Estimating the potential value of MSM-focused evidence-based implementation interventions in three Ending the HIV Epidemic jurisdictions in the United States: a model-based analysis.

INTRODUCTION: Improving the delivery of existing evidence-based interventions to prevent and diagnose HIV is key to Ending the HIV Epidemic in the United States. Structural barriers in the access and delivery of related health services require municipal or state-level policy changes; however, suboptimal implementation can be addressed directly through interventions designed to improve the reach, effectiveness, adoption or maintenance of available interventions. Our objective was to estimate the cost-effectiveness and potential epidemiological impact of six real-world implementation interventions designed to address these barriers and increase the scale of delivery of interventions for HIV testing and pre-exposure prophylaxis (PrEP) in three US metropolitan areas. METHODS: We used a dynamic HIV transmission model calibrated to replicate HIV microepidemics in Atlanta, Los Angeles (LA) and Miami. We identified six implementation interventions designed to improve HIV testing uptake ("Academic detailing for HIV testing," "CyBER/testing," "All About Me") and PrEP uptake/persistence ("Project SLIP," "PrEPmate," "PrEP patient navigation"). Our comparator scenario reflected a scale-up of interventions with no additional efforts to mitigate implementation and structural barriers. We accounted for potential heterogeneity in population-level effectiveness across jurisdictions. We sustained implementation interventions over a 10-year period and evaluated HIV acquisitions averted, costs, quality-adjusted life years and incremental cost-effectiveness ratios over a 20-year time horizon (2023-2042). RESULTS: Across jurisdictions, implementation interventions to improve the scale of HIV testing were most cost-effective in Atlanta and LA (CyBER/testing cost-saving and All About Me cost-effective), while interventions for PrEP were most cost-effective in Miami (two of three were cost-saving). We estimated that the most impactful HIV testing intervention, CyBER/testing, was projected to avert 111 (95% credible interval: 110-111), 230 (228-233) and 101 (101-103) acquisitions over 20 years in Atlanta, LA and Miami, respectively. The most impactful implementation intervention to improve PrEP engagement, PrEPmate, averted an estimated 936 (929-943), 860 (853-867) and 2152 (2127-2178) acquisitions over 20 years, in Atlanta, LA and Miami, respectively. CONCLUSIONS: Our results highlight the potential impact of interventions to enhance the implementation of existing evidence-based interventions for the prevention and diagnosis of HIV.

The Role of Stigma and Resilience in Healthcare Engagement Among Transgender Latinas in the U.S. South: Baseline Findings from the ChiCAS Study.

Research demonstrates that stigma and resilience influence transgender peoples' healthcare use. Less is known about transgender Latinas in the U.S. South who face multilevel barriers to healthcare access. We used baseline data from the ChiCAS intervention study. Using logistic regression, we examined how stigma (perceived discrimination related to gender identity, race/ethnicity, sexual behavior and perceived documentation status and internalized transphobia), and resilience (ethnic group pride and social support) are associated with two healthcare outcomes (use of routine medical care and medically supervised gender-affirming hormones). We also explored barriers to accessing both types of care. After removing 13 participants with missing data, our sample size was 131 transgender Latinas in the U.S. South. Most participants (74.8%, n = 98) received routine medical care in the past year and 57.3% (n = 75) had ever received medically supervised gender-affirming hormones. Reports of discrimination were highest for gender identity and documentation status. Race/ethnicity-based discrimination was positively associated with accessing routine medical care in the past year (OR = 1.94, p = 0.048). Having more social support was positively associated with care (routine care: OR = 3.48, p = 0.002 and gender-affirming hormones: OR = 2.33, p = 0.003). The most commonly reported barriers to accessing both types of care included cost, insurance, and not knowing where to go. Findings highlight the importance of social support for healthcare use among transgender Latinas. Social support may be especially important when considering the unique experiences of discrimination faced by transgender Latinas in the U.S. South.

Prominin 1 is crucial for the early development of photoreceptor outer segments.

