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Introduction: N-methyl-d-aspartate receptor (NMDAR) and tau protein play an important role in neuronal death due to cerebral ischemia or ischemic stroke. Unfortunately, no drug has been discovered except tissue plasminogen activator (tPA) to fight against ischemic stroke. Virtual high throughput screening to find out possibilities of bioactive molecules to target NMDAR and tau protein to treat ischemic stroke may be an option for drug discovery. Objective: The current study aimed to assess the molecular interaction of some bioactive molecules with NMDAR and tau protein in silico to incriminate ischemic stroke. Methods: A computational method based on ligand-protein interaction technique has been used in the present study to identify the therapeutic potential of some bioactive molecules for the possible treatment of ischemic stroke. For this purpose, 50 bioactive molecules were screened and docking analysis was performed for two target proteins, NMDAR and tau protein. In this study, for each protein target, the best poses were identified based on binding energy and inhibition constant. Different pharmacological properties of selected bioactive molecules were also analyzed to determine their absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties in silico. All were found in the acceptable range and followed Lipinski’s rule. Results: In the present study of the 50 screened bioactive molecules, top 10 molecules have been identified, of which best two bioactive molecules such as gossypin, viniferin have been predicted to be potential neuroprotective agents against cerebral ischemia induced alteration of NMDAR and tau protein functional integrities. Conclusion: Gossypin’ was the best bioactive compound interacting with NMDAR and tau protein.

Objective: The phytochemical analysis of Terminalia chebula, Terminalia bellirica, Phyllanthus emblica fruit extract as well as to evaluate the potential synergistic activity of screened plant extracts for anti-oxidant, anti-inflammatory and anti-cancer activity on MCF-7 breast cancer cell line. Methodology: In present study phytochemical constituent from selected plant material was extracted in different solvents. Antioxidant activity was evaluated by DPPH and FRAP assay against standard antioxidant. MTT assay was performed to find out cytotoxic and anti-inflammatory effect on MCF- breast cancer cell line. Result: Phytochemical analysis of the performed which showed that alkaloids, phenols, flavonoids and saponins. In context of antioxidant assays almost selected extracts showed moderate activity but ethanol extract of Terminalia chebula, proven to be having significant antioxidant activity over all extracts. Anti-inflammatory activity of MCF-7 breast cancer cell line exhibited that good activity with IC50 value 228.82µg/ml. Whereas Methanol extract of Terminalia bellirica and Aqueous extract of Phyllanthus emblica shown 432.45µg and 259.02µg respectively. Conclusion: The present study concludes that in among three tested extracts, Ethanol extract of Terminalia chebula exhibited prominent anticancer activity against Breast cancer (MCF-7) with significant IC50 value 228.82 µg. However further studies are needed to find out the structural of bioactive compounds and investigate mechanisms of antioxidant and anticancer activities of the bioactive compounds in in-vivo animal study.

Introduction and Aim Cadmium is an environmental pollutant and potential nepho-toxicant to humans. Increase in industrialization interruptions heavy metal pollution in the world. Heavy metal chemicals destruction of organ functions and disrupts physiological homeostasis. Only the chelation therapy that involve the remove the heavy metal. Our study was designed to resolve the nehro-protective possessions of tea beverage on experimentally persuaded cadmium toxicity in the renal of rats. Tea was given orally while cadmium was administered subcutaneously. Method: Adult rats were divided into four groups (n=6/group). One control group (normal saline), two cadmium chloride group (CdCl2, 1.0 mg/kg, b.wt; i.p), Three Black tea extract group (black tea extract, 2.5 gm tea leaf/dl of water that is 2.5% of aqueous BTE) and Cadmium chloride plus black tea extract group (cadmium chloride + BTE). Simultaneously for 21 days. Results: Supplementation of black tea remarkably improves kidney architecture of rats treated with cadmium chloride group. Conclusion: Black tea extract seems to be nephron-protective against cadmium induced oxidative stress.

SARS-CoV-2 the new strain of SARS corona virus is an RNA virus that inflicts acute respiratory distress syndrome due to infection of the alveolar epithelial cells, its primary target. No effective drug is currently available to treat this viral infection. Therefore, we focused on identifying inhibitors of the main viral protease domain (Mpro) which plays important role in the virus life cycle. Two tired computer-aided drug discovery approach were adopted for screening of novel inhibitors against Mpro, the target protein. First, based on their ADME/T properties, phytochemicals as well as synthetic drugs six compounds were selected from the available database. In second screening by molecular docking based on binding affinity and molecular interactions of these compounds with Mpro led to the identification of the best phytochemical and synthetic compound against Mpro. The result of docking complex showed that, interacting residues for myricetin are continuous while, in case of fosamprenavir, these are non-contiguous. Both molecules interact with the residues in the active site occupying the site for the catalytic activity indicate possible competitive inhibitors of the Mpro.

