Miracle-dz/UniFAR-FTUs huggingface dataset:
A molecule‐based genetic association approach implicates a range of voltage‐gated calcium channels associated with schizophrenia

Traditional genome‐wide association studies (GWAS) have successfully detected genetic variants associated with schizophrenia. However, only a small fraction of heritability can be explained. Gene‐set/pathway‐based methods can overcome limitations arising from single nucleotide polymorphism (SNP)‐based analysis, but most of them place constraints on size which may exclude highly specific and functional sets, like macromolecules. Voltage‐gated calcium (Cav) channels, belonging to macromolecules, are composed of several subunits whose encoding genes are located far away or even on different chromosomes. We combined information about such molecules with GWAS data to investigate how functional channels associated with schizophrenia. We defined a biologically meaningful SNP‐set based on channel structure and performed an association study by using a validated method: SNP‐set (sequence) kernel association test. We identified eight subtypes of Cav channels significantly associated with schizophrenia from a subsample of published data (N = 56,605), including the L‐type channels (Cav1.1, Cav1.2, Cav1.3), P‐/Q‐type Cav2.1, N‐type Cav2.2, R‐type Cav2.3, T‐type Cav3.1, and Cav3.3. Only genes from Cav1.2 and Cav3.3 have been implicated by the largest GWAS (N = 82,315). Each subtype of Cav channels showed relatively high chip heritability, proportional to the size of its constituent gene regions. The results suggest that abnormalities of Cav channels may play an important role in the pathophysiology of schizophrenia and these channels may represent appropriate drug targets for therapeutics. Analyzing subunit‐encoding genes of a macromolecule in aggregate is a complementary way to identify more genetic variants of polygenic diseases. This study offers the potential of power for discovery the biological mechanisms of schizophrenia.
Programa de adherencia al ejercicio físico, dirigido a usuarios de Programas de Mantenimiento con Metadona (PMM)

From a psycho-social perspective, current initiatives that seek to improve the life quality of Spanish inmates involved in MMPs are few and far between. Within certain parameters and a precisely applied methodology, physical and sports activities are the best complementary therapies in the treatment of substance abuse because they deal with the biological, psychological and social aspects of the problem. The aim of this program is that a group of people, all of whom are users of the MMP in the ‘Centro Penitenciario Madrid- V’, acquire the habit of taking physical exercise. The improvement in their physical condition and stamina will lead to the MMP participant to reduce his methadone intake, and also increase his self-esteem and improve his social image. Key words: Health exercise. Methadone. Drug Therapy.
Prospective study of postpartum depression in eastern Turkey prevalence, socio-demographic and obstetric correlates, prenatal anxiety and early awareness.

AIMS AND OBJECTIVES The study was undertaken to provide an estimate of the prevalence of postpartum depression and its correlates. Further, we sought to evaluate the predictive power of the Edinburgh Postnatal Depression Scale when administered at postpartum week one for symptoms of depression at postpartum week six. BACKGROUND Postpartum depression is a major health issue for women worldwide with well-documented negative health consequences for the mother and family. It is therefore important to evaluate prenatal detection of women at risk for developing postpartum depression. DESIGN A prospective study. METHODS The study involved 479 pregnant women in Erzurum, Turkey who were evaluated during the third trimester of pregnancy and at one and six weeks postpartum by community midwives. Questionnaires were used for data collection. Anxiety/social support scales were used for baseline evaluation, and the Edinburgh Postpartum Depression Scale was administered at one and six weeks postpartum. RESULTS The prevalence of depressive symptoms according to the Edinburgh Postpartum Depression Scale was 17.7% at first week and 14% at sixth week postpartum. The factors that were most predictive of postpartum depression were psychiatric history during pregnancy; prenatal anxiety; poor marital relationship in the first postpartum weeks; lack of health insurance and lack of contraceptive use. The correlation between symptoms of depression at one and six weeks in the postpartum period was significant. CONCLUSIONS The prevalence of postpartum depression and its correlates were similar to the results of Western studies. Early identification of potential risk factors may aid in recognition of and treatment for postpartum depression. The Edinburgh scale is a simple yet useful tool to use during the early postpartum period for evaluation of depressive symptoms. RELEVANCE TO CLINICAL PRACTICE This study highlights the utility of screening for risk of postpartum depression during pregnancy and also during the early postpartum period.
Protein Kinase C Controls Vesicular Transport and Secretion of Apolipoprotein E from Primary Human Macrophages*