Prominin 1 (PROM1) is a pentaspan transmembrane glycoprotein localized on the nascent photoreceptor discs. Mutations in PROM1 are linked to various retinal diseases. In this study, we assessed the role of PROM1 in photoreceptor biology and physiology using the PROM1 knockout murine model (rd19). Our study found that PROM1 is essential for vision and photoreceptor development. We found an early reduction in photoreceptor response beginning at post-natal day 12 (P12) before eye opening in the absence of PROM1 with no apparent loss in photoreceptor cells. However, at this stage, we observed an increased glial cell activation, indicative of cell damage. Contrary to our expectations, dark rearing did not mitigate photoreceptor degeneration or vision loss in PROM1 knockout mice. In addition to physiological defects seen in PROM1 knockout mice, ultrastructural analysis revealed malformed outer segments characterized by whorl-like continuous membranes instead of stacked disks. In parallel to the reduced rod response at P12, proteomics revealed a significant reduction in the levels of protocadherin, a known interactor of PROM1, and rod photoreceptor outer segment proteins, including rhodopsin. Overall, our results underscore the indispensable role of PROM1 in photoreceptor development and maintenance of healthy vision.

Understanding uptake of COVID-19 testing, vaccination, and boosters among Spanish-speaking Latines in the United States: Qualitative insights from Spanish speakers and key informants.

BACKGROUND: Latine communities in the United States have been disproportionately affected by COVID-19. It is critical to gain a better understanding of the sociocultural determinants that challenge and facilitate COVID-19 testing, vaccination, and booster uptake within these vulnerable communities to inform culturally congruent strategies and interventions. METHODS: In summer 2022, our community-based participatory research partnership conducted 30 key informant interviews and 7 focus groups with 64 Spanish-speaking Latine participants in North Carolina. Interviewees consisted of representatives from health and service organizations, most of whom were engaged with direct service to Spanish speakers. Interviews were conducted in either English or Spanish, depending on the preference of the participant; all focus groups were conducted in Spanish. Interviews and focus groups were conducted in person or by videoconference. RESULTS: Twenty themes emerged that we organize into four domains: general perceptions about COVID-19; barriers to COVID-19 testing, vaccination, and booster uptake; facilitators to COVID-19 testing, vaccination, and booster uptake; and recommendations to promote testing, vaccination, and booster uptake. DISCUSSION: Results underscore important sociocultural determinants of ongoing COVID-19 testing, vaccination, and booster uptake to consider in developing interventions for Spanish-speaking Latines in the United States. Based on this formative work, our partnership developed Nuestra Comunidad Saludable (Our Healthy Community). We are implementing the intervention to test whether trained peer navigators can increase COVID-19 testing, vaccination, and booster uptake among Spanish-speaking Latines through blending in-person interactions and mHealth (mobile health) strategies using social media.

Excessive tubulin glutamylation leads to progressive cone-rod dystrophy and loss of outer segment integrity.

Mutations in Cytosolic Carboxypeptidase-like Protein 5 (CCP5) are associated with vision loss in humans. To decipher the mechanisms behind CCP5-associated blindness, we generated a novel mouse model lacking CCP5. In this model, we found that increased tubulin glutamylation led to progressive cone-rod dystrophy, with cones showing a more pronounced and earlier functional loss than rod photoreceptors. The observed functional reduction was not due to cell death, levels, or the mislocalization of major phototransduction proteins. Instead, the increased tubulin glutamylation caused shortened photoreceptor axonemes and the formation of numerous abnormal membranous whorls that disrupted the integrity of photoreceptor outer segments (OS). Ultimately, excessive tubulin glutamylation led to the progressive loss of photoreceptors, affecting cones more severely than rods. Our results highlight the importance of maintaining tubulin glutamylation for normal photoreceptor function. Furthermore, we demonstrate that murine cone photoreceptors are more sensitive to disrupted tubulin glutamylation levels than rods, suggesting an essential role for axoneme in the structural integrity of the cone outer segment. This study provides valuable insights into the mechanisms of photoreceptor diseases linked to excessive tubulin glutamylation.

Preexposure Prophylaxis Uptake Among Spanish-Speaking Transgender Women: A Randomized Controlled Trial in North and South Carolina, 2019-2022.

