Perception of understanding COVID-19 among doctors at Patan Hospital, Nepal

Introduction: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and presents with fever, dry cough, fatigue, myalgia, and dyspnea. This study aims to is find out the understanding of COVID-19 among doctors at Patan Hospital. Method: A cross sectional was conducted among doctors at Patan Hospital, Patan Academy of Health Sciences, Nepal. The questionnaire in Google form consisted, part1 perception on COVID-19 and part2 understanding using multiple choice questions corresponding to the one to fifteen questionnaire in part1. Ethnical approval was obtained. Result: Sixty-one doctors participated in the study, of which 65.5% were directly involved in management of COVID-19. Perception and understanding regarding transmission status in country was 65.6% and 63.95% respectively, about case definition 90.1% and 62.2%, about when to do diagnostic tests 75.4% and 90.2%. Conclusion: There was difference in perception and understanding regarding COVID-19 among doctors, and areas to be reinforced were case definition, transmission classification, diagnostic tests. Keyword: COVID-19, doctors, perception, understandin

Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes.

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function

Loss of TLE3 promotes the mitochondrial program in beige adipocytes and improves glucose metabolism.

Prolonged cold exposure stimulates the recruitment of beige adipocytes within white adipose tissue. Beige adipocytes depend on mitochondrial oxidative phosphorylation to drive thermogenesis. The transcriptional mechanisms that promote remodeling in adipose tissue during the cold are not well understood. Here we demonstrate that the transcriptional coregulator transducin-like enhancer of split 3 (TLE3) inhibits mitochondrial gene expression in beige adipocytes. Conditional deletion of TLE3 in adipocytes promotes mitochondrial oxidative metabolism and increases energy expenditure, thereby improving glucose control. Using chromatin immunoprecipitation and deep sequencing, we found that TLE3 occupies distal enhancers in proximity to nuclear-encoded mitochondrial genes and that many of these binding sites are also enriched for early B-cell factor (EBF) transcription factors. TLE3 interacts with EBF2 and blocks its ability to promote the thermogenic transcriptional program. Collectively, these studies demonstrate that TLE3 regulates thermogenic gene expression in beige adipocytes through inhibition of EBF2 transcriptional activity. Inhibition of TLE3 may provide a novel therapeutic approach for obesity and diabetes

Noggin depletion in adipocytes promotes obesity in mice.

ObjectiveObesity has increased to pandemic levels and enhanced understanding of adipose regulation is required for new treatment strategies. Although bone morphogenetic proteins (BMPs) influence adipogenesis, the effect of BMP antagonists such as Noggin is largely unknown. The aim of the study was to define the role of Noggin, an extracellular BMP inhibitor, in adipogenesis.MethodsWe generated adipose-derived progenitor cells and a mouse model with adipocyte-specific Noggin deletion using the AdiponectinCre transgenic mouse, and determined the adipose phenotype of Noggin-deficiency.ResultsOur studies showed that Noggin is expressed in progenitor cells but declines in adipocytes, possibly allowing for lipid accumulation. Correspondingly, adipocyte-specific Noggin deletion in vivo promoted age-related obesity in both genders with no change in food intake. Although the loss of Noggin caused white adipose tissue hypertrophy, and whitening and impaired function in brown adipose tissue in both genders, there were clear gender differences with the females being most affected. The females had suppressed expression of brown adipose markers and thermogenic genes including peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1alpha) and uncoupling protein 1 (UCP1) as well as genes associated with adipogenesis and lipid metabolism. The males, on the other hand, had early changes in a few BAT markers and thermogenic genes, but the main changes were in the genes associated with adipogenesis and lipid metabolism. Further characterization revealed that both genders had reductions in VO2, VCO2, and RER, whereas females also had reduced heat production. Noggin was also reduced in diet-induced obesity in inbred mice consistent with the obesity phenotype of the Noggin-deficient mice.ConclusionsBMP signaling regulates female and male adipogenesis through different metabolic pathways. Modulation of adipose tissue metabolism by select BMP antagonists may be a strategy for long-term regulation of age-related weight gain and obesity

IDOL regulates systemic energy balance through control of neuronal VLDLR expression.

Liver X receptors limit cellular lipid uptake by stimulating the transcription of Inducible Degrader of the LDL Receptor (IDOL), an E3 ubiquitin ligase that targets lipoprotein receptors for degradation. The function of IDOL in systemic metabolism is incompletely understood. Here we show that loss of IDOL in mice protects against the development of diet-induced obesity and metabolic dysfunction by altering food intake and thermogenesis. Unexpectedly, analysis of tissue-specific knockout mice revealed that IDOL affects energy balance, not through its actions in peripheral metabolic tissues (liver, adipose, endothelium, intestine, skeletal muscle), but by controlling lipoprotein receptor abundance in neurons. Single-cell RNA sequencing of the hypothalamus demonstrated that IDOL deletion altered gene expression linked to control of metabolism. Finally, we identify VLDLR rather than LDLR as the primary mediator of IDOL effects on energy balance. These studies identify a role for the neuronal IDOL-VLDLR pathway in metabolic homeostasis and diet-induced obesity

Étude de l’effet d’Al2O3, B2O3 et SiO2 sur les verres de phosphate possédant une faible Tg : approche structurale par RMN 1D/2D

Les verres de phosphates à faible Tg et forte stabilité thermique sont étudié dans le système (66-x)ZnO- xNa2O-33.4 P2O5. Les mesures DSC ont montré un écart Tx-Tg de 197 °C et une Tg de 339 °C pour x= 20. La RMN 31P 1D/2D révèle la diminution du désordre due à la substitution progressive de Zn par Na. Les formulations x=20 et x=33 ont été dopé par de l’Al2O3, B2O3 et SiO2 (1-4 % mol.) et ses effets sur les propriétés physiques comme la température de transition vitreuse, la stabilité thermique et la durabilité chimique ont été investiguées. La DRX et la RMN 31P ont été réalisés pour suivre le processus de cristallisation en isotherme à 130°C (au-delà de la Tg). La plus forte stabilité thermique a été identifiée pour les verres dopés au bore. Le Raman et la RMN 31P ont mis en évidence l’existence de connections P-O-X (X=27Al ou 11B). La RMN a entre autre montré la coordinence majoritaire VI, IV et IV respectivement pour l’aluminium, le bore et la silice. L’utilisation de D-INEPT, REDOR et DQ-SQ permet d’approfondir nos connaissances sur la structure particulièrement sur les connectivités P-O-X mais également la diversité des connections possibles.Pyrophosphate glass with low Tg and high stability is investigated within the (66-x) ZnO- xNa2O-33.4 P2O5 system. DSC measurement indicated Tx-Tg=197 °C with Tg = 339 °C at x= 20. 1D/2D 31P NMR revealed the decrease in extent of disorder with the progressive substitution of Zn by Na. The x=20 and x=33 formulations were doped with (1-4 mol.%) of Al2O3, B2O3 and SiO2 and its effect on the physical properties such as the glass transition temperature, thermal stability and chemical durability is investigated. XRD and 1D 31P solid state NMR were used to monitor the isothermal crystallization process occurring at 130 °C above Tg and the highest thermal stability is presented by the B-doped glasses. Raman and 31P NMR suggested the existence of P-O-X (X=27Al or 11B) bonds. The MAS NMR distinguished the dominant coordination states of doping elements AlVI , BIV and SiIV respectively. The use of D-INEPT, REDOR and DQ-SQ helped in producing deeper insights onto the glass structure about the P-O-X connectivity, the wide range of phosphate speciation