From hit to vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation.

Vaccination can help prevent infection and can also be used to treat cancer, allergy, and potentially even drug overdose. Adjuvants enhance vaccine responses, but currently, the path to their advancement and development is incremental. We used a phenotypic small-molecule screen using THP-1 cells to identify nuclear factor-κB (NF-κB)-activating molecules followed by counterscreening lead target libraries with a quantitative tumor necrosis factor immunoassay using primary human peripheral blood mononuclear cells. Screening on primary cells identified an imidazopyrimidine, dubbed PVP-037. Moreover, while PVP-037 did not overtly activate THP-1 cells, it demonstrated broad innate immune activation, including NF-κB and cytokine induction from primary human leukocytes in vitro as well as enhancement of influenza and SARS-CoV-2 antigen-specific humoral responses in mice. Several de novo synthesis structural enhancements iteratively improved PVP-037's in vitro efficacy, potency, species-specific activity, and in vivo adjuvanticity. Overall, we identified imidazopyrimidine Toll-like receptor-7/8 adjuvants that act in synergy with oil-in-water emulsion to enhance immune responses.

Experiences and attitudes towards Menstrual Suppression among Women with Bacterial vaginosis Randomised to Continuous Use of NuvaRing in Kenya.

Background: The contraceptive vaginal ring (NuvaRing), one of the Multipurpose Prevention Technologies (MPT) products, is effective in preventing unintended pregnancies and may contribute to reducing the frequency of Bacterial Vaginosis (BV), which is a risk factor for HIV acquisition, transmission, and shedding among women. NuvaRing may cause irregular menstruation, including menstrual suppression, which may influence women's decision on product choice, use, and acceptability. In this prospective cohort study, we assessed women's experiences with menstruation suppression following continued NuvaRing use. Methods: A total of 18 in-depth interviews were conducted using a semi-structured interview guide among purposively selected women with BV in Thika, Kenya, aged 18-40 years, who used NuvaRing continuously. All women received counseling on possibility of menstrual suppression following continuous NuvaRing use. Audio recordings were transcribed verbatim and thematically analyzed. Results: Participants who expected and were aware that menstrual suppression was a possible side effect of Nuvaring accepted its benefits, and expressed acceptance and desire to continue using NuvaRing. Participants who had not anticipated menstrual suppression expressed anxiety and fear, with some expressing desire to continue using NuvaRing but worried about unintended negative consequences. The ability to perform daily activities uninterrupted, reduced expenses on sanitary supplies, enhanced sexual pleasure and relationships, and absence of menstrual pain were benefits of menstrual suppression. Although all participants received counseling on menstrual suppression, some expressed anxiety over the possibility of unintended pregnancy. As a result, they frequented medical facilities for health check-ups and pregnancy tests, and some used combined oral contraceptives to induce menses. Conclusion: Understanding perceptions regarding menstrual suppression is crucial in offering targeted and comprehensive counseling to improve women's understanding of menstruation suppression to influence acceptance and use of NuvaRing. Additionally, improved male involvement in reproductive health concerns and women's autonomy in discussing reproductive health issues with partners is essential.

Attitudes Toward Menstrual Suppression Among Cyclic and Continuous Contraceptive Vaginal Ring Users in Kenya.

