METABOLIC SYNDROME IN FEMALE WORKERS FROM A TEXTILE MILL: EFFECT OF NOISE

Objective: Noise creates alteration in human health in both physical as well as psychological variations. Effect of noise on components of metabolic syndrome (MetS) has been discussed but not well established. The aim of this study was to investigate the MetS in female workers from textile mill.Methods: A total of 65 female workers were recruited for the study from the high noise (>70 dB) area and low noise (<40 dB) area of a textile mill. Body mass index (BMI), blood pressure (BP), blood sugar (BS), and lipid profile were investigated of the female workers. BP was estimated by auscultatory method. BS was investigated by glucose oxidase-peroxidase (POD) method. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were investigated by cholesterol oxidase (CHOD)-POD method, GPO- PAP method, CHOD-POD/phosphotungustate method, and friedewald formula, respectively.Results: Significant outcomes were obtained in this study. BMI was significantly (<0.01) higher in workers working in high noise area compared to low noise (<40 dB) area. Systolic BP and diastolic BP was also significantly (<0.01) higher in high noise area. Fasting BS level was found to be significantly (<0.01) lower in low noise area. In case of lipid profile significant (<0.01) results were obtained except LDL-C. TC and TG were found to be related with noise since their concentration was higher in high noise area compared to low noise area. However, HDL-C was found to be lower in high noise area compared to low noise area.Conclusion: Continuous exposure to occupational noise might be reason for developing cardiovascular disease depending on the degree of MetS in industrial workers. BP and BS seems to be better predictor of MetS in assessing cardiovascular risk.Keywords: Occupational noise, Metabolic syndrome, Dyslipidemia

High Prevalence of Abdominal, Intra-Abdominal and Subcutaneous Adiposity and Clustering of Risk Factors among Urban Asian Indians in North India

OBJECTIVE: To assess the prevalence of abdominal obesity including intra-abdominal and subcutaneous adiposity along with other cardiometabolic risk factors in urban Asian Indians living in New Delhi. METHODS: We conducted a cross-sectional epidemiological descriptive study with 459 subjects (217 males and 242 females), representing all socio-economic strata in New Delhi. The anthropometric profile [body mass index (BMI), waist circumference (WC) and skinfold thickness], fasting blood glucose (FBG) and lipid profile were recorded. Percent body fat (%BF), total abdominal fat (TAF), intra-abdominal adipose tissue (IAAT) and subcutaneous abdominal adipose tissue (SCAT) were quantified using predictive equations for Asian Indians. RESULTS: The overall prevalence of obesity was high [by BMI (>25 kg/m(2)), 50.1%]. The prevalence of abdominal obesity (as assessed by WC) was 68.9%, while that assessed by TAF was 70.8%. Increased IAAT was significantly higher in females (80.6%) as compared to males (56.7%) (p = 0.00) with overall prevalence being 69.3%. The overall prevalence of high SCAT was 67.8%, more in males (69.1%) vs. females (66.5%, p = 0.5). The prevalence of type 2 diabetes, the metabolic syndrome and hypertension was 8.5%, 45.3% and 29.2%, respectively. Hypertriglyceridemia, hypercholesterolemia and low levels of HDL-c were prevalent in 42.7%, 26.6% and 37% of the subjects, respectively. The prevalence of hypertriglyceridemia was significantly higher in males (p = 0.007); however, low levels of HDL-c were more prevalent in females as compared to males (p = 0.00). CONCLUSION: High prevalence of generalized obesity, abdominal obesity (by measurement of WC, TAF, IAAT and SCAT) and dysmetabolic state in urban Asian Indians in north India need immediate public health intervention

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Sugar Intake, Obesity, and Diabetes in India

