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Background: Exposure to ambient PM 2.5 is known to affect lipid metabolism through systemic inflammation and oxidative stress. Evidence from developing countries, such as India with high levels of ambient PM 2.5 and distinct lipid profiles, is sparse., Methods: Longitudinal nonlinear mixed-effects analysis was conducted on >10,000 participants of Centre for cArdiometabolic Risk Reduction in South Asia (CARRS) cohort in Chennai and Delhi, India. We examined associations between 1-month and 1-year average ambient PM 2.5 exposure derived from the spatiotemporal model and lipid levels (total cholesterol [TC], triglycerides [TRIG], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]) measured longitudinally, adjusting for residential and neighborhood-level confounders., Results: The mean annual exposure in Chennai and Delhi was 40 and 102 μg/m 3 respectively. Elevated ambient PM 2.5 levels were associated with an increase in LDL-C and TC at levels up to 100 µg/m 3 in both cities and beyond 125 µg/m 3 in Delhi. TRIG levels in Chennai increased until 40 µg/m 3 for both short- and long-term exposures, then stabilized or declined, while in Delhi, there was a consistent rise with increasing annual exposures. HDL-C showed an increase in both cities against monthly average exposure. HDL-C decreased slightly in Chennai with an increase in long-term exposure, whereas it decreased beyond 130 µg/m 3 in Delhi., Conclusion: These findings demonstrate diverse associations between a wide range of ambient PM 2.5 and lipid levels in an understudied South Asian population. Further research is needed to establish causality and develop targeted interventions to mitigate the impact of air pollution on lipid metabolism and cardiovascular health., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report. K.A. was involved in conceptualization, developing methodology, conducting the formal analysis, visualization, and writing the original draft. G.K.W. was involved in conceptualization, developing methodology, and writing the original draft. S.M. and J.D.S. provided methodological and analysis supervision. J.S.M. provided data analysis resources. R.G., N.T., K.M.V.N., M.K.A., V.M., D.P., and J.D.S. contributed to the conceptualization, investigation, resources, and funding acquisition of the CARRS cohort. All authors edited and approved the final version of the manuscript., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: A heavy burden of cardiometabolic conditions on low- and middle-income countries like India that are rapidly undergoing urbanization remains unaddressed. Indians are known to have high levels of triglycerides and low levels of HDL-C along with moderately higher levels of LDL-C. The genome-wide findings from Western populations need to be validated in an Indian context for a better understanding of the underlying etiology of dyslipidemia in India. Objective: We aim to validate 12 genetic variants associated with lipid levels among rural and urban Indian populations and derive unweighted and weighted genetic risk scores (uGRS and wGRS) for lipid levels among the Indian population. Methods: Assuming an additive model of inheritance, linear regression models adjusted for all the possible covariates were run to examine the association between 12 genetic variants and total cholesterol, triglycerides, HDL-C, LDL-C, and VLDL-C among 2,117 rural and urban Indian participants. The combined effect of validated loci was estimated by allelic risk scores, unweighted and weighted by their effect sizes. Results: The wGRS for triglycerides and VLDL-C was derived based on five associated variants (rs174546 at FADS1 , rs17482753 at LPL , rs2293889 at TRPS1 , rs4148005 at ABCA8 , and rs4420638 at APOC1 ), which was associated with 36.31 mg/dL of elevated triglyceride and VLDL-C levels ( β = 0.95, SE = 0.16, p < 0.001). Similarly, every unit of combined risk score (rs2293889 at TRPS1 and rs4147536 at ADH1B ) was associated with 40.62 mg/dL of higher total cholesterol ( β = 1.01, SE = 0.23, p < 0.001) and 33.97 mg/dL of higher LDL-C ( β = 1.03, SE = 0.19, p < 0.001) based on its wGRS (rs2293889 at TRPS1 , rs4147536 at ADH1B , rs4420638 at APOC1 , and rs660240 at CELSR2 ). The wGRS derived from five associated variants (rs174546 at FADS1 , rs17482753 at LPL , rs4148005 at ABCA8 , rs4420638 at APOC1 , and rs7832643 at PLEC ) was associated with 10.64 mg/dL of lower HDL-C ( β = -0.87, SE = 0.14, p < 0.001). Conclusion: We confirm the role of eight genome-wide association study (GWAS) loci related to different lipid levels in the Indian population and demonstrate the combined effect of variants for lipid traits among Indians by deriving the polygenic risk scores. Similar studies among different populations are required to validate the GWAS loci and effect modification of these loci by lifestyle and environmental factors related to urbanization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Walia, Panniyammakal, Agarwal, Jalal, Gupta, Ramakrishnan, Tandon, Roy, Krishnan and Prabhakaran.)

Aims: The aim of this study was to evaluate the effects of yoga-based cardiac rehabilitation (Yoga-CaRe) on the endothelial system, oxidative stress, and inflammatory markers in patients with acute myocardial infarction (MI)., Methods: A sub-study was conducted in two clinical sites of the Yoga-CaRe trial (a multicenter randomized controlled trial). Participants with acute MI were randomized and allocated to either the Yoga-CaRe program (13 sessions with encouragement to home practice) or enhanced standard care (three educational sessions). Endothelial function, oxidative stress, and inflammatory biomarkers were assessed using biomarkers such as asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), E-selectin, P-selectin, vascular cell adhesion molecule (VCAM), intercellular cell-adhesion molecule-1, total nitric oxide concentration (NOx), oxidized low-density lipoprotein (Oxd-LDL), superoxide dismutase, total antioxidant capacity (TAOC), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) at baseline and 12 weeks. Laboratory and statistical analysis were done by staff blinded to group allocation., Results: Eighty-two patients (of the 110 patients recruited) completed the study. The mean age was 53.1 ± 10.6 and 51.9 ± 10.7 years in enhanced standard care and Yoga-CaRe group, respectively. At 12 weeks, Yoga-CaRe significantly reduced ADMA, ET-1, and ICMA-1 than the enhanced standard care group. Although E-selectin and VCAM at 12 weeks were reduced in both groups, enhanced standard care had a significantly higher reduction than the Yoga-CaRe group. Among markers of oxidative stress, TAOC increased in the Yoga-CaRe group. We found no difference in eNOS, NOx, P-selectin, TNFα, CRP, and Oxd-LDL between the two groups., Conclusion: Yoga-CaRe improved the endothelial function (through a reduction in ET-1 and modulating adhesion molecules) and enhanced antioxidant capacity., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 International Journal of Yoga.)

