Anterior Insular Cortex is Critical for the Propensity to Relapse Following Punishment-Imposed Abstinence of Alcohol Seeking.

Humans with alcohol use disorder typically abstain because of the negative consequences associated with excessive drinking, and exposure to contexts previously associated with alcohol use can trigger relapse. We used a rat model that captures a characteristic of this human condition: namely voluntary abstinence from alcohol use because of contingent punishment. There is substantial variability in the propensity to relapse following extended periods of abstinence, and this is a critical feature preventing the successful treatment of alcohol use disorder. Here we examined relapse following acute or prolonged abstinence. In male alcohol preferring P rats, we found an increased propensity to relapse in Context B, the punishment context after prolonged abstinence. Next, we found that neither alcohol intake history nor the motivational strength of alcohol predicted the propensity to relapse. We next examined the putative circuitry of context-induced relapse to alcohol seeking following prolonged abstinence using Fos as a marker of neuronal activation. The anterior insular cortex (AI) was the only brain region examined where Fos expression correlated with alcohol seeking behavior in Context B after prolonged abstinence. Finally, we used local infusion of GABAA and GABAB receptor agonists (muscimol + baclofen) to show a causal role of the AI in context-induced relapse in Context B, the punishment context after prolonged abstinence. Our results show that there is substantial individual variability in the propensity to relapse in the punishment-associated context after prolonged abstinence, and this is mediated by activity in the AI.SIGNIFICANCE STATEMENT A key feature of alcohol use disorder is that sufferers show an enduring propensity to relapse throughout their lifetime. Relapse typically occurs despite the knowledge of adverse consequences including health complications or relationship breakdowns. Here we use a recently developed rodent model that recapitulates this behavior. After an extended period of abstinence, relapse propensity is markedly increased in the "adverse consequence" environment, akin to humans with alcohol use disorder relapsing in the face of adversity. From a circuitry perspective, we demonstrate a causal role of the anterior insular cortex in relapse to alcohol seeking after extended abstinence following punishment imposed voluntary cessation of alcohol use.

How can we objectively categorise partnership type? A novel classification of population survey data to inform epidemiological research and clinical practice.

BACKGROUND: Partnership type is a determinant of STI risk; yet, it is poorly and inconsistently recorded in clinical practice and research. We identify a novel, empirical-based categorisation of partnership type, and examine whether reporting STI diagnoses varies by the resulting typologies. METHODS: Analyses of probability survey data collected from 15 162 people aged 16-74 who participated in Britain's third National Survey of Sexual Attitudes and Lifestyles were undertaken during 2010-2012. Computer-assisted self-interviews asked about participants' ≤3 most recent partners (N=14 322 partners/past year). Analysis of variance and regression tested for differences in partnership duration and perceived likelihood of sex again across 21 'partnership progression types' (PPTs) derived from relationship status at first and most recent sex. Multivariable regression examined the association between reporting STI diagnoses and partnership type(s) net of age and reported partner numbers (all past year). RESULTS: The 21 PPTs were grouped into four summary types: 'cohabiting', 'now steady', 'casual' and 'ex-steady' according to the average duration and likelihood of sex again. 11 combinations of these summary types accounted for 94.5% of all men; 13 combinations accounted for 96.9% of all women. Reporting STI diagnoses varied by partnership-type combination, including after adjusting for age and partner numbers, for example, adjusted OR: 6.03 (95% CI 2.01 to 18.1) for men with two 'casual' and one 'now steady' partners versus men with one 'cohabiting' partner. CONCLUSIONS: This typology provides an objective method for measuring partnership type and demonstrates its importance in understanding STI risk, net of partner numbers. Epidemiological research and clinical practice should use these methods and results to maximise individual and public health benefit.

Painful sex (dyspareunia) in women: prevalence and associated factors in a British population probability survey.

