Growth Profile of Baiga Children – A Primitive Tribe of District Dindori of Madhya Pradesh, India

The present study has been carried out on 795 Baiga children (453 males and 342 females) of Baiga-chak area of Dindori district in Madhya Pradesh (MP) varying between 1–18 years of age with an aim to understand their growth profile using cross sectional design. Fourteen body measurements (weight, height, sitting height, lengths, breadths, circumferences and skin folds) were studied. Four indices namely Sitting height / Leg length, Bicristal breadth / Biacromial breadth, Head circumference / Chest circumference & Cephalic index were computed to study the proportionate body changes. All body measurements except for skin folds increased progressively in each age group showing insignificant difference between boys and girls in most of age groups with no evident peak velocity during pubertal age in both sexes. However skin folds showed inconsistent pattern with each successive age. The present children were slightly heavier and taller than tribal children of other areas but lighter and shorter than Bharia children32. However, these children were comparable with all India rural children20 but found below 10th percentile when compared with National Centre for Health Statistics (NCHS) standards38. The absence of peak velocity and poor growth in studied children may be due to low intensity of growth rate. Proportionate changes observed in the present study were similar to Indian Punjabi girls44

Depression, Anxiety and Stress among Saudi Arabian Dermatology Patients : Cross-sectional study

Objectives: This study aimed to determine the prevalence of depression, anxiety and stress among Saudi Arabian dermatology patients and to assess associations with sociodemographic and clinical characteristics. Methods: This cross-sectional study was conducted among 300 consecutive dermatology patients visiting King Abdulaziz Medical City in Riyadh, Saudi Arabia, in August 2015. The Arabic version of the Depression, Anxiety and Stress Scale was used to screen for symptoms of depression, anxiety and stress. Quality of life (QOL) was assessed using the Dermatology Life Quality Index. Results: A total of 254 dermatology patients participated in the study (response rate: 84.7%). The prevalence of depression, anxiety and stress was 12.6%, 22.1% and 7.5%, respectively. The presence of at least one of these negative emotional states was noted among 24.4% of the cohort (95% confidence interval: 19.3–30.2%). Depression was significantly higher among subjects who lacked family support (26.5% versus 10.7%; P = 0.006) while anxiety was less common among patients who engaged in physical exercise (14.5% versus 29.4%; P = 0.005). According to the multivariate logistic regression analysis, poor QOL and a lack of family support were significant predictors of a negative emotional state. Conclusion: Almost a quarter of the studied Saudi Arabian dermatology patients were found to suffer from at least one negative emotional state. A lack of family support and poor QOL were the primary factors associated with a negative emotional state. Interventional studies are needed to examine the effects of social and family support on psychological conditions among Saudi Arabian dermatology patients

Essential amino acids in total knee and hip joint replacement: a narrative review

The increasing availability of total joint replacement especially for knee and hip joints has increased their rates substantially across the globe. It is associated with increased risk of sarcopenia with loss of muscle mass and strength in the postoperative period. The supplementation of proteins along with exercises have been mainframe strategy to improve the functional ability after total knee arthroplasty and total hip arthroplasty. However, supplementation of proteins necessitates effective proteolytic digestion and conversion to amino acids for exerting substantial effects. In overcoming this challenge, supplementation with essential amino acids can be an attractive approach In this article, we review the clinical evidence with use of essential amino acids in patients undergoing TKA and THA. In the nine studies included in the review, seven assessed EAAs in TKA and two in THA. In TKA studies, improvement in muscle mass, muscle strength and functional recovery has been significant over 6 weeks postoperatively in majority of the studies. Over long term (2 years), improved recovery of rectus femoris and quadriceps had been reported. In THA as well, significant improvement in hip function and stability has been reported. Thus, EAAs in addition to the existing rehabilitation program are helpful to improve sarcopenia and enhances the recovery to perform activities of daily living. We propose from current evidence that administration of EAAs 7 to 10 days prior to planned TKA or THA and continued for 14 to 20 days in the postoperative period along with rehabilitation program is optimal in enhancing the muscle strength and help in physical functional recovery. Current evidence indicates supplementation with EAAs should be a part of routine management protocol in patients undergoing TKA or THA

A non-interventional, prospective, multicentric real life Indian study to assess safety and effectiveness of un-denatured type 2 collagen in management of osteoarthritis

