Implications of reactive oxygen species in lung cancer and exploiting it for therapeutic interventions.

Lung cancer is the second (11.4%) most commonly diagnosed cancer and the first (18%) to cause cancer-related deaths worldwide. The incidence of lung cancer varies significantly among men, women, and high and low-middle-income countries. Air pollution, inhalable agents, and tobacco smoking are a few of the critical factors that determine lung cancer incidence and mortality worldwide. Reactive oxygen species are known factors of lung carcinogenesis resulting from the xenobiotics and their mechanistic paths are under critical investigation. Reactive oxygen species exhibit dual roles in cells, as a tumorigenic and anti-proliferative factor, depending on spatiotemporal context. During the precancerous state, ROS promotes cancer origination through oxidative stress and base-pair substitution mutations in pro-oncogenes and tumor suppressor genes. At later stages of tumor progression, they help the cancer cells in invasion, and metastases by activating the NF-kB and MAPK pathways. However, at advanced stages, when ROS exceeds the threshold, it promotes cell cycle arrest and induces apoptosis in cancer cells. ROS activates extrinsic apoptosis through death receptors and intrinsic apoptosis through mitochondrial pathways. Moreover, ROS upregulates the expression of beclin-1 which is a critical component to initiate autophagy, another form of programmed cell death. ROS is additionally involved in an intermediatory step in necroptosis, which catalyzes and accelerates this form of cell death. Various therapeutic interventions have been attempted to exploit this cytotoxic potential of ROS to treat different cancers. Growing body of evidence suggests that ROS is also associated with chemoresistance and cancer cell immunity. Considering the multiple roles of ROS, this review highlights the exploitation of ROS for various therapeutic interventions. However, there are still gaps in the literature on the dual roles of ROS and the involvement of ROS in cancer cell immunity and therapy resistance.

Fluid and electrolyte management in preterm infants with patent ductus arteriosus.

Optimal fluid management of preterm babies with suspected or confirmed diagnosis of patent ductus arteriosus (PDA) is frequently challenging for neonatal care physician because of paucity of clinical trials. There is wide variation in practice across neonatal units, resulting in significant impact on outcomes in Extremely Low Birth Weight (ELBW) babies with hemodynamically significant PDA. A delicate balance is required in fluid management to reduce mortality and morbidity in this population. The purpose of this review is to lay out the current understanding about fluid and electrolyte management in ELBW babies with hemodynamically significant PDA and highlight areas for future research.

Cognitive function and behavioral problems in children born to mothers with preeclampsia: an Indian study.

Studies from high-income countries report associations of preeclampsia (PE) with reduced cognitive function and adverse behavioural outcomes in children. We examined these associations in Indian children aged 5-7 years. Children of mothers with PE (n=74) and without PE (non-PE; n=234) were recruited at delivery at Bharati Hospital, Pune, India. The cognitive performance was assessed using 3 core tests from the Kaufman Assessment Battery and additional tests including Verbal fluency, Kohs block design, and Coding A (from Wechsler Intelligence Scale for Children). The parent-reported Strengths and Difficulties Questionnaire (SDQ) was used to assess children's behavioral characteristics. Scores were compared between children from PE and non-PE groups, and associations analyzed further using regression models, adjusted for potential confounders. After adjusting for age, sex, socio-economic status and maternal education, children of PE mothers had lower Kohs block design scores (adjusted odds ratio per score category 0.57, [95% CI 0.34-0.96] p=0.034; 0.62 [95%CI (0.36, 1.07), p=0.09 on further adjustment for birth weight and gestation) compared to children of mothers without PE. In the SDQ, there was a lower prevalence of abnormal 'conduct problem' scores in PE group than non-PE group (OR=0.33, 95% CI 0.13-0.83, p=0.018, in the fully adjusted model); there were no differences for other behavioral domains. This preliminary study in Indian children suggests that fetal exposure to maternal PE may have an adverse impact on visuo-spatial performance but does not adversely affect behavior. Further studies with larger sample sizes are essential to understand effects of maternal PE on cognitive/behavioral outcomes in children.

Adverse childhood experiences and substance misuse in young people in India: results from the multisite cVEDA cohort.

BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).