Objectives. To evaluate Chicas Creando Acceso a la Salud (Girls Creating Access to Health; ChiCAS), a Spanish-language, small-group intervention designed to increase preexposure prophylaxis (PrEP) use, consistent condom use, and medically supervised gender-affirming hormone therapy use among Spanish-speaking transgender Latinas who have sex with men. Methods. Participants were 144 HIV-negative Spanish-speaking transgender Latinas, aged 18 to 59 years, living in North and South Carolina. From July 2019 to July 2021, we screened, recruited, and randomized them to the 2-session ChiCAS intervention or the delayed-intervention waitlist control. Participants completed assessments at baseline and 6-month follow-up. Follow-up retention was 94.4%. Results. At follow-up, relative to control participants, ChiCAS participants reported increased PrEP use (adjusted odds ratio [AOR] = 4.64; 95% confidence interval [CI] = 1.57, 13.7; P < .006). However, ChiCAS participants did not report increased use of condoms or medically supervised gender-affirming hormone therapy. ChiCAS participants reported increases in knowledge of HIV (P < .001), sexually transmitted infections (P < .001), and gender-affirming hormone therapy (P = .01); PrEP awareness (P < .001), knowledge (P < .001), and readiness (P < .001); condom use skills (P < .001); and community attachment (P < .001). Conclusions. The ChiCAS intervention was efficacious in increasing PrEP use among Spanish-speaking, transgender Latinas in this trial. (Am J Public Health. 2024;114(1):68-78. https://doi.org/10.2105/AJPH.2023.307444).

Exploring Individual and Contextual Factors Associated With Sexual Risk and Substance Use Among Underserved GBQMSM and Transgender and Nonbinary Persons in South Central Appalachia.

Gay, bisexual, queer, and other men who have sex with men (GBQMSM) and transgender and nonbinary persons are at elevated risk for HIV, sexually transmitted infections (STIs), and hepatitis C (HCV); in Appalachia, these communities experience more disease burden. However, little is known about the factors influencing risk. Sixteen semistructured in-depth interviews were conducted examining factors influencing prevention and care. Data were analyzed using constant comparison methodology. Fifteen themes emerged within four domains: social environment (e.g., microaggressions across gender, sexual orientation, and racial identities), substance use (e.g., high prevalence, use as coping mechanism), sexual health (e.g., misinformation and denial of risk for HIV and STIs), and access to health care (e.g., cost and transportation barriers, lack of local respectful care). Findings highlighted salient barriers and assets influencing prevention and care and suggest that multilevel interventions are needed to improve access to and use of HIV, STI, and HCV prevention and care services.

Prenylation is essential for the enrichment of cone phosphodiesterase-6 (PDE6) in outer segments and efficient cone phototransduction.

Phosphodiesterase-6 (PDE6) is the key phototransduction effector enzyme residing in the outer segment (OS) of photoreceptors. Cone PDE6 is a tetrameric protein consisting of two inhibitory subunits (γ') and two catalytic subunits (α'). The catalytic subunit of cone PDE6 contains a C-terminus prenylation motif. Deletion of PDE6α' C-terminal prenylation motif is linked to achromatopsia (ACHM), a type of color blindness in humans. However, mechanisms behind the disease and roles for lipidation of cone PDE6 in vision are unknown. In this study, we generated two knock-in mouse models expressing mutant variants of cone PDE6α' lacking the prenylation motif (PDE6α'∆C). We find that the C-terminal prenylation motif is the primary determinant for the association of cone PDE6 protein with membranes. Cones from PDE6α'∆C homozygous mice are less sensitive to light, and their response to light is delayed, whereas cone function in heterozygous PDE6α'∆C/+ mice is unaffected. Surprisingly, the expression level and assembly of cone PDE6 protein were unaltered in the absence of prenylation. Unprenylated assembled cone PDE6 in PDE6α'∆C homozygous animals is mislocalized and enriched in the cone inner segment and synaptic terminal. Interestingly, the disk density and the overall length of cone OS in PDE6α'∆C homozygous mutants are altered, highlighting a novel structural role for PDE6 in maintaining cone OS length and morphology. The survival of cones in the ACHM model generated in this study bodes well for gene therapy as a treatment option for restoring vision in patients with similar mutations in the PDE6C gene.

Experiences of peer navigators implementing a bilingual multilevel intervention to address sexually transmitted infection and HIV disparities and social determinants of health.

