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BACKGROUND. Hyaluronan (HA), an extracellular matrix glycosaminoglycan, has been implicated in the pathophysiology of COVID-19 infection, pulmonary hypertension, pulmonary fibrosis, and other diseases, but is not targeted by any approved drugs. We asked whether hymecromone (4-methylumbelliferone [4-MU]), an oral drug approved in Europe for biliary spasm treatment that also inhibits HA in vitro and in animal models, could be repurposed as an inhibitor of HA synthesis in humans. METHODS. We conducted an open-label, single-center, dose-response study of hymecromone in healthy adults. Subjects received hymecromone at 1200 (n = 8), 2400 (n = 9), or 3600 (n = 9) mg/d divided into 3 doses daily, administered orally for 4 days. We assessed safety and tolerability of hymecromone and analyzed HA, 4-MU, and 4-methylumbelliferyl glucuronide (4-MUG; the main metabolite of 4-MU) concentrations in sputum and serum. RESULTS. Hymecromone was well tolerated up to doses of 3600 mg/d. Both sputum and serum drug concentrations increased in a dose-dependent manner, indicating that higher doses lead to greater exposures. Across all dose arms combined, we observed a significant decrease in sputum HA from baseline after 4 days of treatment. We also observed a decrease in serum HA. Additionally, higher baseline sputum HA levels were associated with a greater decrease in sputum HA. CONCLUSION. After 4 days of exposure to oral hymecromone, healthy human subjects experienced a significant reduction in sputum HA levels, indicating this oral therapy may have potential in pulmonary diseases where HA is implicated in pathogenesis. TRIAL REGISTRATION. ClinicalTrials.gov NCT02780752. FUNDING. Stanford Medicine Catalyst, Stanford SPARK, Stanford Innovative Medicines Accelerator program, NIH training grants 5T32AI052073-14 and T32HL129970., Introduction Hyaluronan (HA), an extracellular matrix glycosaminoglycan, plays an important role in inflammation (1, 2). Within injured and infected tissues, HA is produced by stromal cells in response to inflammatory [...]

Background: Adolescent girls and young women (AGYW) account for most new HIV infections in sub-Saharan Africa. WHO has endorsed oral PrEP and dapivirine vaginal ring (ring) for women at substantial [...]

Introduction: Antiretroviral (ARV)‐based pre‐exposure prophylaxis (PrEP) is a promising new HIV prevention strategy. However, variable levels of adherence have yielded mixed results across several PrEP trials and populations. It is not clear how taking ARV – traditionally used for HIV treatment – is perceived and how that perception may affect the use of these products as preventives. We explored the views and experiences of VOICE participants, their male partners and community members regarding the use of ARV as PrEP in the VOICE trial and the implications of these shared meanings for adherence. Methods: VOICE‐C was a qualitative ancillary study conducted at the Johannesburg site of VOICE, a multisite, double‐blind, placebo‐controlled randomised trial testing tenofovir gel, oral tenofovir and oral Truvada[sup.®] for HIV PrEP. We interviewed 102 randomly selected female VOICE participants, 22 male partners and 40 community members through in‐depth interviews, serial ethnography, or focus group discussions. All interviews were audiotaped, transcribed, translated and coded thematically for analysis. Results: The concept of ARV for prevention was understood to varying degrees across all study groups. A majority of VOICE participants understood that the products contained ARV, more so for the tablets than for the gel. Although participants knew they were HIV negative, ARV was associated with illness. Male partners and community members echoed these sentiments, highlighting confusion between treatment and prevention. Concerned that they would be mistakenly identified as HIV positive, VOICE participants often concealed use of or hid their study products. This occasionally led to relationship conflicts or early trial termination. HIV stigma and its association with ARV, especially the tablets, was articulated in rumour and gossip in the community, the workplace and the household. Although ARV were recognised as potent and beneficial medications, transforming the AIDS body from sickness to health, they were regarded as potentially harmful for those uninfected. Conclusions: VOICE participants and others in the trial community struggled to conceptualise the idea of using ARV for prevention. This possibly influenced willingness to adopt ARV‐based prevention in the VOICE clinical trial. Greater investments should be made to increase community understanding of ARV for prevention and to mitigate pervasive HIV stigma., Introduction Recently, oral antiretroviral (ARV)‐based pre‐exposure prophylaxis (PrEP) was established as an effective new HIV prevention strategy. Nevertheless, adequate protection hinges on correct and consistent product use. Adherence challenges have [...]

Brittle nails are a common reason why patients consult a dermatologist. The incidence of brittle nails in the European and North American population is approximately 20%, and women suffer from [...]