Level of endosulfan among women in Talwandi Sabo Block of Southern Punjab, India.

Endosulfan is one of the most prevalent organochlorine pesticides used in the agricultural sector in the developing countries including India. It affects the physiological functioning of different organ systems including nervous, immune, hepatic, and reproductive system. Realizing the safety and health concern, restrictions have been imposed at various levels, but the usage has still continued in the plantation crops. Owing to pesticide beneficiary of north India, the cotton belt commonly called the Malwa region of Punjab was evaluated for identifying the levels of Endosulfan in the blood samples of women working in agricultural fields. Gas chromatograph with electron capture detector was used for detecting the levels of endosulfan metabolites among twenty active female workers. The mean level of endosulfan recorded in the tested population was observed to be 2.22 ppb. It is difficult to draw a certain conclusion based on these findings because the subjects were less in number. However, detection of even very low concentrations of endosulfan residues signifies its continued accessibility to the women population. Encouragement of more such population-based research needs to be adopted to determine the body burden of such pesticides in humans. The effective implementation of the ban on Endosulfan could be checked by a combined retrospective and prospective study to infer a justifiable impact.

Association of sociodemographic and nutritional factors with risk of neural tube defects in the North Indian population: a case-control study.

OBJECTIVE: To assess the role of sociodemographic and nutritional factors in the incidence of births affected by neural tube defects (NTD) in the North Indian population. DESIGN: Case-control study. SETTING: Government hospitals of Delhi, India. SUBJECTS: Subjects comprised 284 mothers of NTD children (cases) and 568 mothers of healthy children (controls). RESULTS: Significant differences were found between case and control mothers with respect to maternal age (P = 0·005), type of drinking water (P = 0·03) and consumption of milk (P = 0·01). Univariate and multivariate analysis suggested an association of unpasteurized milk use, low consumption of vegetables, low consumption of fruits and vegetarian dietary habits with NTD births. Further, variation in the risk factors for upper and lower NTD types was also observed, pointing towards phenotypic heterogeneity in the aetiology. CONCLUSIONS: The results of the present study suggest an increased risk of NTD infants in mothers with low consumption of vegetables, fruits and milk and having vegetarian dietary habits. So, in order to reduce these devastating birth defects in future offspring, better nutritional care should be provided to mothers by suggesting dietary modifications and augmenting additional micronutrient supplementation during the periconceptional period.

Barriers and Facilitators during Community Reintegration of People with Spinal Cord Injury: A Qualitative Study.

Introduction: Spinal cord injury (SCI) individuals face challenges in community reintegration due to various factors. This study explores the barriers and facilitators affecting their reintegration, aiming to understand and address their diverse needs and challenges in different cultural contexts. Methods: The present qualitative study was conducted between December 2021 to June 2022 among 71 SCI individuals as data saturation was achieved. Data was collected via structured in-depth interview. Participants were identified through purposive sampling method, admitted, or visited to rehabilitation center, India. Data was analyzed according to Braun and Clarke's thematic analysis method using MAXQDA 2020. Results: Data analysis led to the emergence of four major themes and several sub-themes specific to the single problem domain. The four major themes of barriers included environmental, cultural, psychological and health-related barriers. However, four facilitators (Family support, financial stability, religious practices, friends and leisure activity) came up which may help in overcoming from the challenges faced by the SCI individuals. Conclusion: People with SCI face various problems in their care, management and social lives. It is important to give attention to their needs along with comprehensive health support and strengthen the patient-provider interaction. This may generate a sense of self efficacy, self-esteem and promotes the mental well-being of people with spinal cord injuries. Working on the above mentioned issues can help SCI people in low- and middle-income countries become more integrated into their communities.

Factors Influencing the Consumption of Tobacco amongst the Khasi Indigenous People in Northeast India.

