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In non-endemic countries, surveillance of non-travel cases of enteric fever is important to identify carriers and reduce secondary transmission. We characterised these cases in England between 2012 and 2021 and assessed potential sources of infection to inform guidance revision. Retrospective case–case. We identified enteric fever cases from the national surveillance dataset. Non-travel cases were defined as no travel to an endemic country or travel but onset of >60 days after return. Multivariable logistic regression was used to identify factors associated with non-travel cases. We reviewed the case records of cases with unknown source of infection. Compared to travel cases, non-travel cases (7%; 225/3075) were older (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.02–1.04), asymptomatic (OR = 9.3: 95% CI: 4.3–20.3), and confirmed with Salmonella typhi infection (OR = 1.74, 95% CI: 1.26–2.4). Non-travel cases had lower odds of being of Indian (OR = 0.27, 95% CI: 0.16–0.45) or Pakistani ethnicity (OR = 0.34, 95% CI: 0.16–0.45) than White British. Surveillance questionnaires identified a possible infection source for 53%: case records review identified a further 23%: 33% secondary transmission, mostly household; 21% had overseas visitors, or travelling family; 12% were carriers (cases with enteric fever in the past), 12% travelled to endemic country outside of the 60-day window, and 22% had other possible sources. Case records differentiated between travel 60–90 days (5%) vs travel years prior to onset (7%), suggesting carrier status. Not all possible carriers were identified through the surveillance questionnaire. Therefore, we recommend additional questions to systematically capture travel history beyond 60 days to assist in classifying carrier status and to updating the source of infection. [ABSTRACT FROM AUTHOR]

Little is known about the patterning of multiple long‐term conditions (MLTCs) by age, ethnicity and across conceptualisations of MLTCs (e.g. MLTCs with/without mental health conditions [MHCs]). We examined ethnic inequalities in age‐related patterns of MLTCs, and combinations of physical and MHCs using the English GP Patient Survey and Clinical Practice Research Datalink. We described the association between MLTCs and age using multilevel regression models adjusting for sex and area‐level deprivation with patients nested within GP practices. Similar analyses were repeated for MLTCs that include MHCs. We observed ethnic inequalities from middle‐age onwards such as older Pakistani, Indian, Black Caribbean and Other ethnic people had increased risk of MLTCs compared to white British people, even after adjusting for area‐level deprivation. Compared to white British people, Gypsy and Irish Travellers had higher levels of MLTCs across the age groups, and Chinese people had lower levels. Pakistani and Bangladeshi people aged 50–74 years were more likely than white people to report MLTCs that included MHCs. We find clear evidence of ethnic inequalities in MLTCs. The lower prevalence of MLTCs that include MHCs among some minoritised ethnic groups may be an underestimation due to underdiagnosis and/or inadequate primary care and requires further scrutiny. [ABSTRACT FROM AUTHOR]

Substantial comorbidity exists between posttraumatic stress disorder and sleep disturbances/disorders. Such comorbidities are understudied in minority groups, including Asian Indians residing in countries outside India. Thus, we synthesized the existing literature specific to this group of Asian Indians to determine (a) prevalence estimates of posttraumatic stress disorder (PTSD) and sleep disturbances/disorders; and (b) PTSD-sleep comorbidity estimates. For this systematic review, we searched four databases (PubMed, PsycInfo, PTSDpubs, Web of Science) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 3,796 screened articles, 9 articles (10 studies) met inclusion criteria. Study sample sizes ranged from 11 to 2,112 Asian Indians; studies were conducted in Singapore or Malaysia. No reviewed study examined PTSD. All studies examined sleep disturbances/disorders among Asian Indians; prevalence estimates were: 8.3% to 70.4% for short sleep duration, 2.0% to 22.9% for long sleep duration, 25.9% to 56.3% for poor sleep quality, 3.4% to 67.5% for insomnia diagnosis or probable insomnia, 7.7% for excessive daytime sleepiness, 3.8% to 54.6% for obstructive sleep apnea (OSA) diagnosis or high OSA risk, and 5.1% to 11.1% for sleep-disordered breathing. Specific to Asian Indians residing in countries outside India, this review advances PTSD-sleep literature by (a) suggesting substantial prevalence of sleep disturbances/disorders; (b) highlighting the need for culturally relevant sleep interventions; and (c) highlighting research gaps (e.g., no PTSD-focused research). [ABSTRACT FROM AUTHOR]

Background: Skin mottling as a clinical perfusion marker in septic shock is significantly associated with severity and outcome in white-skinned population and its validity as a clinical sign in dark-skinned population is not known. The objectives of this study were to evaluate mottling in septic shock in the Indian ethnic population who has different skin color as compared to the white-skinned population and to assess mottling as an outcome predictor with capillary refill time (CRT) and other biochemical parameters which are the established clinical markers of perfusion in septic shock. Materials and methods: We conducted a prospective observational study of patients with skin color categories 21-34 on the von Luschan scale or Fitzprick type IV-VI who had septic shock needing a high dose of norepinephrine ≥0.2 µg/kg/min after fluid optimization. The study was conducted in a mixed medical-surgical ICU over 12 months. Two blinded experts (a Dermatologist and a plastic surgeon) independently classified the skin type, validated the occurrence of mottling, and scored mottling in our patients. We recorded the demographics, hemodynamic variables, and mottling score and observed the incidence of mottling and its correlation with predictors of the severity of septic shock. We also compared CRT, arterial lactate, central venous oxygen saturation, and venoarterial PCO2 gap with occurrence of mottling in septic shock patients. Results: We included 108 patients with age 61 ± 16 years. Mean Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at enrolment were 10.3-21.9, respectively. Incidence of mottling was 20.3% (22/108). CRT >3 seconds was observed in 50.9% (55/108). Development of mottling was significantly associated with 90-day mortality; 20/22 (90.9%) patients died in the mottling group versus 58/86 (65.1%) in the non-mottling group (p = 0.028). Capillary refill time >3 seconds did not corelate with mortality; 40/55 (72.7%) Patients with CRT >3 seconds died versus 32/53 (60.4%) patients died in CRT ≤3 seconds group. Occurrence of mottling could predict mortality; positive predictive value of 90.9% which was comparable to positive predictive value of lactate levels >4 mmol/L, i.e., 94.1%. Conclusion: The incidence of mottling in septic shock is much less in patients of Indian ethnicity with brown skin color than in white-skinned population. Occurrence of mottling and not delayed CRT, is a better predictor of outcome in this setting. [ABSTRACT FROM AUTHOR]