Introduction: Oxidative stress is an imbalance between an organism's reactive oxygen species [ROS] production and antioxidant defence capacity. Long-term oxidative stress contributes to cellular ageing and plays a role in the pathogenesis of several diseases. Several investigations indicated that oxidative stress has a role in the pathogenesis of ASD. Objectives: Present study was undertaken to record the association of GSTTT1 and GSTM1 null genotype among the autistic population of India. Methods: Genomic DNA was isolated from 108 autistic children along with healthy age-matched control. The quality and quantity of the isolated genomic DNA were analysed. GSTT1 and GSTM1 null genotype was analysed using polymerase chain reaction with internal positive control. Statistical analysis was performed using SPSS 15.0. Results: Present study included 85 males and 23 females with a mean age of 11.7±3.5 and 75 males and 33 females with a mean age of 11±2.0 in the control group. 32 (29.6%) autistic cases showed null genotypes for GSTT1 and 21(19.4%) autistic children showed null genotypes for GSTM1. 3 (2.85%) control children showed a null genotype for GSTT1 and 5 (4.6%) control children showed a null genotype for GSTM1. The GSTT1 and GSTM1 null genotypes were observed to be significantly associated with the risk of autism (p value-0.0001, OR-14.73, 95% CI 4.35-49.90) and (p value-0.003, OR-4.731, 95% CI 1.71-13.08) respectively. Conclusion: The findings of our study suggested that GSTT1 and GSTM1 null genotype is one of the potential risk factors for autism through oxidative stress mechanism in our population. other: None

Objective To assess the influence of oxidative stress on the gene expression of nitric oxide synthases (NOS 3 and NOS 2) and, hence, the cardiovascular responses in preeclampsia. Methods This was a case control study in which patients with preeclampsia (PE group) and normal pregnancy controls (NP group) were included according to the guidelines of the American College of Obstetricians and Gynecologists (ACOG). The serum levels of malondialdehyde (MDA), total antioxidant capacity, and nitric oxide (NO) were estimated, and the heart rate andmean arterial pressure were recorded. The gene profiling of NOS3 and NOS2 was performed through real-time polymerase chain reaction (RT-PCR). The statistical analysis was performed using the Student t-test, and values of p

Background Hemophilia B (HB) is an X-linked bleeding disorder resulting from coagulation factor IX defects. Over 3,000 pathogenic, HB-associated mutations in the F9 gene have been identified. We aimed to investigate the role of F9 variants in 150 HB patients using sequencing technology. Methods F9 gene sequences were amplified from peripheral blood-derived DNA and sequenced on an Applied Biosystems (ABI) 3500 Sanger sequencing platform. Functional and structural predictions of mutant FIX were analyzed. Results Among 150 HB patients, 102 (68%), 30 (20%), and 18 (12%) suffered from severe, moderate, and mild HB, respectively. Genetic analysis identified 16 mutations, including 3 novel mutations. Nine mutations (7 missense and 2 stop-gain) were found to be pathogenic. Only 3 mutations (c.127C>T, c.470G>A, and c.1070G>A) were associated with different severities. While 2 mutations were associated with mild HB cases (c.304C>T and c.580A>G), 2 (c.195G>A and c.1385A>G) and 3 mutations (c.223C>T, c.1187G>A, and c.1232G>A) resulted in moderate and severe disease, respectively. Additionally, 1 mutation each was associated with mild-moderate (c.*1110A>G) and mild-severe HB disease (c.197A>T), 4 mutations were associated with moderate-severe HB cases (c.314A>G, c.198A>T, c.676C>T, and c.1094C>A). FIX concentrations were lower in the mutated group (5.5±2.5% vs. 8.0±2.5%). Novel p.E66D and p.S365 mutations were predicted to be pathogenic based on changes in FIX structure and function. Conclusion Novel single nucleotide polymorphisms (SNPs) largely contributed to the pathogenesis of HB. Our study strongly suggests that population-based genetic screening will be particularly helpful to identify risk prediction and carrier detection tools for Indian HB patients.