Background: Osteoarthritis (OA) is the most common musculoskeletal condition affecting the quality of life. Undenatured collagen type II has emerged as one of the promising treatment options in treatment of OA. Despite being available in India, clinical safety and efficacy have not been evaluated. We performed a non-interventional, real-life study to determine its safety and efficacy in Indian population.Methods: A non-interventional, real-life study was performed in patients with OA of knee by 18 orthopaedicians in India. Patients enrolled were followed-up at day 30 (visit 2), day 60 (visit 3) and day 90 (visit 4). Efficacy was assessed by Western Ontario McMaster Osteoarthritis Index (WOMAC) and Visual Analogue scale (VAS) on each visit. Safety was assessed by incidence of suspected adverse events (AEs), and abnormal laboratory parameters.Results: Among 291 enrolled patients 226 patients completed the study. Mean age of the population was 56.2±8.7 years and 53.3% of them were females. In 291 patients included in safety analysis, at least one treatment emergent adverse event (TEAE) was seen in 4.47% patients. None of the AEs were serious or resulted in termination of patient from the study. Nausea (1.37%) and headache (1.03%) were the common AEs. Treatment with undenatured collagen type II was associated with significant reduction in WOMAC score (p<0.0001) and VAS scores (p<0.0001) from baseline to day 90.Conclusions: Undenatured collagen type II is safe and efficacious in Indian patients with OA. This can be considered early in the initial management of OA

Transposable Elements Are Co-opted as Oncogenic Regulatory Elements by Lineage-Specific Transcription Factors in Prostate Cancer

Transposable elements hold regulatory functions that impact cell fate determination by controlling gene expression. However, little is known about the transcriptional machinery engaged at transposable elements in pluripotent and mature versus oncogenic cell states. Through positional analysis over repetitive DNA sequences of H3K27ac chromatin immunoprecipitation sequencing data from 32 normal cell states, we report pluripotent/stem and mature cell state–specific “regulatory transposable elements.” Pluripotent/stem elements are binding sites for pluripotency factors (e.g., NANOG, SOX2, OCT4). Mature cell elements are docking sites for lineage-specific transcription factors, including AR and FOXA1 in prostate epithelium. Expanding the analysis to prostate tumors, we identify a subset of regulatory transposable elements shared with pluripotent/stem cells, including Tigger3a. Using chromatin editing technology, we show how such elements promote prostate cancer growth by regulating AR transcriptional activity. Collectively, our results suggest that oncogenesis arises from lineage-specific transcription factors hijacking pluripotent/stem cell regulatory transposable elements.</p

Transposable Elements Are Co-opted as Oncogenic Regulatory Elements by Lineage-Specific Transcription Factors in Prostate Cancer

Transposable elements hold regulatory functions that impact cell fate determination by controlling gene expression. However, little is known about the transcriptional machinery engaged at transposable elements in pluripotent and mature versus oncogenic cell states. Through positional analysis over repetitive DNA sequences of H3K27ac chromatin immunoprecipitation sequencing data from 32 normal cell states, we report pluripotent/stem and mature cell state–specific “regulatory transposable elements.” Pluripotent/stem elements are binding sites for pluripotency factors (e.g., NANOG, SOX2, OCT4). Mature cell elements are docking sites for lineage-specific transcription factors, including AR and FOXA1 in prostate epithelium. Expanding the analysis to prostate tumors, we identify a subset of regulatory transposable elements shared with pluripotent/stem cells, including Tigger3a. Using chromatin editing technology, we show how such elements promote prostate cancer growth by regulating AR transcriptional activity. Collectively, our results suggest that oncogenesis arises from lineage-specific transcription factors hijacking pluripotent/stem cell regulatory transposable elements.</p

A novel nucleoid-associated protein of Mycobacterium tuberculosis is a sequence homolog of GroEL

The Mycobacterium tuberculosis genome sequence reveals remarkable absence of many nucleoid-associated proteins (NAPs), such as HNS, Hfq or DPS. In order to characterize the nucleoids of M. tuberculosis, we have attempted to identify NAPs, and report an interesting finding that a chaperonin-homolog, GroEL1, is nucleoid associated. We report that M. tuberculosis GroEL1 binds DNA with low specificity but high affinity, suggesting that it might have naturally evolved to bind DNA. We are able to demonstrate that GroEL1 can effectively function as a DNA-protecting agent against DNase I or hydroxyl-radicals. Moreover, Atomic Force Microscopic studies reveal that GroEL1 can condense a large DNA into a compact structure. We also provide in vivo evidences that include presence of GroEL1 in purified nucleoids, in vivo crosslinking followed by Southern hybridizations and immunofluorescence imaging in M. tuberculosis confirming that GroEL1: DNA interactions occur in natural biological settings. These findings therefore reveal that M. tuberculosis GroEL1 has evolved to be associated with nucleoids

Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial

OBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumonia after treatment with tocilizumab, an anti-interleukin-6 receptor antibody, using data from the COVACTA trial in patients hospitalized with severe coronavirus disease 2019 pneumonia. DESIGN: Exploratory analysis from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. SETTING: Hospitals in North America and Europe. PATIENTS: Adults hospitalized with severe coronavirus disease 2019 pneumonia receiving standard care. INTERVENTION: Randomly assigned 2:1 to IV tocilizumab 8 mg/kg or placebo. MEASUREMENTS AND MAIN RESULTS: Candidate biomarkers were measured in 295 patients in the tocilizumab arm and 142 patients in the placebo arm. Efficacy outcomes assessed were clinical status on a seven-category ordinal scale (1, discharge; 7, death), mortality, time to hospital discharge, and mechanical ventilation (if not receiving it at randomization) through day 28. Prognostic and predictive biomarkers were evaluated continuously with proportional odds, binomial or Fine-Gray models, and additional sensitivity analyses. Modeling in the placebo arm showed all candidate biomarkers except lactate dehydrogenase and d-dimer were strongly prognostic for day 28 clinical outcomes of mortality, mechanical ventilation, clinical status, and time to hospital discharge. Modeling in the tocilizumab arm showed a predictive value of ferritin for day 28 clinical outcomes of mortality (predictive interaction, p = 0.03), mechanical ventilation (predictive interaction, p = 0.01), and clinical status (predictive interaction, p = 0.02) compared with placebo. CONCLUSIONS: Multiple biomarkers prognostic for clinical outcomes were confirmed in COVACTA. Ferritin was identified as a predictive biomarker for the effects of tocilizumab in the COVACTA patient population; high ferritin levels were associated with better clinical outcomes for tocilizumab compared with placebo at day 28

Is Early Puberty Triggered by Catch-Up Growth Following Undernutrition?

Undernutrition during fetal and postnatal life is still a major problem in many low- and middle-income countries. Even in high-income countries malnutrition may exist in cases of intrauterine growth retardation, as well as in chronic conditions such as anorexia nervosa and inflammatory bowel disease. Children adopted from developing countries are often chronically malnourished. Nutritional rehabilitation, resulting in catch-up growth, is often complicated by influences originating in fetal life as well as during postnatal growth. This may result in hormonal and metabolic changes as well as alterations in pubertal development. The present review focuses on fetal, postnatal and fetal-postnatal undernutrition and subsequent catch-up growth as well as catch-up growth in relation to pubertal development. Catch-up growth in children can be associated with early puberty following fetal or combined fetal-postnatal undernutrition. However, early puberty does not seem to occur following catch-up growth after isolated postnatal undernutrition. Gonadotropins have been reported to be elevated in prepubertal adopted girls as well as during catch-up growth in animals. Even if other factors may contribute, linear catch-up growth seems to be associated with the timing of pubertal development. The mechanisms behind this are still unknown. Future research may elucidate how to carry out nutritional rehabilitation without risk for early pubertal development

A Mycobacterium leprae Hsp65 Mutant as a Candidate for Mitigating Lupus Aggravation in Mice

Hsp60 is an abundant and highly conserved family of intracellular molecules. Increased levels of this family of proteins have been observed in the extracellular compartment in chronic inflammation. Administration of M. leprae Hsp65 [WT] in [NZBxNZW]F1 mice accelerates the Systemic Lupus Erythematosus [SLE] progression whereas the point mutated K409A Hsp65 protein delays the disease. Here, the biological effects of M. leprae Hsp65 Leader pep and K409A pep synthetic peptides, which cover residues 352–371, are presented. Peptides had immunomodulatory effects similar to that observed with their respective proteins on survival and the combined administration of K409A+Leader pep or K409A pep+WT showed that the mutant forms were able to inhibit the deleterious effect of WT on mortality, indicating the neutralizing potential of the mutant molecules in SLE progression. Molecular modeling showed that replacing Lysine by Alanine affects the electrostatic potential of the 352–371 region. The number of interactions observed for WT is much higher than for Hsp65 K409A and mouse Hsp60. The immunomodulatory effects of the point-mutated protein and peptide occurred regardless of the catalytic activity. These findings may be related to the lack of effect on survival when F1 mice were inoculated with Hsp60 or K409A pep. Our findings indicate the use of point-mutated Hsp65 molecules, such as the K409A protein and its corresponding peptide, that may minimize or delay the onset of SLE, representing a new approach to the treatment of autoimmune diseases