Molecular characterization of Mumps virus genotype C detected from Dibrugarh district of Assam, India.

Background & objectives Mumps, a contagious disease caused by the mumps virus (MuV) involves parotid gland inflammation, with potential complications affecting organs other than the parotid glands and central nervous system. Despite successful vaccination, a resurgence of mumps occurred, raising concerns about vaccine effectiveness. This study aimed to examine the entire genome of a representative MuV genotype C from Dibrugarh, Assam, and compare it with references to detect genetic variations in the circulating strain. Methods Representative MuV genotype C from our published study was subjected to whole genome sequencing. MuV genome was analyzed against the reference genome and vaccine strains before being subjected to mutational profiling, N-glycosylation site determination, and phylogenetic analysis. The Immune Epitope Database was used for epitope screening, and selected epitopes were mapped against Assam MuV for conservancy studies. Results Mutational analysis of Assam MuV with WHO (World health Organization) reference, vaccine strains Jeryl Lynn (Genotype A), and L Zagreb (Genotype N) showed variations in seven genes. Phylogenetic analysis established Assam MuV as genotype C. Epitope conservancy analysis highlighted subtle variations in experimentally determined T-cell epitopes for HN and F proteins, emphasizing overall epitope stability. Interpretation & conclusions Genome sequencing has evolved into a standard and potent method for investigating and recording circulating MuV as it provides information on surveillance, mutation analysis, and transmission dynamics. Despite mumps' global effect, genomic studies are limited, particularly in north-east. Our study provides first comprehensive whole-genome report on circulating MuV genotype C in Assam. This research contributes vital genomic data, filling gaps in MuV genetic epidemiology, supporting global research, and assessing vaccine effectiveness.

Co-circulation of two Mumps virus genotypes in Assam, India.

Mumps is a vaccine-preventable disease, and research on the vaccine's efficacy has recently indicated declining efficacy that has failed to protect against primary infections or reinfections, leading to a global resurgence in nations that use mumps vaccine in their national immunization programmes (NIPs). Lack of reports on its infection, documentation and published studies prevents it from being recognized as a public health issue in India. The waning of immunity is ascribed to the changes between the circulating and vaccine strains. The goal of the current study was to describe the circulating MuV strains in the Dibrugarh district of Assam, India, from 2016 to 2019. Blood samples were examined for IgM antibodies, and throat swab samples were put through Taqman assay for molecular detection. The small hydrophobic (SH) gene was targeted for genotyping through sequencing, and its genetic variations and phylogenetic analysis were carried out. Mumps RNA was found in 42 cases, and Mumps IgM in 14, of which 60% (25/42) of the cases were male and 40% (17/42) were female mostly affecting children between the ages of 6 and 12. Sequence and phylogeny analyses of SH gene revealed Genotypes C (83%) and G (17%) were simultaneously circulating during the study period. The study offers crucial genetic baseline information for the creation of Mumps prevention and control measures. Therefore, based on the research, it is clear that developing an effective vaccination strategy should take into account all currently prevalent genotypes in order to provide better protection against the disease's comeback.

Cohort profile of the largest health & demographic surveillance system (Dibrugarh-HDSS) from North-East India.

Dibrugarh Health and Demographic Surveillance System (Dibrugarh-HDSS), was started in the year 2019 with the objective to create the health and demographic database of a population from a defined geographical area and a surveillance system for providing technical assistance for the implementation of programmes and formulating intervention strategies for reducing disease morbidities and mortalities in the population. Dibrugarh-HDSS adopted a panel design and covered 60 contiguous villages and 20 tea gardens. Line listing of all the households was conducted and a unique identification number detailing State, district, village/tea garden and serial number was provided along with geotagging. Detailed sociodemographic variables, anthropometric measurements (subjects ≥five years) and blood pressure data (subjects ≥18 yr), disease morbidity and mortality were collected. All data were collected in pre-designed and pre-tested questionnaires using a mobile application package developed for this purpose. Dibrugarh-HDSS included a total of 106,769 individuals (rural: 46,762, tea garden: 60,007) with 52,934 males (49.6%) and 53,835 females (50.4%). The number of females per thousand males were significantly higher (1042 in tea garden vs. 985 in rural populations) in the tea-garden community as compared to the village population. More than one-third (35.1%) of tea populations were illiterate compared to the rural population (17.1%). Villagers had significantly higher body mass index than the tea-garden community. The overall prevalence of hypertension (adjusted for age) was 29.4 vs. 28.2 per cent, respectively, for the village and tea-garden population. For both these communities, males (village=30.8%, tea garden=31.1%) showed a higher prevalence of hypertension (adjusted for age) than females (village=28.2%, tea garden=25.8%). The findings of the present study give an insight into the profile of the native rural and tea-garden populations that will help to identify risk factors of different health problems, review the effectiveness of different ongoing programmes, implement intervention strategies for reducing morbidity and mortality and assist the State health authorities in prioritizing their resource allocation and implementation strategies.

