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Despite widespread prevalence of lubricant use and rectal douching for receptive anal intercourse (RAI) among men who have sex with men (MSM), research evaluating the association of these behaviors with sexually transmitted infections (STIs) is limited. This is an observational analysis of a longitudinal cohort of predominantly Black/Latino MSM in Los Angeles. Every six months from August 2014 to January 2018, participants received STI screening and surveys evaluating lubricant use, douching, substance use, and sexual risk behaviors. General estimating equations evaluated the association between consistent lubricant use and douching for RAI with positive rectal Neisseria gonorrhoeae, Chlamydia trachomatis, and/or syphilis (positive STI). Among 313 participants across 552 study visits, 16.5% (91/552) had positive STI. Consistent lubricant use was reported in 52.7% (243/552) and rectal douching in 57.6% (318/552) of study visits. Consistent lubricant use was associated with STI diagnosis (adjusted OR [AOR] 1.81; 95% CI 1.11-2.96; p = 0.018). Each episode of rectal douching before RAI was associated with 2% increased odds of positive STI (AOR 1.02; 95% CI 1.00-1.04; p = 0.041). Among this cohort of HIV-positive and high-risk HIV-negative MSM, lubricant use and douching was common and independently associated with an STI, suggesting the utility of prevention messaging around barrier methods/condoms for sexual encounters involving douching/lubricant use.

Abstract Background Spatial repellents (SRs) have been widely used for prevention of mosquito bites, but their efficacy in reducing Aedes-borne viruses (ABV) has not been tested rigorously at large scale in Asia. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a transfluthrin SR, was developed in Gampaha District of Sri Lanka across three Medical Officer of Health areas; i.e., Negombo, Wattala, and Kelaniya. Methods This trial is a cluster-randomized, placebo-controlled, double-blinded clinical trial. A total of ~14,430 subjects aged ≥ 6 months in 30 clusters (15 intervention, 15 placebo) from ~3900 households (HH) will be randomly selected for enrolment into a “febrile surveillance cohort.” A subset of the surveillance cohort, ~3570 subjects aged ≥4–16 years that test seronegative (naïve) or are serologically positive for a previous single dengue virus (DENV) infection (monotypic) at baseline sampling, will be enrolled into a “longitudinal cohort” for measuring DENV infection based on laboratory-confirmed seroconversion during the trial. Persons identified positive for antibodies against multiple DENV serotypes (multitypic) at baseline will be monitored for secondary analyses. Active ABV disease will be assessed using an enhanced passive surveillance system with case ascertainment performed in designated healthcare facilities. Serum samples will be taken from longitudinal cohort subjects within 1–2 weeks of when intervention is first deployed (T0) with additional samples taken ~12 (T1) and ~24 months (T2) from baseline sampling. DENV seroconversion and ABV active disease rates from baseline (pre-intervention) and follow-up (post-intervention) samples will be compared between intervention and placebo clusters. Participating houses will be monitored entomologically (indoor adult Aedes aegypti population densities and adult female blood fed status) within 3 months before intervention deployment and monthly during the intervention phase. Entomological surveys will monitor indoor adult Ae. aegypti population densities and blood fed status. Dengue incidence in each cohort will be estimated and compared to determine the public health benefit of using an SR. Entomological parameters will be measured to determine if there are entomological correlates of SR efficacy that may be useful for the evaluation of new SR products. Discussion The trial will serve as an efficacy assessment of SR products in South Asia. Results will be submitted to the World Health Organization Vector Control Advisory Group for assessment of public health value towards an endorsement to recommend inclusion of SRs in ABV control programs. Trial registration Sri Lanka Clinical Trial Registry SLCTR /2022/018. Registered on July 1, 2022. ClinicalTrials.gov NCT05452447 . Registered on July 11, 2022. The Universal Trial Number is U1111-1275-3055.

Abstract Background Short tandem repeats (STRs) compose approximately 3% of the genome, and mutations at STR loci have been linked to dozens of human diseases including amyotrophic lateral sclerosis, Friedreich ataxia, Huntington disease, and fragile X syndrome. Improving our understanding of these mutations would increase our knowledge of the mutational dynamics of the genome and may uncover additional loci that contribute to disease. To estimate the genome-wide pattern of mutations at STR loci, we analyze blood-derived whole-genome sequencing data for 544 individuals from 29 three-generation CEPH pedigrees. These pedigrees contain both sets of grandparents, the parents, and an average of 9 grandchildren per family. Results We use HipSTR to identify de novo STR mutations in the 2nd generation of these pedigrees and require transmission to the third generation for validation. Analyzing approximately 1.6 million STR loci, we estimate the empirical de novo STR mutation rate to be 5.24 × 10−5 mutations per locus per generation. Perfect repeats mutate about 2 × more often than imperfect repeats. De novo STRs are significantly enriched in Alu elements. Conclusions Approximately 30% of new STR mutations occur within Alu elements, which compose only 11% of the genome, but only 10% are found in LINE-1 insertions, which compose 17% of the genome. Phasing these mutations to the parent of origin shows that parental transmission biases vary among families. We estimate the average number of de novo genome-wide STR mutations per individual to be approximately 85, which is similar to the average number of observed de novo single nucleotide variants.

