Catalytic Potential of Post-Transition Metal Doped Graphene-Based Single-Atom Catalysts for the CO2 Electroreduction Reaction

Catalysts are required to ensure electrochemical reduction of CO2 to fuels proceeds at industrially acceptable rates and yields. As such, highly active and selective catalysts must be developed. Herein, a density functional theory study of p-block element and noble metal doped graphene-based single-atom catalysts in two defect sites for the electrochemical reduction of CO2 to CO and HCOOH is systematically undertaken. It is found that on all of the systems considered, the thermodynamic product is HCOOH. Pb/C3, Pb/N4 and Sn/C3 are identified as having the lowest overpotential for HCOOH production while Al/C3, Al/N4, Au/C3 and Ga/C3 are identified as having the potential to form higher order products due to the strength of binding of adsorbed HCOOH

Usability and Psychosocial Impact of Decision Support to Increase Sexual Health Education in American Indian and Alaska Native Communities

Despite sexual and reproductive health disparities, few evidence-based sexual health education programs exist for American Indian/Alaska Native (AI/AN) youth, with even fewer tools available to assist AI/AN communities in adopting, implementing, and maintaining such programs. iCHAMPSS (Choosing And Maintaining effective Programs for Sex education in Schools) is a theory- and web-based decision-support-system designed to address dissemination barriers and increase the reach and fidelity of evidence-based programs (EBPs), specifically sexual health education programs. To investigate the potential of iCHAMPSS in AI/AN communities, we pilot-tested iCHAMPSS with adult stakeholders (N = 36) from agencies across the country that serve AI/AN communities. Stakeholders were recruited to review selected iCHAMPSS tools over two weeks in spring 2016. Pre- and post-surveys were administered to assess usability constructs, short-term psychosocial outcomes, and perceived feasibility. Data were analyzed using descriptive and non-parametric statistics. iCHAMPSS was perceived as acceptable, easy to use, credible, appealing, more helpful than current resources, and impactful of EBP adoption, implementation, and maintenance. Conversely, using iCHAMPSS significantly increased participants’ perceived barriers to adopting an EBP (p = 0.01). Overall, AI/AN stakeholders responded positively to iCHAMPSS, indicating the potential for adaptation to support the dissemination and implementation of evidence-based sexual health education in AI/AN communities

Identification of acid reflux cough using serial assays of exhaled breath condensate pH

BACKGROUND: Chronic cough is a common problem, frequently caused or exacerbated by acid reflux. Diagnosis of acid reflux cough is haphazard currently, often relying on long therapeutic trials of expensive medications. We tested the hypothesis that the most relevant mechanistic component of acid reflux in chronic cough is when it rises to the level of the airway where acid can potentially be aspirated. We further wished to determine if multi-sample exhaled breath condensate (EBC) pH profiles can identify chronic cough patients likely to respond to proton pump inhibitor therapy. METHODS: 59 subjects were recruited for this study. Initially we examined EBC pH (gas-standardized with Argon) in the setting of 15 experimental pharyngeal acid challenges to determine duration of EBC acidification. Subsequently, we enrolled 22 healthy subjects to determine a normal multi-sample exhaled breath condensate pH profile over 1–3 days. We additionally obtained multi-sample EBC pH profiles in 22 patients with chronic cough. These samples were timed to occur after coughing episodes. Exhaled breath condensate pH was measured after gas standardization. RESULTS: We found that exhaled breath condensate pH is substantially reduced for approximately 15 minutes after pharyngeal acid load. Healthy subjects rarely have any low EBC pH values (defined as < 7.4 based on a normative reference range from 404 healthy subjects). Patients with chronic cough who subsequently responded well to proton pump inhibition (n = 8) invariably had one or more cough episodes associated with EBC acidification. No patient who had normal EBC pH with each of their cough episodes reported a clinically relevant response to proton-pump inhibition. CONCLUSION: Patients whose cough responds to proton pump inhibition have transient exhaled breath condensate acidification with coughing episodes, supporting the role of airway acidification in reflux-triggered cough. Multi-sample EBC pH profiles, involving samples collected immediately subsequent to a coughing episode, may be useful appropriately to direct therapy to those patients with cough who have relevant acid reflux

