Reorganization of mental health services: from institutional to community-based models of care.

Mental health services in the Eastern Mediterranean Region are predominantly centralized and institutionalized, relying on scarce specialist manpower. This creates a major treatment gap for patients with common and disabling mental disorders and places an unnecessary burden on the individual, their family and society. Six steps for reorganization of mental health services in the Region can be outlined: (1) integrate delivery of interventions for priority mental disorders into primary health care and existing priority programmes; (2) systematically strengthen the capacity of non-specialized health personnel for providing mental health care; (3) scale up community-based services (community outreach teams for defined catchment, supported residential facilities, supported employment and family support); (4) establish mental health services in general hospitals for outpatient and acute inpatient care; (5) progressively reduce the number of long-stay beds in mental hospitals through restricting new admissions; and (6) provide transitional/bridge funding over a period of time to scale up community-based services and downsize mental institutions in parallel

Quantitative trait loci and candidate gene mapping of aluminum tolerance in diploid alfalfa

Aluminum (Al) toxicity in acid soils is a major limitation to the production of alfalfa (Medicago sativa subsp. sativa L.) in the USA. Developing Al-tolerant alfalfa cultivars is one approach to overcome this constraint. Accessions of wild diploid alfalfa (M. sativa subsp. coerulea) have been found to be a source of useful genes for Al tolerance. Previously, two genomic regions associated with Al tolerance were identified in this diploid species using restriction fragment length polymorphism (RFLP) markers and single marker analysis. This study was conducted to identify additional Al-tolerance quantitative trait loci (QTLs); to identify simple sequence repeat (SSR) markers that flank the previously identified QTLs; to map candidate genes associated with Al tolerance from other plant species; and to test for co-localization with mapped QTLs. A genetic linkage map was constructed using EST-SSR markers in a population of 130 BC(1)F(1) plants derived from the cross between Al-sensitive and Al-tolerant genotypes. Three putative QTLs on linkage groups LG I, LG II and LG III, explaining 38, 16 and 27% of the phenotypic variation, respectively, were identified. Six candidate gene markers designed from Medicago truncatula ESTs that showed homology to known Al-tolerance genes identified in other plant species were placed on the QTL map. A marker designed from a candidate gene involved in malic acid release mapped near a marginally significant QTL (LOD 2.83) on LG I. The SSR markers flanking these QTLs will be useful for transferring them to cultivated alfalfa via marker-assisted selection and for pyramiding Al tolerance QTLs

Pharmacogenetics Meets Metabolomics: Discovery of Tryptophan as a New Endogenous OCT2 Substrate Related to Metformin Disposition

Genetic polymorphisms of the organic cation transporter 2 (OCT2), encoded by SLC22A2, have been investigated in association with metformin disposition. A functional decrease in transport function has been shown to be associated with the OCT2 variants. Using metabolomics, our study aims at a comprehensive monitoring of primary metabolite changes in order to understand biochemical alteration associated with OCT2 polymorphisms and discovery of potential endogenous metabolites related to the genetic variation of OCT2. Using GC-TOF MS based metabolite profiling, clear clustering of samples was observed in Partial Least Square Discriminant Analysis, showing that metabolic profiles were linked to the genetic variants of OCT2. Tryptophan and uridine presented the most significant alteration in SLC22A2-808TT homozygous and the SLC22A2-808G>T heterozygous variants relative to the reference. Particularly tryptophan showed gene-dose effects of transporter activity according to OCT2 genotypes and the greatest linear association with the pharmacokinetic parameters (Clrenal, Clsec, Cl/F/kg, and Vd/F/kg) of metformin. An inhibition assay demonstrated the inhibitory effect of tryptophan on the uptake of 1-methyl-4-phenyl pyrinidium in a concentration dependent manner and subsequent uptake experiment revealed differential tryptophan-uptake rate in the oocytes expressing OCT2 reference and variant (808G>T). Our results collectively indicate tryptophan can serve as one of the endogenous substrate for the OCT2 as well as a biomarker candidate indicating the variability of the transport activity of OCT2

