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Objective: To report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise. Study Design and Methods: The primary endpoint of this open‐label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT‐induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality of life. The trial will recruit high‐risk PCa patients (n = 310) undergoing external beam radiation therapy with adjuvant subcutaneous ADT. Participants will be stratified and randomized in a 1:1 ratio to either the E2 + ADT arm or the ADT‐only control arm. Additionally, a subset of patients (n = 120) will be randomized into a supervised exercise programme. Results: The primary outcome is assessed according to the efficacy of E2 in mitigating the deterioration of Expanded Prostate Cancer Index Composite sexual function domain scores. Secondary outcomes are assessed according to the occurrence of ADT‐induced adverse effects, safety and tolerability of E2, impact of E2 with or without exercise on physical performance, body composition, bone mineral density, muscle size, systematic biomarkers, and quality of life. Conclusion: The ESTRACISE study's innovative design can offer novel insights about the benefits of E2 gel, and the substudy can reinforce the benefits resistance training and deliver valuable new novel insights into the synergistic benefits of E2 gel and exercise, which are currently unknown. Trial Registration: The protocol has been registered in euclinicaltrials.eu (2023‐504704‐28‐00) and in clinicaltrials.gov (NCT06271551). [ABSTRACT FROM AUTHOR]

Stable isotopes of carbon ([sup.12]C and [sup.13]C) and sulphur ([sup.32]S and [sup.34]S) are fractionated during some of the transformations between reservoirs in the global carbon and sulphur cycles. The main processes controlling the isotopic composition of Earth surface reservoirs are, for carbon, photosynthesis, respiration and equilibration between oceanic dissolved inorganic carbon and atmospheric C[O.sub.2], and, for sulphur, bacterial sulphate reduction and sulphide reoxidation. Thus the different reservoirs of carbon and sulphur in the global cycles attain characteristic isotopic compositions that can be used as a 'fingerprint' for different carbon and sulphur sources and to track changes in the balance of carbon and sulphur stored in different reservoirs. These isotopic signals can be used both to examine contemporary anthropogenic impacts on the cycling of carbon and sulphur and, where isotopic compositions are faithfully preserved in ancient sediments, to examine historical changes in global geochemical cycles through geological time. A number of case studies are discussed to illustrate how isotopic techniques represent one of the most powerful and important tools available in the study of both the causes and affects of ancient and modem global environmental change.

Human herpesvirus 8 (HHV-8) is very strongly linked to Kaposi's sarcoma in South Africa. Among 3,344 black South Africans who had cancer, 51 had Kaposi's sarcoma, which is a type of skin tumor common in AIDS patients. Blood tests revealed that 83% of these 51 patients had antibodies against HHV-8 compared to 32% of the patients with other types of cancer. However, the presence of HHV-8 did not seem to be associated with HIV infection.

Abstract Background Infection with human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the necessary causal agent in the development of Kaposi's sarcoma (KS). Infection with HIV-1, male gender and older age all increase risk for KS. However, the geographic distribution of HHV-8 and KS both prior to the HIV/AIDS epidemic and with HIV/AIDS suggest the presence of an additional co-factor in the development of KS. Methods Between January 1994 and October 1997, we interviewed 2576 black in-patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 and the study was restricted to 2191 HIV-1 negative patients. Antibodies against the latent nuclear antigen of HHV-8 encoded by orf73 were detected with an indirect immunofluorescence assay. We examined the relationship between high anti-HHV-8 antibody titers (≥1:51,200) and sociodemographic and behavioral factors using unconditional logistic regression models. Variables that were significant at p = 0.10 were included in multivariate analysis. Results Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.0%) were positive for antibodies against HHV-8 according to the immunofluorescent assay. Among those seropositive for HHV-8, 530 (62.1%) had low titers (1:200), 227 (26.6%) had medium titers (1:51,200) and 97 (11.4%) had highest titers (1:204,800). Among the 2191 HIV-1 negative patients, the prevalence of high anti-HHV-8 antibody titers (≥1:51,200) was independently associated with increasing age (ptrend = 0.04), having a marital status of separated or divorced (p = 0.003), using wood, coal or charcoal as fuel for cooking 20 years ago instead of electricity (p = 0.02) and consuming traditional maize beer more than one time a week (p = 0.02; p-trend for increasing consumption = 0.05) although this may be due to chance given the large number of predictors considered in this analysis. Conclusions Among HIV-negative subjects, patients with high anti-HHV-8 antibody titers are characterized by older age. Other associations that may be factors in the development of high anti-HHV-8 titers include exposure to poverty or a low socioeconomic status environment and consumption of traditional maize beer. The relationship between these variables and high anti-HHV-8 titers requires further, prospective study.

