Aim and objective
The aim of the study was to investigate the relationships between insulin receptor substrate (
IRS
) 1 (Gly972Arg) and
IRS2
(Gly1057Asp) genes with obstructive sleep apnea (OSA) and ...non-alcoholic fatty liver disease (NAFLD) in Asian Indians.
Method
A total of 410 overweight/obese subjects (130 with OSA with NAFLD, 100 with OSA without NAFLD, 95 without OSA and with NAFLD and 85 without OSA and without NAFLD) were recruited. Degree of NAFLD was based on liver ultrasound and of OSA on overnight polysomnography. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by gene sequencing.
Result
Mean values of blood pressure, body fat markers, blood glucose, lipids, liver function, and markers of insulin resistance were significantly increased in OSA and NAFLD subjects (p<0.05). In addition, according to age (years) categories, blood pressure, blood glucose, lipids, obesity markers, and markers of insulin resistance were significantly higher in 45–60 years group as compared to 20–45 years group (p<0.05). In
IRS1
gene, the genotype frequency (%) of Arg/Arg was significantly higher in NAFLD and OSA subjects. In addition, Gly/Arg genotype of
IRS1
gene was associated with significantly higher body mass index, fat mass, %body fat, triglycerides, cholesterol, alkaline phosphate, aspartate transaminase, fasting insulin and HOMA-IR levels in OSA and NAFLD subjects. No significant difference in genotype frequencies of
IRS2
was observed between four groups. Further we found that subjects carrying
IRS1
Gly/Arg (OR 4.49, 95% C.I. 1.06–12.52, p = 0.002) genotype possess a much higher risk of OSA and NAFLD compared to
IRS2
Gly/Asp (OR 1.01, 95% C.I. 0.8–2.56, p = 0.05). In sub group analysis of
IRS1
Gly/Arg have significant differences between the mild, moderate and severe group (P<0.05). In addition, patients with the ‘Gly’ allele were inclined to develop more severe OSA.
Conclusion
We concluded that Asian Indian subject carrying the allele Gly972Arg polymorphism of
IRS1
is predisposed to develop OSA and NAFLD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectiveTo investigate gender discrimination in access to healthcare and its relationship with the patient’s age and distance from the healthcare facility.Design and settingAn observational study ...based on outpatient data from a large referral public hospital in Delhi, India.ParticipantsConfirmed clinical appointments.Primary and secondary outcome measuresEstimates from the logistic regression are used to compute sex ratios (male/female) of patient visits with respect to distance from the hospital and age. Missing female patients for each state—a measure of the extent of gender discrimination—is computed as the difference in the actual number of female patients who came from each state and the number of female patients that should have visited the hospital had male and female patients come in the same proportion as the sex ratio of the overall population from the 2011 census.ResultsOf 2377028 outpatient visits, excluding obstetrics and gynaecology patients, the overall sex ratio was 1.69 male to one female visit. Sex ratios, adjusted for age and hospital department, increased with distance. The ratio was 1.41 for Delhi, where the facility is located; 1.70 for Haryana, an adjoining state; 1.98 for Uttar Pradesh, a state further away; and 2.37 for Bihar, the state furthest from Delhi. The sex ratios had a U-shaped relationship with age: 1.93 for 0–18 years, 2.01 for 19–30 years, and 1.75 for 60 years or over compared with 1.43 and 1.40 for the age groups 31–44 and 45–59 years, respectively. We estimate there were 402 722 missing female outpatient visits from these four states, which is 49% of the total female outpatient visits for these four states.ConclusionWe found gender discrimination in access to healthcare, which was worse for female patients who were in the younger and older age groups, and for those who lived at increasing distances from the hospital.
Air pollution is a major planetary health risk, with India estimated to have some of the worst levels globally. To inform action at subnational levels in India, we estimated the exposure to air ...pollution and its impact on deaths, disease burden, and life expectancy in every state of India in 2017.