Examination of a pre-exercise, high energy supplement on exercise performance

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to examine the effect of a pre-exercise high energy drink on reaction time and anaerobic power in competitive strength/power athletes. In addition, the effect of the pre-exercise drink on subjective feelings of energy, fatigue, alertness and focus was also explored.</p> <p>Methods</p> <p>Twelve male strength/power athletes (21.1 ± 1.3 y; 179.8 ± 7.1 cm; 88.6 ± 12.1 kg; 17.6 ± 3.3% body fat) underwent two testing sessions administered in a randomized and double-blind fashion. During each session, subjects reported to the Human Performance Laboratory and were provided with either 120 ml of a high energy drink (SUP), commercially marketed as Redline Extreme^®or 120 ml of a placebo (PL) that was similar in taste and appearance but contained no active ingredients. Following consumption of the supplement or placebo subjects rested quietly for 10-minutes prior to completing a survey and commencing exercise. The survey consisted of 4 questions asking each subject to describe their feelings of energy, fatigue, alertness and focus for that moment. Following the completion of the questionnaire subjects performed a 2-minute quickness and reaction test on the Makoto testing device (Makoto USA, Centennial CO) and a 20-second Wingate Anaerobic Power test. Following a 10-minute rest subjects repeated the testing sequence and after a similar rest period a third and final testing sequence was performed. The Makoto testing device consisted of subjects reacting to both a visual and auditory stimulus and striking one out of 30 potential targets on three towers.</p> <p>Results</p> <p>Significant difference in reaction performance was seen between SUP and PL in both average number of targets struck (55.8 ± 7.4 versus 51.9 ± 7.4, respectively) and percent of targets struck (71.9 ± 10.5% versus 66.8 ± 10.9%, respectively). No significant differences between trials were seen in any anaerobic power measure. Subjective feelings of energy (3.5 ± 0.5 versus 3.1 ± 0.5) and focus (3.8 ± 0.5 versus 3.3 ± 0.7) were significantly higher during SUP compared to PL, respectively. In addition, a trend towards an increase in average alertness (p = 0.06) was seen in SUP compared to P.</p> <p>Conclusion</p> <p>Results indicate a significant increase in reaction performance, with no effect on anaerobic power performance. In addition, ingestion of this supplement significantly improves subjective feelings of focus and energy in male strength/power athletes.</p

Socio-demographic factors associated with pet ownership amongst adolescents from a UK birth cohort

Background: In developed nations, pet ownership is common within families. Both physical and psychological health benefits may result from owning a pet during childhood and adolescence. However, it is difficult to determine whether these benefits are due to pet ownership directly or to factors linked to both pet ownership and health. Previous research found associations between a range of socio-demographic factors and pet ownership in seven-year-old children from a UK cohort. The current study extends this research to adolescence, considering that these factors may be important to consider in future Human-Animal Interaction (HAI) research across childhood.Results:The Avon Longitudinal Study of Parents and Children (ALSPAC) collected pet ownership data prospectively via maternal reports from gestation up to age 10 years old and via self-report retrospectively at age 18 for ages 11(n= 3063) to 18 years old (n= 3098) on cats, dogs, rabbits, rodents, birds, fish, tortoise/turtles and horses. The dataset also contains a wide range of potential confounders, including demographic and socio-economic variables.The ownership of all pet types peaked at age 11 (80%) and then decreased during adolescence, with the exclusion of cats which remained constant (around 30%), and dogs which increased through 11–18 years (26–37%). Logistic regression was used to build multivariable models for ownership of each pet type at age 13 years, and the factors identified in these models were compared to previously published data for 7 year-olds in the same cohort. There was some consistency with predictors reported at age 7. Generally sex, birth order, maternal age, maternal education, number of people in the household, house type, and concurrent ownership of other pets were associated with pet ownership at both 7 and 13 years (the direction of association varied according to pet type).Factors that were no longer associated with adolescent pet ownership included child ethnicity, paternal education,and parental social class.Conclusions:A number of socio-demographic factors are associated with pet ownership in childhood and adolescence and they differ according to the type of pet, and age of child. These factors are potential confounders that must be considered in future HAI studies

A Geospatial Modelling Approach Integrating Archaeobotany and Genetics to Trace the Origin and Dispersal of Domesticated Plants

