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Environmental and genetic factors play important roles in the development of schizophrenia (SCZ), bipolar disorder (BPD) or major depressive disorder (MDD). Some risk loci are identified with shared genetic effects on major psychiatric disorders. To investigate whetherWe focussed on 11 single-nucleotide polymorphisms (SNPs) harbouringWe found that rs3743592 was significantly associated with MDD and rs6498263 with BPD in both allele and genotype distributions. Before correction, rs3743592 showed allelic and genotypic significance with SCZ, rs6498263 showed allelic significance with SCZ. WGCNA identified top 10 modules of co-expressed genes. Gene Ontology (GO) and pathway analysis were used to examine the functions of SNX29, which revealed that SNX29 was involved in the regulation of a number of biological processes, such as TGF-beta, ErbB, and Wnt signalling pathway, etc.Our results supported common risk factors in

Type 2 diabetes (T2DM) is strongly associated with cognitive impairment but the factors within T2DM that predispose to cognitive impairment are less well understood, while previous studies have investigated samples with T2DM of widely varying duration. We aimed to investigate the factors associated with cognitive impairment in patients with newly diagnosed T2DM.In a multi-ethnic sample with T2DM diagnosed in the last 6 months, we assessed cognitive function using the 13-item modified telephone interview for cognitive status (TICS-M). Cognitive function was assessed both categorically (impairment defined as lowest 10% of scores with the remainder as controls) and as continuous TICS-M score. Its associations were tested in univariate and multivariate analyses with a range of biological, psychological and sociodemographic factors.Of 1790 participants, 1680 had a complete TICS-M assessment at baseline. After controlling for covariates, older age (p0.001) and lower verbal intelligence (p0.001) were associated with both cognitive impairment and lower TICS-M scores, while non-white ethnicity (p0.001), female gender (p = 0.02) and higher HbA1c (p = 0.002) were associated with lower TICS-M scores. Depression (defined as Patient Health Questionnaire-9 score ≥10), elevated inflammatory markers and body mass index were not associated with cognitive function after controlling for covariates.Age, verbal intelligence, female gender and HbA1c are associated with cognitive performance in T2DM soon after diagnosis. Previously reported associations with depression and inflammatory markers may occur later as causes or consequences of T2DM. Longitudinal analyses are needed to assess potentially modifiable factors predicting cognitive decline in early T2DM.

Objective: To explore the effect of ever having tried to conceive for more than 12 months on levels of anxiety and depressive symptoms and to investigate if symptom levels of anxiety and depression in infertile women who remain childless, or go on to have children, respectively, differ from symptom levels in mothers without reports of infertility. Methods: Analyses were based on information from 12 584 Norwegian women aged 19–45 years who participated in the North-Trøndelag Health Study from 1995 to 1997 and data from the Medical Birth Registry of Norway. Anxiety and depressive symptoms were measured by the Hospital Anxiety and Depression Scale. Results: Having tried to conceive for more than 12 months (ever) was weakly associated with higher levels of depressive symptoms. In the categorical analyses, women with resolved infertility had higher levels of anxiety symptoms (B = 0.25 (95% confidence interval (CI) = 0.04–0.47)) and voluntarily childfree had lower levels of depressive symptoms (B = –0.05 (95% CI = –0.50 to –0.21)) than mothers without infertility. However, women with current primary or current secondary infertility had levels of anxiety and depression not significantly different from mothers without infertility. Conclusion: At the population level, and from a longitudinal perspective, unresolved infertility is less burdensome than findings from studies on women seeking help for infertility would suggest. publishedVersion

