Effort, reward and self-reported mental health: a simulation study on negative affectivity bias.

Background : In the present article, we propose an alternative method for dealing with negative affectivity (NA) biases in research, while investigating the association between a deleterious psychosocial environment at work and poor mental health. First, we investigated how strong NA must be to cause an observed correlation between the independent and dependent variables. Second, we subjectively assessed whether NA can have a large enough impact on a large enough number of subjects to invalidate the observed correlations between dependent and independent variables.Methods : We simulated 10,000 populations of 300 subjects each, using the marginal distribution of workers in an actual population that had answered the Siegrist's questionnaire on effort and reward imbalance (ERI) and the General Health Questionnaire (GHQ).Results : The results of the present study suggested that simulated NA has a minimal effect on the mean scores for effort and reward. However, the correlations between the effort and reward imbalance (ERI) ratio and the GHQ score might be important, even in simulated populations with a limited NA.Conclusions : When investigating the relationship between the ERI ratio and the GHQ score, we suggest the following rules for the interpretation of the results: correlations with an explained variance of 5% and below should be considered with caution; correlations with an explained variance between 5% and 10% may result from NA, although this effect does not seem likely; and correlations with an explained variance of 10% and above are not likely to be the result of NA biases. [Authors]

Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy

BACKGROUND: Vitamin D is an important immune modulator and preliminary data indicated an association between vitamin D deficiency and sustained virologic response (SVR) rates in patients with chronic hepatitis C. We therefore performed a comprehensive analysis on the impact of vitamin D serum levels and of genetic polymorphisms within the vitamin D cascade on chronic hepatitis C and its treatment. METHODS: Vitamin D serum levels, genetic polymorphisms within the vitamin D receptor and the 1α- hydroxylase were determined in a cohort of 468 HCV genotype 1, 2 and 3 infected patients who were treated with interferon-alfa based regimens. RESULTS: Chronic hepatitis C was associated with a high incidence of severe vitamin D deficiency compared to controls (25(OH)D3<10 ng/mL in 25% versus 12%, p<0.00001), which was in part reversible after HCV eradication. 25(OH)D3 deficiency correlated with SVR in HCV genotype 2 and 3 patients (63% and 83% SVR for patients with and without severe vitamin D deficiency, respectively, p<0.001). In addition, the CYPB27-1260 promoter polymorphism rs10877012 had substantial impact on 1-25- dihydroxyvitamin D serum levels and SVR rates in HCV genotype 1, 2 and 3 infected patients. CONCLUSIONS: Chronic hepatitis C virus infection is associated with vitamin D deficiency. Reduced 25- hydroxyvitamin D levels and CYPB27-1260 promoter polymorphism are associated with failure to achieve SVR in HCV genotype 1, 2, 3 infected patients.

The effects of the generalized use of iodized salt on occupational patterns in Switzerland.

This paper examines the impact of salt iodization in Switzerland in the 1920s and 1930s on occupational patterns of cohorts born after the intervention. The generalized use of iodized salt successfully combatted iodine deficiency disorders, which were previously endemic in some areas of Switzerland. The most important effect of universal prophylaxis by means of iodized salt was the eradication of mental retardation inflicted in utero by lack of iodine. This paper looks for evidence of increased cognitive ability of those treated with iodine in utero by examining the occupational choice and characteristics of occupations chosen by cohorts born after the intervention. By exploiting variation in pre-existing conditions and in the timing of the intervention, I find that cohorts born in previously highly-deficient areas after the introduction of iodized salt self-selected into higher-paying occupations. I also find that the characteristics of occupations in those areas changed, and that cohorts born after the intervention engaged to a higher degree in occupations with higher cognitive demands, whereas they opted out of physical-labor-intensive occupations.

The management of iron deficiency in inflammatory bowel disease--an online tool developed by the RAND/UCLA appropriateness method.

BACKGROUND: Iron deficiency is a common and undertreated problem in inflammatory bowel disease (IBD). AIM: To develop an online tool to support treatment choice at the patient-specific level. METHODS: Using the RAND/UCLA Appropriateness Method (RUAM), a European expert panel assessed the appropriateness of treatment regimens for a variety of clinical scenarios in patients with non-anaemic iron deficiency (NAID) and iron deficiency anaemia (IDA). Treatment options included adjustment of IBD medication only, oral iron supplementation, high-/low-dose intravenous (IV) regimens, IV iron plus erythropoietin-stimulating agent (ESA), and blood transfusion. The panel process consisted of two individual rating rounds (1148 treatment indications; 9-point scale) and three plenary discussion meetings. RESULTS: The panel reached agreement on 71% of treatment indications. 'No treatment' was never considered appropriate, and repeat treatment after previous failure was generally discouraged. For 98% of scenarios, at least one treatment was appropriate. Adjustment of IBD medication was deemed appropriate in all patients with active disease. Use of oral iron was mainly considered an option in NAID and mildly anaemic patients without disease activity. IV regimens were often judged appropriate, with high-dose IV iron being the preferred option in 77% of IDA scenarios. Blood transfusion and IV+ESA were indicated in exceptional cases only. CONCLUSIONS: The RUAM revealed high agreement amongst experts on the management of iron deficiency in patients with IBD. High-dose IV iron was more often considered appropriate than other options. To facilitate dissemination of the recommendations, panel outcomes were embedded in an online tool, accessible via http://ferroscope.com/.

