A hamster model for stress-induced weight gain.

This review addresses the translational relevance of animal models of stress and their effects on body weight. In humans, stress, whether chronic or acute, has often been associated with increased food intake and weight gain. In view of the current obesity epidemic, this phenomenon is especially relevant. Such observations contrast with reports with commonly used laboratory animals, especially rats and mice. In these species, it is common to find individuals gaining less weight under stress, even with potent social stressors. However, there are laboratory species that present increased appetite and weight gain under stress, such as golden hamsters. Furthermore, these animals also include metabolic and behavioral similarities with humans, including hoarding behavior which is also enhanced under stress. Consequently, we propose that our comparative perspective provides useful insights for future research on the development of obesity in humans as a consequence of chronic stress exposure.

The phylogeny and evolutionary ecology of hoverflies (Diptera: Syrphidae) inferred from mitochondrial genomes.

Hoverflies (Diptera: Syrphidae) are a diverse group of pollinators and a major research focus in ecology, but their phylogenetic relationships remain incompletely known. Using a genome skimming approach we generated mitochondrial genomes for 91 species, capturing a wide taxonomic diversity of the family. To reduce the required amount of input DNA and overall cost of the library construction, sequencing and assembly was conducted on mixtures of specimens, which raises the problem of chimera formation of mitogenomes. We present a novel chimera detection test based on gene tree incongruence, but identified only a single mitogenome of chimeric origin. Together with existing data for a final set of 127 taxa, phylogenetic analysis on nucleotide and amino acid sequences using Maximum Likelihood and Bayesian Inference revealed a basal split of Microdontinae from all other syrphids. The remainder consists of several deep clades assigned to the subfamily Eristalinae in the current classification, including a clade comprising the subfamily Syrphinae (plus Pipizinae). These findings call for a re-definition of subfamilies, but basal nodes had insufficient support to fully justify such action. Molecular-clock dating placed the origin of the Syrphidae crown group in the mid-Cretaceous while the Eristalinae-Syrphinae clade likely originated near the K/Pg boundary. Transformation of larval life history characters on the tree suggests that Syrphidae initially had sap feeding larvae, which diversified greatly in diet and habitat association during the Eocene and Oligocene, coinciding with the diversification of angiosperms and the evolution of various insect groups used as larval host, prey, or mimicry models. Mitogenomes proved to be a powerful phylogenetic marker for studies of Syrphidae at subfamily and tribe levels, allowing dense taxon sampling that provided insight into the great ecological diversity and rapid evolution of larval life history traits of the hoverflies.

Effectiveness of the SMART Sex Ed program among 13-18 year old English and Spanish speaking adolescent men who have sex with men.

Adolescent men who have sex with men (AMSM) have a high HIV incidence and low utilization of testing and prevention services. However, very few HIV prevention programs exist that focus on the unique sexual health needs of AMSM. SMART is a stepped care package of eHealth interventions that comprehensively address the sexual and HIV prevention needs of AMSM. This study examines the impact of the first step of SMART, "SMART Sex Ed," on 13- to 18-year-old AMSM (n = 983) from baseline to three-month follow-up across 18 separate outcomes measuring HIV prevention attitudes, skills, and behaviors. We observed significant change from baseline to three-month post-intervention in nine HIV-related outcomes (e.g., receipt of HIV and STI test, HIV knowledge), as well as largely consistent effects across demographic subgroups (e.g., race, age, rural, low SES). Analyses observed no effects on condom use behaviors. SMART Sex Ed shows promise as an effective sexual health education program for diverse AMSM.

