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

Implementation of REDCap mobile app in an oral HIV clinical study

Abstract Background In Peru, HIV cases are highly concentrated among men who have sex with men (MSM). Despite the availability of anti-retroviral therapy, people living with HIV (PWH) have higher levels of oral diseases. Alcohol use disorder (AUD) is significantly present among PWH. Our overarching goal was to generate foundational evidence on the association of AUD and oral health in MSM with HIV and enhance research capacity for future intersectional research on AUD, oral health and HIV. Our specific aim was to implement an on-site electronic data collection system through the use of a REDCap Mobile App in a low-middle income country (LMIC) setting. Methods Five validated surveys were utilized to gather data on demographics, medical history, HIV status, alcohol use, HIV stigma, perceived oral health status, and dietary supplement use. These surveys were developed in REDCap and deployed with the REDCap Mobile App, which was installed on ten iPads across two medical HIV clinics in Lima, Peru. REDCap app as well as the protocol for data collection were calibrated with feedback from trial participants and clinical research staff to improve clinical efficiency and participant experience. Results The mean age of participants (n = 398) was 35.94 ± 9.13y, of which 98.5% identified as male, and 85.7% identified as homosexual. 78.1% of participants binge drank, and 12.3% reported being heavy drinkers. After pilot testing, significant modifications to the structure and layout of the surveys were performed to improve efficiency and flow. The app was successfully deployed to replace cumbersome paper records and collected data was directly stored in a REDCap database. Conclusions The REDCap Mobile App was successfully used due to its ability to: (a) capture and store data offline, (b) timely translate between multiple languages on the mobile app interface, and (c) provide user-friendly interface with low associated costs and ample support. Trial registration 1R56DE029639-01

Salivary Cathelicidin (LL-37) in Children and Adolescents Living with HIV

Introduction: Human cathelicidin LL-37 is a salivary antimicrobial peptide (AMP) with broad-spectrum activity against oral diseases, but few studies have assessed its role in children and adolescents living with HIV (CALHIV). We assessed salivary LL-37 levels and correlates in a long-term cohort of Kenyan CALHIV followed since antiretroviral therapy (ART) initiation. Methods: Saliva was collected from 76 CALHIV who were recruited from two ongoing pediatric HIV studies in Nairobi, Kenya. Oral examinations documenting oral manifestations of HIV, dental caries, and gingivitis were completed. Additional variables included age, sex, HIV treatment (initial ART regimen) and disease parameters, caregivers’ demographics, and oral pathologies were conducted. Data were statistically analyzed using the independent T test on the log-transformed LL-37. Results: At the oral exam visit, the mean age of participants was 13.3 years (±SD = 3.4), and the median CD4 count was 954 cells/mm3. Mean salivary cathelicidin values of the cohort were 23.7 ± 21.1 ng/mL. Children with permanent dentition at time of oral examination, and children who initiated ART at ≥2 years old had higher mean LL-37 concentrations compared to those with mixed dentition and those who initiated ART <2 years old (p = 0.0042, 0.0373, respectively). LL-37 levels were not found to differ by initial type of ART regimen, CD4 count, or oral disease. Conclusion: Further research and longitudinal studies are necessary to evaluate and improve the innate immunity of CALHIV in Kenya

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 Mul- tipurpose, 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 15 wt.% 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 (24 h) and long-term (6 months) of water storage. Data were analyzed using ANOVA and Tukey ( ̨ = 5%) and the Weibull analysis. Results. DC was greater for the CHX-free HNT-modified adhesive, whereas the other exper- imental adhesives showed similar DC as compared with the control. Primers were less viscous than the adhesives, without significant differences within the respective materials. At 24 h, 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

Phased whole-genome genetic risk in a family quartet using a major allele reference sequence.

Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date (< 1,000 base pairs). We use family inheritance state analysis to control sequencing error and inform family-wide haplotype phasing, allowing quantification of genome-wide compound heterozygosity. We develop a sequence-based methodology for Human Leukocyte Antigen typing that contributes to disease risk prediction. Finally, we advance methods for analysis of disease and pharmacogenomic risk across the coding and non-coding genome that incorporate phased variant data. We show these methods are capable of identifying multigenic risk for inherited thrombophilia and informing the appropriate pharmacological therapy. These ethnicity-specific, family-based approaches to interpretation of genetic variation are emblematic of the next generation of genetic risk assessment using whole-genome sequencing

Data from: Phased whole-genome genetic risk in a family quartet using a major allele reference sequence

Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date (<1,000 base pairs). We use family inheritance state analysis to control sequencing error and inform family-wide haplotype phasing, allowing quantification of genome-wide compound heterozygosity. We develop a sequence-based methodology for Human Leukocyte Antigen typing that contributes to disease risk prediction. Finally, we advance methods for analysis of disease and pharmacogenomic risk across the coding and non-coding genome that incorporate phased variant data. We show these methods are capable of identifying multigenic risk for inherited thrombophilia and informing the appropriate pharmacological therapy. These ethnicity-specific, family-based approaches to interpretation of genetic variation are emblematic of the next generation of genetic risk assessment using whole-genome sequencing

YRIref.fasta

YRIref.fast

CEUref.fasta

CEUref.fast

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease