccinated. Hourly employees will receive up to one hour of paid time off to visit the clinic of their choice for each vaccine dose during work hours, coordinated in advance with their supervisors.  Employees should record this time by using the pay code “COVID” on their time cards, with supervisor approval.

    If you have any questions about Knox Together safety protocols or vaccines, please email Health Services at health@knox.edu.

    TERESA L. AMOTT
    President

    April 8

    Knox Together Email - Week of April 5, 2021

    Dear Knox Community,

    Today, we want to address the trial of Derek Chauvin, the former Minneapolis police officer charged with the murder of George Floyd, and its impact. People are making choices daily on how to engage with the trial, whether that is watching it in full or reading news reports. We want to acknowledge that the information being presented and shared is difficult to hear, and may be amplified by racial battle fatigue for our Black community members.  

    This trial acts as another mirror to the history of racial violence in the United States as much as it is about Derek Chauvin's actions. George Floyd’s murder follows an all-too-familiar pattern that our country must commit to undoing -- the systemic racism and violence communities of color have faced for hundreds of years. This offers an opportunity for each of us to ask ourselves how we can take action in our lives to address racial injustice.  Intercultural Life has provided a set of resources to help us learn more about anti-racism efforts and direct actions that can be taken.

    As the trial continues, we also wanted to share a number of resources with all of you that may be of help during the next few weeks. The HOPE Center will be hosting a racial healing circle for Black students, faculty and staff in the coming weeks, more details to come. The Center is also open for students, faculty and staff who want a space to talk or be in community with others. Staff are available to meet one on one with students as well. Counseling Services continues to provide remote sessions, and can be reached simply by emailing counseling@knox.edu to request an appointment. You can find a number of mental health resources related to the Chauvin trial on the NAMI Minnesota website. There are also many racial justice resources that provide ideas for actions you can take now to educate yourself and hold police accountable, including Campaign Zero, Black Lives Matter, the NAACP, and Color of Change. 

    Last Fall during Opening Convocation, our speaker, Randall Strickland ‘90, challenged us to fight for the oppressed, saying “it is so vital to understand that as justice touches everyone, so does injustice.” He encouraged us to “say their names” at every opportunity. So we remember George Floyd. Rayshard Brooks. Breonna Taylor. Atatianna Jefferson. Stephon Clark. Botham Jean. Jamar Clark. Philando Castile. Michael Brown. Eric Garner, and many others. We must continue our work together to fight racism in the United States in all its forms and create a more just world. Today, especially, we ask that you join us in supporting our Black students and colleagues, and in remembering that each of us is obligated to stand up to injustice whenever and wherever it occurs.

    Teresa Amott, President
    Tianna Cervantez, Executive Director for Diversity, Equity and Inclusion

    April 1

    KNOX TOGETHER EMAIL - Week of March 29, 2021

    Dear Knox Community,

    Earlier this week, we announced our current Commencement plan for the class of 2021, and we also shared with the class of 2020 that we are planning a Commencement celebration for them during Homecoming on the afternoon of Sunday, October 10. While both celebrations are contingent upon public health guidance, we are hopeful that we will be able to deliver the joyful, celebratory experience our graduates deserve.

    COVID-19 Update

    This week, the Illinois Department of Public Health reported that an increase in COVID-19 cases, positivity rates, and hospitalizations will keep the state from entering the next phase of Governor Pritzker’s reopening plan. Currently, the Illinois Department of Public health is monitoring key indicators in all 11 health regions of the state that potentially signify a resurgence. The state will continue to monitor for 14 days to determine if current mitigations should remain in place. 

    Since the beginning of Spring term, we have seen three positive student cases, which came with a significant number of close contacts who are currently in quarantine. While our campus positivity rate remains low at 0.53% for the term so far, it is more important than ever for us all to abide by the Knox Together Pledge. We must continue to commit to keeping our campus community healthy.

    Vaccine Update

    The Galesburg Register-Mail has also reported that eligibility for the COVID-19 vaccine in Knox County is expanding to all adults in the county. The Illinois Department of Health advised local health departments to expand eligibility if they have available vaccines. Adults 18 years and over must contact the Knox County Health Department to schedule an appointment.

    We just learned that Cottage Hospital Clinics has COVID vaccine availability this Friday, April 2nd, from 8 am to 4 pm for anyone age 18 and older. You can call 309-343-7130 during normal business hours to ask for an appointment time. 

    There is no shuttle planned for this event. However, Cottage Hospital is within walking distance of the College and the city bus is free to students. Please reach out to Health Services if you have further questions. 

    This expansion is yet another positive step toward our return to the “human-powered” experience that is so special at Knox. We strongly encourage all eligible Knox community members 18 years and over to make an appointment if you have not done so already. 

    We certainly understand that it has been more than a year since the pandemic began its deadly spread across our country, and with the warmer weather and the start of spring term, we are all getting restless to spend time with others. Now, more than ever, we need every member of our community to commit to keeping one another safe and continuing to follow necessary safety protocols. Thank you in advance for your cooperation at this critical time.

    TERESA L. AMOTT
    President

    March 25

    KNOX TOGETHER EMAIL - Week of March 22, 2021

    Dear Knox Community,

    Following a brief Spring Break, classes have resumed and Spring Term, our final term of this academic year, is underway. The white tents used for outdoor classrooms and gatherings in the fall are going up again on our campus (tent reservations are available through the Room Reservations App on MyKnox; login required).

    I do want to remind our community to stay vigilant and continue to follow the protocols outlined in The Knox Together Pledge. Yesterday, Illinois Governor Pritzker indicated concern over very recent reversals in several positive trends, stating public health officials are monitoring to see whether the data indicate spreading COVID-19 variants or just a temporary situation. 

    Vaccine Update

    The Governor has now included higher education employees as a priority group for vaccination, starting this week. This expansion is another step toward returning to the face-to-face residential community that is so special at Knox. We strongly encourage any Knox community members who are eligible for a vaccine to make an appointment

    Also, we want to remind you that last week, the Governor announced that COVID-19 vaccinations will be expanded to all residents 16 and older outside of Chicago beginning Monday, April 12. We recommend that students take something with their College address on it just in case they are asked about a local address prior to receiving a vaccine.  

    For your reference, here are links to those offering vaccines in the area:

    Last week, the Governor announced a phased approach to reopening that will offer us more opportunities over time to gather in groups both inside and outside. We all eagerly anticipate these next stages, as long as the reversals reported yesterday are temporary, and we return to positive trends. 

    Parents and students have asked about COVID-19 vaccination requirements for Knox students. As long as public health guidance continues to support that it is safe and effective, as evidenced by FDA approval beyond emergency use, we anticipate that we will require our students to be vaccinated unless they have a medical, physical, or philosophical objection. We will follow legal and public health guidance. We do not anticipate implementing this requirement until the 2021-2022 academic year.

    Limited Spectator Capacity at Knox Athletic Outdoor Contests

    Beginning March 28, a limited number of spectators will be allowed to attend Knox College athletic outdoor contests for baseball, football, men’s and women’s golf, men’s and women’s soccer, softball, and track and field. Designated seating areas will be assigned for the Knox community (students, faculty and staff) and Prairie Fire student-athletes’ family members. No members of the general public will be admitted to athletics events at this time, and no visiting team spectators are allowed. Our spectator policies are contingent upon COVID-19 guidance and information provided by state and county public health officials. 

    Many Prairie Fire competitions on the Knox campus will be livestreamed to give our fans, families, and friends an opportunity to remain engaged and see our student-athletes in action. All competitions that are planned for livestreaming are already designated as such on the schedules on the Prairie Fire website. 

    For more details on spectator seating areas and expectations at Knox College sports events, please visit our Fan Zone. Check back frequently, as changes may occur at the NCAA, MWC, federal, state, and local levels. Please check for updates on game-day.

    Hope remains on the horizon if we all continue to do our part! Please stay safe and well, and continue to send your questions and ideas to together@knox.edu.

    TERESA L. AMOTT
    President

    March 18

    KNOX TOGETHER EMAIL - Week of March 15, 2021

    Dear Knox Community,

    As we finish our winter term and look forward to the spring, we want to provide a few brief but important updates to you. 

    Spectators at Spring Athletics Events

    The Midwest Conference (MWC) announced its redefined spectator policy on Thursday, March 10th. Each campus will be allowed to make spectator decisions based on its campus conditions and the state and local restrictions in effect. The MWC granted member schools the discretion to make these decisions due to the varying venue and facility situations on each campus and each institution’s ability to control access to its facilities and address the entire campus community’s overall safety. 

    We are hopeful that by early April, we will have the opportunity to open up our athletic events in a safe, limited manner. We are in constant touch with the local public health authorities and medical professionals and are confident that we will be able to accommodate limited spectators in the near future. 

    There are many moving parts to consider as we develop manageable options based on NCAA, Midwest Conference, state, and local requirements, as well as our facility configurations, capacity, and staff size, so please stay tuned for announcements about spectators.

    Vaccinations

    Illinois Governor Pritzker announced earlier today a plan for gradually reopening the state, and stated COVID-19 vaccinations will be expanded to all residents 16 and older outside of Chicago beginning April 12. Illinois is receiving increasing shipments of doses from the federal government. When 70% of Illinois residents 65 and over are vaccinated, capacity limits will be relaxed, (unless the downward trend in COVID-19 metrics reverses during a 28-day monitoring period). As of this morning, 58% of those 65 and  older had been vaccinated. As Knox has been guided by the Illinois capacity limits, these changes will offer us opportunities to gather -- masked and distanced in groups in groups larger than are currently permitted. 

    As vaccines become more available, we strongly encourage any Knox community members who are eligible for a vaccine to make an appointment. Depending upon the location, you may be asked to show proof that you are living in the area. We recommend that students take something with their College address on it just in case they are asked prior to receiving a vaccine.  

    Right now the vaccine clinics continue to be offered by pharmacies, hospitals, and the Knox County Health Department. Additionally, the state of Illinois is adding new statewide mass vaccine clinics every week. It is strongly advised that individuals register themselves, as there are questions specific to the registrant, such as potential for allergic reactions and use of blood thinners.

    We are providing you with a number of links to ensure you have the resources you need to determine eligibility and find a vaccination site.

    State and County Resource Links:

    Pharmacies:

    Students - Spring Break

    The three-day spring break is scheduled for Sunday, March 21 through Tuesday, March 23.  We recognize that this is a very short period of time between two intensive academic terms, and that many members of our community are feeling stress and burnout. We wish there were an opportunity for a longer break, but the short break allows us to complete the year on time while also protecting the community from transmission of the new variants which are circulating across the country. So, we ask you to stay focused on health and safety, and to please use this time to rest, recover and relax. Practice self-care and if you are feeling stressed, reach out to someone who can assist you.

    Thank you for all you have done during the past year to keep our campus safe. I am confident that together, we can all successfully complete this academic year. I hope you all take pride in knowing we all did our part to take care of our community during these unprecedented times.

    TERESA L. AMOTT
    President

    March 12

    Dear Knox Community,

    There has been some confusion and several questions on COVID testing times. Please view the information below for times and dates of testing. 

    Faculty and staff: 

    Knox College employees are able to access saliva testing through MySHIELDIllinois at Knox College. As a courtesy, the College is allowing any employee that feels ill, has been exposed, or would like to take part in COVID-19 testing to do so at no charge. 

    Please do not schedule a test outside of these time frames. The Shield Illinois website will allow you to schedule for any day and time of the week, even days that Knox College is not conducting testing. 

    You should refrain from eating, drinking, tooth brushing, mouth washing, and tobacco use for 1 hour before submitting your saliva sample. 

    Please feel free to contact Human Resources at hr@knox.edu or Health Services at health@knox.edu with any questions you may have.

    Students: 

    Students are required to test every other week, based on the first letter of their last name. Students should also test if they have symptoms of COVID-19 or have been exposed. Testing occurs in the T. Fleming Fieldhouse and the schedule is as follows: 

    Please do not schedule a test outside of these time frames. The Shield Illinois website will allow you to schedule for any day and time of the week, even days that Knox College is not conducting testing.

    Students should visit their MyShield portal to schedule their bi-weekly COVID test.  

    You should refrain from eating, drinking, tooth brushing, mouth washing, and tobacco use for 1 hour before submitting your saliva sample.

    March 11

    KNOX TOGETHER EMAIL - Week of March 8, 2021

    Dear Knox Community,

    This week marks one year of the world taking extraordinary measures to stem the spread of COVID-19. Reaching this significant milestone, we are all feeling hopeful as more and more vaccines are distributed and administered across the globe. This week’s email addresses questions about whether we plan to resume in-person learning and operations in the fall. It also includes some important reminders about ensuring we all do our part to preserve the health and safety of our campus community.

