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Background: The life expectancy of people with intellectual disability (ID) has increased across the world with the advancements in public health policies and in the medical sciences. Still, people with ID have higher risks of dying prematurely due to associated medical and genetic conditions. However, there is no estimation of the mortality and life expectancy rate available for the ID population in India. In this context, this study was aimed to investigate the mortality rate in ID and its association with age in rural and urban settings in India. Method: Secondary data from the Disability Report for 2003 of the National Sample Survey Organization (NSSO) is used for analysis. Spearman correlation distinguishing age and rural and urban settings, t-test to measure the difference between rural and urban contexts and simple regression with age groups and settings, are carried out. Results: Age was highly associated with the mortality rate in ID. This association was strongly positive in both rural (ϱ =.954, p = .001) and urban ID adults (ϱ = .957, p = .001). However, the mortality rate did not differ statistically between rural and urban adults (t = 2.16, p = .062). For every one-year increase in the age of the population, the mortality rate was found to increase by 3.3 and 3.0 persons per 100,000 in rural and urban ID adults, respectively. Conclusion: This data analysis demonstrates a high mortality rate which significantly increases from the beginning of adulthood in ID Population. Further research is needed to support the findings of this study, and discover determinates of higher mortality rate or low life-span of the ID population in India. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a disorder that is commonly found in people with intellectual disability (ID). The prevalence of epilepsy increases with the severity of ID. The objective of this study was to determine if there is an association between intelligence quotient (IQ) and epilepsy in children with ID. Materials and Methods: A total of 262 children, aged 3-18 years, with ID were identified as part of a community-based rehabilitation project. These children were examined for epilepsy and diagnosed by a psychiatrist and physicians based on results of electroencephalogram tests. A Spearman's correlation (ρ) was used to determine if there was an association between IQ scores and the occurrence of epilepsy. X2 statistics used to examine the relationship of epilepsy with gender, socioeconomic status, population type, severity of ID, family history of mental illness, mental retardation, epilepsy, and coexisting disorder. Results: Spearman's rho -0.605 demonstrates inverse association of IQ with epilepsy. X2 demonstrates statistically significant association (P < 0.05) with gender, severity of ID, cerebral palsy, behavior problems, and family history of mental illness, mental retardation, and epilepsy. Conclusions: Lower IQ score in children with ID has association with occurrence of epilepsy. Epilepsy is also found highly associated with male gender and lower age. [ABSTRACT FROM AUTHOR]

The reactions of benzoylisothiocyanates with salicylamide in pyridine-xylene solution occurs chemoselectively at the hydroxyl group of the salicylamide to afford the corresponding O-benzoyl derivatives. The latter products, on prolonged heating in pyridine-xylene solution, undergo cyclodehydration to give 2-aryl-4H-benzo[e][1,3]oxazin-4-ones in good yields. These compounds could also be synthesized by a direct one-pot reaction of benzoylisothiocyanates with salicylamide by slow addition of benzoylisothiocyanates into a solution of salicylamide in xylene-pyridine solution under reflux. The products have been characterized on the basis of satisfactory analytical and spectral data. [ABSTRACT FROM AUTHOR]

Background & objectives: Multiple drug resistance in epilepsy is a common problem and one third of epilepsy patients remain non responsive to antiepileptic drug (AED) therapy. In this study we aimed to investigate the relationship between the genetic polymorphism of cytochrome P450 genes, namely CYP2C9 and CYP2CI9 with multiple drug resistance in epilepsy patients. Methods: A total of 402 patients with epilepsy were enrolled in this study; 128 were drug resistant and 274 were drug responsive. The peripheral blood samples of the patients with epilepsy were collected. Drug compliance was confirmed in 20 per cent patient population using HPLC. Genotyping of CYP2C9 (*2 and *3), and CYP2C19 (*2 and*3) was carried out by PCR-RFLP. Results: The genotype frequencies of CYP2C9 430 C>T (*2 variant) and CYP2C9 1075 A>C (*3 variant) did not differ significantly in drug resistant versus responsive patients. After combining CYP2C9*2 and CYP2C9*3, the frequency of CYP2C9*1/*3 was significantly lower in drug resistant as compared to drug responsive epilepsy patients (P=0.03, OR=0.53, 95%CI=0.30-0.95). Similarly, combined frequency of all the slow and poor metabolizer variants (2C9 *1/*2, *1/*3 and *2/*3) was also lower as compared to drug resistant group (P=0.03, OR=0.60, 95% CI 0.38-0.96). There was no significant differences in genotypic or allelic distribution of CYP2C19*2 while CYP2C19*3 was monomorphic in northern Indian population. Interpretation & conclusions: Our results demonstrated significant involvement of CYP2C9 genetic variants in the modulation of epilepsy pharmacotherapy confirming the important role of CYP2C9 mutants preventing epilepsy patients from developing drug resistance. [ABSTRACT FROM AUTHOR]