Sugar and sweet consumption have been popular and intrinsic to Indian culture, traditions, and religion from ancient times. In this article, we review the data showing increasing sugar consumption in India, including traditional sources (jaggery and khandsari) and from sugar-sweetened beverages (SSBs). Along with decreasing physical activity, this increasing trend of per capita sugar consumption assumes significance in view of the high tendency for Indians to develop insulin resistance, abdominal adiposity, and hepatic steatosis, and the increasing “epidemic” of type 2 diabetes (T2DM) and cardiovascular diseases. Importantly, there are preliminary data to show that incidence of obesity and T2DM could be decreased by increasing taxation on SSBs. Other prevention strategies, encompassing multiple stakeholders (government, industry, and consumers), should target on decreasing sugar consumption in the Indian population. In this context, dietary guidelines for Indians show that sugar consumption should be less than 10% of total daily energy intake, but it is suggested that this limit be decreased

Attenuation of opioid tolerance by ETB receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice

Aim: ETA receptor antagonists reverse opioid tolerance but the involvement of ETB receptors is unknown. In morphine or oxycodone tolerant mice we investigated (1) the effect of ETB receptor agonist, IRL-1620, on analgesic tolerance; (2) changes in expression of the brain ETA and ETB receptors; and (3) alterations in the brain VEGF, NGF, PI3K and notch-1 expression. Main methods: Body weight, body temperature, and tail-flick latency were assessed before and after a challenge dose of morphine or oxycodone in vehicle or IRL-1620 treated mice. Expression studies were carried out using Western blots. Key findings: Tail flick latency to a challenge dose of opioid was significantly increased by IRL-1620 from 39% to 100% in morphine tolerant and from 8% to 83% in oxycodone tolerant mice. Morphine or oxycodone did not alter ETA or ETB receptor expression. IRL-1620 had no effect on ETA however it increased (61%) expression of ETB receptors. IRL-1620-induced increase in ETB receptor expression was attenuated by morphine (39.8%) and oxycodone (51.8%). VEGF expression was not affected by morphine or oxycodone and was unaltered by IRL-1620. However, NGF and PI3K expression was decreased (P < 0.001) by morphine and oxycodone and was unaffected by IRL-1620. Notch-1 expression was not altered by morphine, oxycodone or IRL-1620. Significance: ETB receptor agonist, IRL-1620, restored analgesic tolerance to morphine and oxycodone, but it did not affect morphine and oxycodone induced decrease in NGF/PI3K expression. It is concluded that IRL-1620 attenuates opioid tolerance without the involvement of NGF/PI3K pathway

Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double -blind control trial

Abstract Background Nutritional modulation remains central to the management of metabolic syndrome. Intervention with cinnamon in individuals with metabolic syndrome remains sparsely researched. Methods We investigated the effect of oral cinnamon consumption on body composition and metabolic parameters of Asian Indians with metabolic syndrome. In this 16-week double blind randomized control trial, 116 individuals with metabolic syndrome were randomized to two dietary intervention groups, cinnamon [6 capsules (3 g) daily] or wheat flour [6 capsules (2.5 g) daily]. Body composition, blood pressure and metabolic parameters were assessed. Results Significantly greater decrease [difference between means, (95% CI)] in fasting blood glucose (mmol/L) [0.3 (0.2, 0.5) p = 0.001], glycosylated haemoglobin (mmol/mol) [2.6 (0.4, 4.9) p = 0.023], waist circumference (cm) [4.8 (1.9, 7.7) p = 0.002] and body mass index (kg/m2 ) [1.3 (0.9, 1.5) p = 0.001] was observed in the cinnamon group compared to placebo group. Other parameters which showed significantly greater improvement were: waist-hip ratio, blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, and high-density lipoprotein cholesterol. Prevalence of defined metabolic syndrome was significantly reduced in the intervention group (34.5%) vs. the placebo group (5.2%). Conclusion A single supplement intervention with 3 g cinnamon for 16 weeks resulted in significant improvements in all components of metabolic syndrome in a sample of Asian Indians in north India. Trial registration The clinical trial was retrospectively registered (after the recruitment of the participants) in ClinicalTrial.gov under the identification number: NCT02455778 on 25th May 2015