Miracle-dz/UniFAR-FTUs huggingface dataset:
A twin study of schizoaffective‐mania, schizoaffective‐depression, and other psychotic syndromes

The nosological status of schizoaffective disorders remains controversial. Twin studies are potentially valuable for investigating relationships between schizoaffective‐mania, schizoaffective‐depression, and other psychotic syndromes, but no such study has yet been reported. We ascertained 224 probandwise twin pairs [106 monozygotic (MZ), 118 same‐sex dizygotic (DZ)], where probands had psychotic or manic symptoms, from the Maudsley Twin Register in London (1948–1993). We investigated Research Diagnostic Criteria schizoaffective‐mania, schizoaffective‐depression, schizophrenia, mania and depressive psychosis primarily using a non‐hierarchical classification, and additionally using hierarchical and data‐derived classifications, and a classification featuring broad schizophrenic and manic syndromes without separate schizoaffective syndromes. We investigated inter‐rater reliability and co‐occurrence of syndromes within twin probands and twin pairs. The schizoaffective syndromes showed only moderate inter‐rater reliability. There was general significant co‐occurrence between syndromes within twin probands and MZ pairs, and a trend for schizoaffective‐mania and mania to have the greatest co‐occurrence. Schizoaffective syndromes in MZ probands were associated with relatively high risk of a psychotic syndrome occurring in their co‐twins. The classification of broad schizophrenic and manic syndromes without separate schizoaffective syndromes showed improved inter‐rater reliability, but high genetic and environmental correlations between the two broad syndromes. The results are consistent with regarding schizoaffective‐mania as due to co‐occurring elevated liability to schizophrenia, mania, and depression; and schizoaffective‐depression as due to co‐occurring elevated liability to schizophrenia and depression, but with less elevation of liability to mania. If in due course schizoaffective syndromes show satisfactory inter‐rater reliability and some specific etiological factors they could alternatively be regarded as partly independent disorders. © 2011 Wiley Periodicals, Inc.
RISK FACTORS OF TUBERCULOSIS TREATMENT FAILURE IN SOUTH-EAST OF IRAN

Background and Objective: Failure of tuberculosis (TB) treatment is a major problem of health systems in developing countries. This study was done to identify the Risk factors of tuberculosis treatment failure in the Sistan and Bulochestan province, the high risk region in South-East of Iran. Methods: This case – control study was carried out on 52 tuberculosis patients (smear -positive and category- I therapy) treated during six months period. Patients with treatment failure were considered as cases and patients with negative smear after 6 months of treatment with anti-tuberculosis (TB) medicines were considered as control group. Demographic, clinical and treatment outcomes were recorded for each patient. The multivariate logistic regression was performed to determine the predictors of treatment failure. Results: Family history of tuberculosis (95% CI: 1-12.56, OR=3.55, P=0.04, ), smoking (95% CI:1.5851.21, OR=9, P=0.01), drug addiction before or during the treatment period (95% CI: 5.28-123.91, OR=25.6, P=0.0001) and low body weight (95% CI:1.05-12.6, OR=3.65, P=0.04 ) were risk factors for treatment failure.
Maternal smoking during pregnancy and child emotional problems: The relevance of maternal and child 5‐HTTLPR genotype

Serotonin is involved in the development of neural circuits modulating emotional behavior. The short allele (s) of a polymorphism (5‐HTTLPR) of the serotonin transporter gene is a risk factor for psychopathology in the presence of environmental stressors. Maternal smoking is associated with growth restriction of the human fetal brain and adverse effects of nicotine on the developing serotonin system have been documented. We hypothesized that maternal smoking interacts with both child and mother 5‐HTTLPR genotype as a risk factor for later child emotional problems. In a sample of n = 1,529 mother–child dyads, smoking habits were assessed by questionnaires during pregnancy. Child emotional problems were measured by the Child Behavior Checklist at the child's age of 3 years. Maternal smoking during pregnancy significantly increased the risk for emotional problems in children carrying the s‐allele; β = 0.24, P = 0.03 (mother‐report), and β = 0.46, P = 0.001 (father‐report). In children heterozygous at 5‐HTTLPR and exposed to maternal prenatal smoking (n = 79) risk of emotional problems increased with each additional s‐allele the mother carried. The associations between 5‐HTTLPR and child emotional problems were not moderated by paternal prenatal smoking. These findings imply that the vulnerability for emotional problems in s‐allele carriers may already originate in fetal life. © 2012 Wiley Periodicals, Inc.
Health at work in small and medium sized enterprises: Issues of engagement

