An Intrinsically Disordered Region of the Acetyltransferase p300 with Similarity to Prion-Like Domains Plays a Role in Aggregation

Several human diseases including neurodegenerative disorders and cancer are associated with abnormal accumulation and aggregation of misfolded proteins. Proteins with high tendency to aggregate include the p53 gene product, TAU and alpha synuclein. The potential toxicity of aberrantly folded proteins is limited via their transport into intracellular sub-compartments, the aggresomes, where misfolded proteins are stored or cleared via autophagy. We have identified a region of the acetyltransferase p300 that is highly disordered and displays similarities with prion-like domains. We show that this region is encoded as an alternative spliced variant independently of the acetyltransferase domain, and provides an interaction interface for various misfolded proteins, promoting their aggregation. p300 enhances aggregation of TAU and of p53 and is a component of cellular aggregates in both tissue culture cells and in alpha-synuclein positive Lewy bodies of patients affected by Parkinson disease. Down-regulation of p300 impairs aggresome formation and enhances cytotoxicity induced by misfolded protein stress. These data unravel a novel activity of p300, offer new insights into the function of disordered domains and implicate p300 in pathological aggregation that occurs in neurodegeneration and cancer

HIV Risk Behavior Self-Report Reliability at Different Recall Periods

Few studies have investigated the optimal length of recall period for self-report of sex and drug-use behaviors. This meta-analysis of 28 studies examined the test-retest reliability of three commonly used recall periods: 1, 3, and 6 months. All three recall periods demonstrated acceptable test-retest reliability, with the exception of recall of needle sharing behaviors and 6-months recall of some sex behaviors. For most sex behaviors, a recall period of 3 months was found to produce the most reliable data; however, 6 months was best for recalling number of sex partners. Overall, shorter periods were found to be more reliable for recall of drug-use behaviors, though the most reliable length of recall period varied for different types of drugs. Implications of the findings and future directions for research are discussed

Initial Commitment to Pre-Exposure Prophylaxis and Circumcision for HIV Prevention amongst Indian Truck Drivers

Studies of HIV prevention interventions such as pre-exposure prophylaxis (PREP) and circumcision in India are limited. The present study sought to investigate Indian truck-drivers initial commitment to PREP and circumcision utilizing the AIDS Risk Reduction Model. Ninety truck-drivers completed an in-depth qualitative interview and provided a blood sample for HIV and HSV-2 testing. Truck-drivers exhibited low levels of initial commitment towards PREP and even lower for circumcision. However, potential leverage points for increasing commitment were realized in fear of infecting family rather than self, self-perceptions of risk, and for PREP focusing on cultural beliefs towards medication and physicians. Cost was a major barrier to both HIV prevention interventions. Despite these barriers, our findings suggest that the ARRM may be useful in identifying several leverage points that may be used by peers, health care providers and public health field workers to enhance initial commitment to novel HIV prevention interventions in India

Sexual behavior and experience of sexual coercion among secondary school students in three states in North Eastern Nigeria

BACKGROUND: Interest in the reproductive health of adolescents continues to grow throughout the world. Few studies had explored the reproductive health knowledge, sexual behavior and experience of sexual coercion among secondary school students in North Eastern states of Nigeria. The objectives of this descriptive survey were to collect data to plan appropriate interventions that meet the reproductive health knowledge, service and skills needs of students in Bauchi, Borno and Gombe states. METHODS: Face-to-face interviews were conducted for 624 consenting students who were randomly selected from eighteen secondary schools using an 83-item structured questionnaire. Data were collected on demographic profile, reproductive health knowledge, sexual behavior and experience of sexual coercion. RESULTS: The mean age of the respondents was 16.5 years. There were slightly more males (52%) than females (48%). Students' knowledge about reproductive health was generally low even though girls had better knowledge than boys. Thirteen percent of the entire students had had sexual experience; significantly more males (19%) than females (6%) had done so (p < 0.001). Among boys the age at sexual debut ranged from 10–26 with a mean of 15.7 and median of 16. By contrast, the age at first sex among girls ranged from 10 to 18 years with a mean and median of 16.1 and 17 years respectively. Only 24% of those who were sexually active used a condom during their last sexual encounter. Overall 11% of the students reported that they had been tricked into having sex, 9% had experienced unwanted touch of breast and backside, and 5% reported rape. CONCLUSION: Students low reproductive health knowledge and involvement in risky sexual activities predispose them to undesirable reproductive health outcomes

Normative Beliefs and Sexual Risk in China

We examined normative beliefs about multiple sexual partners and social status in China and their association with risky sexual behaviors and sexually transmitted infections (STIs). Self-reported and biological markers of sexual risk were examined among 3,716 market vendors from a city in eastern China. Men who were older or with less education believed having multiple sexual partners was linked to higher social status. Adjusting for demographic characteristics, normative beliefs were significantly associated with having multiple sexual partners, while having multiple sexual partners was significantly associated with STIs. Normative beliefs regarding sexual behaviors may play an important role in individual risk behaviors. Future HIV/STI interventions must address community beliefs about the positive meaning of sexual risks, particularly among men with traditional beliefs about gender roles

The socio-demographic patterning of sexual risk behaviour: a survey of young men in Finland and Estonia