Polyoxometalates (POMs) are versatile anionic clusters which have attracted a lot of attention in biomedical investigations. To counteract the increasing resistance effect of cancer cells and the high toxicity of chemotherapeutic treatments, POM-based metallodrugs can be strategically synthesized by adjusting the stereochemical and physicochemical features of POMs. In the present report a polyoxomolybdate (POMo) based organic-inorganic hybrid solid (C 6 H 16 N)(C 6 H 15 N) 2 [Mo 8 O 26 ]·3H 2 O, solid 1, has been synthesized and its antitumoral activities have been investigated against three cancer cell lines namely, A549 (Lung cancer), HepG2 (Liver cancer), and MCF-7 (Breast cancer) with IC50 values 56.2 μmol L -1 , 57.3 μmol L -1 , and 55.2 μmol L -1 respectively. The structural characterization revealed that solid 1 consists of an octa molybdate-type cluster connected by three triethylamine molecules via hydrogen bonding interactions. The electron microscopy analysis suggests the nanocapsule-like morphology of solid 1 in the size range of 50-70 nm. The UV-vis absorption spectra were used to assess the binding ability of synthesized POM-based solid 1 to calf thymus DNA (ctDNA), which further explained the binding interaction between POMo and ctDNA and the binding constant was calculated to be 2.246 × 10 3 giving evidence of groove binding., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Zearalenone and its metabolites, a group of endocrine disrupting mycotoxins, have been linked to adverse reproductive health effects. They cross the placental barrier, potentially reaching the fetus. In this study, we adapted and optimized our protocol previously used for urine, to measure these mycotoxins in human placentas. We combined a supported liquid extraction step using Chem Elut cartridges with solid phase extraction on Discovery® DSC-NH2 tubes. The optimized extraction efficiencies were between 68 and 80% for all metabolites. Analysis was performed by UHPLC-HRMS using a Betasil™ Phenyl-Hexyl column eluted with a gradient of acetonitrile-methanol-water. The chromatography method separated all analytes in under 15 min. Validation experiments confirmed the method's sensitivity, with LODs ranging from 0.0055 to 0.011 pg/mg tissue. The method was linear over a range of 0.0025-1.5 pg/mg tissue with R 2 values ≥ 0.994. Precision and accuracy calculations ranged from 4.7-7.9% and 0.6-6.7% respectively. The method was then successfully applied to a subset of placenta samples (n = 25) collected from an ongoing prospective birth cohort. Interestingly, 92% of the samples contained at least one measurable zearalenone metabolite, providing initial indication of potentially widespread exposure during pregnancy., Competing Interests: We declare that none of the authors have any known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Infants born with critical congenital heart defects (CCHDs) have unique transitional pathophysiology that often requires special resuscitation and management considerations in the delivery room (DR). While much is known about neonatal resuscitation of infants with CCHDs, current neonatal resuscitation guidelines such as the neonatal resuscitation programme (NRP) do not include algorithm modifications or education specific to CCHDs. The implementation of CCHD specific neonatal resuscitation education is further hampered by the large number of healthcare providers (HCPs) that need to be reached. Online learning modules (eLearning) may provide a solution but have not been designed or tested for this specific learning need. Our objective in this study is to design targeted eLearning modules for DR resuscitation of infants with specific CCHDs and compare HCP knowledge and team performance in simulated resuscitations among HCPs exposed to these modules compared with directed CCHD readings., Methods and Analysis: In a prospective multicentre trial, HCP proficient in standard NRP education curriculum are randomised to either (a) directed CCHD readings or (b) CCHD eLearning modules developed by the study team. The efficacy of these modules will be evaluated using (a) individual preknowledge/postknowledge testing and (b) team-based resuscitation simulations., Ethics and Dissemination: This study protocol is approved by nine participating sites: the Boston Children's Hospital Institutional Review Board (IRB-P00042003), University of Alberta Research Ethics Board (Pro00114424), the Children's Wisconsin IRB (1760009-1), Nationwide Children's Hospital IRB (STUDY00001518), Milwaukee Children's IRB (1760009-1) and University of Texas Southwestern IRB (STU-2021-0457) and is under review at following sites: University of Cincinnati, Children's Healthcare of Atlanta, Children's Hospital of Los Angeles and Children's Mercy-Kansas City. Study results will be disseminated to participating individuals in a lay format and presented to the scientific community at paediatric and critical care conferences and published in relevant peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite advances in neurology, drug delivery to the central nervous system is considered a challenge due to the presence of the blood brain barrier (BBB). In this study, the role of magnetic hyperthermia induced by exposure of magnetic nanoparticles (MNPs) to an alternating magnetic field (AMF) in synergy with an external magnetic field (EMF) was investigated to transiently increase the permeability of the MNPs across the BBB. A dual magnetic targeting approach was employed by first dragging the MNPs by an EMF for an intended enhanced cellular association with the brain endothelial cells and then activating the MNPs by an AMF for the temporary disruption of the tight junctions of BBB. The efficacy of the BBB permeability for the MNPs under the influence of dual magnetic targeting was evaluated in vitro using transwell models developed by co-culturing murine brain endothelial cells with astrocytes, as well as in vivo in mouse models. The in vitro results revealed that the exposure to AMF transiently opened the tight junctions at the BBB, which, after 3 h of treatment, were observed to recover back to their comparable control levels. A biodistribution analysis of nanoparticles confirmed targeted accumulation of MNPs in the brain following dual targeting. This dual targeting approach was observed to open the tight junctions, thus increasing the transport of MNPs into the brain with higher specificity as compared to using EMF targeting alone, suggesting that a dual magnetic targeting-induced transport of MNPs across the BBB is an effective measure for delivery of therapeutics.

Background: Oral cancer, a leading cancer-site in India, is often detected at advanced stages. We evaluated the time intervals from first symptom to help-seeking and diagnosis among oral cancer patients., Methodology: In this cross-sectional study, we recruited 226 consecutive oral cancer patients (mean age ( ± SD) 51.9 years ( ± 10.9); 81.9% men; 70.3% advanced stage) registered for diagnosis and treatment, between 2019 and 2021 at a cancer care centre in South India. We used WHO framework and previously standardized tools to record time intervals (appraisal, help-seeking and diagnostic) and baseline characteristics. We utilized multivariable logistic regression models to test the associations between 'prolonged (i.e., over 1 month) time intervals') and patient-level factors to estimate odds ratios (ORs) with 95% confidence intervals (CIs)., Results: Over a half of patients presented with prolonged appraisal (60%) and help-seeking intervals (57%), and a third (34%) reported prolonged diagnostic interval. Patients with no formal education, no routine healthcare visits, no self-reported risk factors, and those who did not perceive initial symptoms to be serious were 2-4 times more likely to have prolonged appraisal and help-seeking than the rest. High travel costs and self-decision for visiting healthcare facility prolonged help-seeking. Diagnostic interval was prolonged only among women OR= 2.7 (95% CI: 1.2-6.1)) and in patients whose first doctor's opinion was 'nothing to worry' OR (=7.3 (95% CI: 2.6-20.5)). 'Correct knowledge of cancer' shortened appraisal and help-seeking intervals and 'incorrect knowledge and negative beliefs' prolonged diagnostic interval., Conclusion: Our findings highlight that interventions targeting sociocultural and economic determinants, symptom awareness, sensitizing persons at risk (especially women) and primary care providers might reduce overall time to diagnosis. Further, patients without any known risk factors for oral cancer might be at-risk for prolonged appraisal interval. These might help inform 'pull' strategies for cancer control in India and similar settings., Competing Interests: Conflicts of Interest The authors declare no conflict of interest. We declare the commercial affiliation (Genentech Roche, CA, USA) of one of our authors (PKD). This does not alter our adherence to policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

