Caffeinated Coffee, Decaffeinated Coffee and Endometrial Cancer Risk: A Prospective Cohort Study among US Postmenopausal Women

There is plausible biological evidence as well as epidemiologic evidence to suggest coffee consumption may lower endometrial cancer risk. We evaluated the associations between self-reported total coffee, caffeinated coffee and decaffeinated coffee, and endometrial cancer risk using the Women’s Health Initiative Observational Study Research Materials obtained from the National Heart, Lung, and Blood Institute Biological Specimen and Data Repository Coordinating Center. Our primary analyses included 45,696 women and 427 incident endometrial cancer cases, diagnosed over a total of 342,927 person-years of follow-up. We used Cox-proportional hazard models to evaluate coffee consumption and endometrial cancer risk. Overall, we did not find an association between coffee consumption and endometrial cancer risk. Compared to non-daily drinkers (none or <1 cup/day), the multivariable adjusted hazard ratios for women who drank ≥4 cups/day were 0.86 (95% confidence interval (CI) 0.63, 1.18) for total coffee, 0.89 (95% CI 0.63, 1.27) for caffeinated coffee, and 0.51 (95% CI 0.25, 1.03) for decaf coffee. In subgroup analyses by body mass index (BMI) there were no associations among normal-weight and overweight women for total coffee and caffeinated coffee. However among obese women, compared to the referent group (none or <1 cup/day), the hazard ratios for women who drank ≥2 cups/day were: 0.72 (95% CI 0.50, 1.04) for total coffee and 0.66 (95% CI 0.45, 0.97) for caffeinated coffee. Hazard ratios for women who drank ≥2 cups/day for decaffeinated coffee drinkers were 0.67 (0.43-1.06), 0.93 (0.55-1.58) and 0.80 (0.49-1.30) for normal, overweight and obese women, respectively. Our study suggests that caffeinated coffee consumption may be associated with lower endometrial cancer risk among obese postmenopausal women, but the association with decaffeinated coffee remains unclear

Indeterminate and discrepant rapid HIV test results in couples' HIV testing and counselling centres in Africa

<p>Abstract</p> <p>Background</p> <p>Many HIV voluntary testing and counselling centres in Africa use rapid antibody tests, in parallel or in sequence, to establish same-day HIV status. The interpretation of indeterminate or discrepant results between different rapid tests on one sample poses a challenge. We investigated the use of an algorithm using three serial rapid HIV tests in cohabiting couples to resolve unclear serostatuses.</p> <p>Methods</p> <p>Heterosexual couples visited the Rwanda Zambia HIV Research Group testing centres in Kigali, Rwanda, and Lusaka, Zambia, to assess HIV infection status. Individuals with unclear HIV rapid antibody test results (indeterminate) or discrepant results were asked to return for repeat testing to resolve HIV status. If either partner of a couple tested positive or indeterminate with the screening test, both partners were tested with a confirmatory test. Individuals with indeterminate or discrepant results were further tested with a tie-breaker and monthly retesting. HIV-RNA viral load was determined when HIV status was not resolved by follow-up rapid testing. Individuals were classified based on two of three initial tests as "Positive", "Negative" or "Other". Follow-up testing and/or HIV-RNA viral load testing determined them as "Infected", "Uninfected" or "Unresolved".</p> <p>Results</p> <p>Of 45,820 individuals tested as couples, 2.3% (4.1% of couples) had at least one discrepant or indeterminate rapid result. A total of 65% of those individuals had follow-up testing and of those individuals initially classified as "Negative" by three initial rapid tests, less than 1% were resolved as "Infected". In contrast, of those individuals with at least one discrepant or indeterminate result who were initially classified as "Positive", only 46% were resolved as "Infected", while the remainder was resolved as "Uninfected" (46%) or "Unresolved" (8%). A positive HIV serostatus of one of the partners was a strong predictor of infection in the other partner as 48% of individuals who resolved as "Infected" had an HIV-infected spouse.</p> <p>Conclusions</p> <p>In more than 45,000 individuals counselled and tested as couples, only 5% of individuals with indeterminate or discrepant rapid HIV test results were HIV infected. This represented only 0.1% of all individuals tested. Thus, algorithms using screening, confirmatory and tie-breaker rapid tests are reliable with two of three tests negative, but not when two of three tests are positive. False positive antibody tests may persist. HIV-positive partner serostatus should prompt repeat testing.</p

Lack of Awareness of Human Immunodeficiency Virus (HIV) Infection: Problems and Solutions With Self-reported HIV Serostatus of Men Who Have Sex With Men

