Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation-contraction coupling.

Excitation-contraction coupling (ECC) is the physiological process in which an electrical signal originating from the central nervous system is converted into muscle contraction. In skeletal muscle tissue, the key step in the molecular mechanism of ECC initiated by the muscle action potential is the cooperation between two Ca2+ channels, dihydropyridine receptor (DHPR; voltage-dependent L-type calcium channel) and ryanodine receptor 1 (RyR1). These two channels were originally postulated to communicate with each other via direct mechanical interactions; however, the molecular details of this cooperation have remained ambiguous. Recently, it has been proposed that one or more supporting proteins are in fact required for communication of DHPR with RyR1 during the ECC process. One such protein that is increasingly believed to play a role in this interaction is the SH3 and cysteine-rich domain-containing protein 3 (STAC3), which has been proposed to bind a cytosolic portion of the DHPR α1S subunit known as the II-III loop. In this work, we present direct evidence for an interaction between a small peptide sequence of the II-III loop and several residues within the SH3 domains of STAC3 as well as the neuronal isoform STAC2. Differences in this interaction between STAC3 and STAC2 suggest that STAC3 possesses distinct biophysical features that are potentially important for its physiological interactions with the II-III loop. Therefore, this work demonstrates an isoform-specific interaction between STAC3 and the II-III loop of DHPR and provides novel insights into a putative molecular mechanism behind this association in the skeletal muscle ECC process.

"Oh I try, but it's so hard": parental experiences of health promotion in children withdisabilities.

PURPOSE: The purpose of this study was to explore how parents support the health behaviours of their child with a disability, and their motivations for registering their child in a health promotion program for children with physical and/or intellectual disabilities. METHODS: Using a descriptive qualitative design, semi-structured face-to-face interviews were conducted with individual parents (n = 8) and one group (n = 3) to explore their experiences of health promotion for their child with a disability. Data were analyzed using thematic analysis to identify themes and patterns to develop an understanding of parental perspectives. RESULTS: Three themes were identified in the analysis of parents' experiences supporting their children in health behaviours and registering them in a disability health promotion program: (1) Parents struggle to meet all of their child's health promotion needs; (2) Parents recognize the social components of healthy behaviours; and (3) Health promotion opportunities tailored for children with disabilities are limited. These themes were not mutually exclusive and had overlapping factors that influenced parental experiences. CONCLUSION: Parents experience many challenges supporting the health behaviours of their children with disabilities. This study reinforces the need for accessible, developmentally appropriate, social health promotion programs for children with disabilities.IMPLICATIONS FOR REHABILITATIONChildren with disabilities frequently demonstrate significantly higher sedentary behaviours, lower rates of physical activity and consumption of high-fat foods than their typically developing peers.Promoting healthy behaviours such as healthy eating and physical activity among children with disabilities and their families is therefore crucial to the child's physical and psychosocial wellbeing.Parents of children with disabilities have sufficient health literacy and knowledge but report a lack of appropriate opportunities and strategies to support their child in developing healthy behaviours.Parents need increased availability and accessibility of socially inclusive programs that promote healthy behaviours for children of all physical and cognitive abilities.

Prioritizing core components of successful transitions from child to adult mental health care: a national Delphi survey with youth, caregivers, and health professionals.

Youth accessing mental health care often experience a disruption in care as they attempt to transition between child and adolescent mental health services (CAMHS) and adult mental health services (AMHS). Few studies have evaluated interventions seeking to improve the experience and outcomes of CAMHS-AMHS transitions, in part due to lack of consensus on what constitutes best practices in intervention success. As such, the aim of this study was to engage patients, caregivers, and clinicians to prioritize core components of successful CAMHS-AMHS transitions which can be used in the design or evaluation of transition interventions. As such, a Delphi study was conducted to determine core components of successful CAMHS-AMHS transitions. Guided by the principles of patient-oriented research, three balanced expert panels consisting of youth, caregivers, and clinicians ranked and provided feedback on the importance and feasibility of core components of CAMHS-AMHS transitions. Components endorsed as feasible or important with ≥ 70% agreement from any panel moved to the next round. As a result, a list of 26 core components of CAMHS-AMHS transitions has been refined which can be used in the design, implementation, or evaluation of interventions intended to improve transition experiences and outcomes for youth in mental health care. Youth and families were engaged in an expert advisory role throughout the research process, contributing their important perspectives to the design and implementation of this study, as well as interpretation of the findings.

Identifying core components and indicators of successful transitions from child to adult mental health services: a scoping review.

The aim of this scoping review was to identify the core components of interventions that facilitate successful transition from child and adolescent mental health services to adult mental health services. In the absence of rigorous evaluations of transition program effectiveness for transitioning youth with mental health care needs, these core components can contribute to informed decisions about promising program and intervention strategies. This review examined data from 87 peer-reviewed and non-academic documents to determine the characteristics that support the transition process and to identify opportunities for system and program improvement. Data were extracted and synthesized using a descriptive analytic framework. A major finding of this review is a significant lack of measurable indicators in the academic and gray literature. This review did identify 26 core components organized within the framework of the six core elements of healthcare transitions. Policy makers, practitioners, and administrators can use the core components to guide decisions about transition program and intervention content. Confirmation of the impact of these core program components on youth outcomes awaits the conduct of rigorous randomized trials. Future research also needs to explicitly focus on the development of indicators to evaluate transition programs and interventions.

Institutional ethnography as a unique tool for improving health systems.

Qualitative research in the health system has made tremendous developments in the last decade to better understand patient experiences. What is often overlooked, are the influences that the internal structures, policies and people have on the individuals that use health services. Institutional ethnography is a qualitative approach that aims to capture the social organization of "everyday life" at various system levels. An institutional ethnographic framework was applied to two research studies exploring how families experience care in neonatal intensive care units. Data were collected to develop a deep understanding of the social contexts that exist within institutional boundaries. This paper provides evidence that how care is organized and delivered can significantly influence patient experiences, perceptions and ultimately health outcomes. Adopting institutional ethnographic techniques as a common research method is a valuable tool for health leaders seeking to understand and develop recommendations for health system reform.

Benefits of a primary care clinic co-located and integrated in a mental health setting for veterans with serious mental illness.

INTRODUCTION: Efficacy trials have shown that primary care co-located in the mental health setting improves the receipt of high-quality medical care among people with serious mental illness. We tested whether implementation of such a program affected health service use and cardiovascular risk factor control among veterans with serious mental illness who had previously demonstrated limited primary care engagement. METHODS: We performed a cohort study of veterans enrolled in a co-located, integrated primary care clinic in the mental health outpatient unit through targeted chart review. Two successive 6-month periods in the year before and in the year following enrollment in the co-located primary care clinic were examined for primary care and emergency department use and for goal attainment of blood pressure, fasting blood lipids, body mass index (BMI), and, among patients with diabetes, hemoglobin A1c (HbA1c). We used repeated-measures logistic regression to analyze goal attainment and repeated measures Poisson regression to analyze service use. RESULTS: Compared with the period before enrollment, the 97 veterans enrolled in the clinic had significantly more primary care visits during 6 months and significantly improved goal attainment for blood pressure, low-density lipoprotein cholesterol, triglycerides, and BMI. Changes with regard to goal attainment for high-density lipoprotein cholesterol and HbA1c were not significant. CONCLUSION: Enrollment in a co-located, integrated clinic was associated with increased primary care use and improved attainment of some cardiovascular risk goals among veterans with serious mental illness. Such a clinic can be implemented effectively in the mental health setting.

VAPOL phosphoric acid catalysis: the highly enantioselective addition of imides to imines.

The first highly enantioselective catalytic method for the preparation of chiral aminals via the addition of imide nucleophiles to imines is reported.

Organocatalytic enantioselective Friedel-Crafts reaction of pyrrole derivatives with imines.

A highly enantioselective Friedel-Crafts reaction of pyrrole derivatives with N-acyl imines catalyzed by chiral phosphoric acids was developed. The reactions produced the pyrrole derivatives in high yields and enantioselectivity.

The highly enantioselective addition of indoles to N-acyl imines with use of a chiral phosphoric acid catalyst.

The highly enantioselective organocatalytic addition of N-benzyl indoles to N-acyl imines is reported. A total of 15 examples with product yield ranging from 89% to 99% and enantioselectivities from 90% to 97% are presented. A chiral phosphoric acid catalyst derived from a hindered binol derivative was employed most effectively in the reaction. Attractive features of the reaction include desirable catalyst loadings, good reactivity, generality of substrates, and easily removable groups from both nitrogen atoms.

Brønsted acid-catalyzed imine amidation.

A new method for the Brønsted acid-catalyzed addition of amide nucleophiles to imines to produce protected aminal products is described. Simple Brønsted acids (phenyl phosphinic acid and trifluoromethanesulfonimide) were shown to be excellent catalysts, providing high yields of the aminal product. A catalytic asymmetric imine amidation using sulfonamides as nucleophiles was successful when a hindered biaryl phosphoric acid catalyst derived from 2,2'-diphenyl-[3,3'-biphenanthrene]-4,4'-diol (VAPOL) was used. Excellent yields and enantioselectivities were found in these additions (up to 99% ee).