    Plans for Fall Term 2021 

    Many of you have asked whether we will resume normal operations starting Fall 2021. I want to let you know that it is our intention to fully return to our regular, in-person classroom and intercollegiate athletics environment starting with the Fall Term. 

    The residential character of our College, coupled with our human-powered educational delivery model, are our institution’s greatest strengths. We are committed to bringing both fully back for our students’ benefit as soon as conditions permit. 

    When we move back to normal operations, remote learning requests will be evaluated on a case-by-case basis, as they were in pre-pandemic times.  

    Students Returning to Campus for Spring Term

    Those of you who are not currently living on campus but are returning to campus housing for Spring Term should have received an email from Campus Life yesterday. The email covers the following important items: 

    If you did not receive this email, please contact Assistant Dean for Campus Life Jacob McLean at jrmclean@knox.edu. 

    Please Don’t Travel During Spring Break

    The three-day spring break is scheduled for March 21-23, and we are advising you to please refrain from traveling during this brief, three-day period. This will help to preserve the safety and wellbeing of our community, and it will prevent the potential spread of COVID-19, including its newer and more transmissible variants. If you have an essential reason to travel outside of Knox County during this period, please consult with Health Services in advance of your travel.

    If You’ve Been Vaccinated, You Still Must Wear a Mask on Campus

    Health officials are reporting that after you get vaccinated against COVID-19, you still need to practice the usual pandemic precautions, including continuing to wear a mask and maintaining six feet or more of distance from people outside your household. Here’s why:

    Vaccinated Employees - Use HealthCheck Through Remainder of Year

    We have received questions about whether employees who have been fully vaccinated and are past the two-week waiting period after their second shot should continue to use the HealthCheck app. Health Services has advised that everyone must continue to use HealthCheck through the remainder of the academic year. As research into the vaccines and immunity progresses and everyone has been offered the vaccine, we may be able to relax our precautions. 

    This pandemic year has upset our sense of the passage of time in so many ways, and we are only now starting to understand how much has changed and how much has been lost. Some of you have said that you are sorry that I had to spend the last year of my presidency coping with the pandemic, but I want you to know that I have never been more proud of Knox  because of all that we have done as a community to preserve one another’s health and safety. Thank you for your continued support and vigilance. 

    TERESA L. AMOTT
    President

    March 4

    KNOX TOGETHER EMAIL - Week of March 1, 2021

    Dear Knox Community,

    We have heard feedback from many of you that these emails are helpful -- but too long. Going forward, we will make every effort to keep them brief and informative. We are providing reminders about spring return and vaccines in this email.

    I want to again recognize the dedication of our students in keeping our campus healthy. You can see how we’re doing on our COVID-19 Testing Dashboard. 

    Spring Term Return and Protocols - Students and Parents

    Vaccine News for All

    Some key points to keep in mind:

    While the news continues to be hopeful and our future is indeed bright, we still have new COVID-19 variants out there to worry about. Please continue to follow safety protocols and the principles in the Knox Together Pledge.

    Thank you for reading and for your continued support for our efforts to keep the Knox community safe.

    TERESA L. AMOTT
    President

    February 25

    Dear Knox Community,

    Unlike some of the emails we have sent in recent months, this email shares some heartening and hopeful news with you. 

    As of last Friday, we wrapped up the second round of COVID-19 baseline testing with our students. During the two weeks of baseline testing, we conducted 1,589 tests and had 1 positive result, which means we had a 0.06% test positivity rate. Amazing! The low number of positive tests we had throughout our two rounds of baseline testing is a clear indication that all of our students remain committed to our Knox Together Pledge. I am so proud of the dedication our students have exhibited to ensure that our campus remains safe and healthy. 

    COVID Testing Changes for Students

    As a result of this impressive positivity rate, this past Monday, we started testing one half of the campus each week. Students have been assigned alternating weeks based on their last names (A through K during the week of February 22, L through Z during the week of March 1, and so on). Students should visit their MyShield portal and schedule a testing time that is convenient for them each week they are to test.

    Spring Term Return and Protocols

    Students not currently residing on campus but who plan to live on campus for the spring term should return on Sunday, March 21. Students will receive their first COVID test upon arrival and a second one approximately five days later. Students must quarantine in their rooms until they receive notice that their first test result is negative, and may not attend in-person classes or other group activities until receiving a second negative result. Returning students must be in close communication with their spring course instructors to make arrangements to participate in course activities during their quarantine.

    If you have not yet contacted Campus Life about your plans to return to campus housing for the spring term, please do so immediately by emailing campuslife@knox.edu. Additionally, if the March 21 return date is not feasible for you given your finals schedule, please notify Campus Life of this as well, and they will make arrangements to accommodate you.

    Finally, on February 7 you should have received an email from NO-REPLY@UILLINOIS.EDU to create an account to participate in our SHIELD Illinois COVID saliva testing. This email gave you instructions and an activation code to help you set up your account. Once you have done this, you will be directed to schedule a COVID test appointment. Please schedule your appointment for March 21 or for the alternative date Campus Life assigned you to arrive on campus if March 21 does not work for you. Please create your account now; the activation code expires in early March. If you cannot locate your email or if your activation code expires, please call SHIELD at 217-265-6059 to get a new one. 

    MWC Resuming Competition for Spring Sports

    The Midwest Conference (MWC) announced last Friday that it will resume competition for the spring sports of baseball, softball, men’s tennis, women’s tennis, men’s outdoor track & field and women’s outdoor track & field. Member institutions, based upon campus and local realities of the pandemic, retain ultimate authority over the decision whether or not to participate in intercollegiate athletics this spring. At this time, Knox College is optimistic that Prairie Fire student-athletes will participate in competition this spring under the MWC umbrella.

    Vaccine Update

    Vaccine information changes daily as the new administration seeks to ramp up the pace of vaccination ahead of greater transmission of the new variants. This week, the Associated Press is reporting that COVID-19 vaccine makers told the U.S. Congress to expect a big jump in the delivery of doses over the coming month, assuring that they will provide enough shots for most Americans to get vaccinated by summer. 

    In Illinois, vaccines continue to be distributed to county health departments, pharmacies and hospitals, and the state is currently deeming as eligible individuals who are 65+ and certain frontline workers. As of February 25, eligibility was expanded to include individuals under 65 with health conditions that put them at risk of severe COVID illness. From an education sector standpoint, the state continues to restrict eligibility to the K-12 education sector. We continue to monitor eligibility requirements and will notify our campus as soon as anything changes.

    The Knox County Health Department appointment links go live at 2:00 pm every Friday on their Facebook page and their website. You can also check out the Hy-Vee Pharmacy and Walgreens sites for vaccine availability. We know that some Knox retirees and employees who are 65+ have received  vaccinations through those sites, so keep checking. 

    Please continue to ask questions and send ideas and suggestions to together@knox.edu. Your feedback has been incredibly helpful in ensuring we are thorough in our planning and decision making. I continue to be so grateful and impressed by our students, faculty and staff, and their commitment to one another’s safety. And while this week brings us hopeful news, we must remain vigilant in ensuring our community of care stays as strong as it can be for the foreseeable future.

    TERESA L. AMOTT
    President

    February 20

    With a happy heart, I share with you the Midwest Conference (MWC) has opted to move forward with competition for spring sports under the MWC umbrella!

    The Midwest Conference (MWC) announced today that it will resume competition for the spring sports of baseball, softball, men’s tennis, women’s tennis, men’s outdoor track & field and women’s outdoor track & field. Member institutions, based upon campus and local realities of the pandemic, retain ultimate authority over the decision as to whether or not to participate in intercollegiate athletics this spring. 

    At this time, Knox College is optimistic that Prairie Fire student-athletes will be able to participate this spring under the MWC umbrella. 

    “We are thrilled that we have this opportunity to get our student-athletes back into MWC competition,” said Knox College Director of Athletics Daniella Irle. “This is a great day for our Fire family. While the seasons will not be normal, I know that our spring sport student-athletes are looking forward to championship competition after losing that opportunity last spring. As always, Knox College and the Midwest Conference are moving forward with COVID-19 protocols and the health of our student-athletes and staff in mind.”

    “Our student-athletes have been through so much in the last year and have had to adapt, improvise, and overcome,” said Knox College Head Baseball Coach Jami Isaacson. “This is a great day for Prairie Fire and MWC student-athletes because it means that all the work they have been putting in over the last year will come to fruition in MWC competition.”

    “It will feel good to get back on the field after only playing four games in the last 22 months,” added Knox College Head Softball Coach Erin Rutledge. “The team is very excited to show what they can do on the field of play. It is critical that our student-athletes are able to compete against someone outside of our own team.”

    MWC schools are allowed to engage in spring competition against non-league opponents as long as they adhere to the league’s COVID-19 return-to-play protocol and end competition against non-MWC institutions 15 days prior to the start of league play in each respective sport. MWC competition in most spring sports is expected to start between late March and mid-April and will conclude by mid-May. Conference schedules will be posted online in the coming weeks but are subject to change due to the current health circumstances.

    “It’s been nearly eleven months since our student-athletes have played against each other due to COVID-19,” said Ripon College President Zach Messitte, the MWC Executive Committee Chair. “While we are excited to resume league play later this spring, the Conference will continue to adhere to best practices in order to maximize the safety and health of our students, coaches, officials and spectators.”

    The MWC will closely monitor the COVID-19 environment on MWC campuses, local communities and at the regional and national levels as the ten member schools prepare for the upcoming spring season. At this time, no decision about spectators has been made so current guidance (no spectators at MWC events) remains in place and will be reviewed at a later date.

    The Prairie Fire men’s and women’s golf teams compete in the St. Louis Intercollegiate Athletic Conference (SLIAC). At this time, the SLIAC is committed to pursuing competition in the spring.

    DANIELLA J. IRLE
    Director of Athletics

    February 20

    Welcome back to winter term.

    As we return to in-person instruction on February 22, campus buildings will return to regular opening hours with a few additional requirements. 

    Please remember that classroom use follows comparatively strict Knox Together protocol during regular class times to allow for air recirculation in rooms between class meetings. Please use the Library, Science Commons, lounges, and other unscheduled spaces if you are looking for a study space during class times. Meeting spaces can be reserved through the online calendar.

    Departments and program offices may set policies to manage use of spaces, such as labs and studios, in their areas. Please pay attention to locally posted occupancy limits and usage guidelines, and don’t hesitate to seek clarification from the department chairs or office managers.

    CFA Music Practice Rooms are open, but students must reserve a time and room through the room reservation system (available on your my.knox portal, or by emailing Andy Crawford at acrawfor@knox.edu).

    Seymour Library and the Amott Science Commons will be open initially according to the following schedule. Updates will be posted.

    Seymour Library
    Sunday - Thursday: noon - 10:00 pm 
    Friday: noon - 6:00 pm
    Saturday: noon - 5:00 pm

    Amott Science Commons
    Sunday: noon - 10:00 pm
    Monday - Thursday: noon - 8:00 pm
    Friday: noon - 6:00 pm
    Saturday: noon - 5:00 pm

    Help Desk and Computer Lab Hours will be open and adhering to the schedule below.

    Help Desk
    Monday - Thursday 7:30 am - Midnight
    Friday 7:30 am - Midnight
    Saturday Noon - 6:00 pm
    Sunday Noon - 6:00 pm

    Cat/Stellyes Lab
    Monday - Thursday 8:00 am - Midnight
    Friday 8:00 am - 6:00 pm
    Saturday Noon - 6:00 pm
    Sunday Noon - Midnight

    Founders Lab
    Everyday 7:30 am - 2:00 am

    WAC Lab
    Monday - Thursday 8:00 am - Midnight
    Friday 8:00 am - 6:00 pm
    Saturday Noon - 6:00 pm
    Sunday Noon - Midnight

    GDH (Burkhardt) Lab
    Monday - Friday 8:00 am - 4:00 pm

    Your commitment to the Knox Together plan during the fall term allowed us to successfully complete the term. We are optimistic that, with your help, conditions will permit us to keep these spaces open for the remainder of the academic year.

    Michael A. Schneider
    Provost and Dean of the College

    February 18

    KNOX TOGETHER Email for February 18, 2021 - Commencement Updates for Knox Classes of 2021 and 2020

    Dear Knox Community,

    For this week’s email update, we are sharing two emails we sent this afternoon to the Knox Classes of 2021 and 2020 regarding Commencement planning. We wanted to be sure you were aware of these emails in the event that you receive or have any questions about the status of both Commencements.

    Email to the Knox Class of 2021

    Email to the Knox Class of 2020 

    As you can see, we are committed to providing both classes with meaningful celebrations, while balancing the need for campus and personal safety and wellbeing. We will continue to update you as our plans develop. In the meantime, if you have any questions or concerns, please email together@knox.edu. 