Native IYG: Improving Psychosocial Protective Factors for HIV/STI and Teen Pregnancy Prevention among Youth in American Indian/Alaska Native Communities

Background: Few HIV/STI and pregnancy prevention programs for youth in American Indian and Alaska Native (AI/AN) communities have been rigorously evaluated despite sexual health disparities in this population. This study reports the evaluation of a culturally adapted Internet-based HIV/STI and pregnancy prevention program for AI/AN youth, Native It’s Your Game (Native IYG). Methods: A randomized study was conducted with 523 youth (12 to 14 years old), recruited from 25 tribal sites in Alaska, Arizona, and the Pacific Northwest. Participants were surveyed at baseline and upon completion of treatment or comparison interventions. Multivariable linear regression models were used to assess impact on short term psychosocial determinants of sexual initiation. Results: A sample of 402 intervention (n=290) and comparison (n=112) youth completed the post-intervention survey (76.9% retention) from 1 to 462 days post-baseline (mean = 114, SD = ±96.67). Participants were 55.5% female, mean age of 13.0 (± 0.97) years with 86.1% self-reporting as AI/AN. Reasons not to have sex, STI knowledge, condom knowledge, condom availability self-efficacy, and condom use self-efficacy were significantly impacted (all P ≤ .01). Limitations included variability in intervention exposure and time between data collection time points. Conclusions: Native IYG demonstrated efficacy to impact short-term psychosocial determinants of sexual behavior in a sample of predominantly AI/AN middle school youth

Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model.

Many risk genes for the development of Alzheimer's disease (AD) are exclusively or highly expressed in myeloid cells. Microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for their survival. We designed and synthesized a highly selective brain-penetrant CSF1R inhibitor (PLX5622) allowing for extended and specific microglial elimination, preceding and during pathology development. We find that in the 5xFAD mouse model of AD, plaques fail to form in the parenchymal space following microglial depletion, except in areas containing surviving microglia. Instead, Aβ deposits in cortical blood vessels reminiscent of cerebral amyloid angiopathy. Altered gene expression in the 5xFAD hippocampus is also reversed by the absence of microglia. Transcriptional analyses of the residual plaque-forming microglia show they exhibit a disease-associated microglia profile. Collectively, we describe the structure, formulation, and efficacy of PLX5622, which allows for sustained microglial depletion and identify roles of microglia in initiating plaque pathogenesis

Rapid Training and Implementation of the Pollock Technique, a Safe, Effective Newborn Circumcision Procedure, in a Low-Resource Setting

Male circumcision is highly protective against urinary tract infections, inflammatory conditions of the penis, sexually transmitted infections, and urogenital cancers. We aimed to reintroduce newborn male circumcision through the creation of a training program in Port-au-Prince, Haiti?an area with a considerable burden of preventable urogenital infections, sexually transmitted infections, and low circumcision rate?after an earlier study reported that a majority of Haitian medical providers were in need of and wanted newborn circumcision training. The program was conducted at the GHESKIO Health Centers, a large, non-governmental clinic offering comprehensive pediatric and adult health services. Two Haitian obstetricians and seven nurses learned circumcision procedures. On training completion, one of two obstetricians achieved surgical competence. Introduction of a newborn male circumcision training program was feasible, achieving an acceptable rate of procedural competency and high-quality services. Permanent resources now exist in Haiti to train additional providers to perform newborn male circumcisions

Knowledge, Attitudes, Practices and Beliefs about Medical Male Circumcision (MMC) among a Sample of Health Care Providers in Haiti