Background: The study of the prehistoric origins and dispersal routes of domesticated plants is often based on the analysis of either archaeobotanical or genetic data. As more data become available, spatially explicit models of crop dispersal can be used to combine different types of evidence. Methodology/Principal Findings: We present a model in which a crop disperses through a landscape that is represented by a conductance matrix. From this matrix, we derive least-cost distances from the geographical origin of the crop and use these to predict the age of archaeological crop remains and the heterozygosity of crop populations. We use measures of the overlap and divergence of dispersal trajectories to predict genetic similarity between crop populations. The conductance matrix is constructed from environmental variables using a number of parameters. Model parameters are determined with multiple-criteria optimization, simultaneously fitting the archaeobotanical and genetic data. The consilience reached by the model is the extent to which it converges around solutions optimal for both archaeobotanical and genetic data. We apply the modelling approach to the dispersal of maize in the Americas. Conclusions/Significance: The approach makes possible the integrative inference of crop dispersal processes, whil

Retrograde trafficking of β-dystroglycan from the plasma membrane to the nucleus

β-Dystroglycan (β-DG) is a transmembrane protein with critical roles in cell adhesion, cytoskeleton remodeling and nuclear architecture. This functional diversity is attributed to the ability of β-DG to target to, and conform specific protein assemblies at the plasma membrane (PM) and nuclear envelope (NE). Although a classical NLS and importin α/β mediated nuclear import pathway has already been described for β-DG, the intracellular trafficking route by which β-DG reaches the nucleus is unknown. In this study, we demonstrated that β-DG undergoes retrograde intracellular trafficking from the PM to the nucleus via the endosome-ER network. Furthermore, we provided evidence indicating that the translocon complex Sec61 mediates the release of β-DG from the ER membrane, making it accessible for importins and nuclear import. Finally, we show that phosphorylation of β-DG at Tyr890 is a key stimulus for β-DG nuclear translocation. Collectively our data describe the retrograde intracellular trafficking route that β-DG follows from PM to the nucleus. This dual role for a cell adhesion receptor permits the cell to functionally connect the PM with the nucleus and represents to our knowledge the first example of a cell adhesion receptor exhibiting retrograde nuclear trafficking and having dual roles in PM and NE

Staff understanding of recovery-orientated mental health practice: a systematic review and narrative synthesis

Background: Mental health policy is for staff to transform their practice towards a recovery orientation. Staff understanding of recovery-orientated practice will influence the implementation of this policy. The aim of this study was to conduct a systematic review and narrative synthesis of empirical studies identifying clinician and manager conceptualisations of recovery-orientated practice. Methods: A systematic review of empirical primary research was conducted. Data sources were online databases (n = 8), journal table of contents (n = 5), internet, expert consultation (n = 13), reference lists of included studies and references to included studies. Narrative synthesis was used to integrate the findings. Results: A total of 10,125 studies were screened, 245 full papers were retrieved, and 22 were included (participants, n = 1163). The following three conceptualisations of recovery-orientated practice were identified: clinical recovery, personal recovery and service-defined recovery. Service-defined recovery is a new conceptualisation which translates recovery into practice according to the goals and financial needs of the organisation. Conclusions: Organisational priorities influence staff understanding of recovery support. This influence is leading to the emergence of an additional meaning of recovery. The impact of service-led approaches to operationalising recovery-orientated practice has not been evaluated. Trial Registration: The protocol for the review was pre-registered (PROSPERO 2013: CRD42013005942)

Novel roles of the chemorepellent axon guidance molecule RGMa in cell migration and adhesion

The repulsive guidance molecule A (RGMa) is a contact-mediated axon guidance molecule that has significant roles in central nervous system (CNS) development. Here we have examined whether RGMa has novel roles in cell migration and cell adhesion outside the nervous system. RGMa was found to stimulate cell migration from Xenopus animal cap explants in a neogenin-dependent and BMP-independent manner. RGMa also stimulated the adhesion of Xenopus animal cap cells, and this adhesion was dependent on neogenin and independent of calcium. To begin to functionally characterize the role of specific domains in RGMa, we assessed the migratory and adhesive activities of deletion mutants. RGMa lacking the partial von Willebrand factor type D (vWF) domain preferentially perturbed cell adhesion, while mutants lacking the RGD motif affected cell migration. We also revealed that manipulating the levels of RGMa in vivo caused major migration defects during Xenopus gastrulation. We have revealed here novel roles of RGMa in cell migration and adhesion and demonstrated that perturbations to the homeostasis of RGMa expression can severely disrupt major morphogenetic events. These results have implications for understanding the role of RGMa in both health and disease