HER2-positive breast cancer is an aggressive subtype of breast cancer with five-year survival rates of 30% for the advanced stage. The development of anti-HER2 treatments has led to a paradigm shift in the management and clinical outcomes of advanced HER2-positive breast cancer patients. The standard first-line treatment consists of taxane-based chemotherapy plus dual anti-HER2 therapies with trastuzumab and pertuzumab. The antibody-drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1) has been a second-line therapeutic standard, but the second-line treatment approach is rapidly evolving. Given a substantial advantage of another ADC, Fam-trastuzumab deruxtecan (T-DXd), compared to T-DM1 in a recent randomized trial in the second-line setting, T-DXd is currently the preferred second-line option. Optimal third-line treatment strategies are still not established, and multiple approaches have been used including combinations based on capecitabine, trastuzumab, or both with oral anti-HER2 tyrosine kinase inhibitors. Tucatinib plus capecitabine and trastuzumab, lapatinib plus trastuzumab, neratinib or lapatinib plus capecitabine are some of the FDA approved combinations. Another newer agent approved for third- or later-line therapy in the metastatic setting is margetuximab, an Fc-engineered anti-HER2 monoclonal antibody, in combination with chemotherapy. Other novel agents currently under clinical trials are the drugs that indirectly target HER2, including immune cell cycle inhibitors, PI3K/mTOR inhibitors, and immunotherapy agents., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Few longitudinal data characterize kidney function decline among South Asians, one of the world's largest population groups. We aimed to identify estimated glomerular filtration rate (eGFR) trajectories in a population-based cohort from India and assess predictors of rapid kidney function decline., Methods: We used 6-year longitudinal data from participants of a population-representative study from Delhi and Chennai, India who had at least two serum creatinine measures and baseline CKD-EPI eGFR> 60 ml/min/1.73m 2 ( n =7779). We used latent class trajectory modeling to identify patterns of kidney function trajectory (CKD-EPI eGFR) over time. In models accounting for age, sex, education, and city, we tested the association between 15 hypothesized risk factors and rapid kidney function decline., Findings: Baseline mean eGFR was 108 (SD 16); median eGFR was 110 [IQR: 99-119] ml/min/1.73m 2 . Latent class trajectory modeling and functional characterization identified three distinct patterns of eGFR: class-1 (no decline; 58%) annual eGFR change 0.2 [0.1, 0.3]; class-2 (slow decline; 40%) annual eGFR change -0.2 [-0.4, -0.1], and class-3 (rapid decline; 2%) annual eGFR change -2.7 [-3.4, -2.0] ml/min/1.73m 2 . Albuminuria (>30 mg/g) was associated with rapid eGFR decline (OR for class-3 vs class-1 : 5.1 [95% CI: 3.2; 7.9]; class-3 vs. class-2 : 4.3 [95% CI:2.7; 6.6]). Other risk factors including self-reported diabetes, cardiovascular disease, peripheral arterial disease, and metabolic biomarkers such as HbA1c and systolic blood pressure were associated with rapid eGFR decline phenotype but potential 'non-traditional' risk factors such as manual labor or household water sources were not., Interpretation: Although mean and median eGFRs in our population-based cohort were higher than those reported in European cohorts, we found that a sizeable number of adults residing in urban India are experiencing rapid kidney function decline. Early and aggressive risk modification among persons with albuminuria could improve kidney health among South Asians., Funding: The CARRS study has been funded with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, under Contract No. HHSN2682009900026C and P01HL154996. Dr. Anand was supported by NIDDK K23DK101826 and R01DK127138., Competing Interests: Nothing to disclose., (© 2022 The Author(s).)

Background: Markers of ideal cardiovascular health (CVH) predict cardiovascular events. We estimated the prevalence of ideal CVH markers in two levels of cities and villages in India., Methods: We did pooled analysis of individual-level data from three cross sectional surveys of adults ≥ 30 years over 2010-14 (CARRS: Centre for cArdiometabolic Risk Reduction in South Asia; UDAY and Solan Surveillance Study) representing metropolitan cities; smaller cities and rural areas in diverse locations of India. We defined ideal CVH using modified American Heart Association recommendations: not smoking, ≥ 5 servings of fruits and vegetables (F&V), high physical activity (PA), body mass index (BMI) <25 Kg/m 2 , blood pressure (BP) <120/80 mm Hg, fasting plasma glucose (FPG) <100 mg/dl, and total cholesterol (TC) <200 mg/dL. We estimated (1) age-and sex-standardized prevalence of ideal CVH and (2) prevalence of good (≥6 markers), moderate (4-5), and poor CVH (≤3) adjusted for age, sex, education, and stratified by setting and asset tertiles., Results: Of the total 22,144 participants, the prevalence of ideal CVH markers were: not smoking (76.7% [95% CI 76.1, 77.2]), consumed ≥5 F&V (4.2% [3.9, 4.5]), high PA (67.5% [66.8, 68.2]), optimum BMI (59.6% [58.9, 60.3]), ideal BP (34.5% [33.9, 35.2]), FPG (65.8% [65.1, 66.5]) and TC (65.4% [64.7, 66.1]). The mean number of ideal CVH metrics was 3.7(95% CI: 3.7, 3.8). Adjusted prevalence of good, moderate, and poor CVH, varied across settings: metropolitan (3.9%, 41.0%, and 55.1%), smaller cities (7.8%, 49.2%, and 43%), and rural (10.4%, 60.9%, and 28.7%) and across asset tertiles: Low (11.0%, 55.9%, 33.1%), Middle (6.3%, 52.2%, 41.5%), and High (5.0%, 46.4%, 48.7%), respectively., Conclusion: Achievement of ideal CVH varied, with higher prevalence in rural and lower asset tertiles. Multi-sectoral and targeted policy and program actions are needed to improve CVH in diverse contexts in India., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Development of multifunctional magnetic nanomaterials (MNPs) with improved heat-generating capabilities and effective combination with localized chemotherapy has emerged as a promising therapeutic regime for solid tumors like glioblastoma. In this regard, the shape-dependent hyperthermic and chemo-therapeutic potential of nanomaterials, has not been extensively explored. Here we present, development of various morphological designs of MNPs including spherical, clusters, rods and cubic; to compare the effect of shape on tuning the properties of MNPs that are relevant to many potential biomedical applications like drug delivery, cellular uptake and heat generation. The study includes extensive comparison of morpho-structural characteristics, size distributions, chemical composition, surface area measurements and magnetic properties of the variable shaped MNPs. Further the heating efficiencies in aqueous and cellular environments and heat triggered drug release profiles for successful magneto-chemotherapy were compared among all in-house synthesized MNPs. Under biosafety limit considerations given by Hergt's limit (H*f value <5 × 10 9 Am -1  s -1 ), cuboidal shaped MNPs demonstrated highest heating efficiency owing to magnetosome-like chain formation along with sustained drug release profile as compared to other synthesized MNPs. The mechanism of cancer cell death mediated via magneto-chemotherapy was elucidated to be the oxidative stress-mediated apoptotic cell death pathway. In vivo studies further demonstrated complete tumor regression only in the magneto-chemotherapy treated group. These findings suggest the potential of combinatorial therapy to overcome the clinical limitations of the independent therapies for advanced thermotherapy of glioblastoma., (Copyright © 2022 Elsevier B.V. All rights reserved.)

When ROS production exceeds the cellular antioxidant capacity, the cell needs to eliminate the defective mitochondria responsible for excessive ROS production. It has been proposed that the removal of these defective mitochondria involves mitophagy, but the mechanism of this regulation remains unclear. Here, we demonstrate that moderate mitochondrial superoxide and hydrogen peroxide production oxidates KEAP1, thus breaking the interaction between this protein and PGAM5, leading to the inhibition of its proteasomal degradation. Accumulated PGAM5 interferes with the processing of the PINK1 in the mitochondria leading to the accumulation of PINK1 on the outer mitochondrial membrane. In turn, PINK1 promotes Parkin recruitment to mitochondria and sensitizes mitochondria for autophagic removal. We also demonstrate that inhibitors of the KEAP1-PGAM5 protein-protein interaction (including CPUY192018) mimic the effect of mitochondrial ROS and sensitize mitophagy machinery, suggesting that these inhibitors could be used as pharmacological regulators of mitophagy. Together, our results show that KEAP1/PGAM5 complex senses mitochondrially generated superoxide/hydrogen peroxide to induce mitophagy., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. While patients with COVID-19 most frequently present with pneumonia, respiratory failure and acute respiratory distress syndrome, increasing cases of immune-mediated disorders such as autoimmune thrombocytopenia, haemolytic anaemia and antiphospholipid syndrome have been reported. In this article we describe a rare case of cold agglutinin syndrome (CAS) in a patient with COVID-19. The patient was a 77-year-old man with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency who presented with COVID-19 infection and acute respiratory failure. Initially he was started on intravenous steroids, antibiotics and hydroxychloroquine. Laboratory analysis revealed haemolytic anaemia with a positive direct anti-globulin test (DAT) and high titres of cold agglutinins. Hydroxychloroquine was stopped due to suspicion of haemolysis due to G6PD deficiency but the haemolysis persisted. Unfortunately, the respiratory failure progressed and the patient died. In summary, this article describes a rare case of CAS associated with COVID-19. CAS is a heterogenous group of cold autoimmune haemolytic anaemias occurring secondary to infections or malignancies. No definite treatment for CAS in COVID-19 patients has been approved so far., Learning Points: Autoimmune haemolytic anaemia has been reported in COVID-19 patients.Cold agglutinin syndrome (CAS) can occur in patients with COVID-19.Efforts to determine the optimal management of CAS in COVID-19 patients must continue., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2021.)