Background: Macrophage-specific apolipoprotein E (apoE) secretion has been implicated as protective in atherosclerosis. Results: Protein kinase C (PKC) inhibition or knockdown in macrophages inhibits apoE secretion at a post-Golgi, vesicular transport level and is mediated by MARCKS. Conclusion: Classical PKC isoforms regulate apoE secretion. Significance: Current drug therapies targeting PKC may have an off-target effect on macrophage apoE secretion and atherosclerosis. Macrophage-specific apolipoprotein E (apoE) secretion plays an important protective role in atherosclerosis. However, the precise signaling mechanisms regulating apoE secretion from primary human monocyte-derived macrophages (HMDMs) remain unclear. Here we investigate the role of protein kinase C (PKC) in regulating basal and stimulated apoE secretion from HMDMs. Treatment of HMDMs with structurally distinct pan-PKC inhibitors (calphostin C, Ro-31-8220, Go6976) and a PKC inhibitory peptide all significantly decreased apoE secretion without significantly affecting apoE mRNA or apoE protein levels. The PKC activator phorbol 12-myristate 13-acetate (PMA) stimulated apoE secretion, and both PMA-induced and apoAI-induced apoE secretion were inhibited by PKC inhibitors. PKC regulation of apoE secretion was found to be independent of the ATP binding cassette transporter ABCA1. Live cell imaging demonstrated that PKC inhibitors inhibited vesicular transport of apoE to the plasma membrane. Pharmacological or peptide inhibitor and knockdown studies indicate that classical isoforms PKCα/β and not PKCδ, -ϵ, -θ, or -ι/ζ isoforms regulate apoE secretion from HMDMs. The activity of myristoylated alanine-rich protein kinase C substrate (MARCKS) correlated with modulation of PKC activity in these cells, and direct peptide inhibition of MARCKS inhibited apoE secretion, implicating MARCKS as a downstream effector of PKC in apoE secretion. Comparison with other secreted proteins indicated that PKC similarly regulated secretion of matrix metalloproteinase 9 and chitinase-3-like-1 protein but differentially affected the secretion of other proteins. In conclusion, PKC regulates the secretion of apoE from primary human macrophages.
Organisational climate, organisational commitment and intention to leave amongst hospital nurses in Taiwan.

AIMS AND OBJECTIVES To examine: (1) Taiwanese nurses' perceptions of organisational climate, levels of organisational commitment and intention to leave, as well as relationships between these three variables; (2) demographic differences in the levels of these variables; and (3) mediating effects of organisational commitment on the relationship between organisational climate and intention to leave. BACKGROUND Organisational climate is related to organisational commitment and affects nurses' performances and attitudes towards an organisation. DESIGN A cross-sectional, descriptive design. METHOD Registered nurses working in eight hospitals in southern Taiwan for more than six months were recruited. Data were collected using the Litwin and Stringer's Organisational Climate Questionnaire, Organizational Commitment Questionnaire and a five-item scale measuring intention to leave. Questionnaires were distributed to 612 potential participants; 486 valid returned questionnaires were analysed. RESULTS The study's participants were generally satisfied with their hospital's climate and yet claimed low commitment to their organisation and, nevertheless, reported low intention to leave their job. Single nurses were more satisfied with their hospital's climate and were more committed to their hospital and had a lower intention to leave their job compared to married nurses. Nurses working in district hospitals perceived a better hospital climate and had a lower intention to leave than nurses working in teaching or regional hospitals. Staff nurses perceived a better organisational climate than did nurse managers. Organisational climate, organisational commitment and intention to leave were intercorrelated. Organisational climate had almost 60% indirect effect on organisational commitment related to intention to leave. CONCLUSIONS Creating a good organisational climate may increase nurses' organisational commitment and, in turn, decrease their intention to leave. RELEVANCE TO CLINICAL PRACTICE To motivate nurses' positive organisational behaviours and to address their diverse needs, hospital administrators are encouraged to understand nurses' work-climate perceptions and to address nurses' varied demographic factors.
Health‐related quality of life measures in genetic disorders: An outcome variable for consideration in clinical trials

