Reelin gene polymorphisms in the Indian population: a possible paternal 5'UTR-CGG-repeat-allele effect on autism.

Autism is a neurodevelopmental disorder with high heritability factor and the reelin gene, which codes for an extracellular matrix protein involved with neuronal migration and lamination is being investigated as a positional and functional candidate gene for autism. It is located on chromosome 7q22 within the autism susceptible locus (AUTS1); identified in earlier genome scans and several investigations have been carried out on various ethnic groups to assess possible association and linkage of the gene with autism. However, the findings are still inconclusive. In the present study which represents the first report of such a study on the Indian population, genotyping analyses of CGG repeat polymorphism at 5'UTR, two single nucleotide polymorphisms (SNP) at exon 6 and exon 50 were performed in 73 autistic subjects, 129 parents, and 80 controls. The allelic distributions of the repeat polymorphism and exon 50 T/C SNP were quite different from earlier reports in other populations. Allelic and genotypic distribution of the markers did not show any differences between the cases and controls. While our preliminary data on family-based association studies on 58 trios showed no preferential transmission of any allele from the parents to the affected offspring, TDT and HHRR analyses revealed significant paternal transmission distortions for 10- and > or =11-repeat alleles of CGG repeat polymorphism. Thus, the present study suggests that 5'UTR of reelin gene may have a role in the susceptibility towards autism with the paternal transmission and non-transmission respectively of 10- and > or =11-repeat alleles, to the affected offspring.     

Impact of the RHANI Wives intervention on marital conflict and sexual coercion

Objective

To assess the effects of the RHANI (Reducing HIV among Non-Infected) Wives intervention on marital conflict and intimate partner violence (IPV) in urban India.

Methods

A 2-armed cluster-randomized controlled trial (7 intervention, 6 control clusters) of the RHANI Wives intervention was conducted with 220 women contending with a history of IPV and/or husband’s drunken behavior. Participants were surveyed at baseline and 4.5-month follow-up. Outcome measures included marital conflict (arguments with husband in past 3 months), marital IPV (physical or sexual violence from husband in past 3 months), and marital sexual coercion (husband forcing sex at last sex). Intention-to-treat logistic generalized linear mixed models were used to determine intervention impact.

Results

One-third (35.0%) of participants reported physical or sexual abuse from their husband in the past 3 months, and 58.6% reported that their husband was drunk in the past 30 days. Intention-to-treat analyses indicated time × treatment reductions in marital conflict (risk ratio [RR] 0.4; 90% confidence interval [CI], 0.1–0.9; P = 0.06) and marital sexual coercion (RR 0.2; 90% CI, 0.05–0.9; P = 0.08), but not IPV.

Conclusion

The findings suggest the potential utility of this intervention in reducing marital conflict and sexual coercion among women in urban India.ClinicalTrials.gov: NCT01592994.     

Global Urine Metabolomics in Patients Treated with First-Line Tuberculosis Drugs and Identification of a Novel Metabolite of Ethambutol

Population level variation of drug metabolism phenotype (DMP) has great implications in treatment outcome, drug-related side effects, and resistance development. In this study, we used a gas chromatography-time of flight-mass spectrometry (GC-TOF-MS)-based untargeted urine metabolomics approach to understand the DMP of a tuberculosis (TB) patient cohort (n = 20) from Tripura, a state in the northeastern part of India. Urine samples collected at different postdose time points (2 h, 6 h, 12 h, 24 h, 36 h, and 48 h) from these newly diagnosed TB patients receiving first-line anti-TB drugs were analyzed, and we have successfully detected three of the four first-line drugs, viz., isoniazid (INH), ethambutol (ETB), and pyrazinamide (PZA). The majority of their known metabolites, acetyl-isoniazid (AcINH), isonicotinic acid (INA), isonicotinuric acid (INTA), 2,2′-(ethylenediimino)-dibutyric acid (EDBA), 5-hydroxypyrazinamide (5OH-PZA), pyrazinoic acid (POA), and 5-hydroxypyrazinoic acid (5OH-POA), were also detected. Analyzing the variation in abundances of drugs and their known metabolites and calculating the metabolic ratios in these samples, we offer comprehensive DMP information on this small patient cohort that represents Tripura, India. The majority (75%) of these patients are found to be slow acetylators of INH. The average metabolic ratios of POA/PZA and 5OH-POA/POA are 3.16 ± 3.03 and 6.09 ± 6.15, respectively. Employing correlation analysis of the metabolomics metadata and a manual prediction of drug catabolism, we have proposed 2-aminobutyric acid (AABA) as a novel metabolite of ETB. These observations indicate the usefulness of GC-MS-based metabolomics to characterize the DMP at a population level and also to identify novel drug metabolites.     

