A highly strained nuclear conformation of the exportin Cse1p revealed by molecular dynamics simulations

SummaryTo investigate the stability of the open nuclear state of the exportin Cse1p and its closing mechanism at the atomic level, we have performed multiple molecular dynamics simulations. The simulations revealed a strikingly fast transition of Cse1p from the open conformation to the closed cytoplasmic form, consistent with the proposal that Cse1p represents a “spring-loaded molecule.” The structure of the ring-shaped state obtained in the simulations is remarkably close to the crystal structure of the cytoplasmic state, though the open nuclear structure was used as the only input. The conformational change is initially driven by release of strain due to RanGTP/importin-α binding. Subsequently, a stable closed state is formed, driven by attraction of electrostatically complementary interfaces. These results are consistent with and extend previous proposals. Reverse-charge and neutral mutants remained in an open state. The simulations predict a detailed reaction pathway and resolve the role of suggested hinge regions

Duration of Psoriatic Skin Disease as Risk Factor for Subsequent Onset of Psoriatic Arthritis

It is unclear whether psoriasis is a progressive disease that requires early aggressive intervention. This population-based study identified patients with psoriasis and psoriatic arthritis (PsA). Survival analysis and Kaplan–Meier life table techniques were used. The study comprised 10,011 psoriasis patients (severe n = 4,618), and 1,269 patients also had PsA. Incidence of PsA increased with duration of cutaneous symptoms (p = 0.0001). Psoriasis diagnosed before age 20 or 30 years, respectively, suggested a lower risk of PsA than psoriasis diagnosed after age 50 years, yet age at first cutaneous symptoms did not predict development of PsA. No clear association with disease severity was found. PsA incidence appeared stable with longer duration of psoriasis, but further data are needed to firmly establish the relationship with age of psoriasis onset

The effect of spiritual healing on in vitro tumour cell proliferation and viability – an experimental study

Alternative treatments such as spiritual healing and prayer are increasingly popular, especially among patients with life-threatening diseases such as cancer. According to theories of spiritual healing, this intervention is thought to influence living cells and organisms independently of the recipient's conscious awareness of the healer's intention. The aim of this study was to test the hypothesis that spiritual healing will reduce proliferation and viability of two cancer cell lines in vitro. Three controlled experiments were conducted with three different healers and randomised allocation of cells to five different doses of healing or control. Researchers conducting the assays and statistical analyses were blinded to the experimental conditions. Main outcome measures were MTT viability, 3H-thymidine incorporation and counts of an adherent human breast cancer cell line (MCF-7), and a nonadherent mouse B-lymphoid cell line (HB-94). Analyses of variance (ANOVAs) revealed no significant main or dose-related effects of spiritual healing compared to controls for either of the two cell lines or any of the assays (P-values between 0.09 and 0.96). When comparing healing and control across all three experimental days, doses, assays, and cells, 34 (51.6%) of 66 independent comparisons showed differences in the hypothesised direction (P=0.90). The average effect size across cell lines, days, assays, and doses approached zero (Cohen's d=−0.01). The results do not support previous reports of beneficial effects of spiritual healing on malignant cell growth in vitro. Reported beneficial effects of spiritual healing on the well-being of cancer patients seem more likely to be mediated by psychosocial and psychophysiological effects of the healer–patient relationship

A liver fibrosis cocktail? Psoriasis, methotrexate and genetic hemochromatosis

BACKGROUND: Pathologists are often faced with the dilemma of whether to recommend continuation of methotrexate therapy for psoriasis within the context of an existing pro-fibrogenic risk factor, in this instance, patients with genetic hemochromatosis. CASE PRESENTATIONS: We describe our experience with two male psoriatic patients (A and B) on long term methotrexate therapy (cumulative dose A = 1.56 gms and B = 7.88 gms) with hetero- (A) and homozygous (B) genetic hemochromatosis. These patients liver function were monitored with routine biochemical profiling; apart from mild perivenular fibrosis in one patient (B), significant liver fibrosis was not identified in either patient with multiple interval percutaneous liver biopsies; in the latter instance this patient (B) had an additional risk factor of partiality to alcohol. CONCLUSION: We conclude that methotrexate therapy is relatively safe in patients with genetic hemochromatosis, with no other risk factor, but caution that the risk of fibrosis be monitored, preferably by non-invasive techniques, or by liver biopsy

Analyzing the link between anxiety and eating behavior as a potential pathway to eating-related health outcomes

Anxiety is a widespread phenomenon that affects various behaviors. We want to analyze in how far anxiety is connected to eating behaviors since this is one potential pathway to understanding eating-related health outcomes like obesity or eating disorders. We used data from the population-based LIFE-Adult-Study (n = 5019) to analyze the connection between anxiety (GAD-7) and the three dimensions of eating behaviors (FEV)-Cognitive Restraint, Disinhibition, and Hunger-while controlling for sociodemographic variables, smoking, physical activity, personality, and social support. Multivariate regression analyses showed significant positive associations between anxiety and Disinhibition as well as Hunger, but not between anxiety and Cognitive Restraint. Interventions that help individuals to better regulate and cope with anxiety, could be one potential pathway to reducing eating disorders and obesity in the population

Different areas of chronic stress and their associations with depression

Background: Research shows a connection between stress and depression, but there is little differentiation between areas of stress, making it difficult to identify and address specific areas in the context of public health measures. We utilized a multi-dimensional approach to chronic stress to better understand the relationship between different areas of stress and depression. Methods: We conducted linear regression analyses and used data from a sub-sample of the LIFE-Adult-Study (N = 1008) to analyze the connection between nine different areas of chronic stress (TICS) and depression (CES-D). In the second analysis, we controlled for sociodemographic variables, personality, physical activity, and social support. Results: There was a significant positive association between the stress domains Excessive Demands from Work, Lack of Social Recognition, Social Isolation, and Chronic Worrying and depression and a significant negative association between Pressure to Perform and depression. After adding control variables, only Pressure to Perform, Social Isolation, and Chronic Worrying remained significant predictors. Conclusions: By focusing on the connections between chronic stress and depression, researchers can help identify the areas that matter most and contribute to the creation of meaningful and efficient interventions. On the basis of our results, measures for the prevention of depression that focus on the reduction of worrying and social isolation are recommended