PGC-1α Agonist Rescues Doxorubicin-Induced Cardiomyopathy by Mitigating the Oxidative Stress and Necroptosis.

Cardiomyopathy (particularly dilated cardiomyopathy (DCM)) significantly contributes to development and progression of heart failure (HF), and inflammatory factors further deteriorate the symptoms. Morphological and functional defects of the heart in doxorubicin (DOX)-induced cardiomyopathy (cardiotoxicity) are similar to those of DCM. We used anagonist of PGC-1α (PPAR (peroxisome proliferator-activated receptor-gamma)-γ coactivator-1α) that is considered as the 'master regulator' of mitochondrial biogenesis with an aim to rescue the DOX-induced deleterious effects on the heart. Forty male C57BL/6J mice (8 weeks old) were divided in four groups, Control, DOX, ZLN005, and ZLN005 + DOX (n = 10 each group). The DOX-induced (10 mg/kg, single dose) cardiomyopathy mimics a DCM-like phenotype with marked morphologic alteration in cardiac tissue and functional derangements. Significant increased staining was observed for Masson Trichrome/Picrosirius red and α-Smooth Muscle Actinin (α-SMA) that indicated enhanced fibrosis in the DOX group compared to the control that was attenuated by (peroxisome proliferator-activated receptor-gamma (PPAR-γ) coactivator) (PGC)-1α (alpha) agonist (four doses of 2.5 mg/kg/dose; cumulative dose = 10 mg/kg). Similarly, elevated expression of necroptosis markers along with enhanced oxidative stress in the DOX group were alleviated by PGC-1α agonist. These data collectively suggested the potent therapeutic efficacy of PGC-1α agonist in mitigating the deleterious effects of DOX-induced cardiomyopathy, and it may be targeted in developing the future therapeutics for the management of DCM/HF.

Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17).

BACKGROUND: Non-communicable disease (NCD) rates are rapidly increasing in India with wide regional variations. We aimed to quantify the prevalence of metabolic NCDs in India and analyse interstate and inter-regional variations. METHODS: The Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, a cross-sectional population-based survey, assessed a representative sample of individuals aged 20 years and older drawn from urban and rural areas of 31 states, union territories, and the National Capital Territory of India. We conducted the survey in multiple phases with a stratified multistage sampling design, using three-level stratification based on geography, population size, and socioeconomic status of each state. Diabetes and prediabetes were diagnosed using the WHO criteria, hypertension using the Eighth Joint National Committee guidelines, obesity (generalised and abdominal) using the WHO Asia Pacific guidelines, and dyslipidaemia using the National Cholesterol Education Program-Adult Treatment Panel III guidelines. FINDINGS: A total of 113 043 individuals (79 506 from rural areas and 33 537 from urban areas) participated in the ICMR-INDIAB study between Oct 18, 2008 and Dec 17, 2020. The overall weighted prevalence of diabetes was 11·4% (95% CI 10·2-12·5; 10 151 of 107 119 individuals), prediabetes 15·3% (13·9-16·6; 15 496 of 107 119 individuals), hypertension 35·5% (33·8-37·3; 35 172 of 111 439 individuals), generalised obesity 28·6% (26·9-30·3; 29 861 of 110 368 individuals), abdominal obesity 39·5% (37·7-41·4; 40 121 of 108 665 individuals), and dyslipidaemia 81·2% (77·9-84·5; 14 895 of 18 492 of 25 647). All metabolic NCDs except prediabetes were more frequent in urban than rural areas. In many states with a lower human development index, the ratio of diabetes to prediabetes was less than 1. INTERPRETATION: The prevalence of diabetes and other metabolic NCDs in India is considerably higher than previously estimated. While the diabetes epidemic is stabilising in the more developed states of the country, it is still increasing in most other states. Thus, there are serious implications for the nation, warranting urgent state-specific policies and interventions to arrest the rapidly rising epidemic of metabolic NCDs in India. FUNDING: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare, Government of India.

Prevalence and Correlates of Vitamin D Deficiency among Adult Population in Urban and Rural Areas of the National Capital Region of Delhi, India.