Pre-therapeutic Biomarkers for Ranibizumab Therapy among Type 2 Diabetic Patients with Diabetic Macular Edema.

SIGNIFICANCE: A differential outcome in randomized controlled trials of anti-vascular endothelial growth factor (anti-VEGF) therapy, including ranibizumab, for diabetic macular edema is a major dilemma for planning, optimizing, and managing clinical usage. The variable outcome of the therapeutics necessitates the importance of finding a predictive biomarker for anti-VEGF therapy to improve subject selection. PURPOSE: Our study correlates the baseline pro- and anti-VEGF isoforms and its three receptors (VEGFReceptor1, VEGFReceptor2, and VEGFReceptor3) for circulatory candidate protein molecules among diabetic patients with macular edema, with the clinical outcome of ranibizumab therapy. METHODS: This study included 86 individuals who were anti-VEGF naive at the time of ascertainment but have completed the standardized therapy regimen of the clinic. Plasma proteins for pro- and anti-VEGF isoforms and its three receptors were determined in replicate by an enzyme-linked immunosorbent assay. RESULTS: The study demonstrated that 56 (65.12%) individuals benefited from the therapy in terms of letter gain (Snellen chart). Baseline plasma soluble VEGF receptor 2 (sVEGFR-2) was significantly higher among responders (65.10 pg/mL; 95% confidence interval, 55.41 to 74.80 pg/mL) compared with nonresponders (46.38 pg/mL; 95% confidence interval, 38.69 to 54.07 pg/mL; PFDR = .03). Diffuse diabetic macular edema with proliferative diabetic retinopathy increases the risk of nonresponse to the therapy by 3.03-fold (PFDR = .04). CONCLUSIONS: The present study postulates that diffuse diabetic macular edema with proliferative diabetic retinopathy and baseline circulatory soluble VEGF receptor 2 may be potential candidates as therapy-stratifying markers for ranibizumab treatment among patients with diabetic macular edema.

Salt-sensitive phenotypes: A community-based exploratory study from northeastern India.

Background: Salt sensitivity is known to increase the risk of cardiovascular diseases in both normotensive and hypertensive subjects. The population in the northeastern region of India consumes excess dietary salt but their saltsensitive phenotype is not known. Methods: We did a community-based exploratory study using volunteers in the northeastern region of India to determine salt-sensitive (SS) and salt-resistant (SR) phenotypes. A total of 374 (206 normotensive and 168 hypertensive) subjects who gave informed consent were stabilized for salt with 7 days of a low-salt (2.9 g/day) diet followed by 7 days of a high-salt (15.2 g/day) diet. SS was defined as an increase of mean arterial blood pressure ≥9 mmHg after a high-salt diet. Results: We noted an increase in systolic blood pressure of 9.3 mmHg in normotensive subjects and 10.7 mmHg in hypertensive subjects, with a modest effect on diastolic blood pressure (6.9 mmHg in normotensive and 8.2 mmHg in hypertensive subjects) after a high-salt diet. Salt-sensitive phenotype was present in 40.8% of normotensive and 47.6% of hypertensive subjects. Resistance to introduction of high salt was observed in 43.7% of normotensive and 33.9% of hypertensive subjects. Consumption of extra salt (adjusted OR 1.99, 95% CI 1.25-3.18) was independently associated with salt sensitivity. Conclusion: Salt sensitivity was found in a large proportion of normotensive and hypertensive subjects. Restriction of salt intake could be an effective intervention to control hypertension among salt-sensitive subjects.

Renin-Angiotensin System Gene Polymorphisms and Hypertension.