Background Haiti has the highest number of people living with HIV infection in the Caribbean/Latin America region. Medical male circumcision (MMC) has been recommended to help prevent the spread of HIV. We sought to assess knowledge, attitudes, practices and beliefs about MMC among a sample of health care providers in Haiti. Methods A convenience sample of 153 health care providers at the GHESKIO Centers in Haiti responded to an exploratory survey that collected information on several topics relevant to health providers about MMC. Descriptive statistics were calculated for the responses and multivariable logistic regression was conducted to determine opinions of health care providers about the best age to perform MMC on males. Bayesian network analysis and sensitivity analysis were done to identify the minimum level of change required to increase the acceptability of performing MMC at age less than 1 year. Results The sample consisted of medical doctors (31.0%), nurses (49.0%), and other health care professionals (20.0%). Approximately 76% showed willingness to offer MMC services if they received training. Seventy-six percent believed that their male patients would accept circumcision, and 59% believed infancy was the best age for MMC. More than 90% of participants said that MMC would reduce STIs. Physicians and nurses who were willing to offer MMC if provided with adequate training were 2.5 (1.15–5.71) times as likely to choose the best age to perform MMC as less than one year. Finally, if the joint probability of choosing “the best age to perform MMC” as one year or older and having the mistaken belief that MMC prevents HIV entirely is reduced by 63% then the probability of finding that performing MMC at less than one year acceptable to health care providers is increased by 35%. Conclusion Participants demonstrated high levels of knowledge and positive attitudes towards MMC. Although this study suggests that circumcision is acceptable among certain health providers in Haiti, studies with larger and more representative samples are needed to confirm this finding

A proposal for the addressing the needs of the pediatric pulmonary work force

Unprecedented opportunities and daunting difficulties are anticipated in the future of pediatric pulmonary medicine. To address these issues and optimize pediatric pulmonary training, a group of faculty from various institutions met in 2019 and proposed specific, long-term solutions to the emerging problems in the field. Input on these ideas was then solicited more broadly from faculty with relevant expertise and from recent trainees. This proposal is a synthesis of these ideas. Pediatric pulmonology was among the first pediatric specialties to be grounded deliberately in science, requiring its fellows to demonstrate expertise in scientific inquiry (1). In the future, we will need more training in science, not less. Specifically, the scope of scientific inquiry will need to be broader. The proposal outlined below is designed to help optimize the practices of current providers and to prepare the next generation to be leaders in pediatric care in the future. We are optimistic that this can be accomplished. Our broad objectives are (a) to meet the pediatric subspecialty workforce demand by increasing interest and participation in pediatric pulmonary training; (b) to modernize training to ensure that future pediatric pulmonologists will be prepared clinically and scientifically for the future of the field; (c) to train pediatric pulmonologists who will add value in the future of pediatric healthcare, complemented by advanced practice providers and artificial intelligence systems that are well-informed to optimize quality healthcare delivery; and (d) to decrease the cost and improve the quality of care provided to children with respiratory diseases

Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways

Background The Chr17q12-21.2 region is the strongest and most consistently associated region with asthma susceptibility. The functional genes or single nucleotide polymorphisms (SNPs) are not obvious due to linkage disequilibrium. Objectives We sought to comprehensively investigate whole-genome sequence and RNA sequence from human bronchial epithelial cells to dissect functional genes/SNPs for asthma severity in the Severe Asthma Research Program. Methods Expression quantitative trait loci analysis (n = 114), correlation analysis (n = 156) of gene expression and asthma phenotypes, and pathway analysis were performed in bronchial epithelial cells and replicated. Genetic association for asthma severity (426 severe vs 531 nonsevere asthma) and longitudinal asthma exacerbations (n = 273) was performed. Results Multiple SNPs in gasdermin B (GSDMB) associated with asthma severity (odds ratio, >1.25) and longitudinal asthma exacerbations (P < .05). Expression quantitative trait loci analyses identified multiple SNPs associated with expression levels of post-GPI attachment to proteins 3, GSDMB, or gasdermin A (3.1 × 10−9 < P < 1.8 × 10−4). Higher expression levels of GSDMB correlated with asthma and greater number of exacerbations (P < .05). Expression levels of GSDMB correlated with genes involved in IFN signaling, MHC class I antigen presentation, and immune system pathways (false-discovery rate–adjusted P < .05). rs1031458 and rs3902920 in GSDMB colocalized with IFN regulatory factor binding sites and associated with GSDMB expression, asthma severity, and asthma exacerbations (P < .05). Conclusions By using a unique set of gene expression data from lung cells obtained using bronchoscopy from comprehensively characterized subjects with asthma, we show that SNPs in GSDMB associated with asthma severity, exacerbations, and GSDMB expression levels. Furthermore, its expression levels correlated with asthma exacerbations and antiviral pathways. Thus, GSDMB is a functional gene for both asthma susceptibility and severity