Association of dietary fat intakes with risk of esophageal and gastric cancer in the NIH-AARP diet and health study

The aim of our study was to investigate whether intakes of total fat and fat subtypes were associated with esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), gastric cardia or gastric noncardia adenocarcinoma. From 1995–1996, dietary intake data was reported by 494,978 participants of the NIH-AARP cohort. The 630 EAC, 215 ESCC, 454 gastric cardia and 501 gastric noncardia adenocarcinomas accrued to the cohort. Cox proportional hazards regression was used to examine the association between the dietary fat intakes, whilst adjusting for potential confounders. Although apparent associations were observed in energy-adjusted models, multivariate adjustment attenuated results to null [e.g., EAC energy adjusted hazard ratio (HR) and 95% confidence interval (95% CI) 1.66 (1.27–2.18) p for trend <0.01; EAC multivariate adjusted HR (95% CI) 1.17 (0.84–1.64) p for trend 5 0.58]. Similar patterns were also observed for fat subtypes [e.g., EAC saturated fat, energy adjusted HR (95% CI) 1.79 (1.37–2.33) p for trend <0.01; EAC saturated fat, multivariate adjusted HR (95% CI) 1.27 (0.91–1.78) p for trend 5 0.28]. However, in multivariate models an inverse association for polyunsaturated fat (continuous) was seen for EAC in subjects with a body mass index (BMI) in the normal range (18.5–<25 kg/m2) [HR (95% CI) 0.76 (0.63–0.92)], that was not present in overweight subjects [HR (95% CI) 1.04 (0.96–1.14)], or in unstratified analysis [HR (95% CI) 0.97 (0.90–1.05)]. p for interaction 5 0.02. Overall, we found null associations between the dietary fat intakes with esophageal or gastric cancer risk; although a protective effect of polyunsaturated fat intake was seen for EAC in subjects with a normal BMI.

Association of MYH9/APOL1 with chronic kidney disease in a UK population

Following the first report on the association between MYH9 gene variants and glomerular disorders [1], many studies have evaluated MYH9 loci for association with a range of kidney diseases [2]. In 2010, functional mutations in the adjacent APOL1 gene were identified as the primary variants responsible for associations with kidney disease that had previously been attributed to the MHY9 gene [3]. Nevertheless, several loci within MHY9 continue to be independently reported as risk factors for chronic kidney disease (CKD) [2, 4].

Delayed association of the NADPH oxidase complex with macrophage vacuoles containing the opportunistic pathogen Burkholderia cenocepacia

Burkholderia cenocepacia causes chronic lung infections in patients suffering from cystic fibrosis and chronic granulomatous disease. We have previously shown that B. cenocepacia survives intracellularly in macrophages within a membrane vacuole (BcCV) that delays acidification. Here, we report that after macrophage infection with live B. cenocepacia there is a approximately 6 h delay in the association of NADPH oxidase with BcCVs, while heat-inactivated bacteria are normally trafficked into NADPH oxidase-positive vacuoles. BcCVs in macrophages treated with a functional inhibitor of the cystic fibrosis transmembrane conductance regulator exhibited a further delay in the assembly of the NADPH oxidase complex at the BcCV membrane, but the inhibitor did not affect NADPH oxidase complex assembly onto vacuoles containing heat-inactivated B. cenocepacia or live Escherichia coli. Macrophages produced less superoxide following B. cenocepacia infection as compared to heat-inactivated B. cenocepacia and E. coli controls. Reduced superoxide production was associated with delayed deposition of cerium perhydroxide precipitates around BcCVs of macrophages infected with live B. cenocepacia, as visualized by transmission electron microscopy. Together, our results demonstrate that intracellular B. cenocepacia resides in macrophage vacuoles displaying an altered recruitment of the NADPH oxidase complex at the phagosomal membrane. This phenomenon may contribute to preventing the efficient clearance of this opportunistic pathogen from the infected airways of susceptible patients.

A genome-wide association study provides evidence for association of chromosome 8p23 (MYP10) and 10q21.1 (MYP15) with high myopia in the French population.