RESUMEN: Los adolescentes hombres que tienen sexo con otros hombres (AHSH) experimentan alta incidencia del VIH y baja utilización de servicios de prueba y prevención. Sin embargo, existen muy pocos programas de prevención del VIH enfocados en las necesidades particulares para la salud sexual de AHSH. SMART es un paquete de intervenciones de cuidado escalonado que usa plataformas electrónicas (eHealth) y que atiende de forma integrada las necesidades de salud sexual y prevención del VIH de AHSH. Este estudio examina el impacto de la primera etapa de SMART, llamada "SMART Sex Ed", entre AHSH (n = 983) entre las edades de 13 a 18 años e integra datos desde el reclutamiento con seguimiento cada 3 meses. Se recopilaron datos de 18 indicadores de actitudes, destrezas y prácticas de prevención del VIH (Ej. Historial de pruebas de VIH o ITS; conocimiento sobre VIH), así como los efectos en diferentes grupos demográficos (Ej. Raza, edad, área rural, y bajo nivel socioeconómico). Los análisis realizados demuestran que las características demográficas no tienen efecto en las prácticas de uso de condón. SMART Sex Ed es una intervención prometedora para educación sexual efectiva para AHSH.

"It's Very Inconvenient for Me": A Mixed-Method Study Assessing Barriers and Facilitators of Adolescent Sexual Minority Males Attending PrEP Follow-Up Appointments.

Researching PrEP retention in adolescent sexual minority men (ASMM) is critical to increasing persistence of PrEP in this priority population, yet this research is lacking. ASMM (N = 1433) completed a baseline survey for an online HIV prevention program between 2018 and 2020. Open- and closed-ended survey items identified their beliefs about attending 3-month PrEP follow-up appointments and examined the association of Andersen's Behavioral Model factors (predisposing, enabling, and need) and confidence to attend these appointments. Qualitative and quantitative findings show that perceived parental support is a salient factor in ASMM attending PrEP follow-up appointments. Participants did not want to have to go to the doctor and get bloodwork done trimonthly, and qualitative findings elucidated rationales for this, such as perceptions that follow-ups might be time-consuming, costly, and could out their sexuality to their parents. This study suggests that parents are gatekeepers for ASMM to initiate and sustain the PrEP care continuum.

Lifelong enhancement of body mass from adolescent stress in male hamsters.

In hamsters, exposure to stress in adulthood causes increased body weight. We addressed how social stress during puberty would impact food intake and body weight. Stressed hamsters started gaining significantly more weight than controls after only two days of stress exposure. Over a two-week period, stressed subjects gained 10% more weight and consumed more food than controls. At the end of the stress period, stressed hamsters collected nearly twice as many palatable sugar pellets from an arena than controls. Stressed subjects presented 15-20% more body fat in mesenteric, inguinal, and retroperitoneal fat pads. In order to assess the duration of these effects, we analyzed data from previous studies keeping hamsters for over two months past the stress period in puberty. Our analysis shows that stressed hamsters stopped gaining more weight after the stress period, but their body weights remained elevated for over two months, consistently weighing 10% more than their non-stressed counterparts. We also analyzed conditioning training data collected after the period of stress in late puberty and early adulthood (P56 to P70) that was part of the original studies. Training consisted of lever pressing for palatable food rewards. At these times, previously stressed hamsters retrieved similar numbers of food pellets from the conditioning chambers, suggesting no difference in appetite after the stress period. These data showing a long-lasting effect of stress on body weight may be relevant to studies on the ontogeny of lifelong obesity.

Patterns of Online and Offline Partnering, Partnership Characteristics, and Condomless Sex Among Adolescent Sexual Minority Males in the USA.

Online partner-seeking among adolescent sexual minority males (ASMM) has been associated with condomless anal sex. Two hypotheses may explain this association: that online venues facilitate HIV transmission risk behavior more than offline venues (accentuation), or that individuals who tend to engage in these behaviors are more likely to seek partners online (self-selection). We examined these hypotheses in 700 13-18 year-old ASMM who completed the baseline survey of an effectiveness trial of an HIV prevention program in 2018-2020. The survey assessed demographic, sexual, and venue characteristics of male anal sex partnerships in the past 3 months. Many participants (83%) reported ≥ 1 online-met partner; most were met via sexual networking applications and were older than offline-met partners. Having met partners online, but not whether a particular partner was met online, was associated with greater odds of receptive condomless sex. Findings support the self-selection hypothesis, which has implications for HIV prevention in ASMM.