Abstract Hydroxycarbamide (HC) is used as a cytoreductive treatment in myeloproliferative neoplasms (MPN). Observational studies have raised the possibility that HC contributes to the development of secondary malignancies, including skin tumours in MPN patients. In this retrospective observational study, we report a single‐centre experience of 324 HC‐treated MPN patients with long‐term follow‐up, compared to 47 MPN patients not on HC. Thirty‐three patients (10.2%) (HC) versus one patient (2.1%) (no HC) developed skin tumours during follow‐up (Hazard ratios [HR] 5.70, 95% confidence intervals 0.66–48.09, p = 0.112). However, male gender, age at MPN diagnosis, type of MPN (polycythaemia rubra vera) and previous history of skin cancer were prognostic variables associated with development of skin cancer.

Follicular lymphoma can transform to a more aggressive histology. Here, the authors use bulk and single cell analysis to create a 26 marker panel which could be used to profile FL samples and predict the risk of transformation using flow cytometry.

Abstract Vector-borne diseases are among the most burdensome infectious diseases worldwide with high burden to health systems in developing regions in the tropics. For many of these diseases, vector control to reduce human biting rates or arthropod populations remains the primary strategy for prevention. New vector control interventions intended to be marketed through public health channels must be assessed by the World Health Organization for public health value using data generated from large-scale trials integrating epidemiological endpoints of human health impact. Such phase III trials typically follow large numbers of study subjects to meet necessary power requirements for detecting significant differences between treatment arms, thereby generating substantive and complex datasets. Data is often gathered directly in the field, in resource-poor settings, leading to challenges in efficient data reporting and/or quality assurance. With advancing technology, mobile data collection (MDC) systems have been implemented in many studies to overcome these challenges. Here we describe the development and implementation of a MDC system during a randomized-cluster, placebo-controlled clinical trial evaluating the protective efficacy of a spatial repellent intervention in reducing human infection with Aedes-borne viruses (ABV) in the urban setting of Iquitos, Peru, as well as the data management system that supported it. We discuss the benefits, remaining capacity gaps and the key lessons learned from using a MDC system in this context in detail.

Research has shown that motor imagery (MI) interventions, involving the systematic and repeated imagination of visual and kinaesthetic components of movements, can enhance performance in sport. Twenty years ago, Holmes and Collins (2001) published the PETTLEP model as a framework to improve the delivery and outcome of MI interventions. The model outlined seven principles to be considered when designing effective imagery interventions: Physical, Environment, Task, Timing, Learning, Emotion, Perspective (i.e., PETTLEP). The incorporation of these principles within MI interventions was assumed to facilitate performance through the optimisation of a functional equivalence between the neurophysiological substrates of motor preparation and execution, and that of MI. Since its conception, this model has become a standard for many in the delivery of imagery interventions in sport and has been corroborated through research and practice. This 20-year review first covers the reach and impact of this influential model and the more recent empirical investigations related to PETTLEP. We then outline how PETTLEP-based imagery may be integrated with action observation to support an increasingly popular approach to the delivery of imagery interventions in sport. Research indicates that combining these two simulation states can enhance sport performance whilst also providing the sport psychologist more control over the imagery experience than is possible through traditional imagery interventions. This article discusses the application of PETTLEP within a combined action observation and imagery framework and provides guidance for sport psychologists for the creation of new PETTLEP-informed interventions.

Entomological research studies on mosquito vector biology, vector competence, insecticide resistance, dispersal, and survival (using mark-release-recapture techniques) often rely on laboratory-reared mosquito colonies to produce large numbers of consistently reared, aged, and sized mosquitoes. We developed a low-cost blood feeding apparatus that supports temperatures consistent with warm blooded animals, using commonly available materials found in low resource environments. We compare our system ("Caserotek") to Hemotek and glass/membrane feeding methods. Two experiments were conducted with Aedes aegypti (Linnaeus 1762) and one with Anopheles darlingi (Root 1926) (Diptera: Culicidae); 3 replicates were conducted for each experiment. Aedes aegypti female mosquitoes were provided chicken blood once per week for 30 min (Experiment #1) for 14 days or 1 hour (Experiment #2) for 21 days. Anopheles darlingi were fed once for 1 hour (Experiment #3). Blood-feeding rates, survival rates, and egg production were calculated across replicates. Caserotek had a significantly higher 30-min engorgement rate (91.1%) than Hemotek (47.7%), and the glass feeder (29.3%) whereas for 1-hour feeding, Hemotek had a significantly lower engorgement rate than either of the other two devices (78% versus 91%). Thirty-day survival was similar among the feeding devices, ranging from 86% to 99%. Mean egg production was highest for the Caserotek feeder (32 eggs per female) compared to the glass feeder and Hemotek device (21-22 eggs per female). Our new artificial feeding system had significantly higher blood feeding rates than for more expensive artificial systems and was equivalent to other fitness parameters. Caserotek only requires the ability to boil water to maintain blood temperatures using a Styrofoam liner. It can be easily scaled up to large production facilities and used under austere conditions.