Background. Lack of human immunodeficiency virus (HIV) infection awareness may be a driver of racial disparities in HIV infection amongmen who have sex withmen (MSM). Lack of awareness is typicallymeasured by comparing HIV test result to self-reported HIV status. This measure may be subject to reporting bias and alternatives are needed. Methods. The InvolveMENt study examined HIV disparities between black and whiteMSM from Atlanta. Among HIV-positive participants who did not report knowing they were positive, we examined other measures of awareness: HIV viral load (VL)/mL (low VL), antiretroviral (ARV) drugs in blood, and previous HIV case surveillance report. Results. Using self-report only, 32% (62 of 192) of black and 16% (7 of 45) of white MSM were not aware of their HIV infection (P = .03). Using self-report and low VL, 25% (48 of 192) black and 16% (7 of 45) white MSM lacked awareness (P = .18). Using self-report and ARVs, 26% (50 of 192) black and 16% (7 of 45) white MSM lacked awareness (P = .14). Using self-report and surveillance report, 15% (28 of 192) black and 13% (6 of 45) white MSM lacked awareness (P = .83). Conclusions. Self-report only may overestimate true lack of awareness of HIV status for black MSM. If, as our data suggest, black MSM are not less likely to be aware of their HIV infection than are white MSM, then this factor is not a substantial driver of HIV disparity. Future HIV research that depends on accuratemeasurement of HIV status awareness should consider including additional laboratory and case surveillance data

Targeting the Conserved Stem Loop 2 Motif in the SARS-CoV-2 Genome.

RNA structural elements occur in numerous single-stranded positive-sense RNA viruses. The stem-loop 2 motif (s2m) is one such element with an unusually high degree of sequence conservation, being found in the 3' untranslated region (UTR) in the genomes of many astroviruses, some picornaviruses and noroviruses, and a variety of coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. The evolutionary conservation and its occurrence in all viral subgenomic transcripts imply a key role for s2m in the viral infection cycle. Our findings indicate that the element, while stably folded, can nonetheless be invaded and remodeled spontaneously by antisense oligonucleotides (ASOs) that initiate pairing in exposed loops and trigger efficient sequence-specific RNA cleavage in reporter assays. ASOs also act to inhibit replication in an astrovirus replicon model system in a sequence-specific, dose-dependent manner and inhibit SARS-CoV-2 replication in cell culture. Our results thus permit us to suggest that the s2m element is readily targeted by ASOs, which show promise as antiviral agents. IMPORTANCE The highly conserved stem-loop 2 motif (s2m) is found in the genomes of many RNA viruses, including SARS-CoV-2. Our findings indicate that the s2m element can be targeted by antisense oligonucleotides. The antiviral potential of this element represents a promising start for further research into targeting conserved elements in RNA viruses.ERC, BBSR

Ancient genomes in South Patagonia reveal population movements associated with technological shifts and geography

Archaeological research documents major technological shifts among people who have lived in the southern tip of South America (South Patagonia) during the last thirteen millennia, including the development of marine-based economies and changes in tools and raw materials. It has been proposed that movements of people spreading culture and technology propelled some of these shifts, but these hypotheses have not been tested with ancient DNA. Here we report genome-wide data from 20 ancient individuals, and co-analyze it with previously reported data. We reveal that immigration does not explain the appearance of marine adaptations in South Patagonia. We describe partial genetic continuity since ~6600 BP and two later gene flows correlated with technological changes: one between 4700–2000 BP that affected primarily marine-based groups, and a later one impacting all <2000 BP groups. From ~2200–1200 BP, mixture among neighbors resulted in a cline correlated to geographic ordering along the coast.Fil: Nakatsuka, Nathan. Harvard Medical School; Estados UnidosFil: Luisi, Pierre. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades; ArgentinaFil: Motti, Josefina María Brenda. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Salemme, Monica Cira. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina. Universidad Nacional de Tierra del Fuego; ArgentinaFil: Santiago, Fernando Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: D'angelo del Campo, Manuel Domingo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales. Grupo de Estudios Interdisciplinarios sobre Poblaciones Humanas de Patagonia Austral; Argentina. Universidad Autónoma de Madrid; EspañaFil: Vecchi, Rodrigo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur; ArgentinaFil: Espinosa Parrilla, Yolanda. Consejo Superior de Investigaciones Científicas; EspañaFil: Prieto, Alfredo. Universidad de Magallanes; ChileFil: Adamski, Nicole. Harvard Medical School; Estados UnidosFil: Lawson, Ann Marie. Harvard Medical School; Estados UnidosFil: Harper, Thomas K.. University of Pennsylvania; Estados UnidosFil: Culleton, Brendan J.. University of Pennsylvania; Estados UnidosFil: Kennett, Douglas J.. University of California; Estados UnidosFil: Lalueza Fox, Carles. Consejo Superior de Investigaciones Científicas; EspañaFil: Mallick, Swapan. Harvard Medical School; Estados UnidosFil: Rohland, Nadin. Harvard Medical School; Estados UnidosFil: Guichón, Ricardo A.. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Cabana, Graciela S.. University of Tennessee; Estados UnidosFil: Nores, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Antropología de Córdoba. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Instituto de Antropología de Córdoba; ArgentinaFil: Reich, David. Harvard Medical School. Department Of Medicine; Estados Unido

