Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Characterization of chlorhexidine-loaded calcium-hydroxide microparticles as a potential dental pulp-capping material

10.3390/bioengineering4030059Bioengineering435

Effect of chitosan/riboflavin modification on resin/dentin interface: Spectroscopic and microscopic investigations

10.1002/jbm.a.34482Journal of Biomedical Materials Research - Part A101 A71846-1856JBMR

Riboflavin as a dentin crosslinking agent: Ultraviolet A versus blue light

10.1016/j.dental.2012.09.009Dental Materials28121284-1291DEMA

The Dietary Mixture of Betaine, Lactic Acid Bacteria, and Exogenous Digestive Enzymes Enhanced the Growth Performance, Intestinal Health, and Immunity of Nile Tilapia (\u3ci\u3eOreochromis niloticus\u3c/i\u3e) Grown in Outdoor Concrete Tanks

It has been illustrated that using mixtures of feed additives is more efficient than using individual additives in aquaculture. Hence, this study aimed to study a dietary mixture of betaine, lactic acid bacteria, and exogenous digestive enzymes (ble) on the growth perfor-mance, digestion capacity, intestinal health, and blood indices of Nile tilapia reared outdoors in concrete tanks. Five diets were prepared where the basal diets were mixed with BLE at 0, 0.25, 0.5, 0.75, and 1%. After 90 days, the growth performance of Nile tilapia fed BLE was markedly enhanced in fish fed 0.25 and 0.5% of BLE, while the feed conversion ratio (FCR) was reduced (P\u3c0.05). The lipase activ-ity was significantly higher in tilapia fed BLE at 0.25, 0.5, and 0.75% than 0 and 1%. The amylase activity was meaningfully increased by 0.5% of BLE than 0, 0.25, 0.75, and 1%. The protease activity was significantly higher in tilapia fed BLE at 0.25 and 0.5 than 0, 0.75, and 1% (P\u3c0.05). The intestine of fish fed on BLE showed an increase in intestinal villi density. The villi length, width, and the number of goblet cells were markedly higher in the anterior, middle, and posterior segments of the intestines of tilapia fed ble than in the control group (P\u3c0.05). Further, fish fed BLE had higher intestinal morphometry indices and count of goblet cells than the control. Significantly fish fed 0.25, and 0.5% of BLE had higher hemoglobulin, and hematocrit levels than fish fed 0, 0.75, and 1%. While, fish fed 0.5% had higher red blood cells than fish fed the remaining BLE levels (P\u3c0.05). On the other hand, no marked effects for BLE supplementation were seen on the alanine aminotransferase (alT), aspartate aminotransferase (asT), total protein, albumin, globulin, creatinine, uric acid, and urea. The regression analysis showed that the maximum dose of BLE supplementation to achieve the highest final weight and the lowest FCR is 0.46% and 0.42%, respectivel

Chitosan/Riboflavin-modified demineralized dentin as a potential substrate for bonding

10.1016/j.jmbbm.2012.09.008Journal of the Mechanical Behavior of Biomedical Materials17278-28

Effect of High-Intensity Focused Ultrasound on Enterococcus Faecalis Planktonic Suspensions and Biofilms

10.1016/j.ultrasmedbio.2012.12.006Ultrasound in Medicine and Biology395825-833USMB