Peak Bone Mineral Density of Physically Active Healthy Indian Men With Adequate Nutrition and No Known Current Constraints to Bone Mineralization

We undertook this study to characterize peak bone density and evaluate its determinants in a healthy cohort of young adult male paramilitary personnel. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry in 473 healthy men aged 21–40 yr. The effect of anthropometry and biochemical parameters on BMD was determined. Mean BMD values of L1–L4, forearm, total hip, and femoral neck were 1.170 ± 0.137, 0.755 ± 0.089, 1.129 ± 0.130, and 1.115 ± 0.133 g/cm², respectively. BMD values for 31- to 40-yr age group were lower than those of 20- to 30-yr age group except for forearm, which was higher in the former. Significant positive correlation was observed between height, weight, and body mass index with BMD. On multivariate regression analysis, weight was the most consistent contributor to variance in the BMD. Compared with age-matched US males, BMD of total hip and femoral neck were higher for Indian paramilitary personnel by 3.58% and 4.2%, whereas lumbar spine BMD was lower by 4.1%. In conclusion, peak BMD in healthy Indian males was achieved by 30 yr of age at lumbar spine and hip, with weight being the most consistent contributor to variance in BMD. Peak BMD in this population was comparable to that reported in white US males.     

What Have We Learned about Trial Design From NIMH-Funded Pragmatic Trials?

At the 2008 annual meeting of the American College of Neuropsychopharmacology (ACNP), a symposium was devoted to the following question: ‘what have we learned about the design of pragmatic clinical trials (PCTs) from the recent costly long-term, large-scale trials of psychiatric treatments?'' in order to inform the design of future trials. In all, 10 recommendations were generated placing emphasis on (1) appropriate conduct of pragmatic trials; (2) clinical, rather than, merely statistical significance; (3) sampling from the population clinicians are called upon to treat; (4) clinical outcomes of patients, rather than, on outcome measures; (5) use of stratification, controlling, or adjusting when necessary and not otherwise; (6) appropriate consideration of site differences in multisite studies; (7) encouragement of ‘post hoc'' exploration to generate (not test) hypotheses; (8) precise articulation of the treatment strategy to be tested and use of the corresponding appropriate design; (9) expanded opportunity for training of researchers and reviewers in RCT principles; and (10) greater emphasis on data sharing.     

Effects of age, gender and educational background on strength of motivation for medical school

The aim of this study was to determine the effects of selection, educational background, age and gender on strength of motivation to attend and pursue medical school. Graduate entry (GE) medical students (having Bachelor’s degree in Life Sciences or related field) and Non-Graduate Entry (NGE) medical students (having only completed high school), were asked to fill out the Strength of Motivation for Medical School (SMMS) questionnaire at the start of medical school. The questionnaire measures the willingness of the medical students to pursue medical education even in the face of difficulty and sacrifice. GE students (59.64 ± 7.30) had higher strength of motivation as compared to NGE students (55.26 ± 8.33), so did females (57.05 ± 8.28) as compared to males (54.30 ± 8.08). 7.9% of the variance in the SMMS scores could be explained with the help of a linear regression model with age, gender and educational background/selection as predictor variables. Age was the single largest predictor. Maturity, taking developmental differences between sexes into account, was used as a predictor to correct for differences in the maturation of males and females. Still, the gender differences prevailed, though they were reduced. Pre-entrance educational background and selection also predicted the strength of motivation, but the effect of the two was confounded. Strength of motivation appears to be a dynamic entity, changing primarily with age and maturity and to a small extent with gender and experience.     

Persistence and Dissipation of Flubendiamide and Des-iodo Flubendiamide in Cabbage (Brassica oleracea Linne) and Soil

Flubendiamide belongs to a novel class of insecticide which controls lepidopteran pest complex of cabbage such as diamondback moth, cabbage white butterfly, cluster caterpillar etc. Being a newly introduced insecticide no information is available on its residue persistence in cabbage. A study was undertaken to evaluate the residue persistence of flubendiamide in cabbage and soil following 2 applications of flubendiamide 480 SC at the recommended and double the recommended dose of 24 and 48 g a.i. ha⁻¹. Initial residue deposits of flubendiamide in cabbage were 0.33 and 0.49 mg kg⁻¹ respectively. The residues persisted for 10 days from the both the treatments and dissipated with the half-life of 3.9 and 4.45 days, respectively. Des-iodo flubendiamide, a metabolite of flubendiamide, was not detected in cabbage at any time during the study period. Soil sample collected from the treated field after 15 days was free from any residue of flubendiamide or its metabolite.     