Comparing CxBladder to Urine Cytology as Adjunct to Cystoscopy in Surveillance of Non-muscle Invasive Bladder Cancer-A Pilot Study.

Purpose: Guidelines advocate cystoscopy surveillance (CS) for non-muscle invasive bladder cancer (NMIBC) post-resection. However, cystoscopy is operator dependent and may miss upper tract lesions or carcinoma in-situ (CIS). Urine cytology is a common adjunct but lacks sensitivity and specificity in detecting recurrence. A new mRNA biomarker (CxBladder) was compared with urine cytology as an adjunct to cystoscopy in detecting a positive cystoscopy findings during surveillance cystoscopy in our center. Materials and Methods: Consented patients older than 18, undergoing CS for NMIBC, provide paired urine samples for cytology and CxBladder test. Patients with positive cystoscopy findings would undergo re-Trans Urethral Resection of Bladder Tumor (TURBT). Results: Thirty-five patients were enrolled from April to June 2019. Seven contaminated urine samples were excluded. The remaining cohort of 23 (82%) and 5 (18%) females had a mean age of 66.69 (36-89). Eight (29%) patients with positive cystoscopy finding underwent TURBT. All 8 patients also had positive CxBladder result. This shows that CxBladder has a sensitivity and negative predictive value (NPV) of 100%, specificity of 75% and positive predictive value (PPV) of 62% in predicting a positive cystoscopy finding. TURBT Histo-pathological findings showed Low-grade Ta NMIBC in one patient (4%), and 7 (25%) patients had inflammatory changes. Urine cytology was only positive in one patient with a positive cystoscopy finding. This led to a sensitivity of merely 13% and NPV of 74%, while specificity and PPV was 100% in predicting a positive cystoscopy finding. Conclusion: CxBladder had high NPV and sensitivity which accurately predicted suspicious cystoscopy findings leading to further investigation. It has great potential for use as adjunct to cystoscopy for surveillance of NMIBC.

Clinical profiles and risk factors for early and medium-term mortality following heart transplantation in a pediatric population: A single-center experience.

AIMS AND OBJECTIVES: There is a paucity of data regarding the outcomes of Heart transplantation in children from the Indian subcontinent. The data of patients under the age of 18 undergoing an isolated heart transplantation was analyzed for patient clinical profiles and risk factors for early and medium-term mortality. Hospital mortality was defined as death within 90 days of transplantation and medium-term survival as follow up of up to 6 years. MATERIALS AND METHODS: A total of 97 patients operated between March 2014 and October 2019 were included in this study. Data was collected about their INTERMACS status, pulmonary vascular resistance, donor heart ischemic times, donor age, donor to recipient weight ratio and creatinine levels. RESULTS: The age range was from 1 to 18 with a mean of 10.6 ± 4.6 years. 67 % patients were in INTERMACS category 3 or less.12 children were on mechanical circulatory support at the time of transplant. The 90 day survival was 89 %. The risk factors for hospital mortality was lower INTERMACS category (odd's ratio 0.2143, P = 0.026), elevated creatinine (odd's ratio 5.42, P = 0.076) and elevated right atrial pressure (odd's ratio 1.19, P = 0.015). Ischemic time, pulmonary vascular resistance (PVR) and PVR index (PVRI) had no effect on 90 day survival. Kaplan Meier estimates for 5 year survival was 73 %. The medium term survival was affected by INTERMACS category (Hazard ratio 0.7, P = .078), donor age > 25 (Hazard ratio 1.6, P = 0.26) and raised serum creatinine values.(Hazard ratio 2.7, P = 0.012). All the survivors are in good functional class. CONCLUSIONS: Excellent outcomes are possible after heart transplantation in a pediatric population even in a resource constrained environment of a developing economy. More efforts are needed to promote pediatric organ donation and patients need to be referred in better INTERMACS category for optimal outcomes.

How do we improve adolescent diet and physical activity in India and sub-Saharan Africa? Findings from the Transforming Adolescent Lives through Nutrition (TALENT) consortium.