Background: Tobacco use in any form is a major public health concern. It accounts for nearly 1.35 million deaths every year. Many chronic illnesses occur due to the consumption of tobacco, either smoke or smokeless form. The study aims to explore how smoking and smokeless tobacco consumption are distributed across a range of demographic and socioeconomic markers among Khasi indigenous people in Northeast India. Materials and Methods: It is a case-control study conducted in adults over 31 years of age. The study was carried out between June 2020 and August 2021. An Independent t-test was performed to determine the significant difference in age between smoking/smokeless tobacco users and non-tobacco users. Univariate and Multivariate analyses were conducted to determine the significant predictors affecting the use of smoking/smokeless tobacco in the respondents. Results: A total of 505 respondents were included in the present study. There was a high statistically significant difference in the income level of tobacco and non-tobacco users (P value- 0.002). In Univariate analysis, it was found that the odds of consuming both forms of tobacco were significantly lower in the respondents aged between 51-60 (OR = 0.61, P value = 0.0453). The participants who studied till graduation and above had lower odds of both using forms of tobacco as compared to respondents who were illiterate/primary educated only (OR = 0.85, P value = 0.046). Conclusion: In conclusion, smoking and smokeless tobacco consumption are still widely prevalent in this region and strongly associated with age, gender, level of education, and place of residence. There is a need for further detailed analysis to identify risk factors that are strongly associated with the use of smoke and smokeless tobacco so that the community will be conscious about the hazardous effects of tobacco use in any form.

Relational Empathy, Holistic Care, and Quality of Life in Persons With Spinal Cord Injuries: A Cross-sectional Study.

INTRODUCTION: High-quality health systems are built on the concept of patient-centered approach, which includes holistic care and empathy. With time, this has progressively been recognized as a valuable paradigm for better health outcomes, particularly in chronic diseases. OBJECTIVES: The study aims to determine the patients' perception during their consultation and to assess the relationship between Consultation and Relational Empathy measure with demographic/injury variables and quality of life. METHODS: The present cross-sectional study was conducted among 226 individuals with spinal cord injuries. Data were collected via structured questionnaire, World Health Organization-Quality of life BREF, and Consultation and Relational Empathy measure. Independent t test is used to compare World Health Organization-Quality of life BREF domains with two groups of Consultation and Relational Empathy measure. Logistic regression was used to determine the significant factors of Consultation and Relational Empathy measure. RESULTS: In the logistic regression analysis, it was observed that higher quality of life score has significantly higher odds of getting higher Consultation and Relational Empathy score with a remarkable odds ratio (odds ratio = 1.0264, 95% confidence interval = 1.0121-1.0261, P = 0.0001, 0.0472, 0.0001). CONCLUSIONS: The quality of life of the present population is closely associated with greater perceptions of holistic care and empathy in the therapeutic patient-provider relationship. Lack of coordination, poor quality of life, and limited communication between patient and provider may arise when the latter focuses only on treating disease rather than treating a patient as a "whole person."

Effect of maternal Tp53 gene G412C polymorphism on neural tube defects: A study from North India.

CONTEXT: Tumor protein 53 (tp53) is one of the candidate gene proposed for neural tube defects, which affects central nervous system during early embryonic development, on the basis of mouse models. AIMS: The present study is an attempt to unfold the possible role of tp53 G412C polymorphism in the incidence of neural tube defect (NTDs) in humans. SETTINGS AND DESIGN: Case-control study was carried out in government hospitals of Delhi, India. MATERIALS AND METHODS: Subjects comprised of 100 mothers of NTD children and 100 matched control mothers. Information on some environmental exposures was collected along with blood samples. After DNA extraction, the genotyping of tp53 G412C polymorphism was carried out by PCR-RFLP method. STATISTICAL ANALYSYS: Fisher Exact or Chi square test, binary logistic model, and odds ratio (95% confidence interval) calculations were used to evaluate effect of risk factors on NTDs using SPSS v17.0. RESULTS: The 'CC' genotype of tp53 G412C showed protective effect towards the development of anencephaly and/or encephalocele (OR: 0.44; 95% CI: 0.19-1.00); however, no significant difference among overall NTD cases and controls was observed (P>0.05). Further segregation of all subjects based on 2 different communities, Hindus and Muslims, the association of 'CC' genotype of the polymorphism with reduced NTD risk was observed among Hindu community (OR: 0.33; 95% CI: 0.13-0.79). CONCLUSION: The study highlights the selective advantage provided by maternal 'CC' genotype, thereby reducing risk of cephalic NTDs, probably due to the lower apoptotic activity of the protein, however, more specifically in the presence of community-specific microenvironment.

Pharmacogenetic typing for oral anti-coagulant response among factor V Leiden mutation carriers.

