Structure of an Enclosed Dimer Formed by the Drosophila Period Protein

Period (PER) is the major transcription inhibitor in metazoan circadian clocks and lies at the center of several feedback loops that regulate gene expression. Dimerization of Drosophila PER influences nuclear translocation, repressor activity, and behavioral rhythms. The structure of a central, 346-residue PER fragment reveals two associated PAS (Per-Arnt-Sim) domains followed by a protruding α-helical extension (αF). A closed, pseudosymmetric dimer forms from a cross handshake interaction of the N-terminal PAS domain with αF of the opposing subunit. Strikingly, a shift of αF against the PAS β-sheet generates two alternative subunit interfaces in the dimer. Taken together with a previously reported PER structure in which αF extends, these data indicate that αF unlatches to switch association of PER with itself to its partner Timeless. The variable positions of the αF helix provide snapshots of a helix dissociation mechanism that has relevance to other PAS protein systems. Conservation of PER interaction residues among a family of PAS-AB-containing transcription factors suggests that contacts mediating closed PAS-AB dimers serve a general function

The Provider Perspective on Behavioral Health Care for Transgender and Gender NonConforming Individuals in the Central Great Plains: A Qualitative Study of Approaches and Needs

Purpose—Transgender and gender nonconforming (TGNC) individuals interact with mental health care systems at high rates and experience substantial barriers to care. Rural TGNC individuals face additional disparities in accessing appropriate mental health services. Little research has focused on the mental healthcare providers who work with TGNC individuals in underserved areas. The current study sought to describe the mental health care services delivered by providers perceived as affirming by TGNC community members in the Central Great Plains. Methods—We conducted qualitative interviews with 10 providers to understand how providers seek cultural competency and conceptualize and work with their TGNC clients given the barriers to care. Results—Providers held diverse theoretical orientations and described challenges to working with TGNC clients including the impact of stigma and marginalization and financial and structural barriers to care. Emphasis was placed on individualizing care, helping clients manage stigma and build resiliency, connecting clients to resources (when available) and support systems, and navigating the intersections of physical health care and mental health care such as writing letters for medical transition. Providers largely educated themselves on TGNC topics and had previous experience working with marginalized populations. Conclusions—Overall, the providers’ approaches to working with TGNC clients mapped on to models of cultural competency but few providers described their work in the context of an evidence-based model. Implications for increasing the quality and availability of mental health care services for TGNC individuals in underserved areas are discussed. Public Policy Statement—Affirming mental healthcare providers working with transgender and gender nonconforming (TGNC) clients in underserved areas strive towards cultural competency, but lack of resources and structural barriers to care prohibit wide dissemination of affirming evidence-based care. This study highlights the need for increased research and evidence-informed policy regarding the delivery of mental health services to TGNC individuals in underserved areas

The Rise of Transgender and Gender Diverse Representation in the Media: Impacts on the Population

In recent years, the transgender and gender diverse (TGD) population has gained a stronger voice in the media. Although these voices are being heard, there are limits on the types of TGD representation displayed in media. The current study interviewed 27 TGD individuals. These interviews exposed how participants view the rise of TGD media representation. The main themes that emerged were TGD awareness and TGD identity discovery and role modeling. Clearly, there is a disconnect between transnormativity in the media and transnormativity in reality

Effects of post-exercise sodium bicarbonate ingestion on acid-base balance recovery and time-to-exhaustion running performance: a randomised crossover trial in recreational athletes

This study investigated the effect of post-exercise sodium bicarbonate (NaHCO3) ingestion on acid-base balance recovery and time-to-exhaustion (TTE) running performance. Eleven male runners (stature, 1.80 ± 0.05 m; body mass, 74.4 ± 6.5 kg; maximal oxygen consumption, 51.7 ± 5.4 ml.kg-1.min-1) participated in this randomised, single-blind, counterbalanced and crossover design study. Maximal running velocity (v-VO2max) was identified from a graded exercise test. During experimental trials, participants repeated 100% v-VO2max TTE protocols (TTE1, TTE2) separated by 40 min following the ingestion of either 0.3 g.kg-1 BM NaHCO3 (SB) or 0.03 g.kg-1 BM sodium chloride (PLA) at the start of TTE1 recovery. Acid-base balance (blood pH and bicarbonate, HCO3-) data were studied at baseline, post-TTE1, after 35 min recovery and post-TTE2. Blood pH and [HCO3-] were unchanged at 35 min recovery (p > 0.05), but [HCO3-] was elevated post-TTE2 for SB vs. PLA (+2.6 mmol.l-1; p = 0.005; g = 0.99). No significant differences were observed for TTE2 performance (p > 0.05), although a moderate effect size was present for SB vs. PLA (+14.3 s; g = 0.56). Post-exercise NaHCO3 ingestion is not an effective strategy for accelerating the restoration of acid-base balance or improving subsequent TTE performance when limited recovery is available.
 Novelty bullets:
 •Post-exercise sodium bicarbonate ingestion did not accelerate the restoration of blood pH or bicarbonate after 35 minutes
 •Performance enhancing effects of sodium bicarbonate ingestion may display a high degree of inter-individual variation
 •Small-to-moderate changes in performance were likely due to greater up-regulation of glycolytic activation during exercise
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Overcoming barriers to engaging socio-economically disadvantaged populations in CHD primary prevention: a qualitative study