OBJECTIVE: Adolescent diet, physical activity and nutritional status are generally known to be sub-optimal. This is an introduction to a special issue of papers devoted to exploring factors affecting diet and physical activity in adolescents, including food insecure and vulnerable groups. SETTING: Eight settings including urban, peri-urban and rural across sites from five different low- and middle-income countries. DESIGN: Focus groups with adolescents and caregivers carried out by trained researchers. RESULTS: Our results show that adolescents, even in poor settings, know about healthy diet and lifestyles. They want to have energy, feel happy, look good and live longer, but their desire for autonomy, a need to 'belong' in their peer group, plus vulnerability to marketing exploiting their aspirations, leads them to make unhealthy choices. They describe significant gender, culture and context-specific barriers. For example, urban adolescents had easy access to energy dense, unhealthy foods bought outside the home, whereas junk foods were only beginning to permeate rural sites. Among adolescents in Indian sites, pressure to excel in exams meant that academic studies were squeezing out physical activity time. CONCLUSIONS: Interventions to improve adolescents' diets and physical activity levels must therefore address structural and environmental issues and influences in their homes and schools, since it is clear that their food and activity choices are the product of an interacting complex of factors. In the next phase of work, the Transforming Adolescent Lives through Nutrition consortium will employ groups of adolescents, caregivers and local stakeholders in each site to develop interventions to improve adolescent nutritional status.

Comparing BMI with skinfolds to estimate age at adiposity rebound and its associations with cardio-metabolic risk markers in adolescence.

BACKGROUND: Body mass index (BMI) reaches a nadir in mid-childhood, known as the adiposity rebound (AR). Earlier AR is associated with a higher risk of cardio-vascular diseases in later life. Skinfolds, which are a more direct measure of adiposity, may give better insight into the relationship between childhood adiposity and later obesity and cardio-metabolic risk. OBJECTIVE: We aimed to assess whether AR corresponds to a rebound in skinfolds, and compare associations of BMI-derived AR and skinfold-derived AR with cardio-metabolic risk markers in adolescence. METHODS: We used penalised splines with random coefficients to estimate BMI and skinfold trajectories of 604 children from the Mysore Parthenon Birth Cohort. Age at AR was identified using differentiation of the BMI and skinfold growth curves between 2 and 10 years of age. At 13.5 years, we measured blood pressure, and glucose, insulin and lipid concentrations. RESULTS: BMI and skinfolds had different growth patterns. Boys reached BMI-derived AR earlier than skinfold-derived AR (estimated difference: 0.41 years; 95% CI:[0.23, 0.56]), whereas the opposite was observed in girls (estimated difference: -0.71 years; 95% CI:[-0.90, -0.54]). At 13.5 years, children with earlier BMI-derived AR had higher BMI (-0.58 SD per SD increase of AR; 95%CI:[-0.65, -0.52]), fat mass (-0.44; 95%CI:[-0.50, -0.37]), insulin resistance (HOMA-IR: -0.20; 95%CI:[-0.28, -0.12]) and systolic blood pressure (-0.20; 95%CI:[-0.28, -0.11]), and lower HDL-cholesterol (0.12; 95%CI:[0.04, 0.21]). The associations were independent of BMI at time of rebound, but were fully explained by fat mass at 13.5 years. Similar associations were found for skinfold-derived AR. CONCLUSION: BMI-derived adiposity rebound predicts later cardio-metabolic risk markers similarly to that derived from skinfolds, a direct measure of adiposity.

Efficacy of a virtual assistance-based lifestyle intervention in reducing risk factors for Type 2 diabetes in young employees in the information technology industry in India: LIMIT, a randomized controlled trial.

AIMS: To investigate a virtual assistance-based lifestyle intervention to reduce risk factors for Type 2 diabetes in young employees in the information technology industry in India. METHODS: LIMIT (Lifestyle Modification in Information Technology) was a parallel-group, partially blinded, randomized controlled trial. Employees in the information technology industry with ≥3 risk factors (family history of cardiometabolic disease, overweight/obesity, high blood pressure, impaired fasting glucose, hypertriglyceridaemia, high LDL cholesterol and low HDL cholesterol) from two industries were randomized to a control or an intervention (1:1) group. After initial lifestyle advice, the intervention group additionally received reinforcement through mobile phone messages (three per week) and e-mails (two per week) for 1 year. The primary outcome was change in prevalence of overweight/obesity, analysed by intention to treat. RESULTS: Of 437 employees screened (mean age 36.2 ± 9.3 years; 74.8% men), 265 (61.0%) were eligible and randomized into control (n=132) or intervention (n=133) group. After 1 year, the prevalence of overweight/obesity reduced by 6.0% in the intervention group and increased by 6.8% in the control group (risk difference 11.2%; 95% CI 1.2-21.1; P=0.042). There were also significant improvements in lifestyle measurements, waist circumference, and total and LDL cholesterol in the intervention group. The number-needed-to-treat to prevent one case of overweight/obesity in 1 year was 9 (95% CI 5-82), with an incremental cost of INR10665 (£112.30) per case treated/prevented. A total of 98% of participants found the intervention acceptable. CONCLUSIONS: A virtual assistance-based lifestyle intervention was effective, cost-effective and acceptable in reducing risk factors for diabetes in young employees in the information technology industry, and is potentially scalable.