We estimated exposure to air pollution, including ambient particulate matter pollution, defined as the annual average gridded concentration of PM2.5, and household air pollution, defined as percentage of households using solid cooking fuels and the corresponding exposure to PM2.5, across the states of India using accessible data from multiple sources as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. The states were categorised into three Socio-demographic Index (SDI) levels as calculated by GBD 2017 on the basis of lag-distributed per-capita income, mean education in people aged 15 years or older, and total fertility rate in people younger than 25 years. We estimated deaths and disability-adjusted life-years (DALYs) attributable to air pollution exposure, on the basis of exposure–response relationships from the published literature, as assessed in GBD 2017; the proportion of total global air pollution DALYs in India; and what the life expectancy would have been in each state of India if air pollution levels had been less than the minimum level causing health loss.
The annual population-weighted mean exposure to ambient particulate matter PM2·5 in India was 89·9 μg/m3 (95% uncertainty interval UI 67·0–112·0) in 2017. Most states, and 76·8% of the population of India, were exposed to annual population-weighted mean PM2·5 greater than 40 μg/m3, which is the limit recommended by the National Ambient Air Quality Standards in India. Delhi had the highest annual population-weighted mean PM2·5 in 2017, followed by Uttar Pradesh, Bihar, and Haryana in north India, all with mean values greater than 125 μg/m3. The proportion of population using solid fuels in India was 55·5% (54·8–56·2) in 2017, which exceeded 75% in the low SDI states of Bihar, Jharkhand, and Odisha. 1·24 million (1·09–1·39) deaths in India in 2017, which were 12·5% of the total deaths, were attributable to air pollution, including 0·67 million (0·55–0·79) from ambient particulate matter pollution and 0·48 million (0·39–0·58) from household air pollution. Of these deaths attributable to air pollution, 51·4% were in people younger than 70 years. India contributed 18·1% of the global population but had 26·2% of the global air pollution DALYs in 2017. The ambient particulate matter pollution DALY rate was highest in the north Indian states of Uttar Pradesh, Haryana, Delhi, Punjab, and Rajasthan, spread across the three SDI state groups, and the household air pollution DALY rate was highest in the low SDI states of Chhattisgarh, Rajasthan, Madhya Pradesh, and Assam in north and northeast India. We estimated that if the air pollution level in India were less than the minimum causing health loss, the average life expectancy in 2017 would have been higher by 1·7 years (1·6–1·9), with this increase exceeding 2 years in the north Indian states of Rajasthan, Uttar Pradesh, and Haryana.
India has disproportionately high mortality and disease burden due to air pollution. This burden is generally highest in the low SDI states of north India. Reducing the substantial avoidable deaths and disease burden from this major environmental risk is dependent on rapid deployment of effective multisectoral policies throughout India that are commensurate with the magnitude of air pollution in each state.
Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.
BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the ...effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection.
We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 – odds ratio) × 100%.
Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33–62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22–62) and administered at least 42 days before testing was 57% (21–76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29–61).
This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures.
None.
For the Hindi translation of the abstract see Supplementary Materials section.
Global deregulation in miRNA expression is a hallmark of cancer cell. An estimated 2300 mature miRNAs are encoded by human genome; role of many of which in carcinogenesis and as cancer biomarkers ...remains unexplored. In this study, we investigated the utility of miR-3692-3p, miR-3195, and miR-1249-3p as biomarkers in non-small cell lung cancer (NSCLC). For this prospective study, 115 subjects, including 75 NSCLC patients and 40 controls, were recruited. The expression of miR-3692-3p, miR-3195, and miR-1249-3p was checked using qRT-PCR. The miRNA expression was correlated with survival outcome and therapeutic response. There were no significant differences in the mean age of NSCLC patients and controls (56.2 and 55.3 years, respectively;
p
= 0.3242). Majority of NSCLC patients (67%) were smokers. We observed a significant upregulation of miR-3692-3p expression (
p
< 0.0001), while the expression of miR-3195 (
p
= 0.0017) and miR-1249-3p was significantly downregulated (
p
< 0.0001) in the serum of NSCLC patients as compared to controls. The expression of miR-1249-3p was significantly upregulated in lung adenocarcinoma versus lung squamous cell carcinoma (
p
= 0.0178). Interestingly, patients who responded to chemotherapy had higher expression of miR-1249-3p than non-responders (
p
= 0.0107). Moreover, patients with higher expression of miR-3195 had significantly longer overall survival (
p
= 0.0298). In multivariate analysis, miR-3195 emerged as independent prognostic factor for overall survival. We conclude that the miR-3195 may have prognostic significance, while miR-1249-3p may predict therapeutic response in NSCLC. Further studies are warranted to elucidate the role of these miRNAs in lung carcinogenesis and their utility as candidate cancer biomarkers.