Abstract: Background: GABAA receptors influence the susceptibility to seizures, and variations in the receptor genes can contribute to antiepileptic drug resistance also. Methods: We investigated the possible associations of single nucleotide polymorphisms (SNPs) present in GABRA6 c. 1512 T>C, GABRB2 c. 1412 C>T, and GABRR2 c. IVS2C>G genes of GABAA receptors in epilepsy susceptibility and drug resistance in northern Indian patients with epilepsy. After screening a total of 202 healthy controls and 401 epilepsy patients were enrolled in study. The genotyping was done by PCR-RFLP methods. Results: The GABRA6 c. 1512 T>C, polymorphism was conferring risk for epilepsy susceptibility for TC (P=0.018), CC (P=0.0001) genotype and for C allele (P=0.0002). Another polymorphism GABRB2 c. 1412 C>T was also conferring high risk for epilepsy susceptibility CT (P=0.012), TT (P=0.778) genotype and for variant T allele (P=0.034) but was not associated with drug resistance. No association was found with epilepsy susceptibility or with drug resistance in case of GABRR2 c. IVS2C>G gene polymorphism. Conclusion: Overall, our findings suggest significant involvement of alpha (GABRA6) and beta (GABRB2) subunits of GABAA receptor in epilepsy susceptibility in north Indian population. [Copyright &y& Elsevier]

The purpose of this study was to conduct an assessment of knowledge, attitudes and practices related to intellectual disability among families with such children in Barwani, India. A total of 41 parents (tribal - 28 & non tribal - 13) from 43 villages covering 55,366 population of two blocks of Barwani district were interviewed in their own languages in order to understand their knowledge, attitudes and practices toward their children. A questionnaire with 15 items comprising of major rehabilitation components (medical, educational, economical, social and behavioral) was used for the study. Data were analyzed and the results are discussed based on responses of tribal versus non-tribal and male versus female. Implications for practice are presented. [ABSTRACT FROM AUTHOR]

