Differential effects of RGS proteins on Gαq and Gα11 activity

Heterotrimeric G proteins play a pivotal role in GPCR signalling; they link receptors to intracellular effectors and their inactivation by RGS proteins is a key factor in resetting the pathway following stimulation. The precise GPCR:G protein:RGS combination determines the nature and duration of the response. Investigating the activity of particular combinations is difficult in cells which contain multiples of each component. We have therefore utilised a previously characterised yeast system to express mammalian proteins in isolation. Human Gαq and Gα11 spontaneously activated the yeast pheromone-response pathway by a mechanism which required the formation of Gα-GTP. This provided an assay for the specific activity of human RGS proteins. RGS1, RGS2, RGS3 and RGS4 inhibited the spontaneous activity of both Gαq and Gα11 but, in contrast, RGS5 and RGS16 were much less effective against Gα11 than Gαq. Interestingly, RGS2 and RGS3 were able to inhibit signalling from the constitutively active Gαq QL/Gα11 QL mutants, confirming the GAP-independent activity of these RGS proteins. To determine if the RGS-Gα specificity was maintained under conditions of GPCR stimulation, minor modifications to the C-terminus of Gαq/Gα11 enabled coupling to an endogenous receptor. RGS2 and RGS3 were effective inhibitors of both Gα subunits even at high levels of receptor stimulation, emphasising their GAP-independent activity. At low levels of stimulation RGS5 and RGS16 retained their differential Gα activity, further highlighting that RGS proteins can discriminate between two very closely related Gα subunits

The effect of social categorization on trust decisions in a trust game paradigm

This study investigates whether participants use categorical or individual knowledge about others in order to make cooperative decisions in an adaptation of the trust game paradigm. Concretely, participants had to choose whether to cooperate or not with black and white unknown partners as a function of expected partners’ reciprocity rates. Reciprocity rates were manipulated by associating three out of four members of an ethnic group (blacks or whites consistent members) with high (or low) reciprocity rates, while the remaining member of the ethnic group is associated with the reciprocity of the other ethnic group (inconsistent member). Results show opposite performance’s patterns for white and black partners. Participants seemed to categorize white partners, by making the same cooperation decision with all the partners, that is, they cooperated equally with consistent and inconsistent white partners. However, this effect was not found for black partners, suggesting a tendency to individuate them. Results are discussed in light of the implications of these categorization-individuation processes for intergroup relations and cooperative economic behavior.This research was financially supported by the Spanish Ministry of Education, with research grants (PSI2013-45678-P and PSI2014-52764-P) to RRB and JL

Description and evaluation of an EBM curriculum using a block rotation

BACKGROUND: While previous authors have emphasized the importance of integrating and reinforcing evidence-based medicine (EBM) skills in residency, there are few published examples of such curricula. We designed an EBM curriculum to train family practice interns in essential EBM skills for information mastery using clinical questions generated by the family practice inpatient service. We sought to evaluate the impact of this curriculum on interns, residents, and faculty. METHODS: Interns (n = 13) were asked to self-assess their level of confidence in basic EBM skills before and after their 2-week EBM rotation. Residents (n = 21) and faculty (n = 12) were asked to assess how often the answers provided by the EBM intern to the inpatient service changed medical care. In addition, residents were asked to report how often they used their EBM skills and how often EBM concepts and tools were used in teaching by senior residents and faculty. Faculty were asked if the EBM curriculum had increased their use of EBM in practice and in teaching. RESULTS: Interns significantly increased their confidence over the course of the rotation. Residents and faculty felt that the answers provided by the EBM intern provided useful information and led to changes in patient care. Faculty reported incorporating EBM into their teaching (92%) and practice (75%). Residents reported applying the EBM skills they learned to patient care (86%) and that these skills were reinforced in the teaching they received outside of the rotation (81%). All residents and 11 of 12 faculty felt that the EBM curriculum had improved patient care. CONCLUSIONS: To our knowledge, this is the first published EBM curriculum using an individual block rotation format. As such, it may provide an alternative model for teaching and incorporating EBM into a residency program

The political, research, programmatic, and social responses to adolescent sexual and reproductive health and rights in the 25 years since the International Conference on Population and Development