Objective: Multipurpose prevention technologies (MPTs) are developmental dual-purpose options that would provide women with a contraceptive as well as a prevention modality aimed at sexually transmitted infections. The contraceptive vaginal ring (CVR) has many properties that makes it an ideal MPT candidate. The objective of this study is to understand women's attitudes towards menstrual suppression, a potential side effect of using a CVR, and how to address these attitudes for MPT vaginal rings in development. Materials and methods: We analyzed data derived from a subset of cohort study participants (n=45) in Thika, Kenya between January 2016- December 2018. The primary study enrolled 121 women 18-40 years with bacterial vaginosis and randomized them to cyclic or continuous CVR use for eight months. During the 6-month follow-up, a questionnaire eliciting attitudes towards menstrual suppression was administered. Responses to the menstrual suppression questionnaire between participants in the cyclic and continuous CVR use groups were compared. Likert-scale responses were summed to create a menstrual suppression attitude summary score, and a hierarchical cluster analysis was conducted to identify similarities in response patterns among all participants. Results: Totally 81.8% of continuous CVR users believed that one was less likely to get pregnant after using hormonal medication to suppress menses, compared to 47.8% of cyclic CVR users (P=0.02), and were more worried it would cause long-term health effects (86.4% vs 60.9%, p = 0.05). The menstrual suppression attitude summary score ranged from 8 to 42, with lower scores indicating negative attitudes. The summary score identified three distinct clusters. When asked if menstrual suppression effects long-term health; 100% of Cluster 3 was worried compared to 80.8% of Cluster 2 and 46.2% of Cluster 1 (p = 0.03). The average summary score among Cluster 3 (Mean = 14.8, SD = 4.6) was lower (p < 0.001) and women were more worried about discomfort during sex (p=0.05) as well as their sexual partners feeling the ring (p=0.02). Conclusion: Women are more likely to have negative attitudes if they believe menstrual suppression hinders future reproductive health. Education on cycle control and fertility could mitigate negative attitudes and improve uptake of CVRs.

Response accuracy of hazard identification in migrant farm workers.

This study assessed potential biases introduced by using maternal proxies for reporting work hazards, illness symptoms, and acute agricultural injuries in studies of migrant farmworker families. A convenience sample of 79 mother/spouse and mother/oldest child pairs was obtained from a two-year cohort study of migrant farmworker families from Starr County, Texas. Pairs completed an interviewer-administered survey including 27 close-ended items describing work history, illness symptoms, and acute injuries during the 2001 migration season. Data analysis included prevalence, sensitivity, and specificity measures. Maternal proxy reports of subjective symptoms of a spouse or child were approximately 50% lower than spouse or child self-reports. Sensitivity and specificity of mothers' responses regarding hazard items were higher for spouses than for children. For items measuring illness symptoms, sensitivity of mothers' responses for spouses and oldest child pairs was generally less than 30%; however, specificity was generally above 90%. For acute agricultural injury, the mother/spouse sensitivity was 75%, the mother/child 40%, and specificities were 100% and 97%, respectively. Sensitivity and specificity for mother/ spouse pairs was generally higher than mother/child pairs for work hazards, illness symptoms and acute injuries. While mothers may be acceptable proxies for spouses in this population, efforts should be made to collect data directly from adolescent children in studies of agricultural injuries.

Disseminating a sun safety program to zoological parks: the effects of tailoring.

Previous research found that a sun safety program for visitors at 1 zoo increased sun safety behaviors. This randomized study compared the effects of tailored dissemination materials plus 2 brief follow-up phone calls (tailored group) versus generic materials (basic group) on implementation by other zoos of the previously evaluated sun safety program. Education directors of 126 zoos completed surveys several months following initial dissemination and 1 year later. During Summer 1, 40% of tailored group zoos and 24% of basic group zoos offered visitors at least 1 sun safety activity (odds ratio=2.2, 95% confidence interval=1.0-4.8). During Summer 2, these rates were 34% and 44%, respectively (ns). The pattern of findings suggests that tailoring had no incremental long-term impact and that the generic materials produced a good level of dissemination.

Promotion of frequent tanning sessions by indoor tanning facilities: two studies.

BACKGROUND: Indoor tanning may increase the risk of melanoma and other health problems. Frequent users of indoor tanning facilities may be at particularly high risk. OBJECTIVE: In study 1 our purpose was to assess the prevalence and nature of indoor tanning advertisements; in study 2 we aimed to assess tanning facility compliance to recommended exposure schedules. METHODS: In study 1, tanning facility advertisements over a 4-month period from 24 San Diego County newspapers were monitored. In study 2, we assessed compliance with recommended exposure schedules via a telephone interview of 60 San Diego County tanning facilities. RESULTS: Approximately 75% of the indoor tanning advertisements promoted unlimited tanning. Only 5% of facilities were in compliance with recommended tanning schedules, and 100% offered "unlimited" tanning packages. CONCLUSIONS: These findings suggest that the indoor tanning industry, through pricing incentives that allow frequent sessions, may be promoting overexposure to UVR. Stronger legislation is needed to address this issue.