ABSTRACT: High prevalence of Vitamin D deficiency has been reported among selective population, but its population prevalence from representative adult population is lacking in India. The aim of this study was to estimate the prevalence and identify the correlates of Vitamin D deficiency among urban and rural areas of the National Capital Region (NCR) of Delhi, India. Serum Vitamin D levels of 1403 adults (aged 30 years above), 702 from urban and 701 from rural NCR of Delhi, who participated in a representative cross-sectional survey were measured using the quantitative chemiluminescent immunoassay method. The prevalence of Vitamin D deficiency was classified as severe deficient, and insufficient at three serum levels of 25-hydroxyvitamin D-<10, 10-<20, and 20-<30 ng/mL, respectively. The median (interquartile range) 25-hydroxyvitamin D levels in urban and rural areas were 7.7 (5.2, 10.8) ng/mL and 16.2 (10.9, 22.3) ng/mL, respectively. The prevalence of Vitamin D severe deficiency, deficiency, and insufficiency in urban areas were 71%, 27%, and 2%, respectively. The corresponding prevalence in rural areas was 20%, 47%, and 25%. Urban location (odds ratio [OR] [95% confidence interval [CI]: 11.7 [8.6, 15.9]), female gender (OR [95% CI]: 1.5 [1.1, 2.2]), and abdominal obesity (OR [95% CI]:1.5 [1.1, 2.0]) were independently associated with severe deficiency. This study revealed a high prevalence of severe vitamin deficiency among the adult living in NCR, more so among urban areas, women, and obese.

Interleukin-33 Induces Neutrophil Extracellular Trap (NET) Formation and Macrophage Necroptosis via Enhancing Oxidative Stress and Secretion of Proatherogenic Factors in Advanced Atherosclerosis.

Interleukin-33 (IL-33) acts as an 'alarmin', and its role has been demonstrated in driving immune regulation and inflammation in many human diseases. However, the precise mechanism of action of IL-33 in regulating neutrophil and macrophage functioning is not defined in advanced atherosclerosis (aAT) patients. Further, the role of IL-33 in neutrophil extracellular trap (NET) formation in aAT and its consequent effect on macrophage function is not known. In the present study, we recruited n = 52 aAT patients and n = 52 control subjects. The neutrophils were isolated from both groups via ficoll/percoll-based density gradient centrifugation. The effect of IL-33 on the NET formation ability of the neutrophils was determined in both groups. Monocytes, isolated via a positive selection method, were used to differentiate them into macrophages from each of the study subjects and were challenged by IL-33-primed NETs, followed by the measurement of oxidative stress by calorimetric assay and the expression of the proinflammatory molecules by quantitative PCR (qPCR). Transcript and protein expression was determined by qPCR and immunofluorescence/ELISA, respectively. The increased expression of IL-33R (ST-2) was observed in the neutrophils, along with an increased serum concentration of IL-33 in aAT compared to the controls. IL-33 exacerbates NET formation via specifically upregulating CD16 expression in aAT. IL-33-primed NETs/neutrophils increased the cellular oxidative stress levels in the macrophages, leading to enhanced macrophage necroptosis and the release of atherogenic factors and matrix metalloproteinases (MMPs) in aAT compared to the controls. These findings suggested a pathogenic effect of the IL-33/ST-2 pathway in aAT patients by exacerbating NET formation and macrophage necroptosis, thereby facilitating the release of inflammatory factors and the release of MMPs that may be critical for the destabilization/rupture of atherosclerotic plaques in aAT. Targeting the IL-33/ST-2-NETs axis may be a promising therapeutic target for preventing plaque instability/rupture and its adverse complications in aAT.

Detecting sub-clinical disease activity in patients with chronic rheumatic valvular heart disease.