Among the ground-breaking achievements of the International Conference on Population and Development (ICPD) was its call to place adolescent sexual and reproductive health (ASRH) on global health and development agendas. This article reviews progressmade in low- and middle-income countries in the 25 years since the ICPD in six areas central to ASRH-adolescent pregnancy, HIV, child marriage, violence against women and girls, female genital mutilation, and menstrual hygiene and health. It also examines the ICPD's contribution to the progress made. The article presents epidemiologic levels and trends; political, research, programmatic and social responses; and factors that helped or hindered progress. To do so, it draws on research evidence and programmatic experience and the expertise and experiences of a wide number of individuals, including youth leaders, in numerous countries and organizations. Overall, looking across the six health topics over a 25-year trajectory, there has been great progress at the global and regional levels in putting adolescent health, and especially adolescent sexual and reproductive health and rights, higher on the agenda, raising investment in this area, building the epidemiologic and evidence-base, and setting norms to guide investment and action. At the national level, too, there has been progress in formulating laws and policies, developing strategies and programs and executing them, and engaging communities and societies in moving the agenda forward. Still, progress has been uneven across issues and geography. Furthermore, it has raced ahead sometimes and has stalled at others. The ICPD's Plan of Action contributed to the progress made in ASRH not just because of its bold call in 1994 but also because it provided a springboard for advocacy, investment, action, and research that remains important to this day. (C) 2019 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine

Conducting High-Value Secondary Dataset Analysis: An Introductory Guide and Resources

Secondary analyses of large datasets provide a mechanism for researchers to address high impact questions that would otherwise be prohibitively expensive and time-consuming to study. This paper presents a guide to assist investigators interested in conducting secondary data analysis, including advice on the process of successful secondary data analysis as well as a brief summary of high-value datasets and online resources for researchers, including the SGIM dataset compendium (www.sgim.org/go/datasets). The same basic research principles that apply to primary data analysis apply to secondary data analysis, including the development of a clear and clinically relevant research question, study sample, appropriate measures, and a thoughtful analytic approach. A real-world case description illustrates key steps: (1) define your research topic and question; (2) select a dataset; (3) get to know your dataset; and (4) structure your analysis and presentation of findings in a way that is clinically meaningful. Secondary dataset analysis is a well-established methodology. Secondary analysis is particularly valuable for junior investigators, who have limited time and resources to demonstrate expertise and productivity

Sexual Abuse-Current Medico-legal, Forensic and Psychiatric Aspects

Abstract Violence against women and minors is a worldwide problem that has not yet been sufficiently acknowledged. There are many obstacles especially when sexual abuses have to be evaluated. These problems are present both when victims of sexual abuse are evaluated and when sex offenders are dealt with, especially when the offenders are juvenile sex offenders (JSO). These issues give cause for great concern about prognosis, and the resulting psychosocial implications, and call for a special effort from the scientific community in identifying appropriate prevention and treatment methods. This chapter is divided into two parts. The first part deals with the forensic and psychiatric features, such as diagnostic and therapeutic/rehabilitative strategies for JSO, while the second part analyzes the legal–medicine aspects related to rape/sexual assault in a European context

Effects of backpacking holidays in Australia on alcohol, tobacco and drug use of UK residents

BACKGROUND: Whilst alcohol and drug use among young people is known to escalate during short holidays and working breaks in international nightlife resorts, little empirical data are available on the impact of longer backpacking holidays on substance use. Here we examine changes in alcohol, tobacco and drug use when UK residents go backpacking in Australia. METHODS: Matched information on alcohol and drug use in Australia and the UK was collected through a cross sectional cohort study of 1008 UK nationals aged 18–35 years, holidaying in Sydney or Cairns, Australia, during 2005. RESULTS: The use of alcohol and other drugs by UK backpackers visiting Australia was common with use of illicit drugs being substantially higher than in peers of the same age in their home country. Individuals showed a significant increase in frequency of alcohol consumption in Australia compared to their behaviour in the UK with the proportion drinking five or more times per week rising from 20.7% (UK) to 40.3% (Australia). Relatively few individuals were recruited into drug use in Australia (3.0%, cannabis; 2.7% ecstasy; 0.7%, methamphetamine). However, over half of the sample (55.0%) used at least one illicit drug when backpacking. Risk factors for illicit drug use while backpacking were being regular club goers, being male, Sydney based, travelling without a partner or spouse, having been in Australia more than four weeks, Australia being the only destination on their vacation and drinking or smoking five or more days a week. CONCLUSION: As countries actively seek to attract more international backpacker tourists, interventions must be developed that target this population's risk behaviours. Developing messages on drunkenness and other drug use specifically for backpackers could help minimise their health risks directly (e.g. adverse drug reactions) and indirectly (e.g. accidents and violence) as well as negative impacts on the host country

Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals