Do bipolar subjects' responses to personality questionnaires lack reliability? Evidence from the PsyCoLaus study.

Differences in personality scores between subjects with and without mood disorders might result from response biases rather than specific personality traits per se. The aim of this study was to compare subjects with bipolar disorders (BPD) to non-bipolar subjects in terms of response quality to the NEO-FFI. Using data from the population-based cohort study PsyCoLaus, subjects were compared in terms of responses to the NEO-FFI, and indices of response quality were calculated. Hierarchical regression analyses were performed and controlled for sociodemographic factors, depressive episodes, dysthymia, anxiety disorders and substance use disorders. Consistent with the literature, subjects with BPD had higher scores in neuroticism and openness, and lower scores in conscientiousness. However, significant differences were measured for response reliability and validity. In particular, the indices of response quality including response reliability were lower in subjects with BPD suggesting that bipolar subjects might have more difficulty in providing consistent answers throughout questionnaires. However, regression models resulted in small associations between mania/hypomania and response quality, and showed that differences in response quality were mainly attributable to correlates of BPD instead of the presence of mania/hypomania itself. The current findings suggest that bipolar subjects' responses to questionnaires are biased, making them less reliable

Psychiatric symptoms and response quality to self-rated personality tests: Evidence from the PsyCoLaus study.

Despite the fact that research has demonstrated consistent associations between self-rated measures of personality dimensions and mental disorders, little has been undertaken to investigate the relation between psychiatric symptoms and response patterns to self-rated tests. The aim of this study was to investigate the association between psychiatric symptoms and response quality using indices from our functional method. A sample of 1,784 participants from a Swiss population-based cohort completed a personality inventory (NEO-FFI) and a symptom checklist of 90 items (SCL-90-R). Different indices of response quality were calculated based on the responses given to the NEO-FFI. Associations among the responses to indices of response quality, sociodemographic characteristics and the SCL-90-R dimensions were then established. Psychiatric symptoms were associated with several important differences in response quality, questioning subjects' ability to provide valid information using self-rated instruments. As suggested by authors, psychiatric symptoms seem associated with differences in personality scores. Nonetheless, our study shows that symptoms are also related to differences in terms of response patterns as sources of differences in personality scores. This could constitute a bias for clinical assessment. Future studies could still determine whether certain subpopulations of subjects are more unable to provide valid information to self-rated questionnaires than others

Cholesterol-metabolism, plant sterols, and long-term cognitive decline in older people - Effects of sex and APOEe4.

Neurodegenerative, vascular, and dementia diseases are linked to dysregulations in cholesterol metabolism. Dietary plant sterols, or phytosterols, may interfere to neurodegeneration and cognitive decline, and have cholesterol-lowering, anti-inflammatory, and antioxidant qualities. Here, we investigated the potential associations between circulating cholesterol precursors and metabolites, triglycerides, and phytosterols with cognitive decline in older people by performing multivariate analysis on 246 participants engaged in a population-based prospective study. In our analysis we considered the potential effect of sex and APOEe4. We reveal particular dysregulations of diet-derived phytosterols and endogenous cholesterol synthesis and metabolism, and their variations over time linked to cognitive decline in the general population. These results are significant to the development of interventions to avoid cognitive decline in older adults and suggest that levels of circulating sterols should be taken into account when evaluating risk

Prevalence and correlates of DSM-5 major depressive and related disorders in the community.

Although the DSM-5 has suggested the two new categories of Persistent Depressive Disorders (PDD) and Other Specified Depressive Disorders (OSDD), no study so far has applied the DSM-5 criteria throughout the range of depressive disorders. The aims of the present study were to 1) establish the lifetime prevalence of specific depressive disorders according to the new DSM-5 definitions in a community sample, and 2) determine their clinical relevance in terms of socio-demographic characteristics, comorbidity, course and treatment patterns. The semi-structured Diagnostic Interview for Genetic Studies was administered by masters-level psychologists to a random sample of an urban area (n=3720). The lifetime prevalence was 15.2% for PDD with persistent major depressive episode (MDE), 3.3% for PDD with pure dysthymia, 28.2% for Major Depressive Disorder (MDD) and 9.1% for OSDD. Subjects with PDD with persistent MDE were the most severely affected, followed by those with recurrent MDD, single episode MDD, PDD with pure dysthymia and OSDD and finally those without depressive disorders. Our data provide further evidence for the clinical significance of mild depressive disorders (OSDD), but cast doubt on the pertinence of lumping together PDD with persistent MDE and the former DSM-IV dysthymic disorder within the new PDD category