Minority Stressors and Identity Affirmation as Predictors of Condomless Sex Among Self-Identified Bisexual Men: The Role of Partner Gender.

Bisexual men are at increased risk for HIV/STI and early pregnancy involvement compared to heterosexual men, and minority stressors (e.g., enacted and internalized stigma) are associated with sexual risk behavior in samples of gay and bisexual men. However, few studies have specifically focused on bisexual men, and little is known about the unique predictors of sexual risk behavior in this population. Further, few studies have focused on positive sexual orientation-related factors such as identity affirmation, which may be protective against sexual risk behavior. As such, the goals of the current study were to examine minority stressors and identity affirmation as predictors of condomless sex among self-identified bisexual men, and whether these associations differed as a function of partner gender. We used four waves of data spanning 24 months from a subset of self-identified bisexual men in a larger cohort of gay and bisexual men ages 16-29 years at enrollment. At each wave, participants reported on up to four partners, allowing us to examine within-person associations. We used mixed effects negative binomial models to examine the associations between our predictors (discrimination, internalized binegativity, and identity affirmation) and condomless sex acts. In addition, we tested whether partner gender moderated each of the associations by including interaction effects in each of the models. Results indicated that higher levels of internalized binegativity and lower levels of identity affirmation were associated with less condomless sex with female partners, but they were not associated with condomless sex with male partners. Discrimination was not associated with condomless sex with male or female partners. These findings suggest that predictors of condom use among self-identified bisexual men differ as a function of partner gender, and they highlight the need to identify strategies to promote sexual health while also supporting positive identity development in this population.

Differences in HIV Risk Behaviors Between Self-Identified Gay and Bisexual Young Men Who are HIV-Negative.

Young men who have sex with men (MSM) are disproportionately affected by HIV, but it remains unclear whether there are differences in HIV risk behaviors between self-identified gay and bisexual young men. To address this, the current study examined differences in condomless sex and substance use before sex with male partners between self-identified gay and bisexual young men who are HIV-negative. Additionally, we examined differences in HIV risk behaviors with male versus female partners among the bisexual men. We used four waves of data spanning 24 months from a cohort of young MSM ages 16-29. At each wave, participants reported on up to four partners, allowing us to examine within-person associations. Compared to gay men, bisexual men reported more insertive condomless anal sex (CAS) with casual partners, they were more likely to report marijuana use before sex, and they were less likely to report lifetime HIV testing and PrEP use. Alcohol and marijuana use before sex were associated with CAS for both gay and bisexual men, but the association between marijuana use and insertive CAS was stronger for bisexual men. Bisexual men reported more condomless sex with female partners compared to male partners, but this was not significant after accounting for alcohol and marijuana use. Bisexual men were more likely to report alcohol and marijuana use with female partners compared to male partners, but both alcohol and marijuana use were associated with condomless sex regardless of partner gender. Findings support the need for tailored HIV prevention for self-identified bisexual men to address their lack of preventive behaviors, their increased engagement in certain risk behaviors with male partners, and their engagement in risk behaviors with female partners.

Paediatric cardiopulmonary resuscitation: Knowledge and perceptions of surf lifeguards.

AIM: To conduct a comprehensive analysis of surf lifeguards' real and perceived ability in paediatric cardiopulmonary resuscitation (CPR), knowledge of child resuscitation protocols and technical competency during a simulated CPR scenario. METHODS: Surf lifeguards aged 16 years and over were invited to complete a written survey and simulated test of five cycles of single-rescuer CPR on a paediatric manikin. In accordance with the latest Australia and New Zealand Committee on Resuscitation (ANZCOR) guidelines, practical skills were assessed by trained observers. A manikin fitted with electronic data-collection capability recorded technical compression and ventilation skills. RESULTS: A total of 244 participants were entered into the study. Most previous CPR training did not include a paediatric component (53%). Lifeguards rated their ability to perform CPR on an adult as 'highly effective' or 'effective' in 56% of responses. Less than a quarter (23%), however, gave this response when compared to a child. Observed CPR skills were mostly compliant with ANZCOR guidelines (80-99%). Manikin data provided a median compression rate of 115.6 min-1 , compression depth of 3.7 cm and tidal volume of 220.0 mL. Almost half of ventilations were too little (45%), and around one fifth were too much (22%). CONCLUSIONS: Surf lifeguards are less confident in paediatric CPR. The overall performance of observed and technical CPR skills, which were mostly ANZCOR guideline compliant, suggests that performance could be improved if paediatric-specific training is provided to supplement the adult-focused methods currently in use. The use of electronic feedback manikins is recommended to address the technical compression and ventilation issues identified in this study.