Background: Cilnidipine belongs to fourth generation dihydropyridine calcium channel blocker (CCB). It is a dual L & N-type CCB. L- type calcium channels are present on the vascular smooth muscle and N-type calcium channels are present on the presynaptic nerve terminals. Cilnidipine has a vasodilating effect, its action is slow and long lasting. Aim and objectives: Aim of present study was to demonstrate the beneficial effects of cilnidipine on the hypertensive renal injury rats. And our objectives is to assess renal injury parameters (Proteinuria, Creatinine clearance, Renal fibrosis/glomerulosclerosis) in response to chronic NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) treatment in the presence or absence of cilnidipine treatment. Material and methods: Male albino Wister rats were procured from institutional animal house, divided into 4 groups (n=6 in each group). Group1 treated with vehicle (control), group2 treated with cilnidipine, group3 treated with L-NAME, group4 treated with L-NAME & cilnidipine. 24 hour urinary protein and creatinine clearance were measured. Serum urea and creatinine levels are also measured. Urinary and serum Angiotensin II levels were measured. Histopathological examination of kidneys was performed. Results: Our results demonstrate that treatment with cilnidipine (group4) there is reduction in 24hr urinary protein, improvement in creatinine clearance. We observed there was renal glomerulosclerosis and tubular degeneration of kidney tubules in group3 rats and reduction of renal injury in group4 rats. We also found reduced urinary and serum Angiotensin II level in cilnidipine treated (group 4) rats. Conclusion: These findings indicated that cilnidipine act as renoprotective agent and reduces glomerular damage in L-NAME induced hypertensive rats.

Objectives: Vascular stiffness due to ageing assessed by alteration in mean arterial blood pressure, brachial-ankle and carotid-femoral pulse wave velocity (b-f PWV/c-f PWV) and brachial and ankle arterial stiffness index (ASI). The present study aimed to determine the influence of ageing on vascular health and its relation to oxygen sensing protein that is, erythropoietin (EPO), in both genders (men and women). Materials and Methods: Randomly selected 204 healthy participants involving men and women between 20 and 95 years among the general population of city. The total sample size was split into six groups from Group I to VI, each containing 17 men participants and 17 women participants. We determined PWV [brachial-ankle and carotid-femoral (PWV)] and ASI (brachial ASI and ankle ASI) by using periscope and estimated serum erythropoietin (Epo) by ELISA method and implemented a one-way ANOVA post hoc test for statistical analysis by using SPSS software version 23. Results: Decreased serum EPO with increased vascular parameters such as mean arterial pressure (MAP), PWV and ASI observed in Group 5 and 6 of both genders. Conclusion: We conclude that ageing influences PWV, ASI, MAP and EPO in men and women participants.

Objectives Dietary high fat possibly causes oxidative stress; also it makes deleterious effect on kidney functions and land up in lipotoxicity in renal tissue. Lipotoxicity is the pathological situation where lipid Peroxidation occurs and generates reactive oxygen species (ROS). Overproduction of ROS than antioxidant present in tissues cause oxidative stress. Terminalia arjuna is found to be potential antioxidant that counteract oxidative stress and possibly maintain glomerular integrity. Methods Ethanolic extract of T. arjuna (ETO) was prepared and phytochemical analysis was done. Rats were divided into four groups, having six rats in each group as following; group 1-Control (20% fat); group 2 (ETO 100 mg/kg/b.wt); group 3 (30% fat) and group 4 (30% fat + ETO 100 mg/kg/b.wt). Dietary and ETO supplementation were continued for 21 days. Gravimetric, kidney functions (blood urea and serum creatinine) and oxidative stress markers like MDA, SOD and GSH were evaluated. Histopathological analysis was done on kidney along with measurement of glomerular integrity. Morphometrical analysis of glomerular integrity was evaluated by measuring glomerular length, width, glomerular area and Bowman’s capsule radius. One way ANOVA was done for analysis of data. Results Blood urea and serum creatinine levels were significantly higher in high fat fed rats indicating renal dysfunction. High fat diet showed significant increase in MDA, decrease in SOD and GSH in rats fed with high fat diet, which indicate generation of oxidative stress. Supplementation of ETO showed amelioratic effect against high fat diet induced renal dysfunction and oxidative stress. Histopathological findings were significantly corroborated with morphometrical analysis of glomerular integrity. Conclusions Ethanolic extracts of T. arjuna supplementation found to be beneficial against high fat induced renal alterations in terms of functions and architecture.