OBJECTIVE: Valve disease progression in rheumatic heart disease(RHD) is generally attributed to recurrent attacks of acute rheumatic fever(ARF). However, persistence of chronic sub-clinical inflammation remains a plausible but unproven cause. Non-invasive means to identify sub-clinical inflammation may facilitate research efforts towards understanding its contribution to disease progression. METHODS: Patients with chronic RHD, without clinical evidence of ARF, undergoing elective valve surgery were enrolled. Sub-clinical inflammation was ascertained by histological evaluation of left atrial appendage and valve tissue excised during surgery. We assessed the diagnostic utility of Gallium-67 scintigraphy imaging, and inflammatory biomarkers, hsCRP, IL-2, IL-6, Tumor Necrosis Factor-Alpha(TNF-α), Interferon-gamma(IFN-γ), and Serum Amyloid A(SAA), in identifying patients with sub-clinical inflammation. RESULTS: Of the 93 RHD patients enrolled(mean age 34 ± 11 years, 45% females), 86 were included in final analysis. Sub-clinical inflammation was present in 27 patients(31.4%). Patients with dominant regurgitant lesions were more likely to have sub-clinical inflammation compared to those with stenotic lesions, though this association was not statistically significant(dominant regurgitant lesions vs isolated mitral stenosis: OR 3.5, 95%CI 0.68-17.96, p = 0.133). Inflammatory biomarkers were elevated in the majority of patients: hsCRP, IL-2, IL-6, TNF-α, and IFN-γ in 44%, 89%, 90%, 79%, and 81% patients, respectively. However, there was no significant association between biomarker elevation and histologically ascertained sub-clinical inflammation. Ga-67 imaging was unable to identify inflammation in the 15 patients in whom it was performed. CONCLUSION: Sub-clinical inflammation is common in RHD patients. Conventional inflammatory markers are elevated in the majority, but aren't discriminatory enough to identify the presence of histologic inflammation.

Intraoperative lung protective ventilation in peritonitis patients undergoing emergency laparotomy: A randomised controlled trial.

BACKGROUND AND AIMS: Lung protective ventilation (LPV) is recommended in acute respiratory distress syndrome. However, role of intraoperative LPV in elective laparotomy is controversial and it has not been evaluated in emergency laparotomy (EL). The aim of the study was to identify whether use of intraoperative LPV in EL in peritonitis patients reduces postoperative pulmonary complications (POPC). METHODS: After institutional ethics committee approval and informed written consent, 98 adult patients undergoing EL for peritonitis were randomised into two groups. Patients in group 1 received LPV (tidal volume 6-8 ml/kg, positive end expiratory pressure (PEEP) 6-8 cm H2O and recruitment manoeuvre every 30 min) and patients in group 2 received conventional ventilation (tidal volume 10-12 ml/kg, without PEEP/recruitment). Primary outcome was incidence of POPC on day 7. RESULTS: Data of 94 patients (n = 45 in group 1 & n = 49 in group 2) were available. Baseline demographic & laboratory parameters were comparable. Incidence of POPC was similar in both the groups [42.9% in group 1 vs. 53.3% in group 2; risk difference -10.4% (-30.6%, 9.6%); P = 0.31]. Mortality during hospital stay was 26.7% patients in group 1 and 26.5% patients in group 2 [risk difference (95% CI) 0.14%, (-17.7, 18.0); P = 0.98]. Length of hospital stay [median interquartile range (IQR) 13 (9-18) days in group 1 vs. 13 (8-21) days in group 2; P = 0.82] and length of intensive care unit stay [median (IQR) 7 (4-10) days vs. 6 (3-12) days; P = 0.88] were also similar in both groups. CONCLUSION: LPV during EL in peritonitis patients does not reduce the incidence of POPC compared to conventional ventilation.

Role of inflammation in initiation and maintenance of atrial fibrillation in rheumatic mitral stenosis - An analytical cross-sectional study.