Body size and body composition: a comparison of children in India and the UK through infancy and early childhood.

BACKGROUND: Indian babies are characterised by the 'thin-fat phenotype' which comprises a 'muscle-thin but adipose' body composition compared with European babies. This body phenotype is of concern because it is associated with an increased risk of diabetes and cardiovascular disease. We examined whether the 'thin-fat phenotype' persists through early childhood, comparing Indian children with white Caucasians in the UK at birth, infancy and childhood, using comparable measurement protocols. METHODS: We used data from two cohorts, the Pune Maternal Nutrition Study (N=631) and the Southampton Women's Survey (N=2643). Measurements of weight, head circumference, mid-upper arm circumference, height, triceps and subscapular skinfold thickness were compared at birth, 1, 2, 3 and 6 years of age. SD scores were generated for the Pune children, using the Southampton children as a reference. Generalised estimating equations were used to examine the changes in SD scores across the children's ages. RESULTS: The Indian children were smaller at birth in all body measurements than the Southampton children and became relatively even smaller from birth to 2 years, before 'catching up' to some extent at 3 years, and more so by 6 years. The deficit for both skinfolds was markedly less than for other measurements at all ages; triceps skinfold showed the least difference between the two cohorts at birth, and subscapular skinfold at all ages after birth. CONCLUSIONS: The 'thin-fat phenotype' previously found in Indian newborns, remains through infancy and early childhood. Despite being shorter and lighter than UK children, Indian children are relatively adipose.

Protective effects of caffeic acid on lactate dehydrogenase isoenzymes, electrocardiogram, adenosine triphosphatases, and hematology on isoproterenol-induced myocardial infarcted rats.

The present study aims to evaluate the protective effects of caffeic acid on isoproterenol-treated myocardial infarction. Male albino Wistar rats were pretreated with caffeic acid (15 mg/kg) daily for 10 days. After the pretreatment, rats were injected with isoproterenol (100 mg/kg) at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol-treated rats showed increased intensity of lactate dehydrogenase-1 and 2 isoenzyme bands and elevated ST segments. The activity of the heart sodium potassium adenosine triphosphatase was decreased, and the activities of the heart magnesium adenosine triphosphatase and calcium adenosine triphosphatase were increased in isoproterenol-treated rats. Isoproterenol-treated rats also showed a significant increase in the concentration of heart calcium. Furthermore, it significantly increased the counts of red blood cells, hemoglobin, white blood cells, and neutrophils and decreased significantly the concentration of erythrocyte sedimentation rate and the counts of lymphocytes and eosinophils. Pretreatment with caffeic acid showed protective effects on all the biochemical parameters, hematology and minimized alterations in lactate dehydrogenase isoenzymes and electrocardiogram. In vitro study confirmed the free radical scavenging potential of caffeic acid. The observed effects might be due to the free radical scavenging and membrane-stabilizing property of caffeic acid.

Preventive effect of caffeic acid on lysosomal dysfunction in isoproterenol-induced myocardial infarcted rats.

