KLF5 and NFYA factors as novel regulators of prostate cancer cell metabolism.

Prostate cancer (PCa) cells rely on the androgen receptor (AR) signaling axis to reprogram metabolism to sustain aberrant proliferation. Whether additional transcription factors participate to this reprogramming remains mostly unknown. To identify such factors, DNA motif analyses were performed in the promoter and regulatory regions of genes sensitive to androgens in PCa cells. These analyses identified two transcription factors, KLF5 and NFYA, as possibly associated with PCa cell metabolism. In clinical datasets, KLF5 and NFYA expression levels were associated with disease aggressiveness, being significantly decreased and increased, respectively, during PCa progression. Their expression was next investigated by qPCR and Western blot in human PCa cell models, revealing a positive regulation of KLF5 by androgens and a correlation between NFYA and AR protein expression status. siRNA-mediated knockdown of KLF5 increased human PCa cell proliferation rate in AR-positive cell models, suggesting a tumor suppressor function. Live-cell metabolic assays showed that knockdown of KLF5 promoted mitochondrial respiration, a key metabolic pathway associated with PCa progression. The opposite was observed for knockdown of NFYA regarding proliferation and respiration. RNA-seq analyses following the knockdown of either KLF5 and NFYA confirmed that both factors regulated distinct metabolic gene signatures, as well as other gene signatures, explaining their differential impact on PCa cell proliferation and metabolism. Overall, our findings identify KLF5 and NFYA as novel regulators of PCa cell metabolism.

Prevalence and correlates of psychological distress among 13-14 year old adolescent girls in North Karnataka, South India: a cross-sectional study.

BACKGROUND: Mental health disorders among adolescents have emerged as a major public health issue in many low and middle-income countries, including India. There is a paucity of research on the determinants of psychological distress, particularly among the poorest girls in the poorest communities. The purpose of this study was to assess the prevalence and correlates of different indicators of psychological distress among 13-14 year old low caste girls in rural, south India. METHODS: Cross-sectional survey of 1191 low caste girls in two districts in north Karnataka, conducted as part of a cluster randomised-control trial. Bivariate and multivariate logistic regression analysis assessed correlates of different indicators of psychological distress. RESULTS: More than one third of girls (35.1%) reported having no hope for the future. 6.9% reported feeling down, depressed or hopeless in the past 2 weeks. 2.1% reported thinking they would be better off dead or of hurting themselves in some way in the past 2 weeks. 1.6% reported sexual abuse, 8.0% rrecent eve teasing and 6.3% having no parental emotional support. Suicidal ideation was independently associated with sexual abuse (AOR 11.9 (3.0-47.0)) and a lack of parental emotional support (AOR 0.2 (0.1-0.5)). Feeling down, depressed or hopeless was independently associated with recent eve-teasing (AOR 2.9 (1.6-5.4)), a harassing or abusive school environment (AOR 3.9 (1.8-8.2)), being frequently absent (AOR 2.8 (1.5-5.5)) or having dropped out of school (AOR 2.1 (1.0-4.3)), and living in Vijayapura district (AOR 2.5 (1.6-4.1)). Having no hope for the future was independently associated with a range of factors, including recent "eve-teasing" (AOR 1.5 (1.0-2.4)), being engaged (AOR 2.9 (0.9-9.7)), not participating in groups (AOR 0.5 (0.4-0.6)) and a lack of emotional support (AOR 0.6 (0.4-0.7)). CONCLUSIONS: Rather than being a time of optimism, a third of low caste girls in rural north, Karnataka have limited hope for the future, with some contemplating suicide. As well as having important development benefits, interventions that address the upstream structural and gender-norms based determinants of poor mental health, and provide adolescent services for girls who require treatment and support, should have important benefits for girls' psychological wellbeing. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.GovNCT01996241 . November 27, 2013.

Developing a Mental Health Measurement Strategy to Capture Psychological Problems among Lower Caste Adolescent Girls in Rural, South India.

