Child Maltreatment, Exposure to Violence, and Adolescent Weapon Carrying

This study examined associations between child maltreatment, violence exposure, and gender in predicting subsequent adolescent weapon carrying. Data from the National Survey of Child and Adolescent Well- Being, a nationally representative longitudinal study of families in contact with the child welfare system, were used. Participants included 821 youth who were followed over five years. Results from a logistic regression suggested that male youth who reported physical abuse at baseline were less likely to report carrying a weapon any time across the follow up period, while physical abuse did not predict weapon carrying in females. These counterintuitive findings demonstrated a complex relationship between violence exposure and subsequent risk behaviors among a vulnerable population of youth

Clindamycin-modified Triple Antibiotic Nanofibers: A Stain-free Antimicrobial Intracanal Drug Delivery System

INTRODUCTION: A biocompatible strategy to promote bacterial eradication within the root canal system after pulpal necrosis of immature permanent teeth is critical to the success of regenerative endodontic procedures. This study sought to synthesize clindamycin-modified triple antibiotic (metronidazole, ciprofloxacin, and clindamycin [CLIN]) polymer (polydioxanone [PDS]) nanofibers and determine in vitro their antimicrobial properties, cell compatibility, and dentin discoloration. METHODS: CLIN-only and triple antibiotic CLIN-modified (CLIN-m, minocycline-free) nanofibers were processed via electrospinning. Scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR), and tensile testing were performed to investigate fiber morphology, antibiotic incorporation, and mechanical strength, respectively. Antimicrobial properties of CLIN-only and CLIN-m nanofibers were assessed against several bacterial species by direct nanofiber/bacteria contact and over time based on aliquot collection up to 21 days. Cytocompatibility was measured against human dental pulp stem cells. Dentin discoloration upon nanofiber exposure was qualitatively recorded over time. The data were statistically analyzed (P < .05). RESULTS: The mean fiber diameter of CLIN-containing nanofibers ranged between 352 ± 128 nm and 349 ± 128 nm and was significantly smaller than PDS fibers. FTIR analysis confirmed the presence of antibiotics in the nanofibers. Hydrated CLIN-m nanofibers showed similar tensile strength to antibiotic-free (PDS) nanofibers. All CLIN-containing nanofibers and aliquots demonstrated pronounced antimicrobial activity against all bacteria. Antibiotic-containing aliquots led to a slight reduction in dental pulp stem cell viability but were not considered toxic. No visible dentin discoloration upon CLIN-containing nanofiber exposure was observed. CONCLUSIONS: Collectively, based on the remarkable antimicrobial effects, cell-friendly, and stain-free properties, our data suggest that CLIN-m triple antibiotic nanofibers might be a viable alternative to minocycline-based antibiotic pastes

Chlorhexidine-modified nanotubes and their effects on the polymerization and bonding performance of a dental adhesive

Objectives: The purpose of this study was to synthesize chlorhexidine (CHX)-encapsulated aluminosilicate clay nanotubes (Halloysite®, HNTs) and to incorporate them into the primer/adhesive components of an etch-and-rinse adhesive system (SBMP; Scotchbond Multipurpose, 3M ESPE) and to test their effects on degree of conversion, viscosity, immediate and long-term bonding to dentin. Methods: CHX-modified HNTs were synthesized using 10% or 20% CHX solutions. The primer and the adhesive components of SBMP were incorporated with 15wt.% of the CHX-encapsulated HNTs. Degree of conversion (DC) and viscosity analyses were performed to characterize the modified primers/adhesives. For bond strength testing, acid-etched dentin was treated with one of the following: SBMP (control); 0.2%CHX solution before SBMP; CHX-modified primers+SBMP adhesive; SBMP primer+CHX-modified adhesives; and SBMP primer+CHX-free HNT-modified adhesive. The microtensile bond strength test was performed after immediate (24h) and long-term (6 months) of water storage. Data were analyzed using ANOVA and Tukey (α=5%) and the Weibull analysis. Results: DC was greater for the CHX-free HNT-modified adhesive, whereas the other experimental adhesives showed similar DC as compared with the control. Primers were less viscous than the adhesives, without significant differences within the respective materials. At 24h, all groups showed similar bonding performance and structural reliability; whereas at the 6-month period, groups treated with the 0.2%CHX solution prior bonding or with the CHX-modified primers resulted in greater bond strength than the control and superior reliability. Significance: The modification of a primer or adhesive with CHX-encapsulated HNTs was an advantageous approach that did not impair the polymerization, viscosity and bonding performance of the materials, showing a promising long-term effect on resin-dentin bonds

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

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 hospitalization2–4 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

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

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

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Resin-based dental materials containing 3-aminopropyltriethoxysilane modified halloysite-clay nanotubes for extended drug delivery

OBJECTIVE: To synthesize and characterize a novel resin-based dental material containing 3-aminopropyltriethoxysilane (APTES) surface-modified halloysite-clay nanotubes (HNTs) for long-term delivery of guest molecules. METHODS: The optimal concentrations of HNT (10, 15, 20 wt.%) and silane (0, 2, 4 vol.%sil) to be incorporated into the resin-based materials were determined (15 wt.%HNT, 4 vol.%sil) after assessment of the mechanical properties (DC%, degree of conversion; FS, flexural strength; FM, flexural modulus; and UTS, ultimate tensile strength). The HNTsil-powder was loaded with chlorhexidine (CHX) to evaluate the effect of the silanization on drug release. Resin-discs were prepared for the following groups: RES (resin), HNT (resin+15 wt.%HNT), HNTsil (resin+15 wt.%HNT silanized), HNT-CHX (resin+15 wt.%HNT loaded with chlorhexidine), HNTsil-CHX (resin+15 wt.%HNTsil-CHX), and 0.2 vol.%CHX (resin+0.2 vol.%CHX solution). Specimens were stored in water for 1, 3, 5, 10, and 15 days at 37 °C. Aliquots from each time point and the final 15-day specimens were evaluated for the zone of inhibition (ZOI) against Streptococcus mutans. CHX release was analyzed using spectrophotometry at absorbance of 300 nm. Data were statistically analyzed (α = 0.05). RESULTS: All materials presented similar DC%. Reduced FS but increased FM was detected for 20 wt.%HNT-4%APTES. Groups with 15 wt.% and 20 wt.%HNT with/without APTES presented higher values of UTS. Agar diffusion data indicates that the HNTsil-CHX had a greater ZOI than all other groups over 15 days. HNTsil-CHX had the highest absorbance for day 1 but presented similar values to other groups every time point after. SIGNIFICANCE: Silanization of nanotubes followed by encapsulation of chlorhexidine is a promising technique for long-term delivery of guest molecules