Non-syndromic sensory neural hearing defect is one of the genetic diseases inherited from parents to offerings. The autosomal recessive form affects a large population worldwide and has become a major concern in the social and professional lives of many people. There are many factors and genes which are involved in hearing loss but the Gap Junction Beta 2 (GJB2) gene which encodes the connexin 26 protein, is a major cause of non-syndromic recessive deafness (NSRD). This study aims to record and analyze GJB2 gene mutations in the hearing-impaired population of North Karnataka, India. In this study, we included 368 congenitally hearing-impaired children from North Karnataka, India, under 18 years of age. After thorough clinical examinations, patient's history and proper audiological results, peripheral blood samples were collected and subjected to genetic analysis. We recorded that 54.8% of the NSRD cases have an autosomal recessive mutation in the coding region of the GJB2 gene. The frequency of W24X (25%) mutation was found to be high in the present study population. From this study we can suggest that, identifying this mutation in new-borns definitely helps in the early diagnosis of hearing loss.

Background: The COVID-19 pandemic has encouraged doctors to look for novel ways of treating patients with respiratory failure, due to the limited availability of ventilators and high flow nasal cannula. The aim of the study is to assess the efficacy of using Bains circuit as an alternative to HFNC and NIV as a life saving tool, in patients with respiratory failure, during COVID-19 pandemic second wave in India. Methods: This is a prospective interventional study carried out in the intensive care unit of Shri B.M Patil Medical College Hospital and Research Centre, Vijayapur, India, from May 2021 to June 2021. All patients (n=90) in respiratory failure, not responding to therapy by oxygen mask, were included in the study. Patients were started on Bain circuits, one end connected to a non-invasive ventilation mask fitting to the face of the patients and the other end connected to a central oxygen port. Patient vital parameters were assessed on an hourly basis. The blood gas analyses were done before and after using Bains. Results: The study showed diabetes (33.4%), hypertension (22.2%), and diabetes with hypertension(11.1%) as comorbid factors among the ICU admitted patients. The results from the arterial blood gas analyses showed a statistically significant increase in SP02 (%) and a decrease in respiratory rate (cycles/min) in the patients after being kept on Bains (p Conclusion: The study highlights a novel concept of using Bains circuit as an effective alternative to HFNC and NIV for oxygenation in critically ill COVID-19 patients during scarcity of NIV and HFNC at the peak of pandemic.

Reactive oxygen species by uncoupled eNOS is linked to endothelial dysfunction. Ellagic acid (EA), a polyphenol possesses numerous biological activities including radical scavenging. whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels remains unknown. Molecular docking provides an initial model of protein and molecular interactions in various physiological and/or pathological functions. To identify a eNOS modulatory biomolecule through molecular docking as possible vascular protective agent. On the basis of binding affinities and other physicochemical features, a molecular docking-based approach was used to classify and evaluate eNOS binding micronutrients found in natural sources, Lipinski's rule was used taking into account their adsorption, delivery, metabolism, and excretion (ADME). An insilico approach focused on the ligand–protein interaction technique to determine the therapeutic potential of certain phytochemical-based drugs for the vascular remodelling.20 bioactive molecules were screened, docking analysis on human eNOS proteins was performed. The best poses for target protein was established based on binding energy and inhibition constant. EA and caffeine acid are the strongest candidates for eNOS protein functional norms. This provides a novel insight into the interaction properties of known human eNOS protein with EA and used as a therapeutic agent in various pathologies. Predicting interaction of ellagic acid with eNOS protein by molecular docking in endothelial dysfunction. [Image: see text]

In this report, novel pH-sensitive interpenetrated network (IPN) polyspheres were developed utilizing polyacrylamide-g-locust bean gum (PAAm-g-LBG) in combination with sodium alginate (SA) to achieve intestinal targeted delivery of ketoprofen. PAAm-g-LBG was synthesized under microwave irradiation wherein ceric ammonium nitrate was used as reaction initiator and then conversion of PAAm-g-LBG as pH-sensitive copolymer was carried out by alkaline hydrolysis. The PAAm-g-LBG copolymer was characterized through 1H-NMR, FTIR and elemental analysis. The IPN polyspheres exhibited pH-depended swelling or de-swelling with the alteration of surrounding pH. The in-vitro release of drug from IPN polyspheres was found to be higher (≈ 90%) in phosphate buffer of pH 7.4 in comparison with that in pH 1.2 buffer (10.6%). The in-vivo pharmacokinetic, anti-inflammatory screening and stomach histopathology studies performed on Wistar rats revealed pH sensitivity of IPN polyspheres where ketoprofen was successfully targeted to small intestine resulting in reduced side effects of ketoprofen like ulcer formation, erosion of gastric mucosa and hemorrhages.