Human GnRH deficiency: a unique disease model to unravel the ontogeny of GnRH neurons.

Evolutionary survival of a species is largely a function of its reproductive fitness. In mammals, a sparsely populated and widely dispersed network of hypothalamic neurons, the gonadotropin-releasing hormone (GnRH) neurons, serve as the pilot light of reproduction via coordinated secretion of GnRH. Since it first description, human GnRH deficiency has been recognized both clinically and genetically as a heterogeneous disease. A spectrum of different reproductive phenotypes comprised of congenital GnRH deficiency with anosmia (Kallmann syndrome), congenital GnRH deficiency with normal olfaction (normosmic idiopathic hypogonadotropic hypogonadism), and adult-onset hypogonadotropic hypogonadism has been described. In the last two decades, several genes and pathways which govern GnRH ontogeny have been discovered by studying humans with GnRH deficiency. More importantly, detailed study of these patients has highlighted the emerging theme of oligogenicity and genotypic synergism, and also expanded the phenotypic diversity with the documentation of reversal of GnRH deficiency later in adulthood in some patients. The underlying genetic defect has also helped understand the associated nonreproductive phenotypes seen in some of these patients. These insights now provide practicing clinicians with targeted genetic diagnostic strategies and also impact on clinical management.

Reduced Prostasin (CAP1/PRSS8) Activity Eliminates HAI-1 and HAI-2 Deficiency-Associated Developmental Defects by Preventing Matriptase Activation.

Loss of either hepatocyte growth factor activator inhibitor (HAI)-1 or -2 is associated with embryonic lethality in mice, which can be rescued by the simultaneous inactivation of the membrane-anchored serine protease, matriptase, thereby demonstrating that a matriptase-dependent proteolytic pathway is a critical developmental target for both protease inhibitors. Here, we performed a genetic epistasis analysis to identify additional components of this pathway by generating mice with combined deficiency in either HAI-1 or HAI-2, along with genes encoding developmentally co-expressed candidate matriptase targets, and screening for the rescue of embryonic development. Hypomorphic mutations in Prss8, encoding the GPI-anchored serine protease, prostasin (CAP1, PRSS8), restored placentation and normal development of HAI-1-deficient embryos and prevented early embryonic lethality, mid-gestation lethality due to placental labyrinth failure, and neural tube defects in HAI-2-deficient embryos. Inactivation of genes encoding c-Met, protease-activated receptor-2 (PAR-2), or the epithelial sodium channel (ENaC) alpha subunit all failed to rescue embryonic lethality, suggesting that deregulated matriptase-prostasin activity causes developmental failure independent of aberrant c-Met and PAR-2 signaling or impaired epithelial sodium transport. Furthermore, phenotypic analysis of PAR-1 and matriptase double-deficient embryos suggests that the protease may not be critical for focal proteolytic activation of PAR-2 during neural tube closure. Paradoxically, although matriptase auto-activates and is a well-established upstream epidermal activator of prostasin, biochemical analysis of matriptase- and prostasin-deficient placental tissues revealed a requirement of prostasin for conversion of the matriptase zymogen to active matriptase, whereas prostasin zymogen activation was matriptase-independent.

Macrophage Migration Inhibitory Factor Deficiency Is Associated With Impaired Killing of Gram-Negative Bacteria by Macrophages and Increased Susceptibility to Klebsiella pneumoniae Sepsis.

The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacterial uptake and clearance by professional phagocytes, using wild-type and MIF-deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but it strongly impaired the killing of gram-negative bacteria by macrophages and host defenses against gram-negative bacterial infection, as shown by increased mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor κB activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF or TNF corrected the killing defect of MIF-deficient macrophages. Together, these data show that MIF is a key mediator of host responses against gram-negative bacteria, acting in part via a modulation of bacterial killing by macrophages.

Toxoplasmosis and mental retardation: report of a case-control study

A case-control study evaluating the association between mental retardation and toxoplasmosis was conducted among 845 school children in Belo Horizonte, MG, Brazil. Cases (450) were mentally retarded children attending a public school for special education. Controls (395) were children from the regular public school system. Clinical and anthropometric examinations and interviews were carried out to determine risk factors for toxoplasmosis and mental retardation. Diagnosis of Toxoplasma gondii infection was based upon an indirect immunofluorescent test (IFA); 55% of cases and 29% of controls were positive. The Relative Odds of mental retardation in children with positive serology was 3.0 (95% CI 2.2-4.0). Maternal exposure to cats and contact with soil were associated with an increased risk of mental retardation. Retinochoroiditis was fourfold more prevalent among cases than controls and was only diagnosed in T. gondii IFA positive participants. Congenital toxoplasmosis, in its subclinical form, appears to be an important component in the etiology of mental retardation, especially in high risk (lower socio-economic) groups. The population attributable risk was estimated as 6.0 - 9.0%, suggesting the amount of mental retardation associated with this infection.