    TERESA L. AMOTT
    President

    February 11

    KNOX TOGETHER EMAIL - Week of February 8, 2021

    Dear Knox Community,

    It is wonderful to have our students coming back to campus this week. Their return -- even in the dead of winter -- is a glimmer of hope for the new normal. Thank you to our students and parents for following all arrival protocols, including testing and quarantine, and to our staff and faculty for ensuring our students have the support needed for a smooth transition back to campus. 

    While arriving back to campus is a joyous time for all, please continue to stay vigilant and adhere to the Knox Together Pledge; the safety and wellness of our campus depends upon you. 

    Commencement Decision Announcement Next Week

    In a previous email, we committed to February 15 as the date we would announce our decision regarding the Class of 2021 Commencement. There will be a slight delay in timing, so look for that commencement information arriving by Thursday, February 18.

    Vaccine Distribution Update

    Last week I shared an update on vaccine distribution in Illinois and locally. I’m sure that you will be as pleased as I am to hear that the federal government is stepping up distribution to the states. We anticipate that there will finally be more vaccination opportunities in Illinois in the coming weeks.

    Reminder - Sign up for SHIELD and HEALTHCHECK360

    By now, students, faculty, and staff should have received an emailed invitation to sign up for an account to participate in saliva testing. The email is from NO-REPLY@UILLINOIS.EDU. On February 15, students will receive an email from HEALTHCHECK360. This is the same symptom tracker program that the College used during fall term. You must re-register for the program, and please be sure to choose the time that the email or text comes to you (based on your schedule). 

    On-Campus Event Planning Policy 

    The Campus Meeting and Event Planning Guidelines remain the same as those from fall term. Anyone who is considering hosting a meeting or event must abide by the policy and guidelines, designed to build community while keeping us as safe as possible during the pandemic. Please be sure to review these guidelines before you begin your event planning. 

    Elective S/U Grading Due Date Changed 

    For the remainder of the academic year, the due date for electing S/U grading for a course has been changed to match the course withdrawal date in winter, spring, and summer terms. In winter, the due date for elective S/U grading is March 5.

    Students considering elective S/U grading for a course should consult their academic advisors during the upcoming advising and pre-enrollment period. All other rules and regulations for S/U grading remain unchanged. Elective S/U grading aims to encourage students to take courses outside of their major. We hope that this change for additional time to consider elective S/U grading will support students during this unusual year. 

    For any questions about this change, please contact the Registrar’s Office at registrar@knox.edu. 

    Alumni Achievement Awards

    I encourage you to tune in tomorrow, February 12, at 5:00 p.m. CT when Knox honors our six alumni achievement award winners who are meeting the moment in true Knox ways. From careers in medicine to international  economics, funding for the arts, popular television drama, and life-long learning, this year’s recipients, including two young alumni recipients, truly epitomize the value of a liberal arts education. 

    Looking Ahead

    I am heartened by the focus on vaccine production and distribution, the downward daily trends in the number of COVID-19 cases in our country as reported by the CDC, and the corresponding downward trend in Illinois. 

    However, we must continue to be mindful of the risks of spreading and contracting COVID-19, particularly with the CDC reporting on three emerging variants of the virus (with potential for more severe disease, spreading more easily, requiring different treatments, and/or a change in effectiveness of current vaccines). 

    To help prevent the spread of COVID-19 and its variants, infectious disease experts are recommending double masking -- a cloth mask over a surgical mask. A recent CDC study found that double masking offers substantially improved protection against transmission of and exposure to infectious aerosols, so please layer up!

    Let’s continue to work together to ensure we are keeping each other safe as we move forward to when we can put these trying pandemic times behind us. Thank you for your continued support.

    TERESA L. AMOTT
    President

    February 5

    Dear Colleagues,

    I know many of you are eager to receive the COVID-19 vaccinations and like many of us have found it difficult, and frustrating, to sort through the decentralized information that is out there. Here is what we know at this moment, but we also know that the information is changing daily as the new administration seeks to ramp up the pace of vaccination ahead of greater transmission of the new variants.

    At present, vaccines are being distributed by the federal government to states, which determine who is eligible, where vaccines can be administered, and how many vaccine doses are distributed week by week. 

    In Illinois, vaccines are currently being distributed to county health departments, pharmacies and hospitals, and the state is currently deeming as eligible individuals 65+ and certain frontline workers. We had hoped that higher education would be considered eligible frontline workers, but the state is restricting eligibility to the K-12 education sector. 

    Starting February 5, these sites in Galesburg are receiving vaccines on a weekly basis: Hy-Vee Pharmacy, Walgreens, OSF, Cottage Hospital, along with the Knox County Health Department which is setting up vaccine sites. OSF is prioritizing vaccines for their patients, and they are reaching out to patients on an individual basis. The volume of available vaccines is very sparse at this point, so we all have to be patient and check the websites for the participating sites often. The good news is that we do believe that more vaccines will become available each week.

    The Knox County Health Department appointment links will go live at 2 pm every Friday starting February 5th on their Facebook page and at their website. You can also check out the Hy-Vee Pharmacy and Walgreens sites for availability. We know that some Knox retirees and employees 65+ have been able to get vaccinations through those sites, so keep checking.

    If any of this information changes, we will try to provide links to the new info. I have also found that checking the Register-Mail and WGIL websites has been helpful.

    TERESA L. AMOTT
    President

    February 4

    KNOX TOGETHER UPDATE - Week of February 1, 2021

    Dear Knox Community,

    We are all eagerly awaiting the arrival of students on campus next week.

    Following the required student quarantine period, I’m looking forward to seeing all of you -- masked, physically distanced, and ready to continue your winter term studies -- bringing our campus to life. Today, I am sharing some important reminders with you as you begin your return to Knox. 

    Student COVID Testing and HealthCheck 360 

    All students will be tested twice upon their return to campus and will also be tested every other week for the remainder of the academic year. The test is free and is required for all students taking courses on the Knox campus. 

    Please watch your email for two important items. This week, you will receive an email from NO-REPLY@UILLINOIS.EDU to create an account to participate in saliva testing. This email will give you very specific instructions and an activation code to help you set up your account. Once you have set up your account, you will be directed to schedule a COVID test appointment. Please schedule your appointment on the day you were assigned by Campus Life to arrive on campus. The only testing times available for initial testing are Monday-Thursday 2/8-2/11, 9:00 am to 6:45 pm. 

    On February 15, you will receive an email from HEALTHCHECK360. This is the same symptom tracker program that the College used during fall term. You must re-register for the program, and please be sure to choose the time that the email or text comes to you (based on your schedule). 

    Move-in and Quarantine Safety Protocols 

    If you need assistance moving back into campus housing, you are limited to one move-in helper. Move-in helpers should enter the fieldhouse with you and will be screened for COVID symptoms. Additional guests are permitted to come to campus, but they cannot enter the residence halls. You and your guests must wear masks at all times when on campus except when in your private room or when outside and able to maintain at least six feet of physical distance. 

    Upon your return to campus, it is important that you quarantine in your room until you have received a negative test result. While we anticipate getting results within 24 hours, you should anticipate that your initial quarantine could last for up to 48 hours. Initial quarantine means that you are required to remain in your assigned room, except to use the restroom and pick up meals up to three times a day from dining services. You must wear a mask and maintain at least six feet of physical distance whenever you are outside of your own room (both indoors and outdoors). 

    After you receive a negative test result, you will participate in modified quarantine until Sunday, February 21. During this time, you can hang out in your own suite/house’s common area as long as you wear a mask and maintain at least six feet of physical distance. You can also get fresh air, walk around campus, engage in recreational activities, and visit with friends outdoors, while continuing to follow our safety protocols, including wearing a mask and maintaining six feet of physical distance. 

    You cannot travel during initial quarantine. However, you can travel within Knox County during modified quarantine as long as you wear a mask and practice appropriate physical distancing.

    All students are asked to participate in modified quarantine, even if they have been on campus for the first part of winter term. 

    Winter Term Classes 

    From midnight Friday, February 5 until midnight Saturday, February 13 is our “hard pause” in all courses. Academic work, including preparation for class meetings, resumes on Sunday, February 14. Class meetings resume remotely on Monday, February 15. Students will not have access to academic buildings, including the library, until the academic buildings formally reopen for in-person instruction on Monday, February 22. The only exception to this rule is a small number of cases for maintenance of labs and equipment. The Dean of the College will communicate directly with students who have received approval to access academic buildings in the first half of the winter term about access during the modified quarantine.

    Until the modified quarantine is complete, no group activities will be permitted in academic buildings. 

    Spring Term Advising and Pre-Enrollment Begins

    Advising and pre-enrollment for spring term courses begins on Monday, February 15 and continues until Friday, February 26. All students must meet with their academic advisors during this time to select courses for next term.

    Also, please contact Campus Life if your plans for living on campus for the spring term have changed. 

    Dining During Move-In and Testing/Quarantine Periods

    Knox Dining Services will offer modified service during the move in and testing period. All meals will be provided through the Hard Knox Café. Once the quarantine period has concluded, the Gizmo, Outpost, and Grab n’ Go will resume regular service hours.

    Mealtime hours during quarantine are below. Enter Hard Knox through the doors on the side with the gallery, and exit through the Campus Card office. Dine-in seating will not be available during this time.

    Monday through Sunday:

    Breakfast         7:30 am – 9:30 am

    Lunch               11:00 am – 2:00 pm

    Dinner              4:30 pm – 7:30 pm

    Menu choices will be posted in the following locations: on the dining services webpage, through an optional daily menu mail, on digital screens in the gallery, and at the service counters. To reduce wait times, two counters in Hard Knox will offer take-away food items, including two packaged hot entree choices, rice or potato, vegetables, sides, desserts, and canned or bottled beverages. A vegan meal option will also be available. 

    As with last Spring and Fall terms, any dietary or spiritual food needs can be communicated directly with Chef Joe; arrangements for requested accommodations will gladly be made on an individual basis. Dining inquiries can be directed to Doug Stenfeldt, Dining Services General Manager, at djstenfeldt@knox.edu, or Joseph Peterson, Executive Chef, at jdpeterson@knox.edu.  

    Postal Services During Move-In and Testing/Quarantine Periods

    Knox Postal Services will modify operations during the move-in and testing periods. Hours of operation from Monday, February 8 through Saturday, February 21 are:

    Monday through Friday:  10:00am to 4:00pm
    Saturday:                         10:00am to 11:00am

    You may pick up and drop off your packages and mail by proceeding to the service windows in the lower level of Seymour Union. Please do not access your PO box to retrieve mail. The staff at the service window will retrieve it for you. 

    There will be a postal services employee stationed in the hallway to monitor and limit the number of individuals queued to the service windows. We ask that you follow the instructions of this employee before proceeding to a service window. Also, please use the stairs to proceed to the lower level if possible, so that we may preserve use of the elevator for those who are unable to use the stairs. Once you have concluded your business, exit the area promptly.

    Sherrill Zaric, long time Director of Postal Services, retired from the College on January 25. Please direct any postal services queries to Russell Frakes, Interim Manager of Postal Services ( rffrakes@knox.edu).

    The Knox Together Pledge

    Please remember that adherence to the testing and quarantine protocols are core expectations of the Knox Together Pledge. Please take a moment to review and sign the Pledge if you have not already done so. And if you have already signed the pledge, please revisit it before returning to campus so you fully understand what we are requiring of you to support our campus safety and wellness. 

    Looking forward to seeing you very soon. Safe travels.

    TERESA L. AMOTT
    President

    January 28

    KNOX TOGETHER UPDATE - Week of January 25, 2021

    Dear Knox Community,

    Thank you to those of you who participated in our virtual forum yesterday. We appreciate your questions and ideas; they help us ensure we are keeping our campus as healthy and safe as possible. We are so looking forward to students returning to campus for winter term starting February 8! Our faculty and staff are working tirelessly to prepare an engaging educational experience. We are also looking forward to the next few months, when we hope to carefully ramp up our in-person learning as it becomes safer to do so.

    Important Health and Wellness Policies Update

    As we anticipate returning to campus, I encourage everyone to spend some time reviewing the Knox Together Pledge that we committed to at the start of the academic year. If you are new to Knox and have not yet signed the Pledge, you may do so here. 

    Additionally, I encourage you to refamiliarize yourself with Knox's COVID Health and Wellness Policies. We must take these policies seriously to keep ourselves and each other as safe as possible. The choices you make will impact not only your own health and safety, but also the health and safety of your friends, colleagues, and those who clean our suites and classrooms. 