We evaluated the preventive effect of caffeic acid (CA) on lysosomal enzymes in isoproterenol (ISO)-treated myocardial infarcted rats. Male albino Wistar rats were pretreated with CA (15 mg/kg) daily for a period of 10 days. After the pretreatment period, ISO (100 mg/kg) was subcutaneously injected to rats twice at an interval of 24 h. The activity of serum creatine kinase-MB and lactate dehydrogenase was increased significantly (P < 0.05) in ISO-induced myocardial infarcted rats. The levels of plasma thiobarbituric acid reactive substances and lipid hydroperoxides were significantly (P < 0.05) increased, and the level of plasma-reduced glutathione was significantly (P < 0.05) decreased in ISO-induced myocardial infarcted rats. The activities of lysosomal enzymes (beta-glucuronidase, beta-N-acetylglucosaminidase, beta-galactosidase, cathepsin-B and cathepsin-D) were increased significantly (P < 0.05) in the serum and heart of ISO-induced myocardial infarcted rats. ISO induction also resulted in decreased stability of membranes, which was reflected by lowered activities of beta-glucuronidase and cathepsin-D in different fractions except cytosol. Pretreatment with CA (15 mg/kg) to ISO-treated rats significantly (P < 0.05) prevented the changes in the activities of cardiac marker enzymes, the levels of lipid peroxidation products, reduced glutathione and the activities of lysosomal enzymes in the serum, heart, and subcellular fractions. Oral treatment with CA (15 mg/kg) to normal control rats did not show any significant effect. Thus, the results of our study showed that CA prevented the lysosomal membrane damage against ISO-induced myocardial infarction. The observed effects of CA are due to membrane-stabilizing, antilipo peroxidative, and antioxidant effects.

Protective effect of caffeic acid on cardiac markers and lipid peroxide metabolism in cardiotoxic rats: an in vivo and in vitro study.

Myocardial infarction affects a large population in the world. Lipid peroxide metabolism plays an important role in the pathology of myocardial infarction. This study aims to evaluate the preventive effect of caffeic acid on lipid peroxides, antioxidants, cardiac marker enzymes, and histopathological findings in isoproterenol (ISO)-induced myocardial-infarcted male Wistar rats. Myocardial infarction was induced in rats by subcutaneous injection of ISO (100 mg/kg) at an interval of 24 hours for 2 days. The ISO-induced rats showed significant increase in the levels of thiobarbituric acid reactive substances, lipid hydroperoxides in the heart, plasma uric acid, and serum cardiac marker enzymes, and significant decrease in the activities of heart superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and the levels of reduced glutathione, vitamin E, and vitamin C in the plasma and heart. Oral pretreatment with caffeic acid (15 mg/kg) daily for 10 days showed significant decrease in the levels of serum cardiac marker enzymes, heart lipid peroxidation products and plasma uric acid and significant increase in the levels of antioxidant system. Histopathology of myocardium also confirmed the protective effect of caffeic acid in myocardial-infarcted rats. In vitro study on total antioxidant activity (2,2'-azinobis-[3-ethylbenzothiazoline-6-sulfonic acid](+) assay) confirmed the strong antioxidant action of caffeic acid. Thus, the present study revealed that caffeic acid ameliorates cardiac damage in ISO-induced myocardial infarction by maintaining lipid peroxide metabolism due to its free radical scavenging and antioxidant effects. A diet containing caffeic acid may be beneficial to myocardial infarction.

Relationships of maternal and paternal birthweights to features of the metabolic syndrome in adult offspring: an inter-generational study in South India.

AIMS/HYPOTHESIS: The association between lower birthweight and metabolic syndrome may result from fetal undernutrition (fetal programming hypothesis) and/or genes causing both low birthweight and insulin resistance (fetal insulin hypothesis). We studied associations between the birthweight of parents and metabolic syndrome in the offspring. METHODS: We identified men and women (aged 35-68 years), who had been born in Holdsworth Memorial Hospital, Mysore, India. We also identified the offspring (20-46 years) of these men and women. In total, 283 offspring of 193 mothers and 223 offspring of 144 fathers were studied. Investigations included anthropometry, oral glucose tolerance, plasma insulin and lipid concentrations and blood pressure. The metabolic syndrome was defined using WHO criteria. RESULTS: Among the offspring, lower birthweight was associated with an increased risk of glucose intolerance (impaired glucose tolerance, impaired fasting glucose or type 2 diabetes) and higher cholesterol and triacylglycerol concentrations (p < 0.05 for all adjusted for sex and age). Most outcomes in the offspring, including most individual components of the metabolic syndrome, were unrelated to parental birthweight. However, both maternal and paternal birthweight were inversely related to offspring metabolic syndrome (odds ratio [OR] 0.36 [95% CI: 0.13-1.01] per kg, p = 0.053 for mother-offspring pairs; OR 0.26 [0.07-0.93], p = 0.04 for father-offspring pairs, adjusted for offspring age, sex, BMI and socioeconomic status). Maternal birthweight was inversely related to offspring systolic blood pressure (beta = -2.5 mmHg [-5.00 to 0.03] per kg maternal birthweight; p = 0.052). CONCLUSIONS/INTERPRETATION: Factors in both parents may influence the risk of metabolic syndrome in their offspring. There are several possible explanations, but the findings are consistent with the fetal insulin (genetic) hypothesis.

