Perceived discrimination against diabetics in the workplace and in work-related insurances in Switzerland.

To investigate the prevalence and risk factors of perceived diabetes-related discrimination in the workplace and in work-related insurances in persons with diabetes mellitus in Switzerland. 509 insulin-treated diabetic subjects representative of the northwestern Swiss population responded to a self-report questionnaire on perceived diabetes-related discrimination in the workplace and in work-related insurances (salary loss insurance, supplementary occupational plan). Discrimination was defined as being treated differently at least once in relation to diabetes. The reported rates of different aspects of discrimination in the workplace and in work-related insurances ranged between 5-11% and 4-15% respectively. Risk factors that independently increased the risk of not being hired due to diabetes were the presence of at least two severe hypoglycaemic events/year and relevant diabetic complications (OR 5.6 and OR 2.6 respectively; both<0.05). The presence of at least two severe hypoglycaemic events/year was also associated with an increased risk of losing one's job (OR 6.5, <0.01). Overweight or obesity were related to increased discrimination in work-related insurances (OR for denial 2.1-2.4; OR for reserve 3.9-4.4; all<0.05). Perceived diabetes-related discrimination in the workplace and by work-related insurances is a common problem. In the light of our findings the introduction of effective non-discrimination legislation for patients with chronic illnesses appears to be desirable.

Nicotinamide phosphoribosyltransferase as a target in inflammation- related disorders.

NAD(+) biosynthesis through nicotinamide phosphoribosyltransferase (NAMPT) holds potential as a target for the treatment of inflammatory disorders due to NAD(+)'s role in immune cell signaling and metabolism. In addition to its activity as an enzyme, NAMPT is also secreted in the extracellular space where it acts as a pro-inflammatory and proangiogenic cytokine. NAMPT inhibition with FK866 has anti-inflammatory activity in different models of immune disorders and it prevents ischemia-reperfusion-induced heart damage by dampening the production of neutrophil chemoattractants. NAMPT blockade with a neutralizing antibody has beneficial effects in an acute lung injury model. Last, but not least, the anticancer activity of NAMPT inhibitors may also reflect, at least in part, their ability to modify the cancer microenvironment through their anti-inflammatory properties. Overall, NAMPT inhibition holds potential for the treatment of inflammation-related disorders and the development of effective and safe NAMPT inhibitors remains an area of strong interest in pharmaceutical research.

Copeptin as a diagnostic biomarker for sepsis-related deaths.

Copeptin has been shown to increase in patients with sepsis, severe sepsis and septic shock. In the study herein described, copeptin was measured in a series of sepsis-related fatalities and control cases that underwent medico-legal investigations. No age-dependent differences in copeptin levels in either sepsis or control cases were observed. No correlation between copeptin concentrations and postmortem interval was identified in either group. Copeptin levels were significantly higher in sepsis cases. Moreover, copeptin concentrations in septic cases correlated with procalcitonin, C-reactive protein and interleukin 6 values. These preliminary findings seem to indicate that copeptin can be reliably measured in biological samples collected during postmortem investigations. These results also suggest that hemodynamic instability associated with sepsis and septic shock can be characterized by copeptin measurement also in the forensic casework.

Deletion of CREB-Regulated Transcription Coactivator 1 Induces Pathological Aggression, Depression-Related Behaviors, and Neuroplasticity Genes Dysregulation in Mice.

BACKGROUND: Mood disorders are polygenic disorders in which the alteration of several susceptibility genes results in dysfunctional mood regulation. However, the molecular mechanisms underlying their transcriptional dysregulation are still unclear. The transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and the neurotrophin brain-derived neurotrophic factor (BDNF) have been implicated in rodent models of depression. We previously provided evidence that Bdnf expression critically rely on a potent CREB coactivator called CREB-regulated transcription coactivator 1 (CRTC1). METHODS: To further evaluate the role of CRTC1 in the brain, we generated a knockout mouse line and analyzed its behavioral and molecular phenotype. RESULTS: We found that mice lacking CRTC1 associate neurobehavioral endophenotypes related to mood disorders. Crtc1(-/-) mice exhibit impulsive aggressiveness, social withdrawal, and decreased sexual motivation, together with increased behavioral despair, anhedonia, and anxiety-related behavior in the novelty-induced hypophagia test. They also present psychomotor retardation as well as increased emotional response to stressful events. Crtc1(-/-) mice have a blunted response to the antidepressant fluoxetine in behavioral despair paradigms, whereas fluoxetine normalizes their aggressiveness and their behavioral response in the novelty-induced hypophagia test. Crtc1(-/-) mice strikingly show, in addition to a reduced dopamine and serotonin turnover in the prefrontal cortex, a concomitant decreased expression of several susceptibility genes involved in neuroplasticity, including Bdnf, its receptor TrkB, the nuclear receptors Nr4a1-3, and several other CREB-regulated genes. CONCLUSIONS: Collectively, these findings support a role for the CRTC1-CREB pathway in mood disorders etiology and behavioral response to antidepressants and identify CRTC1 as an essential coactivator of genes involved in mood regulation.