PURPOSE. Myopia is a complex trait affected by both genetic and environmental factors. High myopia is associated with increased risk of sight-threatening eye disorders such as retinal detachment. The purpose of this genome-wide association study was to identify susceptibility genes contributing to high myopia in the French population. METHODS. High myopic cases were genotyped using Affymetrix SNP 6.0 chips and population controls were selected from the GABRIEL French dataset in which samples were genotyped by Illumina Human610 quad array. The association study was conducted using 152,234 single nucleotide polymorphisms that were present on both manufacturers' chips in 192 high myopic cases and 1064 controls to identify associated regions. Imputation was performed on peak regions. RESULTS. Associations were found at known myopia locus MYP10 on chromosome 8p23 and MYP15 on chromosome 10q21.1. Rs189798 (8p23) and rs10825992 (10q21.1) showed the strongest associations in these regions (P=6.32x10-7 and P=2.17x10-5, respectively). The imputed results at 8p23 showed 2 peaks of interest. The first spanned 30kb including rs189798 between MIR4660 and PPP1R3B with the most significant association at rs17155227 (P=1.07x10-10). The second novel peak was 4kb in length, encompassing MIR124-1 and the MSRA gene, with the strongest association at rs55864141 (P=1.30x10-7). The peak of imputed data at 10q21.1 was 70kb in length between ZWINT and MIR3924, with rs3107503 having the lowest P value (P=1.54x10-7). CONCLUSION. We provide evidence for the association of MYP10 at 8p23 and MYP15 at 10p21.1 with high myopia in the French population and refine these regions of association.

Vibrational state-selected photodissociation of ClO+

We report on the UV photodissociation of specific vibrational states (v = 2–45) of ClO+ using velocity map
ion imaging. The high vibrational states of ClO+ are prepared via a double resonant scheme through the
ClO (A 2P) state and ion-pair states followed by photoionization with a third photon. The absorption of a
fourth photon results in photodissociation of the ClO+ into two dominant asymptotic channels. The Cl+
and O+ fragment ion images reveal information on both the energetics of high-lying cation vibrational
states and the low-lying dissociative electronic states that correlate to Cl+(3P) + O(3P) and Cl(2P) + O+(4S)
asymptotic channels. We also report ab initio potentials for the bound ClO+ and ion-pair states as well as
calculations of the ClO+ excited states relevant to the photodissociation process.

Association of retinal arteriolar dilatation with lower verbal memory::The Edinburgh Type 2 Diabetes Study

Abstract


AIMS/HYPOTHESIS:

Retinal vascular calibre changes may reflect early subclinical microvascular disease in diabetes. Because of the considerable homology between retinal and cerebral microcirculation, we examined whether retinal vascular calibre, as a proxy of cerebral microvascular disease, was associated with cognitive function in older people with type 2 diabetes.

METHODS:

A cross-sectional analysis of 954 people aged 60-75 years with type 2 diabetes from the population-based Edinburgh Type 2 Diabetes Study was performed. Participants underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. The Mill Hill Vocabulary Scale was used to estimate pre-morbid cognitive ability. Retinal vascular calibre was measured from an image field with the optic disc in the centre using a validated computer-based program.

RESULTS:

After age and sex adjustment, larger retinal arteriolar and venular calibres were significantly associated with lower scores for the Wechsler Logical Memory test, with standardised regression coefficients -0.119 and -0.084, respectively (p?<?0.01), but not with other cognitive tests. There was a significant interaction between sex and retinal vascular calibre for logical memory. In male participants, the association of increased retinal arteriolar calibre with logical memory persisted (p?<?0.05) when further adjusted for vocabulary, venular calibre, depression, cardiovascular risk factors and macrovascular disease. In female participants, this association was weaker and not significant.

CONCLUSIONS/INTERPRETATION:

Retinal arteriolar dilatation was associated with poorer memory, independent of estimated prior cognitive ability in older men with type 2 diabetes. The sex interaction with stronger findings in men requires confirmation. Nevertheless, these data suggest that impaired cerebral arteriolar autoregulation in smooth muscle cells, leading to arteriolar dilatation, may be a possible pathogenic mechanism in verbal declarative memory decrements in people with diabetes.

The Association of Skin-Intrinsic Fluorescence With Type 1 Diabetes Complications in the DCCT/EDIC Study

OBJECTIVESTo determine whether skin-intrinsic fluorescence (SIF) is associated with long-term complications of type 1 diabetes (T1D) and, if so, whether it is independent of chronic glycemic exposure and previous intensive therapy.RESEARCH DESIGN AND METHODSWe studied 1,185 (92%) of 1,289 active Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) participants from 2010 to 2011. SIF was determined using a fluorescence spectrometer and related cross-sectionally to recently determined measures of retinopathy (stereo fundus photography), cardiac autonomic neuropathy (CAN; R-R interval), confirmed clinical neuropathy, nephropathy (albumin excretion rate [AER]), and coronary artery calcification (CAC).RESULTSOverall, moderately strong associations were seen with all complications, before adjustment for mean HbA1c over time, which rendered these associations nonsignificant with the exception of sustained AER >30 mg/24 h and CAC, which were largely unaffected by adjustment. However, when examined within the former DCCT treatment group, associations were generally weaker in the intensive group and nonsignificant after adjustment, while in the conventional group, associations remained significant for CAN, sustained AER >30 mg/24 h, and CAC even after mean HbA1c adjustment.CONCLUSIONSSIF is associated with T1D complications in DCCT\EDIC. Much of this association appears to be related to historical glycemic exposure, particularly in the previously intensively treated participants, in whom adjustment for HbA1c eliminates statistical significance.