Purpose – This paper aims to explore a health at work initiative (“Fair Chance at Work”) for small and medium sized enterprises (SMEs) and identify opportunities for improving engagement of businesses in such activities.Design/methodology/approach – A case study approach is usedFindings – Two problems are identified ‐ engagement and participation. A model of engagement incorporating aspects of Prochaska and DiClemente's transtheoretical model of behaviour change is proposed based on findings from the case study and existing literature. It is concluded that improving the engagement of SMEs requires a greater understanding of their current needs, perceptions and attitudes towards health at work. Schemes such as the Teaching Companies Scheme could be useful in testing the model.Research limitations/implications – The Teaching Companies Scheme could be useful in testing the model.Practical implications – These findings may inform the development of health promotion projects to SMEs using an applied model beha.
Association of genetic variations in DTNBP1 with cognitive function in schizophrenia patients and healthy subjects

The dystrobrevin‐binding protein 1 gene (DTNBP1) has been regarded as a susceptibility gene for schizophrenia. Recent studies have investigated its role on cognitive function that is frequently impaired in schizophrenia patients, and generated inconsistent results. The present study was performed to elucidate effects of genetic variations in DTNBP1 on various cognitive domains in both schizophrenia patients and healthy subjects. Comprehensive neuropsychological tests were administered to 122 clinically stable schizophrenia patients and 119 healthy subjects. Based on positive findings reported in previous association studies, six SNPs were selected and genotyped. Compared to healthy subjects, schizophrenia patients showed expected lower performance for all of the cognitive domains. After adjusting for age, gender, and educational level, four SNPs showed a nominally significant association with cognitive domains. The association of rs760761 and rs1018381 with the attention and vigilance domain remained significant after applying the correction for multiple testing (P < 0.001). Similar association patterns were observed both, in patients and healthy subjects. The observed results suggest the involvement of DTNBP1 not only in the development of attention deficit of schizophrenia, but also in the inter‐individual variability of this cognitive domain within the normal functional range. © 2012 Wiley Periodicals, Inc.
An association and haplotype analysis of porcine maternal infanticide: A model for human puerperal psychosis?

An association analysis using the Illumina porcine SNP60 beadchip was performed to identify SNPs significantly associated with porcine maternal infanticide. We previously hypothesised that this was a good animal model for human puerperal psychosis, an extreme form of postnatal mood disorder. Animals were selected from carefully phenotyped unrelated infanticide and control groups (representing extremes of the phenotypic spectrum), from four different lines. Permutation and sliding window analyses and an analysis to see which haplotypes were in linkage disequilibrium (LD) were compared to identify concordant regions. Across all analyses, intervals on SSCs 1, 3, 4, 10, and 13 were constant, contained genes associated with psychiatric or neurological disorders and were significant in multiple lines. The strongest (near GWS) consistent candidate region across all analyses and all breeds was the one located on SSC3 with one peak at 23.4 Mb, syntenic to a candidate region for bipolar disorder and another at 31.9 Mb, syntenic to a candidate region for human puerperal psychosis (16p13). From the haplotype/LD analysis, two regions reached genome wide significance (GWS): the first on SSC4 (KHDRBS3 to FAM135B), which was significant (−logP 5.57) in one Duroc based breed and is syntenic to a region in humans associated with cognition and neurotism; the second on SSC15, which was significant (−log10P 5.68) in two breeds and contained PAX3, which is expressed in the brain. © 2012 Wiley Periodicals, Inc.
Regulation of Endothelial Nitric-oxide Synthase (NOS) S-Glutathionylation by Neuronal NOS