Self-perceived health status and mental health outcomes in young adults born with less than 1000 g.

AIM: To assess self-perceived health status and mental health outcomes of former extremely low-birth-weight (ELBW) infants at young adulthood compared with community norms and to analyse predictors of poor outcome. METHODS: Fifty-five ELBW adults, 18 men (33%), with median (range) gestational age of 28.7 (25.0-34.0) weeks and birth weight of 930 (680-990) grams, born in Switzerland, were included. They self-rated their health status and mental health at a mean (range) age of 23.3 (21.8-25.9) years. Health status was measured by the Medical Outcomes Study Short Form-36 questionnaire and mental health by the Brief Symptom Inventory. RESULTS: The mean scores for both outcome measures were in the normal range. However, the study group self-rated significantly higher physical health status and lower mental health status compared with the community norms, and scores for self-perceived mental health tended to be worse in the former. ELBW adults reported more problems in socio-emotional role functioning compared with the community norms. Female sex was associated with poorer and bronchopulmonary dysplasia with better mental health status. CONCLUSION: Health status and mental health of former ELBW adults were overall satisfying. However, the comparison with the community norms revealed differences, which may be important for parental and patient counselling and developing support strategies.

Toxoplasma gondii Antigenuria in Patients with Acquired Immune Deficiency Syndrome

A longitudinal study was performed with sera and urine of patients with acquired immune deficiency syndrome (AIDS), taken before, during and after clinically Toxoplasma infection. The tested patients were followed for an average of two years. The titres of the specific IgG and IgM antibodies were measured by an indirect fluorescent antibody test (IFAT), and the appearance of circulating antigens of T. gondii was determined in 36 urine samples of 13 patients with neurotoxoplasmosis by means of the coagglutination test. The presence of T. gondii antigens in the urine of AIDS patients by this test was correlated with the immunoblot technique, with clinical symptoms and also with pathological findings. Our results indicate that the detection of T. gondii antigens in the urine of AIDS patients can be regarded as a rapid and efficient method for the diagnosis of acute toxoplasmosis

Frequent users of emergency departments present very high prevalence of mental health and substance use disorders, which are largely underdiagnosed by clinicians

Background: The objective of this study was to determine if mental health and substance use diagnoses were equally detected in frequent users (FUs) compared to infrequent users (IUs) of emergency departments (EDs). Methods: In a sample of 399 adult patients (>= 18 years old) admitted to a teaching hospital ED, we compared the mental health and substance use disorders diagnoses established clinically and consigned in the medical files by the ED physicians to data obtained in face-to-face research interviews using the Primary Care Evaluation of Mental Disorders (PRIME-MD) and the Alcohol, Smoking and Involvement Screening Test (ASSIST). Between November 2009 and June 2010, 226 FUs (>4 visits within a year) who attended the ED were included, and 173 IUs (<= 4 visits within a year) were randomly selected from a pool of identified patients to comprise the comparison group. Results: For mental health disorders identified by the PRIME-MD, FUs were more likely than IUs to have an anxiety (34 vs. 16%, Chi2(1) = 16.74, p <0.001), depressive (47 vs. 25%, Chi2(1) = 19.11, p <0.001) or posttraumatic stress (PTSD) disorder (11 vs. 5%, Chi2(1) = 4.87, p = 0.027). Only 3/76 FUs (4%) with an anxiety disorder, 16/104 FUs (15%) with a depressive disorder and none of the 24 FUs with PTSD were detected by the ED medical staff. None of the 27 IUs with an anxiety disorder, 6/43 IUs (14%) with a depressive disorder and none of the 8 IUs with PTSD were detected. For substance use disorders identified by the ASSIST, FUs were more at risk than IUs for alcohol (24 vs. 7%, Chi2(1) = 21.12, p <0.001) and drug abuse/dependence (36 vs. 25%, Chi2(1) = 5.52, p = 0.019). Of the FUs, 14/54 (26%) using alcohol and 8/81 (10%) using drugs were detected by the ED physicians. Of the IUs, 5/12 (41%) using alcohol and none of the 43 using drugs were detected. Overall, there was no significant difference in the rate of detection of mental health and substance use disorders between FUs and IUs (Fisher's Exact Test: anxiety, p = 0.567; depression, p = 1.000; PTSD, p = 1.000; alcohol, p = 0.517; and drugs, p = 0.053). Conclusions: While the prevalence of mental health and substance use disorders was higher among FUs, the rates of detection were not significantly different for FUs vs. IUs. However, it may be that drug disorders among FUs were more likely to be detected.