OBJECTIVE: Patients exposed to chronic sustained hypoxia frequently develop cardiovascular disease risk factors to ultimately succumb to adverse cardiovascular events. In this context, the present study intends to assess the role of cilnidipine (Cil), a unique calcium channel blocker that blocks both L-type and N-type calcium channels, on cardiovascular pathophysiology in face of chronic sustained hypoxia exposure. MATERIALS AND METHODS: The study involved Wistar strain albino rats. The group-wise allocation of the experimental animals is as follows - Group 1, control (21% O2); Group 2, chronic hypoxia (CH) (10% O2, 90% N); Group 3, Cil + 21% O2; and Group 4, CH (10% O2, 90% N) + Cil (CH + Cil). Cardiovascular hemodynamics, heart rate variability, and endothelial functions (serum nitric oxide [NO], serum endothelial nitric oxide synthase [NOS3], and serum vascular endothelial growth factor [VEGF]) were assessed. Cardiovascular remodeling was studied by histopathological examination of the ventricular tissues, coronary artery (intramyocardial), and elastic and muscular arteries. Normalized wall index of the coronary artery was also calculated. RESULTS AND CONCLUSION: The results demonstrated altered cardiovascular hemodynamics, disturbed cardiovascular autonomic balance, increased levels of VEGF and NOS3, and decreased bioavailability of NO on exposure to chronic sustained hypoxia. The histopathological examination further pointed toward cardiovascular remodeling. Treatment with Cil ameliorated the cardiovascular remodeling and endothelial dysfunction induced by CH exposure, which may be due to its blocking actions on L/N-type of calcium channels, indicating the possible therapeutic role of Cil against CH-induced cardiovascular pathophysiology.

Aim: This study aimed at screening and development of TG2 inhibitors as anti lung cancer agent. Background: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from the transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative diseases, and also cancer. Objective : The proposed study focused on screening potent inhibitors of TG2 by in-silico method and synthesize their derivative as well as analyse its activity by utilizing an in-vitro approach. Material and Methods: Molecular docking studies have been carried out on the different classes of TG2 inhibitors against the target protein. Nearly thirty TG2 inhibitors were selected from literature and docking was performed against transglutaminase 2. The computational ADME property screening was also carried out to check their pharmacokinetic properties. The compounds which exhibited positive ADME properties with good interaction while possessing the least binding energy were further validated for their anti-lung cancer inhibition property against A549 cell lines using cytotoxicity studies. Results: The results of the present study indicate that the docked complex formed by cystamine showed better binding affinity towards target protein, so this derivative of cystamine was formed using 2,5 dihydrobenzoic acid. Invitro results revealed that both molecules proved to be good cytotoxic agents against A549 lung cancer (875.10, 553.22 μg/ml), respectively. Further, their activity needs to be validated on TG2 expressing lung cancer. Conclusion : Cystamine and its derivative can act as a potential therapeutic target for lung cancer but its activity should be further validated on TG2 expressing lung cancer.

Background: Critical hypoxia in this COVID-19 pandemic results in high mortality and economic loss worldwide. Initially, this disease’ pathophysiology was poorly understood and interpreted as a SARS (Severe Acute Respiratory Syndrome) pneumonia. The severe atypical lung CAT scan images alerted all countries, including the poorest, to purchase lacking sophisticated ventilators. However, up to 88% of the patients on ventilators lost their lives. It was suggested that COVID-19 could be similar to a High-Altitude Pulmonary Edema (HAPE). New observations and pathological findings are gradually clarifying the disease. Methods: As high-altitude medicine and hypoxia physiology specialists working and living in the highlands for over 50 years, we perform a perspective analysis of hypoxic diseases treated at high altitudes and compare them to Covid-19. Oxygen transport physiology, SARS-Cov-2 characteristics, and its transmission, lung imaging in COVID-19, and HAPE, as well as the causes of clinical signs and symptoms, are discussed. Results: High-altitude oxygen transport physiology has been systematically ignored. COVID-19 signs and symptoms indicate a progressive and irreversible failure in the oxygen transport system, secondary to pneumolysis produced by SARS-Cov-2’s alveolar-capillary membrane “attack”. HAPE’s pulmonary compromise is treatable and reversible. COVID-19 is associated with several diseases, with different individual outcomes, in different countries, and at different altitudes. Conclusions: The pathophysiology of High-altitude illnesses can help explain COVID-19 pathophysiology, severity, and management. Early diagnosis and use of EPO, acetylsalicylic-acid, and other anti-inflammatories, oxygen therapy, antitussives, antibiotics, and the use of Earth open-circuit- astronaut-resembling suits to return to daily activities, should all be considered. Ventilator use can be counterproductive. Immunity development is the only feasible long-term survival tool.