Purpose: To describe the epidemiology of Microbial Keratitis (MK) in Uganda. Methods: We prospectively recruited patients presenting with MK at two main eye units in Southern Uganda between December 2016 and March 2018. We collected information on clinical history and presentation, microbiology and 3-month outcomes. Poor vision was defined as vision < 6/60). Results: 313 individuals were enrolled. Median age was 47 years (range 18–96) and 174 (56%) were male. Median presentation time was 17 days from onset (IQR 8–32). Trauma was reported by 29% and use of Traditional Eye Medicine by 60%. Majority presented with severe infections (median infiltrate size 5.2 mm); 47% were blind in the affected eye (vision < 3/60). Microbiology was available from 270 cases: 62% were fungal, 7% mixed (bacterial and fungal), 7% bacterial and 24% no organism detected. At 3 months, 30% of the participants were blind in the affected eye, while 9% had lost their eye from the infection. Delayed presentation (overall p =.007) and prior use of Traditional Eye Medicine (aOR 1.58 [95% CI 1.04–2.42], p =.033) were responsible for poor presentation. Predictors of poor vision at 3 months were: baseline vision (aOR 2.98 [95%CI 2.12–4.19], p <.0001), infiltrate size (aOR 1.19 [95%CI 1.03–1.36], p <.020) and perforation at presentation (aOR 9.93 [95% CI 3.70–26.6], p <.0001). Conclusion: The most important outcome predictor was the state of the eye at presentation, facilitated by prior use of Traditional Eye Medicine and delayed presentation. In order to improve outcomes, we need effective early interventions. [ABSTRACT FROM AUTHOR]

Purpose: Microbial keratitis (MK), is a frequent cause of sight loss worldwide, particularly in low and middle-income countries. This study aimed to investigate the risk factors of MK in Uganda. Methods: Using a nested case control, we recruited healthy community controls for patients presenting with MK at the two main eye units in Southern Uganda between December 2016 and March 2018. Controls were individually matched for age, gender and village of the cases on a 1:1 ratio. We collected information on demographics, occupation, HIV and Diabetes Mellitus status. In STATA version 14.1, multivariable conditional logistic regression was used to generate odds ratios for risk factors of MK and a likelihood ratio test used to assess statistical significance of associations. Results: Two hundred and fifteen case-control pairs were enrolled. The HIV positive patients among the cases was 9% versus 1% among the controls, p =.0003. Diabetes 7% among the cases versus 1.4% among the controls, p =.012. Eye trauma was 29% versus 0% among the cases and controls. In the multivariable model adjusted for age, sex and village, HIV (OR 83.5, 95%CI 2.01–3456, p =.020), Diabetes (OR 9.38, 95% CI 1.48–59.3, p =.017) and a farming occupation (OR 2.60, 95%CI 1.21–5.57, p =.014) were associated with MK. Compared to a low socio-economic status, a middle status was less likely to be associated with MK (OR 0.29, 95%CI 0.09–0.89, p <.0001). Conclusion: MK was associated with HIV, Diabetes, being poor and farming as the main occupation. More studies are needed to explore how these factors predispose to MK. [ABSTRACT FROM AUTHOR]