OBJECTIVE: South Asians are diagnosed with type 2 diabetes (T2D) more than a decade earlier in life than seen in European populations. We hypothesized that studying the genomics of age of diagnosis in these populations may give insight into the earlier age diagnosis of T2D among individuals of South Asian descent. RESEARCH DESIGN AND METHODS: We conducted a meta-analysis of genome-wide association studies (GWAS) of age at diagnosis of T2D in 34,001 individuals from four independent cohorts of European and South Asian Indians. RESULTS: We identified two signals near the TCF7L2 and CDKAL1 genes associated with age at the onset of T2D. The strongest genome-wide significant variants at chromosome 10q25.3 in TCF7L2 (rs7903146; P = 2.4 × 10−12, β = −0.436; SE 0.02) and chromosome 6p22.3 in CDKAL1 (rs9368219; P = 2.29 × 10−8; β = −0.053; SE 0.01) were directionally consistent across ethnic groups and present at similar frequencies; however, both loci harbored additional independent signals that were only present in the South Indian cohorts. A genome-wide signal was also obtained at chromosome 10q26.12 in WDR11 (rs3011366; P = 3.255 × 10−8; β = 1.44; SE 0.25), specifically in the South Indian cohorts. Heritability estimates for the age at diagnosis were much stronger in South Indians than Europeans, and a polygenic risk score constructed based on South Indian GWAS explained ∼2% trait variance. CONCLUSIONS: Our findings provide a better understanding of ethnic differences in the age at diagnosis and indicate the potential importance of ethnic differences in the genetic architecture underpinning T2D. [ABSTRACT FROM AUTHOR]

Genome-wide polygenic risk scores (PRS) for lifestyle disorders, like Type 2 Diabetes (T2D), are useful in identifying at-risk individuals early on in life, and to guide them towards healthier lifestyles. The current study was aimed at developing PRS for the Indian population using imputed genotype data from UK Biobank and testing the developed PRS on data from GenomegaDB of Indians living in India. 959 T2D cases and 2,818 controls were selected from Indian participants of UK Biobank to develop the PRS. Summary statistics available for South Asians, from the DIAMANTE consortium, were used to weigh genetic variants. LDpred2 algorithm was used to adjust the effect of linkage disequilibrium among the variants. The association of PRS with T2D, after adjusting for age, sex and top ten genetic principal components, was found to be very significant (AUC = 0.7953, OR = 2.9856 [95% CI: 2.7044–3.2961]). When participants were divided into four PRS quartile groups, the odds of developing T2D increased sequentially with the higher PRS groups. The highest PRS group (top 25%) showed 5.79 fold increased risk compared to the rest of the participants (75%). The PRS derived using the same set of variants was found to be significantly associated with T2D in the test dataset of 445 Indians (AUC = 0.7781, OR = 1.6656 [95%CI = 0.6127–4.5278]). Our study demonstrates a framework to derive Indian-specific PRS for T2D. The accuracy of the derived PRS shows it's potential to be used as a prognostic metric to stratify individuals, and to recommend personalized preventive strategies. [ABSTRACT FROM AUTHOR]

Breast cancer is the third most common cancer in women after skin and lung cancer. Pesticides are of interest in etiologic studies of breast cancer because many pesticides mimic estrogen, a known breast cancer risk factor. In this study, we discerned the toxic role of the pesticides atrazine, dichlorvos, and endosulfan in inducing breast cancer. Various experimental studies, such as biochemical profiling of pesticide-exposed blood samples, comet assays, karyotyping analysis, pesticide and DNA interaction analysis by molecular docking, DNA cleavage, and cell viability assays, have been carried out. Biochemical profiling showed an increased level of blood sugar, WBC, hemoglobin, and blood urea in the patient exposed to pesticides for more than 15 years. The comet assay for DNA damage performed on patients exposed to pesticides and pesticide-treated blood samples revealed more DNA damage at the 50 ng concentration of all three pesticides. Karyotyping analysis showed enlargements in the heterochromatin region and 14pstk+, and 15pstk+in the exposed groups. In molecular docking analysis, atrazine had the highest glide score (− 5.936) and glide energy (− 28.690), which reveals relatively high binding capability with the DNA duplex. The DNA cleavage activity results showed that atrazine caused higher DNA cleavage than the other two pesticides. Cell viability was the lowest at 50 ng/ml (72 h). Statistical analysis performed using SPSS software unveiled a positive correlation (< 0.05) between pesticide exposure and breast cancer. Our findings support attempts to minimize pesticide exposure. [ABSTRACT FROM AUTHOR]

Background & objectives: Screening of individuals for early detection and identification of undiagnosed diabetes can help in reducing the burden of diabetic complications. This study aimed to evaluate the performance of Madras Diabetes Research Foundation (MDRF)-Indian Diabetes Risk Score (IDRS) to screen for undiagnosed type 2 diabetes in a large representative population in India. Methods: Data were acquired from the Indian Council of Medical Research–INdia DIABetes (ICMR–INDIAB) study, a large national survey that included both urban and rural populations from 30 states/union territories in India. Stratified multistage design was followed to obtain a sample of 113,043 individuals (94.2% response rate). MDRF-IDRS used four simple parameters, viz. age, waist circumference, family history of diabetes and physical activity to detect undiagnosed diabetes. Receiver operating characteristic (ROC) with area under the curve (AUC) was used to assess the performance of MDRF-IDRS. Results: We identified that 32.4, 52.7 and 14.9 per cent of the general population were under high-, moderate- and low-risk category of diabetes. Among the newly diagnosed individuals with diabetes [diagnosed by oral glucose tolerance test (OGTT)], 60.2, 35.9 and 3.9 per cent were identified under high-, moderate- and low-risk categories of IDRS. The ROC-AUC for the identification of diabetes was 0.697 (95% confidence interval: 0.684-0.709) for urban population and 0.694 (0.684-0.704) for rural, as well as 0.693 (0.682-0.705) for males and 0.707 (0.697-0.718) for females. MDRF-IDRS performed well when the population were sub-categorized by state or by regions. Interpretation & conclusions: Performance of MDRF-IDRS is evaluated across the nation and is found to be suitable for easy and effective screening of diabetes in Asian Indians. [ABSTRACT FROM AUTHOR]