The critical hypoxia in COVID-19 patients during this pandemic, has taken away many lives all around the globe. The mechanism has been poorly understood and initially, word got around that it was a SARS (Severe Acute Respiratory Syndrome) pneumonia. The atypical images in lung computerized axial tomography (CAT) scans were alarming. This immediately alerted everyone including poor countries to purchase lacking sophisticated ventilator equipment. However, in some countries, even 88% of the patients on ventilators lost their lives. New observations and pathological findings are gradually clarifying the disease. What seems evident is that it is not only one disease but several, with different responses in different countries and different altitudes. The critical hypoxia and «gasping» present in some patients are not totally understood. It was mentioned that it could be like a High-Altitude Pulmonary Edema (HAPE). Hereby, as high-altitude medicine and hypoxia physiology specialists, we compare the pathophysiology with that of high-altitude exposure in order to understand the mechanisms involved. Some differences in lung radiological images along with transmission and viral attack mechanisms are discussed. The oxygen transport triad used at high-altitude can be applied on this pathology in order to propose even the use of erythropoietin (EPO) early in the treatment. The immune system is the most important long-term survival tool, so we suggest a short-term strategy: the use of special Earth open-circuit astronaut-resembling suits with effective outside air filtering re-breathing mechanisms in order to return to work and daily activities, without contamination risk. Thereby, the curve can be flattened without quarantine and the economy could recover.

The most prevalent severe inherited hemorrhagic condition is hemophilia, which means "love of blood." Hemophilia A and B are caused by a lack or malfunction of the factor VIII and factor IX proteins.The present study is to determine the prevalence and clinical profile of hereditary coagulation disorder, particularly hemophilia B, in Karnataka.The study comprised 150 HB patients with a mean age of 25, nIn our study cohort, the majority of the 58 (38.7%) cases belong to 21-30 years of age. The mean age of onset was 2.0 ± 1.0 years in severe, 7.5 ± 2.8 0 years in moderate, and 10.0 ± 3.5 years in mild HB patients. Out of 150 HB cases, 102 (68%) cases were diagnosed as severe, 30 (20%) as moderate, and 18 (12%) as mild. Mean factor IX levels were 0.6 ± 0.2, 2.5 ± 1.3, and 8.0 ± 2.6 in the severe, moderate, and mild group, respectively. A family history of bleeding was observed in 97 [64.7%] HB patients. Forty-seven (32.3%) HB patients had a history of consanguinity. The most common initial site of bleed was in joints in 86 [57.3%].The present study is one of the fewer studies from Karnataka studying the demographic and clinicopathological features of hemophilia B. Early diagnosis can be only helpful with knowledge of spectral presentation of hemophilia B in a local population.

Autism is a complex neurodevelopmental condition which is clinically, etiologically and genetically heterogeneous. The predisposition of genes and genetic loci has been under study over the last few decades. Autism is increasing dramatically over the last few years in India. Mutations in two x-linked neuroligin genes viz. NLGN3 and NLGN4X have been recently implicated in autism pathogenesis. In the current study, for the first time in India, we screened the genetic variations in transmembrane neuroligin 4× gene in the Indian autistic population using sequencing technology. 1828 mentally ill children were screened around the North Karnataka region of India and 136 autistic children were identified, out of which 108 autistic children who were fulfilling the inclusion criteria were taken for the study. DNA was isolated from the clinical samples and exonic regions were amplified. Sanger sequencing was carried to screen the genetic variations and expression profiling was performed using Real time PCR. Sequencing results revealed 25 different variants (eight 5′UTR variants, four missense variants, four synonymous variants, one frameshift variant and eight 3′ UTR variants). One novel frameshift variation (p.Gly214GlyfsTer2) was recorded in 19 (17.5%) autistic individuals. This novel frameshift mutation leads to a premature stop codon. Relative expression of the NLGN4X gene in autistic children with novel frameshift mutation was largely reduced compared to the control group [0.052 and 1.217 respectively, p-value 0.00001]. The present study shows novel frameshift mutation causes abnormal NLGN4× protein that leads to loss of binding to presynaptic neurexin during synapses. Therefore neuroligin 4× is the potential target gene in the Indian autistic population for future functional analysis.