Adolescent girls vulnerable to early marriage and school dropout in rural India may be at elevated risk of psychosocial problems. However, few screening instruments have been culturally adapted and validated to measure this risk. This paper describes the process by which the Primary Health Questionnaire PHQ-9, a screening instrument for depression, was tested for cultural validity as part of the Samata evaluation - an intervention to support low caste adolescent girls in rural south India to attend and complete secondary school and to delay marriage until adulthood. Three focus groups discussions (FGDs) were held with 20 adolescent girls and six outreach workers of the Samata programme in rural north Karnataka, south India. The FGDs were used to explore local expressions of psychosocial problems and to understand the acceptability and appropriateness of PHQ-9 items. A thematic content analysis was conducted on the transcripts of the FGDs. Descriptions of local expressions of psychosocial problems generally matched the items on the PHQ-9. However, not all representations of psychological symptoms were captured by this tool. Persistent worry, loneliness and isolation, and externalised behaviours were also described by participants as common expressions of psychosocial distress. Based on the limitations of translation methods, local stakeholders must be involved in evaluating the cultural appropriateness of mental health screening tools. The current research demonstrates a strategy by which to assess the cultural validity of Western psychiatric instruments with key stakeholders in low- and middle-income settings.

Reducing violence and increasing condom use in the intimate partnerships of female sex workers: study protocol for Samvedana Plus, a cluster randomised controlled trial in Karnataka state, south India.

BACKGROUND: Female sex workers (FSWs) are at increased risk of HIV and STIs compared to women in the general population, and frequently experience violence in their working and domestic lives from a variety of perpetrators, which can enhance this risk. While progress has been made in addressing violence by police and clients, little work has been done to understand and prevent violence by intimate partners (IPs) among FSW populations. METHODS: Samvedana Plus is a multi-level intervention programme that works with FSWs, their IPs, the sex worker community, and the general population, and aims to reduce violence and increase consistent condom use within these 'intimate' relationships. The programme involves shifting norms around the acceptability of beating as a form of discipline, challenging gender roles that give men authority over women, and working with men and women to encourage new relationship models based on gender equity and respect. The programme will aim to cover 800 FSWs and their IPs living in 47 villages in Bagalkot district, northern Karnataka. The study is designed to assess two primary outcomes: the proportion of FSWs who report: (i) physical or sexual partner violence; and (ii) consistent condom use in their intimate relationship, within the past 6 months. The evaluation will employ a cluster-randomised controlled trial design, with 50 % of the village clusters (n = 24) randomly selected to receive the intervention for the first 24 months and the remaining 50 % (n = 23) receiving the intervention thereafter. Statisticians will be blinded to treatment arm allocation. The evaluation will use an adjusted, cluster-level intention to treat analysis, comparing outcomes in intervention and control villages at midline (12 months) and endline (24 months). The evaluation design will involve quantitative and qualitative assessments with (i) all FSWs who report an IP (ii) IPs; and process/ implementation monitoring. Baseline data collection was completed in April 2015, and endline data collection is anticipated in May 2017. CONCLUSIONS: This is an innovative intervention programme that aims to address violence by IPs as part of HIV prevention programming with FSWs. Reducing violence is expected to reduce vulnerability to HIV acquisition, and help women to work and live without fear of violence. TRIAL REGISTRATION: Clinical Trials NCT02807259 Jun 24 2016 (retrospectively registered).

Fertility intentions, power relations and condom use within intimate and other non-paying partnerships of women in sex work in Bagalkot District, South India.