Cluster randomized controlled trial of a multilevel physical activity intervention for older adults.

BACKGROUND: Older adults are the least active population group. Interventions in residential settings may support a multi-level approach to behavior change. METHODS: In a cluster randomized control trial, 11 San Diego retirement communities were assigned to a physical activity (PA) intervention or a healthy aging attention control condition. Participants were 307 adults over 65 years old. The multilevel PA intervention was delivered with the assistance of peer leaders, who were trained older adult from the retirement communities. Intervention components included individual counseling & self-monitoring with pedometers, group education sessions, group walks, community advocacy and pedestrian community change projects. Intervention condition by time interactions were tested using generalized mixed effects regressions. The primary outcomes was accelerometer measured physical activity. Secondary outcomes were blood pressure and objectively measured physical functioning. RESULTS: Over 70% of the sample were 80 years or older. PA significantly increased in the intervention condition (56 min of moderate-vigorous PA per week; 119 min of light PA) compared with the control condition and remained significantly higher across the 12 month study. Men and participants under 84 years old benefited most from the intervention. There was a significant decrease in systolic (p < .007) and diastolic (p < .02) blood pressure at 6 months. Physical functioning improved but the changes were not statistically significant. CONCLUSIONS: Intervention fidelity was high demonstrating feasibility. Changes in PA and blood pressure achieved were comparable to other studies with much younger participants. Men, in particular, avoided a year-long decline in PA. TRIAL REGISTRATION: clincialtrials.gov Identifier: NCT01155011 .

Threefold Increase in PrEP Uptake Over Time with High Adherence Among Young Men Who Have Sex With Men in Chicago.

The goal of this work is to better understand utilization and uptake of pre-exposure prophylaxis (PrEP) among young men who have sex with men (YMSM) and transgender women (TGW). We assessed trends and correlates of PrEP use and adherence across three time points of longitudinal data collection among 885 YMSM and TGW (aged 16-29) from the RADAR cohort in Chicago, 2015-2017. Past 6-month PrEP use increased across three visits: from 6.6 to 17.5%. In multivariable models, past 6-month PrEP use was significantly associated with participation in condomless sex, having more sexual partners, and older age. At least three-quarters of current PrEP users reported being ≥ 90% adherent to PrEP medication across all visits. Past 6-month PrEP use increased over time with those who participated in high-risk HIV behaviors also those most likely to have taken PrEP. As PrEP uptake continues to rise, more research will be needed to understand predictors of PrEP usage, as well as patterns of sexual behavior change following uptake.

Implementation of the 2017 Berlin Concussion in Sport Group Consensus Statement in contact and collision sports: a joint position statement from 11 national and international sports organisations.

The 2017 Berlin Concussion in Sport Group Consensus Statement provides a global summary of best practice in concussion prevention, diagnosis and management, underpinned by systematic reviews and expert consensus. Due to their different settings and rules, individual sports need to adapt concussion guidelines according to their specific regulatory environment. At the same time, consistent application of the Berlin Consensus Statement's themes across sporting codes is likely to facilitate superior and uniform diagnosis and management, improve concussion education and highlight collaborative research opportunities. This document summarises the approaches discussed by medical representatives from the governing bodies of 10 different contact and collision sports in Dublin, Ireland in July 2017. Those sports are: American football, Australian football, basketball, cricket, equestrian sports, football/soccer, ice hockey, rugby league, rugby union and skiing. This document had been endorsed by 11 sport governing bodies/national federations at the time of being published.

Complex Surgical Infants Benefit From Postdischarge Telemedicine Visits.