Introduction: Ipilimumab plus nivolumab has been approved for intermediate- and poor-risk metastatic renal cell carcinoma (RCC). However, the activity in non-clear cell RCC (nccRCC) is unknown., Patients and Methods: Patients from Cleveland Clinic and the University of Texas Southwestern who had received ipilimumab plus nivolumab for metastatic nccRCC from October 2017 to May 2019 were retrospectively identified. Ipilimumab plus nivolumab was administered in accordance with the CHECKMATE 214 trial. Imaging was obtained at baseline and every 12 weeks. The baseline patient characteristics, objective response per Response Evaluation Criteria in Solid Tumors, version 1.1, and treatment-related adverse events (TRAEs) per Common Terminology Criteria for Adverse Events, version 5.0, were analyzed., Results: Eighteen patients were identified. The median age was 59 years (range, 32-81 years), 77.8% were men, and the Eastern Cooperative Oncology Group performance status was 0 (38%) or 1 (50%). The median treatment duration was 2.4 months (range, 0.7-12.3 months). The non-clear cell histologic types included 6 papillary, 5 chromophobe, 3 unclassified, 2 adenocarcinoma of renal origin, 1 translocation, and 1 medullary. Most had an intermediate (66%) or poor (22%) International Metastatic Database Consortium risk. The best objective response included 6 partial responses (PRs; 33.3%) and 3 with stable disease (16.7%). Of the patients with a PR, the median time to the best response was 3.0 months, and median duration of the PR was 4.3 months. The median progression-free survival was 7.1 months. All-grade TRAEs were noted in 11 patients (61.1%) and included colitis (22%), hepatotoxicity (16%), rash (11%), and fatigue (11%). Eleven patients (61%) had TRAEs requiring high-dose glucocorticoids (> 40 mg of prednisone equivalent daily)., Conclusions: Ipilimumab plus nivolumab demonstrated objective responses and notable toxicity in patients with nccRCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Sparse data exist on population distributions of serum fibroblast growth factor-23 (FGF23) levels from developing, middle-income economies. FGF23 levels may differ substantially across regions based on differences in diet and urbanization. In a population-based study from North India, we tested the hypothesis that urinary phosphate excretion and FGF23 levels are lower among rural compared with urban participants, and among vegetarian compared with nonvegetarian participants., Methods: We measured 24-hour urinary phosphate, and serum parathyroid hormone and FGF23 in a subsample of the population-based Cardiometabolic Risk Reduction in South Asia and Indian Council of Medical Research Coronary Heart Disease surveys. We categorized participants according to diet and residence: urban nonvegetarians (n = 70), urban vegetarians (n = 564), and rural vegetarians (n = 558). Using least square means, we compared the groups' 24-hour urinary phosphate (with urban vegetarians as reference) and FGF23 levels after accounting for age, sex, diabetes, and body mass index., Results: Among 1,192 study participants, mean FGF23 was 41 ± 18 pg/mL, median parathyroid hormone was 44 (interquartile range [IQR] 31-60) pg/mL, and median 24-hour urinary phosphate excretion was 419 (IQR: 47-622) mg/day. Urinary phosphate was significantly higher in rural compared with urban vegetarians (median, 503; IQR, 334-543 versus 365; IQR, 199-399 mg/day), but adjusted mean FGF23 levels did not differ across study groups., Conclusion: In rural and urban India, urinary phosphate excretion was low, but FGF23 levels did not differ by residence or dietary preference. Homogenously low dietary phosphate intake across different settings and diets may partly explain the lack of differences in FGF23., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to measure the change in prevalence of Coronary Heart Disease (CHD) and Cardiovascular Diseases (CVDs) risk among those aged 35-64 years in urban and rural areas of National Capital Region (NCR) of Delhi, between 1991-1994 (survey 1) and 2010-2012 (survey 2)., Methods: Both surveys used similar sampling methodology and mean ages of participants were similar. A total of 3048 and 2052 subjects were studied in urban Delhi and 2487 and 1917 participants recruited from rural Ballabgarh in survey 1 and in survey 2 respectively. CHD was diagnosed based on a Minnesota coded ECG and Rose angina questionnaire. Data on behavioural, physical, clinical and biochemical parameters were collected using standard methods. CVD Risk of participants was calculated using the gender specific Framingham risk equation., Results: The age and sex standardised prevalence of CHD in urban Delhi increased from 10.3% (95% CI: 9.2-11.4) to 14.1% (95% CI: 12.6-15.6) between the two surveys as compared to an increase from 6.0% (95% CI: 5.0-6.9) to 7.4% (95% CI: 6.3-8.6) in rural Ballabgarh. The highest increase in the prevalence of CHD was reported among urban women (10.1% to 16.6%).The proportion of population with high 10-year CVD risk increased to 4.1% from 1.2% in rural areas as compared to 4.8% from 2.5% in urban areas., Conclusions: The CHD and CVD risk has increased over 20 years period in and around Delhi and the increase was more in rural population and women, traditionally considered to be at low risk., Competing Interests: Conflicts of interest All authors have none to declare., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: Despite treatment with abiraterone acetate and prednisone (AA/P), most patients with metastatic hormone sensitive prostate cancer (mHSPC) will develop castration-resistant disease (metastatic castration-resistant prostate cancer [mCRPC]). The early identification of who will progress on AA/P is limited., Objective: This study investigates the role of prostate surface antigen (PSA) kinetics as a predictor of progression in mHSPC patients treated with AA/P., Patients and Methods: All patients with mHSPC who initiated androgen deprivation therapy (ADT) and AA/P from June 2017 to February 2019 at the Cleveland Clinic were eligible. PSA-mCRPC was defined as a PSA rise at two consecutive time points. Patients were followed until first mCRPC or last contact after AA/P. Patterns of PSA change were evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months from AA/P initiation. The association between PSA profile at 3 months and PSA-mCRPC was examined using survival analysis. Radiographic progression (Rad-mCRPC) was also analyzed., Results: A total of 130 men with follow-up were included. The median (interquartile range [IQR]) follow-up time was 15.3 (10.5, 22.5) months. Eighty-two percent were Caucasian (median age 68.5 years); participants had a median (IQR) PSA of 16.8 (5.3, 48.0) ng/mL. Half of the patients had de novo disease, and 46.2% had high-risk disease (61% had a Gleason score ≥ 8, 16% had visceral disease, and 54% had three or more bony lesions). The greatest PSA percentage reduction from baseline after AA/P initiation occurred at the first 3 months (median 98.3%). The reduction at 6-12 months from baseline was small (99.7-100%). Patients without PSA-mCRPC had a significantly greater 3-month reduction of PSA values compared to patients who developed PSA-mCRPC (p interaction = 0.0002). 50.8% of patients were able to achieve a non-detectable PSA (median 13.1 months). PSA-mCRPC (n = 20) was observed from 4 to 24 months after AA/P, with the majority of events occurring within the first 12 months. Patients with PSA < 0.3 ng/mL (12-month PSA-mCRPC-free 94.5% vs. 69.4%, p = 0.0004) or a ≥ 98% reduction (94.9% vs. 68.0%, p = 0.0002) at 3 months had better PSA-mCRPC-free survival compared to their counterparts. Absolute reduction at 3 months was not associated with PSA-mCRPC. Similar PSA patterns were seen in those who had Rad-mCRPC compared to no Rad-mCRPC (p interaction < 0.05)., Conclusion: The degree of PSA decline at 3 months predicted serologic progression to mCRPC. Those who developed castration-resistant disease had higher PSA and a lower percentage reduction by 3 months. Tracking early PSA pattern changes may alert clinicians to poor treatment effect and potential progression; they should consider frequent PSA measurement and imaging, as well as the initiation of sequential therapy.