Prevalence and correlates of DSM-5 bipolar and related disorders and hyperthymic personality in the community.

BACKGROUND: To 1) establish the lifetime and 12-month prevalence of DSM-5 bipolar and related disorders including the new algorithmically defined conditions grouped within Other Specified Bipolar and Related Disorders (OSBARD) as well as hyperthymic personality in a randomly selected community sample, and 2) determine the clinical relevance of the OSBARD category in terms of sociodemographic characteristics, course, comorbidity and treatment patterns by comparing the subjects of this category to those with bipolar-I (BP-I), bipolar-II (BP-II), major depressive disorder (MDD), and those with no history of mood disorders. METHODS: The semi-structured Diagnostic Interview for Genetic Studies was administered by masterslevel psychologists to a random sample of an urban area (n=3'719). RESULTS: The lifetime prevalence was 1.0% for BP-I, 0.8% for BP-II, 1.0% for OSBARD and 3% for hyperthymic personality. Subjects with OSBARD were more severely affected than subjects without a history of mood disorders regarding almost all clinical correlates. Compared to those with MDD, they also revealed an elevated risk of suicidal attempts, lower global functioning, more treatment seeking and more lifetime comorbidity including anxiety, substance use and impulse-control disorders. However, they did not differ from subjects with BP-II. LIMITATIONS: Small sample sizes for bipolar and related disorders and potential inaccurate recall of symptoms. CONCLUSIONS: The modifications of diagnostic criteria for manic/hypomanic episodes according to the DSM-5 only marginally affect the prevalence estimates for BP-I and BP-II. The new DSM-5 OSBARD category is associated with significant clinical burden, is hardly distinct from BP-II with respect to clinical correlates and deserves similar clinical attention.

The influence of drinking pattern, at individual and aggregate levels, on alcohol-related negative consequences.

AIM: To determine the extent drinking patterns (at the individual and country level) are associated with alcohol-related consequences over and above the total alcohol the person consumes. METHODS: Hierarchical linear models were estimated based on general population surveys conducted in 18 countries participating in the GENACIS project. RESULTS: In general, the positive association between drinking pattern scores and alcohol-related consequences was found at both the individual and country levels, independent of volume of drinking. In addition, a significant interaction effect indicated that the more detrimental the country's drinking pattern, the less steep the association between the volume of drinking and its consequences. CONCLUSION: Drinking patterns have an independent impact on consequences over and above the relationship between volume and consequences.

Dégénérescence maculaire liée à l'âge exsudative: efficacité et limites des différents traitements [Exudative age-related macular degeneration: efficacy and limits of the different treatments].

Ocular neovascularizations are responsible for irreversible loss of vision in various diseases, including age-related macular degeneration. Treatments have changed greatly, and photodynamic therapy with verteporfin has come into common use. However, the visual prognosis remains poor. The recent approval of new antiangiogenic molecules such as ranibizumab and pegaptanib should allow for new therapeutical possibilities. The unapproved ophthalmological use of bevacizumab requires further studies. This paper updates what is known about old and new neovascularization treatments: their mechanism of action, their efficacy, and their toxicity. It reviews the principal clinical studies, and concludes with the recognized recommendations. For the first time, ophthalmologists can hope not only to stabilize loss of vision, but also to improve visual acuity. Complementary treatments can now be tested in associations, concomitantly or not, with the hope of improving visual results.

Health-related quality of life in long-term survivors of relapsed childhood acute lymphoblastic leukemia.

BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL). Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL) was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS) we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976-2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36), which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%). Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6) compared to those without (55.8;p=0.005), but after adjusting for self-reported late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients' HRQOL.

Association of working conditions with self-reported work-related symptoms: results from the Swiss dataset of the European Working Conditions Survey

Working conditions are important determinants of health. The aims of this article are to 1) identify working conditions and work characteristics that are associated with workers' perceptions that their work is harmful to their health and 2) identify with what symptoms these working conditions are associated.We used the Swiss dataset from the 2005 edition of the European Working Conditions Survey. The dependent variable was based on the question "Does your work affect your health?". Logistic regression was used to identify a set of variables collectively associated with self-reported work-related adverse health effects.A total of 330 (32%) participants reported having their health affected by work. The most frequent symptoms included backache (17.1%), muscular pains (13.1%), stress (18.3%) and overall fatigue (11.7%). Scores for self-reported exposure to physicochemical risks, postural and physical risks, high work demand, and low social support were all significantly associated with workers' perceptions that their work is harmful to their health, regardless of gender or age. A high level of education was associated with stress symptoms, and reports that health was affected by work was associated with low job satisfaction.Many workers believe that their work affects their health. Health specialists should pay attention to the potential association between work and their patients' health complaints. This is particularly relevant when patients mention symptoms such as muscular pains, backache, overall fatigue, and stress. Specific attention should be given to complaints of stress in highly educated workers.