The DOSE study: a clinical trial to examine efficacy and dose response of exercise as treatment for depression

The Depression Outcomes Study of Exercise (DOSE) was a randomized clinical trial to determine whether exercise is an efficacious treatment for mild to moderate major depressive disorder (MDD) in adults ages 20 to 45 years. The specific hypotheses under investigation were (1) active exercise is an efficacious monotherapy for mild to moderate levels of MDD, and (2) there is a dose-response relation between the exercise amount and reduction in depressive symptoms. The primary outcome measure was the Hamilton Rating Scale for Depression (HRSD) collected weekly over 12 weeks. Secondary outcome measures were the Inventory of Depressive Symptoms (clinician and self-report), HRSD scores at 24 weeks, cardiorespiratory fitness, self-efficacy, and quality of life. Eighty men and women who were diagnosed with a Structured Clinical Interview for Depression and who had mild (HRSD 12-16) to moderate (HRSD 17-25) MDD were randomized to one of five doses of exercise: 7.0 kcal/kg/week in 3 days/week; 7.0 kcal/kg/week in 5 days/week; 17.5 kcal/kg/week in 3 days/week; 17.5 kcal/kg/week in 5 days/week; or 3 days/week of stretching and flexibility exercises for 15 to 20 min/session. Participants exercised under supervision in our laboratory over the course of 12 weeks. Symptoms of depression were measured weekly by trained clinical raters blinded to the participant's treatment assignment. The design of the study restricted participant characteristics to mild to moderate MDD and controlled exercise features to permit the evaluation of exercise as a sole treatment for depression. This study is the first to examine dose-response effects of exercise in participants diagnosed with MDD.     

Endotoxemia and sepsis mortality reduction by non-anticoagulant activated protein C

Activated protein C (APC) reduces mortality of severe sepsis patients but increases the risk of serious bleeding. APC exerts anticoagulant activity by proteolysis of factors Va/VIIIa. APC also exerts antiinflammatory and antiapoptotic effects and stabilizes endothelial barrier function by APC-initiated cell signaling that requires two receptors, endothelial cell protein C receptor (EPCR) and protease-activated receptor 1 (PAR1). The relative importance of APC's various activities for efficacy in sepsis is unknown. We used protein engineering of mouse APC and genetically altered mice to clarify mechanisms for the efficacy of APC in mouse sepsis models. Mortality reduction in LPS-induced endotoxemia required the enzymatic active site of APC, EPCR, and PAR-1, highlighting a key role for APC's cytoprotective actions. A recombinant APC variant with normal signaling but <10% anticoagulant activity (5A-APC) was as effective as wild-type APC in reducing mortality after LPS challenge, and enhanced the survival of mice subjected to peritonitis induced by gram-positive or -negative bacteria or to polymicrobial peritoneal sepsis triggered by colon ascendens stent implantation. Thus, APC's efficacy in severe sepsis is predominantly based on EPCR- and PAR1-dependent cell signaling, and APC variants with normal cell signaling but reduced anticoagulant activities retain efficacy while reducing the risk of bleeding.     

Autosomal recessive otofaciocervical syndrome type 2 with novel homozygous small insertion in PAX1 gene

Otofaciocervical syndrome (OTFCS) is described as a single gene disorder of both autosomal dominant and autosomal recessive inheritance. The major clinical features of OTFCS include ear malformations (external/middle/inner ear), facial dysmorphism, shoulder girdle abnormalities, vertebral anomalies, and mild intellectual disability. The autosomal recessive form of OTFCS syndrome (OTFCS2) has been recently reported to be caused due to homozygous mutations in PAX1 gene. Here we report a third family of OTFCS2 phenotype wherein whole exome sequencing identified a novel homozygous small insertion in PAX1 as the underlying genetic cause.