Altered Nuclear Expression of the Deubiquitylase BAP1 Cannot be Used as a Prognostic Marker for Canine Melanoma.

BRCA1-associated protein-1 (BAP1) is a nuclear localized deubiquitylating enzyme that belongs to the ubiquitin c-terminal hydrolase subfamily. The encoded protein is highly homologous between man and dogs, suggesting a functional significance preserved by evolution. BAP1 has multiple properties, including tumour suppressor activity. Loss of BAP1 function is implicated in the oncogenesis of several types of cancers including uveal, mucosal and some cutaneous melanomas in humans, as well as in mesothelioma. In this study we investigate the significance of BAP1 in canine melanoma. Nuclear BAP1 protein was detected in five canine oral melanoma cell lines using an antibody commonly used for analysis of human tissues. BAP1 loss of function mutations often lead to loss of nuclear BAP1 (nBAP1) expression in humans; this is associated with a poorer prognosis in uveal and mucosal melanoma. Therefore, as a prelude to a study evaluating the prognostic significance of nBAP1 expression in dogs, immunohistochemistry (IHC) was used to assess cases of canine melanoma for nBAP1 expression. In 89 cases where tumour cells were identified by melan-A labelling, 100% of tumour cells were positive for nBAP1 expression, including eight uveal tract and 29 oral mucosal melanomas. This finding indicates that BAP1 IHC cannot be used as a prognostic marker in canine uveal and mucosal melanoma. Moreover, this observation suggests that either BAP1 has a different functional significance in canine melanoma or that loss of BAP1 function is achieved by a different route. This is a novel finding that warrants further investigation to determine the comparative biological relevance.

Exploring the care provided to mothers and children by community health workers in South Africa: missed opportunities to provide comprehensive care.

BACKGROUND: Community health workers (CHWs) provide maternal and child health services to communities in many low and middle-income countries, including South Africa (SA). CHWs can improve access to important health interventions for isolated and vulnerable communities. In this study we explored the performance of CHWs providing maternal and child health services at household level and the quality of the CHW-mother interaction. METHODS: A qualitative study design was employed using observations and in-depth interviews to explore the content of household interactions, and experiences and perceptions of mothers and CHWs. Fifteen CHWs and 30 mothers/pregnant women were purposively selected in three rural districts of KwaZulu-Natal, SA. CHW household visits to mothers were observed and field notes taken, followed by in-depth interviews with mothers and CHWs. Observations and interviews were audio-recorded. We performed thematic analysis on transcribed discussions, and content analysis on observational data. RESULTS: CHWs provided appropriate and correct health information but there were important gaps in the content provided. Mothers expressed satisfaction with CHW visits and appreciation that CHWs understood their life experiences and therefore provided advice and support that was relevant and accessible. CHWs expressed concern that they did not have the knowledge required to undertake all activities in the household, and requested training and support from supervisors during household visits. CONCLUSIONS: Key building blocks for a successful CHW programme are in place to provide services for mothers and children in households but further training and supervision is required if the gaps in CHW knowledge and skills are to be filled.

Effect of sex and time to slaughter (transportation and lairage duration) on the levels of cortisol, creatine kinase and subsequent relationship with pork quality.

The study determined the effect of sex and time to slaughter on cortisol and creatine kinase levels, and pork quality in commercial crossbred pigs. Saliva samples were before collected transportation, on arrival at the abattoir, and after a 20 hour lairage period. Cortisol levels from saliva (SC), serum (SeC) and urine (UC) were determined. Creatine kinase (CK) levels were determined from serum samples. Fifteen boars vs. 15 gilts were immediately slaughtered on arrival (SOA), and the other 15 boars vs. 15 gilts were rested for 20 h before slaughter. Meat quality parameters were also determined. In both sexes, SC significantly increased in response to time to slaughter. There was a significant interaction of sex and time to slaughter on SeC. Gilts had higher CK levels and lower muscle L* values than boars. There were correlations among baseline SC, SeC, UC and most meat quality parameters. Time to slaughter influenced levels of SC, UC, CK and pork quality between boars and gilts.

Impact of stepping stones on incidence of HIV and HSV-2 and sexual behaviour in rural South Africa: cluster randomised controlled trial.

OBJECTIVE: To assess the impact of Stepping Stones, a HIV prevention programme, on incidence of HIV and herpes simplex type 2 (HSV-2) and sexual behaviour. DESIGN: Cluster randomised controlled trial. SETTING: 70 villages (clusters) in the Eastern Cape province of South Africa. PARTICIPANTS: 1360 men and 1416 women aged 15-26 years, who were mostly attending schools. INTERVENTION: Stepping Stones, a 50 hour programme, aims to improve sexual health by using participatory learning approaches to build knowledge, risk awareness, and communication skills and to stimulate critical reflection. Villages were randomised to receive either this or a three hour intervention on HIV and safer sex. Interviewers administered questionnaires at baseline and 12 and 24 months and blood was tested for HIV and HSV-2. PRIMARY OUTCOME MEASURE: incidence of HIV. Other outcomes: incidence of HSV-2, unwanted pregnancy, reported sexual practices, depression, and substance misuse. RESULTS: There was no evidence that Stepping Stones lowered the incidence of HIV (adjusted incidence rate ratio 0.95, 95% confidence interval 0.67 to 1.35). The programme was associated with a reduction of about 33% in the incidence of HSV-2 (0.67, 0.46 to 0.97; P=0.036)-that is, Stepping Stones reduced the number of new HSV-2 infections over a two year period by 34.9 (1.6 to 68.2) per 1000 people exposed. Stepping Stones significantly improved a number of reported risk behaviours in men, with a lower proportion of men reporting perpetration of intimate partner violence across two years of follow-up and less transactional sex and problem drinking at 12 months. In women desired behaviour changes were not reported and those in the Stepping Stones programme reported more transactional sex at 12 months. CONCLUSION: Stepping Stones did not reduce incidence of HIV but had an impact on several risk factors for HIV-notably, HSV-2 and perpetration of intimate partner violence. TRIAL REGISTRATION: Clinical Trials NCT00332878.