Sarcoidosis is a multisystem granulomatous disease with nonspecific clinical manifestations that commonly affects the pulmonary system and other organs including the eyes, skin, liver, spleen, and ...lymph nodes. Sarcoidosis usually presents with persistent dry cough, eye and skin manifestations, weight loss, fatigue, night sweats, and erythema nodosum. Sarcoidosis is not influenced by sex or age, although it is more common in adults (< 50 years) of African-American or Scandinavians decent. Diagnosis can be difficult because of nonspecific symptoms and can only be verified following histopathological examination. Various factors, including infection, genetic predisposition, and environmental factors, are involved in the pathology of sarcoidosis. Exposures to insecticides, herbicides, bioaerosols, and agricultural employment are also associated with an increased risk for sarcoidosis. Due to its unknown etiology, early diagnosis and detection are difficult; however, the advent of advanced technologies, such as endobronchial ultrasound-guided biopsy, high-resolution computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography has improved our ability to reliably diagnose this condition and accurately forecast its prognosis. This review discusses the causes and clinical features of sarcoidosis, and the improvements made in its prognosis, therapeutic management, and the recent discovery of potential biomarkers associated with the diagnostic assay used for sarcoidosis confirmation.
India has 18% of the global population and an increasing burden of chronic respiratory diseases. However, a systematic understanding of the distribution of chronic respiratory diseases and their ...trends over time is not readily available for all of the states of India. Our aim was to report the trends in the burden of chronic respiratory diseases and the heterogeneity in their distribution in all states of India between 1990 and 2016.
Using all accessible data from multiple sources, we estimated the prevalence of major chronic respiratory diseases and the deaths and disability-adjusted life-years (DALYs) caused by them for every state of India from 1990 to 2016 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016. We assessed heterogeneity in the burden of chronic obstructive pulmonary disease (COPD) and asthma across the states of India. The states were categorised into four groups based on their epidemiological transition level (ETL). ETL was defined as the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa. We also assessed the contribution of risk factors to DALYs due to COPD. We compared the burden of chronic respiratory diseases in India against the global average in GBD 2016. We calculated 95% uncertainty intervals (UIs) for the point estimates.
The contribution of chronic respiratory diseases to the total DALYs in India increased from 4·5% (95% UI 4·0–4·9) in 1990 to 6·4% (5·8–7·0) in 2016. Of the total global DALYs due to chronic respiratory diseases in 2016, 32·0% occurred in India. COPD and asthma were responsible for 75·6% and 20·0% of the chronic respiratory disease DALYs, respectively, in India in 2016. The number of cases of COPD in India increased from 28·1 million (27·0–29·2) in 1990 to 55·3 million (53·1–57·6) in 2016, an increase in prevalence from 3·3% (3·1–3·4) to 4·2% (4·0–4·4). The age-standardised COPD prevalence and DALY rates in 2016 were highest in the less developed low ETL state group. There were 37·9 million (35·7–40·2) cases of asthma in India in 2016, with similar prevalence in the four ETL state groups, but the highest DALY rate was in the low ETL state group. The highest DALY rates for both COPD and asthma in 2016 were in the low ETL states of Rajasthan and Uttar Pradesh. The DALYs per case of COPD and asthma were 1·7 and 2·4 times higher in India than the global average in 2016, respectively; most states had higher rates compared with other locations worldwide at similar levels of Socio-demographic Index. Of the DALYs due to COPD in India in 2016, 53·7% (43·1–65·0) were attributable to air pollution, 25·4% (19·5–31·7) to tobacco use, and 16·5% (14·1–19·2) to occupational risks, making these the leading risk factors for COPD.