    Because it is so important that we each do our part to minimize  the spread of COVID-19, the consequences for violating our community’s health and wellness policies are serious. Students who willfully disregard campus protocols regarding wearing masks, physical distancing, participating in large gatherings, and other critical public health restrictions will lose the privilege of living on campus and taking on-campus classes. Student organizations will lose College recognition and funding opportunities. Details about potential sanctions can be found here. All members of the campus community are empowered to remind each other about and request adherence to our COVID-19 health and wellness policies, and may report alleged violations here.

    I am proud that we were able to maintain low positivity rates on campus throughout the fall term and am truly optimistic that we will be able to continue that trend throughout the winter and spring. Let's all do our part to ensure a successful remainder of the academic year.

    CARES 2.0 Funding Update

    Knox is expected to receive $1,982,465 in federal funds from the Coronavirus Relief and Response Supplemental Appropriations Act (CRRSAA) within the next three to six weeks. The funds will again be allocated in two separate portions: One for students, and one for institutional relief. Our student portion will be the same amount as it was in the first CARES Act round of funding -- $664,035. We will again distribute the funds to students with the highest levels of demonstrated financial need. 

    We continue to review the guidance provided by the Department of Education so that we understand the restrictions regarding how we can spend the two funding allocations, and we will keep you informed.

    Faculty and Staff  - Phase 3 of Knox Together Plan on February 1

    Last week, we sent an email to faculty and staff about moving to our Knox Together Plan Phase 3 on February 1. The guidelines for Phase 3 are: 

    We realize departments may have different work arrangements and needs and will require different workplace modifications. Please work with your supervisor to address departmental and individual arrangements.

    Academic Building Opening Schedule Now Through February 22

    We have received a number of questions regarding access to academic buildings in the coming weeks. Most academic buildings will be open during the week of February 1-5 during regular work hours. During the “hard pause” break, students will not have any access to academic buildings, except for the few exceptional cases for maintenance of labs and equipment. 

    Until the modified quarantine is complete, no group activities will be permitted in academic buildings. 

    The Dean of the College will communicate directly with students who have received approval to access academic buildings in the first half of the winter term about access during the modified quarantine. Academic buildings will formally reopen at the end of the modified quarantine on Monday, February 22. 

    Common Topics from Yesterday’s Forum

    We have summarized our answers to some of the most common topics discussed at yesterday’s forum, below. We have also provided you with a link to the student and parent virtual forum for your reference, should you have missed the forum and want to view it.

    Vaccinations: We are doing all we can to facilitate vaccine distribution. We are in touch with the local health officials, who are in charge of allocating vaccine doses to entities authorized to distribute them. Locally, Hy-Vee Pharmacy, Cottage Hospital, OSF, and Walgreen’s are vaccinating those who qualify. Right now, those who are employed by the K-12 schools and those over 65 years of age are able to get vaccinated. There will be more information in the coming months, but as of now, we must wait.

    Regarding COVID-19 vaccination requirements for Knox students, as long as public health guidance continues to support that it is safe and effective, we anticipate that we will require our students to be vaccinated unless they have a medical, physical, or philosophical objection. We will follow legal and public health guidance. We do not anticipate implementing this requirement until the 2021-2022 academic year. 

    When students, faculty and staff will be back on campus: We all recognize that we are on a long arc that stretches incrementally in steps over the months ahead. We will slowly gain new comfort levels and learn more about the new vaccine and vaccination progress. There is no single milestone that will drive a full return to campus for all. Over time, we anticipate that the balance will shift to more and more in-person courses.  We are designing courses to be responsive to public health context and will continue to use social distancing and classroom capacities as we did in the fall. As we get into warmer weather, we will begin using our tents for classes, and will have more outdoor instruction.

    Commencement: We understand that commencement is a critical milestone in the lives of our students and their families, and members of our campus community. And we know that you are eager to hear how we are planning to celebrate that milestone.

    It is very difficult for us to look as far ahead as June, because we don’t know what public health conditions will be by that time. Many colleges are planning hybrid commencements and are offering a combination of live and virtual events. We are reviewing all options for both the Class of 2021 and the Class of 2020, and we will have an announcement about our preliminary plans in mid-February; we hope to have more guidance from public health authorities about travel and gathering size by that time. We currently have a team actively working on commencement planning and options, so please stay tuned.

    Protocols for student return for spring term: From an academic perspective, students need to be in communication with their instructors for spring term so that they know what is expected of them. We know there are a number of students who want to finish out the winter term remotely and return to campus for the spring term. 

    The return date for spring is March 24, 2021. Please contact Campus Life ( campuslife@knox.edu or 309-341-7527) to ensure that you have a housing assignment that meets your needs for the spring term.

    During the forum, we answered nearly 50 questions from participants. I encourage all of you to view the recording to learn more about our plans for the remainder of winter term. This will help ensure that you are apprised of our plans to keep our community safe while offering an engaging Knox experience. 

    Personally, I have appreciated the expressions of support and suggestions for improvement that I have received from you over the past months. I have been so impressed by our students, faculty and staff and their commitment to one another’s safety. I am confident that we will emerge stronger and wiser because of your commitment to our Knox community of care.

    TERESA L. AMOTT
    President

    January 22

    KNOX TOGETHER: Moving to Phase 3 on February 1

    Dear Knox Faculty and Staff,

    As you already know, Governor Pritzker announced on Monday, January 18 that our region (Region 2) will be moving to Tier 1 mitigation rules, further lifting restrictions because our region met the state’s COVID-19 metrics. With this development and through close consultation with public health experts, on February 1 we will move to our Knox Together Plan Phase 3. As a reminder, the guidelines for Phase 3 are:

    We realize departments may have different work arrangements and needs and will require different workplace modifications. Please work with your supervisor to address departmental and individual arrangements.

    As a reminder, during the week of January 4, we began implementation of our updated plan for testing faculty and staff. Everyone must be tested for COVID-19 prior to returning to campus. Please refer to the email dated December 17, 2020 for employee testing dates/times and location. 

    If you have recently traveled via public transportation or participated in a gathering with individuals outside of your household, you should not return to campus until you have received a negative COVID-19 test result. The ideal testing window is five to eight days after possible exposure. Please feel free to reach out to Human Resources or Health Services with any questions about testing options. 

    Please be assured that we will continue to keep you informed as we work together to navigate the continued uncertainties of this time, and will also closely monitor guidance from public health authorities, as we have done since the start of the pandemic. We appreciate your support as our plans to ensure our campus community remains healthy and safe continue to evolve with the pandemic. If you have any questions, send them to together@knox.edu.

    TERESA L. AMOTT
    President

    January 21

    KNOX TOGETHER UPDATE - Week of January 18, 2021

    Dear Knox Community,

    As you may have already heard, Governor Pritzker announced over the weekend that our region in Illinois (Region 2) has moved to Tier 1 mitigation rules, further lifting restrictions because our region met the state’s C OVID-19 metrics. While this is promising news, we need to continue to abide by our Knox Together Pledge to ensure our campus remains safe until the pandemic is under control.

    CARES 2.0 Funding Confirmed

    Last week, Knox received notification from the US Department of Education that we would be receiving a total of $1,982,465 from the Coronavirus Relief and Response Supplemental Appropriations Act (CRRSAA). This funding is a supplement to the CARES Act funding that we received last year. At this point, we know that the funds will again be allocated in two separate portions: one for students and one for institutional relief. Our student portion will be the same amount as it was in the first CARES Act round of funding -- $664,035. 

    We do not yet know when we can draw down the funding, but we anticipate that this will occur sometime in the next three to six weeks. We are continuing to review the guidance provided by the Department of Education so that we understand the restrictions regarding how we can spend the two funding allocations, and we will keep you informed.

    Answering Your Questions

    Following our announcement last week about students returning to campus starting on February 8, we received a few questions. A few of the most common ones are posted below, and we hope that our answers are helpful to you. Should you have further questions, please email together@knox.edu.

    Also, please remember that we are holding two virtual forums to answer any questions you may have about the return to campus, testing and safety protocols, and other issues related to our Knox Together plan. They will both be held on Wednesday, January 27. A faculty and staff forum will take place at 12:00 PM Central Time, and a forum for family and students will be held at 7:00 PM Central Time.  An email will be sent early next week with further details and links to the virtual forums.

    All students will again be tested twice upon their return to campus, and  all students will be tested every other week for the remainder of the academic year. The test administered will be the Shield Illinois Saliva Test, a PCR test created and used by the University of Illinois system, and also used by many other educational institutions in Illinois and other states. The test is free, and it is required for all students who are taking courses on the Knox campus. 

    Knox College Health Services is in constant communication with local officials to determine when the vaccine will be available for the Knox College community, and we will continue to share updates with you.

    At the present time, vaccine allotments are being distributed to county health departments. Each county in Illinois is prioritizing available vaccines according to the guidance of local health experts. At this time we don’t have any additional information, but we will keep you informed. 

    Yes, organizations will be allowed to meet. We understand that these meetings and events play a key role in creating a welcoming, vibrant campus community. All meetings and events must follow our COVID protocols for masks and physical distancing as detailed in the updated guidelines on the Knox Together site.

    All in-person and remote student organization events, with the exception of regular meetings, must be registered with the Campus Life Office. In addition, all in-person event registrations must include a formal safety plan that outlines how the event organizers will ensure compliance with the College’s COVID protocols. 

    We are requiring the same protocols as fall term. We are continuing the rigorous cleaning and sanitation processes for all classrooms and other academic spaces, residence halls and meeting spaces.

    All participants attending in-person classes must wear masks or face coverings at all times. Physical distancing will require that classes meet in smaller subgroups, interactions with faculty and peers will occur both in virtual and in-person settings. Classroom meeting schedules are set to support student engagement while ensuring classrooms have adequate time for air recirculation between meetings. Classroom occupancies are clearly marked. Courses that rely heavily on classroom, lab and studio spaces have been reenvisioned so that physical distancing and cleaning protocols can be observed. 

    Most courses will operate in hybrid modes, with a combination of in-person and remote components to serve students who are on campus as well as those learning from home. We will slowly and intentionally add more in-person components consistent with our data from testing and in response to the availability of vaccinations for our community. In the interests of health and wellness of the entire community, we will follow a careful and deliberate process. 

    If you were planning to live in the dorm, please contact campuslife@knox.edu, or 309-341-7527. Please also notify Tim Foster, Associate Dean of the College: tfoster@knox.edu or 309-341-7214. Share this information with your instructors and academic advisor. Some courses have significant on-campus components in the second half of the term, which you should clarify with your instructors.

    Contact the Campus Life office at campuslife@knox.edu / 309-341-7527. 

    I hope that like me, you are seeing progress and hope on the horizon. While we continue to manage through these uncertain times, we are doing all we can to provide certainty to our Knox College community. Faculty and staff are working very hard to deliver the quality education our students want and deserve, and as we update any processes or protocols, we will let you know as soon as possible. 

    Thank you for your questions; keep them coming. I’m looking forward to seeing you soon.

    Take care,

    TERESA L. AMOTT
    President

    January 14

    KNOX TOGETHER UPDATE - Week of January 11, 2021

    Dear Knox Community,

    Following a significant amount of research and consultation with public health authorities, we have determined that students can begin returning to campus starting Monday, February 8. Students received a  communication from the Campus Life Office in November with their assigned return to campus/testing date and time. Campus Life will also resend this email for your convenience by the end of next week. If you have any questions about your return to campus, please contact campuslife@knox.edu.

    Why we made this decision

    Governor Pritzker announced that Friday, our region (Region 2) will be moving to Tier 2 mitigation rules, relaxing restrictions from Tier 3. The governor indicated in a statement that Illinois did not experience the post-Thanksgiving uptick in COVID cases that plagued most of the rest of the country. While closely watching the post-holiday positivity rates, his administration is cautiously optimistic. 

    We are ever mindful of the consequences of the pandemic for our educational mission. Numerous studies and news articles -- and our own experiences and internal data -- have shown that prolonged isolation is stressful for all of us. This impact is especially profound for our students, who have selected a residential college experience as the best place for their learning. The remote instructional environment has allowed us to keep moving forward while protecting the health of the community during this stage of the pandemic. At the same time, we know that a return to campus is necessary to provide the full range of human-powered, engaging experiences that our students have come to expect from Knox College.

    We also learned a great deal about mitigating the virus on our campus during the fall term and have developed an even stronger plan to keep our campus healthy. Our plan includes a new more comprehensive and less-invasive testing regimen combined with an updated quarantine strategy. Many colleges in our peer group are implementing similar plans, and when we look at ours in comparison to others, we are confident that our enhanced Knox Together plan is the right one for our community. 

