Bone mineral parameters in healthy young Indian adults with optimal vitamin D availability

Background: Several recent studies indicate a marked prevalence of vitamin D deficiency in asymptomatic, apparently healthy urban subjects from different socioeconomic groups in north India. Methods: To further examine this trend, we studied 40 men and 50 women, 20–30 years of age, from the Indian paramilitary forces. These individuals consume a nutritious, high-protein diet, have optimal exposure to sunlight and undertake strenuous outdoor physical exercise. Results: The mean serum calcium, phosphorus and alkaline phosphatase levels were normal in both men and women. The mean (SD) serum intact parathyroid hormone and 25-hydroxy-vitamin D3 levels were 19.3 (8.2) pg/ml and 18.4 (5.3) ng/ml in men, and 11.9 (6.6) pg/ml and 25.3 (7.4) ng/ml in women. Bone mineral density estimated in 20 men and 22 women revealed that in comparison with white Caucasians, 35%–50% of men and 14%–32% of women were osteopenic at different sites, while an additional 10% of men had osteoporosis of the lumbar spine. Conclusion: We found that with optimal nutrition, good sunlight exposure and regular physical exercise, healthy young individuals have normal bone and mineral biochemical values. The reasons for the abnormalities detected in bone mineral density in them needs further study. The impact of childhood nutrition on accumulation of peak bone mass may contribute to our findings. There is a need for establishing normative bone mineral density data for Indians

Can curriculum design influence medical students’ attitudes to psychiatry? A comparison of two different approaches

Medical students with poor attitudes toward psychiatry are unlikely to choose it as a career, and current psychiatry recruitment is inadequate for future NHS needs. Amending medical school curricula has been suggested as one solution. We performed a unique naturalistic mixed-methods cross-sectional survey of two sequential cohorts in a UK medical school, before and after the restructuring of the entire MBChB curriculum. As well as increasing integration with other specialties, the emphasis placed on psychiatry increased throughout the course, but the final psychiatry block reduced from 8 to 6 weeks. Students experiencing the refreshed curriculum had better attitudes to psychiatry and psychiatric patients and were more positive about psychiatry as a career for themselves and others, compared to students on the old curriculum. This was demonstrated both quantitatively using validated rating scales (12/30 questions ATP-30 and 1/6 questions PEAK-6) and qualitatively using free-text responses. Restructuring undergraduate medical curricula to enhance integration may yield added value, including the potential to improve attitudes to specialties previously learned in silos, such as psychiatry. This may improve recruitment and the understanding of mental health for all future doctors

TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic?

In 2005 a newly discovered T helper cell subset that secreted interleukin (IL)-17 became the center of attention in immunology. Initial studies painted Th17 cells as the culprit for destruction in many different autoimmune and auto-inflammatory diseases. Subsequently, the discovery of patients with primary immunodeficiencies in the IL-17 pathway taught us that Th17 cells have a critical role in defense against certain fungal and bacterial infections. Moreover, the paradoxical exacerbation of Crohn’s disease in the clinical trials of a Secukinumab (AIN457), a fully human neutralizing antibody to IL-17A, has cast into doubt a universal pro-inflammatory and harmful role for Th17 cells. Evidence now suggests that depending on the environment Th17 cells can alter their differentiation program, ultimately giving rise to either protective or pro-inflammatory cells. In this review we will summarize the evidence from patients with immunodeficiencies, autoimmune, or auto-inflammatory diseases that teaches us how the pro-inflammatory versus protective function of Th17 cells varies within the context of different human diseases

Prevalence of diaphragmatic muscle weakness and dyspnoea in Graves' disease and their reversibility with carbimazole therapy

Objectives: Dyspnoea is a common complaint among patients with thyrotoxicosis. However, its causative mechanisms have not been identified. We assessed the role of thoracic diaphragmatic muscle weakness in dyspnoea among patients with active Graves' disease. Methods: Twenty-seven patients (19 female, 8 male) with active Graves' disease were assessed for the clinical severity of dyspnoea, functional (pressure generating capacity) and anatomical aspects (thickness and excursion) of the diaphragm at presentation. The severity of dyspnoea was assessed using a visual analogue scale (VAS) and the 6 min walk test. Lung function tests, diaphragmatic strength (sniff oesophageal pressure, SniffPoeso), maximum inspiratory and expiratory pressures, diaphragmatic thickness and movements on real time ultrasonography were evaluated during normal and deep respiration. Twenty of the 27 patients were reassessed after achieving euthyroidism with carbimazole therapy at a mean interval of 5±2 months. Results: Reevaluation after carbimazole therapy revealed a significant reduction in dyspnoea on the VAS (59±26 to 23±13%). Patients covered a similar distance during the 6 min walk before and after euthyroidism. Significant improvement was observed in the vital capacity (2.57±0.62 to 2.94±0.60 l), forced expiratory volume in the first second (2.21±0.49 to 2.45±0.47 l), total lung capacity (3.57±1.19 to 4.1±1.12 l), diaphragmatic movement during deep respiration (5.5±1.0 to 6.6±1.1 cm) and SniffPoeso (68.7±23 to 93.1±25.2 cmH2O). There was no significant change in the distance walked in 6 min, tidal volume, lung diffusion capacity and diaphragmatic thickness. There was no significant correlation between the net change in dyspnoea score and net change in lung function tests, diaphragmatic movement and SniffPoeso. Conclusions: Significant functional weakness of diaphragm muscle is present in patients with active Graves' disease. This weakness is more marked during a maximal respiratory manoeuvre, indicating a diminished diaphragmatic reserve which could be the cause of dyspnoea observed on exertion among patients with thyrotoxicosis

