TB STIGMA – MEASUREMENT GUIDANCE

TB is the most deadly infectious disease in the world, and stigma continues to play a significant role in worsening the epidemic. Stigma and discrimination not only stop people from seeking care but also make it more difficult for those on treatment to continue, both of which make the disease more difficult to treat in the long-term and mean those infected are more likely to transmit the disease to those around them. TB Stigma – Measurement Guidance is a manual to help generate enough information about stigma issues to design and monitor and evaluate efforts to reduce TB stigma. It can help in planning TB stigma baseline measurements and monitoring trends to capture the outcomes of TB stigma reduction efforts. This manual is designed for health workers, professional or management staff, people who advocate for those with TB, and all who need to understand and respond to TB stigma

Brain volumes in alcohol use disorder : Do females and males differ? A whole-brain magnetic resonance imaging mega-analysis

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxelbased, multi-tissue mega-analytic approach, thereby extending our recent surfacebased region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller groupby- sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD

Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning

Lymphocyte egress from lymph nodes (LNs) is dependent on sphingosine-1-phosphate (S1P), but the cellular source of this S1P is not defined. We generated mice that expressed Cre from the lymphatic vessel endothelial hyaluronan receptor 1 (Lyve-1) locus and that showed efficient recombination of loxP-flanked genes in lymphatic endothelium. We report that mice with Lyve-1 CRE-mediated ablation of sphingosine kinase (Sphk) 1 and lacking Sphk2 have a loss of S1P in lymph while maintaining normal plasma S1P. In Lyve-1 Cre+ Sphk-deficient mice, lymphocyte egress from LNs and Peyer's patches is blocked. Treatment with pertussis toxin to overcome Gαi-mediated retention signals restores lymphocyte egress. Furthermore, in the absence of lymphatic Sphks, the initial lymphatic vessels in nonlymphoid tissues show an irregular morphology and a less organized vascular endothelial cadherin distribution at cell–cell junctions. Our data provide evidence that lymphatic endothelial cells are an in vivo source of S1P required for lymphocyte egress from LNs and Peyer's patches, and suggest a role for S1P in lymphatic vessel maturation

The relationships between workaholism and symptoms of psychiatric disorders: a large-scale cross-sectional study

Despite the many number of studies examining workaholism, large-scale studies have been lacking. The present study utilized an open web-based cross-sectional survey assessing symptoms of psychiatric disorders and workaholism among 16,426 workers (Mage = 37.3 years, SD = 11.4, range = 16–75 years). Participants were administered the Adult ADHD Self-Report Scale, the Obsession-Compulsive Inventory-Revised, the Hospital Anxiety and Depression Scale, and the Bergen Work Addiction Scale, along with additional questions examining demographic and work-related variables. Correlations between workaholism and all psychiatric disorder symptoms were positive and significant. Workaholism comprised the dependent variable in a three-step linear multiple hierarchical regression analysis. Basic demographics (age, gender, relationship status, and education) explained 1.2% of the variance in workaholism, whereas work demographics (work status, position, sector, and annual income) explained an additional 5.4% of the variance. Age (inversely) and managerial positions (positively) were of most importance. The psychiatric symptoms (ADHD, OCD, anxiety, and depression) explained 17.0% of the variance. ADHD and anxiety contributed considerably. The prevalence rate of workaholism status was 7.8% of the present sample. In an adjusted logistic regression analysis, all psychiatric symptoms were positively associated with being a workaholic. The independent variables explained between 6.1% and 14.4% in total of the variance in workaholism cases. Although most effect sizes were relatively small, the study’s findings expand our understanding of possible psychiatric predictors of workaholism, and particularly shed new insight into the reality of adult ADHD in work life. The study’s implications, strengths, and shortcomings are also discussed

Genetic variation in human NPY expression affects stress response and emotion

Understanding inter- individual differences in stress response requires the explanation of genetic influences at multiple phenotypic levels, including complex behaviours and the metabolic responses of brain regions to emotional stimuli. Neuropeptide Y ( NPY) is anxiolytic(1,2) and its release is induced by stress(3). NPY is abundantly expressed in regions of the limbic system that are implicated in arousal and in the assignment of emotional valences to stimuli and memories(4-6). Here we show that haplotype- driven NPY expression predicts brain responses to emotional and stress challenges and also inversely correlates with trait anxiety. NPY haplotypes predicted levels of NPY messenger RNA in postmortem brain and lymphoblasts, and levels of plasma NPY. Lower haplotype- driven NPY expression predicted higher emotion- induced activation of the amygdala, as well as diminished resiliency as assessed by pain/ stress- induced activations of endogenous opioid neurotransmission in various brain regions. A single nucleotide polymorphism ( SNP rs16147) located in the promoter region alters NPY expression in vitro and seems to account for more than half of the variation in expression in vivo. These convergent findings are consistent with the function of NPY as an anxiolytic peptide and help to explain inter- individual variation in resiliency to stress, a risk factor for many diseases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62768/1/nature06858.pd

Sheehan's syndrome: a single centre experience

Background: Sheehan's syndrome (SS) occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. It is one of the most common causes of hypopituitarism in developing countries. Objective: To study the clinical profile of patients with SS presenting to the Endocrinology Department at a tertiary care teaching hospital in South India. Methods: All patients diagnosed as SS during the study period of 2007-2012 were identified. Their clinical, biochemical, hormonal, radiological and bone mineral density (BMD) data were collected. Results: Eighteen patients were identified. Median age of diagnosis was 40 years [interquartile range (IQR = 32-51 years); median (IQR) diagnostic delay was 11 (5-17 years)]. Failure to resume menstruation and lactation failure was the most common clinical presentation. The median total tetraiodothyronine (T4), peak stimulated cortisol, stimulated growth hormone (GH), and prolactin (PRL) levels were low. The gonadotropins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)] were inappropriately normal in the presence of amenorrhea. Hyponatremia was the most common electrolyte abnormality seen in 14 patients. Seven patients had anaemia and five of them had normocytic normochromic anaemia. BMD assessment (n = 9) was suggestive of low bone mass. Conclusion: SS resulted in multiple pituitary hormone deficiencies in all the patients. Hyponatremia, anaemia, and low bone mass were frequently seen in patients with SS

The neural signature of satiation is associated with ghrelin response and triglyceride metabolism

Eating behavior is guided by a complex interaction between signals conveying information about energy stores, food availability, and palatability. How peripheral signals regulate brain circuits that guide feeding during sensation and consumption of a palatable food is poorly understood. We used NM to measure brain response to a palatable food (milkshake) when n = 32 participants were fasted and fed with either a fixed-portion or ad libitum meal. We found that larger post-prandial reductions in ghrelin and increases in triglycerides were associated with greater attenuation of response to the milkshake in brain regions regulating reward and feeding including the midbrain, amygdala, pallidum, hippocampus, insula and medial orbitofrontal cortex. Satiation-induced brain responses to milkshake were not related to acute changes in circulating insulin, glucose, or free fatty adds. The impact of a meal on the response to milkshake in the midbrain and dorsolateral prefrontal cortex differed depending upon whether meal termination was fixed or volitional, irrespective of the amount of food consumed. We conclude that satiation-induced changes in brain response to a palatable food are strongly and specifically associated with changes in circulating ghrelin and triglycerides and by volitional meal termination. (C) 2014 Elsevier Inc. All rights reserved