CONTEXT: Factor V Leiden mutation is the most common inherited predisposition for hypercoagulability and thereby a common genetic cause for initiation of oral anti-coagulation therapy. There is a dearth of knowledge of coumarin response profile in such thrombophilic population. AIMS: The current pilot study aims to estimate coumarin sensitivity in an Indian cohort with an inherited thrombophilia risk factor (Factor V Leiden mutation carriers) based on the observed frequency of CYP2C9 (*)2, (*)3 and VKORC1-1639G >A genotype combinations. SETTINGS AND DESIGN: A retrospective study carried out in a tertiary health care center in India. MATERIALS AND METHODS: Carriers of FVL mutation were genotyped for CYP2C9 ((*)2, F(*)3) and VKORC1 (-1639G >A) variants by PCR-RFLP technique. STATISTICAL ANALYSIS USED: Chi-square test to analyze difference in expected and observed genotype frequency. RESULTS: Sixty-one (n = 61) unrelated carriers of FVL mutation were observed in the 13 years study period. The allele frequency of CYP2C9 (*)2, CYP2C9 (*)3, and VKORC1-1639A in this cohort was 0.06, 0.11, and 0.16, respectively. Six (9.7%) individuals had two of the three variant alleles (heterozygous or homozygous), and 28 (45.9%) were heterozygous for at least one polymorphism. CONCLUSIONS: Pre-prescription genotyping for coumarin drugs, if introduced in Indians with inherited thrombophilia (in whom oral anti-coagulant therapy may be necessary), is likely to identify 9.7% (hypersensitive) subjects in whom the optimum anti-coagulation may be achieved with reduced dosages, 44.3% (normal sensitivity) who may require higher dose and also 55.6% (hyper and moderate sensitivity) subjects who are likely to experience bleeding episodes.

Folate supplementation, MTHFR gene polymorphism and neural tube defects: a community based case control study in North India.

The present study analyses the potential role of MTHFR gene polymorphism, folate supplementation and dietary pattern among the mothers of NTD neonates and controls in heterogeneous populations of North India, with the special focus on their ethnic labels. Results indicated significant increased risk for neural tube defects with respect to low folic acid supplementation and vegetarian diet in univariate and multivariate analyses. There was no significant difference in the genotypic or allelic distribution of MTHFR C677T polymorphism, however, high frequency of CT genotype, as observed, among controls suggests heterozygous advantage probably due to supplementary folate. Among the two communities, Muslim NTD mothers had higher TT genotype showing increased risk for neural tube defects (adjusted OR: 12.9; 95% CI: 1.21-136.8) and lower folic acid supplementation (adjusted OR: 3.5; 95% CI: 1.18-10.22). Whereas, marginal increased risk for NTDs with vegetarian diet was observed among Hindus. Cultural and ethnic variation in the risk factors for neural tube defects is highlighted in the study.

Sociodemographic Pattern of Postmenopausal Women and Health Issues: A Study in Rural Bathinda, Punjab.

BACKGROUND: The diminishing hormonal concentrations in women after menopause may trap them into a number of reproductive health deficits. Their lifestyle, occupation, dietary constituents, etc., affect the overall health. Unfortunately, women belonging to rural areas lack basic amenities and cultural aspects give them a backseat to pay heed to personal health. Therefore, it is important to take into consideration the demographic profile of rural women. OBJECTIVE: The objective of the study is to evaluate postmenopausal women of rural Punjab for sociodemographic, reproductive parameters and health issues. RESULTS: This study analyzed 425 women showing a high rate of illiteracy (74.6%), agricultural occupancy (85.2%), and consumption of vegetarian food (94.4%). The mean age at menarche and menopause was observed as 14.04 ± 1.12 and 47.97 ± 3.4 years, respectively. The most frequent complaints were fatigue (70.4%), backache (69.4), breathing problems (52.2%), and abdominal discomfort (43.1%). CONCLUSION: Later age at menopause in women was found concurrent with involvement in agriculture and exposure to pesticides. Delayed menopause may indicate a risk of reproductive cancers while protection in cardiovascular diseases. Therefore, age at menopause and dependent sociodemographic parameters should be considered important tools in determining the reproductive health of aging women. Large-scale studies dealing with this health aspect are warranted at village level.

Folic acid, dietary habits, and homocysteine levels in relation to neural tube defects: A case-control study in North India.