OBJECTIVE: To estimate the prevalence of painful sex among women in Britain, and to explore associated sexual, relationship and health factors that should be considered in assessment. DESIGN: Multi-stage, clustered and stratified population probability sample survey, using computer-assisted self-interview. Sample frame was the British Postcode Address File. SETTING: Participants interviewed at home between 2010 and 2012. SAMPLE: A total of 15 162 adults aged 16-74 years (8869 women). Data reported from 6669 sexually active women. METHODS: Age-adjusted logistic regressions to examine associations between painful sex and indicators of sexual, relational, mental and physical health. MAIN OUTCOME MEASURE: Physical pain as a result of sex for ≥3 months in the past year, plus measures of symptom severity. RESULTS: Painful sex was reported by 7.5% (95% CI 6.7-8.3) of sexually active women, of whom one-quarter experienced symptoms very often or always, for ≥6 months, and causing distress. Reporting painful sex was strongly associated with other sexual function problems, notably vaginal dryness (age adjusted odds ratio 7.9; 6.17-10.12), anxiety about sex (6.34; 4.76-8.46) and lacking enjoyment in sex (6.12; 4.81-7.79). It was associated with sexual relationship factors [such as not sharing same level of interest in sex (2.56; 1.97-3.33)], as well as with adverse experiences such as non-volitional sex (2.17; 1.68-2.80). Associations were also found with measures of psychological and physical health, including depressive symptoms (1.68; 1.28-2.21). CONCLUSION: Painful sex is reported by a sizeable minority of women in Britain. Health professionals should be supported to undertake holistic assessment and treatment which takes account of the sexual, relationship and health context of symptoms. TWEETABLE ABSTRACT: Painful sex-reported by 7.5% of women in Britain-is linked to poorer sexual, physical, relational and mental health.

Conceptualizing Sexual Wellbeing: A Qualitative Investigation to Inform Development of a Measure (Natsal-SW).

Despite increasing scientific and policy interest in sexual wellbeing, it remains poorly conceptualized. Many studies purporting to measure it instead measure related but distinct concepts, such as sexual satisfaction. This lack of conceptual clarity impedes understanding, measuring, and improving sexual wellbeing. We present qualitative research from multi-stage, mixed-methods work to develop a new measure of sexual wellbeing (Natsal-SW) for the fourth British National Survey of Sexual Attitudes & Lifestyles. Literature review and discussion generated a conceptual framework with seven proposed domains: respect, self-esteem, comfort, self-determination, safety and security, forgiveness, and resilience. Semi-structured interviews with 40 adults aged 18-64 then explored whether and how these domains aligned with participants' own understandings, experiences, and language of sexual wellbeing. Data were analyzed thematically. Participants conceptualized sexual wellbeing as distinct from sexual satisfaction and sexual health and as multidimensional, dynamic, and socially and structurally influenced. All seven proposed domains resonated with accounts of sexual wellbeing as a general construct. The personal salience of different domains and their dimensions varied between individuals (especially by gender and sexual orientation) and fluctuated individually over time. This study clarifies dimensions of domains that participants considered important, providing an empirical basis to inform development of a new measure of sexual wellbeing.

Salivary Testosterone and Sexual Function and Behavior in Men and Women: Findings from the Third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

Using data from the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) we examined associations between salivary testosterone (Sal-T) and sexual function and behavior. Single morning saliva samples were self-collected from a subsample of participants aged 18-74 years and analyzed using mass spectrometry. 1,599 men and 2,123 women were included in the analysis (40.6% of those invited to provide a sample). We adjusted for confounders in a stepwise manner: in model 1 we adjusted for age only; model 2 for age, season and relationship status, and model 3 we added BMI and self-reported health. In the fully adjusted models, among men, Sal-T was positively associated with both partnered sex (vaginal sex and concurrent partners) and masturbation. Among women, Sal-T was positively associated with masturbation, the only association with partnered sex was with ever experience of same-sex sex. We found no clear association between Sal-T and sexual function. Our study contributes toward addressing the sparsity of data outside the laboratory on the differences between men and women in the relationship between T and sexual function and behavior. To our knowledge, this is the first population study, among men and women, using a mass spectrometry Sal-T assay to do so.

Does the number of doses matter? A qualitative study of HPV vaccination acceptability nested in a dose reduction trial in Tanzania.