Human protein reference database--2006 update.

Human Protein Reference Database (HPRD) (http://www.hprd.org) was developed to serve as a comprehensive collection of protein features, post-translational modifications (PTMs) and protein-protein interactions. Since the original report, this database has increased to >20 000 proteins entries and has become the largest database for literature-derived protein-protein interactions (>30 000) and PTMs (>8000) for human proteins. We have also introduced several new features in HPRD including: (i) protein isoforms, (ii) enhanced search options, (iii) linking of pathway annotations and (iv) integration of a novel browser, GenProt Viewer (http://www.genprot.org), developed by us that allows integration of genomic and proteomic information. With the continued support and active participation by the biomedical community, we expect HPRD to become a unique source of curated information for the human proteome and spur biomedical discoveries based on integration of genomic, transcriptomic and proteomic data.

Intergenerational effects on size at birth in South India.

Several studies have shown that a baby's birthweight correlates with the birthweight and adult size of both its parents, but more strongly with those of its mother, suggesting that both the 'maternal environment' and inherited genes influence size at birth. There are no previous such intergenerational data from India. Holdsworth Memorial Hospital (HMH), Mysore, South India, has preserved birth records containing the birthweight, length and head circumference of all newborns since 1934. We identified 468 mother-offspring and 341 father-offspring pairs born in the hospital. Daughters and sons (born 1990-95) were heavier at birth than their mothers and fathers, respectively, with a mean (SD) increase in birthweight of 121 g (24 g) between the two generations. The birthweight of both parents predicted offspring birthweight equally (mother: regression slope beta = 255 g/kg; father beta = 251 g/kg; P < 0.001 for both). Paternal birth length had a stronger effect than maternal birth length on offspring birth length. The mother's adult body mass index (BMI) had a greater effect than paternal BMI on offspring birthweight (mother: 18 g/kg/m(2); P < 0.001; father: 15 g/kg/m(2); P = 0.04). In a regression model including data for both parents (available for 57 children) this difference was greater (mother: 46 g/kg/m(2); P < 0.001; father: -10 g/kg/m(2); ns). In contrast, paternal height had stronger effects than maternal height on offspring birth length (mother: 0.8 mm/cm; ns; father: 1.5 mm/cm; P < 0.001). In conclusion, size at birth is influenced by a combination of environmental and genetic factors. Both maternal and paternal birthweight correlate with offspring size at birth. Maternal nutritional status (BMI) influences birthweight. Paternal factors appear to contribute to neonatal skeletal size.

Cortisol and the metabolic syndrome in South Asians.

OBJECTIVE: The cardiovascular risk factors which comprise the metabolic syndrome are associated with increased hypothalamic-pituitary-adrenal axis (HPAA) activity in some Caucasian populations. South Asians have high rates of cardiovascular disease and its risk factors. We have investigated the relationships between HPAA activity, adiposity and the metabolic syndrome in a South Asian population. DESIGN: Cross-sectional cohort study. PARTICIPANTS: A total of 509 men and women born at the Holdsworth Memorial Hospital, Mysore, South India between 1934 and 1954 and still living in the area. MEASUREMENTS: Fasting 09.00 h cortisol and corticosteroid-binding globulin. The cohort had previously been investigated for features of the metabolic syndrome. RESULTS: At 09.00 h, cortisol concentration was strongly associated with systolic and diastolic blood pressure (r = 0.25 and r = 0.24, respectively; P < 0.001), fasting glucose concentration (r = 0.26; P < 0.001), insulin resistance (r = 0.20; P < 0.001) and fasting triglyceride concentration (r = 0.17; P < 0.001). In general, higher cortisol concentrations added to the effect of adiposity in increasing cardiovascular risk factors, but there was evidence of an interaction between cortisol and adiposity in determining fasting glucose concentration (P = 0.045) and insulin resistance (P = 0.006). CONCLUSIONS: Associations between 09.00 h cortisol concentration and cardiovascular risk factors in this South Asian cohort were stronger than those previously shown in Caucasian populations, despite similar mean cortisol concentrations, and were amplified by adiposity. This suggests that increased glucocorticoid action may contribute to ethnic differences in the prevalence of the metabolic syndrome, particularly among men and women with a higher body mass index.