PURPOSE: The present study attempts to understand the complex contribution of biochemical (plasma homocysteine) and nutritional parameters (dietary pattern and folate supplementation) to the neural tube defects (NTDs) affected pregnancies and controls in North Indian population. METHODS: Case-control study design was adopted to assess the role of folic acid, dietary habits, and homocysteine in relation to NTD births. The subjects comprised of 130 mothers of affected children (cases) and 233 mothers of healthy children (controls), who were either carrying NTD fetus or gave birth to NTD child. RESULTS: The mean homocysteine levels were elevated in cases (15.71 ± 8.35 µmol/L) as compared to controls (12.87 ± 5.95 µmol/L) but were lower among the non-vergetarians (13.55 ± 6.64 µmol/L) than the vegetarians (14.78 ± 7.93 µmol/L). Vegetarian dietary habit increased the NTD risk by 1.6 fold (95% CI = 1.0-2.7) while folic acid supplementation demonstrated a protective effect for conceptions (OR = 0.59; 95% CI = 0.3-0.9). Consumption of folic acid with non-vegetarian diet witnessed lowering of homocysteine in cases (12.88 ± 6.81 µmol/L) and in controls (11.85 ± 5.54 µmol/L), with an odds ratio depicting a 3.1 fold risk for consuming vegetarian diet without folic acid supplementation during the peri-conceptional period. CONCLUSION: It is suggested that plasma hyperhomocysteinemia bears negative impact on child-bearing women group, of north Indian ancestry, in modulating the risk of NTDs. Efforts should be made to enhance awareness regarding folic acid and vitamin B12 (non-vegetarian diet) supplementations alongwith proper nutritional intake among women, especially those consuming vegetarian diet to control homocysteine levels in order to reduce the risk of NTDs.

Toxicological profile of organochlorines aldrin and dieldrin: an Indian perspective.

Several epidemiological studies have suggested various environmental factors as a possible cause for increased incidence of various abnormalities. Of the various environmental contaminants, the most prevalent and the most discussed are the endocrine disrupting chemicals. Contact of such disruptors with humans has become inevitable today. They are cosmopolitan and present from agriculture to industrial sectors, even in day-to-day consumer products. Aldrin and dieldrin belong to one such class of substances which are known to have a toxic effect on various physiological systems of the human body. Despite an imposed ban on their manufacture and commercial use, these pesticides could still be detected in probable areas of consumption like agriculture. The present review discusses the known possible toxic effects of aldrin and dieldrin and their current existence in the ecosystem across India.

Sickness Status and Neural Tube Defects: A Case-Control Study in a North Indian Population.

BACKGROUND: The prevalence of neural tube defects (NTDs) in India is high in comparison to other regions in the world, with the Northern part reporting the highest prevalence. METHODS: To explore the risk factors for NTDs, a case-control study was carried out in Delhi from January 2008 to June 2011. Using multivariate logistic regression model analysis, 308 cases were compared with 580 controls and adjusted odds ratio (AOR) was calculated using SPSS version 17. RESULTS: Maternal factors that were significantly associated with increased risk of NTDs were inter-pregnancy interval (AOR = 3.175; 95% confidence interval [CI], 2.007-5.024), hyperthermia during the first trimester (AOR = 2.07; 95% CI, 1.131-3.788), maturation ill pregnancy (AOR = 1.956; 95% CI, 1.385-2.763), chronic illness (AOR = 1.648; 95% CI, 1.103-2.462), and use of antibiotics (AOR = 5.589; 95% CI, 1.789-17.455). Differences in the risk were also found between upper and lower NTD. It was observed that all of the former five variables, except for chronic illness, were associated with risk for upper NTDs (AOR = 1.532; 95% CI, 0.916-2.563). In contrast, hyperthermia before conception (and not during the first trimester) was found to be additionally associated with risk for lower NTDs (AOR = 2.782; 95% CI, 1.302-5.944). CONCLUSION: These findings highlight heterogeneity in the etiology of upper and lower NTDs. The study also highlights the risk factors that should be considered in combating the risk of NTDs. Birth Defects Research 109:1393-1399, 2017.© 2017 Wiley Periodicals, Inc.

Seventeen Novel Mutations in PCCA and PCCB Genes in Indian Propionic Acidemia Patients, and Their Outcomes.

