Nicotinamide adenine dinucleotide (NAD) extends longevity in experimental organisms, raising interest in its impact on human health. De novo NAD biosynthesis from tryptophan is evolutionarily conserved yet considered supplanted among higher species by biosynthesis from nicotinamide (NAM). Here we show that a bottleneck enzyme in de novo biosynthesis, quinolinate phosphoribosyltransferase (QPRT), defends renal NAD and mediates resistance to acute kidney injury (AKI). Following murine AKI, renal NAD fell, quinolinate rose, and QPRT declined. QPRT mice exhibited higher quinolinate, lower NAD, and higher AKI susceptibility. Metabolomics suggested an elevated urinary quinolinate/tryptophan ratio (uQ/T) as an indicator of reduced QPRT. Elevated uQ/T predicted AKI and other adverse outcomes in critically ill patients. A phase 1 placebo-controlled study of oral NAM demonstrated a dose-related increase in circulating NAD metabolites. NAM was well tolerated and was associated with less AKI. Therefore, impaired NAD biosynthesis may be a feature of high-risk hospitalizations for which NAD augmentation could be beneficial.

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Snail family zinc finger 1 (SNAI1) is a transcription factor expressed during renal embryogenesis, and re-expressed in various settings of acute kidney injury (AKI). Subjected to tight regulation, SNAI1 controls major biological processes responsible for renal fibrogenesis, including mesenchymal reprogramming of tubular epithelial cells, shutdown of fatty acid metabolism, cell cycle arrest and inflammation of the microenvironment surrounding tubular epithelial cells. The present review describes in detail the interactions of SNAI1 with AKI-associated signalling pathways. We also discuss how this central factor has been iteratively (and promisingly) targeted in a number of animal models in order to prevent or slow down renal fibrogenesis.

The COVID-19 crisis necessitated abrupt transition to remote learning in medical schools. We aimed to assess the impact of COVID-19 on French undergraduate students and teachers, to identify practice changes, and to evaluate successes and areas for improvement of this remote learning experience. Data from 2 online questionnaires were analyzed with 509 participants among students and 189 among teachers from Sorbonne University. Responses to multiple choice, Likert response scale, and open-ended questions were evaluated. COVID-19 had negative impact on teaching continuity. Sixty-seven percent of students were in a dropout situation, and many suffered from psychological stress, leading to set up of a psychological support unit. Although most teachers (81%) and students (72%) had limited knowledge of digital resources, distance learning was quickly implemented, with a predominant use of Zoom. The analysis of several parameters revealed that students were significantly more satisfied than teachers by remote learning. Nevertheless, both students and teachers agreed to replace classical lectures by digital media and to promote in-person teaching in small interactive groups. This paper shares tips for faculty rapidly establishing remote learning. This comparative study of the students’ and teachers’ points of view underlines that new medical curricula should include more digital contents. We make recommendations regarding general university organization, equipment, and curricular development for long-term implementation of digital resources with reinforced relationships between faculty and students.

Background/Aims: Fatty acid oxidation (FAO), the main source of energy produced by tubular epithelial cells in the kidney, was found to be defective in tubulo-interstitial samples dissected out in kidney biopsies from patients with chronic kidney disease (CKD). Experimental data indicated that this decrease was a strong determinant of renal fibrogenesis, hence a focus for therapeutic interventions. Nevertheless, whether persistently differentiated renal tubules, surviving in a pro-fibrotic environment, also suffer from a decrease in FAO, is currently unknown. Methods: To address this question, we isolated proximal tubules captured ex vivo on the basis of the expression of an intact brush border antigen (Prominin-1) in C57BL6/J mice subjected to a controlled, two-hit model of renal fibrosis (reversible ischemic acute kidney injury (AKI) or sham surgery, followed by angiotensin 2 administration). A transcriptomic high throughput sequencing was performed on total mRNA from these cells, and on whole kidneys. Results: In contrast to mice subjected to sham surgery, mice with a history of AKI displayed histologically more renal fibrosis when exposed to angiotensin 2. High throughput RNA sequencing, principal component analysis and clustering showed marked consistency within experimental groups. As expected, FAO transcripts were decreased in whole fibrotic kidneys. Surprisingly, however, up- rather than down-regulation of metabolic pathways (oxidative phosphorylation, fatty acid metabolism, glycolysis, and PPAR signalling pathway) was a hallmark of the differentiated tubules captured from fibrotic kidneys. Immunofluorescence co-staining analysis confirmed that the expression of FAO enzymes was dependent of tubular trophicity. Conclusions: These data suggest that in differentiated proximal tubules energetic hyperactivity is promoted concurrently with organ fibrogenesis.

Question addressedIn contrast with pain, dyspnoea is not visible to the general public who lack the corresponding experiential baggage. We tested the hypotheses that the generalised use of face masks to fight SARS-CoV2 dissemination could change this and sensitise people to respiratory health.MethodsGeneral population polling (1012-person panel demographically representative of the adult French population –quota sampling method–; 517 women, 51%). 860 (85%) answered “no” to “treated for a chronic respiratory disease” (“respiratory healthy”, RH) and 152 “yes” (“respiratory disease”, RD). 14% of RH respondents reported having a close family member treated for a chronic respiratory disease (RH-family+ and RH-family−). Respondents described mask-related attitudes, beliefs, inconveniencies, dyspnoea, and changes in their respiratory health vision.ResultsCompliance with masks was high (94.7%). Dyspnoea ranked first among mask inconveniencies (RD 79.3%, RH 67.3%, p=0.013). “Air hunger” was the main sensory dyspnoea descriptor. Mask-related dyspnoea was independently associated with belonging to RH-family+ (Odds Ratio [OR] [95% confidence interval (CI)]: 1.85 [1.16–2.98]) and removing masks to improve breathing (OR 5.21 [3.73–7.28]). It was negatively associated with considering masks effective to protect others (OR]: 0.42 [0.25–0.75]). Half the respondents were more concerned with their respiratory health since wearing masks; 41% reported better understanding patients’ experiences.Answer to the questionWearing protective face masks leads to the mass discovery of breathing discomfort. It raises the public's awareness of what respiratory diseases involve and sensitises to the importance of breathing. These data should be used as the fulcrum of respiratory-health-oriented communication actions.

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Preeclampsia is a hypertensive disorder of pregnancy and the clinical manifestation of severe endothelial dysfunction associated with maternal and foetal morbidity and mortality. The primum movens of the disease is the defect of invasion of the uterine arteries by foetal syncytiotrophoblasts, which causes a maladaptive placental response to chronic hypoxia and the secretion of the soluble form of type 1 vascular growth endothelial factor receptor, also called soluble fms-like tyrosine kinase 1 (sFlt-1), the major player in the pathophysiology of the disease. Among its different effects, sFlt-1 induces abnormal sensitivity of the maternal vessels to the vasoconstrictor angiotensin II. This leads to the hypertensive phenotype, recently shown to be abrogated by the administration of sildenafil citrate, which can potentiate the vasodilatory mediator nitrite oxide. This review focuses on the mechanisms of maternal endothelial dysfunction in preeclampsia and discusses the therapeutic window of sildenafil use in the context of preeclampsia, based on the results from preclinical studies and clinical trials. Safety issues recently reported in neonates have considerably narrowed this window.