Background and aims: Hashimoto's thyroiditis (HT) is a commonly observed autoimmune thyroid disease and a frequent cause of hypothyroidism. The nexus between hypothyroidism and the risk of cardiovascular diseases is of current interest globally. Chronic inflammation culminating in endothelial dysfunction is perceived as a link. The association of HT with cardiovascular diseases still needs to be clearly delineated. The inflammatory markers and their association with thyroid autoimmunity in HT patients are attempted herein. Material and methods: Eighty (80) HT patients and an equal number of controls were enrolled in this study. The serum concentration of TSH, FT4, FT3, anti-thyroperoxidase antibodies (Anti-TPO), interleukin-6 (IL-6), interleukin- 10 (IL-10) and high sensitivity - C reactive protein (hs-CRP) were estimated. Results: A significant increase in the levels of IL-6 and hs-CRP in HT patients (p<0.01) was observed as against healthy controls. IL-10 levels significantly declined in HT patients. IL-6 was found to be positively correlated with both TSH and Anti-TPO (p<0.01) among HT subjects. Conclusion: An imbalance of pro- and anti-inflammatory cytokines prevalent in HT could be a valuable tool to assess cardiovascular risk. [ABSTRACT FROM AUTHOR]

Introduction: We present a new diabetes risk score developed and validated in a multi-ethnic population in Guyana, South America. Measurement of in-country diabetes prevalence is a vital epidemiologic tool to combat the pandemic. It is believed that for every person diagnosed with type 2 diabetes there is another undiagnosed. The International Diabetes Federation (IDF) recommends a two-step detection programme using a risk score questionnaire to identify high-risk individuals followed by glycaemic measure. Methods: Data on 798 persons from the 2016 STEPwise Approach to Chronic Disease Risk Factor Surveillance (STEPS) were used to correlate responses to 36 questions with glycated haemoglobin (HbA1C) and fasting plasma glucose (FPG) results. Bootstrapping was used to internally validate the derived seven-variable model. This model with the addition of family history questions was tested in a convenience sample of 659 Guyanese adults and externally validated in a cohort of another 528. Results: An 8-item Guyana Diabetes Risk Score (GDRS) was derived. The final model performed with an area under the curve (AUC) of 0.812 Conclusions: The validated eight-item Guyana Diabetes Risk Score will be extremely useful in identifying individuals at high risk of having diabetes in Caribbean, Black or East Indian populations. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a well-established risk factor for cardiovascular diseases. Although, advances in genome-wide technologies have enabled the discovery of hundreds of genes associated with blood lipid phenotypes, most of the heritability remains unexplained. Here we performed targeted resequencing of 13 bona fide candidate genes of dyslipidemia to identify the underlying biological functions. We sequenced 940 Sikh subjects with extreme serum levels of hypertriglyceridemia (HTG) and 2,355 subjects were used for replication studies; all 3,295 participants were part of the Asian Indians Diabetic Heart Study. Gene-centric analysis revealed burden of variants for increasing HTG risk in GCKR (p = 2.1x10-5), LPL (p = 1.6x10-3) and MLXIPL (p = 1.6x10-2) genes. Of these, three missense and damaging variants within GCKR were further examined for functional consequences in vivo using a transgenic zebrafish model. All three mutations were South Asian population-specific and were largely absent in other multiethnic populations of Exome Aggregation Consortium. We built different transgenic models of human GCKR with and without mutations and analyzed the effects of dietary changes in vivo. Despite the short-term of feeding, profound phenotypic changes were apparent in hepatocyte histology and fat deposition associated with increased expression of GCKR in response to a high fat diet (HFD). Liver histology of the GCKRmut showed severe fatty metamorphosis which correlated with ~7 fold increase in the mRNA expression in the GCKRmut fish even in the absence of a high fat diet. These findings suggest that functionally disruptive GCKR variants not only increase the risk of HTG but may enhance ectopic lipid/fat storage defects in absence of obesity and HFD. To our knowledge, this is the first transgenic zebrafish model of a putative human disease gene built to accurately assess the influence of genetic changes and their phenotypic consequences in vivo. [ABSTRACT FROM AUTHOR]

Background: Down syndrome (DS), also called as trisomy 21, is one of the most leading cause of intellectual disability. DS is associated with a number of phenotypes including Congenital Heart Disease (CHD), Leukemia, Alzheimer's disease, Hirschsprung's disease and others. DS affects about 1 in 700 live births. Objectives: The study aims to investigate the association of MTRR (Methionine synthase reductase) gene polymorphisms (C524T and A66G) with the risk of CHD in DS patients. Methods: PCR and PCR-RFLP methods were used for the genotyping of study samples and results were validated using Sanger's sequencing. Results: MTRR C524T and A66G were significantly associated with the increased risk of CHD in DS. We have also reported two novel polymorphisms, T19775C and 19778_19778delG, in DS with CHD cases with a frequency of 93% and 40%, respectively. These two polymorphisms were not found among DS without CHD group. Conclusion: Results from this study indicate that the MTRR C524T and A66G polymorphisms influence the risk of the occurrence of CHD in DS patients of Indian Origin. This is the first report from India highlighting the potential association of MTRR C524T and A66G polymorphisms with CHD in DS. We are also the first one to report two novel polymorphisms, T19775C and 19778_19778delG in DS with CHD group. Hence these four polymorphisms can be used to evaluate the risk of CHD in DS patients. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on the critical intervention at prediabetes stage to control epidemic among Asian Indians. Topics mentioned include the use of lifestyle intervention and metformin drug in preventing type-2 diabetes (T2DM), the challenge in implementing lifestyle intervention in India which has limited population awareness, and the multiple risk factors in Asian Indians. It also suggested a multi-centric trial on the benefits of metformin.