Left ventricular mass and arterial compliance: relation to coronary heart disease and its risk factors in South Indian adults.

BACKGROUND: Rates of coronary heart disease (CHD) in India are rising, and are now similar to those in Western countries. The prevalence of conventional CHD risk factors such as hypercholesterolaemia, hypertension, smoking and obesity, tend to be lower in Indian than Western populations, and fail to explain these high rates of disease. Increased left ventricular (LV) mass and decreased arterial compliance predict a higher risk of CHD in Western populations, but there are no published data from India. We have measured LV mass and arterial compliance, and examined their relation to CHD and other known risk factors, in men and women living in Mysore, South India. METHODS: We examined 435 men and women born in Mysore during 1934-1953. LV mass was measured by echocardiography and arterial compliance (derived from pulse wave velocity, PWV) was measured by a non-invasive optical method in three arterial segments. RESULTS: The mean LV mass was 149 g (S.D. 37) in men and 125 g (S.D. 32) in women. The mean PWV was 4.14 m/s in the aorto-radial, 3.28 m/s in the aorto-femoral and 13.59 m/s in the femoro-popliteal-posterior tibial segments. LV mass and PWV were positively correlated with each other and with systolic and diastolic blood pressures, non-insulin dependant diabetes mellitus, fasting plasma glucose, insulin, proinsulin concentrations and serum triglyceride concentrations (p<0.05 for all), independently of age, sex and body size. In addition, LV mass correlated negatively with fasting serum HDL-cholesterol (p=0.02). Higher LV mass was associated with an increased risk of CHD (p=0.05). CONCLUSIONS: The mean LV mass in this Indian population is low compared with Western populations, though as in the West, increased LV mass is associated with an increased risk of CHD. Greater LV mass and reduced arterial compliance are associated with higher levels of many known CHD risk factors especially with those which form the Insulin Resistance Syndrome.

Blood pressure, arterial compliance, and left ventricular mass: no relation to small size at birth in south Indian adults.

OBJECTIVE: To determine whether reduced fetal growth leads to raised blood pressure, reduced arterial compliance, and increased left ventricular mass in an Indian population. DESIGN: A retrospective cohort study of men and women (age range 40-61 years) whose weight, length, and head circumference at birth were recorded. SETTING: The Holdsworth Memorial Hospital, Mysore, South India. SUBJECTS: 435 men and women born in the hospital between 1934 and 1953. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures; compliance in four arterial segments derived from pulse wave velocity, measured by a non-invasive optical method; and left ventricular mass measured using M mode echocardiography. RESULTS: Small size at birth was not associated with increased adult blood pressure or left ventricular mass, or with reduced arterial compliance. Systolic blood pressure and left ventricular mass were higher in subjects who were greater in length at birth, rising by 1.64 mm Hg (95% confidence interval (CI) -0.08 to +3.37 mm Hg) and 1.63 g/m(2) (95% CI 0.13 to 3.13 g/m(2)), respectively, per one inch (2.5 cm) increase in birth length, independently of adult size. Arterial compliance was reduced in people whose mothers were lighter and had smaller pelvic (external conjugate) diameters. CONCLUSIONS: The higher prevalence of coronary heart disease in Indian men and women of lower birth weight, shown in an earlier study of the same cohort, cannot be explained by changes in blood pressure, arterial compliance, and left ventricular mass. The association of raised blood pressure and left ventricular mass with longer birth length suggests that the way in which the intrauterine environment influences coronary heart disease differs between Indian and Western populations.