INTRODUCTION: Sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) disproportionately affect young gay, bisexual and other men who have sex with men (GBMSM) and transgender women of colour. We explored the experiences of community-based peer navigators ('Community Navigators') who participated in Impact Triad, a bilingual multilevel intervention developed by our community-based participatory research partnership to reduce STIs and HIV and address social determinants of health (e.g., employment, education, social support and discrimination) among young GBMSM and transgender women of colour. METHODS: Individual in-depth interviews were conducted with 15 Community Navigators who participated in Impact Triad. Themes were identified through constant comparison. RESULTS: Community Navigators' mean age was 31.4 years. Seven were self-identified as African American/Black, 5 as Latine, 2 as multiracial/multiethnic, 1 as Asian American, 10 as cisgender men, 4 as transgender women and 1 as gender nonbinary. Thirteen themes emerged in three domains: (1) key aspects of the Community Navigator role (e.g., desire to serve as a community resource, the importance of being part of the communities in which one was working, the value of having an official role, being connected to other Community Navigators to problem-solving and sustaining intervention aspects long-term); (2) experiences implementing Impact Triad (e.g., engaging community members, meeting prioritized needs, building trust, using social media, increasing awareness and knowledge and challenges related to COVID-19) and (3) lessons learned for future interventions (e.g., facilitating access to broader resources, building additional skills and increasing interactions among Community Navigators). CONCLUSION: Interviews identified important learnings about serving as Community Navigators and implementing Impact Triad that can guide future efforts to address STI/HIV disparities and social determinants of health through community-based peer navigation. PATIENT OR PUBLIC CONTRIBUTION: Throughout this intervention trial, our partnership worked collaboratively with a study-specific community advisory board (CAB) comprised primarily of young GBMSM and transgender women of colour. Members of this CAB participated in all aspects of the trial including trial design, intervention development, recruitment and retention strategies, data collection and analysis, interpretation of findings and dissemination.

Factors Influencing Entry-Level Physical Therapy Graduates' Decisions to Participate in Residency Education.

INTRODUCTION: All Doctor of Physical Therapy (DPT) programs in the United States prepare students to demonstrate entry-level clinical performance upon graduation. Clinical residency programs are an option for DPT graduates seeking to specialize in a practice area. REVIEW OF LITERATURE: There is little research published on why DPT graduates decide to pursue residency education (RE) or not. This study aimed to determine factors influencing a Physical Therapist's (PT) decision-making process in choosing to pursue a postgraduate residency. SUBJECTS: PTs within 3 years of graduation and third-year DPT program students were surveyed. Most respondents were from DPT programs in the northeastern United States. METHODS: A survey was created, piloted, and disseminated to various DPT programs. The survey asked participants their perceptions of motivating factors or barriers to pursuing a RE using multiple choice questions and Likert items. Descriptive statistics and frequencies were reported. One-way analysis of variances, chi-square analysis, and unpaired t tests were used. RESULTS: Students who considered residency in their second year are 26.5× more likely to apply for a residency (P < .001). Participants strongly agreed with the statements that residency will increase confidence when practicing in their specialty area (1.39 ± 0.48), expand their knowledge as clinicians (1.39 ± 0.051), and expedite proficient practice (1.72 ± 0.057). Participants considered student burnout, the cost of residency, student loan debt, and geographical relocation as the top barriers to pursuing residency. Men were significantly more confident in their ability to apply to residency (F = 8.219, P = .005). Married individuals perceived loans or financial obligations (F = 3.607, P = .029), family obligations (F = 17.170, P < .001), and geographical limitations (F = 3.825, P = .024) as barriers more than single individuals. DISCUSSION AND CONCLUSION: There are many variables DPT students and recent graduates consider when deciding whether to pursue RE. RPs and entry-level DPT programs should consider these factors to promote increased participation in postprofessional RE.

Exploring the consequences of food insecurity and harnessing the power of peer navigation and mHealth to reduce food insecurity and cardiometabolic comorbidities among persons with HIV: protocol for development and implementation trial of weCare/Secure.