Purpose: To investigate the role of genetic variations and expression alterations of BRCA1 and BRCA2 genes in the pathophysiology of endometriosis. Methods: A genetic association study was conducted in 573 endometriosis cases and 490 controls of Indian origin. We genotyped 13 selected promoter SNPs of BRCA1 gene and 2 selected promoter SNPs of BRCA2 gene by PCR-sequencing analysis. In addition, to better understand genetic contributions to the pathophysiology of endometriosis, the expression pattern of BRCA1 & 2 was analyzed in the eutopic endometria of endometriosis cases and controls by western-blot and immunohistochemical analysis. Results: Our results revealed significant association between BRCA1 rs71361504 (− /GTT) SNP and endometriosis risk in Indian women ( P < 0.0001), while the remaining SNPs of both BRCA1 & 2 genes showed no difference between cases and controls. Western-blot and immunohistochemical analysis revealed significantly decreased BRCA1 expression levels in eutopic endometria of patients compared with controls ( P < 0.05). Furthermore, nuclear BRCA1 was frequently lost compared with cytoplasmic BRCA1 in eutopic endometria of patients. Expression of BRCA2 did not differ between patients and controls. Conclusions: BRCA1 rs71361504 SNP may modify the endometriosis risk in Indian women. In addition, decreased expression of BRCA1 may play an important role in the pathophysiology of endometriosis. The analysis of BRCA1 genetic variants and/or expression might help to identify patients at high risk for disease outcome. [ABSTRACT FROM AUTHOR]

Background: Enlargement of adipocyte is associated with their dysfunction and alterations in metabolic functions. Objectives: We evaluated the association of adipocyte size of subcutaneous and omental adipose tissue with body composition and cardiovascular risk factors in Asian Indians. Methodology: Eighty (40 males and 40 females) non-diabetic adult subjects undergoing elective abdominal surgery were included. Pre-surgery evaluation included anthropometric measurements, % body fat by bioimpedance, abdominal fat area at L2–3 level (computed tomography) and biochemical investigations (fasting blood glucose and insulin, lipids and hsCRP). During surgery, about 5 grams each of omental and subcutaneous adipose tissue was obtained for adipocyte size determination. Results: Females had higher BMI, % body fat, skinfold thickness, total and subcutaneous abdominal fat area as compared to males. Overweight was present in 42.5% and 67.5%, and abdominal obesity in 5% and 52.5% males and females, respectively. Subcutaneous adipocyte size was significantly higher than omental adipocyte size. Omental adipocyte size correlated more strongly than subcutaneous adipocyte size with measures of adiposity (BMI, waist circumference, %BF), total and subcutaneous abdominal fat area and biochemical measures (fasting glucose, total cholesterol, triglycerides and HOMA-IR), the correlations being stronger in females. The correlation of adipocyte size with metabolic parameters was attenuated after adjusting for measures of adiposity. Conclusion: Omental adipocyte size, though smaller than the subcutaneous adipocyte size, was more closely related to measures of adiposity and metabolic parameters. However, the relationship was not independent of measures of adiposity. [ABSTRACT FROM AUTHOR]

Genetic association studies have linked a number of single nucleotide polymorphisms (SNPs) with unconjugated hyperbilirubinemia. The present study was undertaken to validate the association of SNPs with development of hyperbilirubinemia in Indian neonates. Genotyping of five SNPs in two candidate genes was performed in 126 infants with hyperbilirubinemia and 181 controls by PCR-RFLP, Gene Scan analysis and direct DNA sequencing. Genetic polymorphisms of the UGT1A1 promoter, specifically the -3279 T➔G phenobarbital responsive enhancer module (rs4124874) and (TA)7 dinucleotide repeat (rs8175347) as well as the coding region variants (rs2306283 and rs4149056) of the OATP2 gene were significantly higher among the cases than the controls. The presence of the mutant haplotypes either in homozygous, heterozygous or compound heterozygous state had a significant effect on neonatal hyperbilirubinemia as well as on the requirement of phototherapy than those with the wild haplotype. Further, a significantly higher number of hyperbilirubinemic cases had ≥3 variants than the controls (73.80% vs 40.36%, p<0.0001) and the mean total serum bilirubin levels and requirement of phototherapy also increased according to the number of variants co-expressed. This study demonstrates that UGT1A1 and OATP2 polymorphisms were associated with altered bilirubin metabolism and could be genetic risk factors for neonatal hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Aim: To assess the prevalence and risk factors for diabetic retinopathy (DR) in people with young onset type 1 (T1DM-Y) and type 2 diabetes (T2DM-Y). Methods: T1DM-Y(n = 150) and T2DM-Y(n = 150) participants, age between 10 and 25 years at diagnosis, had a complete clinical evaluation, biochemical assessment, and four field digital retinal colour photography. The Early Treatment Diabetic Retinopathy Study grading system was used to grade DR. Proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) were considered as sight threatening DR. Results: The prevalence of any DR was 53.3% [95% CI 45.3–61.3] in T1DM-Y (duration of diabetes: 12.4 ± 7.4years) and 52.7% [44.7–60.7] in T2DM-Y (11.8 ± 8.3 years). The age and gender adjusted prevalence of DR, DME and PDRwas 62.5%, 10% and 7.3% in T1DM-Y,whereas itwas 65.8%,12.7% and 9.3% in T2DM-Y respectively. In multivariable logistic regression, diabetes duration [Odds ratio (OR) 1.99 per 5 years; CI 1.42–2.79], waist circumference [1.28 per 5 cm;1.05–1.56] and microalbuminuria [2.39 per 50 μg;1.07–5.31]were associatedwith DR in T1DM-Y, and diabetes duration [2.21 per 5 years; 1.61–3.02], diastolic blood pressure [1.54 per 5 mmHg;1.18–2.02], Glycated hemoglobin [1.37 per %;1.07–1.75] and lower stimulated C-peptide [1.54 per 0.5 pmol/ml;1.15–2.05;] were associated with DR in T2DM-Y. Conclusion: Over half of the people with young-onset diabetes, regardless of type, have retinopathy within 10–12 years of diabetes duration, emphasizing the need for regular eye screening and aggressive control of glucose and blood pressure to prevent DR. [ABSTRACT FROM AUTHOR]

