SARS-CoV-2 Transmission in Belgian French-Speaking Primary Schools: An Epidemiological Pilot Study

Schools have been a point of attention during the pandemic, and their closure one of the mitigating measures taken. A better understanding of the dynamics of the transmission of SARS-CoV-2 in elementary education is essential to advise decisionmakers. We conducted an uncontrolled non-interventional prospective study in Belgian French-speaking schools to describe the role of attending asymptomatic children and school staff in the spread of COVID-19 and to estimate the transmission to others. Each participant from selected schools was tested for SARS-CoV-2 using a polymerase chain reaction (PCR) analysis on saliva sample, on a weekly basis, during six consecutive visits. In accordance with recommendations in force at the time, symptomatic individuals were excluded from school, but per the study protocol, being that participants were blinded to PCR results, asymptomatic participants were maintained at school. Among 11 selected schools, 932 pupils and 242 school staff were included between January and May 2021. Overall, 6449 saliva samples were collected, of which 44 came back positive. Most positive samples came from isolated cases. We observed that asymptomatic positive children remaining at school did not lead to increasing numbers of cases or clusters. However, we conducted our study during a period of low prevalence in Belgium. It would be interesting to conduct the same analysis during a high prevalence period.     

Differences in receipt of recommended eye examinations by comorbidity status and healthcare utilization among nonelderly adults with diabetes

BackgroundTo evaluate the effect of diabetes comorbidities by baseline healthcare utilization on receipt of recommended eye examinations.MethodsRetrospective analysis of 310 691 nonelderly adults with type 2 diabetes in the IBM MarketScan Commercial Database from 2016 to 2019. Patients were grouped based on diabetes‐concordant (related) or ‐discordant (unrelated) comorbidities. Logistic regression was used to estimate the prevalence ratio (PR) for eye examinations by comorbidity status, healthcare utilization, and an interaction between comorbidities and utilization, controlling for age, sex, region, and major eye disease.ResultsPrevalence of biennial eye examinations varied by the four comorbidity groups: 43.5% (diabetes only), 52.7% (concordant + discordant comorbidities), 48.0% (concordant comorbidities only), and 45.3% (discordant comorbidities only). In the lowest healthcare utilization tertile, the concordant‐only and concordant + discordant groups had lower prevalence of examinations compared to diabetes only (PR 0.95 [95% CI 0.92–0.98] and PR 0.91 [95% CI 0.88–0.95], respectively). In the medium utilization tertile, the discordant‐only and concordant + discordant groups had lower prevalence of examinations (PR 0.89 [0.83–0.95] and PR 0.94 [0.90–0.98], respectively). In the highest utilization tertile, the concordant‐only and concordant + discordant groups had higher prevalence of examinations.ConclusionsAmong patients with low healthcare utilization, having comorbid conditions is associated with lower prevalence of eye examinations. Among those with medium healthcare utilization, patients with diabetes‐discordant comorbidities are particularly vulnerable. This study highlights populations of diabetes patients who would benefit from increased assistance in receiving vision‐preserving eye examinations.     

High prevalence of unusual KRAS,NRAS, and BRAF mutations in POLE ‐ hypermutated colorectal cancers

Exonucleasic domain POLE (edPOLE) mutations, which are responsible for a hypermutated tumor phenotype, occur in 1–2% of colorectal cancer (CRC) cases. These alterations represent an emerging biomarker for response to immune checkpoint blockade. This study aimed to assess the molecular characteristics of edPOLE‐mutated tumors to facilitate patient screening. Based on opensource data analysis, we compared the prevalence of edPOLE mutations in a control group of unselected CRC patients (n = 222) vs a group enriched for unusual BRAF/RAS mutations (n = 198). Tumor mutational burden (TMB) and immune infiltrate of tumors harboring edPOLE mutations were then analyzed. In total, 420 CRC patients were analyzed: 11 edPOLE‐mutated tumors were identified, most frequently in microsatellite (MMR)‐proficient young (< 70 years) male patients, with left‐sided tumors harboring noncodon 12 KRAS mutation. The prevalence of edPOLE‐mutated tumors in the control vs the experimental screening group was, respectively, 0.45% (n = 1) vs 5.0% (n = 10). Among the 11 edPOLE‐mutated cases, two had a low TMB, three were hypermutated, and six were ultramutated. EdPOLE‐mutated cases had a high CD8⁺ tumor‐infiltrating lymphocyte (TIL) infiltration. These clinicopathological and molecular criteria may help to identify edPOLE mutations associated with a high TMB in CRC, and improve the selection of patients who could benefit from immunotherapy.     