BACKGROUND: Transition from the neonatal intensive care unit (NICU) to home is challenging for caregivers of complex surgical infants. A prospective, observational cohort pilot study using telemedicine to improve transition was implemented in a quaternary level IV NICU. PURPOSE: (1) To assess, identify, and resolve patient care concerns in the immediate postdischarge period. (2) To improve caregiver knowledge and care practices. DESIGN METHODS: Caregivers of medically complex infants participated in telemedicine visits with neonatal providers within 1 week of discharge. Providers reviewed infant health, equipment use, and outpatient follow-up. Video was used to visualize the infant, home environment, and care practices. Caregivers completed a postvisit satisfaction survey. RESULTS: Ninety-three visits were performed from May 2015 to March 2017. Seventy-six percent of visits were postsurgery patients. Seventy-eight postdischarge issues were identified: medication administration (13%), respiratory (19%), feeding (33%), and surgical site (35%). Fifty percent of caregivers reported that telemedicine visits prevented an additional call or visit to a clinician; 12% prompted an earlier visit (n = 93). Caregiver satisfaction rating was high. Median estimation of total mileage saved by respondents was 1755 miles. CONCLUSIONS: Postdischarge telemedicine visits with complex surgical NICU graduates identify clinical issues, provide caregivers with support, and save travel time. Advanced practice nurses are instrumental in patient recruitment, with patient visits, and in providing postdischarge continuity of care. Barriers to implementation were identified. IMPLICATION FOR PRACTICE AND RESEARCH: A randomized controlled study is warranted to measure the value of telemedicine visits for specific patient cohorts.

Surf, sand, scrapes and stings: First aid incidents involving children at New Zealand beaches, 2007­2012.

Aims: In spite of the popularity of beaches for family recreation, little is known about childhood injuries sustained at beaches. It is the purpose of this study to analyse data from incidents necessitating first aid treatment from reports compiled by surf lifeguards on New Zealand beaches.Method: A retrospective analysis of first aid incidents involving children (<16 years) was conducted using data obtained from Surf Life Saving New Zealand incident report forms during five summer seasons from 2007 to 2012. In addition to demographic data, the incident reports included such detail as the type of injury, the activity and location prior to injury, the injury outcome, and the first aid equipment used.Results: Children (n = 4407) accounted for one-half (52%) of all injuries; of these, 55% were male, and incidence peaked in the 11- to 15-year age group (24%). Most incidents (90%) required minor treatment, with lacerations (44%) the most common injury. Marine stings accounted for one-quarter (24%) of injuries and were most frequent among younger children (<10 years). Injuries to the extremities were frequently noted in the incident reports, the feet (33%) and hands (8%) being common sites.Conclusions: Although most (90%) injury incidents were minor in nature, their frequency (880 cases per season) suggests that greater emphasis on prevention rather than cure would be efficacious. Ways of promoting child beach safety via greater care giver awareness, the use of protective clothing and footwear, and child safety promotion via health professionals and safety organisations are discussed.

Survival and decannulation across indications for infant tracheostomy: a twelve-year single-center cohort study.

OBJECTIVE: Describe survival and decannulation following infant tracheostomy based on indication for tracheostomy placement. STUDY DESIGN: Retrospective cohort study of infants who received tracheostomy at a single pediatric hospital over a twelve-year period. Primary and secondary indications were categorized into pulmonary, anatomic, cardiac, neurologic/musculoskeletal, and others. RESULTS: A total of 378 infants underwent tracheostomy; 323 had sufficient data to be included in analyses of post-discharge outcomes. Overall mortality was 26.3%; post-operative and post-discharge mortality differed across primary indications (P = 0.03 and P = 0.005). Among survivors, 69.3% decannulated at a median age of 3.0 years (IQR 2.3, 4.5 years). Decannulation among survivors varied across primary indications (P = 0.002), ranging from 17% to 75%. In multivariable analysis, presence of a neurologic or musculoskeletal indication for tracheostomy was a significant negative predictor of future decannulation (aOR 0.10 [95% CI 0.02-0.44], P = 0.003). CONCLUSIONS: Early childhood outcomes vary across indications for infant tracheostomy.