BACKGROUND: Food insecurity, or the lack of consistent access to nutritionally adequate and safe foods, effects up to 50% of people living with HIV (PWH) in the United States (US). PWH who are food insecure have lower antiretroviral adherence, are less likely to achieve viral suppression, and are at increased risk developing of serious illnesses, including cardiometabolic comorbidities. The objectives of this study are to better understand how food insecurity contributes to the development of cardiometabolic comorbidities among PWH and to test a novel bilingual peer navigation-mHealth intervention (weCare/Secure) designed to reduce these comorbidities in food-insecure PWH with prediabetes or Type 2 diabetes (T2DM). METHODS: In Aim 1, we will recruit a longitudinal cohort of 1800 adult (≥18 years) PWH from our clinic-based population to determine the difference in the prevalence and incidence of cardiometabolic comorbidities between food-secure and food-insecure PWH. Food insecurity screening, indicators of cardiometabolic comorbidities, and other characteristics documented in the electronic health record (EHR) will be collected annually for up to 3 years from this cohort. In Aim 2, we will conduct a randomized controlled trial among a sample of food-insecure PWH who have prediabetes or T2DM to compare changes in insulin sensitivity over 6 months between participants in weCare/Secure and participants receiving usual care. In Aim 3, we will conduct semi-structured individual in-depth interviews to explore the effect of the intervention among intervention participants with varying insulin sensitivity outcomes. TRIAL STATUS: Aim 1 (longitudinal cohort) recruitment began in May 2022 and is ongoing. Aim 2 (intervention) recruitment is planned for spring 2023 and is expected to be completed in spring 2024. Aim 3 (process evaluation) data collection will occur after sufficient completion of the 6-month assessment in Aim 2. Final results are anticipated in fall 2025. CONCLUSIONS: This research seeks to advance our understanding of how food insecurity impacts the development of cardiometabolic comorbidities among PWH and how food insecurity interventions may alleviate relevant comorbidities. Given the growing interest among health systems in addressing food insecurity, if the intervention is found to be efficacious, it could be broadly disseminated across HIV clinical care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04943861 . Registered on June 29, 2021.

Adapting a Group-Level PrEP Promotion Intervention Trial for Transgender Latinas During the COVID-19 Pandemic.

The COVID-19 pandemic has profoundly affected the conduct of community-based and community-engaged research. Prior to the pandemic, our community-based participatory research partnership was testing ChiCAS, an in-person, group-level behavioral intervention designed to promote uptake of pre-exposure prophylaxis (PrEP), condom use, and medically supervised gender-affirming hormone therapy among Spanish-speaking transgender Latinas. However, the pandemic required adaptations to ensure the safe conduct of the ChiCAS intervention trial. In this article, we describe adaptations to the trial within five domains. Transgender women are disproportionately affected by HIV, and it is essential to find ways to continue research designed to support their health within the context of the COVID-19 pandemic and future infectious disease outbreaks, epidemics, and pandemics. These adaptations offer guidance for ongoing and future community-based and community-engaged research during the COVID-19 pandemic and/or potential subsequent outbreaks (e.g., monkeypox), epidemics, and pandemics, particularly within under-served marginalized and minoritized communities.

Increasing COVID-19 testing and vaccination among Spanish speakers in the USA: protocol for the development and evaluation of the Nuestra Comunidad Saludable intervention using a group-randomised trial design.

INTRODUCTION: Our community-based participatory research partnership aims to expand understanding of the social, ethical and behavioural implications of COVID-19 testing and vaccination to inform the development of an integrated intervention that harnesses community-based peer navigation and mHealth strategies to improve COVID-19 testing and vaccination; test the intervention; and develop and disseminate practice, research and policy recommendations to further increase COVID-19 testing and vaccination among Spanish-speaking Latine communities in the USA. METHODS AND ANALYSIS: We will conduct 50 individual in-depth interviews with health providers, who have conducted COVID-19 testing and/or vaccination activities within Spanish-speaking communities, and with representatives from Latine-serving community-based organisations. We will also conduct six focus groups with 8-12 Spanish-speaking Latine community member participants each for a total number of about 60 focus group participants. Next, we will develop the Nuestra Comunidad Saludable intervention based on findings from interviews and focus groups and use a longitudinal group-randomised trial design with two arms (intervention and delayed intervention) to evaluate the impact of the intervention. We will recruit, enrol and collect baseline data from 20 community-based peer navigators (Navegantes) and their social network members (n=8 unique social network members per Navegante). Navegantes (coupled with their social networks) will be randomised to intervention or delayed intervention groups (10 Navegantes and 80 social network members per group). ETHICS AND DISSEMINATION: Ethical approval for data collection was granted by the Wake Forest University School of Medicine Institutional Review Board. Following the description of study procedures, we will obtain consent from all study participants. Study findings will be disseminated through an empowerment theory-based community forum, peer-reviewed publications and presentations at scientific meetings, and reports and briefs for lay, community and practitioner audiences. TRIAL REGISTRATION NUMBER: NCT05302908.