BACKGROUND: Inflammation has been implicated in the initiation and perpetuation of non-valvular atrial fibrillation (AF). However, there is a lack of similar data on AF in rheumatic heart disease (RHD). The objective of this study was to analyze the association of inflammation as measured by serum inflammatory biomarkers with AF in rheumatic mitral stenosis (Rh-MS). METHODS: A comparative cross-sectional analytical study was conducted on 181 Rh-MS patients in normal sinus rhythm (NSR; n = 69), subclinical transient AF (SCAF; detected by 24-hours Holter monitoring; n = 30) and chronic AF (n = 82). Serum hs-CRP, IL-6, and sCD-40L were assessed using ELISA immunoassay and compared in all groups of Rh-MS with or without AF. RESULTS: We found significantly higher serum hs-CRP and sCD-40L levels in the overall AF (Chronic AF + SCAF) group (hs-CRP: 4.5 ± 3.4 vs 2.3 ± 2.9 mg/L, P < .01; sCD-40L: 6.4 ± 4.8 vs 3.1 ± 3.4 ng/mL, P < .01) and chronic AF subgroup (hs-CRP: 4.9 ± 3.4 vs 2.3 ± 2.9 mg/L, P < .01; sCD-40L: 6.9 ± 5.1 vs 3.1 ± 3.4 ng/mL, P < .01) compared to patients with sinus rhythm. There was a statistically significant graded increase of serum IL-6 level from the NSR to the SCAF (vs NSR: 6.8 ± 3.9 vs 4.0 ± 2.2 pg/mL, P = .03), and chronic AF subgroups (vs NSR: 9.3 ± 6.5 vs 4.0 ± 2.2 pg/mL, P < .01; vs SCAF: 9.3 ± 6.5 vs 6.8 ± 3.9, P = .05) of atrial fibrillation. CONCLUSIONS: Elevated levels of serum hs-CRP, IL-6, and sCD-40L were strongly associated with overall AF and also with SCAF and chronic AF in Rh-MS patients indicating a potential role of inflammation in the pathophysiology of rheumatic AF.

Association of Single Nucleotide Polymorphisms (SNPs) in Genes Encoding for Folate Metabolising Enzymes with Glioma and Meningioma in Indian Population

Background: The association of primary brain tumors with Single Nucleotide polymorphisms (SNPs) in genes of folate metabolising enzymes have been reported to vary among different ethnic population. Here, we have studied the association of SNPs of folate metabolizing genes with the primary brain tumors (glioma and meningioma) in North Indian population. Methods: SNPs of genes coding for folate metabolizing enzymes was carried out in 288 study population from North India [Glioma (n=108), Meningioma (n=76) and healthy-control (n=104)]. The allele-specific polymerase chain reaction (ARMS-PCR) was used to analyse the SNP A1298C of the MTHFR (Methylenetetrahydrofolate-reductase) and the SNP A66G of the methionine synthase reductase (MTRR) genes. The PCR-RLFP (Restriction Fragment Length Polymorphism) was used to analyse the SNP C677T of the Methylene tetrahydrofolate-reductase and the SNP A2756G of the methionine-synthase (MTR) genes. Serum homocysteine, vitamin B12 and folate levels were evaluated in controls/ patients serum using Chemiluminescence immunoassay and the levels were correlated with SNPs genotype. Results: The CC genotype of MTHFR A1298C was observed to have reduced risk of having meningioma than AA genotype (odd ratio=0.62, 95%CI 0.32-0.97, p=0.03). Similarly, the AG genotype of MTRR A66G showed reduced risk of glioma than AA genotype (odd ratio=0.56, 95%CI 0.32-0.97, p=0.039). Furthermore, in patients with AA genotype of MTR A2756G and CT genotype of MTHFR C677T showed higher serum homocysteine level than GG genotype (8.6 µmol/L, p=0.048) and CC genotype (11.2µmol/L, p=0.039) respectively. Conclusion: Our findings provide an insight into the risk association of SNPs in MTHFR A1298C and MTRR A66G genes with glioma/meningioma patients. Further studies are needed to evaluate their clinical implications.

Admission Vitamin D status does not predict outcome of critically ill patients on mechanical ventilation: An observational pilot study.

BACKGROUND AND AIMS: Effect of serum 25-hydroxy vitamin D (25[OH] D) levels on the recovery of critically ill mechanically ventilated patients is unclear. Hence, this study assessed 25(OH)D levels of critically ill patients on mechanical ventilation at the time of admission to the Intensive Care Unit (ICU) and its relationship with clinical outcome. METHODS: In this prospective observational pilot study, forty adult patients receiving mechanical ventilation in the ICU were included. Serum 25(OH)D was assessed within 24 h of admission. Primary outcome was 30-day mortality and secondary outcomes were days on mechanical ventilation, ICU-length of stay (ICU-LOS), days to reach spontaneous breathing trial (SBT), requirement of advanced care modality and complications. RESULTS: Seventy-five percent patients had low serum 25(OH)D (65% deficient and 10% insufficient). Between patients with low and normal vitamin D, there was no significant difference in 30-day mortality (10% vs. 16.7%; P = 0.81), days on mechanical ventilation (16.2 ± 8.9 vs. 19.9 ± 8.4; P = 0.23), ICU-length of stay (18.7 ± 8.5 vs. 23.3 ± 11.4; P = 0.28), days to reach SBT (11.5 (0-20) vs. 21 (8-30); P = 0.78), complications developed during ICU stay (P = 0.60) and need for advanced care modalities (P = 0.72). CONCLUSION: Low Vitamin D level at admission did not affect 30-day mortality of critically ill patients on mechanical ventilation.

