SARS-CoV-2 Causes a Specific Dysfunction of the Kidney Proximal Tubule

Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with COVID-19 present specific manifestations of proximal tubule dysfunction remains unknown. To test this, we examined a cohort of 49 patients requiring hospitalization in a large academic hospital in Brussels, Belgium. There was evidence of proximal tubule dysfunction in a subset of patients with COVID-19, as attested by low-molecular-weight proteinuria (70-80%), neutral aminoaciduria (46%), and defective handling of uric acid (46%) or phosphate (19%). None of the patients had normoglycemic glucosuria. Proximal tubule dysfunction was independent of pre-existing comorbidities, glomerular proteinuria, nephrotoxic medications or viral load. At the structural level, kidneys from patients with COVID-19 showed prominent tubular injury, including in the initial part of the proximal tubule, with brush border loss, acute tubular necrosis, intraluminal debris, and a marked decrease in the expression of megalin in the brush border. Transmission electron microscopy identified particles resembling coronaviruses in vacuoles or cisternae of the endoplasmic reticulum in proximal tubule cells. Among features of proximal tubule dysfunction, hypouricemia with inappropriate uricosuria was independently associated with disease severity and with a significant increase in the risk of respiratory failure requiring invasive mechanical ventilation using Cox (adjusted hazard ratio 6.2, 95% CI 1.9-20.1) or competing risks (adjusted sub-distribution hazard ratio 12.1, 95% CI 2.7-55.4) survival models. Thus, our data establish that SARS-CoV-2 causes specific manifestations of proximal tubule dysfunction and provide novel insights into COVID-19 severity and outcome

Psychological distress among hospital caregivers during and after the first wave of COVID-19: Individual factors involved in the severity of symptoms expression

Coronavirus disease 2019 has spread rapidly over the globe and has put an unprecedent psychological pressure on health care workers (HCWs). The present study aimed at quantifying the psychological consequences of the COVID-19 pandemic on HCWs during and after the first wave and identify sociodemographic, situational, and psychological risk/protective factors for symptoms severity. An online survey was sent by e-mail to all nurses and physicians employed by a teaching hospital in Brussels, Belgium. 542 (20,62%) completed the survey. 47%, 55%, 32% and 52% of participants reported posttraumatic stress, anxiety, depression and insomnia symptoms, respectively, during the peak. Two to three months later, posttraumatic symptoms emerged de novo in 54% of HCWs. It persisted in 89% of those presenting severe symptoms initially. Neuroticism was the strongest predictor of posttraumatic stress, anxiety, and insomnia. Work overload was the strongest predictor of depression and second predictor of posttraumatic stress, anxiety, and insomnia. Other significant predictors included being a nurse, the number of past traumatic experiences, avoidant coping style, and expressive suppression of emotion

Genetic diversity of wild and cultivated grapevine accessions from southeast Turkey

INRA UMR 1334 AGAP, Equipe DAVEM = Diversité et Adaptation de la Vigne et des Espèces MéditerranéennesWild grapevine genetic diversity in southeast Turkey has not been documented to date. In the present work, in order to clarify the relationships between wild and cultivated grape accessions from southeastern Turkey, 22 nuclear and three chloroplast microsatellite loci were used on 21 wild grapevine Vitis vinifera L. ssp. sylvestris (Gmelin) and 13 cultivated grapevine Vitis vinifera ssp. sativa accessions. The number of alleles per SSR locus ranged from 4 (VVIn16) to 20 (VVIv67) and the mean allele number per locus was 10.09. Expected locus heterozygosity ranged from 0.586 (locus VVIb01) to 0.898 (locus (VVIv67)). The three cpSSR molecular markers presented variation in size both in cultivars and in wild Turkish accessions. Two size variants were detected for cpSSR3 (106 and 107 bp) for cpSSR5 (104 and 105 bp), and for cpSSR10 (115 and 116 bp). The six alleles in wild grapevines fell into three haplotypes B, C and D. A genetic structure according to accessions taxonomic status (wild or cultivated) was revealed by UPGMA analysis. This highlighted a clear separation between domesticated and wild accessions in Turkish germplasm. The results pointed out the need to further collect and characterize this wild and cultivated grapevine germplasm

Towards an optimal sampling strategy for assessing genetic variation within and among white clover (Trifolium repens L.) cultivars using AFLP

