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Targeting the activation function-1 (AF-1) domain located in the N-terminus of the androgen receptor (AR) is an attractive therapeutic alternative to the current approaches to inhibit AR action in prostate cancer (PCa). Here we show that the AR AF-1 is bound by the cochaperone Bag-1L. Mutations in the AR interaction domain or loss of Bag-1L abrogate AR signaling and reduce PCa growth. Clinically, Bag-1L protein levels increase with progression to castration-resistant PCa (CRPC) and high levels of Bag-1L in primary PCa associate with a reduced clinical benefit from abiraterone when these tumors progress. Intriguingly, residues in Bag-1L important for its interaction with the AR AF-1 are within a potentially druggable pocket, implicating Bag-1L as a potential therapeutic target in PCa.

Background: The effect of hypertension is aggravated by lifestyle factors such as alcohol consumption. This study sought to determine the association between alcohol consumption and the level of blood pressures among HIV seronegative and seropositive cohorts. Methods: This secondary analysis was performed on a cross-sectional survey data of 17 922 participants during the period between 2018 and 2020. A questionnaire was used to obtain participants’ alcohol consumption history, which was categorized into non-alcohol consumers, non-heavy alcohol consumers, and heavy alcohol consumers. A linear regression model was used to establish relationships among participants with raised blood pressure (BP ≥ 140/90 mmHg). Results: Out of the total participants, 3553 (19.82%) were hypertensives. Almost 13% of the hypertensives (n = 458; 12.89%) were undiagnosed, and 12.44 % (442) had uncontrolled hypertension. About 14.52% of the hypertensives (3553) were not on any antihypertensive medication. Male non-consumers of alcohol had the highest systolic and diastolic BP; uncontrolled systolic BP (165.53 ± 20.87 mmHg), uncontrolled diastolic BP (102.28 ± 19.21mmHg). Adjusted for covariates, moderate alcohol consumption was associated with HTN among participants who were HIV seropositive [unadjusted (RR = 1.772, P = .006, 95% CI (1.178-2.665)], [RR = 1.772, P = .005, 95% CI (1.187-2.64)]. [unadjusted RR = 1.876, P = .036, 95% CI (1.043-3.378)], adjusted RR = 1.876, P = .041, 95% CI (1.024-3.437). Both moderate and heavy alcohol consumption were significantly related to hypertension among HIV sero-negative [unadjusted model, moderate consumption RR = 1.534 P = .003, 95% CI (1.152-2.044)], [adjusted model, moderate alcohol consumption RR = 1.535, P = .006, 95% CI (1.132-2.080)], [unadjusted model, heavy alcohol consumption, RR = 2.480, P = .030, 95% CI (1.091-5.638)], [adjusted model RR = 2.480, P = .034, 95% CI (1.072-5.738)]. Conclusion: Alcohol consumption is significantly related to increase BP regardless of HIV infection.

BackgroundOne of the most common medical problems associated with pregnancy is hypertension. Hypertensive disorders of pregnancy (HDP), which has been attributable to abnormal placentation may have adverse effects on both mother and foetus if left unchecked. The objective of this study was to determine the prevalence of this condition and its effect on placental morphology as well as maternal and perinatal outcomes.Materials and methodsThis was a prospective case-control study, conducted at Komfo Anokye Teaching Hospital (KATH), Ghana between February 2018 and July 2018. The progression of pregnancy in normotensive and hypertensive pregnant women, and the eventual perinatal outcomes were closely followed. Statistical analysis was performed using IMB-SPSS version 23. Associations were considered significant at p values of ≤ 0.05.ResultsFrom a total of 214 deliveries recorded during the period of study, 84 (39.25%) were hypertensives. Forty four (52%) of the hypertensives had preeclampsia, 28 (33.3%) had gestational hypertension, 6 (7.1%) had eclampsia, 4 (4.8%) had chronic hypertension, and 2 (2.4%) had preeclampsia superimposed on chronic hypertension. The frequency of placental haematoma, placental infarction, and placental calcification in the normotensives were significantly (p = 0.001) lower than that of the hypertensives. The mean placental weight (p = 0.01), placental volume (p = 0.001), placental diameter (p = 0.03), and placental thickness (p = 0.001) of the normotensives were significantly higher than those of the hypertensives. The number of normotensives in whom labour was induced, who had their babies delivered by caesarean section, and who were admitted after they had given birth were significantly (p = 0.001) lower than that of hypertensives who underwent similar procedures. No stillbirths were recorded in the normotensives compared with four in the hypertensives. The number of babies delivered to the normotensives who were admitted to the NICU was significantly (p = 0.001) lower than those delivered by hypertensives.ConclusionThere was a high prevalence of hypertensive disorders of pregnancy in the study site. Pregnant women who developed HDP are at a risk of developing placental abnormalities that adversely affected perinatal outcomes. These adverse effects can be curtailed by embarking on a vigorous health education drive.