Effect of administration of allopurinol on postoperative outcomes in patients undergoing intracardiac repair of tetralogy of Fallot.

OBJECTIVE: To determine effects of allopurinol administration on outcomes following intracardiac repair of tetralogy of Fallot (TOF). MATERIALS AND METHODS: Fifty patients undergoing TOF repair were randomized to 2 groups of 25 each: the allopurinol group (n = 25) and the placebo group (n = 25). Postoperatively, inotropic score, rhythm, duration of mechanical ventilation, cardiac output, intensive care unit (ICU) stay, and hospital stay were assessed. Plasma troponin-I, superoxide dismutase (SOD), interleukin (IL) 1-ß, IL-6, and malondialdehyde were measured serially. RESULTS: Inotropic score was lower in the allopurinol compared with placebo group (11.04 ± 5.70 vs 17.50 ± 7.83; P = .02). Duration of ICU and hospital stay was lower in the allopurinol group. Plasma levels of SOD preoperative were (2.87 ± 1.21 U/mL vs 4.5 ± 2.08 U/mL; P = .012), immediately following release of crossclamp (2.32 ± 0.98 U/mL vs 5.32 ± 2.81 U/mL; P < .001), and after termination of CPB (2.18 ± 1.0.78 U/mL vs 3.44 ± 1.99 U/mL; P = .003) between the placebo versus allopurinol group, respectively. Postoperative levels of IL1-ß and IL-6 were lower in the allopurinol group. Malondialdehyde levels following CPB were lower in the allopurinol group (11.80 ± 2.94 pg/mL in the placebo vs 9.16 ± 3.02 g/mL in the allopurinol group; P < .001). CONCLUSIONS: Allopurinol administration in patients undergoing intracardiac repair of TOF is associated with reduced inotropic scores, duration of mechanical ventilation, ICU stay, and hospital stay and favorable biochemical markers of inflammation. Further studies in multiple setups are needed before recommending it as a routine practice.

A controlled study of plasma fatty acids in Indian patients with depressive episode.

AIM: To study the plasma omega 3 and omega 6 fatty acid levels in patients with depressive episode and in matched healthy controls. METHOD: Thirty patients with first episode depression and thirty healthy matched control subjects were recruited from a tertiary care hospital setting. We measured plasma omega-3 and omega-6 fatty acid levels of the study and the control group. RESULT: There were no significant differences in plasma omega 3 fatty acid levels between study group and control group. The plasma omega 6 fatty acid levels of study group were significantly less than that of control group. CONCLUSIONS: The present study is an initial attempt to investigate the link between fatty acids and depression in a clinical setting in India. This comparative study with normal controls did not etiologically link these polyunsaturated fatty acids in this sample of depressive disorder.

Diabetic status and grade of nonalcoholic fatty liver disease are associated with lower baroreceptor sensitivity in patients with nonalcoholic fatty liver disease.

OBJECTIVES: Baroreceptor sensitivity (BRS), a functional consequence of vascular stiffness, may be affected by the presence of diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). The present study was designed to assess the effect of diabetic status and NAFLD grade on the BRS in patients with NAFLD. METHODS: Seventy-five individuals (25 NAFLD without DM, 25 NAFLD with DM and 25 controls) were recruited for the study who underwent anthropometric and body composition analysis along with estimation of plasma glucose, serum insulin and serum lipids. BRS and blood pressure variability (BPV) analysis was carried out in both time and frequency domains. Carotid-radial and carotid-dorsalis pedis artery pulse wave velocity, and radial artery augmentation index were computed as measures of arterial stiffness. RESULTS: BRS was found to be lower in the NAFLD with DM group as well those with grade II NAFLD compared with the controls. Correlation analysis showed a negative correlation of BRS with postprandial blood glucose level (r=-0.39) and BMI (r=-0.467). The diabetic status and grade of NAFLD were associated independently with a decrease in BRS as well as the low-frequency component of diastolic BPV. The augmentation index and carotid-distal pulse wave velocity were higher in the NAFLD with DM group compared with controls. CONCLUSION: Both the diabetic status and grade of NAFLD were shown to have an independent effect on the decrease in the BRS with a consequent effect on BPV, with a greater influence of diabetic status rather than NAFLD grade on arterial stiffness.