Responding to "Don't Say Gay" Laws in the US: Research Priorities and Considerations for Health Equity.

Introduction: Despite increased legal rights for lesbian, gay, bisexual, transgender, and queer-identifying (LGBTQ +) people in the USA over the past 30 years, there has been an increasing number of anti-LGBTQ + laws proposed and passed at the state level. One of the most notorious laws, Florida's HB 1557, also known as the "Don't Say Gay" law, garnered substantial national attention for prohibiting discussions of sexual orientation or gender identity in public school classrooms. Other states quickly proposed similar laws, but little scholarship exists on the potential impacts of these laws. Methods: We explore the potential health equity ramifications of laws like Florida's HB 1557, focusing on the individual, interpersonal, and broader policy and practice implications. Examining these policies through the lens of political determinants of health, we identify theoretical and methodological approaches needed to address recent "Don't Say Gay" policies. Results: Theoretical approaches emphasizing power, intersectionality, and the role of politics in health should guide research examining the impacts of recent anti-LGBTQ + policies. Laws like Florida's HB 1557 emphasize the need for methodological approaches that emphasize collaborative engagement between researchers and community members, and future research may be needed to understand how stressors created by law and policy can have individual and interpersonal consequences. Conclusions: Public health researchers have a role to play in reversing policies that negatively affect LGBTQ + individuals and undermine health equity. Research combating harmful policies may require theoretical approaches attentive to power differences and methodological approaches that squarely focus on disrupting power imbalances.

Outcomes From a Randomized Trial of a Bilingual mHealth Social Media Intervention to Increase Care Engagement Among Young Gay, Bisexual, and Other Men Who Have Sex With Men and Transgender Women With HIV.

BACKGROUND: The North Carolina Community Research Partnership developed, implemented, and tested weCare, a 12-month bilingual mHealth social media intervention designed to reduce missed HIV care appointments and increase viral suppression among racially/ethnically diverse gay, bisexual, and other men who have sex with men (GBMSM) and transgender women living with HIV by harnessing established social media platforms (i.e., Facebook, texting, and dating apps). METHODS: We randomized 198 GBMSM and transgender women (mean age = 26) living with HIV to the weCare intervention (n = 100) or usual-care (n = 98) group. Inclusion criteria included being newly diagnosed or not in care. Participants completed structured assessments at baseline and 6-month postintervention follow-up (18 months after baseline data collection). HIV care appointment and viral load data were abstracted from each participant's electronic health record at baseline and follow-up. Follow-up retention was 85.5%. RESULTS: Among participants, 94% self-identified as cisgender men, 6% as transgender, 64% as African American/Black, and 13% as Latine. Participants in both groups significantly reduced missed HIV care appointments and increased viral suppression at follow-up compared with baseline. However, there were no significant differences between weCare and usual-care participants for either outcome at follow-up. CONCLUSIONS: An intervention effect was not identified for our two primary outcomes. Several factors may have influenced the lack of significant differences between weCare and usual-care participants at follow-up, including intervention implementation (e.g., staffing changes and lack of fidelity to the intervention as originally designed by the partnership), data collection (e.g., data collection time points and retention strategies), and clinical (e.g., contamination) factors.

The mAB 13A4 monoclonal antibody to the mouse PROM1 protein recognizes a structural epitope.