AIMS: The goal of this study was to identify mutations in the propionyl-CoA carboxylase alpha subunit (PCCA) and propionyl-CoA carboxylase beta subunit (PCCB) genes, and to assess their effects on propionic academia (PA) patients. METHODOLOGY: Twenty-five Indian children with PA were enrolled in this study. Bidirectional Sanger sequencing was performed on both the coding and flanking regions of the PCCA and PCCB genes and the chromatograms were analyzed. Bioinformatic tools were used to classify novel variations into pathogenic or benign. RESULTS: The majority of the cases (19/25, 76%) were of the early-onset (<90 days of age) type and 5 were of the late-onset type. The majority of patients had mutations in the PCCA gene (18/25). A total of 26 mutations were noted: 20 in the PCCA gene and 6 in PCCB gene. Seventeen mutations were novel (14 in PCCA and 3 in PCCB). The SNP c.937C>T (p.Arg313Ter), was noted in 9/36 (25%) alleles in the PCCA gene. All of the children were symptomatic and only three survived who are doing well with no major disabilities. CONCLUSION: The spectrum of mutations in the PCCA and PCCB genes among Indians is distinct from other populations. The absence of a common mutation signifies the heterogeneity and admixture of various subpopulations. These findings also suggest that individuals of Indian origin may not benefit from the mutation-based "carrier screening panels" offered by many genetic laboratories.

Identification of mutations, genotype-phenotype correlation and prenatal diagnosis of maple syrup urine disease in Indian patients.

Maple syrup urine disease (MSUD) is caused by mutations in genes BCKDHA, BCKDHB, DBT encoding E1α, E1ß, and E2 subunits of enzyme complex, branched-chain alpha-ketoacid dehydrogenase (BCKDH). BCKDH participates in catabolism of branched-chain amino acids (BCAAs) - leucine, isoleucine and valine in the energy production pathway. Deficiency or defect in the enzyme complex causes accumulation of BCAAs and keto-acids leading to toxicity. Twenty-four patients with MSUD were enrolled in the study for molecular characterization and genotype-phenotype correlation. Molecular studies were carried out by sequencing of the 3 genes by Sanger method. Bioinformatics tools were employed to classify novel variations into pathogenic or benign. The predicted effects of novel changes on protein structure were elucidated by 3D modeling. Mutations were detected in 22 of 24 patients (11, 7 and 4 in BCKDHB, BCKDHA and DBT genes, respectively). Twenty mutations including 11 novel mutations were identified. Protein modeling in novel mutations showed alteration of structure and function of these subunits. Mutations, c.1065 delT (BCKDHB gene) and c.939G > C (DBT gene) were noted to be recurrent, identified in 6 of 22 alleles and 5 of 8 alleles, respectively. Two-third patients were of neonatal classical phenotype (16 of 24). BCKDHB gene mutations were present in 10 of these 16 patients. Prenatal diagnoses were performed in 4 families. Consanguinity was noted in 37.5% families. Although no obvious genotype-phenotype correlation could be found in our study, most cases with mutation in BCKDHB gene presented in neonatal period. Large number of novel mutations underlines the heterogeneity and distinctness of gene pool from India.

CYP2C9, VKORC1, CYP4F2, ABCB1 and F5 variants: influence on quality of long-term anticoagulation.

AIMS: The study aims to evaluate the impact of genetic, demographic and clinical data on various measures of outcome of anticoagulation quality in patients. PATIENTS AND METHODS: The study consisted of 310 patients receiving long-term oral anticoagulation therapy in our hospital. Apart from demographic and clinical variables, 21 SNPs (in 7 genes) were analyzed and compared with the outcomes of anticoagulation therapy. Various outcomes that were measured are; supra therapeutic INRs (INR >3, >6), anticoagulation stabilization, time taken to stabilize and proportion of INRs within (2-3), above (>3) and below (<2) therapeutic range. RESULTS: Supra therapeutic INRs were influenced by CYP2C9*2, *3, CYP4F2 rs2108622, VKORC1-1639G>A, 1173C>T, rs55894764 along with concomitant drugs, smoking, body weight and height. Persistently fluctuating INRs/absolute instability correlated with VKORC1-1639G>A, gender, height and body mass index. The time taken to stabilize was associated with CYP4F2 rs2108622, CYP2C9*14, smoking, clinical indication and concomitant drugs. The overall distribution of INR was influenced by variants in CYP4F2 rs2108622, CYP2C9*3, rs9332230, VKORC1 1173C>T, -1639G>A, rs55894764, ABCB1 rs2032582, rs1128503, rs1045642 and F5 rs6025, age, smoking and concomitant drugs. CONCLUSIONS: Knowledge of factors influencing the quality of long term anticoagulation can help clinicians to customize therapy either by dose variation, therapy with alternate choice of drug, concurrent heparin therapy and/or frequent INR monitoring.