The field of medical genetics is rapidly advancing, and therapeutic options to treat genetic syndromes are becoming increasingly available. An understanding of the pathophysiology of various genetic disorders has provided researchers the opportunity to propose and test pharmacologic agents in preclinical murine models with hopes of translation to human trials. The development of clinical trials can be costly and time consuming, particularly for rare conditions. Pilot feasibility studies should be performed when designing clinical trials for genetic disorders. The development and selection of appropriate outcome measures are particularly paramount in the implementation of clinical trials. The selection of inappropriate outcome measures can lead to non‐measurable differences or clinically insignificant findings. In addition, just as age appropriate measures are needed, some instruments may not apply to populations with specific genetic disorders that have significant cognitive and physical impairment, as the measures may not be sensitive enough to identify clinically significant changes. In the last decade, health‐related quality of life measures (HRQOL) have been increasingly included as an outcome measure in clinical trials. While traditional clinical outcomes are important, these newly developed instruments should be considered along with clinical indicators as measures of effect in clinical trials of interventions in genetic disorders. © 2009 Wiley‐Liss, Inc.
Apport de l’échographie dans le diagnostic des tumeurs du pancréas au service de radiologie du CHU du Point G

RESUME: But : Preciser l’interet de l’echographie dans le diagnostic des tumeurs pancreatiques dans le service de radiologie et de medecine nucleaire de CHU du Point G. Patients et methodes : Etude transversale de Mai 2008 a Avril 2009. Ont ete inclus dans l’etude tous les malades adresses au service de radiologie pour une echographie dans le cadre d’une suspicion clinique de tumeur du pancreas. Resultats : Pendant la periode d’etude nous avons collige 15 cas de tumeur pancreatique ayant represente 0,33% des echographies effectuees. L’âge moyen des patients etait 58 ans. Le sex-ratio etait 2 en faveur des hommes. Les principaux signes cliniques retrouves etaient: hepatomegalie (66,7%), ictere (41,2%), prurit (30,5%) et l’anorexie (72,73%). L’echographie abdomino-pelvienne a montre une masse pancreatique dans 90% des cas et le scanner dans 90,5% des cas. La tumeur pancreatique pose encore un defi aux praticiens en raison de son diagnostic tardif. Bien que la derivation biliaire puisse ameliorer la qualite de vie des malades, le pronostic de la tumeur pancreatique reste globalement sombre. Conclusion : L’echographie dans le diagnostic de la tumeur du pancreas, permet de preciser le siege de la tumeur, d’evaluer son extension locale et locoregionale ainsi que son retentissement sur les voies bilio-pancreatiques. S Coulibaly et al SUMMARY: Aim: To assess the role of ultrasonography in the diagnosis of pancreatic tumor in the service of radiology and nuclear medicine of the Point G hospital in Bamako. Patients and method: It was a transverse survey from May 2008 to April 2009. All patients referred to the service of radiology for an ultrasound scan for a clinical suspicion pancreatic tumors have been included in the survey. Results: During the period of survey, 15 cases of pancreatic tumor (0.33%) of the ultrasonography were collected. The middle age of the patients was 58 years. The sex - ratio was 2 in favor of men. The main encountered clinical signs were: enlarged liver (66.7%), jaundice (41. 2%), pruritus (30.5%) and anorexia (72.73%). A pancreatic mass was seen in 90% on abdomino-pelvic sonography, and in 90.5% of the cases by CT-scan. Pancreatic tumor is a challenge for the practitioners because of its delayed diagnosis. Although the biliary derivation can improve the quality of life, the prognosis of the pancreatic tumor remains globally poor. Conclusion: Ultrasonography permits to specify the seat of the tumor, to assess its local and regional extension as well as the compression of the biliary and pancreatic ducts.
THE EFFECT ON DIETARY QUALITY OF PARTICIPATION IN THE FOOD STAMP AND WIC PROGRAMS