Purpose This article compares applicants' perceptions of and experiences with virtual and in-person interviews for surgical retina fellowship.

Purpose In this proof-of-concept pilot study, we aimed to increase nurse practitioner (NP) student knowledge of ophthalmology to prepare NPs for encounters in primary care settings. The Association of University Professors of Ophthalmology (AUPO) and the American Academy of Ophthalmology (AAO) endorse core knowledge that medical students should achieve. We assess the effectiveness of an innovative ophthalmologist-led curriculum based on these competencies tailored to issues NPs encounter in primary care.

Roux-en-Y gastric bypass (RYGB) can precipitate protein-calorie malnutrition and micronutrient deficiencies. Sonographically guided endoscopic reversal (ER) via deployment of a stent from the gastric pouch to the remnant stomach in RYGB anatomy has emerged as a novel option for increasing both intestinal transit time and absorptive surface area. In this investigation, short-term nutritional outcomes after ER of a RYGB in patients (age ≥ 18) with severe protein-calorie malnutrition from a single academic health center in Minneapolis, Minnesota over a seven-year period (2015-2021) were retrospectively reviewed pre-procedurally, and at six and twelve months post-procedurally. 17 patients underwent ER for severe protein-calorie malnutrition, or dependence on tube feeds (TF) or total parenteral nutrition (TPN). At 6 months post-ER, two patients were no longer malnourished and only on oral nutrition; three patients were liberated from TPN. Laboratory markers of protein-calorie malnutrition, renal function, and micronutrients were not significantly different at six- or twelve-month follow-up (P > 0.05). In all patients, access to the gastric remnant was maintained via stent placement through the gastric pouch or proximal Roux limb throughout the study period and no complications were noted after ER. Despite the small sample size, this investigation revealed that ER of RYGB may prevent progressive deleterious weight loss, and worsening macro- and micro-nutrient deficiencies, though improvement in weight and nutritional parameters was not observed. Overall, ER was found to be a nuanced and safe, advanced technique useful for when remnant access is desired in RYGB patients.

ABSTRACT Iron acquisition is crucial for virulence of the human pathogen Aspergillus fumigatus. Previous studies indicated that this mold regulates iron uptake via both siderophores and reductive iron assimilation by the GATA factor SreA and the SREBP regulator SrbA. Here, characterization of loss of function as well as hyperactive alleles revealed that transcriptional activation of iron uptake depends additionally on the Zn2Cys6 regulator AtrR, most likely via cooperation with SrbA. Mutational analysis of the promoter of the iron permease-encoding ftrA gene identified a 210-bp sequence, which is both essential and sufficient to impart iron regulation. Further studies located functional sequences, densely packed within 75 bp, that largely resemble binding motifs for SrbA, SreA, and AtrR. The latter, confirmed by chromatin immunoprecipitation (ChIP) analysis, is the first one not fully matching the 5′-CGGN12CCG-3′ consensus sequence. The results presented here emphasize for the first time the direct involvement of SrbA, AtrR, and SreA in iron regulation. The essential role of both AtrR and SrbA in activation of iron acquisition underlines the coordination of iron homeostasis with biosynthesis of ergosterol and heme as well as adaptation to hypoxia. The rationale is most likely the iron dependence of these pathways along with the enzymatic link of biosynthesis of ergosterol and siderophores. IMPORTANCE Aspergillus fumigatus is the most common filamentous fungal pathogen infecting humans. Iron acquisition via siderophores has previously been shown to be essential for virulence of this mold species. Here, we demonstrate that AtrR, a transcription factor previously shown to control ergosterol biosynthesis, azole resistance, and adaptation to hypoxia, is essential for activation of iron acquisition, including siderophore biosynthesis and uptake. Dissection of an iron-regulated promoter identified binding motifs for AtrR and the two previously identified regulators of iron acquisition, SrbA and SreA. Altogether, this study identified a new regulator required for maintenance of iron homeostasis, revealed insights into promoter architecture for iron regulation, and emphasized the coordinated regulation of iron homeostasis ergosterol biosynthesis and adaptation to hypoxia.

Background: The WHO recommended the use of the RTS,S/AS01 malaria vaccine (RTS,S) based on a pilot evaluation in routine use in Ghana, Kenya, and Malawi. A longitudinal qualitative study was conducted to examine facilitators and barriers to uptake of a 4-dose RTS,S schedule. Methods: A cohort of 198 caregivers of RTS,S-eligible children from communities where RTS,S was provided through the pilot were interviewed three times over a ≈22-month, 4-dose schedule. The interviews examined caregiver perceptions and behaviors. Children’s vaccination history was obtained to determine dose uptake. Results: 162 caregivers remained at round 3 (R3); vaccination history was available for 152/162 children. Despite early rumors/fears, the uptake of initial doses was high, driven by vaccine trust. Fears dissipated by R2, replaced with an enthusiasm for RTS,S as caregivers perceived its safety and less frequent and severe malaria. By R3, 98/152 children had received four doses; 34 three doses; 9 one or two doses; and 11 zero doses. The health system and information barriers were important across all under-dose cases. Fears about AEFIs/safety were important in zero-, one-, and two-dose cases. Competing life/livelihood demands and complacency were found in three-dose cases. Regardless of the doses received, caregivers had positive attitudes towards RTS,S by R3. Conclusions: Findings from our study will help countries newly introducing the vaccine to anticipate and preempt reasons for delayed acceptance and missed RTS,S doses.