Inflammatory cytokines are implicated in the pathophysiology of both stroke and depression, and their production is influenced by the transcriptional activity of particular gene polymorphisms. We hypothesised that alleles related to higher pro-inflammatory and/or lower anti-inflammatory cytokine production would be associated with post-stroke depression (PSD).In 276 stroke cases, depression was diagnosed using DSM-IV, and classified into major PSD (N = 29), all (major plus minor) PSD (N = 77), and control (N = 199) groups. Genotyping for six pro-inflammatory polymorphisms (TNF-α -850C/T and -308G/A, IL-1β -511C/T and + 3953C/T, IL-6 -174G/C, and IL-8 -251T/A) and two anti-inflammatory polymorphisms (IL-4 + 33T/C and IL-10 -1082G/A) was conducted. Individual associations with PSD were estimated using logistic regression models. Total numbers of potential risk alleles were calculated for pro-inflammatory and anti-inflammatory cytokine genes and analysed against depression using χ(2)-tests.The IL-4 + 33C/C genotype was associated with major PSD, and the IL-10 -1082A/A genotype was associated with all PSD. Increasing numbers of risk alleles for these two anti-inflammatory cytokine genotypes were significantly associated with both PSD categories. No significant associations were found with any pro-inflammatory cytokine allele.Alleles associated with reduced anti-inflammatory cytokine function were associated with PSD, supporting the cytokine hypothesis in its etiology.

Background: Meropenem is a broad-spectrum carbapenem widely used in the treatment of critically ill patients. A generic meropenem product has recently become available in South Africa and we aimed to compare the generic product with the innovator product using established in vitro microbiological testing methods. Method: Comparative minimum inhibitory concentrations (MICs) were determined for 115 clinically relevant isolates using the broth microdilution reference method. Comparative analysis of MIC was done using categorical and essential agreement. A subset of isolates was evaluated using minimum bactericidal concentration (MBC) testing. Results: The overall essential agreement exceeded the international standard of > 90%. A single major error and six minor errors were detected in 230 comparative MICs. For the 55 Enterobacteriaceae isolates tested, the MIC 50 and MIC 90 were 0.03 µg/ml and 0.06 µg/ml respectively, with no difference between extended–spectrum s-lactamase producers (ESBL) and non-ESBL isolates. Bactericidal activity was demonstrated for both generic and innovator products in all isolates tested. For eight of the 11 isolates, the MBC was only twice the MIC. Conclusion: Reference method MIC and MBC testing of a large sample of clinically relevant microorganisms against meropenem has demonstrated comparable in vitro activity between the innovator and generic products. Low MICs and bactericidal activity at concentrations close to the MIC indicate that meropenem remains a useful agent in the treatment of infections caused by ESBLproducing Enterobacteriaceae.

The Regional Powers and Security Framework provides a systematic method to assess how the relative strength and behavior of regional powers influence regional security orders. This article applies the framework to India as a South Asian regional power. The analysis indicates that although the region is unipolar; India's impact is limited because of its failure to play leadership and custodianship roles. It does serve as a protector of the region from external threats, doing so through a unilateral, status quo, and reactive orientation. Application of this framework points to a lack of a hegemonic security order in South Asia, in spite of India's self-view as the region's natural hegemon. For India to be hegemonic, it would have to play these roles in a comprehensive manner.

The postmortem examination of failed IT projects reveals that long before the failure there were significant symptoms or “early warning signs.” This article describes the top 12 people-related and project-related IT project risks, based on “early warning sign” data collected from a panel of 19 experts and a survey of 55 IT project managers.

This work probes the variability in G7 cohesion in response to relatively new disturbances in the international system. Using a domestic politics model, we argue that G7 cohesion weakens in the face of international terrorism in the context of variable domestic consequences to common foreign policy responses to this systemic disturbance. We compare the predictions from our model with predictions stemming from neorealist and liberal/institutionalist explanations. We find that, consistent with the domestic politics explanation, G7 foreign policy cohesion declines as internal terrorism increases.

This article examines how members of the rural elite in Scotland defend their ownership of large tracts of land in the face of powerful class and nationalist critiques. Referring to unique interview material throughout, we outline the key elements of how owners attempt to legitimate their landed interests. Their response to these two critiques relates to estate economics and more generally the ideology and rhetoric of “responsible” stewardship. The latter allows owners to create a distinct status group identity for themselves as “keepers of land,” one that is cohesive and subordinates any expected differences between them in terms of their residence characteristics, how they acquired their land, and their national identity. This is explained with reference to a diminishing system of private estates in Scotland and the need for landowners to maintain a united ideological front as they defend themselves in the face of mounting political pressure and land reform.