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

Potential of high-intensity focused ultrasound in resin-dentine bonding

Objective: This study introduced the potential and proof-of-concept of high intensity focused ultrasound (HIFU) technology for dentin-surface treatment for resin-dentin bonding without acid-aided demineralization. This new strategy could provide a way to enhance interface-integrity and bond-durability by changing the nature of dentin-substrate; bonded-interface structure and properties; and minimizing denuded-collagen exposure.Methods: The interaction between HIFU waves and dentin-surface in terms of structural, mechanical and chemical variations were investigated by SEM, TEM, AFM, nano-indentation and Raman-analysis. The bonding between HIFU-treated dentin and two-step, etch-and-rinse, adhesive was preliminary explored by characterizing dentin-bound proteases activities, resin-dentin interfacial morphology and bond-durability with HIFU exposure at different time-points of 60, 90 and 120 s compared to conventional acid-etching technique.Results: With the increase in HIFU exposure-time from 60-to-120 s, HIFU waves were able to remove the smear-layer, expose dentinal-tubules and creating textured/rough dentin surface. In addition, dentin surfaces showed a pattern of interlocking ribbon-like minerals-coated collagen-fibrils protruding from the underlaying amorphous dentin-background with HIFU exposure for 90 s and 120 s. This characteristic pattern of dentin-surface showing inorganic-minerals associated/aligned with collagen-fibrils, with 90-to-120 s HIFU-treatment, was confirmed by the Raman-analysis. HIFU-treated specimens showed higher nano-indentation properties and lower concentrations of active MMP-2 and Cathepsin-K compared to the acid-etched specimens. The resin-dentin bonded interface revealed the partial/complete absence of the characteristic hybrid-layer formed with conventional etch-and-rinse bonding strategy. Additionally, resin-infiltration and resin-tags formation were enhanced with the increase in HIFU exposure-time to 120 s. Although, all groups showed significant decrease in bond-strength after 12 months compared to 24 h storage in artificial saliva, groups exposed to HIFU for 90 s and 120 s showed significantly higher μTBS compared to the control acid-etched group.Significance: The implementation of HIFU-technology for dental hard-tissues treatment could be of potential significance in adhesive/restorative dentistry owing to its ability of controlled, selective and localised combined tissue alteration/ablation effects

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

Multiscale in-vitro analysis of photo-activated riboflavin incorporated in an experimental universal adhesive

Objective: To investigate the effect of blue light photoactivated riboflavin modified universal adhesives on dentin collagen biodegradation resistance, dentin apparent elastic modulus, and resin-dentin bond strength with interfacial morphology.Methods: Dentin slabs were treated with 0.1% riboflavin-5-phosphate modified (powder added slowly while shaking and then sonicated to enhance the dispersion process) Universal Adhesive Scotch Bond and Zipbond™ along with control (non-modified) and experimental adhesives, photoactivated with blue light for 20s. Hydroxyproline (HYP) release was assessed after 1-week storage. Elastic-modulus testing was evaluated using universal testing machine at 24 h. Resin-dentin interfacial morphology was assessed with scanning electron-microscope, after 6-month storage. 0.1% rhodamine dye was added into each adhesive and analyzed using CLSM. Detection of free amino groups was carried out using ninhydrin and considered directly proportional to optical absorbance. Collagen molecular confirmation was determined using spectropolarimeter to evaluate and assess CD spectra. For molecular docking studies with riboflavin (PDB ID file), the binding pocket was selected with larger SiteScore and DScore using Schrodinger PB software. After curing, Raman shifts in Amide regions were obtained at 8 μm levels. Data were analyzed using Two-way analysis of variance (ANOVA, p ≤ 0.05) and Tukey–Kramer multiple comparison post hoc tests.Results: At baseline, bond strength reduced significantly (p ≤ 0.05) in control specimens. However, at 6 months’ storage, UVA Zipbond™ had significantly higher μTBS. Resin was able to diffuse through the porous demineralized dentin creating adequate hybrid layers in both 0.1%RF modified adhesives in CLSM images. In riboflavin groups, hybrid layer and resin tags were more pronounced. The circular dichroism spectrum showed negative peaks for riboflavin adhesive specimens. Best fitted poses adopted by riboflavin compound are docked with MMP-2 and -9 proteases. Amide bands and CH2 peaks followed the trend of being lowest for control UA Scotch bond adhesive specimens and increasing in Amides, proline, and CH2 intensities in 0.1%RF modified adhesive specimens. All 0.1%RF application groups showed statistically significant (p < 0.05) less levels of HYP released compared to controls. Dentin Eappr of riboflavin application was significantly (p < 0.05) more as compared to control groups.Conclusion: Blue light photoactivated 0.1% riboflavin modified adhesives improved the biochemical and biomechanical properties of demineralized dentin as well as the long-term resin-dentin interfacial integrity and bond strength of universal adhesive to dentin