Background: Several phase 3 studies reported positive results for combinations of Immune-Oncology (IO) and Vascular Endothelial Growth Factor (VEGF) targeted therapies in patients with metastatic clear cell Renal Cell Carcinoma (ccRCC). However, there are limited data on outcomes to systemic therapy after IO-VEGF combinations., Methods: A retrospective analysis was performed on patients with metastatic ccRCC treated at the Memorial Sloan Kettering Cancer Center and Cleveland Clinic who initiated systemic therapy post IO-VEGF including combinations with VEGF receptor (VEGFR) tyrosine kinase inhibitors (IO-TKI) and combinations with the anti-VEGF monoclonal antibody bevacizumab (IO-Bev). The study objectives were to evaluate the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) on systemic therapy post IO-VEGF. RECIST v1.1 criteria were used to determine radiological responses and progression. Survival estimates were evaluated with the Kaplan-Meier methods and the log-rank test from the start of systemic therapy post IO-VEGF to the event of interest., Results: A total of fifty-nine patients were treated post discontinuation of IO-VEGF regimens which included IO-Bev (n = 35; 59%) and IO-TKI (n = 24; 41%). Fifty-eight patients (98%) received IO-VEGF regimens as part of a clinical trial. Subsequent therapies included cabozantinib (n = 22; 37%), axitinib (n = 18; 31%), pazopanib (n = 4; 7%), lenvatinib and everolimus (n = 4; 7%), mTOR inhibitor monotherapy (n = 3; 5%), axitinib and dalantercept (n = 2; 3%), sunitinib (n = 1; 2%), sorafenib (n = 1; 2%), and treatment with agents on unreported clinical trials (n = 4; 7%). Patients treated on unreported clinical trials were excluded from the efficacy analysis. Post IO-VEGF, the ORR was 25% and median PFS was 12.0 months (95% CI, 8.2-24.5). Median OS was 24.5 months (95% CI, 12-NE) and 12 months OS rate was 63.3% (95% CI, 48.6-74.9). We observed no differences post IO-VEGF OS when comparing IO- TKI vs IO-Bev (Log-rank p = 0.73)., Conclusions: Post IO-VEGF, most patients received VEGFR-TKIs. In this setting, VEGFR-TKIs demonstrated clinical activity and remain a viable option for salvage therapy after progression on IO-VEGF.

Introduction: The mammalian target of rapamycin (mTOR) pathway is up-regulated in prostate cancer (PCa). We evaluated the tumor tissue expression of downstream mTOR targets in patients with intermediate- and high-risk (IR/HR) PCa and their ability to predict outcome after radical prostatectomy (RP)., Patients and Methods: Immunohistochemical (IHC) analysis using antibodies against PTEN, mTOR, p-mTOR, pAKT, pS6, and Ki-67 was performed on a tissue microarray constructed from formalin-fixed paraffin-embedded RP specimens. The marker expression was analyzed to determine their predictability for biochemical recurrence (BCR)., Results: Tumor tissue from 217 patients (86 IR/131 HR) was analyzed. The most frequent markers were p-mTOR, which was expressed in most cases (85%), whereas PTEN and pS6 were detected in 53% and 40% of the cases, respectively. Overexpression of PTEN (P = .02) and pS6 (P < .001) was associated with HR features. With a median follow up of 13.5 years, 39% (77/196) of patients developed BCR after RP, more frequently (31%) in patients with HR disease (P < .001). Overexpression of pS6 (P = .036), Ki67% (P = .024), and lack of expression of mTOR (P = .021) were associated with BCR. The 5- and 10-year survival rate was 81% and 66%, respectively., Conclusions: Protein expression of downstream mTOR molecules was significantly associated with outcome of patients with IR and HR PCa. Markers of the mTOR pathway could be incorporated in clinical studies evaluating inhibitors of the signaling pathway for treatment selection in men with PCa., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Despite definitive local therapy, patients with high-risk prostate cancer have a significant risk for local and distant failure. To date, no systemic therapy given prior to surgery has been shown to improve outcomes. The phosphatidilinositol 3-kinase/AKT/mTOR pathway is commonly dysregulated in men with prostate cancer. We sought to determine the clinical efficacy and safety of the mTOR/TORC1 inhibitor everolimus in men with high-risk prostate cancer undergoing radical prostatectomy. Methods This is a randomized phase II study of everolimus at two different doses (5 and 10 mg daily) given orally for 8 weeks before radical prostatectomy in men with high-risk prostate cancer. The primary endpoint was the pathologic response (histologic P0, margin status, extraprostatic extension) and surgical outcomes. Secondary endpoints included changes in serum PSA level and treatment effects on levels of expression of mTOR, p4EBP1, pS6 and pAKT. Results Seventeen patients were enrolled: nine at 10 mg dose and eight at 5 mg dose. No pathologic complete responses were observed and the majority of patients (88%) had an increase in their PSA values leading to this study being terminated early due to lack of clinical efficacy. Treatment-related adverse events were similar to those previously reported with the use of everolimus in other solid tumors and no additional surgical complications were observed. A significant decrease in the expression of p4EBP1 was noted in prostatectomy samples following treatment. Conclusions Neoadjuvant everolimus given at 5 mg or 10 mg daily for 8 weeks prior to radical prostatectomy did not impact pathologic responses and surgical outcomes of patients with high-risk prostate cancer. Trial registration NCT00526591 .

Background Mammalian target of rapamycin (mTOR) pathway and angiogenesis through vascular endothelial growth factor (VEGF) have been shown to play important roles in prostate cancer progression. Preclinical data in prostate cancer has suggested the potential additive effect dual inhibition of VEGF and mTOR pathways. In this phase I/II trial we assessed the safety and efficacy of bevacizumab in combination with temsirolimus for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). Methods In the phase I portion, eligible patients received temsirolimus (20 mg or 25 mg IV weekly) in combination with a fixed dose of IV bevacizumab (10 mg/kg every 2 weeks). The primary endpoint for the phase II portion was objective response measured by either PSA or RECIST criteria. Exploratory endpoints included changes in circulating tumor cells (CTC) and their correlation with PSA response to treatment. Results Twenty-one patients, median age 64 (53-82), with pre-treatment PSA of 205.3 (11.1-1801.0), previously treated with a median of 2 (0-5) lines of therapy for mCRPC received the combination of temsirolimus weekly at 20 mg (n = 4) or 25 mg (n = 17) with bevacizumab 10 mg/kg every 2 weeks (n = 21). Median time to progression was 2.6 months (95% CI, 1.2-3.9) and the median best PSA change from baseline to 12 weeks was a 32% increase (-40-632%) which met the predefined futility rule and led to early termination of the study. Nine patients (43%) had ≥ grade 3 toxicity that included fatigue (24%), anorexia (10%), nausea/vomiting (5%) and lymphopenia (5%). In exploratory analysis, a decrease in CTC levels was observed in 9 out of 11 patients. No association between PSA levels and CTC levels was detected. Conclusions The combination of temsirolimus and bevacizumab showed limited clinical activity in mCRPC patients previously treated with chemotherapy and was associated with significant adverse events (AEs). Transient decrease in CTC levels was independent from PSA response. NCT01083368.