<p><b>Background:</b> Preventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED) population in primary prevention for coronary heart disease (CHD).</p> <p><b>Methods:</b> The primary prevention element of Have a Heart Paisley (HaHP) offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a) a social marketing campaign and b) a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches.</p> <p><b>Results:</b> Various reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1) processes of engagement; (2) issues of understanding; (3) design of the screening service and (4) the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In contrast, direct face-to-face contact meant that outreach workers could explain what to expect. Participants felt that the procedure for uptake of screening was demanding and inflexible, but that the drop-in sessions employed by the community development project had a major impact on recruitment and retention.</p> <p><b>Conclusion:</b> Socio-economically disadvantaged individuals can be hard-to-reach; engagement requires strategies tailored to the needs of the target population rather than a population-wide approach.</p&gt

Consumption of New Zealand blackcurrant extract improves recovery from exercise-induced muscle damage in non-resistance trained men and women: A double-blind randomised trial

Background: Blackcurrant is rich in anthocyanins that may protect against exercise-induced muscle damage (EIMD) and facilitate a faster recovery of muscle function. We examined the effects of New Zealand blackcurrant (NZBC) extract on indices of muscle damage and recovery following a bout of strenuous isokinetic resistance exercise. Methods: Using a double-blind, randomised, placebo controlled, parallel design, twenty-seven healthy participants received either a 3 g·day−1 NZBC extract (n = 14) or the placebo (PLA) (n = 13) for 8 days prior to and 4 days following 60 strenuous concentric and eccentric contractions of the biceps brachii muscle on an isokinetic dynamometer. Muscle soreness (using a visual analogue scale), maximal voluntary contraction (MVC), range of motion (ROM) and blood creatine kinase (CK) were assessed before (0 h) and after (24, 48, 72 and 96 h) exercise. Results: Consumption of NZBC extract resulted in faster recovery of baseline MVC (p = 0.04), attenuated muscle soreness at 24 h (NZBC: 21 ± 10 mm vs. PLA: 40 ± 23 mm, p = 0.02) and 48 h (NZBC: 22 ± 17 vs. PLA: 44 ± 26 mm, p = 0.03) and serum CK concentration at 96 h (NZBC: 635 ± 921 UL vs. PLA: 4021 ± 4319 UL, p = 0.04) following EIMD. Conclusions: Consumption of NZBC extract prior to and following a bout of eccentric exercise attenuates muscle damage and improves functional recovery. These findings are of practical importance in recreationally active and potentially athletic populations, who may benefit from accelerated recovery following EIMD

Adapting and testing a brief intervention to reduce maternal anxiety during pregnancy (ACORN): study protocol for a randomised controlled trial.

BACKGROUND: National guidelines in the UK, United States of America, Canada, and Australia have recently stressed the importance of identifying and treating antenatal anxiety and depression. However, there is little research into the most effective and acceptable ways of helping women manage their symptoms of anxiety and stress during pregnancy. Research indicates the necessity to consider the unique needs and concerns of perinatal populations to ensure treatment engagement, highlighting the need to develop specialised treatments which could be integrated within routine antenatal healthcare services. This trial aims to develop a brief intervention for antenatal anxiety, with a focus on embedding the delivery of the treatment within routine antenatal care. METHODS/DESIGN: This study is a two-phase feasibility trial. In phase 1 we will develop and pilot a brief intervention for antenatal anxiety, blended with group support, to be led by midwives. This intervention will draw on cognitive behavioural principles and wider learning from existing interventions that have been used to reduce anxiety in expectant mothers. The intervention will then be tested in a pilot randomised controlled trial in phase 2. The following outcomes will be assessed: (1) number of participants meeting eligibility criteria, (2) number of participants consenting to the study, (3) number of participants randomised, (4) number of sessions completed by those in the intervention arm, and (5) number of participants completing the post-intervention outcome measures. Secondary outcomes comprise: detailed feedback on acceptability, which will guide further development of the intervention; and outcome data on symptoms of maternal and paternal anxiety and depression, maternal quality of life, quality of couple relationship, mother-child bonding, infant temperament and infant sleep. DISCUSSION: The study will provide important data to inform the design of a future full-scale randomised controlled trial of a brief intervention for anxiety during pregnancy. This will include information on its acceptability and feasibility regarding implementation within current antenatal services, which will inform whether ultimately this provision could be rolled out widely in healthcare settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95282830 . Registered on 29 October 2014

Heparin Alters Viral Serpin, Serp-1, Anti-Thrombolytic Activity to Anti-Thrombotic Activity

Serine protease inhibitors (serpins) regulate coagulation and inflammation. Heparin, a glycosaminoglycan, is an important cofactor for modulation of the inhibitory function of mammalian serpins. The secreted myxoma viral serpin, Serp-1 exerts profound anti-inflammatory activity in a wide range of animal models. Serp-1 anti-inflammatory and anti-atherogenic activity is dependent upon inhibition of the uPA / uPA receptor thrombolytic complex. We demonstrate here that heparin binds to Serp-1 and enhances Serp-1 inhibition of thrombin, a human pro-thrombotic serine protease, in vitro, altering inhibitory activity to a more predominant anti-thrombotic activity. Heparin also facilitates the simultaneous thrombin-mediated cleavage of Serp-1 and prevents formation of a serpin-typical SDS-resistant complex, implying mutual neutralization of Serp-1 and thrombin. In a cell-based assay, heparin facilitates Serp-1 reversal of cellular activation by stabilizing cellular membrane fluidity in thrombin-activated monocytes. In conclusion, heparin and other GAGs serve as cofactors enhancing Serp-1 regulation of local thrombotic and inflammatory pathway