Taxonomic revision of Romaleosyrphus Bigot (Diptera, Syrphidae), including descriptions of seven new species.

The genus Romaleosyrphus Bigot is reviewed, including the description of seven new species (R.argosi Moran, sp. nov., R.bigoti Moran, sp. nov., R.drysus Moran, sp. nov., R.nephelaeus Moran & Thompson, sp. nov., R.soletluna Moran & Thompson, sp. nov., R.vockerothi Moran & Thompson, sp. nov. and R.woodi Moran, sp. nov.). Romaleosyrphusarctophiloides (Giglio-Tos), comb. nov. is transferred to Romaleosyrphus. Romaleosyrphus stat. rev. is redefined to represent the monophyletic unit of species within Criorhinina which possess holoptic males, a proximal ventral half of vein C with setae, a broad intersection of vein R1 with vein C, the distal part of R4+5 beyond M1 longer than cross-vein h and appressed pile on the abdomen. Descriptions, habitus and genitalia photographs, distributions, and an illustrated key for all nine Romaleosyrphus are presented. DNA barcode data are provided for eight of the species with a cytochrome c oxidase subunit I gene tree presented and discussed.

Age of Occurrence and Severity of Childhood Sexual Abuse: Impacts on Health Outcomes in Men Who Have Sex with Men and Transgender Women.

Childhood sexual abuse (CSA) is associated with a wide range of health outcomes and is more prevalent among men who have sex with men (MSM) compared to men who have sex with women exclusively and among transgender women (TW) compared to cisgender peers; however, there is a lack of consensus regarding an explanatory theoretical model. This analysis examined these models across health outcomes using baseline data from a longitudinal study of MSM and TW in Chicago (n = 1,035) collected from 2015 to 2019. Severity of CSA was measured for two age ranges (prior to 13 and 13-17). Logistic regression and negative binomial regressions were estimated. Teenage experiences of CSA were associated with alcohol problems, cannabis problems, suicide ideation/attempt, depression, condomless anal sex partners, rectal STI, and HIV. Pre-teenage CSA was associated with alcohol use and depressive symptoms. Significant interactions across age of experience of CSA were found for alcohol problems, cannabis problems, and condomless anal sex partners. Consistent with previous literature, this analysis found CSA to be a significant influence on various health outcomes. No single explanatory framework emerged; however, adolescent exposures may be more closely linked to health outcomes and risk behaviors than pre-teenage or cumulative exposures.

Knowledge and perceptions of cardiopulmonary resuscitation amongst New Zealand podiatrists: a web-based survey.

BACKGROUND: Podiatrists in New Zealand have a duty of care to assist patients in an emergency, and current cardiopulmonary resuscitation (CPR) certification is a requirement for registration. However, it is unknown how competent and confident podiatrists are in administering CPR and how they would respond in an emergency. Having a health professional who has a competent knowledge of CPR and skills in basic life support, can improve survival rates from sudden cardiac arrest. Therefore, the aim of this study was to survey New Zealand podiatrists to determine their CPR knowledge and qualifications; beliefs about the application of CPR; and perceptions of their competency in CPR. METHODS: This cross-sectional study used a web-based survey. Participants were New Zealand registered podiatrists with a current annual practising certificate. The 31-item survey included questions to elicit demographic information, CPR practice and attitudes, and CPR knowledge. Responses were collected between March and August 2020. RESULTS: 171 podiatrists responded to the survey. 16 % of the podiatrists (n = 28) had performed CPR in an emergency, with a 50 % success rate. Participants were predominantly female (n = 127, 74 %) and working in private practice (n = 140,82 %). Nearly half of respondents were younger than 40 years (n = 75,44 %) and had less than 10 years of clinical experience (n = 73, 43 %). Nearly all (n = 169,97 %) participants had received formal CPR training in the past two years, with 60 % (n = 105) receiving training in the past 12 months. Most respondents (n = 167,98 %) self-estimated their CPR ability as being effective, very effective, or extremely effective. Participants' knowledge of CPR was variable, with the percentage of correct answers for CPR protocol statements ranging between 20 and 90 %. CONCLUSIONS: This study provides the first insight into New Zealand podiatrists' CPR knowledge and perceptions. Podiatrists were found to have high levels of CPR confidence but demonstrated gaps in CPR knowledge. Currently, New Zealand registered podiatrists require biennial CPR re-certification. However, resuscitation authorities in New Zealand and overseas recommend an annual update of CPR skills. Based on this study's findings, and in line with Australia and the United Kingdom, the authors recommend a change from biennial to annual CPR re-certification for podiatrists in New Zealand. TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12620001144909 ).