Participants in the Food Stamp Program consume more meats, added sugars, and total fats than they would in the absence of the program, while their consumption of fruits, vegetables, grains, and dairy products stays about the same. Participants in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) consume significantly less added sugars, which may reflect the substitution of WIC-supplied juices and cereals in place of higher sugar soft drinks and cereals. These findings come from a study of low-income Americans using the Continuing Survey of Food Intake by Individuals.
A retrospective review of group B streptococcal infection in the Metro East area of the Western Cape province: 2010 to 2011

Effective strategies to prevent infant death rely on knowledge of prevalent pathogens. Recent publications have drawn attention to limited data on the contribution of group B streptococcal infection to neonatal and infant mortality in resource-restricted settings. The aim was to describe all cases of group B streptococcal infection isolated from the blood culture of infants up to 90 days of age in two South African hospitals over a two-year period. A retrospective record review took place of infants in whom group B streptococcus was isolated from blood culture or cerebrospinal fluid from January 2010 and December 2011. The maternal records of infants were also reviewed. Data were analysed using Stata® version 1.1. Forty-one cases of group B streptococcal infection were identified, for which 33 records were available for analysis. There was early-onset disease in 14 (42.4%) and late-onset disease in 19 (57.6%) of the infants. Eight (24%) infants were human immunodeficiency virus (HIV)- exposed. There was a.
Cyclopia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research

Cyclopia is characterized by the presence of a single eye, with varying degrees of doubling of the intrinsic ocular structures, located in the middle of the face. It is the severest facial expression of the holoprosencephaly (HPE) spectrum. This study describes the prevalence, associated malformations, and maternal characteristics among cases with cyclopia. Data originated in 20 Clearinghouse (ICBDSR) affiliated birth defect surveillance systems, reported according to a single pre‐established protocol. A total of 257 infants with cyclopia were identified. Overall prevalence was 1 in 100,000 births (95%CI: 0.89–1.14), with only one program being out of range. Across sites, there was no correlation between cyclopia prevalence and number of births (r = 0.08; P = 0.75) or proportion of elective termination of pregnancy (r = −0.01; P = 0.97). The higher prevalence of cyclopia among older mothers (older than 34) was not statistically significant. The majority of cases were liveborn (122/200; 61%) and females predominated (male/total: 42%). A substantial proportion of cyclopias (31%) were caused by chromosomal anomalies, mainly trisomy 13. Another 31% of the cases of cyclopias were associated with defects not typically related to HPE, with more hydrocephalus, heterotaxia defects, neural tube defects, and preaxial reduction defects than the chromosomal group, suggesting the presence of ciliopathies or other unrecognized syndromes. Cyclopia is a very rare defect without much variability in prevalence by geographic location. The heterogeneous etiology with a high prevalence of chromosomal abnormalities, and female predominance in HPE, were confirmed, but no effect of increased maternal age or association with twinning was observed. © 2011 Wiley Periodicals, Inc.
An Interleukin-6 Receptor-dependent Molecular Switch Mediates Signal Transduction of the IL-27 Cytokine Subunit p28 (IL-30) via a gp130 Protein Receptor Homodimer*