Adequacy of Nutritional Intakes during the Year after Critical Illness: An Observational Study in a Post-ICU Follow-Up Clinic

Whether nutritional intakes in critically ill survivors after hospital discharge are adequate is unknown. The aims of this observational study were to describe the energy and protein intakes in ICU survivors attending a follow-up clinic compared to empirical targets and to explore differences in outcomes according to intake adequacy. All adult survivors who attended the follow-up clinic at 1, 3 and 12 months (M1, M3, M12) after a stay in our intensive care unit (ICU) ≥ 7 days were recruited. Average energy and protein intakes over the 7 days before the face-to-face consultation were quantified by a dietician using food anamnesis. Self-reported intakes were compared empirically to targets for healthy people (FAO/WHO/UNU equations), for critically ill patients (25 kcal/kg/day and 1.3 g protein/kg/day). They were also compared to targets that are supposed to fit post-ICU patients (35 kcal/kg/day and 1.5 g protein/kg/day). Blood prealbumin level and handgrip strength were also measured at each timepoint. A total of 206 patients were analyzed (49, 97 and 60 at the M1, M3 and M12, respectively). At M1, M3 and M12, energy intakes were 73.2 [63.3–86.3]%, 79.3 [69.3–89.3]% and 82.7 [70.6–93.7]% of healthy targets (p = 0.074), respectively. Protein intakes were below 0.8 g/kg/day in 18/49 (36.7%), 25/97 (25.8%) and 8/60 (13.3%) of the patients at M1, M3 and M12, respectively (p = 0.018), and the protein intakes were 67.9 [46.5–95.8]%, 68.5 [48.8–99.3]% and 71.7 [44.9–95.1]% of the post-ICU targets (p = 0.138), respectively. Prealbumin concentrations and handgrip strength were similar in patients with either inadequate energy intakes or inadequate protein intakes, respectively. In our post-ICU cohort, up to one year after discharge, energy and protein intakes were below the targets that are supposed to fit ICU survivors in recovery phase.     

Effects of ciguatoxin on current and voltage clamped frog myelinated nerve fibre

The effects of 0.25 X 10(-9) and 1.25 X 10(-9) g/ml of purified ciguatoxin (CgTX) upon the node of Ranvier of frog isolated nerve fibres were investigated under current and voltage clamp conditions. When added to the external solution, CgTX induced spontaneous action potentials at a frequency of about 100 Hz, which were reversible upon removal of the toxin. Under voltage clamp conditions, CgTX modified neither linear leakage and capacity currents nor K current, but reversibly induced a maintained (late) inward current (IL) during long lasting depolarizations. IL, as well as the peak Na current, was suppressed by tetrodotoxin (300 nM). The steady-state inactivation curve of the Na current showed that a fraction of the current (corresponding to IL) did not inactivate. IL activated and reversed at voltages about 30 mV more negative than the peak Na current (recorded under control conditions or in the presence of CgTX). During a given depolarizing pulse, the amplitude of IL depended on the holding potential. IL was about three times greater when the holding potential was -70 mV rather than -120 mV. We conclude that CgTX specifically interacts with and modifies Na channels. We also conclude that the effects of CgTX depend on membrane potential.     

Forced swimming test in mice: a review of antidepressant activity

Rationale Among all animal models, the forced swimming test (FST) remains one of the most used tools for screening antidepressants.Objective This paper reviews some of the main aspects of the FST in mice. Most of the sensitivity and variability factors that were assessed on the FST are summarized.Mechanisms We have summarized data found in the literature of antidepressant effects on the FST in mice. From this data set, we have extrapolated information on baseline levels of strain, and sensitivity against antidepressants.Results We have shown that many parameters have to be considered in this test to gain good reliability. Moreover, there was a fundamental inter-strain difference of response in the FST.Conclusions The FST is a good screening tool with good reliability and predictive validity. Strain is one of the most important parameters to consider. Swiss and NMRI mice can be used to discriminate the mechanisms of action of drugs. CD-1 seems to be the most useful strain for screening purposes, but this needs to be confirmed with some spontaneous locomotor activity studies.Electronic Supplementary Material Supplementary material is available for this article at .     

Influence of Amodiaquine on the Antimalarial Activity of Ellagic Acid: Crystallographic and Biological Studies

In the search for new antimalarial drugs, design of hybrid molecules is recommended to improve biological activity and to decrease the risk of parasite resistance development. Ellagic acid, as an inhibitor of Plasmodium glutathione, presents an original mode of action and thus appears as a promising antiplasmodial compound. A new complex (AQ–EA) consisting of the well‐known antimalarial drug, amodiaquine, and ellagic acid was obtained. The studied crystal structure of AQ–EA showed that the triclinic centrosymmetrical unit cell of the crystal contains two molecules of amodiaquine (AQ) and two symmetrically independent molecules of ellagic acid (EA). The packing of the molecules in the crystal is dominated by hydrogen bonds between AQ and EA. The antiplasmodial activity of the hybrid complex AQ–EA was also determined and compared with the values of IC₅₀ for AQ and EA separately. Potentiation assays between both molecules were conducted to understand the pharmacological interactions between AQ and EA against Plasmodium falciparum in vitro. The hybrid complex AQ–EA (IC₅₀ of 47 nm ) showed improved antiplasmodial activity in comparison with EA alone.