[This corrects the article DOI: 10.2196/10681.].

Dramatic decreases in HIV transmission are achievable with currently available biomedical and behavioral interventions, including antiretroviral therapy and pre-exposure prophylaxis. However, such decreases have not yet been realized among adolescents and young adults. The Adolescent Medicine Trials Network (ATN) for HIV/AIDS interventions is dedicated to research addressing the needs of youth at high risk for HIV acquisition as well as youth living with HIV. This article provides an overview of an array of efficient and effective designs across the translational spectrum that are utilized within the ATN. These designs maximize methodological rigor and real-world applicability of findings while minimizing resource use. Implementation science and cost-effectiveness methods are included. Utilizing protocol examples, we demonstrate the feasibility of such designs to balance rigor and relevance to shorten the science-to-practice gap and improve the youth HIV prevention and care continua.

BackgroundAmerica's increasing HIV epidemic among youth suggests the need to identify novel strategies to leverage services and settings where youth at high risk (YAHR) for HIV can be engaged in prevention. Scalable, efficacious, and cost-effective strategies are needed, which support youth during developmental transitions when risks arise. Evidence-based behavioral interventions (EBIs) have typically relied on time-limited, scripted, and manualized protocols that were often delivered with low fidelity and lacked evidence for effectiveness.ObjectiveThis study aims to examine efficacy, implementation, and cost-effectiveness of easily mountable and adaptable, technology-based behavioral interventions in the context of an enhanced standard of care and study assessments that implement the guidelines of Centers for Disease Control and Prevention (CDC) for routine, repeat HIV, and sexually transmitted infection (STI) testing for high-risk youth.MethodsYouth aged between 12 and 24 years (n=1500) are being recruited from community-based organizations and clinics serving gay, bisexual, and transgender youth, homeless youth, and postincarcerated youth, with eligibility algorithms weighting African American and Latino youth to reflect disparities in HIV incidence. At baseline and 4-month intervals over 24 months (12 months for lower-risk youth), interviewers monitor uptake of HIV prevention continuum steps (linkage to health care, use of pre- or postexposure prophylaxis, condoms, and prevention services) and secondary outcomes of substance use, mental health, and housing security. Assessments include rapid diagnostic tests for HIV, STIs, drugs, and alcohol. The study is powered to detect modest intervention effects among gay or bisexual male and transgender youth with 70% retention. Youth are randomized to 4 conditions: (1) enhanced standard of care of automated text-messaging and monitoring (AMM) and repeat HIV/STI testing assessment procedures (n=690); (2) online group peer support via private social media plus AMM (n=270); (3) coaching that is strengths-based, youth-centered, unscripted, based on common practice elements of EBI, available over 24 months, and delivered by near-peer paraprofessionals via text, phone, and in-person, plus AMM (n=270); and (4) online group peer support plus coaching and AMM (n=270).ResultsThe project was funded in September 2016 and enrollment began in May 2017. Enrollment will be completed between June and August 2019. Data analysis is currently underway, and the first results are expected to be submitted for publication in 2019.ConclusionsThis hybrid implementation-effectiveness study examines alternative models for implementing the CDC guidelines for routine HIV/STI testing for YAHR of acquiring HIV and for delivering evidence-based behavioral intervention content in modular elements instead of scripted manuals and available over 24 months of follow-up, while also monitoring implementation, costs, and effectiveness. The greatest impacts are expected for coaching, whereas online group peer support is expected to have lower impact but may be more cost-effective.Trial registrationClinicalTrials.gov NCT03134833; https://clinicaltrials.gov/ct2/show/NCT03134833 (Archived by WebCite at http://www.webcitation.org/76el0Viw9).International registered report identifier (irrid)DERR1-10.2196/11165.