Background: Whether neuronal nitric-oxide synthase (nNOS) plays a role in the endothelial NOS (eNOS)-dependent negative inotropic effect of β3-adrenergic stimulation remains to be established. Results: nNOS knock-out or inhibition leads to increased superoxide production, eNOS uncoupling, and abrogation of β3-adrenergic responses. Conclusion: Disabling nNOS disrupts eNOS function and downstream signaling. Significance: nNOS plays a crucial role in preserving myocardial nitroso-redox balance and coupled eNOS activity. Myocardial constitutive No production depends on the activity of both endothelial and neuronal NOS (eNOS and nNOS, respectively). Stimulation of myocardial β3-adrenergic receptor (β3-AR) produces a negative inotropic effect that is dependent on eNOS. We evaluated whether nNOS also plays a role in β3-AR signaling and found that the β3-AR-mediated reduction in cell shortening and [Ca2+]i transient amplitude was abolished both in eNOS−/− and nNOS−/− left ventricular (LV) myocytes and in wild type LV myocytes after nNOS inhibition with S-methyl-l-thiocitrulline. LV superoxide (O2̇̄) production was increased in nNOS−/− mice and reduced by l-Nω-nitroarginine methyl ester (l-NAME), indicating uncoupling of eNOS activity. eNOS S-glutathionylation and Ser-1177 phosphorylation were significantly increased in nNOS−/− myocytes, whereas myocardial tetrahydrobiopterin, eNOS Thr-495 phosphorylation, and arginase activity did not differ between genotypes. Although inhibitors of xanthine oxidoreductase (XOR) or NOX2 NADPH oxidase caused a similar reduction in myocardial O2̇̄, only XOR inhibition reduced eNOS S-glutathionylation and Ser-1177 phosphorylation and restored both eNOS coupled activity and the negative inotropic and [Ca2+]i transient response to β3-AR stimulation in nNOS−/− mice. In summary, our data show that increased O2̇̄ production by XOR selectively uncouples eNOS activity and abolishes the negative inotropic effect of β3-AR stimulation in nNOS−/− myocytes. These findings provide unequivocal evidence of a functional interaction between the myocardial constitutive NOS isoforms and indicate that aspects of the myocardial phenotype of nNOS−/− mice result from disruption of eNOS signaling.
Screening the risk of falls: a general or a specific instrument?

AIMS AND OBJECTIVES The aim of this study is to investigate if a general instrument (Care Dependency Scale; CDS) has the same sensitivity and specificity as a specific instrument (Hendrich Fall Risk Model; HFRM) in a screening for fall risks. BACKGROUND Falls of older patients are a common problem in hospitals. Apart from falls risk, nurses have to use many assessment tools to detect the patients' different care problems. To decrease the workload it would be helpful to have a general instrument used as a first screening for possible risks for different healthcare problems, such as falls, instead of specific risk instruments for each individual healthcare problem. DESIGN A prospective design was used by measuring each patient upon admission and by registering all falls during their hospital stay. METHODS The sample consisted of 560 patients of a geriatric hospital in Germany. All of whom gave their informed consent to participate in the study. Nurses filled in the CDS and the HFRM at the time of hospital admission. RESULTS The CDS (cut off point <or=54) had a sensitivity of 75% (47/63 fallers) and a specificity of 46% (227/497 non-fallers). The HFRM (cut off point >or=11) had a sensitivity of 75% (47/63 fallers) and a specificity of 47% (237/497 non-fallers). CONCLUSION The results of the CDS are similar to those of the HFRM in predicting falls. Relevance to clinical practice. The use of the CDS is preferred as it is more general and more reliable than the HFRM. The workload for nursing staff can be decreased when only one instrument is used.
The Autophagy-related Gene 14 (Atg14) Is Regulated by Forkhead Box O Transcription Factors and Circadian Rhythms and Plays a Critical Role in Hepatic Autophagy and Lipid Metabolism*