Objectives: To assess whether chronic kidney disease of unknown aetiology (CKDu) is present in India and to identify risk factors for it using population-based data and standardised methods., Design: Secondary data analysis of three population-based cross-sectional studies conducted between 2010 and 2014., Setting: Urban and rural areas of Northern India (states of Delhi and Haryana) and Southern India (states of Tamil Nadu and Andhra Pradesh)., Participants: 12 500 individuals without diabetes, hypertension or heavy proteinuria., Outcome Measures: Mean estimated glomerular filtration rate (eGFR) and prevalence of eGFR below 60 mL/min per 1.73 m 2 (eGFR <60) in individuals without diabetes, hypertension or heavy proteinuria (proxy definition of CKDu)., Results: The mean eGFR was 105.0±17.8 mL/min per 1.73 m 2 . The prevalence of eGFR <60 was 1.6% (95% CI=1.4 to 1.7), but this figure varied markedly between areas, being highest in rural areas of Southern Indian (4.8% (3.8 to 5.8)). In Northern India, older age was the only risk factor associated with lower mean eGFR and eGFR <60 (regression coefficient (95% CI)=-0.94 (0.97 to 0.91); OR (95% CI)=1.10 (1.08 to 1.11)). In Southern India, risk factors for lower mean eGFR and eGFR <60, respectively, were residence in a rural area (-7.78 (-8.69 to -6.86); 4.95 (2.61 to 9.39)), older age (-0.90 (-0.93 to -0.86); 1.06 (1.04 to 1.08)) and less education (-0.94 (-1.32 to -0.56); 0.67 (0.50 to 0.90) for each 5 years at school)., Conclusions: CKDu is present in India and is not confined to Central America and Sri Lanka. Identified risk factors are consistent with risk factors previously reported for CKDu in Central America and Sri Lanka., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Several forms of genomic instability are known to drive the development of colorectal cancer (CRC). Chromosomal instability is the most common type found in 85% of the CRC, while 15% patients have microsatellite instability (MSI). MSI tumors are the subset of CRC that are characterized by dysfunction of mismatch repair genes (MMR) causing failure to repair errors in repetitive DNA sequences called microsatellites. Twelve percent of MSI tumors are acquired, caused by methylation-associated silencing of a gene that encodes a DNA MMR protein, while the remaining 3% have germline mutations in one of the MMR genes (Lynch syndrome). The identification of microsatellite stability status is clinically important as studies have revealed that MSI tumors have a better stage-adjusted survival compared with microsatellite stable tumors, and they respond differently to 5FU-based adjuvant chemotherapy depending on this status. There is recent success of immunotherapy (mainly anti-PD1 drugs) in metastatic CRC with MMR dysfunction that has led to the initiation of multiple trials based on immune checkpoint inhibitors. Additionally, it is important to identify patients with Lynch syndrome so that it can guide the frequency of surveillance of CRCs and recommendations of prophylactic surgery. Even though TNM staging remains a key determinant of patient prognosis and guides management in patients with CRC, molecular tumor heterogeneity contributes to significant variability in clinical outcomes despite the same disease stage; therefore, it is vital to know the type of genomic instability pathway that the tumor harbors. In this article, we discuss the unique genetic, pathologic, and clinical characteristics of microsatellite unstable (MSI) and stable CRC (MSS), their predictive value in directing the management with conventional chemotherapy or novel-targeted agents, and their prognostic significance in patient outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Evidence suggests a role for elevated serum calcium in dysregulated glucose metabolism, linked through low-level chronic inflammation., Objectives: We investigated the association of elevated serum calcium concentrations (corrected for albumin) with markers of dysregulated glucose metabolism and type II diabetes and tested if these associations were accounted for by chronic inflammation in a rural Indian population., Methods: A cross-sectional analysis of participants aged 40-84 y from the Andhra Pradesh Children and Parents Study (APCaPS; n  = 2699, 52.2% women) was conducted. Comprehensive information on household, sociodemographic, and lifestyle factors; medical and family history; physical measurements; blood measurements including fasting plasma glucose (FPG), fasting insulin (FI), serum calcium, albumin, phosphorous, vitamin D (in a subset), and creatinine were analyzed. Additionally, in a random sample of healthy participants ( n  = 1000), inflammatory biomarkers (interleukins 6 and 18, soluble intercellular adhesion molecule 1, adiponectin, and high-sensitivity C-reactive protein) were measured and an inflammatory score (IScore) calculated., Results: After adjustments for sociodemographics, lifestyle factors, and anthropometry the highest calcium quartile (Q4 compared with Q1) was associated with FI (β = 1.4 µU/ml; 95% CI: 1.2, 1.5 µU/ml; P -trend < 0.001), the homeostasis model assessment for insulin resistance (HOMA-IR) (β = 1.4; 95% CI: 1.2, 1.5; P -trend < 0.001), and was modestly associated with FPG (β = 2.1 mg/dL; 95% CI: -0.9, 5.2 mg/dL; P -trend = 0.058) and prevalent type II diabetes (OR = 1.6; 95% CI: 1.0, 2.6; P -trend= 0.020). In the healthy subgroup, the association of the highest calcium quartile was similar for FI and HOMA-IR. Additional adjustment with IScore did not alter the associations. Further, in a subset, all these associations were independent of endogenous regulators of calcium metabolism (serum vitamin D, phosphorus, and creatinine). Independently, after accounting for potential confounders, the highest IScore quartile (Q4 compared with Q1) was positively associated with FPG, FI, HOMA-IR, and prevalent prediabetes, and also with serum calcium concentrations in men., Conclusions: Elevated serum calcium was positively associated with markers of dysregulated glucose metabolism and prevalent type II diabetes in a rural Indian population. Chronic inflammation did not mediate this association but was independently associated with markers of dysregulated glucose metabolism. Inflammation might be responsible for elevated serum calcium concentrations in men.

Background/purpose: The optimal time for delivery of neonates with a prenatal diagnosis of gastroschisis (GS) is controversial. We compared the outcomes for GS at three different gestational ages (GAs), 33-34 weeks, 35-36 weeks, and ≥ 37 weeks., Methods: We analyze hospital discharge data of neonates with GS using the 2006, 2009 and 2012 Healthcare Cost and Utilization Project Kids' Inpatient Database (HCUPKIDS). Multivariable analysis was used to compare the association between GS outcomes and the three GAs., Results: Significantly higher number of 33-34 week infants had coexisting morbidities like respiratory distress syndrome, bronchopulmonary dysplasia, small bowel atresia, stenosis, or stricture, large bowel atresia and/or stenosis, malrotation, and atrial septal defect. In multivariable logistic regression, 33-34 week infants had higher NEC (p value = 0.002, 95% CI1.64-10.32), small bowel resection (0.024, 1.12-5.25) and pRBCs transfusion (0.024, 1.05-2.11). No differences were found between 35-36 weeks and ≥37 weeks gest infants for NEC, malabsorption, small bowel resection, TPN cholestasis, sepsis, CLABSI, number of pRBCs transfusion, length of stay and total charges., Conclusion: We did not show benefit for delivering early and in the absence of data, delivery at ≥37 weeks was noninferior to 35-36 weeks. We suggest that waiting for spontaneous onset of labor may be a better approach to balance the effects of prematurity and possible ongoing in utero bowel damage/stillbirth., Levels of Evidence: Level 3 (Retrospective comparative study)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To compare estimates of mean population salt intake in North and South India derived from spot urine samples versus 24-h urine collections., Methods: In a cross-sectional survey, participants were sampled from slum, urban and rural communities in North and in South India. Participants provided 24-h urine collections, and random morning spot urine samples. Salt intake was estimated from the spot urine samples using a series of established estimating equations. Salt intake data from the 24-h urine collections and spot urine equations were weighted to provide estimates of salt intake for Delhi and Haryana, and Andhra Pradesh., Results: A total of 957 individuals provided a complete 24-h urine collection and a spot urine sample. Weighted mean salt intake based on the 24-h urine collection, was 8.59 (95% confidence interval 7.73-9.45) and 9.46 g/day (8.95-9.96) in Delhi and Haryana, and Andhra Pradesh, respectively. Corresponding estimates based on the Tanaka equation [9.04 (8.63-9.45) and 9.79 g/day (9.62-9.96) for Delhi and Haryana, and Andhra Pradesh, respectively], the Mage equation [8.80 (7.67-9.94) and 10.19 g/day (95% CI 9.59-10.79)], the INTERSALT equation [7.99 (7.61-8.37) and 8.64 g/day (8.04-9.23)] and the INTERSALT equation with potassium [8.13 (7.74-8.52) and 8.81 g/day (8.16-9.46)] were all within 1 g/day of the estimate based upon 24-h collections. For the Toft equation, estimates were 1-2 g/day higher [9.94 (9.24-10.64) and 10.69 g/day (9.44-11.93)] and for the Kawasaki equation they were 3-4 g/day higher [12.14 (11.30-12.97) and 13.64 g/day (13.15-14.12)]., Conclusion: In urban and rural areas in North and South India, most spot urine-based equations provided reasonable estimates of mean population salt intake. Equations that did not provide good estimates may have failed because specimen collection was not aligned with the original method.