Affective Instability, Childhood Trauma and Major Affective Disorders

BACKGROUND: Affective instability (AI), childhood trauma, and mental illness are linked, but evidence in affective disorders is limited, despite both AI and childhood trauma being associated with poorer outcomes. Aims were to compare AI levels in bipolar disorder I (BPI) and II (BPII), and major depressive disorder recurrent (MDDR), and to examine the association of AI and childhood trauma within each diagnostic group. METHODS: AI, measured using the Affective Lability Scale (ALS), was compared between people with DSM-IV BPI (n=923), BPII (n=363) and MDDR (n=207) accounting for confounders and current mood. Regression modelling was used to examine the association between AI and childhood traumas in each diagnostic group. RESULTS: ALS scores in descending order were BPII, BPI, MDDR, and differences between groups were significant (p<0.05). Within the BPI group any childhood abuse (p=0.021), childhood physical abuse (p=0.003) and the death of a close friend in childhood (p=0.002) were significantly associated with higher ALS score but no association was found between childhood trauma and AI in BPII and MDDR. LIMITATIONS: The ALS is a self-report scale and is subject to retrospective recall bias. CONCLUSIONS: AI is an important dimension in bipolar disorder independent of current mood state. There is a strong link between childhood traumatic events and AI levels in BPI and this may be one way in which exposure and disorder are linked. Clinical interventions targeting AI in people who have suffered significant childhood trauma could potentially change the clinical course of bipolar disorder

Web based software for the study of USDA soil taxonomy and classification of newly found soil

United States Department of Agriculture (USDA) Soil Taxonomy is based on soil properties that can be objectively observed and measured in the natural conditions as they exist today. There are many soil classification systems but USDA Soil Taxonomy is most accepted worldwide. Ontologies are the new form of knowledge representation that acts in synergy with agents and Semantic Web Architecture. Soil ontology developed for USDA soil taxonomy has been used to develop a query interface that will help in detailed study of soil taxonomy, classification of new soil as well as exchange knowledge between software agents and systems. This is a web based application having N-tier architecture. Application development environment is NetBeans 6.9 editor and Protégé. Web development technology is Java Server Pages (JSP). Programming languages JAVA and SPARQL are used for querying. Client interface is developed with Hyper Text Markup Language (HTML), Cascading Style Sheet (CSS) and JavaScript. Third tier of software consist of database which is in MS-SQL server 2005. Other two layers are Web Ontology Language (OWL) Ontology layer and Semantic Web Framework layer. OWL layer contains soil taxonomy information in the form of Ontology. Semantic Web Framework layer is implemented using JENA. In the search panel user can search anything related to USDA Soil Taxonomy, which comprises of twelve orders. However, this software contains information about seven soil orders reported in India. Domain experts can see and edit the knowledge base (i.e. Soil Ontology) or can suggest anything related to the creation of Soil Taxonomy Ontology through WebProtégé

Prevalence of psychosis in black ethnic minorities in Britain: analysis based on three national surveys

Purpose A considerable excess of psychosis in black ethnic minorities is apparent from clinical studies, in Britain, as in other developed economies with white majority populations. This excess is not so marked in population surveys. Equitable health service provision should be informed by the best estimates of the excess. We used national survey data to establish the difference in the prevalence of psychosis between black ethnic groups and the white majority in the British general population. Methods Analysis of the combined datasets (N = 26,091) from the British national mental health surveys of 1993, 2000 and 2007. Cases of psychosis were determined either by the use of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), or from a combination of screening items. We controlled for sex, age, social class, unemployment, design features and other putative confounders, using a Disease Risk Score. Results People from black ethnic minorities had an excess prevalence rate of psychosis compared with the white majority population. The OR, weighted for study design and response rate, was 2.72 (95 % CI 1.3–5.6, p = 0.002). This was marginally increased after controlling for potential confounders (OR = 2.90, 95 % CI 1.4–6.2, p = 0.006). Conclusions The excess of psychosis in black ethnic minority groups was similar to that in two previous British community surveys, and less than that based on clinical studies. Even so it confirms a considerable need for increased mental health service resources in areas with high proportions of black ethnic minority inhabitants

Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts.

It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2-5. For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases6-8. This includes muscle biopsies from patients with undiagnosed rare muscle disorders6,9, and cultured fibroblasts from patients with mitochondrial disorders7. However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution

Mood instability, mental illness and suicidal ideas : results from a household survey

Purpose: There is weak and inconsistent evidence that mood instability (MI) is associated with depression, post traumatic stress disorder (PTSD) and suicidality although the basis of this is unclear. Our objectives were first to test whether there is an association between depression and PTSD, and MI and secondly whether MI exerts an independent effect on suicidal thinking over and above that explained by common mental disorders. Methods: We used data from the Adult Psychiatric Morbidity Survey 2007 (N = 7,131). Chi-square tests were used to examine associations between depression and PTSD, and MI, followed by regression modelling to examine associations between MI and depression, and with PTSD. Multiple logistic regression analyses were used to assess the independent effect of MI on suicidal thinking, after adjustment for demographic factors and the effects of common mental disorder diagnoses. Results: There are high rates of MI in depression and PTSD and the presence of MI increases the odds of depression by 10.66 [95 % confidence interval (CI) 7.51–15.13] and PTSD by 8.69 (95 % CI 5.90–12.79), respectively, after adjusting for other factors. Mood instability independently explained suicidal thinking, multiplying the odds by nearly five (odds ratio 4.82; 95 % CI 3.39–6.85), and was individually by some way the most important single factor in explaining suicidal thoughts. Conclusions: MI is strongly associated with depression and PTSD. In people with common mental disorders MI is clinically significant as it acts as an additional factor exacerbating the risk of suicidal thinking. It is important to enquire about MI as part of clinical assessment and treatment studies are required