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Humans lacking heme oxygenase 1 (HMOX1) display growth retardation, haemolytic anaemia, and vulnerability to stress; however, cardiac function remains unclear. We aimed to explore the cardiac function of zebrafish lacking hmox1a at baseline and in response to stress. We generated zebrafish hmox1a mutants using CRISPR/Cas9 genome editing technology. Deletion of hmox1a increases cardiac output and further induces hypertrophy in adults. Adults lacking hmox1a develop myocardial interstitial fibrosis, restrain cardiomyocyte proliferation and downregulate renal haemoglobin and cardiac antioxidative genes. Larvae lacking hmox1a fail to respond to hypoxia, whereas adults are insensitive to isoproterenol stimulation in the heart, suggesting that hmox1a is necessary for cardiac response to stress. Haplodeficiency of hmox1a stimulates non-mitochondrial respiration and cardiac cell proliferation, increases cardiac output in larvae in response to hypoxia, and deteriorates cardiac function and structure in adults upon isoproterenol treatment. Intriguingly, haplodeficiency of hmox1a upregulates cardiac hmox1a and hmox1b in response to isoproterenol. Collectively, deletion of hmox1a results in cardiac remodelling and abrogates cardiac response to hypoxia and isoproterenol. Haplodeficiency of hmox1a aggravates cardiac response to the stress, which could be associated with the upregulation of hmox1a and hmox1b. Our data suggests that HMOX1 homeostasis is essential for maintaining cardiac function and promoting cardioprotective effects., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

There is an unmet need for HIV prevention among Black cisgender women. From January to November 2020, we conducted formative research to develop locally informed implementation strategies to enhance pre-exposure prophylaxis (PrEP) uptake among Black cisgender women in New Orleans, Louisiana. Following an iterative process, we conducted in-depth interviews (IDIs) with Black women who were not taking PrEP and used those findings to inform IDIs with Black women taking PrEP. We asked about PrEP awareness, social support, PrEP-related norms, medical mistrust, motivation to take PrEP, and potential implementation strategies. Data were analyzed using applied thematic analysis. We established the Black Women and PrEP (BWAP) Task Force-a diverse group of 25 Black female community representatives who reviewed the IDI findings and identified strategies to address these determinants of PrEP uptake. We interviewed 12 Black women who were not taking PrEP and 13 Black women who were taking PrEP. Two main PrEP uptake barriers were identified from the IDI findings and Task Force discussions. First, Black women do not know of other Black women taking PrEP. Women perceived PrEP as a drug for gay men. Most said that testimonials from Black women taking PrEP would make its use more relatable. Second, Black women are not frequently offered PrEP by their providers. Many preferred accessing PrEP through women's health providers. The Task Force identified two strategies to address these barriers: a social media campaign for women and an educational initiative to train providers to discuss and prescribe PrEP. These implementation strategies require further study.

Introduction: Profound sexual health disparities exist for Black men who have sex with men (MSM) in the US South, including a high prevalence of sexually transmitted infections (STIs). Sexually transmitted infection prevention strategies beyond condoms are needed for Black MSM taking preexposure prophylaxis (PrEP)., Methods: We conducted in-depth interviews with Black MSM taking PrEP in New Orleans, Louisiana. Informed by the Health Belief Model, we asked about participants' perceived susceptibility, severity, and concerns regarding STIs, and perceived benefits of STI prevention. We also asked about willingness to use various STI prevention strategies, including antibiotic prophylaxis. Interviews were audio-recorded and analyzed using applied thematic analysis., Results: We interviewed 24 Black MSM aged 18 to 36 years; half had a recent STI diagnosis. Most participants were concerned about receiving an STI diagnosis, noting shame or disappointment; physical effects were concerning but infrequently considered. Participants described being less likely to use condoms with routine partners or those taking PrEP. Most reported being willing to engage in each of the 6 prevention strategies discussed., Conclusions: Black MSM taking PrEP voiced concern about STIs, and many noted that they infrequently use condoms. They were willing to engage in methods focused on preventing STIs on an individual or population level., Competing Interests: Conflict of Interest and Sources of Funding: M.E.C. has received research support (grants to institution) from Gilead Sciences and Viiv Healthcare, and has served on advisory boards for Viiv Healthcare. This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (K23AI137121) to M.E.C., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Uptake of PrEP remains suboptimal, especially in the Southern United States. Same-day or "Rapid PrEP Initiatives" (RPIs) in sexual health centers (SHCs) could facilitate access and overcome barriers to PrEP. We studied the adaptation of an RPI from Denver, Colorado to an SHC in New Orleans, Louisiana. Through focus group discussions (FGDs) with local SHC staff and PrEP providers, we developed a preliminary RPI model. In 5 FGDs with SHC clients referred for or taking PrEP, we gathered adaptation recommendations and feedback on model acceptability, feasibility, and utility. Providers and clients voiced unanimous support for the RPI. Clients favored the ease of same-day PrEP initiation and emphasized a desire for navigational support, financial counseling, and integration of PrEP care with their other clinical needs. Clients recommended that SHC providers discuss PrEP and HIV with all patients, regardless of providers' perception of risk. Next steps include small-scale implementation and evaluation., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MEC has received research support (grants to institution) from Gilead Sciences and ViiV Healthcare; has received consultancy/advisory board fees from ViiV Healthcare and FHI360; and has received personal fees for educational events from Vindico Medical, Education, Practice Point Communications, and Prime Education. RAL has conducted clinical trials at her institution for Abbott, Becton Dickenson, BioFire, Cepheid, Chembio, Cue, Gilead, Hologic, LabCorp, Merck, QuidelOrtho, Roche, and Visby; has served on a scientific advisory board for Abbott and Roche; and has received personal fees for educational events from Cepheid and Oakstone Publishing.