BACKGROUND: The multi-dose regimen is a known barrier to successful human papillomavirus (HPV) vaccination. Emerging evidence suggests that one vaccine dose could protect against HPV. While there are clear advantages to a single dose schedule, beliefs about vaccine dosage in low and middle income countries (LMICs) are poorly understood. We investigated acceptability of dose-reduction among girls, and parents/guardians of girls, randomised to receive one, two or three doses in an HPV vaccine dose-reduction and immunobridging study (DoRIS trial) in Tanzania. METHODS: Semi-structured interviews with girls (n = 19), and parents/guardians of girls (n = 18), enrolled in the study and completing their vaccine course. RESULTS: Most participants said they entrusted decisions about the number of HPV vaccine doses to experts. Random allocation to the different dose groups did not feature highly in the decision to participate in the trial. Given a hypothetical choice, girls generally said they would prefer fewer doses in order to avoid the pain of injections. Parental views were mixed, with most wanting whichever dose was most efficacious. Nonetheless, a few parents equated a higher number of doses with greater protection. CONCLUSION: Vaccine trials and programmes will need to employ careful messaging to explain that one dose offers sufficient protection against HPV should emerging evidence from ongoing dose-reduction clinical trials support this.

Salivary Testosterone Levels and Health Status in Men and Women in the British General Population: Findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

CONTEXT: Salivary T (Sal-T) measurement by liquid chromatography-tandem mass spectroscopy resents the opportunity to examine health correlates of Sal-T in a large-scale population survey. OBJECTIVE: This study sought to examine associations between Sal-T and health-related factors in men and women age 18-74 years. DESIGN AND SETTING: Morning saliva samples were obtained from participants in a cross-sectional probability-sample survey of the general British population (Natsal-3). Self-reported health and lifestyle questions were administered as part of a wider sexual health interview. PARTICIPANTS: Study participants included 1599 men and 2123 women. METHODS: Sal-T was measured using liquid chromatography-tandem mass spectroscopy. Linear regression was used to examine associations between health factors and mean Sal-T. RESULTS: In men, mean Sal-T was associated with a range of health factors after age adjustment, and showed a strong independent negative association with body mass index (BMI) in multivariable analysis. Men reporting cardiovascular disease or currently taking medication for depression had lower age-adjusted Sal-T, although there was no association with cardiovascular disease after adjustment for BMI. The decline in Sal-T with increasing age remained after adjustment for health-related factors. In women, Sal-T declined with increasing age; however, there were no age-independent associations with health-related factors or specific heath conditions with the exception of higher Sal-T in smokers. CONCLUSIONS: Sal-T levels were associated, independently of age, with a range of self-reported health markers, particularly BMI, in men but not women. The findings support the view that there is an age-related decline in Sal-T in men and women, which cannot be explained by an increase in ill health. Our results demonstrate the potential of Sal-T as a convenient measure of tissue androgen exposure for population research.

Problem solving in undergraduate medical students.

In recent years the systematic development of the skill of clinical reasoning has come to assume a high priority as an explicit aim of medical education. Clinical reasoning, it is contended, is the application of general reasoning and problem-solving skills to the specific knowledge base of medicine. The results presented in this paper constitute a preliminary study designed to investigate the ability of first-year medical undergraduates to solve abstract problems using a simple nonmedical knowledge base. Further studies are being carried out and will continue to extend this into the specific medical knowledge base area. The potential implications for medical education and the development of clinical reasoning are discussed.

Juvenile nephronophthisis and medullary cystic disease--the same disease (report of a large family with medullary cystic disease associated with gout and epilepsy).

A large family with medullary cystic disease is described to show that juvenile nephronophthisis and medullary cystic disease should not be differentiated by age of onset and type of inheritance. The age at diagnosis of six family members with medullary cystic disease ranged from 4-32 years, and age at death from renal failure or commencement of dialysis from 7-48 years. A mother of two children with renal failure in early childhood has histological evidence of medullary cystic disease with normal renal function. We suggest that juvenile nephronophthisis and medullary cystic disease are the same conditions and that the disease be classified as medullary cystic disease, autosomal dominant or recessive form. When undertaking genetic counselling in the parents of children with medullary cystic disease, we suggest that renal biopsy may need to be considered even if their renal function is normal. Three patients presented with gout, and the possibility of an association with medullary cystic disease should be considered when more than one member of a family develops gout. Two patients died of status epilepticus, and epilepsy is probably an added association of medullary cystic disease.

Heterosexual social competence, anxiety, avoidance and self-judged physical attractiveness.

The relationship between self-judged physical attractiveness and opposite-sex behavior was examined as part of a large survey on the interaction patterns of 963 college students. The findings suggest that a self-rated negative physical image is related to significantly high levels of heterosexual difficulties.