Hypertension has emerged as a major public health problem in developing countries including India. Hypertension, a major cardiovascular risk factor is recognized as a multi-factorial trait resulting from the interaction of various environmental and genetic factors. The genetic contribution is speculated to make 30% to 40% of the variation in blood pressure. Identification of variant genes that contribute to the development of hypertension is further complicated because the cardiac output and peripheral resistance, are controlled by other intermediary phenotypes. Sodium has been postulated as the major intermediary in blood pressure regulation. Therefore, polymorphisms of candidate genes encoding proteins influencing renal tubular sodium transport, either directly or indirectly through effects on intra-renal hemodynamics, have been associated with differences in blood pressure level. Considering the importance of genetics on hypertension and the diversity of the related genes, evaluation of these genes and the study of new genes are necessary. It is hoped that by deducting related genes for essential hypertension in individual, will help in prevention of potential patients. We will be able to diagnose those at risk and develop new treatments for these patients.

Pro- and antiangiogenic VEGF and its receptor status for the severity of diabetic retinopathy.

PURPOSE: Alteration of pro- and antiangiogenic homeostasis of vascular endothelial growth factor (VEGF) isoforms in patients with hyperglycemia seems crucial but substantially unexplored at least quantitatively for diabetic retinopathy (DR). Therefore, in the present study we aimed to estimate the difference between the pro- (VEGF165a) and antiangiogenic (VEGF165b) VEGF isoforms and its soluble receptors for severity of DR. METHODS: The study included 123 participants (diabetic retinopathy: 81, diabetic control: 20, non-diabetic control: 22) from the Regional Institute of Ophthalmology, Kolkata. The protein levels of VEGF165a (proangiogenic), VEGF165b (antiangiogenic), VEGF receptor 1 (VEGFR1), VEGFR2, and VEGFR3 in plasma were determined with enzyme-linked immunosorbent assay (ELISA). RESULTS: An imbalance in VEGF homeostasis, a statistically significant concomitant increase (p<0.0001) in the level of VEGF165a and a decrease in the level of VEGF165b, was observed with the severity of the disease. Increased differences between VEGF165a and VEGF165b i.e. VEGF165a-b concomitantly increased statistically significantly with the severity of the disease (p<0.0001), patients with diffuse diabetic macular edema (DME) with proliferative DR (PDR) had the highest imbalance. The plasma soluble form of VEGFR2 concentration consistently increased statistically significantly with the severity of the disease (p<0.0001). CONCLUSIONS: The increased difference or imbalance between the pro- (VEGF165a) and antiangiogenic (VEGF165b) homeostasis of the VEGF isoforms, seems crucial for an adverse prognosis of DR and may be a better explanatory marker compared with either VEGF isoform.

Dimension and Socio-demographic Correlates of Domestic Violence: A study from Northeast India.

Present study was aimed to find out dimension and socio-demographic correlates of domestic violence in Assam, Sikkim and Meghalaya, Northeast India. Two districts from each state were selected at random and women aged 18-35 years from rural and urban localities were interviewed to obtain relevant information. The study included a total of 2249 participants (Rural = 1577 and Urban = 672) from Assam (650), Sikkim (1148) and Meghalaya (451). Domestic violence was recorded in 26.4% of study participants and highest in Meghalaya. Of all types, psychological violence was predominant. A number of socio-demographic factors have been identified as independent predictors for domestic violence in pooled and state specific analysis. Findings of our study may help in formulating strategies to prevent domestic violence.

Insertion/Insertion Genotype of Angiotensin I-Converting-Enzyme Gene Predicts Risk of Myocardial Infarction in North East India.

Myocardial infarction (MI) is common in India and the disease occurs at a relatively younger age. We wanted to look for association of Angiotensin I-converting enzyme (ACE) gene with MI in North East India. We also wanted to examine possible environmental interaction of ACE gene with established cardiovascular risk factors in causation of MI. In the study carried out in Assam Medical College, 200 consecutive confirmed cases of MI were recruited. Equal numbers of age- and sex-matched control subjects from hospital workers and patients attending the hospital for diseases unrelated to cardiovascular disease were enrolled. Structured questionnaires were used to note demographic and clinical factors. Cardiovascular risk factors were determined from history, physical examination and biochemical investigations. ACE insertion/deletion (I/D) polymorphism was determined by PCR method. Interaction of ACE gene with other risk factors was noted. The study identified ACE II genotype (odds ratio = 3.02; 95% CI 1.40-6.51), smoking, hypertension, diabetes and serum triglyceride > 150 mg/dl as independent risk factors for MI. ACE II genotype showed greater risk in non-smokers, non-hypertensives, non-diabetics and in subjects with LDL-C < 130 mg/dl. Low HDL cholesterol enhanced the genetic risk. Subjects with ACE II genotype have an independent risk of developing MI, specially in low cardiovascular risk subjects.