Objectives: Sleep duration and disturbances may be risk factors for hypertension. Despite the high burden of hypertension in South Asia, little is known about this relationship in this region., Methods: We analyzed population-level cross-sectional data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) study that recruited representative samples of adults ≥ 20 years from three cities-Delhi, Chennai (India), and Karachi (Pakistan) during 2010-2011. We defined hypertension as self-reported treatment or measured blood pressure (BP) ≥140/90 mm Hg. Data on usual duration of sleep, insomnia, and snoring were collected using "The Sleep Habits Questionnaire" and excessive daytime sleepiness (EDS) using Epworth Sleepiness Score. Logistic and linear regression were done with hypertension and BP as outcome variables, respectively. Age, gender, education, wealth index, family history, and body mass index (BMI) were included as covariates. We used multiple imputation to account for missing variables., Results: Prevalence of hypertension was 30.1%. The mean (SD) sleep duration was 7.3 (1.2) hours. Insomnia, snoring, and EDS were present in 13.6%, 28.7%, and 4.6%, respectively. Moderate and habitual snoring were associated with increased odds of hypertension (odds ratio [OR] = 1.18, 95% confidence interval [CI] [1.04 to 1.33] and 1.47 [1.29 to 1.67], respectively), after adjusting for covariates. Rare, occasional, and frequent insomnia were associated with increased hypertension (OR 1.41 [1.12 to 1.77], 1.39 [1.16 to 1.67], and 1.34 [1.09 to 1.65], respectively). Sleep duration and EDS were not associated with hypertension., Conclusion: Self-reported snoring and insomnia were associated with hypertension in South Asia. This relationship needs further exploration through robust longitudinal studies in this region., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: The World Health Organization and the Government of India have set targets to reduce burden of noncommunicable diseases. Information on population level trend of risk factors would provide insights regarding the possibility of achieving them., Objective: This study aimed to determine the population trends of cardiovascular disease risk factors in the National Capital Region of Delhi over 2 decades., Methods: Two representative cross-sectional surveys were conducted among men and women ages 35 to 64 years, residing in the urban and rural areas (survey 1 [1991 to 1994] and survey 2 [2010 to 2012]) using similar methodology. The urban sample was collected from the Municipal Corporation of Delhi, and the rural sample was from the Ballabgarh block of the adjoining state of Haryana. A total of 3,048 and 2,052 subjects of urban areas and 2,487 and 1,917 subjects of rural areas were surveyed in surveys 1 and 2, respectively. Behavioral (smoking and alcohol use), physical (overweight, abdominal obesity, and raised blood pressure), and biochemical risk factors (raised fasting blood glucose and raised total cholesterol) were measured using standard tools., Results: Urban and rural prevalence of overweight, alcohol use, raised blood pressure, and blood glucose increased with increases in age-standardized mean body mass index (urban: 24.4 to 26.0 kg/m 2 ; rural: 20.2 to 23.0 kg/m 2 ), systolic blood pressure (urban: 121.2 to 129.8 mm Hg; rural: 114.9 to 123.1 mm Hg), diastolic blood pressure (urban: 74.3 to 83.9 mm Hg; rural: 73.1 to 82.3 mm Hg), and fasting glucose (urban: 101.2 to 115.3 mg/dl; rural: 83.9 to 103.2 mg/dl). The smoking prevalence increased in the rural male population. Raised total cholesterol declined in urban and increased significantly in rural populations., Conclusions: The study indicates an overall worsening of population levels of all cardiovascular disease risk factors in National Capital Region over past 20 years, though some signs of stabilization and reversal are seen in urban Delhi., (Copyright © 2016 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)

Background: Despite high projected burden, hypertension incidence data are lacking in South Asian population. We measured hypertension prevalence and incidence in the Center for cArdio-metabolic Risk Reduction in South Asia (CARRS) adult cohort., Methods: The CARRS Study recruited representative samples of Chennai, Delhi, and Karachi in 2010/11, and socio-demographic and risk factor data were obtained using a standard common protocol. Blood pressure (BP) was measured in the sitting position using electronic sphygmomanometer both at baseline and two year follow-up. Hypertension and control were defined by JNC 7 criteria., Results: In total, 16,287 participants were recruited (response rate=94.3%) and two year follow-up was completed in 12,504 (follow-up rate=79.2%). Hypertension was present in 30.1% men (95% CI: 28.7-31.5) and 26.8% women (25.7-27.9) at baseline. BP was controlled in 1 in 7 subjects with hypertension. At two years, among non-hypertensive adults, average systolic BP increased 2.6mm Hg (95% CI: 2.1-3.1), diastolic BP 0.7mm Hg (95% CI: 0.4-1.0), and 1 in 6 developed hypertension (82.6 per 1000 person years, 95% CI: 80.8-84.4). Risk for developing hypertension was associated with age, low socio-economic status, current alcohol use, overweight, pre-hypertension, and dysglycemia. Risk of incident hypertension was highest (RR=2.95, 95% CI: 2.53-3.45) in individuals with pre-hypertension compared to normal BP. Collectively, 4 modifiable risk factors (pre-hypertension, overweight, dysglycemia, and alcohol use) accounted for 78% of the population attributable risk of incident hypertension., Conclusion: High prevalence and poor control of hypertension, along with high incidence, in South Asian adult population call for urgent preventive measures., (Copyright © 2017. Published by Elsevier B.V.)

The present study reports the Agrobacterium rhizogenes-mediated hairy root induction in of an ethno-medicinally significant herb-Boerhaavia diffusa L., for elucidating the underlying competence regarding its biosynthetic (i.e. boeravinone B and eupalitin) and bioactivity (antibacterial, antioxidant and anti-inflammatory) potentials. Host plant-specific receptiveness towards A. rhizogenes strains and disparity in compatibility threshold of leaf and nodal explants were evident. Only leaf explants responded, attaining hairy root induction with the ATCC 15834 followed by A4 and SA79 strains in reducing order of transformation efficiency. The growth behaviours differed amongst independent rhizoclones, and two clones of A4 (RBH) and ATCC 15834 (RBT8) origin demonstrated higher growth potentials. Polymerase chain reaction amplification of rol genes confirmed their transformed nature. Optimization of the appropriate solvent and reverse phase high-performance liquid chromatography parameters relating to the targeted metabolite production in the selected RBH and RBT8 clones revealed higher accumulation of eupalitin with the RBH clone having the best result of 1.44 times greater yield over the control root. Compared to the selected rhizoclones, the control roots however showed higher boeravinone B content. Devising a modified "stirred-tank" reactor through equipping with marine impellers and ring spargers facilitated high-density RBH root biomass yield with 6.1-fold and 1.15-fold yield increment of the boeravinone B and eupalitin respectively compared to shake-flask cultures. Considering the control roots, the RBH clone revealed analogous antioxidant/antibacterial activities with improved anti-inflammatory potential. The hairy root mediated higher production of boeravinone B and eupalitin could be achieved for the first time in bioreactor.