ObjectiveExamine resiliency among a South African population cohort of children of mothers living with HIV (MLH) and mothers without HIV (MWOH) in low-income townships over the first 5 years of life.DesignA cluster randomized controlled intervention trial evaluating child resiliency and the effects of home visiting in township neighborhoods from pregnancy through 5 years postbirth.MethodsThe population of pregnant women in 24 matched neighborhoods were recruited and randomized by neighborhood to a standard care condition (n = 594) or a paraprofessional home visiting intervention condition (n = 644). Mothers and children were assessed at 2 weeks, 6, 18, 36, and 60 months postbirth (92-84% follow-up; 10.2% mortality). Resilient children were identified based on consistently meeting global standards for growth, cognitive functioning, and behavior. Maternal HIV status (n = 354 MLH; n = 723 mothers without HIV MWOH), intervention condition, maternal risks, caretaking, sociodemographic characteristics, and neighborhood were examined as predictors of child resiliency over time using analysis of variance, chi-square analyses, and Fisher's exact tests, where appropriate.ResultsNone of HIV-seropositive children (n = 17) were resilient; 19% of 345 HIV-exposed but uninfected children of MLH were resilient, a rate very similar to the 16% among MWOH. Resiliency was significantly associated with lower income, food security, not having a live-in partner, and the absence of maternal risk (i.e., not being depressed, using alcohol, or being a victim of intimate partner violence). Being randomized to a home visiting intervention, maternal breastfeeding for at least 3 months and attending a preschool crèche were also unrelated to resiliency. Although matched pairs of neighborhoods had similar rates of resilient children, resiliency varied significantly by neighborhood with rates ranging from 9.5 to 27%.ConclusionWe set a new standard to define resiliency, as consistently recommended by theoreticians. Although seropositive children are not resilient, uninfected children of MLH are as resilient as their peers of MWOH. Typical protective factors (e.g., home visiting, breastfeeding, preschool) were unrelated to resiliency over the first 5 years of life.Trial registrationClinicalTrials.gov registration #NCT00996528.

ObjectiveThis study examines the effect of a home visiting intervention on maternal alcohol use, problematic drinking, and the association of home visiting and alcohol use on children's behavioral, cognitive, and health outcomes at 5 time points over 5 years.MethodWe analyzed 5,099 observations of 1,236 mothers and their children from pregnancy to 5 years postbirth, within a longitudinal cluster-randomized trial evaluating the effect of a home visiting intervention on mothers in Cape Town, South Africa. Paraprofessional home visitors coached mothers on coping with multiple risk factors, including a brief, 1-visit intervention on alcohol prevention in pregnancy. We assessed changes in maternal drinking over time in relation to the intervention, and then examined the impact of these drinking patterns on child outcomes over five years.ResultsDrinking increased over the 5 years postbirth, but it was significantly lower in the intervention condition. Compared with abstinence, mothers' problematic drinking was associated with decreased child weight (-0.21 z-units) at all assessments, increased child aggressive behavior (3 to 7 additional symptoms), and decreased child performance on an executive functioning measure (the silly sounds task; odds ratio = .34) at 3 and 5 years. The intervention's effect was associated with increased child aggression (0.25 to 0.75 of 1 additional symptom), but the intervention appeared to decrease the effect of problem drinking on children's aggressive acts and executive functioning.ConclusionThese findings support the need for sustained interventions to reduce alcohol use, especially for mothers who exhibit problematic drinking. Maternal drinking influences children's health and development over time. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Aspergillosis associated with azole-resistant Aspergillus fumigatus has a mortality rate that can approach 90% in certain patient populations. The best-understood avenue for azole resistance involves changes in the cyp51A gene that encodes the target of azole drugs, lanosterol α-14 demethylase. The most common azole resistance allele currently described is a linked change corresponding to a change in the coding sequence of cyp51A and a duplication of a 34-bp region in the promoter leading to a tandem repeat (TR). Our previous studies identified a positively acting transcription factor called AtrR that binds to the promoter of cyp51A as well as that of an important membrane transporter protein gene called abcG1 In this work, we characterize two different mutant alleles of atrR, either an overproducing or an epitope-tagged form, causing constitutive activation of this factor. Using an epitope-tagged allele of atrR for chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq), the genomic binding sites for AtrR were determined. Close to 900 genes were found to have an AtrR response element (ATRE) in their promoter regions. Transcriptome evaluation by RNA sequencing (RNA-seq) indicated that both alleles led to elevated transcription of a subset of target genes. An electrophoretic mobility shift assay and DNase I protection mapping localized the ATREs in both the abcG1 and cyp51A promoters. The ATRE in cyp51A was located within the 34-bp repeat element. Virulence in a murine model was compromised when AtrR was either deleted or overproduced, indicating that the proper dosage of this factor is key for pathogenesis.IMPORTANCEAspergillus fumigatus is the major filamentous fungal pathogen in humans. Infections associated with A. fumigatus are often treated with azole drugs, but resistance to these antifungal agents is increasing. Mortality from aspergillosis associated with azole-resistant fungi is extremely high. Previous work has identified transcriptional control of the azole drug target-encoding gene cyp51A as an important contributor to resistance in A. fumigatus Here, we demonstrate that the transcription factor AtrR binds to a region in the cyp51A promoter that is associated with alleles of this gene conferring clinically important azole resistance. Using high-throughput genomic technologies, we also uncover a large suite of target genes controlled by AtrR. These data indicate that AtrR coordinately regulates many different processes involved in drug resistance, metabolism, and virulence. Our new understanding of AtrR function provides important new insight into the pathogenesis of A. fumigatus.