Time-dependent, wind-driven flow over a shadow midshelf submarine bank

During summer 2001, high-resolution hydrographic, velocity, and bio-optical surveys were conducted over Heceta Bank off central Oregon. North of the bank, upwelling over simple bottom topography exhibited a classic response with a midshelf, baroclinic coastal jet and upwelled isopycnals. The coastal upwelling jet follows the bank topography as it widens offshore before reaching the southern end of the bank, where the shelf break turns almost 90° back toward the coast. The ensuing adjustment involves the offshelf transport of coastal water and the material it contains. The jet meanders anticyclonically in the ‘‘lee’’ of the bank before resuming its equatorward path seaward of the shelf break. A pool of high-chlorophyll (>15 mg m¯³) near-surface water is found in the low-velocity ‘‘lee’’ region created by the bank. A low-temperature, high-salinity bottom water pool, supplied primarily from the south, lies over the inshore region of the bank. This bottom pool is up to 40 m thick and contains elevated levels of suspended material. By creating an east-west perturbation in the coastal upwelling front, the flow-topography interaction introduces an alongshore pressure gradient. When southward upwelling-favorable winds relax, this alongshore pressure gradient can drive flow back to the north. This leads to northward flow on the inshore side of the bank, ultimately setting up the potential for recirculation around the entire bank complex on a timescale of about 10 days. Strong northward winds during summer lead to downwelling within 15 km of the coast, accompanied by significant (>0.2 m s¯¹) wind-driven northward currents

Progression and mortality in patients with CKD attending outpatient nephrology clinics across Europe: A novel analytic approach

The incidence of renal replacement therapy (RRT) varies across countries. Yet, little is known about the epidemiology of chronic kidney disease (CKD) outcomes. Our aim was to describe progression and mortality risk in CKD patients not on RRT attending outpatient nephrology clinics across Europe. We used individual data from nine CKD cohorts participating in the European CKD Burden Consortium. A joint model was used to estimate mean eGFR change and mortality risk simultaneously, thereby accounting for mortality risk when estimating eGFR decline and vice versa, while also correcting for the measurement error in eGFR. Results were adjusted for important risk factors (baseline eGFR, age, sex, albuminuria, primary renal disease, diabetes, hypertension, obesity and smoking). 27,771 patients from five countries were included. The adjusted mean annual eGFR decline varied from 0.77 (95%CI 0.45,1.08) ml/min/1.73m2 in the Belgium cohort to 2.43 (95%CI 2.11,2.75) ml/min/1.73m2 in the Spanish cohort. As compared to the Italian PIRP cohort, the adjusted mortality hazard ratio varied from 0.22 (95%CI 0.11,0.43) in the London LACKABO cohort to 1.30 (95%CI 1.13,1.49) in the English CRISIS cohort. Outcomes in CKD patients attending outpatient nephrology clinics varied markedly across European regions. Although eGFR decline showed minor variation, the most variation was observed in CKD mortality. Our results suggest that different healthcare organization systems are potentially associated with differences in outcome of CKD patients within Europe. These results can be used by policy makers to plan resources on a regional, national and European level

Urinary tract infections and reduced risk of bladder cancer in Los Angeles

We investigated the association between urinary tract infections (UTIs) and transitional cell carcinoma of the bladder in a population-based case–control study in Los Angeles covering 1586 cases and age-, gender-, and race-matched neighbourhood controls. A history of bladder infection was associated with a reduced risk of bladder cancer among women (odds ratio (OR), 0.66; 95% confidence interval (CI), 0.46–0.96). No effect was found in men, perhaps due to power limitations. A greater reduction in bladder cancer risk was observed among women with multiple infections (OR, 0.37; 95% CI, 0.18–0.78). Exclusion of subjects with a history of diabetes, kidney or bladder stones did not change the inverse association. A history of kidney infections was not associated with bladder cancer risk, but there was a weak association between a history of other UTIs and slightly increased risk among men. Our results suggest that a history of bladder infection is associated with a reduced risk of bladder cancer among women. Cytotoxicity from antibiotics commonly used to treat bladder infections is proposed as one possible explanation

C.E.R.A. once every 4 weeks corrects anaemia and maintains haemoglobin in patients with chronic kidney disease not on dialysis

Background. No previous randomized controlled studies have been reported examining de novo, once every 4 weeks (Q4W) administration of erythropoiesis-stimulating agents in chronic kidney disease (CKD) patients. We report results from a randomized multinational study that compared continuous erythropoietin receptor activator (C.E.R.A.) Q4W with darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) for the correction of anaemia in non-dialysis CKD patients

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

In vivo STED microscopy visualizes morphological changes of large PSD95 assemblies over several hours in the mouse visual cortex

Abstract The post-synaptic density (PSD) is an electron dense region consisting of ~1000 proteins, found at the postsynaptic membrane of excitatory synapses, which varies in size depending upon synaptic strength. PSD95 is an abundant scaffolding protein in the PSD and assembles a family of supercomplexes comprised of neurotransmitter receptors, ion channels, as well as signalling and structural proteins. We use superresolution STED (STimulated Emission Depletion) nanoscopy to determine the size and shape of PSD95 in the anaesthetised mouse visual cortex. Adult knock-in mice expressing eGFP fused to the endogenous PSD95 protein were imaged at time points from 1 min to 6 h. Superresolved large assemblies of PSD95 show different sub-structures; most large assemblies were ring-like, some horse-shoe or figure-8 shaped, and shapes were continuous or made up of nanoclusters. The sub-structure appeared stable during the shorter (minute) time points, but after 1 h, more than 50% of the large assemblies showed a change in sub-structure. Overall, these data showed a sub-morphology of large PSD95 assemblies which undergo changes within the 6 hours of observation in the anaesthetised mouse