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Background Gestational diabetes mellitus (GDM), characterized by hyperglycemia that develops during pregnancy, increases the risk of fetal macrosomia, childhood obesity and cardiometabolic disorders later in life. This process has been attributed partly to DNA methylation modifications in growth and stress-related pathways. Nutrients involved with one-carbon metabolism (OCM), such as folate, choline, betaine, and vitamin B 12 , provide methyl groups for DNA methylation of these pathways. Therefore, this study aimed to determine whether maternal OCM nutrient intakes and levels modified fetal DNA methylation and in turn altered fetal growth patterns in pregnancies with and without GDM. Results In this prospective study at a single academic institution from September 2016 to June 2019, we recruited 76 pregnant women with and without GDM at 25–33 weeks gestational age and assessed their OCM nutrient intake by diet recalls and measured maternal blood OCM nutrient levels. We also collected placenta and cord blood samples at delivery to examine fetal tissue DNA methylation of the genes that modify fetal growth and stress response such as insulin-like growth factor 2 ( IGF2 ) and corticotropin-releasing hormone ( CRH ). We analyzed the association between maternal OCM nutrients and fetal DNA methylation using a generalized linear mixed model. Our results demonstrated that maternal choline intake was positively correlated with cord blood CRH methylation levels in both GDM and non-GDM pregnancies ( r  = 0.13, p  = 0.007). Further, the downstream stress hormone cortisol regulated by CRH was inversely associated with maternal choline intake ( r  = − 0.36, p  = 0.021). Higher maternal betaine intake and serum folate levels were associated with lower cord blood and placental IGF2 DNA methylation ( r  = − 0.13, p  = 0.049 and r  = − 0.065, p  = 0.034, respectively) in both GDM and non-GDM pregnancies. Further, there was an inverse association between maternal betaine intake and birthweight of infants ( r  = − 0.28, p  = 0.015). Conclusions In conclusion, we observed a complex interrelationship between maternal OCM nutrients and fetal DNA methylation levels regardless of GDM status, which may, epigenetically, program molecular pathways related to fetal growth and stress response.

Reproductive aging may impact the vaginal microbiome and genital tract mucosal immune environment and contribute to genital tract health in women living with and at-risk for HIV infection. A cross-sectional study of 102 HIV+ (51 premenopausal, 51 postmenopausal) and 39 HIV-uninfected (HIV-) (20 premenopausal, 19 postmenopausal) women was performed in Bronx and Brooklyn, NY. Cervicovaginal lavage (CVL) was collected for quantification of innate antimicrobial activity against E. coli, HSV-2 and HIV and immune mediators by Luminex and ELISA. Microbiome studies by qPCR and 16S rRNA sequencing were performed on vaginal swabs. HIV+ postmenopausal compared to premenopausal participants had lower median E. coli bactericidal activity (41% vs. 62%, p = 0.001), lower median gene copies of Lactobacillus crispatus (p = 0.005) and Lactobacillus iners (p = 0.019), lower proportions of Lactobacillus iners, higher proportions of Gardnerella and Atopobium vaginae and lower levels of human beta defensins (HBD-2, HBD-3) and secretory leukocyte protease inhibitor (SLPI), p<0.001. HSV-2 inhibitory activity was higher in HIV+ postmenopausal compared to premenopausal participants (37% vs. 17%, p = 0.001) and correlated with the proinflammatory molecules interleukin (IL) 6, IL-8, human neutrophil peptide (HNP) 1-3, lactoferrin and fibronectin. Similar trends were observed in HIV- postmenopausal compared to premenopausal participants. HIV inhibitory activity did not differ by reproductive status in the HIV+ participants but was significantly higher in HIV- postmenopausal compared to premenopausal participants and in participants with suppressed plasma viral load, and inversely correlated with gene copies of G. vaginalis and BVAB2. A significant proportion of HIV+ participants on ART exhibited HIV enhancing activity. HIV+ postmenopausal compared to premenopausal participants have less CVL E. coli bactericidal activity, reflecting a reduction in Lactobacilli and a greater proportion of Gardnerella and A. vaginae, and more HSV-2 inhibitory activity, reflecting increased mucosal inflammation. The effect of menopause on mucosal immunity was greater in HIV+ participants, suggesting a synergistic impact. Promotion of a lactobacillus dominant vaginal microbiome and reduced mucosal inflammation may improve vaginal health and reduce risk for shedding of HIV and potential for HIV transmission in HIV+ menopausal women.

There is limited research examining the sexual health and well-being of older women living with HIV (OWLH). Most studies focus on sexual dysfunction, leaving aside the richer context of sexuality and sexual health, including the effect of age-related psychosocial and interpersonal changes on sexual health behaviors. Guided by the integrative biopsychosocial model and the sexual health model, this study explored the importance of sex and sexuality among OWLH to identify their sexual health and HIV prevention needs for program planning. A purposive sample ( n  = 50) of OWLH was selected from a parent study ( n  = 2052). We conducted 8 focus groups and 41 in-depth interviews with 50 African American and Latina OWLH aged 50–69 years old in three U.S. cities. The triangulation approach was used to synthesize the data. Six salient themes emerged: sexual pleasure changes due to age, sexual freedom as women age, the role of relationships in sexual pleasure, changes in sexual ability and sexual health needs, sexual risk behaviors, and ageist assumptions about older women’s sexuality. We found that sexual pleasure and the need for intimacy continue to be important for OWLH, but that changing sexual abilities and sexual health needs, such as the reduction of sexual desire, as well as increased painful intercourse due to menopause-associated vaginal drying, were persistent barriers to sexual fulfillment and satisfaction. Particular interpersonal dynamics, including low perceptions of the risk of HIV transmission as related to gender, viral suppression, and habitual condomless sex with long-term partners without HIV transmission have resulted in abandoning safer sex practices with serodiscordant partners. These findings suggest that HIV prevention for OWLH should focus on how sexual function and satisfaction intersect with sexual risk. HIV prevention for OWLH should promote ways to maintain satisfying and safe sex lives among aging women.