Federally Qualified Health Centers (FQHCs) have long been important sources of care for publicly insured people living with HIV. FQHC users have historically used emergency departments (EDs) at a higher-than-average rate. This paper examines whether this greater use relates to access difficulties in FQHCs or to characteristics of FQHC users. Zero-inflated Poisson models were used to estimate how FQHC use related to the odds of being an ED user and annual number of ED visits, using claims data on 6,284 HIV-infected California Medicaid beneficiaries in 2008-2009. FQHC users averaged significantly greater numbers of annual ED visits than non-FQHC users and those with no outpatient usage (1.89, 1.59, and 1.70, respectively; P = 0.043). FQHC users had higher odds of being ED users (OR = 1.14; 95%CI 1.02-1.27). In multivariable analyses, FQHC clients had higher odds of ED usage controlling for demographic and service characteristics (OR = 1.15; 95%CI 1.02-1.30) but not when medical characteristics were included (OR = 1.08; 95%CI 0.95-1.24). Among ED users, FQHC use was not significantly associated with the number of ED visits in our models (rate ratio (RR) = 1.00; 95%CI 0.87-1.15). The overall difference in mean annual ED visits observed between FQHC and non-FQHC groups was reduced to insignificance (1.75; 95% CI 1.59-1.92 vs 1.70; 95%CI 1.54-1.85) after adjusting for demographic, service, and medical characteristics. Overall, FQHC users had higher ED utilization than non-FQHC users, but the disparity was largely driven by differences in underlying medical characteristics.

BACKGROUND:In the United States, disparities in the rates of HIV care among youth and young adults result from the intersections of factors that include stigma, substance use, homelessness or marginal housing, institutional neglect, and mental health issues. Novel interventions are needed that are geared to youth and young adults. OBJECTIVE:In this paper, we aim to describe the interventions used by participating sites for Using Social Media initiative, the process for classifying the intervention components, and the methods for conducting a comprehensive evaluation of the interventions. METHODS:In 2015, the Health Resources and Services Administration (HRSA) HIV/AIDS Bureau, Special Projects of National Significance (SPNS) funded the Evaluation and Technical Assistance Center (ETAC) at the University of California, Los Angeles and 10 demonstration projects at sites across the United States that incorporated innovative approaches using a variety of social media and mobile technology strategies designed specifically for youth and young adults living with HIV. The ETAC developed a typology, or a classification system, that systematically summarizes the principal components of the interventions into broader groups and developed a multisite, mixed-methods approach to evaluate them based on the Department of Health and Human Services HIV health outcomes along the HIV care continuum. The mixed-methods approach is key to remove potential biases in assessing the effectiveness of demonstration projects. RESULTS:This SPNS project was funded in September 2015, and enrollment was completed on May 31, 2018. A total of 984 participants have been enrolled in the multisite evaluation. Data collection will continue until August 2019. However, data analysis is currently underway, and the first results are expected to be submitted for publication in 2019. CONCLUSIONS:This HRSA-funded initiative seeks to increase engagement in HIV medical care, improve health outcomes for people living with HIV, and reduce HIV-related health disparities and health inequities that affect HIV-positive youth and young adults. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/10681.

ObjectiveGiven rising incidence of Neisseria gonorrhoeae and Chlamydia trachomatis (GC/CT), development of efficacious screening strategies is critical to interruption of the infection cycle. However, a small proportion of nucleic acid amplification testing (NAAT) results are inconclusive-resulting in delays in diagnosis and treatment. As such, this study seeks to evaluate factors associated with inconclusive rectal GC/CT NAAT.MethodsThis is a retrospective chart review of individuals who received an inconclusive rectal GC/CT NAAT result at a single institution from 3/2016-6/2018. Inconclusive GC/CT NAAT was defined as presence of PCR amplification inhibitors using Roche Cobas v2.0 CT/NG assay. Clinical charts were abstracted for age, gender, HIV status, GC/CT (urogenital, rectal, pharyngeal) and syphilis screening results during the study period, clinic type (HIV clinic, university student health center, other), and whether repeat testing occurred within 6 months following an inconclusive result. Logistic regression analysis was used to calculate adjusted and unadjusted odds ratios of factors associated with receipt of repeat testing following an inconclusive rectal GC/CT NAAT result.ResultsDuring the study period, 6.1% (852/14,015) of rectal GC/CT NAAT were inconclusive for one or both of GC and CT. Among the 413 patients whose inconclusive rectal GC/CT NAAT results that were included in our analysis, 66.6% (275/413) received repeat testing within 6 months, of which 8.7% (24/275) were positive (compared to 5.4% positivity rate of all rectal samples). In multivariable analysis, individuals living with HIV had lower odds of receiving repeat testing following inconclusive rectal GC/CT NAAT compared to HIV uninfected individuals (adj OR 0.25; p = 0.001).ConclusionsDespite being disproportionately affected by the STI epidemic, individuals living with HIV had 75% lower odds of receiving repeat testing following inconclusive rectal GC/CT NAAT compared to HIV-uninfected individuals, representing potentially missed opportunities for treatment and prevention of ongoing STI transmission.