Ambulatory Blood Pressure Monitoring in Frequently Relapsing Nephrotic Syndrome.

OBJECTIVES: To screen patients with frequently relapsing nephrotic syndrome (FRNS) for the presence of ambulatory hypertension and left ventricular hypertrophy. METHODS: Following ethical and parental approvals, consecutive patients with FRNS of ≥2 y duration were enrolled. Those with estimated glomerular filtration rate <60 ml/min/1.73 m2 and known familial hypercholesterolemia or diabetes mellitus were excluded. Clinic blood pressure was measured by oscillometry and 24-h ambulatory blood pressure was recorded by Spacelab 90207; echocardiography was done for left ventricular mass. Ambulatory hypertension was defined as the presence of clinic blood pressure >95th centile for age, sex and height, and systolic blood pressure load exceeding 25 %. RESULTS: Of 99 patients, 73 were boys; their median (IQR) age was 120 (84-156) mo. Clinic blood pressure was >95th percentile in 63 (63.6 %) patients. Ambulatory hypertension was present in 33 (33.3 %), including 14 patients with severe hypertension; 16 (16.1 %) had masked hypertension and 30 (30.3 %) had white coat hypertension. Non-dipping was seen in 72 and 55 patients had high nocturnal systolic blood pressure load. Of 21 patients with increased left ventricular mass index, 9 (42.9 %) had ambulatory hypertension, 3 (14.3 %) had masked hypertension and 6 (28.6 %) patients had white coat hypertension. Compared to those with normal blood pressure, patients with ambulatory hypertension were younger at onset of nephrotic syndrome (odds ratio, OR 0.94; 95 % CI 0.91-0.98; P = 0.002), longer duration of frequently relapsing disease (OR 1.05; 95 % CI 1.00-1.10; P = 0.034) and higher body mass index (BMI) (OR 1.61; 95 % CI 1.07-4.40; P = 0.020). BMI was positively correlated with 24-h systolic blood pressure load (r = 0.23; P = 0.002) and with the left ventricular mass index (r = 0. 57; P = 0.001). CONCLUSIONS: Many patients with FRNS showed high prevalence of clinic, ambulatory and white coat hypertension, emphasizing the need to carefully screen these patients in order to ensure their appropriate management. While clinic blood pressure monitoring detects most patients with hypertension, it misses a significant proportion with masked hypertension, underscoring the need for ambulatory blood pressure monitoring and screening for end organ damage. High BMI was the chief risk factor for hypertension, suggesting that control of overweight and hypertension might improve cardiovascular outcomes.

Vitamin D-binding protein, vitamin D status and serum bioavailable 25(OH)D of young Asian Indian males working in outdoor and indoor environments.

Urban Asian Indians generally have low serum 25(OH)D. Information on serum bioavailable 25(OH)D and the effect of prolonged sun-exposure in them is not known. We assessed serum 25(OH)D and bioavailable 25(OH)D in males with varying durations of sun-exposure in Delhi during August-September. Serum 25(OH)D, vitamin D-binding protein (DBP), bioavailable 25(OH)D, free 25(OH)D index, iPTH, ionized calcium and sun-index were assessed in outdoor, mixed outdoor-indoor and indoor workers (n = 88, 32 and 74, respectively). The mean sun-index (12.0 ± 6.25, 4.3 ± 2.20 and 0.7 ± 0.62, respectively; P < 0.001) was highest outdoors and lowest indoors. Serum 25(OH)D (29.0 ± 8.61, 19.1 ± 5.73 and 10.9 ± 4.19 ng/ml, respectively; P < 0.001), bioavailable 25(OH)D and free 25(OH)D index were maximum in outdoor workers followed by mixed-exposure and indoor workers. Their mean serum DBP levels (241.2 ± 88.77, 239.3 ± 83.40 and 216.6 ± 63.93 µg/ml, respectively; P = 0.12) were comparable. Mean serum iPTH was significantly lower in outdoor than indoor workers and showed inverse correlations with serum 25(OH)D, bioavailable 25(OH)D and free 25(OH)D index (r = -0.401, -0.269 and -0.236, respectively; P < 0.001 in all). Daily dietary-calorie intake was higher and calcium lower in outdoor than indoor workers. On regression analysis, sun-exposure was the only significant variable, increasing serum 25(OH)D by 2.03 ng/ml per hour of sun-exposure (95 % confidence interval 1.77-2.28; P < 0.001). Outdoor workers with prolonged sun-exposure were vitamin D-sufficient, with higher serum bioavailable 25(OH)D than the indoor workers during summer. Use of serum DBP levels did not affect the interpretation of their vitamin D status.