PROM1 (CD133, AC133) is a protein that is required for the maintenance of primary cilia. Mutation in the Prom1 gene in humans and animal models are associated with several forms of retinal degeneration. mAB 13A4 is the main reagent used to detect the mouse PROM1 protein. We endeavored to map the epitope of the rat monoclonal antibody mAB 13A4 to the mouse PROM1 protein. Deletion mutagenesis demonstrated that mAB 13A4 recognizes a structural epitope that is stabilized by two of the extracellular domains of PROM1. Furthermore, the affinity of mAB 13A4 to the major PROM1 isoform in photoreceptor cells is significantly reduced due to the inclusion of a photoreceptor-specific alternative exon in the third extracellular domain. Interestingly, a deletion in the photoreceptor specific isoform of six amino acids adjacent to the alternative exon restored the affinity of mAB 13A4 to PROM1. The results of the mutagenesis are consistent with the computationally predicted helical bundle structure of PROM1 and point to the utility of mAB 13A4 for evaluating the effect of mutations on the PROM1 structure. Our results show that the PROM1 isoform composition needs to be considered when interpreting tissue and developmental expression data produced by mAB 13A4.

Interphotoreceptor matrix proteoglycans IMPG1 and IMPG2 proteolyze in the SEA domain and reveal localization mutual dependency.

The interphotoreceptor matrix (IPM) is a specialized extracellular mesh of molecules surrounding the inner and outer segments of photoreceptor neurons. Interphotoreceptor matrix proteoglycan 1 and 2 (IMPG1 and IMPG2) are major components of the IPM. Both proteoglycans possess SEA (sperm protein, enterokinase and agrin) domains, which may support proteolysis. Interestingly, mutations in the SEA domains of IMPG1 and IMPG2 are associated with vision disease in humans. However, if SEA domains in IMPG molecules undergo proteolysis, and how this contributes to vision pathology is unknown. Therefore, we investigated SEA-mediated proteolysis of IMPG1 and IMPG2 and its significance to IPM physiology. Immunoblot analysis confirmed proteolysis of IMPG1 and IMPG2 in the retinas of wildtype mice. Point mutations mimicking human mutations in the SEA domain of IMPG1 that are associated with vision disease inhibited proteolysis. These findings demonstrate that proteolysis is part of the maturation of IMPG1 and IMPG2, in which deficits are associated with vision diseases. Further, immunohistochemical assays showed that proteolysis of IMPG2 generated two subunits, a membrane-attached peptide and an extracellular peptide. Notably, the extracellular portion of IMPG2 trafficked from the IPM around the inner segment toward the outer segment IPM by an IMPG1-dependent mechanism. This result provides the first evidence of a trafficking system that shuttles IMPG1 and IMPG2 from the inner to outer IPM in a co-dependent manner. In addition, these results suggest an interaction between IMPG1-IMPG2 and propose that mutations affecting one IMPG could affect the localization of the normal IMPG partner, contributing to the disease mechanism of vision diseases associated with defective IMPG molecules.

More than just oral PrEP: exploring interest in rectal douche, dissolvable implant, removable implant and injection HIV prevention approaches among racially diverse men who have sex with men in the Northeast Corridor.

OBJECTIVES: HIV scholars and practitioners have worked to expand strategies for prevention among marginalised populations who are disproportionately impacted by the epidemic, such as racial minority men who have sex with men (MSM). Given this urgency, the objective of this study was to assess interest in biomedical prevention strategies. METHODS: This exploratory and cross-sectional study investigated interest in four biomedical prevention tools-rectal douche, dissolvable implant, removable implant and injection-among a racially diverse sample of MSM from the Northeast Corridor region between Philadelphia and Trenton. Data were collected as part of screening for Connecting Latinos en Pareja, a couples-based HIV prevention intervention for Latino MSM and their partners. RESULTS: A total of 381 individuals participated in the screener and provided information about their interest in bio tools. Approximately 26% of participants identified as black, 28% as white and 42% as 'other' or multiracial; 49% identified as Latino. Majority (54%) reported some form of child sexual abuse. Of the participants who reported being in a primary relationship (n=217), two-thirds reported unprotected anal sex within that relationship over the past 90 days (n=138, 64%) and approximately half (n=117, 54%) reported unprotected anal sex outside of the relationship in this period. Majority of participants reported interest in all bio tools assessed, including dissolvable implants (60%), removable implants (64%), rectal douching (79%) and injection (79%). Although interest in bio tools was broadly unassociated with demographics and sexual risk behaviours, analyses revealed significant associations between reports of child sexual abuse and interest in implant and injection methods. CONCLUSIONS: The authors recommend investing in these prevention methods, particularly rectal douching and injection, as a means of preventing HIV among racial minority MSM. Given the interest in biomedical prevention tools, future studies should explore potential strategies for adherence.