    Virtual forums to answer your questions

    We will host two virtual forums to answer any questions you may have about the return to campus, testing and safety protocols, and other questions related to our Knox Together plan. They will both be held on Wednesday, January 27. A faculty and staff forum will take place at 12:00 PM Central Time, and a forum for family and students will be held at 7:00 PM Central Time. 

    Stay tuned for further details and links to the virtual forums.

    Vaccine rollout and information

    There is hope on the horizon for a faster vaccine rollout. This week, the CDC communicated new vaccine priorities for people 65 years of age and older and those with preexisting conditions that enhance their vulnerability to severe COVID-19 disease. More pharmacies and community centers around the country are being authorized to administer vaccines. Governor Pritzker is also expected to soon announce a timeline for the next phase of the vaccine rollout. 

    Knox College Health Services is in constant communication with local officials to determine when vaccines will be available for the Knox College community, and we will continue to share any updates or changes with you. Each county in Illinois is going to prioritize available vaccines to residents, according to the guidance of local health experts.

    Important improvements to testing protocols 

    We tested all students for COVID-19 twice upon arrival to campus in the fall term, with ongoing surveillance testing throughout the term. While this was successful, we are implementing a much more comprehensive testing program with a less-invasive and equally accurate test for winter and spring terms -- one that delivers results faster and only requires saliva from those being tested. All students will again be tested twice upon their return to campus. Additionally, all students will be tested every other week during both terms. 

    The test administered will be the Shield Illinois Saliva Test, created and used by the University of Illinois system, and also used by many other educational institutions in Illinois and other states. 

    The Shield Illinois Saliva Test will also be available to faculty and staff, who may test for symptoms or concern of exposure.

    An employee or student who develops symptoms or has a concerning exposure will be asked to test as soon as possible. Faster testing and quarantine will help us preserve the health and well-being of our campus community.

    Stay tuned for emails with further details regarding the upcoming terms’ testing days and times.  

    What students need to do upon returning to campus

    Upon your return to campus, please remember that you can transmit the disease to others even if you are exhibiting no symptoms, so for the health of our community, it is important that you quarantine in your room until you have received a negative test result. While we anticipate getting results within 24 hours, you should anticipate that your initial quarantine could last for up to 48 hours. Initial quarantine means that you are required to remain in your assigned room, except to use the restroom and pick up meals three times a day from dining services. You must wear a mask and maintain at least six feet of physical distance whenever you are outside of your own room (both indoors and outdoors). 

    After you receive a negative test result, you will participate in modified quarantine until Sunday, February 21. Modified quarantine means that you can hang out in your own suite/house’s common area as long as you wear a mask and maintain at least six feet of physical distance. You can also get fresh air, walk around campus, engage in recreational activities, and visit with friends outdoors, while continuing to follow our safety protocols, including wearing a mask and maintaining six feet of physical distance. All students are asked to participate in modified quarantine, even if they have been on campus for the first part of winter term. 

    Questions and Answers

    Here are answers to some questions we expect you might have right away; please also remember to visit the Knox Together website for answers to other questions. You can also email together@knox.edu and attend one of the virtual forums we are holding on Wednesday, January 27 if you have additional questions.

    How does this impact quarantine protocols for those arriving from abroad?

    Students arriving from abroad will follow the same quarantine plan as those arriving from within the United States. If a student shows any COVID-related symptoms, their quarantine period may be extended.

    Does this quarantine plan apply to students who stayed on campus during winter break?

    Students who lived on campus during winter break will have a COVID-19 test but do not need to quarantine in their rooms while awaiting test results. However, they must participate in modified quarantine until February 21.

    When will staff be returning to campus?

    Essential employees providing direct services to students, such as dining services, will need to be on campus when students return. Those not providing direct services will continue to work remotely until a vaccine becomes widely available to members of our community.

    What if my roommate and I have different arrival dates, so our initial quarantines end on different days?

    If Roommate A’s initial quarantine ends before Roommate B’s, Roommate A may move into the modified quarantine phase, moving about campus while adhering to mask and physical distance policies. However, no in-person classes or student activities will be allowed until all students have received their first test results.

    What types of meals will be available during quarantine?

    Knox Dining Services will offer modified service during the move in and testing period. All meals will be provided through the Hard Knox Café.  Once the testing and quarantine period has concluded, The Gizmo, The Outpost, and Grab n’ Go will resume regular service hours.

    Mealtime hours during the move in and testing period are below. Enter Hard Knox through the doors on the side with the gallery, and exit through the Campus Card office. Dine-in seating will not be available during this time.

    Monday through Sunday:

    Breakfast         7:30 – 9:30

    Lunch               11:00 – 2:00

    Dinner              4:30 – 7:30

    Menu choices will be posted in the following locations: On the dining services webpage, through an optional daily menu mail, on digital screens in the gallery, and at the service counters. To reduce wait times, two counters in Hard Knox will offer take away food items, including two packaged hot entrée choices, rice or potato, vegetables, sides, desserts, and canned or bottled beverages, as well as a vegan meal option. 

    As with last Spring and Fall terms, any dietary or spiritual food needs can be communicated directly with Chef Joe, and we will make arrangements for accommodations on an individual basis.

    Dining inquiries can be directed to Doug Stenfeldt, Dining Services General Manager, at djstenfeldt@knox.edu, or Joseph Peterson, Executive Chef, at jdpeterson@knox.edu.  

    How will I get my mail/packages/textbooks during quarantine?

    We are working on the details of how this will happen, but we will make sure you can access essential textbooks and mail when you return to campus.

    Can I work in my on-campus job during quarantine?

    You can work in your on-campus job during initial quarantine if you can do so remotely. Exceptions may be made for students who lived on campus during the first part of winter term.

    Can I go off campus during quarantine?

    Not during initial quarantine. You can travel within Knox County during modified quarantine, as long as you wear a mask and practice appropriate physical distancing.

    We know this is asking a lot of you, and we encourage you and your family to regard this as a short-term sacrifice—a collective community effort that will give us the very best chance at continuing in-person instruction for the duration of the term.  

    Please remember that adherence to the quarantine protocol is a core expectation of the Knox Together Pledge. I hope you will take a moment to review and sign the Pledge if you have not already done so. You will need to be logged in to your Google account with your Knox email address and password to access the Pledge.

    Fifth Year Guarantee reminder

    We also want to remind you of our “Fifth Year for Free Guarantee.” If you are enrolled at Knox full-time for the entire 2020-21 academic year, you can return to campus for up to one additional year of study, tuition-free—and take part in more of the opportunities you’ve been looking forward to. If you’re interested in pursuing this option, please work with your academic advisor to determine appropriate course selections. Student-athletes will need to consult with the athletics department about eligibility requirements.

    Hope on the horizon

    The health and wellness of our campus community continues to be our top priority. Faculty and staff are working very hard to deliver the quality education our students want and deserve. There continue to be many aspects of our environment that we cannot control, but we have learned from the fall term, and there is hope on the horizon for the warmer weather months. In the meantime, we need to remain as flexible, nimble, and resourceful as ever, as our country continues its efforts to mitigate the pandemic. 

    Looking forward to seeing you next month!

    TERESA L. AMOTT
    President

    January 7

    KNOX TOGETHER UPDATE - Week of January 4, 2021

    Dear Knox Community,

    Happy New Year! I hope you all had a peaceful, restful and safe holiday season. I also want to extend a warm welcome back to our faculty, staff, and students as we start our winter term virtually. 

    The rollout of the vaccines in Illinois has begun with frontline health workers. We are in touch with the public health authorities and are awaiting information on the sequence of vaccinations. At present, we do not know where higher education will fall in the priorities, but we will share any information we receive as soon as possible.

    We will continue our safety protocols for the foreseeable future, however, as it may take more time than expected for us all to receive the vaccines. Illinois Governor Pritzker’s mitigation plans for our health region (we’re currently at Tier 3) remain in effect, as well.

    Parents and Students - What to do now

    Students will need to complete an online check-in by this Friday, January 8 by logging in to my.knox.edu. Online check-in is very important to the Registrar, Student Financial Services, and other offices needing to know who is enrolled this term. Students will not be able to access any Knox apps or student schedules until the Online Check-in process is completed.

    Our current plan is still to have students return to campus the week of February 8. We have identified next Friday, January 15 as the date by which we will advise you of any necessary modifications to this timeline. If we need to consider alternative options, we will look to guidance from national, state and local public health authorities.

    Faculty and Staff - What to do now

    Please continue to plan for students returning to campus starting February 8. Dean Schneider’s separate report to faculty on December 11 addresses details of the calendar and contingency plans for winter term.

    This week, we began implementation of our updated plan for testing faculty and staff. As you know, everyone must be tested for COVID-19 prior to returning to campus, just as we did in the fall. Please refer to this email from Health Services about return to work testing processes. If you have questions about testing, please contact Health Services.

    If you traveled via public transportation or participated in a gathering with individuals outside of your household during the holiday break, you should not return to campus until you have quarantined at home for 14 days or received a negative COVID-19 test result. You can access testing beyond what Health Services is offering by contacting the Knox County Health Department at (309) 344-2225, or by contacting your primary care provider. The ideal testing window is five to eight days after possible exposure. Please feel free to reach out to Human Resources or Health Services with any questions about testing options. 

    Similarly, students engaging in on-campus work or research activities in your areas must contact Health Services to arrange for a COVID-19 test immediately following any travel or holiday gatherings, and quarantine until they receive a negative test result. 

    Coronavirus Response and Relief, Supplemental Appropriations Act 

    Recently, we were gratified to learn that institutions of higher education will receive some funding from the new Supplemental Appropriations Act recently signed by President Trump. At this time, we do not know how much we will receive, whether there will be restrictions on the use of the funds, or how soon we will receive funds. We will communicate any updates to you when we receive additional information.

    We encourage you to visit the Knox Together website, and follow our social media channels for campus updates. Thank you for your support and care for our campus community as we navigate these uncharted waters together.

    TERESA L. AMOTT
    President

    December 17

    KNOX TOGETHER UPDATE - Week of December 14

    Dear Knox Community,

    I know we are all happy to see some hope on the horizon with the first deliveries of a highly effective COVID-19 vaccine this week. We will still need to practice our safety protocols for the foreseeable future, however, as it will be some time before we can all receive the vaccines. 

    You will likely find some of the content in this email to be similar to the content in last week’s communication, but it is important information that will keep our community updated and safe; that is why we are sending it yet again this week.

    Return to Work Testing for Faculty and Staff

    We have updated our plan for testing faculty and staff starting on Monday, January 4.  Everyone will need to be tested for COVID-19 prior to returning to campus after the holidays, just as we did in the fall. You recently received an email from Health Services about return to work testing processes. If you have any questions about testing, please contact Health Services.

    Travel Guidance

    Additionally, we ask that you be especially vigilant about your safety and health over the coming holidays. If your holiday break plans include traveling via public transportation or participating in a gathering with individuals outside of your household, you should not return to campus until you have quarantined at home for 14 days or received a negative COVID-19 test result. You can access testing by contacting the Knox County Health Department at (309) 344-2225 or by contacting your primary care provider. The ideal testing window is five to eight days after possible exposure. Please feel free to reach out to Human Resources or Health Services with any questions about testing options. 

    Similarly, students engaging in on-campus work or research activities in your areas must contact Health Services to arrange for a COVID-19 test immediately following any travel or holiday gatherings, and quarantine until they receive a negative test result. 

    Plan for Students Return to Campus

    Our current plan is still to have students return to campus the week of February 8. We have identified Friday, January 15 as the date by which we will advise you of any necessary modifications to this timeline. If we need to consider modification options, we will look to guidance from national, state and local public health authorities.

    Stay in the Know About Knox Together 

    Visit the Knox Together website, and follow our social media channels for campus updates and news about Knox students and our extended Knox community. Check your email for these Knox Together Updates.

    Parents and Students - What to do now

    Students will need to prepare for the remote start of the winter term on Monday, January 4, continue to plan for a return to campus the week of February 8, and remember that we will make and communicate a firm decision on January 15 about any plan modifications.

    Faculty and Staff - What to do now

    Please continue to plan for students returning to campus starting February 8. Dean Schneider’s separate report to faculty on December 11 addresses details of the calendar and contingency plans for winter term.

    We also ask that you follow Illinois Governor Pritzker’s mitigation plans for our health region (we’re currently at Tier 3). Watch for the email on January 15 announcing any change in plans for the winter term.  

    We wish you all a happy holiday season and ask that you also stay safe and practice appropriate safety protocols. The safety of our campus community depends on how each one of us celebrates the holidays. Thank you for your support and care for our campus community as we continue to adjust to the unpredictable nature of the pandemic.