No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF)

The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p. Analysis of linkage disequilibrium (LD) across the 252 kb interval encompassing the 7 marker core Icelandic/Scottish NRG1 haplotype revealed two separate regions of modest LD, comprising markers SNP8NRG255133, SNP8NRG249130 and SNP8NRG243177 (telomeric) and microsatellites 478B14-428, 420M9-1395, D8S1810 and 420M9-116I12 (centromeric). From single marker analysis by TRANSMIT and FBAT we found no evidence for association with schizophrenia for any marker. Haplotype analysis for the three SNPs in LD region 1 and, separately, the four microsatellites in LD region 2 (analyzed in overlapping 2-marker windows), showed no evidence for overtransmission of specific haplotypes to affected individuals. We therefore conclude that if NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the ISHDSF.

Community Engagement in Ireland's Developmental Welfare State: a study of the life cycle approach

The idea that people matter in modern democracies, often referred to as 'civic engagement' is recognised at the highest international level (United Nations 2008: 9). Civic or community engagement is essential to how budgets are decided, policy is developed and public services delivered. Significantly, community engagement is crucial in developing policy for sustained economic and social development. In Ireland the idea of the Developmental Welfare State (DWS) is based on the premise that the social policy system should support citizens so as to reach their full potential. Such a system comprises three overlapping elements: tax and welfare transfer, the provision of services and activist initiatives (National Economic and Social Council, 2005: ix-xviii). Civil Society Organisations have been challenged to 'operationalise the DWS' using a 'life cycle framework' as part of Ireland's corporatist partnership model (Department of Taoiseach, 2006: 40).

Association of physical activity with future mental health in older, mid-life and younger women

Background: Mental ill-health, particularly depression and anxiety, is a leading and increasing cause of disability worldwide, especially for women.

Methods: We examined the prospective association between physical activity and symptoms of mental ill-health in younger, mid-life and older working women. Participants were 26 913 women from the ongoing cohort Finnish Public Sector Study with complete data at two phases, excluding those who screened positive for mental ill-health at baseline. Mental health was assessed using the 12-item General Health Questionnaire. Self-reported physical activity was expressed in metabolic equivalent task (MET) hours per week. Logistic regression models were used to analyse associations between physical activity levels and subsequent mental health.

Results: There was an inverse dose–response relationship between physical activity and future symptoms of mental ill-health. This association is consistent with a protective effect of physical activity and remained after adjustments for socio-demographic, work-related and lifestyle factors, health and body mass index. Furthermore, those mid-life and older women who reported increased physical activity by more than 2 MET hours per week demonstrated a reduced risk of later mental ill-health in comparison with those who did not increase physical activity. This protective effect of increased physical activity did not hold for younger women.

Conclusions: This study adds to the evidence for the protective effect of physical activity for later mental health in women. It also suggests that increasing physical activity levels may be beneficial in terms of mental health among mid-life and older women. The alleviation of menopausal symptoms may partly explain age effects but further research is required.

The executive committee of the Greek Professional Association of Social Work in an age of austerity: examining its response

This paper explores the response by the Greek Association of Social Workers (SKLE) to Greece's current economic crisis. Socioeconomic conditions in Greece have deteriorated rapidly since the imposition of a Structural Adjustment Programme as a condition of the loan Troika provided to Greece to address its class-based public debt crisis. Interviews were conducted with SKLE Executive Committee members to examine SKLE's response in the context of newly raised inequalities. Research results show that SKLE recognised the negative consequences to both service users and its members. However, SKLE continues to reformulate its strategy mostly as a social partner. SKLE's previous strategy entailed amongst other things the analysis of policy proposals and participation in welfare related government committees. This strategy is no longer relevant because decision-making powers have been transferred to transnational bodies. This paper elaborates on these findings and discusses the barriers that prohibit SKLE from differentiation of its strategy. Although the research is country specific, it has implications for the broader global debate because professional associations must reformulate their strategies for better serving of both their constituents and the collective good based on the social justice mandate of the profession.