Objective This study aims to determine the frequency that umbilical venous catheters (UVCs) and peripherally inserted central catheters (PICCs) migrate into the cardiothymic silhouette after initial verification of correct placement. Study Design This is a single-center, retrospective study in neonates in whom a PICC or UVC was placed. The frequency of catheter tip migration into the cardiothymic silhouette requiring catheter manipulation was determined radiographically at 1 and 24 hours, respectively, after insertion. Results At 1 and 24 hours, 36 and 23% of UVCs (n = 41) migrated into the cardiothymic silhouette, respectively. At 1 and 24 hours, 23 and 11% of PICCs (n = 63) migrated into the cardiothymic silhouette, respectively. Migration was not associated with birth weight, weight at insertion, or postnatal age at insertion. Conclusion UVCs and PICCs frequently migrate into the cardiothymic silhouette increase the risk for development of a pericardial effusion. Serial radiographic assessment of catheter tip location is needed to assess catheter migration within the first 24 hours of line placement., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Aim: To assess the prevalence of cardiometabolic risk factors by socio-economic position (SEP) in rural and peri-urban Indian population., Subjects and Methods: Cross-sectional survey of 3,948 adults (1,154 households) from Telangana (2010-2012) was conducted to collect questionnaire-based data, physical measurements and fasting blood samples. We compared the prevalence of risk factors and their clustering by SEP adjusting for age using the Mantel Hansel test., Results: Men and women with no education had higher prevalence of increased waist circumference (men: 8 vs. 6.4 %, P  < 0.001; women: 20.9 vs. 12.0 %, P  = 0.01), waist-hip ratio (men: 46.5 vs. 25.8 %, P  = 0.003; women: 58.8 vs. 29.2 %, P  = 0.04) and regular alcohol intake (61.7 vs. 32.5 %, P  < 0.001; women: 25.7 vs. 3.8 %, P  < 0.001) than educated participants. Unskilled participants had higher prevalence of regular alcohol intake (men: 57.7 vs. 38.7 %, P  = 0.001; women: 28.3 vs. 7.3 %, P  < 0.001). In contrast, participants with a higher standard of living index had higher prevalence of diabetes (top third vs. bottom third: men 5.2 vs. 3.5 %, P  = 0.004; women 5.5 vs. 2.4 %, P  = 0.003), hyperinsulinemia (men 29.5 vs. 16.3 %, P  = 0.002; women 31.1 vs. 14.3 %, P  < 0.001), obesity (men 23.3 vs. 10.6 %, P  < 0.001; women 25.9 vs. 12.8 %, P  < 0.001), and raised LDL (men 16.8 vs. 11.4 %, P  = 0.001; women 21.3 vs. 14.0 %, P  < 0.001)., Conclusions: Cardiometabolic risk factors are common in rural India but do not show a consistent association with SEP except for higher prevalence of smoking and regular alcohol intake in lower SEP group. Strategies to address the growing burden of cardiometabolic diseases in urbanizing rural India should be assessed for their potential impact on social inequalities in health.

Objectives: To investigate the sociodemographic patterning of non-communicable disease risk factors in rural India., Design: Cross sectional study., Setting: About 1600 villages from 18 states in India. Most were from four large states due to a convenience sampling strategy., Participants: 1983 (31% women) people aged 20-69 years (49% response rate)., Main Outcome Measures: Prevalence of tobacco use, alcohol use, low fruit and vegetable intake, low physical activity, obesity, central adiposity, hypertension, dyslipidaemia, diabetes, and underweight., Results: Prevalence of most risk factors increased with age. Tobacco and alcohol use, low intake of fruit and vegetables, and underweight were more common in lower socioeconomic positions; whereas obesity, dyslipidaemia, and diabetes (men only) and hypertension (women only) were more prevalent in higher socioeconomic positions. For example, 37% (95% CI 30% to 44%) of men smoked tobacco in the lowest socioeconomic group compared with 15% (12% to 17%) in the highest, while 35% (30% to 40%) of women in the highest socioeconomic group were obese compared with 13% (7% to 19%) in the lowest. The age standardised prevalence of some risk factors was: tobacco use (40% (37% to 42%) men, 4% (3% to 6%) women); low fruit and vegetable intake (69% (66% to 71%) men, 75% (71% to 78%) women); obesity (19% (17% to 21%) men, 28% (24% to 31%) women); dyslipidaemia (33% (31% to 36%) men, 35% (31% to 38%) women); hypertension (20% (18% to 22%) men, 22% (19% to 25%) women); diabetes (6% (5% to 7%) men, 5% (4% to 7%) women); and underweight (21% (19% to 23%) men, 18% (15% to 21%) women). Risk factors were generally more prevalent in south Indians compared with north Indians. For example, the prevalence of dyslipidaemia was 21% (17% to 33%) in north Indian men compared with 33% (29% to 38%) in south Indian men, while the prevalence of obesity was 13% (9% to 17%) in north Indian women compared with 24% (19% to 30%) in south Indian women., Conclusions: The prevalence of most risk factors was generally high across a range of sociodemographic groups in this sample of rural villagers in India; in particular, the prevalence of tobacco use in men and obesity in women was striking. However, given the limitations of the study (convenience sampling design and low response rate), cautious interpretation of the results is warranted. These data highlight the need for careful monitoring and control of non-communicable disease risk factors in rural areas of India.

Background: Developing countries are facing a rise in noncommunicable diseases (NCD), which is a cause for concern. The World Health Organization has recommended a stepwise approach for NCD risk factor surveillance. Screening for risk factors in remote populations is difficult due to lack of resources and technical expertise, including standardized laboratory facilities. The collection of samples on filter paper for the assessment of risk factors circumvents the need for blood processing, storage, and shipment at ultralow temperatures., Method: Samples were collected on 3-mm Whatman filter paper from one industry (National Thermal Power Corporation) located in the periphery of Delhi as part of a surveillance carried out in industries from different parts of India. Total cholesterol was measured in serum and dried blood by the cholesterol oxidase/p-aminophenazone method and triglycerides by the glycerophosphate oxidase-peroxidase/aminophenazone method. Values obtained by the two methods were compared using Pearson correlation, and Bland-Altman plots were prepared to assess bias., Results: The correlation coefficient "r" was 0.78 for cholesterol and 0.94 for triglycerides between dried blood spots and serum. Bland-Altman plots suggest that differences in values obtained by the two methods were within two standard deviations for most of the samples., Conclusions: Blood samples dried on filter paper can be a successful option for population screening in remote areas, provided preanalytical variations arising due to the method of blood spot preparation and storage are well controlled., ((c) 2010 Diabetes Technology Society.)

The present study was designed to evaluate the independent and interactive effects of a once-a-day yoghurt drink providing 2 g plant sterols/d and capsules providing 2 g fish oil n-3 long-chain (LC) PUFA/d on plasma lipids, apolipoproteins and LDL particle size. Following a 2-week run-in period, 200 mildly hypercholesterolaemic Indian adults aged 35-55 years were randomised into one of four groups of a 2 x 2 factorial, double-blind controlled trial. The 4-week treatments consisted of (1) control yoghurt drink and control capsules, (2) control yoghurt drink and fish oil capsules, (3) plant sterol-enriched yoghurt drink and control capsules, or (4) plant sterol-enriched yoghurt drink and fish oil capsules. Blood was drawn before and after the 4-week intervention. Changes in health status, lifestyle and dietary habits, and daily compliance were recorded. The main effects of plant sterols were a 4.5 % reduction in LDL-cholesterol and a 15 % reduction in TAG without a significant change in HDL-cholesterol. Overall, fish oil n-3 LC-PUFA did not significantly affect cholesterol concentrations but reduced TAG by 15 % and increased HDL-cholesterol by 5.4 %. The combination significantly lowered TAG by 15 % v. control. No significant interaction between plant sterols and n-3 LC-PUFA was observed on plasma cholesterol concentrations. In conclusion, once-a-day intake of 2 g plant sterols/d in a yoghurt drink, 2 g fish oil n-3 LC-PUFA/d in capsules, and their combination had beneficial effects on the lipid profile of mildly hypercholesterolaemic Indian adults. The potent hypotriacylglycerolaemic effect of plant sterols observed in the present study and this population warrants additional investigation.

Commercially available analytical kits for the estimation of total antioxidant status are expensive and time-consuming. Most of the commercially available kits for total antioxidants estimation are based on the principle of suppression of ABTS radical cation formation by antioxidant in the serum sample. The method requires stringent assay conditions, like exact incubation time and the temperature (37 degrees C) of the reaction and on an average not more than 40 samples can be analyzed on a day. We have adapted the assay to a microplate, thereby allowing more number of samples to be analyzed per day. Further, the reagent volume required is one fourth than that for the original procedure thereby cutting cost. Thirty samples were analyzed by original method on spectrophotometer and our adapted microplate assay. The values of total antioxidant obtained by the two methods correlated well. Thus, total antioxidant can be estimated reliably using the microplate method.