    TERESA L. AMOTT
    President

    December 17

    Dear Knox Community:

    As we look ahead to returning safely after the break, we are asking that each faculty and staff member be tested for COVID prior to resuming work on campus. Health Services will be administering COVID-19 testing to all faculty and staff. There is no cost to you for this testing. 

    Testing will be offered at the T. Fleming Fieldhouse on the following dates and times:

    You may choose the date and time of your testing. Please select the date closest to when you plan to return to work on campus, keeping in mind that test results take 2-4 days. In order to assist Health Services to plan staffing and supplies, please indicate your preferred test date by clicking here. Test results will be sent to you via email from Health Services. 

    We realize that some of you are essential workers on campus and, therefore, will be returning on or before January 4 (or maybe you never stopped working). In this case, you should plan to test on January 4 or as soon as your schedule allows. There is no quarantine required of employees during the time that they are awaiting test results. We do ask that you follow all usual hand hygiene, physical distancing, and masking protocols. In addition, stay home if you are sick. 

    We look forward to seeing you in January. Best wishes from Health Services!

    Abby A. Putnam MS, NP-C
    Knox College Health Services

    December 10

    KNOX TOGETHER UPDATE - Week of December 7

    Dear Knox Community,

    As we get closer to the holidays, we want to remind you of a few items from last week’s email.

    Plan for Returning to Campus to be Finalized by January 15

    Our current plan is still to have students return to campus the week of February 8. 

    However, with the potential for increased transmission during the holidays, a vaccine rollout plan that may shift frequently, and changing guidance from health officials about the safety of travel, we have identified Friday, January 15 as the date by which we will advise you of any necessary modifications to this timeline. As we consider modification options, we will look to guidance from national, state and local public health authorities.

    For Students and Parents: What to do now

    Please enjoy your holiday season and stay safe, wearing your masks, practicing physical distancing, and quarantining after travel or gatherings that may put you at risk for exposure. Avoid indoor venues that may attract crowds, and if you celebrate with others, try to do it in groups of 10 or fewer. 

    Visit the Knox Together website, and follow our social media channels for campus updates and news about Knox students and our extended Knox community. Check your email for these Knox Together Updates.

    Prepare for the remote start of the winter term on Monday, January 4, continue to plan for a return to campus the week of February 8, and remember that we will make and communicate a firm decision on January 15 about any plan modifications.

    For Faculty and Staff - What to do now

    We wish you a happy holiday season and ask that you also stay safe and practice appropriate safety protocols. The safety of our campus community depends on how each one of us celebrates the holidays.

    Faculty, please continue to plan for students returning to campus starting February 8. Dean Schneider will share a separate communication regarding winter term preparations.

    Staff, please continue to follow Governor Pritzker’s mitigation plans for our health region (we’re currently at Tier 3). Watch for the email on January 15 announcing any change in plans for the winter term.  

    We thank you for your continued resilience and flexibility as we adjust to the unpredictable nature of the pandemic. The coming winter term will likely require that we continue to observe our COVID-19 practices, and yet, there is certainly hope ahead for all of us in 2021. May your holidays be safe, peaceful, and enjoyable.

    TERESA L. AMOTT
    President

    December 3

    KNOX TOGETHER UPDATE - Week of November 30

    Dear Knox Community,

    As we enter winter break and begin preparing for the remainder of the academic year, we want to share recent news from The Midwest Conference, provide information about a decision date for any potential modifications to the current plan for students to return to campus the week of February 8, and update you on our Knox together communications.

    The Midwest Conference Announces Plan for Fall and Winter Sports

    The Midwest Conference (MWC) Presidents Council announced today that it would not sponsor league competition, including championships, for fall and winter sports during the 2020-2021 academic year. The decision was unanimous and covers men’s and women’s basketball, men’s and women’s cross country, football, men’s and women’s soccer, men’s and women’s swimming & diving, men’s and women’s indoor track & field, and volleyball. The recent surge in positive COVID-19 cases, both regionally and nationally, the resulting impact on academic calendars, and the continued uncertainty surrounding the pandemic were all factors in the decision not to play a winter athletic schedule. 

    We know that this is a very disappointing day for our fall and winter sport student-athletes, but they should not be without hope. As we did in the fall, we will keep moving forward to reimagine athletics seasons to ensure our student-athletes have the most robust experience possible this year. The Prairie Fire Athletics Department will provide athletics-centric training to fall and winter student-athletes when they return to campus. Our Prairie Fire student-athletes and coaches will continue to adapt and adjust as we navigate the COVID-19 landscape together, keeping in mind that the health and well-being of our student-athletes is our number one priority. Fall and winter student-athletes will receive more detailed information from the Director of Athletics and head coaches in the weeks ahead.

    Decision Date for Returning to Campus (or not)

    As you know, there is much uncertainty surrounding the pandemic, including the potential for increased transmission during the holidays, a vaccine rollout that is still in the early planning stages, and guidance from federal, state and local health officials about the safety of travel. Our current plan is still to have students return to campus the week of February 8. Nonetheless, given all of the unknowns, we have identified Friday, January 15 as the date by which we will advise all of you of any necessary modifications to this timeline, including the possibility of completing the entire winter term remotely. As we consider modifications, we will look to guidance from national, state and local public health authorities.

    Regular Communications

    With this email, we will begin a regular weekly cadence of communication to you, every Thursday with the exception of Christmas Eve and New Year’s Eve. 

    We will also send special, singular emails as needed to communicate important and urgent news. 

    Prior to returning to campus, students and their parents will also receive emails regarding health protocols to follow once students are back at Knox.  

    For Students and Parents: What to do now

    Please enjoy your holiday season and stay safe, wearing your masks, practicing physical distancing, and quarantining after travel or gathering that may put you at risk for exposure. Avoid indoor venues that may attract crowds, and if you celebrate with others, try to do it in groups of 10 or less. 

    Check the Knox Together website, and be sure to follow our social media channels for updates on what’s happening on campus, and other news about Knox students and our extended Knox community. Check your email regularly for these Knox Together Updates.

    Be prepared for the remote start of the winter term on Monday, January 4, continue to plan for a return to campus the week of February 8, and remember that we will make a firm decision by January 15 about any changes to the current plan.

    For Faculty and Staff - What to do now

    We wish you a happy holiday season and ask that you also stay safe and practice appropriate safety protocols. 

    For Faculty, please continue to plan for the students’ returning to campus starting February 8. You will also want to develop a contingency plan, should the decision on January 15 be that winter term remains remote

    Staff, please continue to follow Governor Pritzker’s mitigation plans for our health region (we’re currently at Tier 3). Watch for the email on January 15 announcing any change in plans for the winter term.  

    Thank you for your continued support and patience as we navigate the rough waters of these unprecedented times.

    TERESA L. AMOTT
    President

    December 3

    Midwest Conference Announces Plans for Fall and Winter Sports in 2020–2021

    November 12

    Dear Colleagues:

    Many of you have asked about the status of our campus after our fall term ends on November 30. As you may recall, in response to rising COVID-19 numbers in our Health Region, Governor Pritzker recently imposed enhanced mitigation measures across the state. Public health officials nationwide are also expressing great concern about the potential for virus transmission during winter indoor gatherings, especially around the holiday season.

    To ensure the health and safety of our campus community during an especially vulnerable time, we will return to Phase 1 of our three-phase plan for reopening the campus on Monday, November 30. Phase 1 encourages remote work for most employees and allows up to 25% of employees to work on campus, following physical distancing, mask wearing, and additional safety protocols. Please speak with your supervisor about any needs to de-densify your work area to ensure compliance with Phase 1 guidelines.

    If your holiday break plans include traveling via public transportation or participating in a gathering with individuals outside of your household, you should not return to campus until you have quarantined at home for 14 days or received a negative COVID-19 test result. You can access testing by contacting the Knox County Health Department at (309) 344-2225 or by contacting your primary care provider. The ideal testing window is five to eight days after possible exposure. Please feel free to reach out to Human Resources or Health Services with any questions about testing options. 

    Similarly, students engaging in on-campus work or research activities in your areas must contact Health Services to arrange for a COVID-19 test immediately following any travel or holiday gatherings, and quarantine until they receive a negative test result. Students who have applied for on-campus housing should have been notified of their approval to engage in on-campus activities. Any students not living on campus but wishing to engage in on-campus academic activities during the winter break or during the remote portion of winter term must apply to the Dean of the College through this form. 

    For safety purposes, we are also implementing a modified lock-down of campus buildings. The following buildings will remain open to campus community members only during the break, and will follow our normal business hours of 8:00 a.m. to 4:30 p.m.:

    The E&L Andrew Fitness Center and outdoor athletics facilities will be available for current on-campus students, faculty, and staff, and will require following physical distance and mask protocols. The outdoor soccer, basketball, track, and tennis facilities will be open. The Memorial Gym, T. Fleming Fieldhouse, and Frank M. Lay Pool will be closed. The Fitness Center hours (as of November 23) will be Monday through Friday 1:00 to 3:00 p.m. and 4:00 to 6:00 p.m., and Saturday 9:00 a.m. to 12:00 p.m. The Center will be closed on Sundays. 

    We appreciate your support as our plans to ensure our campus community remains healthy and safe continue to evolve with the pandemic. If you have any questions, feel free to send them to together@knox.edu. Thanks to you all for your patience as we stand Together at Knox, and please accept my best wishes for a safe, relaxing, and enjoyable holiday season.

    TERESA L. AMOTT
    President

    November 4

    Dear Knox Community,

    On Sunday, November 1, Illinois Governor Pritzker announced enhanced COVID-19 mitigations for our part of the state because our region, one of 11 healthcare regions established in Illinois, has had a COVID positivity rate of more than 8 percent for three consecutive days. 

    The enhanced mitigations, effective today, include limiting social gatherings to no more than 25 people. Although the mandate states that the mitigations do not apply to schools, Knox College will voluntarily adhere to this limit, both indoors and outdoors. Supervised meetings of classes, athletic teams, etc. will continue to be governed by existing protocols. Please remember that our health and wellness policies apply both on and off campus.

    It has been several months since the pandemic became an unwelcome part of our lives. A colleague recently mentioned his desire to see COVID-19 “in the rearview mirror,” and I certainly share that desire. I want to thank each and every one of you for observing our health protocols—wearing masks, remaining physically distant, washing hands frequently, and, above all, having respect for one another as we work to protect the health of our community. As a result of your efforts, our campus positivity rate remains very low. As the pandemic evolves, we will continue to follow state and local guidance to keep our campus community safe.

    TERESA L. AMOTT
    President

    October 28

    With only a few weeks left in Fall Term, I want to celebrate all of your efforts to adhere to the health and wellness policies regarding masks, physical distancing, and other public health measures. It has not been easy, but we are all learning and adapting together.  Your individual efforts have made a difference in our community. Thank you!

    Some of you have asked for clarification about hosting and attending gatherings off campus at Knox student apartments/houses. I want to remind everyone that health and wellness policies apply both on and off campus. Here are a few specific reminders about life off campus:

    There are serious consequences which are outlined in the accountability rubric  for violations of these policies. Specifically, attending an unauthorized party or gathering on or off campus may result in loss of privilege to live/learn on campus, and hosting an unauthorized party or gathering on or off campus either as an individual or as part of a student organization may result in suspension. 

    I share this information because I know you want to make good choices both on and off campus to help protect the students, faculty and staff you come into contact with.

    Deb Southern
    Assistant Vice President and Dean of Students

    October 2

    Dear Knox Community:

    I write to share with you information on our plans for the remainder of the academic year. As you know, we launched our fall term on September 14 and made the transition to in-person and hybrid instruction on September 21. This was made possible by enormous care and discipline by our entire Knox community—students, faculty and staff—to sustain our educational mission at Knox under highly unusual circumstances. We applaud these efforts to embrace the new ways of working and living together on campus while staying connected with the members of our community learning and working remotely.

    Because of the community response, we remain optimistic that we can complete the current academic term in ways that safeguard health while supporting rich in-person and hybrid educational opportunities. At the same time, we have all been hearing strong words of caution from leading public health experts regarding the future course of the pandemic as we approach the colder months and the typical flu season that accompanies our move indoors. To help to safeguard our community, and especially our most vulnerable members, we believe it is essential that we adapt our academic schedule in response to this guidance. Below we describe the various measures we will take to navigate this complex health landscape with ensuring the delivery of the Knox educational program.

    Schedule for Winter and Spring Terms

    Winter and spring terms will unfold largely according to our traditional academic calendar. winter term courses will begin on January 4, 2021, and Commencement is still slated for June 6, 2021. However, within those bookends, we will make changes to the dates students arrive back on campus after the long winter break.