India has a disproportionately high burden of chronic respiratory diseases. The increasing contribution of these diseases to the overall disease burden across India and the high rate of health loss from them, especially in the less developed low ETL states, highlights the need for focused policy interventions to address this significant cause of disease burden in India.
Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.
Background Obesity is known to increase asthma risk and severity. Increased levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are associated with ...mitochondrial toxicity, asthma, and metabolic syndrome. IL-4 upregulates the expression of protein arginine methyltransferases, which are essential for ADMA formation. Importantly, cross-talk between IL-4, ADMA, and mitochondrial dysfunction could explain how obesity and IL-4 can synergize to exacerbate allergic inflammation. Objective We sought to investigate how IL-4, a key asthma-associated cytokine, can influence ADMA-related effects on lungs. Methods BEAS2B (bronchial epithelial) cells were treated with IL-4 followed by ADMA and investigated for oxo-nitrative stress and resultant mitochondrial toxicity after 48 hours by using flow cytometry, confocal imaging, immunoblotting, and fluorimetric assays. Results IL-4–induced mitotoxicity in BEAS2B cells was significantly higher in the presence of exogenous ADMA. IL-4 treatment led to proteolytic degradation of dimethylarginine dimethylaminohydrolase 2, which catabolizes ADMA. IL-4 pretreatment was associated with increased intracellular ADMA accumulation and increased ADMA-induced mitotoxicity. Airway epithelial cells treated with IL-4 followed by ADMA showed exaggerated oxo-nitrative stress and potent induction of the cellular hypoxic response, despite normoxic conditions. The hypoxic response was associated with reduced mitochondrial function but was reversible by overexpression of the mitochondrial biogenesis factor, mitochondrial transcription factor A. Conclusion We conclude that IL-4 promotes intracellular ADMA accumulation, leading to mitochondrial loss through oxo-nitrative stress and hypoxic response. This provides a novel understanding of how obesity, with high ADMA levels, and asthma, with high IL-4 levels, might potentiate each other and highlights the potential of mitochondrial-targeted therapeutics in obese subjects with asthma.
Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are at an increased risk for coinfections; therefore, physicians need to be ...cognizant about excluding other treatable respiratory pathogens. Here, we report coinfection with SARS-CoV-2 and other respiratory pathogens in patients admitted to the coronavirus disease (COVID) care facilities of an Indian tertiary care hospital. From June 2020 through January 2021, we tested 191 patients with SARS-CoV-2 for 33 other respiratory pathogens using an fast track diagnostics respiratory pathogen 33 (FTD-33) assay. Additionally, information regarding other relevant respiratory pathogens was collected by reviewing their laboratory data. Overall, 13 pathogens were identified among patients infected with SARS-CoV-2, and 46.6% (89/191) of patients had coinfection with one or more additional pathogens. Bacterial coinfections (41.4% 79/191) were frequent, with Staphylococcus aureus being the most common, followed by Klebsiella pneumoniae. Coinfections with SARS-CoV-2 and Pneumocystis jirovecii or Legionella pneumophila were also identified. The viral coinfection rate was 7.3%, with human adenovirus and human rhinovirus being the most common. Five patients in our cohort had positive cultures for Acinetobacter baumannii and K. pneumoniae, and two patients had active Mycobacterium tuberculosis infection. In total, 47.1% (90/191) of patients with coinfections were identified. The higher proportion of patients with coinfections in our cohort supports the systemic use of antibiotics in patients with severe SARS-CoV-2 pneumonia with rapid de-escalation based on respiratory PCR/culture results. The timely and simultaneous identification of coinfections can contribute to improved health of COVID-19 patients and enhanced antibiotic stewardship during the pandemic. IMPORTANCE Coinfections in COVID-19 patients may worsen disease outcomes and need further investigation. We found that a higher proportion of patients with COVID-19 were coinfected with one or more additional pathogens. A better understanding of the prevalence of coinfection with other respiratory pathogens in COVID-19 patients and the profile of pathogens can contribute to effective patient management and antibiotic stewardship during the current pandemic.
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