Background: Anti-inflammatory signaling of IL-27, p28, and EBI3 is mediated by gp130 and Wsx-1. Results: Signaling of p28 via IL-6R is mediated by a gp130 homodimer. Conclusion: Signaling of p28 via IL-6R is likely not anti-inflammatory. Significance: We identify the signal receptor complex of p28/IL-6R. IL-27 consists of the cytokine subunit p28 and the non-signaling α-receptor EBI3. p28 was shown to additionally act via the non-signaling membrane-bound IL-6 α-receptor (IL-6R) as an agonistic cytokine but also as a gp130 β-receptor antagonist, leading to inhibition of IL-6 signaling. Here, we developed a strategy for bacterial expression, purification, and refolding of murine p28. We show that p28 did not interfere with IL-6- or IL-27-induced signaling, indicating that p28 has no antagonistic properties. Moreover, we demonstrate that murine p28 acts as an agonistic cytokine via the murine and human IL-6R, indicating that p28 exhibits no species specificity. p28 was able to induce p28-trans-signaling via the soluble IL-6R (sIL-6R), a characteristic property that was initially described for trans-signaling of IL-6 via the sIL-6R. Of notice, p28/sIL-6R trans-signaling was inhibited by the IL-6 trans-signaling antagonist, soluble gp130. At higher concentrations, p28 but not IL-6 was able to induce signaling even in the absence of IL-6R or EBI3. Although IL-27 signals via a heterodimer of the β-receptor chains gp130 and Wsx-1, p28/IL-6R specifically recruits two gp130 β-receptor chains for signal transduction. The binding of p28 to a gp130/Wsx-1 heterodimer or a gp130 homodimer is highly selective and controlled by a novel molecular switch induced by EBI3 or IL-6R, respectively.
The effect of empowerment programs on geriatric depression in daily rehabilitation Farzanegan center of khorramabad city

Background and Aim: This study examined the effect of empowerment programs on geriatric depression in daily rehabilitation center Farzanegan of Khorramabad city. Materials and Methods: In this interventional study, 40 elderly subjects were participated in the city of Khoramabad with a mean age of 65 years old. They were 8 men and 12 women in each group. These people have the ability to perform common tasks without dependence on others and they had no systemic and restrictive disease.Subjects randomly divided into two groups (case and control). In case group, empowerment programs was performed for 40 days and 3 hours in a day. Empowerment program included lifestyle education, rehabilitation services, support services, cultural, sports, arts, tourism and leisure services. Part of the program was general such as training of healthy lifestyle and daily exercise and another part of services was presented based on assessment and diagnosis of treatment and rehabilitation team. This program was produced by designers and experts from the office of country welfare elderly. Depression scores in both group, before the intervention and at the end of intervention was assessed by the beck depression inventory. Results: Using the empowerment program, depression scores were reduced after intervention (P≤0.047 ), however in the control group did not make significant changes in depression scores. Conclusion: The date showed that that regular and consistent application of empowerment program can an effective and complementary method in conjunction with other treatments as well as a nondrug therapy in improving depression.
TRPV4‐associated skeletal dysplasias

Dominant mutations in the TRPV4 gene result in a bone dysplasia family and form a continuous phenotypic spectrum that includes, in decreasing severity, lethal, and nonlethal metatropic dysplasia (MD), spondylometaphyseal dysplasia Kozlowski type (SMDK), and autosomal dominant brachyolmia. Several rare variant phenotypes that have some overlap but deviate in some ways from the general pattern have also been described. The known variant phenotypes are spondyloepiphyseal dysplasia Maroteaux type (Pseudo‐Morquio type 2), parastremmatic dysplasia, and familial digital arthropathy with brachydactyly. Interestingly, different TRPV4 mutations have been associated with dominantly inherited neurologic disorders such as congenital spinal muscular atrophy and hereditary motor and sensory neuropathy. Finally, a small number of patients have been identified in whom a TRPV4 mutation results in a phenotype combining skeletal dysplasia with peripheral neuropathy. The TRPV4 gene encodes a regulated calcium channel implicated in multiple and diverse cellular processes. Over 50 different TRPV4 mutations have been reported, with two codons appearing to be mutational hot spots: P799 in exon 15, mostly associated with MD, and R594 in exon 11, associated with SMDK. While most pathogenic mutations tested so far result in activation of the calcium channel in vitro, the mechanisms through which TRPV4 activation results in skeletal dysplasia and/or peripheral neuropathy remain unclear and the genotype–phenotype correlations in this group of disorders remains somewhat mysterious. Since the phenotypic expression of most mutations seems to be relatively constant, careful clinical and radiographic assessment is useful in directing molecular analysis. © 2012 Wiley Periodicals, Inc.