Sleep duration and endometrial cancer risk

PURPOSE: Recent data indicate that night shift work is associated with increased endometrial cancer risk, perhaps through a pathway involving lower melatonin production. Melatonin is an antiestrogenic hormone, with production in a circadian pattern that is dependent on presence of dark at night. Sleep duration is positively associated with melatonin production and may be an indicator of melatonin levels in epidemiologic studies. METHODS: We evaluated associations between self-reported sleep duration and endometrial cancer risk using publicly available prospective data on 48,725 participants in the Women\u27s Health Initiative Observational Study, among whom 452 adjudicated incident cases of endometrial cancer were diagnosed over approximately 7.5 years of follow-up. Sleep duration was self-reported at baseline. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for endometrial cancer risk with adjustment for potential confounders. RESULTS: Most women reported sleeping ≤ 6 (33.3%) or 7 (38.5%) h each night; fewer reported sleeping 8 (23.4%) or ≥ 9 (4.8%) h each night. In adjusted analyses, there was an indication of reduced risk associated with longer sleep duration, though no statistically significant association was observed. Women who slept ≥ 9 h had a nonsignificant reduced risk of endometrial cancer compared with women who slept ≤ 6 h (HR = 0.87; 95% CI = 0.51-1.46). CONCLUSIONS: We found weak evidence of an association between sleep duration and endometrial cancer risk. Self-reported sleep duration may not adequately represent melatonin levels, thus further studies utilizing urinary melatonin levels are necessary to establish the mechanism by which night shift work increases endometrial cancer risk

PrEP awareness and use among reproductive age women in Miami, Florida.

BackgroundMiami, Florida is an epicenter of the HIV epidemic in the US, with 20% of new HIV infections occurring in women. Despite effectiveness of Pre-Exposure Prophylaxis (PrEP) in preventing HIV, only 10% of eligible women benefit from its use.SettingThis study evaluates PrEP awareness and use, and factors associated with PrEP awareness among sexually active women in Miami, Florida.MethodsResults reported in this study included cross-sectional data that were collected as part of a baseline visit from a parent study. Cis-gender, HIV-negative, 18-45-year-old, sexually active women were recruited as part of a study evaluating recurrent bacterial vaginosis and HIV risk. Participants completed questionnaires assessing socio-demographics, HIV risk factors, prior history of HIV testing and reproductive tract infections, PrEP awareness and use. Relationships between variables and PrEP awareness were analyzed and multivariable logistic regression identified variables strongly associated with PrEP awareness.ResultsAmong the 295 women enrolled, median age was 31 (24-38) years, 49% Black, 39% White, and 34% Hispanic. Of 63% who knew about PrEP, only 5% were on PrEP. Women with income below poverty line (OR = 2.00[1.04,3.87];p = 0.04), more male sexual partners in past month (OR = 1.30[1.01,1.68];p = 0.04), lifetime HIV testing (OR = 6.42[2.83,14.52];pConclusionPrEP awareness is low among reproductive age women in a high-risk setting. Culturally tailored interventions are needed to increase PrEP awareness and uptake, especially among Black and Hispanic women with inconsistent condom use during vaginal sex with male partners

Contrasting Self-Perceived Need and Guideline-Based Indication for HIV Pre-Exposure Prophylaxis Among Young, Black Men Who Have Sex with Men Offered Pre-Exposure Prophylaxis in Atlanta, Georgia

Despite high HIV incidence among young black men who have sex with men (YBMSM), pre-exposure prophylaxis (PrEP) uptake in this group is low. In a cohort of HIV-negative YBMSM in Atlanta, GA, all participants were offered PrEP as standard of care with free clinician visits and laboratory testing. We explored self-perceived need for PrEP among 29 in-depth interview participants by asking about reasons for PrEP uptake or refusal and factors that may lead to future reconsideration. Self-perceived need was compared to US Center for Disease Control and Prevention guidance for clinical PrEP indication using behavioral data and laboratory testing data. Self-perceived need for PrEP consistently underestimated clinical indication, primarily due to optimism for choosing other HIV prevention strategies, such as condom use, abstinence, or monogamy. Many participants cited consistent condom use and lack of sexual activity as reasons for not starting PrEP; however, follow-up survey data frequently demonstrated low condom use and high levels of sexual activity in the period after the interview. Study participants endorsed perceptions that PrEP is only for people with very high levels of sexual activity. Only one participant perceived incident sexually transmitted infection (STI) to be an indication for PrEP, despite the fact that several of the participants had a history of an STI diagnosis. These findings point to an opportunity for clinician intervention at diagnosis. Disconnect between self-perceived and guidance-based PrEP indications, as well as other factors such as medical mistrust or difficulty with access, may contribute to low PrEP uptake among YBMSM. A better understanding of the ways in which these issues manifest may be one tool for clinicians to support PrEP uptake