This study aimed to: (1) examine the relationship between interpersonal as well as social-demographic, cultural and structural factors, and condom non-use by sex workers' main intimate or other non-paying male sex partners (NPPs), as reported by a sample of sex workers (SWs); and (2) understand HIV/sexually transmitted infections (STIs) risk (e.g., numbers of sexual partners; condom use with different partners) among couples comprised of a sub-set of SWs and their NPPs. Bivariate and multivariable logistic regression was used to identify factors associated with condom non-use at last sex by the main NPP, as reported by SWs. Adjusted odds ratios and 95% confidence intervals are reported (AOR[95%CIs]). Data were drawn from cross-sectional surveys in Bagalkot District, Karnataka State, South India. Responses by SWs whose main NPPs agreed to enrol in the study and the main NPP enroled were linked; these responses by couples (pairs of SWs and NPPs) were examined to assess sexual risk for HIV/STIs. Overall, this study included 257 SWs and 76 NPPs. The data from 67 couples (88.2%) could be linked. In over a quarter of partnerships, at least one (SW or NPP) partner reported having another type of partner besides each other (and clients of SWs). In multivariable analysis, significantly increased odds of condom non-use at last sex with the main NPP were found for the following key factors: planning to have a child with their main NPP (AOR = 3.71[1.44-9.58]); and having decisions about condom use made by their main NPP (AOR = 9.87[4.03-24.16]) or both equally (AOR = 3.18[1.39-7.80]) (versus by the SWs herself). Our study highlights the potential risk for HIV/STI acquisition and transmission between NPPs and SWs, and between NPPs and their non-SWs wives and other sex partners. Study results underscore the need for HIV/STI prevention approaches that incorporate informed decision-making about childbearing and parenting, and empowerment strategies for SWs in the context of their relationships with NPPs.

Distribution of uranium concentration in groundwater samples from the Peddagattu/Nambapur and Seripally regions using laser fluorimetry.

Uranium is a naturally occurring element, which is widespread in nature. It is found in low levels within all rocks, soils and water. Peddagattu and Seripally areas of Nalgonda district, Andhra Pradesh, India were known as a rich uranium mineralised zone. Atomic mineral division and Baba Atomic Research Center proposed a uranium mine in this area. This study was carried out to know the distribution of uranium concentration in the groundwater samples by using laser fluorimetry. The observation reveals that the uranium concentration in the groundwater of this region ranges from 0.6 to 521.15 ppb. About 43 % of the groundwater samples had the uranium concentration above the standards set by United States Environmental Protection Agency (30 ppb).

Risky Behaviors among HIV-Positive Female Sex Workers in Northern Karnataka, India.

Purpose. Little is known about the risky sexual behaviors of HIV-positive female sex workers (FSWs) in the developing world, which is critical for programmatic purposes. This study aims to shed light on their condom use with regular clients as well as husband/cohabiting partner, a first in India. Methods. Multivariate logistic regression analyses for consistent condom use with regular clients and husband/cohabiting partner are conducted for the sample of 606 HIV-positive FSWs. Results. Older FSWs are 90% less likely and nonmobile FSWs are 70% less likely to consistently use condoms. FSWs on ART are 3.84 times more likely to use condoms. Additionally, FSWs who changed their occupation after HIV diagnosis are 70% less likely to use condoms. FSWs who are currently cohabiting are more likely to consistently use condoms with repeat clients and are 3.22 times more likely to do so if they have felt stigma associated with being HIV-positive. FSWs who have multiple repeat clients, and who do not know the sexual behavior of these clients, are more likely to use condoms consistently. Conclusion. This study would help inform programs to target the following particularly vulnerable HIV-positive FSWs: those who are older, those who changed their occupation post-HIV diagnosis, and those who are nonmobile.

Characterizing sexual histories of women before formal sex-work in south India from a cross-sectional survey: implications for HIV/STI prevention.