In epilepsy, there is a tendency towards recurrent unprovoked seizures. Seizures result due to the excessive electrical misfiring in the brain between neurons and disturbance in neurotransmitter release. Several gene products affect the behavior of these neurons by regulating neurotransmission via several mechanisms. One such gene, Synapsin-2 ( SYN2), involved in synaptogenesis is also reported to regulate the neurotransmitter release. We hypothesized that SYN2 gene and its polymorphisms could affect the process of epileptogenesis and therapeutic response in humans. In this hospital-based study, we enrolled 372 patients with epilepsy and 199 control subjects. We selected rs3773364 A>G polymorphism in SYN2 gene and analyzed its distribution in north Indian patients with epilepsy and control subjects. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. According to the results obtained, SYN2 'AG' genotype frequency was significantly higher in patients with epilepsy versus control subjects in north Indian population ( P = 0.02, OR = 1.55, 95% CI = 1.06-2.26). After subclassification, we observed higher frequency of AG genotype in idiopathic patients as compared to control subjects ( P = 0.01, OR = 1.67, 95% CI = 1.08-2.56). There were no significant differences in genotypic (AG: OR = 0.80, P = 0.377; GG: P = 0.628, OR = 1.17) or allelic ( P = 0.86, OR = 1.03) frequency distributions in patients with multiple drug resistance versus patients with drug-responsive epilepsy. Results from our study indicate the involvement of SYN2 gene polymorphism in conferring risk to epilepsy; however, the genetic variant does not seem to modulate drug-response in epilepsy pharmacotherapy. Synapse 64:403-408, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: GABA (γ-amino butyric acid) receptors have always been an inviting target in the etiology and treatment of epilepsy because of its role as a major inhibitory neurotransmitter in the brain. The aim of our study was to find out the possible role of single nucleotide polymorphisms (SNPs) present in GABRA1 IVS11+15 A>G (rs2279020) and GABRG2 588C>T (rs211037) genes in seizure susceptibility and pharmaco-resistance in northern Indian patients with epilepsy. A total of 395 epilepsy patients and 199 control subjects were enrolled for present study. The genotyping was done by PCR-RFLP methods. The GABRA1 IVS11+15 A>G polymorphism conferred high risk for epilepsy susceptibility at genotype ‘AG’ (P =0.004, OR=1.77, 95% CI=1.20–2.63), ‘GG’ (P =0.01, OR=1.80, 95% CI=1.15–2.80) and G allele level (P =0.001, OR=1.50, 95% CI=1.16–1.92). Moreover this polymorphism was also associated with multiple drug resistance in patients with epilepsy for homozygous variant ‘GG’ genotype (P =0.031, OR=1.84, 95% CI=1.05–3.23) and G allele (P =0.020, OR=1.43, 95% CI=1.05–1.95). However GABRG2 588C>T polymorphism was not found to be associated either with epilepsy susceptibility or with drug resistance. Overall results indicate differential role of different subunits of GABAA receptor subtypes in epilepsy susceptibility and pharmacotherapy. [Copyright &y& Elsevier]

A simple method is described for the preparation of 3-aryl-2-thioxo-4(3 H)-quinazolinones ( 4) by the reaction of anthranilic acids and ammonium or triethylammonium N-aryl-dithiocarbamates in ethanol. The method is also applicable to the preparation of 3-ethyl-2-thioxo-4(3 H)-quinazolinone. [ABSTRACT FROM AUTHOR]

A series of new 2-imino-3-(4-arylthiazol-2-yl)-4-thiazolidinones and their 5-arylidene derivatives have been synthesized from 2-amino-4-arylthiazoles as starting materials. The reaction mechanism has also been critically examined. Of all the synthetic compounds tested against the agricultural fungi Trichoderma harzianum and Curvularia lunata, two compounds, namely 2-imino-3-(4-p-chlorophenylthiazol-2-yl)-4-thiazolidinone and S-benzylidine-2-imino-3-(4-p-tolylthiazol-2-yl)-4-thiazolidinone exhibited the most potent fungicidal effect. [ABSTRACT FROM AUTHOR]

Intrinsic metabolism shapes the immune environment associated with immune suppression and tolerance in settings such as organ transplantation and cancer. However, little is known about the metabolic activities in an immunosuppressive environment. In this study, we employed metagenomic, metabolomic, and immunological approaches to profile the early effects of the immunosuppressant drug tacrolimus, antibiotics, or both in gut lumen and circulation using a murine model. Tacrolimus induced rapid and profound alterations in metabolic activities within two days of treatment, prior to alterations in gut microbiota composition and structure. The metabolic profile and gut microbiome after seven days of treatment was distinct from that after two days of treatment, indicating continuous drug effects on both gut microbial ecosystem and host metabolism. The most affected taxonomic groups are Clostriales and Verrucomicrobiae (i.e., Akkermansia muciniphila), and the most affected metabolic pathways included a group of interconnected amino acids, bile acid conjugation, glucose homeostasis, and energy production. Highly correlated metabolic changes were observed between lumen and serum metabolism, supporting their significant interactions. Despite a small sample size, this study explored the largely uncharacterized microbial and metabolic events in an immunosuppressed environment and demonstrated that early changes in metabolic activities can have significant implications that may serve as antecedent biomarkers of immune activation or quiescence. To understand the intricate relationships among gut microbiome, metabolic activities, and immune cells in an immune suppressed environment is a prerequisite for developing strategies to monitor and optimize alloimmune responses that determine transplant outcomes. [ABSTRACT FROM AUTHOR]