Variability in CYP2C9 allele frequency: a pilot study of its predicted impact on warfarin response among healthy South and North Indians.

BACKGROUND: Wide variability exists in the frequency of pharmacogeneticmarkers for anticoagulant response in different populations. There is insufficient data on the prevalence of these variant genotypes in the Indian population. This study aims to determine the frequency of various genotype combinations of CYP2C9*2, *3 and VKORC1-1639G>A polymorphisms in the South and North Indians. METHODS: Genotyping was carried out by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) technique in 209 North Indians (NI) and 82 South Indians (SI). Warfarin maintenance dose was predicted for all subjects based on FDA approved genotype-based dose estimates from revised COUMADIN medication guide. Fisher exact test and Χ2 test were applied to compare categorical data among the SI and NI groups. RESULTS: In SI and NI, the allele frequency of CYP2C9*2 was 0.006 and 0.05 (significant variation; p<0.001); of CYP2C9*3 was 0.09 and 0.11; and of VKORC1-1639A was 0.14 and 0.19 (not significant), respectively. The variation in the frequency of combined CYP2C9/ VKORC1 genotypes revealed plausible difference in warfarin response among SI and NI. Based on the FDA approved revised dosing guidelines, significantly higher percentage of NI were likely to require intermediate dose (3-4 mg/day; p=0.015, RR=2.16) and were also predicted to have an increased risk of bleeding episodes and over anticoagulation (p=0.012, RR=1.93). CONCLUSIONS: Genotype frequency of CYP2C9 and VKORC1 SNPs is variable among the two ethno-geographically distinct Indian populations. This could translate into diverse warfarin response among the Indian population.

Implication of novel CYP2C9*57 (p.Asn204His) variant in coumarin hypersensitivity.

INTRODUCTION: Polymorphisms in CYP2C9 can vary the rate of metabolic clearance of oral anticoagulants, risking toxicity in patients. The present study focused on exploring the genetic etiology of idiopathic hyper sensitivity to coumarin anticoagulants in a patient who presented with multiple bleeding episodes and supra-elevated International Normalized Ratios. MATERIALS AND METHODS: Bidirectional gene sequencing of CYP2C9 and VKORC1 was carried out. Using allele-specific polymerase chain reaction, the identified novel variant was genotyped in 309 patients on anticoagulation therapy. The pharmacoproteomic significance of the novel genetic variant was elucidated by structural demonstration of binding of coumarin molecules within the mutant CYP2C9 204His protein model and in silico bioinformatic evolutionary analyses. Three-dimensional structure model of the mutant protein was constructed on the basis of the published X-ray crystal structure of human CYP2C9 protein (Protein Data Bank, 1R9O). RESULTS: The patient was identified to have a novel heterozygous missense mutation in exon 4 of CYP2C9 gene (g.9172A > C; p.Asn204His; CYP2C9*57). The variant was absent in the 309 genotyped patients. In silico bioinformatic analyses indicated the variant to have a deleterious effect on the protein. Analysis of 3D structure model of the mutant protein revealed that the substituted His204 led to restricted binding of the coumarin drug within the binding site of CYP2C9 enzyme, thereby inhibiting its metabolic clearance and thus explaining the enhanced pharmacologic effect and bleeding in the patient. CONCLUSIONS: The study elucidates the structurally deleterious role of the novel CYP2C9*57 missense mutation in coumarin toxicity.

Age at menarche in adolescent Khasi girls, Meghalaya.

The mean and median age at menarche in 360 Khasi girls was found to be 13.22 ± 0.88 and 12.13 ± 0.79 years, respectively; socio-economic status was observed to be a strong predictor of age at menarche in this population.