BackgroundMyanmar has adopted point-of-care (POC) HIV testing for its prevention of mother-to-child transmission of HIV program, and was initiated in 84 townships in 2013. This study assessed the progress of HIV testing uptake from 2012, one year prior to POC testing, to 2015, and the challenges faced by service providers during the rapid rollout of this testing strategy.MethodsThis serial cross-sectional study included 23 townships randomly selected from the 84 townships. An open-question survey was used to collect information on the challenges faced by service providers. A random effects logistic model was used for assessing the progress of HIV testing uptake among urban and rural health center groups.ResultsHIV testing uptake for antenatal care (ANC) attendees increased from 60% to 90% for rural and from 70% to 90% for urban attendees. The proportion of ANC attendees who were tested at their first visit increased from 70% to 80% for rural and from 70% to 90% for urban attendees. In addition, the proportion receiving same-day test results increased from less than 10% to 90% for both groups. Major challenges faced during the initial rollout included low health awareness among pregnant women, fear of stigma and discrimination, long travel times and costs, and increased workloads of providers in rural settings.Conclusions and global health implicationsThe program should consider recruiting local volunteers to help reduce the workloads of service providers. Professional education based on need and continued mentoring and quality control schemes for HIV testing need to be in place. This decentralized strategy would be applicable to other resource-limited countries.

Community-based HIV testing and counseling (HTC) programs have become an important part of the healthcare system in South Africa and other low- and middle-income countries with a high HIV prevalence and strained primary healthcare system. Current HTC programs excel at identifying people living with HIV (PLH) but leave gaps in linkage to care and antiretroviral therapy (ART) as most HTC programs do not have the capacity to ensure that linkage has occurred. This article presents the protocol for an mHealth study, that is, pilot testing a mobile platform in KwaZulu-Natal (KZN), South Africa, to improve linkage to care and ART adherence after home-based HTC. Testing data are shared with designated clinics. PLH are identified using fingerprint scans, mobile numbers, or South African IDs. If PLH do not present at a designated clinic after testing HIV positive, study field staff are sent SMS alerts to prompt follow-up visits. Similarly, if PLH do not refill ART prescriptions after their initial 1-month dose runs out, SMS alerts that are sent to field staff. This paper presents the mHealth study protocol and baseline sample characteristics (N = 101 PLH). Analyses will summarize rates of linkage to care and ART prescription refills. Cost-effectiveness analyses will examine the costs and benefits of linkage and ART adherence using our mHealth system. Linkage to care rates will be compared between our study and a historical control, that is, provided by a prior HTC program that was conducted in KZN without our mHealth system (n = 615).

Abstract Background G protein-coupled receptor (GPCR) is the most targeted protein family by the FDA-approved drugs. GPCR-kinase 3 (GRK3) is critical for GPCR signaling. Our genomic analysis showed that GRK3 expression correlated with poor prognosis of gastric adenocarcinoma (GAC) patients. However, GRK3’s functions and clinical utility in GAC progression and metastases are unknown. Methods We studied GRK3 expression in normal, primary, and metastatic GAC tissues. We identified a novel GRK3 inhibitor, LD2, through a chemical-library screen. Through genetic and pharmacologic modulations of GRK3, a series of functional and molecular studies were performed in vitro and in vivo. Impact of GRK3 on YAP1 and its targets was determined. Results GRK3 was overexpressed in GAC tissues compared to normal and was even higher in peritoneal metastases. Overexpression (OE) of GRK3 was significantly associated with shorter survival. Upregulation of GRK3 in GAC cells increased cell invasion, colony formation, and proportion of ALDH1 + cells, while its downregulation reduced these attributes. Further, LD2 potently and specifically inhibited GRK3, but not GRK2, a very similar kinase to GRK3. LD2 highly suppressed GAC cells’ malignant phenotypes in vitro. Mechanistically, GRK3 upregulated YAP1 in GAC tissues and its transcriptional downstream targets: SOX9, Birc5, Cyr61 and CTGF. Knockdown (KD) YAP1 rescued the phenotypes of GRK3 OE in GAC cells. GRK3 OE significantly increased tumor growth but LD2 inhibited tumor growth in the PDX model and dramatically suppressed peritoneal metastases induced by GRK3 OE. Conclusions GRK3, a poor prognosticator for survival, conferred aggressive phenotype. Genetic silencing of GRK3 or its inhibitor LD2 blunted GRK3-conferred malignant attributes, suggesting GRK3 as a novel therapeutic target in advanced GAC.

During the main COVID-19 global pandemic lockdown period of 2020 an impromptu set of pollination ecologists came together via social media and personal contacts to carry out standardised surveys of the flower visits and plants in gardens. The surveys involved 67 rural, suburban and urban gardens, of various sizes, ranging from 61.18° North in Norway to 37.96° South in Australia, resulting in a data set of 25,174 rows, with each row being a unique interaction record for that date/site/plant species, and comprising almost 47,000 visits to flowers, as well as records of flowers that were not visited by pollinators, for over 1,000 species and varieties belonging to more than 460 genera and 96 plant families. The more than 650 species of flower visitors belong to 12 orders of invertebrates and four of vertebrates. In this first publication from the project, we present a brief description of the data and make it freely available for any researchers to use in the future, the only restriction being that they cite this paper in the first instance. The data generated from these global surveys will provide scientific evidence to help us understand the role that private gardens (in urban, rural and suburban areas) can play in conserving insect pollinators and identify management actions to enhance their potential.