Purpose: Cleft lip and palate, the most common developmental deformity seen worldwide, may be either genetic or environmental in origin. Recent research clearly shows the inter-relationship between environmental risk factors and development of oral clefts. The purpose of this study was to determine the prevalence of deft lip and palate in the Nagpur region of India and to evaluate environmental risk factors associated with the occurrence of this orofacial abnormality. Methods: The parents of infants born with or without cleft lip and palate were subjected to guestionnaires that elicited sociodemographic profiles and histories of maternal dietary, medical, and environmental risk factors as well family histories of cleft. A multifactorial comparison of environmental risk factors associated with this deformity was performed. Results: The prevalence of cleft lip and palate and cleft palate was found to be 0.66% and 027%, respectively, in the Nagpur region. The results demonstrated a positive association between cleft lip and palate and the environmental risk factors of nutritional deficiency, anemia, and self-administered medications. Conclusion: Several environmental risk factors appear to play an important role in the development of cleft lip and palate in a Central Indian population of low socioeconomic status. [ABSTRACT FROM AUTHOR]

Purpose: To describe the prevalence of and risk factors for diabetic retinopathy (DR) in Indian persons living in a newly urbanized society in Asia. Design: Population-based study. Participants: Ethnic Indians aged ≥40 years living in Singapore. Methods: The Singapore Indian Eye Study was conducted between 2007 and 2009. All participants underwent an extensive ophthalmic examination, including retinal photographs obtained after pupil dilation. These images were graded for the presence and severity of DR using the modified Airlie House classification system. Diabetes was defined as hemoglobin A1c level of ≥6.5%, use of diabetic medication, or a physician diagnosis of diabetes. Risk factors were measured using questionnaires, clinical assessments, or laboratory tests. Main Outcome Measures: Any DR, diabetic macular edema (DME), or vision-threatening DR (VTDR). Results: Among the 3400 participants, the age-standardized prevalence was 33.6% (95% confidence interval [CI], 31.4–35.8) for diabetes and 10.5% (95% CI, 9.3–11.8) for DR. Among those with diabetes only, the age-standardized prevalence was 30.4% (95% CI, 26.5–34.8) for any DR, 7.2% (95% CI, 5.3–9.7) for DME, and 7.1% (95% CI, 5.4–9.5) for VTDR. In multivariate analysis, independent risk factors for any DR were younger age (odds ratio [OR], 0.98; 95% CI, 0.96–1.00, per year increase), longer diabetes duration (OR, 1.09; 95% CI, 1.07–1.11 per year increase), higher hemoglobin A1c (OR, 1.23; 95% CI, 1.13–1.34 per percent increase), higher systolic blood pressure (OR, 1.01; 95% CI, 1.00–1.02 per 1-mmHg increase), lower diastolic blood pressure (OR, 0.97; 95% CI, 0.96–0.99 per 1-mmHg increase), history of previous stroke (OR, 2.16; 95% CI, 1.12–4.16), and insulin treatment (OR, 2.99; 95% CI, 1.84–4.87). Similar independent risk factors, except for blood pressure, were found for VTDR. Additionally, persons with lower income and living in smaller houses were associated with VTDR. Conclusions: One in 3 migrant Indians living in newly urbanized Asian societies have diabetes and 1 in 10 has DR. This is similar to rates reported in Western populations and significantly higher than those reported in India. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. [Copyright &y& Elsevier]

Most humans lack a functional CASP12 gene, with the nonfunctional variant ( CASP12p1), found in 100% of the Caucasian and east Asian population, and in approximately 80% of people of African descent. However, 20% of Africans carry an intact allele of CASP12, which produces a full-length pro-enzyme and increases the risk of sepsis. We examined CASP12 allele distribution in persons from central and southern Asia and found that CASP12 was significantly present in members of the Dravidian language group, particularly in persons from the Indian state of Tamil Nadu. [ABSTRACT FROM AUTHOR]

Background/Objectives:Non-alcoholic fatty liver disease (NAFLD) is considered an integral part of metabolic syndrome (MS). We aimed to explore the inter-relations of MS and dietary composition in subjects with and without hepatic steatosis and to identify the nutritional risk factors contributing to NAFLD.Subjects/Methods:In all 98 subjects with steatosis and 102 controls were selected for the study after screening 260 consecutive healthy individuals. Anthropometric and nutritional information, biochemical data and clinical profile were analyzed. Prevalence of MS was determined based on the consensus statement for diagnosis of MS for Asian Indians. Multiple logistic regression analysis was done to predict the dietary risk factors in NAFLD.Results:Prevalence of MS was 44.9% among NAFLD cases and 25.5% among controls (P=0.003). Subjects with NAFLD had significantly higher values of body mass index (BMI), waist circumference (WC), percent body fat, total cholesterol, triglycerides and blood pressure than controls. The total calorie intake, percent of carbohydrate and fat intake of NAFLD cases was significantly higher than controls. Multiple logistic regression analysis showed BMI (odds ratio 6.03 (95% confidence interval 3.26-11.14)), WC (5.49 (2.59-11.57)) and percent dietary fat intake (2.51 (1.99-3.31)) as independent nutritional risk factors in NAFLD.Conclusions:In this study, there is a high prevalence of MS among subjects with steatosis and metabolic disorders were closely related to NAFLD. BMI, WC and percent fat intake are independent dietary risk factors in NAFLD. Decreased nutritional intake with restricted fat may constitute an important therapy in subjects with NAFLD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Syndrome Z is defined as the co-occurrence of obstructive sleep apnea (OSA) and metabolic syndrome. There is a paucity of information on the magnitude of syndrome Z in the community and the factors associated with it. Methods: We conducted a two-stage, cross-sectional, community-based study in four different socioeconomic zones of the South Delhi district, India, from April 2005 through June 2007. In stage 1, a systematic random sample of subjects of either gender aged 30–65years were administered a questionnaire by door-to-door survey. Subjects that responded were classified as habitual and non-habitual snorers. In stage 2, all the habitual and 10% of randomly selected non-habitual snorers were invited for overnight polysomnography and evaluation for metabolic syndrome. The National Cholesterol Education Program–Adult Treatment Panel III (NCEP–ATPIII) criteria were used to define metabolic syndrome. Results: Of the 2860 subjects approached, 2505 (88%) completed stage 1; 452 (18%) were habitual snorers. In stage 2, OSA (defined as apnea–hypopnea index ⩾5) was observed in 94 (32.4%) of 290 habitual snorers and 3 (4%) of 75 non-habitual snorers. Seventy (77%) of the 91 habitual snorers with OSA also had metabolic syndrome; none of the non-habitual snorers with OSA had metabolic syndrome. The estimated population prevalence of metabolic syndrome was 43% [95% CI: (41.0–44.9%)] and syndrome Z was 4.5% (95% CI: 3.7–5.3). On multivariable analysis, age [OR: 1.05 (1.00–1.09)], male gender [OR: 5.64 (2.06–15.49)], percent body fat [OR: 1.08 (1.04–1.13)] and ΔSaO2 (%) (defined as the difference between baseline and minimum SaO2 during overnight sleep study) [OR: 5.80 (2.36–14.26), 17.70 (5.97–52.17) and 57.1 (19.12–170.40) for 10–20%, 20–30% and >30% reduction respectively as compared to <10% reduction] were independently associated with syndrome Z. Conclusions: To the best of our knowledge, this is the first population-based study on the prevalence and risk factors of syndrome Z, and it reveals that a considerable proportion of community-dwelling northern Indian adults have syndrome Z. Age, male gender, percent body fat and severity of nocturnal desaturation were independent risk factors for syndrome Z. [Copyright &y& Elsevier]