Dextrose-containing intraoperative fluid in neonates: a randomized controlled trial.

BACKGROUND: Glucose requirement in neonates during surgery and the impact of glucose supplementation on neonatal metabolism remain unclear. AIM: This study was designed to identify an appropriate perioperative fluid regimen in neonates which maintains carbohydrate and lipid homeostasis. METHODS: Forty-five neonates undergoing primary repair of a trachea-esophageal fistula were randomly allocated into three groups. During surgery, the neonates received either 1% dextrose in Ringer lactate (RL) (group D1) at 10 ml·kg(-1) ·h(-1) , or 2% dextrose in RL (group D2) at 10 ml·kg(-1) ·h(-1) , or 10% dextrose in N/5 saline at 4 ml·kg(-1) ·h(-1) and replacement fluid with 6 ml·kg(-1) ·h(-1) of RL (group D4). Glucose homeostasis, electrolyte balance, acid-base status, and endocrine and metabolic parameters were compared among the groups during the perioperative period. RESULTS: Blood glucose increased in all the three groups at the end of surgery, with no significant difference in blood glucose and incidence of hyperglycemia (BG > 150 mg·dl(-1) ) among them. At 24 h after surgery, blood glucose and incidence of hyperglycemia was significantly higher in Group D1 compared to Group D4. Base excess, bicarbonate, lactate, and pH showed a significant fall in Group D1. There was no significant difference in serum-free fatty acids, serum beta-hydroxy butyrate, and serum cortisol in three groups. At the end of surgery, serum insulin was significantly lower and glucagon : insulin (G : I) ratio was higher in Group D1 compared to Group D4. CONCLUSIONS: All three solutions, when infused at 10 ml·kg(-1) ·h(-1) , are equally effective in maintaining glucose homeostasis, but 1% dextrose-containing fluid promotes catabolism, insulin resistance, rebound hyperglycemia, and acidosis. Therefore, 2-4% dextrose-containing fluids is more suitable compared to 1% dextrose-containing fluids for use during major neonatal surgeries requiring average fluid infusion rate of 10 ml·kg(-1) ·h(-1) .

Dyslipidemia, carotid intima-media thickness and endothelial dysfunction in children with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) predisposes to accelerated atherosclerosis that is measured by carotid artery intima-media thickness (cIMT) and brachial artery flow-mediated dilation (FMD). Information on the association of these parameters with dyslipidemia in pre-dialysis pediatric CKD is limited. METHODS: Eighty patients aged 9.9 ± 3.2 years, with estimated glomerular filtration rate of 38.8 ± 10.8 ml/1.73 m(2)/min, and 42 pediatric controls underwent cross-sectional analysis of lipid profile, cIMT, and brachial artery FMD. Significant differences in these parameters between patients and controls were analyzed using Student's t test. Predictors of cIMT and dyslipidemia were assessed using linear and logistic regression respectively. RESULTS: Patients had elevated blood levels of triglyceride and of total and LDL cholesterol than controls (P ≤ 0.001); 73.8 % were dyslipidemic. Mean cIMT was higher (0.421 ± 0.054 mm vs 0.388 ± 0.036 mm, P = 0.001) and brachial artery FMD was reduced (10.6 ± 4.9 % vs 18.9 ± 4.1 %, P < 0.0001) in patients compared with controls. On multivariate analysis, hypertension (OR 3.68, P = 0.044) and male gender (OR 10.21, P = 0.004) were associated with dyslipidemia; cIMT was significantly associated with LDL cholesterol (ß = 28.36, P = 0.033). CONCLUSION: Dyslipidemia was prevalent and cIMT significantly elevated in pre-dialysis pediatric CKD, indicating increased cardiovascular risk. Elevated LDL cholesterol predicted increased cIMT, strengthening the association between dyslipidemia and atherosclerosis in early CKD.