Distribution of blood pressure & correlates of hypertension in school children aged 5-14 years from North East India.

BACKGROUND & OBJECTIVES: Elevated blood pressure (BP) in the young predicts serious cardiovascular events in the adults. High prevalence of adult hypertension reported from Assam, North East (NE) India may be linked with elevated blood pressure in the childhood. The present study was an attempt to describe the distribution of BP and correlates of hypertension in children aged 5-14 yr. METHODS: A total of 10,003 school children from 99 schools of Dibrugarh district, Assam, NE India, were surveyed by stratified random cluster method. Blood pressure, demographic and anthropometric information were recorded. Blood pressure was categorized in to normal, prehypertension, stage I and stage II hypertension. RESULTS: Girls had significantly higher (104.2 ± 12.0 vs. 103.2 ± 11.6 mm Hg, p0 <0.001) mean systolic blood pressure (SBP) than boys. Both SBP and diastolic blood pressure (DBP) revealed significant correlation with age, height, weight and BMI in overall and in gender specific analysis. Hypertension was found in 7.6 per cent school children (Boys: 7.3%, Girls: 7.8%). In multivariable analysis older age (OR 3.3, 95% CI: 2.82-3.91), children from tea garden community (OR 1.3, 95% CI: 1.08-1.55) and other community (OR 1.4, 95% CI: 1.18-1.73) and overweight (OR 1.5, 95% CI: 1.1-2.1) were independently associated with hypertension. INTERPRETATION & CONCLUSIONS: Mean blood pressure in the young school children of 5-14 yr was high. A programme comprising screening, early detection and health promotion through school health programmes may help prevent future complications of hypertension.

Correlates of Breastfeeding in Villages and Tea-Gardens in Assam, India.

OBJECTIVE: To observe and compare breastfeeding practices in villages and tea-gardens. METHODS: Analytical cross-sectional study among mothers of infants in a health and demographic surveillance site in Dibrugarh, Assam. RESULTS: 1435 mothers (855 from tea-gardens, 580 from villages); and 1437 infants (857 from tea-gardens, 580 from villages), were included in study. Mean maternal age was 25.1 (4.4) years in tea-gardens and 25.8 (4.9) years in villages. Timely initiation of breastfeeding was higher in villages (82.6%) than tea-gardens (76.4%). Feeding colostrum was higher in villages (71.2%) than tea-gardens (60.8%). DISCUSSION: Factors affecting breastfeeding were different in villages and tea-gardens. Timely initiation of breastfeeding was associated with nuclear family in villages and joint family in tea-gardens. Hence, interventions promoting breastfeeding practices should be tailored instead of one-size-fits-all approach.

Predictors of Low Birth Weight: A Study in a Health and Demographic Cohort from Assam, India.

Low birth weight is associated with morbidities and mortality in the later life. Prevalence of anemia and under nutrition in Assam were reported to be high which may correlate with low birth weight of infants. The present study assessed prevalence and risk factors for low birth weight in a health and demographic cohort established in Dibrugarh district, Assam. A total of 1437 deliveries (580 from rural and 857 from tea garden) were recorded during March 2019 to February 2020. Prevalence of low birth weight was 30.34%. Tea-garden community [OR: 1.4 (1.06-1.79)], low levels of maternal education [OR: 1.57(1.12-2.13)], low monthly income [OR: 2.1 (1.1-3.9)], pre-term birth [OR: 4.1 (2.2-7.9)] and mother with low BMI [OR: 1.6 (1.3-2.07)] were found to be significantly associated with low birth weight. Intervention strategies to improve socioeconomic condition, promote antenatal checkup and alleviate under nutrition in pregnant mothers are warranted to reduce low birth weight.

Prevalence of endothelial nitric oxide synthase (eNOS) gene exon 7 Glu298Asp variant in North Eastern India.