Background & objectives: The objective of the study was to determine whether visceral or subcutaneous component of abdominal fat was associated with insulin resistance and metabolic syndrome in non-diabetic Asian Indians. Method: This cross-sectional study had on 120 individuals with normal glucose tolerance (49 males and 71 females). A single slice CT scan at L4- L5 was done for measurement of visceral and subcutaneous abdominal fat. Metabolic syndrome was defined according to the South Asian Modified National Cholesterol Education Program Adult Treatment Panel III criteria (SAM-NCEP) criteria. Insulin Sensitivity Index (ISI-Matsuda) was used to assess insulin sensitivity/resistance. Results: Linear regression analysis revealed that visceral, but not subcutaneous fat was associated with serum triglycerides (R²=0.457, β= 0.34; P=0.006), HDL cholesterol (R²=0.430, β= -0.051; P=0.018) and ISI-Mutsuda (R²=0.437, β= -0.05; P=0.039) after adjusting for age, gender and BMI. Visceral fat showed significant association with metabolic syndrome (OR: 1.013, 95% CI: 1.001- 1.025; P=0.041) even after adjusting for age, gender, body mass index and glycated haemoglobin whereas subcutaneous fat did not show such an association. Interpretation & conclusions: These results indicate that in non-diabetic Asian Indians, visceral, but not subcutaneous component of abdominal fat is associated with insulin resistance, cardiovascular risk factors and metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background:The relationship between plasma leptin and insulin resistance among coronary artery disease (CAD) subjects remains poorly understood. We determined plasma leptin levels in insulin-resistant and insulin-nonresistant CAD patients. We also examined the association of plasma leptin with several cardiometabolic risk factors in all of the study group subjects from an Asian Indian population.Methods:We evaluated 130 subjects among the Asian Indian population. Out of these, 65 were CAD subjects and 65 were age- and sex-matched, healthy, non-CAD controls. Fasting plasma levels of leptin, insulin, glucose, homocysteine, fibrinogen, and lipid parameters were estimated for all the subjects. Body mass index (BMI) and waist circumference (WC) were also determined.Results:We observed raised levels of leptin as well as homocysteine, BMI, and WC among the insulin-resistant CAD subjects compared to the insulin-nonresistant CAD subjects. Similarly, a significant elevation in plasma leptin, homocysteine, BMI, and WC was observed among the insulin-resistant controls compared to the insulin-nonresistant controls. Plasma leptin in CAD patients was correlated significantly with overall and abdominal obesity, insulin resistance, and insulin levels. However, it was nonsignificantly correlated with plasma homocysteine, fibrinogen, mean arterial pressure, and dyslipidemia in CAD subjects. On multiple regression analysis, we observed that raised plasma leptin in CAD was significantly associated with insulin resistance independent of obesity.Conclusions:Our data showed a signifcant association of plasma leptin levels with insulin resistance in CAD that was independent of obesity. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a common public health issue of pregnancy and women who have had GDM are at high risk for developing of diabetes mellitus Type-2. The aim of this study was to find the association between various clinical and biochemical parameters and GDM. One hundred and six consecutive patients who attended the out patient unit of department of gynecology, Kottayam Medical College, were enrolled in the study and followed up through the whole antenatal, intra-partum and post-partum periods to identify the obstetric outcome. We found that the prevalence of GDM was seven times higher in those with higher waist-hip ratio (WHR > 0.85) compared with those having a lower WHR (p < 0.001).Those with higher WHR gained more weight than other group (10.6 kg vs. 8.1 kg; p < 0.001). Obesity (BMI ≥23) and higher WHR were associated with increased risk of gestational diabetes (BMI ≥23: OR = 7.5, CI 95% = (1.61-34.31), p = 0.013; WHR > 0.85: OR = 12.05, CI 95% = (1.82-77.43), p = 0.007). We found that a WHR of 0.849 has the optimal sensitivity and specificity for the prediction of GDM. A waist circumference of 85.5 cm (with sensitivity of 75%, specificity 81.4%) and a BMI of 24.3 kg/m2 (sensitivity 75%, specificity 86.5%) had the best predictive value. In conclusion, we found that maternal obesity has a strong correlation with obstetric complications. We found WHR is more important risk determinant for GDM in overweight/obese women than women with normal weight/lean. [ABSTRACT FROM AUTHOR]