Background: Atg14 is critical for the autophagy initiation. Results: Our data show that the Atg14 gene can be regulated by FoxO and Clock transcription factors, and it has striking impacts on hepatic autophagy and triglycerides. Conclusion: Atg14 is controlled by FoxOs and circadian rhythms, and it modulates hepatic lipid homeostasis. Significance: These findings suggest that Atg14 is crucial for hepatic autophagy and lipid metabolism. Autophagy plays a critical role in cell survival from prolonged starvation and recycling of aggregated proteins and damaged organelles. One of the essential genes involved in the autophagic initiation is autophagy-related 14 (Atg14), also called Barkor for Beclin 1-associated autophagy-related key regulator. Although its crucial role in the autophagic process has been reported, the gene regulation of Atg14 and its metabolic functions remain unclear. In this work we have identified that the Atg14 gene is regulated by forkhead box O (FoxO) transcription factors and circadian rhythms in the mouse liver. Luciferase reporter analyses and chromatin immunoprecipitation assays have revealed well conserved cis-elements for FoxOs and Clock/Bmal1 in the proximal promoter of the Atg14 gene. To examine the functions of hepatic Atg14, we have performed the gene knockdown and overexpression in the mouse livers. Remarkably, knockdown of Atg14 leads to elevated levels of triglycerides in the liver and serum as well. Conversely, overexpression of Atg14 improves hypertriglyceridemia in both high fat diet-treated wild-type mice and FoxO1/3/4 liver-specific knock-out mice. In summary, our data suggest that Atg14 is a new target gene of FoxOs and the core clock machinery, and this gene plays an important role in hepatic lipid metabolism.
Pregnancy-associated Aplastic Anemia: Case Report

Aplastic anemia in pregnancy is a rare condition with high maternal morbidity and mortality rates. Intensive hematological support during antenatal course remains the mainstay of the therapy. A successful obstetric outcome can be best accomplished with the clinical collaboration of the obstetrician and the hematologist. We present a patient with moderately severe aplastic anemia who was managed with intensive hematological support given repeatedly once in a month during pregnancy. She delivered a healthy infant by cesarean section. Gebelikte aplastik anemi yuksek mortalite ve morbidite oranlarina sahip ender bir durumdur. Tedavinin temelini gebelik suresi boyunca uygulanan yogun hematolojik destek olusturmaktadir. Basarili bir obstetrik sonuc en iyi sekilde obstetrisyen ve hematologun klinik isbirligi ile gerceklestirilebilir. Bu yazida orta ciddi aplastik anemisi olup, gebeligi suresince ayda bir kez tekrarlanan yogun hematolojik destekle tedavi edilen bir hasta sunulmaktadir. Hasta sezaryen ile saglikli bir cocuk dogurmustur.
Private prayer as a suitable intervention for hospitalised patients: a critical review of the literature.

AIM This critical review seeks to identify if there is evidence that private (personal) prayer is capable of improving wellbeing for adult patients in hospital. BACKGROUND The review was conducted in the belief that the spiritual needs of hospitalised patients may be enhanced by encouragement and support to engage in prayer. DESIGN Systematic review. METHOD A systematic approach was used to gather evidence from published studies. In the absence of experimental research involving this type of population, evidence from qualitative and correlational studies was critically reviewed. Results. The findings indicate that private prayer, when measured by frequency, is usually associated with lower levels of depression and anxiety. Most of the studies that show positive associations between prayer and wellbeing were located in areas that have strong Christian traditions and samples reported a relatively high level of religiosity, church attendance and use of prayer. Church attenders, older people, women, those who are poor, less well educated and have chronic health problems appear to make more frequent use of prayer. Prayer appears to be a coping action that mediates between religious faith and wellbeing and can take different forms. Devotional prayers involving an intimate dialogue with a supportive God appear to be associated with improved optimism, wellbeing and function. In contrast, prayers that involve pleas for help may, in the absence of a pre-existing faith, be associated with increased distress and possibly poorer function. CONCLUSION Future research needs to differentiate the effects of different types of prayer. RELEVANCE TO CLINICAL PRACTICE Encouragement to engage in prayer should be offered only following assessment of the patient's faith and likely content and form of prayer to be used. Hospitalised patients who lack faith and whose prayers involve desperate pleas for help are likely to need additional support from competent nursing and chaplaincy staff.
Inner power, physical strength and existential well-being in daily life: relatives' experiences of receiving soft tissue massage in palliative home care.