Role of Physicians on Ethics Committees after DobbsDetermining the legality of a necessary procedure such as abortion lies outside the domain of ethics committees, and committees that take on such a task contribute to the erosion of patient autonomy.

Objective Women with HIV (WWH) have up to five times higher risk for cardiovascular disease compared to age-matched women without HIV, and this risk is pronounced in reproductive-aged women. Pregnancy promotes systemic inflammation, leading to remodeling of the heart’s structure and changes in function during and after pregnancy; therefore, we sought to examine the association of pregnancy history and number of live births with changes in cardiac structure and function in women with and without HIV (WWoH). Methods Cross-sectional data from the Multicenter AIDS Cohort Study/Women’s Interagency HIV Study Combined Cohort Study (MWCCS) were analyzed using univariate and multivariable logistic and linear regression models. Data from participants with echocardiograms conducted during or after their last pregnancy were included. The association between echocardiographic parameters and ever having had a live birth and number of live births was examined by HIV status. Results Of 1,646 women (1,156 WWH and 490 WWoH), 83% ( n  = 1,369) had a history of live births. Among WWH, ever having a live birth was associated with decreased left ventricular ejection fraction (β=-1.33, p  = 0.014) and number of live births was associated with increased odds of diastolic dysfunction (OR = 1.14, p  = 0.009). In WWoH, live births were significantly associated with increased left ventricular end-diastolic volume index (β = 0.64, p  = 0.029). Conclusion In this study, live birth history was associated with small but significant changes in cardiac structure and function, with WWH showing greaterlikelihood of adverse echocardiographic changes. This highlights differential cardiac remodeling patterns by HIV status. Longitudinal studies are needed to assess the progression and clinical implications of these findings.

Imposter syndrome is a chronic feeling of doubt leading to a sense of incompetence, which is common among trainees. However, little is known about the effect of gender on imposter syndrome among surgical trainees. An online national survey was distributed to the surgical subspecialty residents between March and September 2022, including demographics, validated Clance Imposter Scale and a short questionnaire evaluating depression and anxiety. Of the participants self identified as women (264, 69.1%) and men (118, 30.9%) (response rate 36.4%), the prevalence of imposterism was higher among women trainees (97% vs. 86%; p ​< ​0.0001). Risk factors were being a gynecologist (156, 59%, p ​< ​0.0001), single (157, 59.7% p ​= ​0.007), having no dependents (233, 88.3% p ​= ​0.001), being a foreign graduate (24, 9.1%, p ​= ​0.024) and having feelings of anxiety (82, 31.1% p ​= ​0.012). When using multivariate logistic regression to adjust for these factors, the prevalence of imposter syndrome remained significantly higher among women. Women trainees belonging to various surgical fields are affected by Imposter syndrome. Residency programs should develop wellness programs and provide mentorship to address this condition. •Women surgical trainees were found to be more affected by imposter syndrome, particularly frequent and intense imposterism.•Risk factors found were being single, having no dependents, being in OBGYN and a foreign medical graduate.•The feelings of anxiety correlated with imposter syndrome.•There is a need for residency programs to develop wellness curriculum to address this entity among all the surgical trainees.

We assessed changes in self-reported sexual activity (SA) over 13 years among HIV-infected and uninfected women. The impact of aging and menopause on SA and unprotected anal or vaginal intercourse (UAVI) was examined among women in the Women’s Interagency HIV Study (WIHS), stratifying by HIV status and detectable viral load among HIV-infected women. Generalized mixed linear models were fitted for each outcome, adjusted for relevant covariates. HIV-uninfected women evidenced higher levels of SA and UAVI than HIV-infected. The odds of SA declined by 62–64 % per decade of age. The odds of SA in a 6-month interval for women aged 40–57 declined by 18–22 % post-menopause (controlling for age). Among HIV+/detectable women only, the odds of any UAVI decreased by 17 % per decade of age; the odds of UAVI were unchanged pre-menopause, and then decreased by 28 % post-menopause. Elucidating the factors accounting for ongoing unprotected sex among older women should inform interventions.

During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection. We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83). Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer. Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk.

ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.

[...] a statement is required that sets forth an accurate rate of deaths due to abortions, including all deaths in which the abortion procedure was a significant contributing factor, and all other known medical risks to the physical health of the woman, including the risk of infection, hemotrhage, danger to subsequent pregnancies, and infertility. By mandating \"ideological speech\" on the part of physicians, use of the legislated script forces them to commit an untenable ethical and professional wrong: deceiving their patients by providing false information and withholding empirically derived, evidence-based clinical data.2 Legal arguments against this approach and its infringement on the first amendment rights of physicians continue to be eloquently sounded.3 First amendment protections for scientific speech should inform, if not govern, the disclosure elements of the informed consent process.