Summary: Objectives: India has the largest burden of diabetes in the world, much of which remains undiagnosed. This study aimed to develop a risk score to predict the likelihood of having undetected diabetes in individuals, based on identification of non-invasive risk factors for Type 2 diabetes. Methodology: The risk score was developed in urban and rural participants, aged 35–64 years, from a representative cross-sectional population survey conducted in Delhi in 1991–1994. Multivariable logistic regression model coefficients were used to assign each categorical risk factor a score value with undiagnosed diabetes as the dependent variable. The validity of the composite risk score was tested in an independent multi-centre cross-sectional survey conducted in 2001–2003 in a different population. Results: Complete baseline data were available for 4044 men and women in the first population, of whom, 440 had diabetes (199 cases undiagnosed). Age, waist circumference, blood pressure and family history of diabetes were significant (p <0.01) non-invasive predictors of diabetes status in the multivariable model. The risk of having diabetes increased progressively as the risk score rose from 0 to 29. When tested in the independent population (n =10566, of whom 1066 had diabetes and 375 were undiagnosed), a score value >16 predicted diabetes status with a sensitivity of 0.79 (95% CI:0.77–0.82), specificity of 0.56 (95% CI:0.55–0.57), and a positive likelihood ratio of 1.8 (95% CI:1.7–1.9) for all cases with diabetes, and a sensitivity of 73%, specificity of 56% and a positive likelihood ratio of 1.6 (95% CI: 1.5–1.7) for undiagnosed diabetes cases. Conclusion: Application of this risk score identified a substantial proportion of individuals with undiagnosed diabetes, using tools easily available in low-resource settings. [Copyright &y& Elsevier]

Background: The APOA1-C3-A5 gene cluster plays an important role in the regulation of lipids. Asian Indians have an increased tendency for abnormal lipid levels and high risk of Coronary Artery Disease (CAD). Therefore, the present study aimed to elucidate the relationship of four single nucleotide polymorphisms (SNPs) in the Apo11q cluster, namely the -75G>A, +83C>T SNPs in the APOA1 gene, the Sac1 SNP in the APOC3 gene and the S19W variant in the APOA5 gene to plasma lipids and CAD in 190 affected sibling pairs (ASPs) belonging to Asian Indian families with a strong CAD history. Methods & results: Genotyping and lipid assays were carried out using standard protocols. Plasma lipids showed a strong heritability (h² 48% - 70%; P < 0.0001). A subset of 77 ASPs with positive sign of Logarithm of Odds (LOD) score showed significant linkage to CAD trait by multipoint analysis (LOD score 7.42, P < 0.001) and to Sac1 (LOD score 4.49) and -75G>A (LOD score 2.77) SNPs by single-point analysis (P < 0.001). There was significant proportion of mean allele sharing (pi) for the Sac1 (pi 0.59), -75G>A (pi 0.56) and +83C>T (pi 0.52) (P < 0.001) SNPs, respectively. QTL analysis showed suggestive evidence of linkage of the Sac1 SNP to Total Cholesterol (TC), High Density Lipoprotein-cholesterol (HDL-C) and Apolipoprotein B (ApoB) with LOD scores of 1.42, 1.72 and 1.19, respectively (P < 0.01). The Sac1 and -75G>A SNPs along with hypertension showed maximized correlations with TC, TG and Apo B by association analysis. Conclusion: The APOC3-Sac1 SNP is an important genetic variant that is associated with CAD through its interaction with plasma lipids and other standard risk factors among Asian Indians. [ABSTRACT FROM AUTHOR]

Purpose: To compare the prevalence and severity of dry eye in patients with rheumatoid arthritis (RA) with that in age- and sex-matched controls in the Indian population. Methods: A cross-sectional study was performed on 84 randomly selected eyes of 84 adult patients with well-documented rheumatoid arthritis and 84 eyes of 84 age- and sex-matched controls in the Department of Ophthalmology, Seth G.S. Medical College and K.E.M. Hospital. McMonnie's dry eye questionnaire was used to classify the patients on the basis of their symptoms. Dry eye was diagnosed if the wetting on Schirmer filter paper test was ≤5 mm at 5 minutes and the tear film breakup time was < 10 seconds on slit-lamp examination after fluorescein staining. Results: Twenty three patients (27.3%) with rheumatoid arthritis had dry eyes based on the Schirmer test as compared to 10 (12%) age- and sex-matched controls; 19 (22.62%) patients with RA had a tear film breakup time of < 10 sec. on slit-lamp examination, compared to 8 (9.52%) patients without RA. The difference in the mean wetting (p = 0.003) and mean tear film breakup time (p < 0.001) between RA and non-RA patients was statistically significant. Ocular symptoms had a limited correlation with the results of these tests. Conclusions: Patients with RA in the Indian population have a significantly higher prevalence and severity of dry eye when compared to age- and sex-matched controls. *This research study was approved by the Committee on Human Research, Seth G.S. Medical College and KEM Hospital. [ABSTRACT FROM AUTHOR]

Abstract: Objective:: Simple risk scores for identifying people with undiagnosed diabetes have been developed, mostly in Caucasian groups. This may not be suitable for Asian Indians, therefore this study was undertaken to develop and validate a simple diabetes risk score in an urban Asian Indian population with a high prevalence of diabetes. We also tested whether this score was applicable to South Asian migrants living in a different cultural context. Research design and methods:: A population based Cohort of 10,003 participants aged ≥20 years was divided into two equal halves (Cohorts 1 and 2), after excluding people with known diabetes. Cohort 1 (n =4993) was used to derive the risk score. Validation of the score was performed in the other half of the survey population (Cohort 2) (n =5010). The validation was also done in a separate survey population in Chennai, India (Cohort 3) (n =2002) (diagnosis of diabetes was based on OGTT) and in the South Asian Cohort of the 1999 Health Survey for England (n =676) (fasting glucose value≥7mmol/l and HbA1c≥6.5% were used for diagnosis). A logistic regression model was used to compute the β coefficients for risk factors. The risk score value was derived from a receiver operating characteristic curve. Results:: The significant risk factors included in the risk score were age, BMI, waist circumference, family history of diabetes and sedentary physical activity. A risk score value of >21 gave a sensitivity, specificity, positive predictive value and negative predictive value of 76.6%, 59.9%, 9.4% and 97.9% in Cohort 1, 72.4%, 59%, 8.3% and 97.6% in Cohort 2 and 73.7%, 61.0%, 12.2% and 96.9% in Cohort 3, respectively. The higher distribution of risk factors in the UK Cohort means that at the same cut point the score was much more sensitive but also less specific. (sensitivity 92.2%, specificity 25.7%, positive predictive value of 21.6% and negative predictive value of 93.7%). Conclusions:: A diabetes risk score involving simple non-biochemical measurements was developed and validated in a native Asian Indian population. This easily applicable simple score could play an important role as the first step in the process of identifying individuals with an increased likelihood of having prevalent but undiagnosed diabetes. The different distribution of risk factors with the migrant Asian Indians living in England and the different relationship between sensitivity and specificity for the same score demonstrate that risk scores and cut-points developed and tested even within one ethnic group cannot be generalized to individuals of the same ethnic group living in a different cultural setting where the distribution of risk factors for diabetes is different. [Copyright &y& Elsevier]