Stability and reliability of glycated haemoglobin measurements in blood samples stored at -20°C.

AIM: To validate the stability of glycated haemoglobin (HbA1c) measurements in blood samples stored at -20°C for up to one month. METHODS: The study group comprised 142 type 2 diabetic subjects visiting a tertiary centre for diabetes at Chennai city in south India. The HbA1c assay was done on a fasting blood sample using the Bio-Rad Variant machine on Day 0 (day of blood sample collection). Several aliquots were stored at -20°C and the assay was repeated on the 3rd, 7th, 15th, and 30th day after the sample collection. Bland-Altman plots were constructed and variation in the HbA1c levels on the different days was compared with the day 0 level. RESULTS: The median differences between HbA1c levels measured on Day 0 and the 3rd, 7th, 15th, and 30th day after blood collection were 0.0%, 0.2%, 0.3% and 0.5% respectively. Bland-Altman plot analysis showed that the differences between the day '0' and the different time points tend to get larger with time, but these were not clinically significant. CONCLUSIONS: HbA1c levels are relatively stable up to 2weeks, if blood samples are stored at -20°C.

Independent association of severe vitamin D deficiency as a risk of acute myocardial infarction in Indians.

BACKGROUND: Association of vitamin D deficiency with coronary heart disease (CHD) has been widely reported. Emerging data has shown high prevalence of vitamin D deficiency among Indians. However, this association has not been studied in Indians. METHODS: A case-control study with 120 consecutive cases of first incident acute myocardial infarction (MI) and 120 age and gender matched healthy controls was conducted at All India Institute of Medical Sciences, New Delhi. The standard clinical and biochemical risk factors for MI were assessed for both cases and controls. Serum 25 (OH) vitamin D assay was performed from stored samples for cases and controls using radioimmunoassay. RESULTS: Vitamin D deficiency [25(OH) D < 30 ng/ml] was highly prevalent in cases and controls (98.3% and 95.8% respectively) with median levels lower in cases (6 ng/ml and 11.1 ng/ml respectively; p < 0.001). The cases were more likely to have diabetes, hypertension and consume tobacco and alcohol. They had higher waist hip ratio, total and LDL cholesterol. Multivariate logistic regression analysis revealed severe vitamin D deficiency [25(OH) vitamin D < 10 ng/ml] was associated with a risk of MI with an odds ratio of 4.5 (95% CI 2.2-9.2). CONCLUSIONS: This study reveals high prevalence of vitamin D deficiency among cases of acute MI and controls from India, with levels of 25 (OH)D being significantly lower among cases. Despite rampant hypovitaminosis, severe vitamin D deficiency was associated with acute MI after adjusting for conventional risk factors. This association needs to be tested in larger studies in different regions of the country.

Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort.

BACKGROUND & OBJECTIVES: Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease. METHODS: Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations. RESULTS: The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI th > 30 kg/m [2] ). Mean systolic blood pressure (SBP) was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm) and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex. INTERPRETATION & CONCLUSIONS: The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function.

Role of dried blood spots in health and disease diagnosis in older adults.

Older adults represent a substantial number of the world population, which is set to grow considerably in the coming years. The health challenges faced by the older adults are unique. Several age-related changes in them make phlebotomy difficult. Application of dried blood has been demonstrated to be useful in the other similarly vulnerable population, the neonates. Similar approach of standardization and demonstration of use of dried blood spots (DBS) for analytes of interest in older adult population would be highly appreciated. There are very few reports of use of DBS in older adults. There are several potential areas of interest for older adults in which DBS assays are available but have not been applied for screening in them. This review describes a brief general overview of DBS, its advantages and disadvantages and potential use in disease diagnosis in older adults.