<p>Abstract</p> <p>Background</p> <p>Sexually transmitted infections (STIs) among the youth are an increasing challenge for public health in Europe. This study provided estimates of men's (18–25 years) sexual risk behaviour and self-reported STIs and their socio-demographic patterning in Finland and Estonia; two countries that are geographically close, but have very different STI epidemics.</p> <p>Method</p> <p>Nationally representative cross-sectional population surveys with comparable survey questions were used. Data from self-administered questionnaires for 1765 men aged 18–25 years in Finland (85% of the age cohort was included in the sampling frame, 95% of the sample responded) and 748 in Estonia, with a response rate of 43% respectively, were analysed. Socio-demographic patterning of multiple partners, condom use and self-reported STIs are presented was studied using multiple logistic regression analysis.</p> <p>Results</p> <p>The main findings focus on associations found within each country. In Finland, higher age, low education and to a lesser extent relationship with a non-steady partner increased the likelihood of reporting multiple lifetime-partners, while in Estonia only higher age and low education revealed this effect. In relation to unprotected intercourse, in Finland, higher age, low education and relationship status with a steady partner increased the likelihood of reporting unprotected intercourse. In Estonia, the same was observed only for relationship status. In Finland the likelihood of self-reported STIs increased by older age and lower education and decreased by being with a non-steady partner, while in Estonia, a non-significant increase in self-reported STIs was observed only in the older age group.</p> <p>Conclusion</p> <p>A clear socio-demographic patterning for sexual behaviour and self-reported STIs was revealed in Finland, but a less consistent trend was seen in Estonia. The findings of this study suggest that prevention strategies should focus in Finland on less educated singles and in Estonia on young men generally.</p

Irinotecan for relapsed Wilms tumor in pediatric patients: SIOP experience and review of the literatureA report from the SIOP Renal Tumor Study Group

While irinotecan has been studied in various pediatric solid tumors, its potential role in Wilms tumor (WT) is less clear. We evaluated response and outcome of irinotecan‐containing regimens in relapsed WT and compared our results to the available literature. Among 14 evaluable patients, one complete response (CR) and two partial responses (PRs) were observed in patients with initial intermediate‐risk (CR and PR) and blastemal‐type histologies (PR). Two patients were alive at last follow‐up showing no evidence of disease. Our results and the reviewed literature suggest some effectiveness of irinotecan in the setting of relapsed WT

Positive deviance control-case life history: a method to develop grounded hypotheses about successful long-term avoidance of infection

<p>Abstract</p> <p>Background</p> <p>Prevalence rates for long-term injection drug users in some localities surpass 60% for HIV and 80% for HCV. We describe methods for developing grounded hypotheses about how some injectors avoid infection with either virus.</p> <p>Methods</p> <p>Subjects: 25 drug injectors who have injected drugs 8 – 15 years in New York City. 17 remain without antibody to either HIV or HCV; 3 are double-positives; and 5 are positive for HCV but not HIV. "Staying Safe" methodology compares serostatus groups using detailed biographical timelines and narratives; and information about how subjects maintain access to physical resources and social support; their strategies and tactics to remain safe; how they handle problems of addiction and demands by drug dealers and other drug users; and how their behaviors and strategies do or do not become socially-embedded practices. Grounded theory and life-history analysis techniques compare and contrast doubly-uninfected with those infected with both viruses or only with HCV.</p> <p>Results</p> <p>Themes and initial hypotheses emerging from analyses included two master hypotheses that, if confirmed, should help shape preventive interventions: 1) Staying uninfected is not simply a question of social structure or social position. It involves agency by drug injectors, including sustained hard work and adaptation to changing circumstances. 2) Multiple intentionalities contribute to remaining uninfected. These conscious goals include balancing one's need for drugs and one's income; developing ways to avoid drug withdrawal sickness; avoiding situations where other drug users importune you to share drugs; and avoiding HIV (and perhaps HCV) infection. Thus, focusing on a single goal in prevention might be sub-optimal.</p> <p>Other hypotheses specify mechanisms of enacting these intentionalities. One example is finding ways to avoid extreme social ostracism.</p> <p>Conclusion</p> <p>We have identified strategies and tactics that some doubly-uninfected IDUs have developed to stay safe. Staying Safe methodology develops grounded hypotheses. These can be tested through cohort studies of incidence and prevention trials of hypothesis-based programs to help drug injectors make their injection and sexual careers safer for themselves and others. This positive deviance control-case life history method might be used to study avoiding other infections like genital herpes among sex workers.</p

Electronic gaming machine characteristics: it's the little things that count

A range of gamblers, from low-frequency social gamblers through to problem gamblers in treatment, participated in focus groups discussing the characteristics of Electronic Gaming Machines (EGMs) that they found attractive. Analyses of the resulting transcripts resulted in two groups of EGM characteristics being identified as important, one group associated with winning and one with betting. Overall, free spin features were identified in all groups as the most attractive characteristic of EGMS. Beyond that it was smaller win-related characteristics, and low-denomination machines with multiple playable lines that were associated with increased duration and intensity of gambling behaviour. The important characteristics were consistent across different levels of gamblers, with the key behavioural difference being a self-reported ‘expertise’, and ‘strategic’ approach to gambling amongst higher-frequency gamblers and problem gamblers in treatment. The key characteristics all occur frequently and result in more wins and extended gambling sessions. The patterns identified resonated with established behavioural principles, and with models describing the development of problem gambling and addictions more generally