The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Evo-devo of human adolescence: beyond disease models of early puberty

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research

Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

Impact of a workplace 'sit less, move more' program on efficiency-related outcomes of office employees.

BACKGROUND: Few studies have examined the impact of 'sit less, move more' interventions on workplace performance. This study assessed the short and mid-term impacts of and patterns of change within, a 19-week workplace web-based intervention (Walk@WorkSpain; W@WS; 2010-11) on employees´ presenteeism, mental well-being and lost work performance. METHODS: A site randomised control trial recruited employees at six Spanish university campuses (n = 264; 42 ± 10 years; 171 female), assigned by worksite and campus to an Intervention (IG; used W@WS; n = 129; 87 female) or an active Comparison group (A-CG; pedometer, paper diary and self-reported sitting time; n = 135; 84 female). A linear mixed model assessed changes between the baseline, ramping (8 weeks), maintenance (11 weeks) and follow-up (two months) phases for the IG versus A-CG on (i) % of lost work productivity (Work Limitations Questionnaire; WLQ); (ii) three scales for presenteeism (WLQ) assessing difficulty meeting scheduling demands (Time), performing cognitive and inter-personal tasks (Mental-Interpersonal) and decrements in meeting the quantity, quality and timeliness of completed work (Output); and (iii) mental well-being (Warwick-Edinburgh Mental Well-being Scale). T-tests assessed differences between groups for changes on the main outcomes. In the IG, a multivariate logistic regression model identified patterns of response according to baseline socio-demographic variables, physical activity and sitting time. RESULTS: There was a significant 2 (group) × 2 (program time points) interaction for the Time (F [3]=8.69, p = 0.005), Mental-Interpersonal (F [3]=10.01, p = 0.0185), Output scales for presenteeism (F [3]=8.56, p = 0.0357), and for % of lost work performance (F [3]=10.31, p = 0.0161). Presenteeism and lost performance rose significantly in both groups across all study time points; after baseline performance was consistently better in the IG than in the A-CG. Better performance was linked to employees being more active (Time, p = 0.041) and younger (Mental-interpersonal, p = 0.057; Output, p = 0.017). Higher total sitting time during nonworking days (Mental-interpersonal, p = 0.019) and lower sitting time during workdays (WLQ Index, p = 0.013) also improved performance. CONCLUSION: Versus an active comparison condition, a 'sit less, move more` workplace intervention effectively reduced an array of markers of lost workday productivity. TRIAL REGISTRATION: NCT02960750 ; Date of registration: 07/11/2016

“Keeping Moving”: factors associated with sedentary behaviour among older people recruited to an exercise promotion trial in general practice

Background Sedentary behaviour is detrimental to health, even in those who achieve recommended levels of physical activity. Efforts to increase physical activity in older people so that they reach beneficial levels have been disappointing. Reducing sedentary behaviour may improve health and be less demanding of older people, but it is not clear how to achieve this. We explored the characteristics of sedentary older people enrolled into an exercise promotion trial to gain insights about those who were sedentary but wanted to increase activity. Method Participants in the ProAct65+ trial (2009–2013) were categorised as sedentary or not using a self-report questionnaire. Demographic data, health status, self-rated function and physical test performance were examined for each group. 1104 participants aged 65 & over were included in the secondary analysis of trial data from older people recruited via general practice. Results were analysed using logistic regression with stepwise backward elimination. Results Three hundred eighty seven (35 %) of the study sample were characterised as sedentary. The likelihood of being categorised as sedentary increased with an abnormal BMI (25 kg/m2) (Odds Ratio 1.740, CI 1.248–2.425), ever smoking (OR 1.420, CI 1.042–1.934) and with every additional medication prescribed (OR 1.069, CI 1.016–1.124). Participants reporting better self-rated physical health (SF-12) were less likely to be sedentary; (OR 0.961, 0.936–0.987). Participants’ sedentary behaviour was not associated with gender, age, income, education, falls, functional fitness, quality of life or number of co-morbidities. Conclusion Some sedentary older adults will respond positively to an invitation to join an exercise study. Those who did so in this study had poor self-rated health, abnormal BMI, a history of smoking, and multiple medication use, and are therefore likely to benefit from an exercise intervention

The changing global distribution and prevalence of canine transmissible venereal tumour.