BACKGROUND: Interventions designed to prevent HIV and STIs in female sex-workers (FSWs) reach women after they formally enter the sex-trade. We aimed to characterize the pattern of sexual behaviour among FSWs from first-sex to when they identify as sex-workers (transition period) in a region with traditional (historically characterized by dedication into sex-work at first-sex) and non-traditional forms of sex-work. METHODS: We conducted a cross-sectional survey of 246 traditional and 765 non-traditional FSWs across three districts in Karnataka, India. We performed univariate and multivariate logistic regression to profile FSWs most likely to engage in a commercial first-sex before identifying as a sex-worker. Sexual life-course patterns were distinguished using univariate and multivariate linear regression based on key events associated with length of transition period. RESULTS: Overall, 266 FSWs experienced a commercial first-sex, of whom 45.9% (95% CI: 38.2,53.7) continued a long-term relationship with the first partner. In adjusted analysis, traditional FSWs were more likely to experience a commercial first-sex (AOR 52.5, 95% CI: 27.4,100.7). The average transition time was 8.8 years (SD 3.9), but there was considerable variability between respondents. Among women who experienced a commercial first-sex, a slower transition was independently associated with non-traditional sex-work, the presence of long-term partnerships during the transition period, and ongoing partnerships at time of entry into sex-work. In the absence of a commercial first-sex, a faster transition was associated with traditional sex-work and the dissolution of long-term partnerships, while a slower transition was associated with the presence of long-term partnerships and widowhood. Only 18.5% (95% CI: 12.7,26.2) and 47.3% (95% CI: 32.7,62.3) of women reported 'always' condom use with their long-term and occasional partners during the transition period, respectively. CONCLUSIONS: FSWs identify as sex-workers several years after becoming sexually active, even when the first-sex is commercial in nature. Long-term partnerships are common after a commercial first-sex, and are associated with a delay in formally entering the sex-trade. The findings call for a better understanding of HIV/STI risk before FSWs identify as sex-workers, and an adaptive programme to reach this period of vulnerability.

The Female Sex Work Industry in a District of India in the Context of HIV Prevention.

HIV prevalence in India remains high among female sex workers. This paper presents the main findings of a qualitative study of the modes of operation of female sex work in Belgaum district, Karnataka, India, incorporating fifty interviews with sex workers. Thirteen sex work settings (distinguished by sex workers' main places of solicitation and sex) are identified. In addition to previously documented brothel, lodge, street, dhaba (highway restaurant), and highway-based sex workers, under-researched or newly emerging sex worker categories are identified, including phone-based sex workers, parlour girls, and agricultural workers. Women working in brothels, lodges, dhabas, and on highways describe factors that put them at high HIV risk. Of these, dhaba and highway-based sex workers are poorly covered by existing interventions. The paper examines the HIV-related vulnerability factors specific to each sex work setting. The modes of operation and HIV-vulnerabilities of sex work settings identified in this paper have important implications for the local programme.

The Intersection between Sex Work and Reproductive Health in Northern Karnataka, India: Identifying Gaps and Opportunities in the Context of HIV Prevention.

Objective. To examine the reproductive health practices of female sex workers (FSWs) in the context of an HIV prevention program in Karnataka, India. Methods. Data obtained from a survey of 1,011 FSWs registered with an HIV prevention program. We examined reproductive health indicators, and performed multivariate logistic regression among primiparous FSWs to assess sex work during pregnancy and antenatal HIV testing. Results. Among primiparous FSWs (N = 251), 92.0% continued sex work during pregnancy, and 55.4% received antenatal HIV testing. A longer duration in sex work (AOR 2.7, 95% CI: 1.0-7.5), rural residence (AOR 3.3, 95% CI: 1.2-8.9), and antenatal HIV testing (AOR 6.3, 95% CI: 2.0-20.1) were associated with continued sex work during pregnancy. Older FSWs (age >25 years, AOR 0.12, 95% CI: 0.05-0.33), who delivered at home (AOR 0.14, 95% CI: 0.09-0.34), were least likely to receive antenatal HIV testing. Antenatal HIV testing was associated with awareness of methods to prevent vertical HIV transmission (AOR 3.9, 95% CI: 1.9-14.1). Conclusions. Antenatal HIV testing remains low in the context of ongoing sex work during pregnancy. Existing HIV prevention programs are well positioned to immediately integrate reproductive health care with HIV interventions targeted to FSWs.