Factors associated with HIV sero-positivity in young, rural South African men.

OBJECTIVE: To describe factors associated with HIV infection in men aged 15-26 years. SETTING: Rural Eastern Cape Province, South Africa. SAMPLE: A total of 1277 sexually experienced Xhosa male volunteers from 70 villages participating in a cluster randomized controlled trial of an HIV behavioural intervention. Xhosas circumcise during manhood initiation rituals. DESIGN: Cross-sectional, analysis of the study's baseline interviews. MAIN MEASURE: HIV sero-status, sexual practices measured with an interviewer-administered questionnaire. RESULTS: About 2% of the men were HIV positive. A logistic regression model showed HIV positivity to be associated with age (OR 1.55; 95%CI 1.22-1.95), having made a woman pregnant (OR 2.93; 95% CI 1.28-6.68), having been circumcised (OR 0.40; 95% CI 0.16-0.98), and having had sex with a man (OR 3.61; 95% CI 1.0-13.0). CONCLUSIONS: Our findings provide further evidence to suggest that circumcision is protective. There was much heterosexual risk taking among men but only pregnancy (with its association with sexual frequency) predicted HIV sero-positivity. Although relatively rare, same-sex sexual experiences were a risk factor. Male-male sexual contact is rarely assessed in HIV research in Africa and almost never addressed in general HIV prevention programming. Our findings suggest that it should be given more attention.

Factors associated with HIV sero-status in young rural South African women: connections between intimate partner violence and HIV.

BACKGROUND: This paper aims to describe factors associated with HIV sero-status in young, rural South African women and the relationship between intimate partner violence (IPV) and HIV. METHODS: A total of 1295 sexually active female volunteers, aged 15-26, from 70 villages were recruited to participate in a cluster randomized controlled trial of an HIV behavioural intervention. The main measures were HIV sero-status, and IPV and sexual practices measured using a questionnaire administered during baseline interviews. RESULTS: About 12.4% of women had HIV and 26.6% had experienced more than one episode of physical or sexual IPV. After adjusting for age, HIV infection was associated with having three or more past year partners [odds ratio (OR) 2.39; 95% confidence interval (95% CI) 1.48-3.85], sex in past 3 months (OR 3.33; 95% CI 1.87-5.94), a partner three or more years older (OR 1.69; 95% CI 1.16-2.48), and a more educated partner (OR 1.91; 95% CI 1.30-2.78). IPV was associated with HIV in two-way analyses (OR 1.56; 95% CI 1.08-2.23), but the effect was non-significant after adjusting for HIV risk behaviours. The experience of IPV was strongly associated with past year partner numbers, time of last sex, and partner's education; it was also marginally associated with partner age difference. Adverse experiences in childhood, including sexual abuse, increased the likelihood of having more past year partners (OR 1.43; 95% CI 1.21-1.69). CONCLUSIONS: IPV was strongly associated with most of the identified HIV risk factors. Our findings provide further evidence of links between IPV and HIV among women and the importance of joint prevention.

A cluster randomized-controlled trial to determine the effectiveness of Stepping Stones in preventing HIV infections and promoting safer sexual behaviour amongst youth in the rural Eastern Cape, South Africa: trial design, methods and baseline findings.

OBJECTIVE: To describe the study design, methods and baseline findings of a behavioural intervention trial aimed at reducing HIV incidence. METHOD: A cluster randomized-controlled trial (RCT) conducted in 70 villages in rural South Africa. A behavioural intervention, Stepping Stones, was implemented in 35 communities in two workshops of 20 men and 20 women in each community who met for 17 sessions (50 h) over a period of 3-12 weeks. Individuals in the control arm communities attended a single session of about 3 h on HIV and safer sex. Impact assessment was conducted through two questionnaire and serological surveys at 12-month intervals. The primary outcome was HIV incidence and secondary measures included changes in knowledge, attitude and sexual behaviours. Qualitative research was also undertaken with 10 men and 10 women from two sites receiving the intervention (one rural and one urban) and five men and five women from one village in the control arm. They were interviewed individually three times prior to the workshops and then 9-12 months later. RESULTS: A total of 2776 participants (1409 intervention and 1367 control) were enrolled at baseline and had an interview, and HIV sero-status was established. HIV baseline prevalence rates in women were 9.8% in the intervention arm and 12.8% in the control arm. In men the prevalence was 1.7% in the intervention arm and 2.1% in the control arm. Demographic and behavioural characteristics were similar in the two arms. In the intervention groups 59.9% of participants attended more than 75% of the sessions. In the control group 66.3% attended the control session. CONCLUSION: This is the third RCT to be conducted in sub-Saharan Africa evaluating a behavioural intervention using HIV incidence as a primary outcome. It is of particular interest as the intervention in question is used in many developing countries. There is good baseline comparability between the study arms and the process data on the workshops suggested that the interventions were feasible and adequately implemented.