Background: Medial knee osteoarthritis (OA) is a common health problem resulting in knee pain and limiting patients' physical activity. After failed conservative treatment, unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are possible surgical treatment options for this condition. There is a paucity of high-quality evidence in the literature comparing objective and subjective outcomes of these procedures. Also, there is no common agreement on whether these procedures provide comparable results in late-stage medial knee OA patients., Methods: We will perform a prospective randomized controlled trial comparing HTO and UKA in patients with late-stage medial knee OA. 100 patients with isolated medial knee OA (KL III-IV) are assigned to either UKA (n = 50) or HTO (n = 50) procedure in patients 45-65 years of age. Our primary outcome will be KOOS 5 at one year postoperatively. Secondary outcomes include OARSI physical assessment, length of stay, wearable activity watch, radiographs (OA progression according to Kellgren-Lawrence classification), patient-reported outcomes (KOOS subscales, pain visual analog scale [VAS], Lysholm, and Oxford knee scores), and adverse events (conversion to total knee arthroplasty, surgery-related complications, need for revision surgery) outcomes. Our hypothesis is that neither of the interventions is superior as measured with KOOS 5 at 12 months., Ethics and Dissemination: The institutional review board of the Helsinki and Uusimaa Hospital District has approved the protocol. We will disseminate the findings through peer-reviewed publications., Trial Registration: ClinicalTrials.gov/TooloH NCT05442242. Registered on 7/1/2022., (© 2023. The Author(s).)

Hyperactive poly(ADP-ribose) polymerases (PARP) promote ischemic heart failure (IHF) after myocardial infarction (MI). However, the role of tankyrases (TNKSs), members of the PARP family, in pathogenesis of IHF remains unknown. We investigated the expression and activation of TNKSs in myocardium of IHF patients and MI rats. We explored the cardioprotective effect of TNKS inhibition in an isoproterenol-induced zebrafish HF model. In IHF patients, we observed elevated TNKS2 and DICER and concomitant upregulation of miR-34a-5p and miR-21-5p in non-infarcted myocardium. In a rat MI model, we found augmented TNKS2 and DICER in the border and infarct areas at the early stage of post-MI. We also observed consistently increased TNKS1 in the border and infarct areas and destabilized AXIN in the infarct area from 4 weeks onward, which in turn triggered Wnt/β-catenin signaling. In an isoproterenol-induced HF zebrafish model, inhibition of TNKS activity with XAV939, a TNKSs-specific inhibitor, protected against ventricular dilatation and cardiac dysfunction and abrogated overactivation of Wnt/β-catenin signaling and dysregulation of miR-34a-5p induced by isoproterenol. Our study unravels a potential role of TNKSs in the pathogenesis of IHF by regulating Wnt/β-catenin signaling and possibly modulating miRNAs and highlights the pharmacotherapeutic potential of TNKS inhibition for prevention of IHF.

Black populations in the U.S. South are disproportionally affected by HIV and COVID-19 due to longstanding inequalities. We conducted 20 in-depth interviews-12 with Black same-gender-loving men and 8 with Black cisgender women-to explore the impact of the initial phase of the COVID-19 pandemic on sexual activities and PrEP use. Almost all participants reduced the frequency of sex and number of partners. Women described little interest in sex, whereas men began to connect with some sexual partners after stay-at-home orders were lifted. Both populations were concerned about contracting COVID-19 through sexual partners, and men described selecting partners based on perceived COVID-19 risk. Participants valued PrEP and could access it, although several men who were not having sex stopped taking it. Risk of acquiring HIV during this time was likely limited. Future qualitative research is needed to understand how sexual behaviors and PrEP use changed as the pandemic continued.

Innovative delivery strategies are needed to facilitate access to HIV pre-exposure prophylaxis (PrEP). The objective of this study was to evaluate a navigator-facilitated PrEP referral process from a sexual health center (SHC) to a co-located PrEP clinic as an alternative delivery model. Electronic health record (EHR) data were used to calculate the number of clients seen at the SHC in 2019. Charts were manually reviewed to determine whether a PrEP clinic referral was made and document type of referral method: face-to-face appointment scheduling with the navigator ( warm handoff ), EHR messaging to navigator to schedule the appointment at a later time ( EHR message ), or provision of navigator's contact information to the client ( card only ). In 2019, 2481 unique potentially PrEP-eligible clients were seen at the SHC; 220 (9%) received a PrEP referral. Of referred clients, median age was 30 years (interquartile range, 24-34), 182 (83%) were male, 89 (40%) were non-Hispanic Black, and 24 (11%) were Latinx. In total, 94/220 (43%) referred clients attended an initial PrEP visit with a provider, and the proportion attending by referral method was 81%, 36%, and 27% for warm handoff, EHR message, and card only, respectively ( p  < 0.0001). Despite co-location of these two clinics, there were significant drop-offs along the PrEP care continuum for this referral system. Warm handoff was the most effective referral method, but further efforts are needed to understand barriers to referral. Implementation of same-day PrEP services at SHCs is one potential solution to engaging additional clients.