BACKGROUND: The canine transmissible venereal tumour (CTVT) is a contagious cancer that is naturally transmitted between dogs by the allogeneic transfer of living cancer cells during coitus. CTVT first arose several thousand years ago and has been reported in dog populations worldwide; however, its precise distribution patterns and prevalence remain unclear. RESULTS: We analysed historical literature and obtained CTVT prevalence information from 645 veterinarians and animal health workers in 109 countries in order to estimate CTVT's former and current global distribution and prevalence. This analysis confirmed that CTVT is endemic in at least 90 countries worldwide across all inhabited continents. CTVT is estimated to be present at a prevalence of one percent or more in dogs in at least 13 countries in South and Central America as well as in at least 11 countries in Africa and 8 countries in Asia. In the United States and Australia, CTVT was reported to be endemic only in remote indigenous communities. Comparison of current and historical reports of CTVT indicated that its prevalence has declined in Northern Europe, possibly due to changes in dog control laws during the nineteenth and twentieth centuries. Analysis of factors influencing CTVT prevalence showed that presence of free-roaming dogs was associated with increased CTVT prevalence, while dog spaying and neutering were associated with reduced CTVT prevalence. Our analysis indicated no gender bias for CTVT and we found no evidence that animals with CTVT frequently harbour concurrent infectious diseases. Vincristine was widely reported to be the most effective therapy for CTVT. CONCLUSIONS: Our results provide a survey of the current global distribution of CTVT, confirming that CTVT is endemic in at least 90 countries worldwide. Additionally, our analysis highlights factors that continue to modify CTVT's prevalence around the world and implicates free-roaming dogs as a reservoir for the disease. Our analysis also documents the disappearance of the disease from the United Kingdom during the twentieth century, which appears to have been an unintentional result of the introduction of dog control policies.This is the author's accepted manuscript. The final version of this article has been published by BioMed Central: http://www.biomedcentral.com/1746-6148/10/168

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function : a report from the COGENT consortium

CORRIGENDUM Molecular Psychiatry (2017) 22, 1651–1652 http://www.nature.com/articles/mp2017197.pdfThe complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (similar to 8M single-nucleotide polymorphisms (SNP) with minor allele frequency >= 1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (PPeer reviewe

Increasing efficacy of primary care-based counseling for diabetes prevention: Rationale and design of the ADAPT (Avoiding Diabetes Thru Action Plan Targeting) trial

<p>Abstract</p> <p>Background</p> <p>Studies have shown that lifestyle behavior changes are most effective to prevent onset of diabetes in high-risk patients. Primary care providers are charged with encouraging behavior change among their patients at risk for diabetes, yet the practice environment and training in primary care often do not support effective provider counseling. The goal of this study is to develop an electronic health record-embedded tool to facilitate shared patient-provider goal setting to promote behavioral change and prevent diabetes.</p> <p>Methods</p> <p>The ADAPT (Avoiding Diabetes Thru Action Plan Targeting) trial leverages an innovative system that integrates evidence-based interventions for behavioral change with already-existing technology to enhance primary care providers' effectiveness to counsel about lifestyle behavior changes. Using principles of behavior change theory, the multidisciplinary design team utilized in-depth interviews and <it>in vivo </it>usability testing to produce a prototype diabetes prevention counseling system embedded in the electronic health record.</p> <p>Results</p> <p>The core element of the tool is a streamlined, shared goal-setting module within the electronic health record system. The team then conducted a series of innovative, "near-live" usability testing simulations to refine the tool and enhance workflow integration. The system also incorporates a pre-encounter survey to elicit patients' behavior-change goals to help tailor patient-provider goal setting during the clinical encounter and to encourage shared decision making. Lastly, the patients interact with a website that collects their longitudinal behavior data and allows them to visualize their progress over time and compare their progress with other study members. The finalized ADAPT system is now being piloted in a small randomized control trial of providers using the system with prediabetes patients over a six-month period.</p> <p>Conclusions</p> <p>The ADAPT system combines the influential powers of shared goal setting and feedback, tailoring, modeling, contracting, reminders, and social comparisons to integrate evidence-based behavior-change principles into the electronic health record to maximize provider counseling efficacy during routine primary care clinical encounters. If successful, the ADAPT system may represent an adaptable and scalable technology-enabled behavior-change tool for all primary care providers.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT01473654">NCT01473654</a></p

P5A-Type ATPase Cta4p Is Essential for Ca2+ Transport in the Endoplasmic Reticulum of Schizosaccharomyces pombe

This study establishes the role of P5A-type Cta4 ATPase in Ca2+ sequestration in the endoplasmic reticulum by detecting an ATP-dependent, vanadate-sensitive and FCCP insensitive 45Ca2+-transport in fission yeast membranes isolated by cellular fractionation. Specifically, the Ca2+-ATPase transport activity was decreased in ER membranes isolated from cells lacking a cta4+ gene. Furthermore, a disruption of cta4+ resulted in 6-fold increase of intracellular Ca2+ levels, sensitivity towards accumulation of misfolded proteins in ER and ER stress, stimulation of the calcineurin phosphatase activity and vacuolar Ca2+ pumping. These data provide compelling biochemical evidence for a P5A-type Cta4 ATPase as an essential component of Ca2+ transport system and signaling network which regulate, in conjunction with calcineurin, the ER functionality in fission yeast