Crozier’s paradox suggests that genetic kin recognition will not be evolutionarily stable. Here, the authors show that allowing for multiple social encounters before each social interaction can eliminate Crozier’s paradox and stabilise genetic kin recognition.

BACKGROUND:Advancing technology has increased functionality and permitted more complex study designs for behavioral interventions. Investigators need to keep pace with these technological advances for electronic data capture (EDC) systems to be appropriately executed and utilized at full capacity in research settings. Mobile technology allows EDC systems to collect near real-time data from study participants, deliver intervention directly to participants' mobile devices, monitor staff activity, and facilitate near real-time decision making during study implementation. OBJECTIVE:This paper presents the infrastructure of an EDC system designed to support a multisite HIV biobehavioral intervention trial in Los Angeles and New Orleans: the Adolescent Medicine Trials Network "Comprehensive Adolescent Research & Engagement Studies" (ATN CARES). We provide an overview of how multiple EDC functions can be integrated into a single EDC system to support large-scale intervention trials. METHODS:The CARES EDC system is designed to monitor and document multiple study functions, including, screening, recruitment, retention, intervention delivery, and outcome assessment. Text messaging (short message service, SMS) and nearly all data collection are supported by the EDC system. The system functions on mobile phones, tablets, and Web browsers. RESULTS:ATN CARES is enrolling study participants and collecting baseline and follow-up data through the EDC system. Besides data collection, the EDC system is being used to generate multiple reports that inform recruitment planning, budgeting, intervention quality, and field staff supervision. The system is supporting both incoming and outgoing text messages (SMS) and offers high-level data security. Intervention design details are also influenced by EDC system platform capabilities and constraints. Challenges of using EDC systems are addressed through programming updates and training on how to improve data quality. CONCLUSIONS:There are three key considerations in the development of an EDC system for an intervention trial. First, it needs to be decided whether the flexibility provided by the development of a study-specific, in-house EDC system is needed relative to the utilization of an existing commercial platform that requires less in-house programming expertise. Second, a single EDC system may not provide all functionality. ATN CARES is using a main EDC system for data collection, text messaging (SMS) interventions, and case management and a separate Web-based platform to support an online peer support intervention. Decisions need to be made regarding the functionality that is crucial for the EDC system to handle and what functionality can be handled by other systems. Third, data security is a priority but needs to be balanced with the need for flexible intervention delivery. For example, ATN CARES is delivering text messages (SMS) to study participants' mobile phones. EDC data security protocols should be developed under guidance from security experts and with formative consulting with the target study population as to their perceptions and needs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/10777.

BackgroundSexual and gender minority (SGM) adolescents and young adults (AYAs) are at increased risk of HIV infection, particularly in the Southern United States. Despite the availability of effective biomedical prevention strategies, such as pre-exposure prophylaxis (PrEP), access and uptake remain low among SGM AYAs. In response, the Louisiana Department of Health initiated the LA TelePrEP Program, which leverages the power of telemedicine to connect Louisiana residents to PrEP. A virtual TelePrEP Navigator guides users through the enrollment process, answers questions, schedules appointments, and facilitates lab testing and medication delivery. To increase the participation of SGM AYAs in the program, the TelePrEP program partnered with researchers to develop a chatbot that would facilitate access to the program and support navigator functions. Chatbots are capable of carrying out many functions that reduce employee workload, and despite their successful use in health care and public health, they are relatively new to HIV prevention. ObjectiveIn this paper, we describe the iterative and community-engaged process that we used to develop an SMS text messaging–based chatbot tailored to SGM AYAs that would support navigator functions and disseminate PrEP-related information. MethodsOur process was comprised of 2 phases: conceptualization and development. In the conceptualization phase, aspects of navigator responsibilities, program logistics, and user interactions to prioritize in chatbot programming (eg, scheduling appointments and answering questions) were identified. We also selected a commercially available chatbot platform that could execute these functions and could be programmed with minimal coding experience. In the development phase, we engaged Department of Health staff and SGM AYAs within our professional and personal networks. Five different rounds of testing were conducted with various groups to evaluate each iteration of the chatbot. After each iteration of the testing process, the research team met to discuss feedback, guide the programmer on incorporating modifications, and re-evaluate the chatbot’s functionality. ResultsThrough our highly collaborative and community-engaged process, a rule-based chatbot with artificial intelligence components was successfully created. We gained important knowledge that could advance future chatbot development efforts for HIV prevention. Key to the PrEPBot’s success was resolving issues that hampered the user experience, like asking unnecessary questions, responding too quickly, and misunderstanding user input. ConclusionsHIV prevention researchers can feasibly and efficiently program a rule-based chatbot with the assistance of commercially available tools. Our iterative process of engaging researchers, program personnel, and different subgroups of SGM AYAs to obtain input was key to successful chatbot development. If the results of this pilot trial show that the chatbot is feasible and acceptable to SGM AYAs, future HIV researchers and practitioners could consider incorporating chatbots as part of their programs. International Registered Report Identifier (IRRID)PRR1-10.2196/42983