AIM AND OBJECTIVES This article explores relatives' experiences of receiving soft tissue massage as a support supplement while caring for a dying family member at home. BACKGROUND In palliative home care, relatives play an important role as carers to seriously ill and dying family members. To improve their quality of life, different support strategies are of importance. Complementary methods, such as soft tissue massage have become an appreciated supplement for these patients. However, only few studies focus on relatives experiences of receiving soft tissue massage as a supplemental support. DESIGN Qualitative design METHOD Nineteen relatives received soft tissue massage (hand or foot) nine times (25 minutes) in their homes. Open-ended semi-structured tape-recorded interviews were conducted once per relative after the nine times of massage, using qualitative content analysis. RESULTS Soft tissue massage gave the relatives' feelings of 'being cared for', 'body vitality' and 'peace of mind'. For a while, they put worries of daily life aside as they just experienced 'being'. During massage, it became apparent that body and mind is constituted of an indestructible completeness. The overarching theme was 'inner power, physical strength and existential well-being in their daily lives'. CONCLUSION All relatives experienced soft tissue massage positively, although they were under considerable stress. Soft tissue massage could be an option to comfort and support relatives in palliative home care. RELEVANCE TO CLINICAL PRACTICE In palliative nursing care, soft tissue massage could present a worthy supplement in supporting caring relatives.
The Stress Protein BAG3 Stabilizes Mcl-1 Protein and Promotes Survival of Cancer Cells and Resistance to Antagonist ABT-737*

Background: Mcl-1 inhibits apoptosis and promotes survival of cancer cells. Results: The Hsp70 co-chaperone, BAG3, prevents Mcl-1 degradation by the proteasome. Conclusion: BAG3 sustains Mcl-1 expression in cancer cells, promoting its antiapoptotic activity. Significance: Mcl-1 expression is a major determinant of resistance in human cancer, so BAG3 is a potential target for anticancer drug discovery. Members of the Bcl-2 family of proteins are important inhibitors of apoptosis in human cancer and are targets for novel anticancer agents such as the Bcl-2 antagonists, ABT-263 (Navitoclax), and its analog ABT-737. Unlike Bcl-2, Mcl-1 is not antagonized by ABT-263 or ABT-737 and is considered to be a major factor in resistance. Also, Mcl-1 exhibits differential regulation when compared with other Bcl-2 family members and is a target for anticancer drug discovery. Here, we demonstrate that BAG3, an Hsp70 co-chaperone, protects Mcl-1 from proteasomal degradation, thereby promoting its antiapoptotic activity. Using neuroblastoma cell lines, with a defined Bcl-2 family dependence, we found that BAG3 expression correlated with Mcl-1 dependence and ABT-737 resistance. RNA silencing of BAG3 led to a marked reduction in Mcl-1 protein levels and overcame ABT-737 resistance in Mcl-1-dependent cells. In ABT-737-resistant cells, Mcl-1 co-immunoprecipitated with BAG3, and loss of Mcl-1 after BAG3 silencing was prevented by proteasome inhibition. BAG3 and Mcl-1 were co-expressed in a panel of diverse cancer cell lines resistant to ABT-737. Silencing BAG3 reduced Mcl-1 protein levels and overcame ABT-737 resistance in several of the cell lines, including triple-negative breast cancer (MDA-MB231) and androgen receptor-negative prostate cancer (PC3) cells. These studies identify BAG3-mediated Mcl-1 stabilization as a potential target for cancer drug discovery.
Gaps: an elusive source of phylogenetic information.

In this paper, we use an example shorebird data set to explore three related questions regarding the interplay between alignment and phylogeny estimation: 1) can gap-rich alignments be used for reasonably accurate and unbiased phylogenetic inference? 2) How much phylogenetic information is contained in gap characters as compared with the nucleotides alone? 3) Are models of the insertion/deletion process advantageous and if so at what level of phylogenetic divergence? We report that there is considerable information created by the indel (insertion/deletion) process that is potentially available for phylogenetic inference. Ideally, we should be able to independently obtain the same tree from both nucleotide characters and from gap characters; however, there is still considerable variability in the alignments produced by different programs.We predict that better and more computationally tractable models of the indel process will be required before the information in gaps can be fully exploited for phylogenetic inference.