Cost reduction in plant breeding and conservation programs depends largely on correctly defining the minimal sample size required for the trustworthy assessment of intra- and inter-cultivar genetic variation. White clover, an important pasture legume, was chosen for studying this aspect. In clonal plants, such as the aforementioned, an appropriate sampling scheme eliminates the redundant analysis of identical genotypes. The aim was to define an optimal sampling strategy, i.e., the minimum sample size and appropriate sampling scheme for white clover cultivars, by using AFLP data (283 loci) from three popular types. A grid-based sampling scheme, with an interplant distance of at least 40 cm, was sufficient to avoid any excess in replicates. Simulations revealed that the number of samples substantially influenced genetic diversity parameters. When using less than 15 per cultivar, the expected heterozygosity (He) and Shannon diversity index (I) were greatly underestimated, whereas with 20, more than 95% of total intra-cultivar genetic variation was covered. Based on AMOVA, a 20-cultivar sample was apparently sufficient to accurately quantify individual genetic structuring. The recommended sampling strategy facilitates the efficient characterization of diversity in white clover, for both conservation and exploitation

Actinomycosis associated with a permanently implanted duodenal over-the-scope clip.

No abstract availabl

Optimal sampling strategies for darunavir and external validation of the underlying population pharmacokinetic model

Purpose: A variety of diagnostic methods are available to validate the performance of population pharmacokinetic models. Internal validation, which applies these methods to the model building dataset and to additional data generated through Monte Carlo simulations, is often sufficient, but external validation, which requires a new dataset, is considered a more rigorous approach, especially if the model is to be used for predictive purposes. Our first objective was to validate a previously published population pharmacokinetic model of darunavir, an HIV protease inhibitor boosted with ritonavir or cobicistat. Our second objective was to use this model to derive optimal sampling strategies that maximize the amount of information collected with as few pharmacokinetic samples as possible. Methods: A validation dataset comprising 164 sparsely sampled individuals using ritonavir-boosted darunavir was used for validation. Standard plots of predictions and residuals, NPDE, visual predictive check, and bootstrapping were applied to both the validation set and the combined learning/validation set in NONMEM to assess model performance. D-optimal designs for darunavir were then calculated in PopED and further evaluated in NONMEM through simulations. Results: External validation confirmed model robustness and accuracy in most scenarios but also highlighted several limitations. The best one-, two-, and three-point sampling strategies were determined to be pre-dose (0 h); 0 and 4 h; and 1, 4, and 19 h, respectively. A combination of samples at 0, 1, and 4 h was comparable to the optimal three-point strategy. These could be used to reliably estimate individual pharmacokinetic parameters, although with fewer samples, precision decreased and the number of outliers increased significantly. Conclusions: Optimal sampling strategies derived from this model could be used in clinical practice to enhance therapeutic drug monitoring or to conduct additional pharmacokinetic studies

Neuromyelitis Optica Spectrum Disorders-Like Relapses in HIV-Infected; Person Correlated with Infectious Activities: A Case Report

Inflammatory optic neuropathy in HIV-infected persons can be dramatic and very little is known about the physiopathology or management of this condition as it has been scarcely described in medical literature

A Case Report of Safe Coadministration of Amiodarone with Short-Term Treatment Nirmatrelvir-Ritonavir

International audienc

There Is a Risk of Spread During a Nebulization Session in a Patient with COVID-19

Introduction An hypothetical risk of SARS-CoV-2 airborne transmission through nebulization was suggested based on a potential environmental contamination by the fugitive aerosol emitted in the environment during the procedure. The aim of this study was to verify this risk from the fugitive aerosol emitted by COVID-19 patients during one nebulization session. Method In this cohort study, COVID-19 patients treated with nebulization were recruited at their admission to the hospital. Patients had to perform a nebulization session while a BioSampler® and a pump were used to vacuum the fugitive aerosol and collect it for SARS-CoV-2 RNA detection. Results Ten consecutive patients hospitalized with COVID-19 were recruited. The median viral load was 6.5x106 copies/mL. Two out of the ten samples from the fugitive aerosol collected were positive to SARS-CoV-2. Conclusion The risk of fugitive aerosol contamination with SARS-CoV-2 during nebulization has now been verified