Individuals of Asian Indian descent have significantly higher cardiovascular event rates as compared with other ethnic groups. The authors investigated the prevalence of metabolic disorders linked to coronary artery disease in an Asian Indian male population compared with non-Asian Indian males. Standard lipid measurements did not discriminate between groups, and the Asian Indian group exhibited less of the high coronary artery disease risk small low-density lipoprotein trait. Despite less of the small low-density lipo- protein trait in the Asian Indian group and no difference in high-density lipoprotein cholesterol, the Asian Indian group had a significantly higher prevalence (p< 0.0002) of low high-density lipo- protein 2b, implying impaired reverse cholesterol transport. This observation remained significant in the subgroup of patients with high-density lipo- protein cholesterol over 40 mg/dL, a region felt not to reflect impaired reverse cholesterol transport. Low high-density lipoprotein 2 b combined with the higher lipoprotein (a) in the Asian Indian group may help explain the high prevalence of coronary artery disease in this ethnic population. [ABSTRACT FROM AUTHOR]

Whether the traditional definition of small for gestational age (SGA) is an appropriate marker of risk for populations that have relatively lower birthweight is unclear. We determined proportions of White and Asian Indian SGA infants and those admitted to the special care nursery. Compared with White infants, Asian Indian infants were more likely to be SGA (14.5% versus 2.7%) and more likely to be admitted to the special care nursery (20.7% versus 3.7%), suggesting that traditional definitions of SGA may be applicable as a marker of risk. (Am J Public Health. 2010;100:820-822. doi:10.2105/AJPH.2009.165001) [ABSTRACT FROM AUTHOR]

This study examined the association of Asian Indians, Chinese and non-Hispanic Whites (NHWs) to multimorbidity. Conclusions Asian Indians and Chinese were associated with a lower prevalence of multimorbidity compared to NHWs after controlling for age, sex, and other risk factors. Although overall multimorbidity rates were lower, Asian Indians and Chinese were more likely to have high-cholesterol and hypertension, risk factors to heart disease and diabetes. [Extracted from the article]

Repeat expansions in the chromosome 9 open reading frame 72 ( C9orf72 ) gene have been recognized as a major contributor to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in the Caucasian population. Intermediate length repeat expansions of CAG (polyQ) repeat in the ATXN2 gene have also been reported to increase the risk of developing ALS in North America and Europe. We screened 131 ALS patients and 127 healthy controls from India for C9orf72 and ATXN2 repeat expansions. We found pathogenic hexanucleotide expansions in 3 of the 127 sporadic ALS patients, in 1 of the 4 familial ALS patients, and in none of the healthy controls. In addition, our findings suggest that the 10 base-pair deletion that masks detection of C9orf72 repeat expansion does not explain the low frequency of this repeat expansion among Indian ALS patients. Intermediate length polyQ expansions (27Qs–32Qs) in the ATXN2 gene were detected in 6 of the 127 sporadic ALS patients and 2 of the 127 of the healthy controls. Long ATXN2 polyQ repeats (≥33Qs) were not present in any of the ALS patients or controls. Our findings highlight the need for large-scale multicenter studies on Indian ALS patients to better understand the underlying genetic causes. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the prevalence of, and risk factors for, diabetic neuropathy among Asian Indian type 2 diabetic subjects. Subjects were recruited from CURES, a population-based study conducted on a representative population of Chennai city in south India. Of the 1529 known diabetic [KD] subjects, 1382 participated in the study [response rate: 90.4%]; in addition, 354 newly detected diabetic [NDD] subjects were also randomly selected. Neuropathy was diagnosed if the vibratory perception threshold of the right great toe measured by biothesiometry (Biomedical Instrument Co., Newbury, Ohio, USA) was ≥25. Of the total of 1736 individuals, biothesiometry studies were performed in 1632 subjects (94.0% response rate). The overall prevalence of neuropathy was 11% [age-standardized-5.8%], while it was 12.2% [age-standardized-6.5%] and 10% [age-standardized-5.2%] in male and female subjects respectively. The prevalence of neuropathy was significantly higher among KD subjects compared to NDD subjects [12.1% vs 6.8%, p=0.006]. It was also higher among subjects with diabetic retinopathy [26.9% vs 16.9%, p=0.001] and proteinuria [9.6% vs 5.3%, p=0.019] compared to those without. There was a linear increase in the prevalence of neuropathy with increasing age among both genders [p<0.0001]. The odds ratio (OR) for neuropathy in subjects having duration of diabetes >15 years was 5.51 [95% confidence interval (CI): 3.04-10.01, p<0.0001]. Multivariate logistic regression analysis showed age [OR: 1.16, 95% CI: 1.13-1.19, p<0.001], height [OR: 1.04, 95% CI: 1.01 -1.07, p=0.016] and fasting plasma glucose [OR: 1.00, 95% CI: 1.00 -1.01, p=0.001] to be significantly associated with neuropathy. Duration of diabetes showed an association with neuropathy but significance was lost when age was introduced into the model. This is the first population-based data on prevalence of diabetic neuropathy from India, which has the largest number of diabetic patients in the world. [ABSTRACT FROM AUTHOR]