Increased cardiovascular risk due to systemic inflammatory changes and enhanced oxidative stress in urban Indian women

The study was undertaken to elucidate the inflammation- and oxidative stress-mediated deterioration of cardiovascular health in urban women exposed to ambient air pollution from vehicular and industrial emissions. A total of 556 urban women (median age, 34 years) and 514 age-matched control women who resided in the rural areas were enrolled. Serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-8 (IL-8) were measured by enzyme-linked immunosorbent assay as markers of inflammation. Generation of reactive oxygen species (ROS) by leukocytes was measured by flow cytometry and erythrocytic superoxide dismutase (SOD) was measured by spectrophotometry. Hypertension was diagnosed following the Seventh Report of the Joint Committee. On the days of sampling, data about particulate matter of diameter less than 10 μm (PM₁₀) in city was obtained from website of State Pollution Control Board and that in rural ambience was measured using real-time aerosol monitor. Compared with control, urban women were exposed to higher levels of ambient air pollution; their serum contained significantly higher levels of IL-6, IL-8, TNF-α, and CRP. ROS generation was increased by 49 % while SOD was depleted by 34.9 %. Urban women were more hypertensive compared to their rural counterparts. PM₁₀ levels were positively associated with inflammatory markers, oxidative stress, and hypertension. Exposure to increased levels of ambient air pollution, which are much higher than the set standard levels, predisposes urban women to increased risk of deteriorating cardiovascular health. Systemic inflammation and oxidative stress are assumed to be the key players in this process.     

Ovarian pregnancy: Two case reports.

Ovarian pregnancy is a rare event occurring in 1-3% of all ectopic pregnancies. Increased reporting might be due to the wider use of intra-uterine devices, ovulatory drugs and assisted reproductive techniques. Though ovarian pregnancy has a distinct pathology, it can be a source of clinical and intraoperative diagnostic difficulty. We report two cases of ovarian pregnancy – one primary and one secondary – that came to our notice within six months span. Unlike tubal ectopic and secondary ovarian pregnancies, patients with primary ovarian pregnancy are likely to experience success in future intra-uterine conception and negligible risk.     

Cardioprotection with phosphodiesterase-5 inhibition--a novel preconditioning strategy

Phosphodiesterase type-5 (PDE-5) inhibitors including sildenafil, vardenafil and tadalafil are a new class of vasoactive drugs that have been developed for treatment of erectile dysfunction in patients. A growing number of studies in recent years suggest that sildenafil may be used clinically for treatment of pulmonary hypertension and endothelial dysfunction. In addition, recent studies primarily from our laboratory suggested that sildenafil has preconditioning-like powerful cardioprotective effect in the animal models of ischemia-reperfusion injury. Sildenafil has been found to exert cardioprotection through nitric oxide generated from endothelial and/or inducible nitric oxide synthases and opening of mitochondrial ATP-sensitive potassium channels. Future demonstration of the cardioprotective effect in patients with the relatively safe and effective FDA-approved PDE-5 inhibitors, such as sildenafil, could have an enormous impact on bringing the long-studied phenomena of ischemic and pharmacologic preconditioning to the clinical forefront.     

Newborn screening: experience of Bangladesh

Newborn screening for early diagnosis of many preventable diseases is already an established program in developed countries as well as in some countries in Asia. With the control of infectious and communicable diseases, the Bangladesh government is now giving more attention to the preventive aspect of health. The country is now preparing to adopt newborn screening as part of the preventive aspect of health. Among the various activities are laboratory set up, expert visits, pilot studies on CH and training of personnel. A national project to screen newborns for congenital hypothyroidism is now under active consideration. A universal newborn screening program is a highly ambitious project for a country like Bangladesh. Funds to run such a program will be the main problem. The social pattern where still more than 80% of deliveries are done at home is another constraint. However, the enthusiasm of the professionals as well as of the government is a very encouraging thing. Now it needs the support of the international communities.