    We will begin all winter term classes in a remote environment for the first half of the term, and students will not begin returning to campus until the week of February 8, 2021. We will pause instruction during a one-week midterm break (February 8-12) to allow students to transition back to campus and undergo initial COVID testing. This transition will unfold much like the fall term, with one week of remote instruction starting February 15 as students complete their testing and quarantine protocols. We will move fully back to in-person and hybrid instruction beginning February 22 and complete winter term as we are the fall term. Room and board charges will be adjusted accordingly.

    Student-athletes will arrive according to their team schedules. Additional details will be forthcoming on those schedules. In addition, the Midwest Conference is scheduled to make a decision on winter sports competition no later than mid-November, so please stay tuned.

    Students will still have the option of learning remotely for the entirety of winter and/or spring terms if they so choose. Please note that students must remain enrolled continuously in order to take advantage of the "Fifth Year for Free" Guarantee. Additionally, students will be able to petition to remain on campus for winter break and the beginning of winter term if returning home presents significant challenges. More information regarding this process will be forthcoming.

    One of the most significant changes to our academic schedule is that spring break will be quite short and intentionally so. Having completed the work of transitioning students back to campus once, we wish to avoid typical spring break travel and instead move directly into a fully in-person spring term in order to safeguard our campus against any potential outbreaks. Spring term instruction will mostly follow our conventional schedule. We know that this modified schedule will ask more of every member of the community, so we will make some adjustments to the schedule to provide students, faculty, and staff breathing space during the term. We believe this approach offers the best prospects for students to pursue their educational goals, for seniors to complete their work and graduate on time, and for the academic program to be disrupted as little as possible.

    Teaching & Learning

    Many of the changes and adaptations to our new teaching and learning environment will carry over from the fall. All winter term courses will begin in a remote delivery mode and then transition to a combination of in-person and hybrid components. Classroom, studio, lab, and other academic space use will follow the physical distancing and cleaning protocols currently in use on campus. Winter and spring courses, however, will benefit from the full range of technology improvements, classroom modifications, and experimentation, adaptation, and innovation at the core of faculty work since last spring. Faculty have begun the work of making minor modifications to winter and spring course schedules in response to these new guidelines and Winter term pre-enrollment will begin in late October.

    Return to Campus

    In order to facilitate safe and efficient COVID testing, students returning to campus for the second part of winter term will be assigned an arrival date between February 8-11. Students may arrive between 9:00 a.m.–Noon or 2:00p.m.–7:00 p.m. on their assigned date. Campus Life will communicate students’ assigned arrival dates via email in early November.

    As in fall term, all students will receive a COVID test immediately upon their arrival on campus, and then again approximately seven days later. Students will initially quarantine in their room until they have a negative test result. Once a student receives a negative test result, they will participate in modified quarantine until February 22, at which point in-person classes and activities will resume.

    Health and Wellness Policies

    Given current public health guidance, we anticipate that current campus health and wellness policies

    Источник: https://www.knox.edu/

    Open Access

    Peer-reviewed

    • David Ekers ,
    • Lisa Webster,
    • Annemieke Van Straten,
    • Pim Cuijpers,
    • David Richards,
    • Simon Gilbody
    • David Ekers, 
    • Lisa Webster, 
    • Annemieke Van Straten, 
    • Pim Cuijpers, 
    • David Richards, 
    • Simon Gilbody
    PLOS

    x

    Abstract

    Background

    Depression is a common, disabling condition for which psychological treatments are recommended. Behavioural activation has attracted increased interest in recent years. It has been over 5 years since our meta-analyses summarised the evidence supporting and this systematic review updates those findings and examines moderators of treatment effect.

    Method

    Randomised trials of behavioural activation for depression versus controls or anti-depressant medication were identified using electronic database searches, previous reviews and reference lists. Data on symptom level and study level moderators were extracted and analysed using meta-analysis, sub-group analysis and meta-regression respectively.

    Results

    Twenty six randomised controlled trials including 1524 subjects were included in this meta-analysis. A random effects meta-analysis of symptom level post treatment showed behavioural activation to be superior to controls (SMD −0.74 CI −0.91 to −0.56, k = 25, N = 1088) and medication (SMD −0.42 CI −0.83 to-0.00, k = 4, N = 283). Study quality was low in the majority of studies and follow- up time periods short. There was no indication of publication bias and subgroup analysis showed limited association between moderators and effect size.

    Conclusions

    The results in this meta-analysis support and strengthen the evidence base indicating Behavioural Activation is an effective treatment for depression. Further high quality research with longer term follow-up is needed to strengthen the evidence base.

    Citation: Ekers D, Webster L, Van Straten A, Cuijpers P, Richards D, Gilbody S (2014) Behavioural Activation for Depression; An Update of Meta-Analysis of Effectiveness and Sub Group Analysis. PLoS ONE 9(6): e100100. https://doi.org/10.1371/journal.pone.0100100

    Editor: André Aleman, University of Groningen, Netherlands

    Received: February 6, 2014; Accepted: May 22, 2014; Published: June 17, 2014

    Copyright: © 2014 Ekers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Funding: Support for this research was provided by the Mental Health Research Centre (Durham University & Tees, Esk & Wear Valleys Foundation Trust) (https://www.dur.ac.uk/school.health/mhrc/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    Competing interests: The authors have declared that no competing interests exist.

    Introduction

    Depression is the most common mental disorder in community settings [1] and recent predictions state that by 2030 it will be the leading cause of disease burden in high-income countries [2]. NICE [1] promote the use of cognitive behavioural therapy (CBT) combining both behavioural and cognitive techniques. More recently a meta-analysis has suggested equivalence across most psychotherapies for depression [3]. If this is the case the idea of parsimony, using the least complex but acceptable theoretically derived treatment, may offer considerable benefit in terms of stability and distribution of the chosen intervention.

    Behavioural Activation (BA) may be one such parsimonious treatment option. It uses the principles of operant conditioning through scheduling to encourage depressed people to reconnect with environmental positive reinforcement. Whereas more complex therapies such as CBT require 1–2 years of intensive training for therapists to acquire the wide range of competencies the relative small set of techniques necessary for effective delivery of BA may be possible to acquire after 5 days [4].

    It has been 5 years since we conducted the searches for our previous two meta-analyses which indicated BA offered an effective and simple intervention in 16 and 17 randomised controlled trials respectively [5], [6]. This systematic review and meta-analysis updates our previous work exploring the effectiveness of BA as a psychological therapy for depression compared to usual care as we were aware that new studies had been conducted. In addition we explore the relationship of study level moderators such as therapist training level, delivery mode, multi-morbidity, number of sessions and severity with treatment effect. The review also adds to the current evidence base by extending the review to explore BA compared to anti-depressant medication.

    Methods

    Identification and Selection of Studies

    We included studies identified in previous meta-analyses [5], [6] and cross referenced with on additional BA review [7]. In addition we searched a database of 352 psychotherapy studies of depression. This database has been used in a series of published meta-analysis examining depression (www.evidencebasedpsychotherapies.org) and has been described in detail elsewhere [8]. It is updated yearly using a systematic and comprehensive review of all published evidence (1966 to January 2013) and included 14,164 abstracts (3,638 from pubmed, 2,824 from psycinfo, 4,682 from embase, and 3,020 from the Cochrane Central Register of Controlled Trials). Reference lists of identified studies and meta-analyses were examined to ensure no studies had been missed. Finally key researchers in BA were contacted to identify any missed studies or studies in press.

    Inclusion Criteria

    We included all randomised controlled trials for adult (≥16 years) patients with a primary diagnosis of depression who were treated in community or in-patient settings with BA. BA was defined as a behaviourally oriented time limited psychotherapeutic intervention including key elements of self-monitoring and activity scheduling. As BA is a relatively recent term used to describe this intervention we also included studies of behavioural therapy for depression if self-monitoring and activity scheduling were core elements of the intervention. Comparators consisted of a range of waiting list, placebo and usual care. We did not explore the comparative effectiveness of BA with other psychotherapies as this has been updated in other recent reviews [3], [9][9], [10]. We also explored studies where BA had been compared with antidepressant medication. This comparison has been missing in previous reviews and represents an important consideration as antidepressants remain the most commonly received treatment for depression [11]. We included studies in any language to reduce the risk of potential publication bias.

    Studies excluded were those which included participants with psychosis or bipolar disorder, substance misuse problems, cognitive impairment or without depression as a primary diagnosis.

    Study Level Moderators

    Subgroup analyses were conducted to explore any potential dispersion across results. We investigated the moderating effects of:

    • Group/Individual therapy
    • Clinical/non clinical populations (i.e. student samples)
    • Recruitment setting/approach
    • Baseline depression severity
    • Method of depression categorisation at assessment
    • Level of therapist experience (psychotherapist/psychologist compared to specifically trained non specialist)
    • Control type
    • Number of sessions
    • Quality of included studies.

    In addition we explored the type of behavioural treatment employed in the study and if these were associated with effect. We examined the number of the elements currently considered core to BA (self-monitoring, activity scheduling, functional analysis, values assessment) included in each study as a continuous variable and if the treatment were considered simple BA (predominantly self-monitoring and scheduling) or complex BA (self-monitoring, scheduling plus additional behavioural components such as functional analysis and/or values focussed interventions). This subgroup analysis represented an important consideration as more complex BA studies have been excluded from recent reviews [9] as they were deemed to represent ‘third wave CBT’. This classification is not commonly accepted however and careful consideration of the cumulative effect of intervention components would represent useful new data relevant to this debate.

    Outcome Measures

    Our primary outcome measure was depression symptom level, collected either via self-rated or via clinician-rated measures. Where studies included multiple symptom measures, all data were entered and the mean effect was calculated, so that each study provided one estimate of effect.

    Quality Assessment

    Quality of studies was rated according to the Cochrane Collaboration’s Tool for Assessing Risk of Bias [12]. The elements used were;

    1. Adequate generation of randomisation sequence
    2. Allocation concealment
    3. Blinding of assessment
    4. Dealing with missing data.

    Due to the difficulties of blinding participants, therapists and other associated health professionals in psychotherapy studies, this quality factor was excluded. Each study was scored against the above to provide a score of between 0 and 4.

    Data Extraction and Sub Group Coding

    Two researchers extracted data from each trial post treatment and where possible at follow up. Those data were checked by LW and DE in a series of meetings. Any inconsistencies were referred back to the original text. Missing data were requested from study authors by email. Missing standard deviation (SD) scores were imputed from other relevant studies where these data were not available, with imputations tested in sensitivity analysis as per accepted procedures [13]. Finally extracted data were reviewed in a group meeting (DE, LW, A VS and PC) where consensus was reached.

    Meta-analyses

    Effect size was calculated using the Comprehensive Meta-analysis (version 2.2.064) [14] computer program using standardised mean difference (SMD) with value ranges of small (0–0.32), medium (0.33–0.55) and large (0.56 and above) as per standard convention [15]. This approach allows analysis of the same outcome (depression symptom level) using different scales by subtracting the post-test mean of the intervention group from the post-test mean of the control group and dividing results by the pooled standard deviation. This provided the SMD, a consistent scale across measures of depression symptom level in included studies. Hedges g was reported to adjust for potential small sample bias anticipated in this review. Where studies included two or more measures of depression, all data were entered and the mean effect size was calculated within the CMA program. Where studies reported stratified results (i.e. high/low severity) these were combined using the study as the unit of analysis in CMA to reduce undue influence on heterogeneity. A hierarchy of reported data was used for entry into meta-analysis, with means and standard deviations taking priority, as these were considered the best assessment of outcome. Where these were not reported we used effect size data, dichotomous data or tests of significance in that order of preference. Where studies reported dichotomous outcomes, data were used to calculate a standardised effect size using a logit transformation in CMA. We present pooled data with 95% confidence intervals. As we were including studies across a long time span and number of control conditions we anticipated heterogeneity, and hence calculated effect sizes using a random effects model [16]. The random effects model takes into account both within- and between-study variance. Statistical heterogeneity was examined using the I2statistic for statistical variation across studies [17]. The I2statistic provides a measure of the proportion of dispersion of effects across studies that reflect real differences rather than random error. Benchmark values of 25%, 50% and 75% reflect low, moderate and high heterogeneity respectively and we report with 95% confidence intervals. The I2statistic does not include a test of significance so we calculated the Q statistic and report P values associated with that. In addition, SMDs were translated into number needed to treat (NNT) using accepted formulae [18] to ease interpretation of results from a clinical perspective. NNT indicates the number of patients requiring intervention to achieve one additional positive outcome over a comparator.

