Modelling the widespread effects of TOC1 signalling on the plant circadian clock and its outputs

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This work was supported by the European Commission FP7 Collaborative Project TiMet (project 245143). SynthSys is a Centre for Integrative and Systems Biology supported by BBSRC and EPSRC award D019621. Work in P.M. laboratory is supported by grants from the Ramón Areces Foundation, from the Spanish Ministry of Science and Innovation (MICINN) (BIO2010-16483) and from EUROHORCS (European Heads Of Research Councils) and the European Science Foundation (ESF) through the EURYI Award.Peer reviewedPublisher PD

Relationships Between Stress Self-Management, Social Support, and Health in Hispanic Informal Caregiver Burnout Prevention

Burnout syndrome is a psychological disorder characterized by physical, emotional, and mental distress and exhaustion resulting in feelings of depression, anxiety, irritability, and negative attitudes. If left unattended, burnout syndrome can lead to new or worsening health outcomes. The purpose of this nonexperimental quantitative study was to examine the relationship between stress self-management, perceived social support, health status, and burden among Puerto Rican informal caregivers. The theoretical foundations for this research were the informal caregiving integrative model and the individual and family self-management theory. Survey data were collected from 415 participants. Multiple regression analyses were performed to determine the relationship between the predictor variables (stress self-management and perceived social support) and dependent variables (self-rated health and caregiver burden). Results showed that higher levels of stress self-management and perceived social support were significant predictors of informal caregivers’ self-rated health and burden. Results suggested that addressing the stress self-management and social support of informal caregivers may improve their health and reduce their burden. Findings may prompt health education and promotion strategies to raise awareness of the experiences and needs of informal caregivers and to develop initiatives for the prevention of burnout syndrome among this community

Relationships Between Stress Self-Management, Social Support, and Health in Hispanic Informal Caregiver Burnout Prevention

Burnout syndrome is a psychological disorder characterized by physical, emotional, and mental distress and exhaustion resulting in feelings of depression, anxiety, irritability, and negative attitudes. If left unattended, burnout syndrome can lead to new or worsening health outcomes. The purpose of this nonexperimental quantitative study was to examine the relationship between stress self-management, perceived social support, health status, and burden among Puerto Rican informal caregivers. The theoretical foundations for this research were the informal caregiving integrative model and the individual and family self-management theory. Survey data were collected from 415 participants. Multiple regression analyses were performed to determine the relationship between the predictor variables (stress self-management and perceived social support) and dependent variables (self-rated health and caregiver burden). Results showed that higher levels of stress self-management and perceived social support were significant predictors of informal caregivers’ self-rated health and burden. Results suggested that addressing the stress self-management and social support of informal caregivers may improve their health and reduce their burden. Findings may prompt health education and promotion strategies to raise awareness of the experiences and needs of informal caregivers and to develop initiatives for the prevention of burnout syndrome among this community

Pengaruh Sales, Working Capital dan Operating Cash Flow Terhadap Net Profit Perusahaan Consumer Goods Listing di Bursa Efek Indonesia Periode 2013-2017

Penyebab persaingan usaha bisnis yang ketat, karena banyaknya perusahaan pesaing yang memiliki kualitas kompetitif yang baik. Salah satunya pada perusahaan sektor industri barang konsumsi. Fenomena yang terjadi di perusahaan adalah peningkatan sales, working capital dan operating cash flow. Masalah dari penelitian dirumuskan sebagai berikut: apakah terdapat pengaruh sales, working capital dan operating cash flow terhadap net profit pada perusahaan consumer goods yang listing di Bursa Efek Indonesia pada periode 2013-2017. Metode penelitian yang digunakan adalah metode penelitian kuantitatif dengan tipe penelitian deskriptif dan sifat penelitian adalah penelitian kausal. Dokumentasi digunakan untuk mengumpulkan data. Analisis regresi linear berganda merupakan metode analisis data, koefisien determinasi, uji F dan uji t. teknik purposive sampling merupakan teknik pengambilan sampel dengan kriteria tertentu ada 24 perusahaan sebagai sampel penelitian. Berdasarkan hasil  penelitian ini menunjukkan bahwa sales, working capital dan operating cash flow secara simultan berpengaruh signifikan terhadap net profit. Secara parsial, sales berpengaruh signifikan terhadap net profit, working capital signifikan terhadap net profit, operating cash flow telah pengaruh signifikan terhadap net profit. &nbsp

Obstetric complications and genetic risk for schizophrenia: Differential role of antenatal and perinatal events in first episode psychosis

Background: Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors. Study Design: 405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis-Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS-SZ) and interactions between these. Results: Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case–control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS-SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe. Conclusions: We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk

Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode

Background Clinical intervention in early stages of psychotic disorders is crucial for the prevention of severe symptomatology trajectories and poor outcomes. Genetic variability is studied as a promising modulator of prognosis, thus novel approaches considering the polygenic nature of these complex phenotypes are required to unravel the mechanisms underlying the early progression of the disorder. Methods The sample comprised of 233 first-episode psychosis (FEP) subjects with clinical and cognitive data assessed periodically for a 2-year period and 150 matched controls. Polygenic risk scores (PRSs) for schizophrenia, bipolar disorder, depression, education attainment and cognitive performance were used to assess the genetic risk of FEP and to characterize their association with premorbid, baseline and progression of clinical and cognitive status. Results Schizophrenia, bipolar disorder and cognitive performance PRSs were associated with an increased risk of FEP [false discovery rate (FDR) ⩽ 0.027]. In FEP patients, increased cognitive PRSs were found for FEP patients with more cognitive reserve (FDR ⩽ 0.037). PRSs reflecting a genetic liability for improved cognition were associated with a better course of symptoms, functionality and working memory (FDR ⩽ 0.039). Moreover, the PRS of depression was associated with a worse trajectory of the executive function and the general cognitive status (FDR ⩽ 0.001). Conclusions Our study provides novel evidence of the polygenic bases of psychosis and its clinical manifestation in its first stage. The consistent effect of cognitive PRSs on the early clinical progression suggests that the mechanisms underlying the psychotic episode and its severity could be partially independent

Metabolic polygenic risk scores effect on antipsychotic-induced metabolic dysregulation: A longitudinal study in a first episode psychosis cohort

[EN] Objective: Metabolic syndrome is a health-threatening condition suffered by approximately one third of schizophrenia patients and largely attributed to antipsychotic medication. Previous evidence reports a common genetic background of psychotic and metabolic disorders. In this study, we aimed to assess the role of polygenic risk scores (PRSs) on the progression of the metabolic profile in a first-episode psychosis (FEP) cohort. Method: Of the 231 FEP individuals included in the study, 192-220 participants were included in basal analysis and 118-179 in longitudinal 6-month models. Eleven psychopathologic and metabolic PRSs were constructed. Basal and longitudinal PRSs association with metabolic measurements was assessed by statistical analyses.Results: No major association of psychopathological PRSs with the metabolic progression was found. However, high risk individuals for depression and cholesterol-related PRSs reported a higher increase of cholesterol levels during the follow-up (FDR <= 0.023 for all analyses). Their effect was comparable to other well-established pharmacological and environmental risk factors (explaining at least 1.2% of total variance).Conclusion: Our findings provide new evidence of the effects of metabolic genetic risk on the development of metabolic dysregulation. The future establishment of genetic profiling tools in clinical procedures could enable practitioners to better personalize antipsychotic treatment selection and dosage

Age-related increase of kynurenine enhances miR29b-1-5p to decrease both CXCL12 signaling and the epigenetic enzyme Hdac3 in bone marrow stromal cells

Mechanisms leading to age-related reductions in bone formation and subsequent osteoporosis are still incompletely understood. We recently demonstrated that kynurenine (KYN), a tryptophan metabolite, accumulates in serum of aged mice and induces bone loss. Here, we report on novel mechanisms underlying KYN's detrimental effect on bone aging. We show that KYN is increased with aging in murine bone marrow mesenchymal stem cells (BMSCs). KYN reduces bone formation via modulating levels of CXCL12 and its receptors as well as histone deacetylase 3 (Hdac3). BMSCs responded to KYN by significantly decreasing mRNA expression levels of CXCL12 and its cognate receptors, CXCR4 and ACKR3, as well as downregulating osteogenic gene RUNX2 expression, resulting in a significant inhibition in BMSCs osteogenic differentiation. KYN's effects on these targets occur by increasing regulatory miRNAs that target osteogenesis, specifically miR29b-1-5p. Thus, KYN significantly upregulated the anti-osteogenic miRNA miR29b-1-5p in BMSCs, mimicking the up-regulation of miR-29b-1-5p in human and murine BMSCs with age. Direct inhibition of miR29b-1-5p by antagomirs rescued CXCL12 protein levels downregulated by KYN, while a miR29b-1-5p mimic further decreased CXCL12 levels. KYN also significantly downregulated mRNA levels of Hdac3, a target of miR-29b-1-5p, as well as its cofactor NCoR1. KYN is a ligand for the aryl hydrocarbon receptor (AhR). We hypothesized that AhR mediates KYN's effects in BMSCs. Indeed, AhR inhibitors (CH-223191 and 3',4'-dimethoxyflavone [DMF]) partially rescued secreted CXCL12 protein levels in BMSCs treated with KYN. Importantly, we found that treatment with CXCL12, or transfection with an miR29b-1-5p antagomir, downregulated the AhR mRNA level, while transfection with miR29b-1-5p mimic significantly upregulated its level. Further, CXCL12 treatment downregulated IDO, an enzyme responsible for generating KYN. Our findings reveal novel molecular pathways involved in KYN's age-associated effects in the bone microenvironment that may be useful translational targets for treating osteoporosis

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London