The PrEP Cascade in a National Cohort of Adolescent Men Who Have Sex With Men.

BACKGROUND: Pre-exposure prophylaxis (PrEP) has been an available biomedical intervention for at-risk adolescents for over 2 years; however, progression from awareness to uptake and adherence has been slow. In response, we map adolescent men who have sex with men (AMSM) onto the PrEP Motivation Cascade to identify stages for intervention. METHODS: We analyzed PrEP-related attitudinal and behavioral data from a US national cohort of 1398 AMSM. RESULTS: A majority of the sample (53.9%) were identified as appropriate PrEP candidates. Of those identified as appropriate candidates, 51.8% were precontemplative (stage 1; unwilling to take or believing they were inappropriate candidates for PrEP), and 48.2% reached contemplation (stage 2; willing and self-identified as appropriate candidates). Only 16.3% of candidates reached preparation (stage 3; seeing PrEP as accessible and planning to initiate PrEP), and 3.1% reached PrEP action (stage 4; prescribed PrEP). Although few of the AMSM identified as appropriate candidates were on PrEP, most users (87%) reported high adherence to 4+ doses per week (stage 5; PrEP maintenance). Factors associated with reaching later stages were being older, being out to parents, and engaging in previous HIV/sexually transmitted infection testing. CONCLUSIONS: AMSM PrEP use falls short of recommended levels. PrEP campaigns are needed to raise awareness by targeting key AMSM subgroups that underestimate the appropriateness of use. Equally important, parents and health providers of AMSM should serve educational roles to help facilitate potential PrEP uptake, by motivating adolescents and giving them the skills needed to request, fill, and adhere to a prescription.

The Discovery and Development of Thienopyrimidines as Inhibitors of Helicobacter pylori That Act through Inhibition of the Respiratory Complex I.

The successful treatment of Helicobacter pylori infections is becoming increasingly difficult due to the rise of resistance against current broad spectrum triple therapy regimens. In the search for narrow-spectrum agents against H. pylori, a high-throughput screen identified two structurally related thienopyrimidine compounds that selectively inhibited H. pylori over commensal members of the gut microbiota. To develop the structure-activity relationship (SAR) of the thienopyrimidines against H. pylori, this study employed four series of modifications in which systematic substitution to the thienopyrimidine core was explored and ultimately side-chain elements optimized from the two original hits were merged into lead compounds. During the development of this series, the mode of action studies identified H. pylori's respiratory complex I subunit NuoD as the target for lead thienopyrimidines. As this enzyme complex is uniquely essential for ATP synthesis in H. pylori, a homology model of the H. pylori NuoB-NuoD binding interface was generated to help rationalize the SAR and guide further development of the series. From these studies, lead compounds emerged with increased potency against H. pylori, improved safety indices, and a good overall pharmacokinetic profile with the exception of high protein binding and poor solubility. Although lead compounds in the series demonstrated efficacy in an ex vivo infection model, the compounds had no efficacy in a mouse model of H. pylori infection. Additional optimization of pharmacological properties of the series to increase solubility and free-drug levels at the sequestered sites of H. pylori infection would potentially result in a gain of in vivo efficacy. The thienopyrimidine series developed in this study demonstrates that NuoB-NuoD of the respiratory complex I can be targeted for development of novel narrow spectrum agents against H. pylori and that thienopyrimines can serve as the basis for future advancement of these studies.