    Subgroup analyses were conducting using a mixed effects model [14], [19]. This process pools results within groups using a random effects model, and tests for significant difference between subgroups using a fixed effects model. Meta -regression was used for exploration of the moderating impact of continuous variables on effect size indicated by a Z-value and associated p value [14], [19]. We examined the impact of our a priori moderators and type of control condition on effect size. Publication bias was assessed through visual inspection of a funnel plot graph on the primary outcome (post-treatment depression score) for asymmetry. This is an accepted approach, but is subject to inconsistency, with sufficient studies (≥10) being required to differentiate real from spurious asymmetry [20]. In order to counter this problem, an Egger weighted regression test [21] was calculated to quantify potential publication bias, and the trim and fill procedure [14], [19] used to estimate effect size after any such bias was taken into account.

    Results

    After examination 44 of the identified studies were excluded. The reasons for exclusion of these 44 studies were as follows: three studies did not randomise participants adequately [22]–[24], eleven only included active intervention comparisons (therefore no control/active control) [25]–[35], five studies reported excessively high attrition rates (≥50%) or incomplete outcome data [36]–[40] In two studies depression was not reported as the primary diagnosis [41], [42], three studies were excluded as participants suffered from primary substance misuse problems (drug/alcohol)[43]–[45]; one study was excluded as participants had a cognitive impairment [46]. Eight studies were excluded due to cognitive or counselling elements being included in the BA [47]–[54] and five studies were excluded as the symptom level measure used were not depression specific (e.g. BADS/HADS) [55]–[58]. Three studies were dissertation abstracts or papers that were not available for download in the UK [59]–[61]; one study was excluded as it was a pilot evaluation of culturally adapted behavioural activation [62] and finally two studies was excluded as they were doctoral dissertation versions of a later included published papers [63], [64].

    Study details are presented in table 1 and inclusion flow chart figure 1.

    Description of Studies

    Twenty five studies compared BA with control treatments with a total of 1088 subjects (BA condition N = 547; Control condition N = 541) matched the inclusion criteria and were included in the current meta-analysis. A summary of the characteristics of the included studies are presented in Table 1. Sixteen studies focused on the general population, four focused on university students, four focused on older adults, and one on women with post-natal depression. Nineteen studies were set in specialist mental health services, four in primary care or physical health care and two were web based. Sixteen studies involved participants contacting the research team, four studies used screening procedures, three studies used referral and two a mixed approach. Nine studies incorporated complex BA as an intervention and the remaining 16 incorporated simple BA. Twelve studies used a structured clinical interview whereas the remaining 13 used other unstructured forms. Ten studies used both clinician and self-rated measures of depression, 11 used only self-rated measures, and four used clinician rated measures. Treatment as usual was used for the control type in six of the studies, waiting list control was used in 15 of the studies, and a psychological placebo intervention was used in three of the studies. One study used both a waiting list and a placebo as control type. The level of therapist varied from specialist in 22 of the studies, and non-specialist in the remaining three. The delivery mode of the therapy was in an individual format in 15 of the studies, a group format in eight and self-help in the remaining two. Baseline depression scores were moderate to severe for 20 of the studies and mild to moderate for four. One study included both mild-moderate and moderate to severe scores. Number of sessions varied between one and 16. Seventeen studies were conducted in the United States, two in Australia, one in Canada, one in Sweden, one in the Netherlands, one in Spain, and two in the UK.

    One additional study [89] and three studies also included in the BA vs. control comparison [68], [72], [82], [89] were included in the BA vs. Medication meta-analysis (BA condition n = 130; anti-depressant medication n = 153). Two studies used SSRI medication ad complex BA [82], [89] with the other two using tri-cyclic medication ad simple BA. Further details of these studies can be seen in table 1.

    We generally classed studies as low quality with only seven reporting three or more of our quality standards (see table 2).

    Meta-Analysis BA vs. Control Interventions

    BA for depression was compared to controls in 25 studies including 31 comparisons and 1088 participants. The SMD (g) at post treatment was −0.74 (95% CI −0.91 to −0.56 p<0.001 NNT 2.5), representing a large effect size (fig. 2). Sensitivity analysis replacing mid-range imputed standard deviations with lowest and highest observed values had minimal influence on results (g = −0.89, 95% CI −1.14 to −0.64 and g = −0.67 95% CI −0.83 to −0.50 respectively). There was moderate between-study heterogeneity of treatment effects beyond what would be expected due to sampling error (Q 51.64 p 0.008 I2 41.91%). Subgroup analysis was used to explore this dispersion further. We found a significant association with effect size and subgroup in two areas, control type and baseline depression severity. All other subgroup comparisons identified similar SMD across groups (see table 3). Study quality was sub optimal in all but six studies, subgroup analysis indicated no significant relationship between study quality and effect size. The SMD (g) of comparisons in low quality studies at post treatment was −0.77 and in high quality studies −0.67 with similar levels of statistical heterogeneity (see table 3). The median number of clinical sessions with a therapist was eight (range one to 16). Meta-regression using session number as a mediator resulted in a slope of 0.03 (95% CI −0.01 to 0.06, Q total 51.92 p = 0.01, Q session number 2.08 p = 0.15), indicating no significant influence on effect size. Meta-regression using BA components as a mediator resulted in a non-significant slope of 0.04 (95% CI −0.11 to 0.20, Q total 51.64 p = 0.01, Q session number 0.32 p = 0.57), indicating minimal influence on effect size.

    Inspection of the funnel plot indicated no evidence of publication bias. Trim and fill procedures supported this observation, suggesting no change in effect sizes when imputation for potential missing data was undertaken. Egger’s test indicated a symmetrical distribution (intercept −0.92 95% CI −2.26 to 0.43 p = 0.17). In 13 (50%) studies with the largest sample sizes an SMD −0.62 (−0.78 to −0.47) was observed indicating only a limited influence of small studies on the overall estimated effect.

    Five studies including eight comparisons and 273 participants provided follow up data between 6–9 months. The SMD (g) at follow up was −0.35 (95% CI −0.59 to −0.11 p<0.001 NNT 5.1), representing a medium effect size. There was no evidence of between-study heterogeneity of treatment effects (Q 5.12, p 0.66, I2 0%).

    Meta-analysis BA vs. Antidepressant Medication

    BA for depression was compared to antidepressant medication in four studies including 283 participants. The SMD (g) at post treatment was −0.42 (95% CI −0.83 to −0.00 p 0.05 NNT 4.27), representing a moderate effect size in favour of BA (see fig. 3). There was moderate between-study heterogeneity of treatment effects beyond what would be expected due to sampling error (Q 8.34 p 0.04, I2 64.02%). Two studies used SSRI [82], [89] with two studies tricyclic antidepressant medication [68], [72] with no apparent association between drug type and effect size (see table 2). There were insufficient studies to allow further exploration of subgroups or potential publication bias. We conducted sensitivity analysis on study quality by removing the two low quality studies from the analysis [68], [72] resulting in a non-significant effect size in favour of BA of −0.38 (95% CI −1.23 to 0.47 p 0.38).

    Discussion

    In this updated review we found that behavioural activation for depression is clinically effective. With the increased interest in BA over previous years such an update was needed as our previous reviews were conducted over 5 years ago [5], [6]. This current review includes 26 studies which is a clear increase over the 16/17 included in those previous reviews. In addition this current update addresses some of the gaps identified in those reviews (BA vs. medication). We found BA to be superior to controls across 31 comparisons in 25 studies and small but significant short term superiority to antidepressant medication.

    We found a large effect size across studies (g−0.74), similar to those found in our previous reviews (d = −0.70 and −0.87 respectively) whilst including considerably more comparisons and participants. The confidence intervals around these results have decreased slightly from previous reviews. However it is of note that generally studies were small, of low quality and results were short term. This is not surprising as psychotherapy studies often include small sample sizes and participants in control arms were also often offered active treatment after a delay period. We have, however, been able to include sufficient studies in our meta-analysis providing a good overview of findings and the ability to explore the moderate heterogeneity found by subgroup analysis.

    We explored the association between the types of participant recruited and the effect size of the intervention in three subgroup comparisons. We could find no difference in effect between recruitment groups (general adult, older adult, student, post natal) nor if a diagnostic interview had been used in studies, although statistical power to detect differences between subgroups was low. We did however find a larger effect size in studies that had higher baseline depression severity. In addition the setting within which recruitment was conducted and the processes used to identify participants did not moderate the effect size of BA.

    Intervention factors appeared to have no association with effect size. Most studies used individual face to face or group therapy with two studies using self-help based BA with a comparable effect size across delivery modes. One of the potential benefits of BA that has been discussed for some time has been the potential for dissemination due to the relative simplicity of the treatment [29]. In our previous meta-analysis we found no evidence to support this claim, however in this review three studies did include non-specialist therapists. The effect sizes in these studies were large and consistent, and no different from those seen in studies using specialists. Despite being few in number, studies using non-specialists were well conducted and no heterogeneity was observed between them, providing the first evidence supporting the dissemination of BA outside expert delivery. In addition we considered the complexity of BA, observations that are timely as recently some reviewers have sought to reclassify complex BA approaches as a third wave CBT distinct from core BA elements [9]. We found no association between effect size and the level of complexity of the BA used in studies where functional analysis and other ‘complex’ elements were added; as such the re-branding of a sub set of BA studies would appear premature. In addition to the complexity we explored the number of sessions via meta-regression. The median number of sessions in included studies was eight, there was no evidence that the number of sessions was associated with effect size.

    BA was compared to a waiting list control in 20 comparisons, usual care in six and a placebo intervention in five. A significant effect was found indicating that the effect size in those studies using a placebo intervention (attention control/relaxation/drug placebo) as control were smaller than those using waiting list or usual care.

    In summary we found no evidence that population, approach to clinical diagnosis, number of sessions or therapist qualification/complexity of BA had any association with outcome. We did however observe a relationship between baseline severity and the type of control group with outcome. The degree to which this explains the overall heterogeneity observed in our main post treatment results is unclear but the findings provide some analysis of that finding.

    Previous reviews have not included a meta-analysis of BA vs. medication due to the limitation of available evidence, NICE [1] reported one study indicating no difference between groups. In this review we were able to include four studies and found a small but significant difference at post treatment in favour of BA. It is of note, however, when low quality studies were removed from the analysis these differences disappeared suggesting caution when interpreting results. There appeared to be no difference between types of anti-depressant, but again both studies that use tri cyclic medication were of low quality limiting reliability of findings.

    A number of limitations exist to this review. Whilst we were able to include a reasonable number of studies it is of note that many were small and of poor quality. The median sample size in the BA arms were 11 and 16 for controls and medication groups, with ranges of 4 to 56 and 9 to 50 respectively. This links directly to the quality of the studies, there were a significant amount of older studies which generally were not subject to the same level of quality standards as those conducted in recent years. Rather than exclude such studies we chose to include them and deal with quality issues via subgroup and sensitivity analysis. Whilst study quality was not associated with effect size when BA was compared to controls it is of note that only seven studies of the 26 included met three or more commonly accepted standards for RCTs. Study quality appears to be improving over time with those seven studies being generally the most recently conducted however the publication of further high quality studies is needed to improve confidence in these findings. In contrast when poor quality studies were excluded in the BA comparison to medication analysis, the significance of the effect in favour of BA disappeared. This suggests that results found in this comparison must be viewed with caution due to the limited numbers of studies and participants included in the review. We focus mainly on depression outcomes post treatment as only five studies include follow up data beyond 6 months. Some other studies do report longer term follow up for BA that appears promising [38] however comparisons are with other active therapeutic interventions, not control participants, and as such did not meet our inclusion criteria. Our analysis of follow up data vs. control interventions indicates a medium effect size between six and nine months however further research is required examining the longer term benefits of BA. Seventeen of the 26 included studies were conducted in the United States (US) and whilst we could observe no difference between the effect sizes between those inside and outside the US this should be considered in the interpretation of results. The key argument linked to the dissemination of BA is the durability within wider dissemination and whilst we were able to conduct the first exploration of this in meta-analysis from a clinical perspective the linked question of cost utility requires more research.

    Despite limitations, our updated meta-analysis provides evidence that supports BA as an effective treatment for depression with outcomes at least as effective as anti-depressant medication. We have found early indications supporting the implementation of the intervention beyond the traditional psychotherapy workforce. Further, individually fully powered and high quality trials are needed to test BA in terms of low cost implementation and the cost effectiveness this may offer. We are aware of at least one large scale randomised controlled trial currently underway to answer these questions [91].

    Author Contributions

    Conceived and designed the experiments: DE LW PC AVS DR SG. Performed the experiments: DE LW PC AVS. Analyzed the data: DE LW PC AVS. Contributed reagents/materials/analysis tools: DE LW PC AVS. Wrote the paper: DE LW PC AVS DR SG.

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    • Depression 
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    Источник: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0100100
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