BACKGROUND & OBJECTIVES: Endothelial nitric oxide is a potent vasodilator and impairment of its generation brought about by gene polymorphism is considered a major predictor for several diseases. A single nucleotide polymorphism G894T within exon 7 of endothelial nitric oxide synthase (eNOS-7) gene, resulting in a replacement of glutamic acid by aspartic acid, has been studied as a putative candidate gene for cardiovascular diseases. The pattern of eNOS-7 Glu298Asp variant in the Indian population is poorly known. The present study was planned to determine the prevalence of the variant of this gene among tea garden community in Assam, North-East India with high prevalence of hypertension. METHODS: Study participants of both sex aged ≥18 yr were recruited randomly from temporary field clinics established in tea gardens of Dibrugarh, Assam. Genomic DNA was extracted from 409 subjects by the conventional phenol-chloroform method. The prevalence of the eNOS exon 7 Glu298Asp variant was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: The study population was in Hardy-Weinberg Equilibrium. The frequency of the eNOS GG, GT and TT genotypes was found to be 75, 22 and 3 per cent respectively and did not show any significant difference in gender wise analysis. INTERPRETATION & CONCLUSIONS: Our results showed that the prevalence of the homozygous GG genotype was high (75%) and the rare mutant genotype (homozygous, TT) was 3 per cent in a population at risk with cardiovascular disease. Such population-based data on various polymorphisms can ultimately be exploited in pharmacogenomics.

Prevalence of Diabetes and Its Relationship With Body Mass Index Among Elderly People in a Rural Area of Northeastern State of India.

Background Diabetes and its complications are a major public health concern in elderly populations. However, there is little population-based data on diabetes and its risk factors among the elderly population living in rural areas of India. The objective of this population-based study was to assess the prevalence of diabetes in the elderly population and its relationship with body mass index (BMI). Methodology A population-based, cross-sectional study was conducted among elderly individuals (≥60 years) during the period 2013-2016 in rural areas of Dibrugarh district of Assam. Multi-stage sampling design was adopted to select the study participants. Data on socio-demographic profile and diagnosis/treatment history of diabetes were collected using pre-designed and pre-tested questionnaire. Fasting blood sugar was tested. Weight and height were measured to calculate BMI. Multivariate logistic regression analysis was performed to assess the relationship between diabetes and BMI. Results Data were collected from 430 (male: 210, female: 220) individuals. The overall prevalence of diabetes was 7.9% (male: 7.1%, female: 8.6%). Higher level of education was associated with increased prevalence of diabetes. Prevalence of diabetes increased as the BMI of participants increased. Prevalence of diabetes among obese individuals (BMI ≥25 kg/m2) was 30.4% compared to only 5% among normal weight individuals. Obesity was associated with eight-fold higher risk of diabetes compared with the individuals of normal weight in multivariate analysis. Conclusions The study reveals nearly 8% population-based prevalence of diabetes in rural elderly people in the study district. Our study provides epidemiological evidence that obesity is a major driver of diabetes among rural elderly people.

A Community-Based Study on Functional Disability and Its Associated Factors Among Elderly Individuals in a Rural Setting in Northeastern India.

Background Functional disability in older adults is common and adversely impacts the quality of life. Given the paucity of population-based data, the present analysis attempted to determine the prevalence and factors associated with functional disability in basic activities of daily living (ADLs) among the elderly population in a rural setting of Northeastern state of India Methods A total of 430 elderly were recruited in a population-based cross-sectional study among elderly individuals (≥60 years) during the period 2013-2016 in rural areas of the Dibrugarh district of Northeastern India. The Barthel index was used to measure ADL. Anyone with a Barthel index score <100 (or having limitations in one or more ADL items) were considered as having a functional disability. The analysis of variance (ANOVA) test and the binary logistic regression analysis were used to examine the factors associated with functional disability. Results Overall, 43.7% % (Male 42.9%, Female 44.5%) of the participants had a functional disability. Increasing age, being widowed, having no formal education, being underweight (body mass index (BMI)<18.5 kg/m2), and increasing numbers of morbidities were significantly associated with functional disability among the elderly in this study in age and gender-adjusted logistic regression analysis. Being ≥80 years was associated with a three-fold greater risk (OR=31.72, 95% CI=1.3-6.91) of functional disability than the youngest age group (60-69 years). On the other hand, the presence of more than five morbidities was associated with a nearly 20 times increased risk (OR=19.61, 95% CI=9.01-42.68) than those with zero to two morbidities. Conclusion A high proportion of the rural elderly residents of Dibrugarh had a functional disability. The study provides epidemiological evidence of the risk factors of functional disability in this setting. This epidemiological information may be useful for developing prevention strategies to reduce the burden of functional disability.