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Gene expression varies due to the intrinsic stochasticity of transcription or as a reaction to external perturbations that generate cellular mutations. Co-regulation, co-expression and functional similarity of substances have been employed for indoctrinating the process of the transcriptional paradigm. The difficult process of analysing complicated proteomes and biological switches has been made easier by technical improvements, and microarray technology has flourished as a viable platform. Therefore, this research enables Microarray to cluster genes that are co-expressed and co-regulated into specific segments. Copious search algorithms have been employed to ascertain diacritic motifs or a combination of motifs that are performing regular expression, and their relevant information corresponding to the gene patterns is also documented. The associated genes co-expression and relevant cis-elements are further explored by engaging Escherichia coli as a model organism. Various clustering algorithms have also been used to generate classes of genes with similar expression profiles. A promoter database ‘EcoPromDB’ has been developed by referring RegulonDB database; this promoter database is freely available at www.ecopromdb.eminentbio.com and is divided into two sub-groups, depending upon the results of co-expression and co-regulation analyses.

The research explored the gender stereotypical representation in curriculum and how the institutions of conventional depiction blemished the actual image and roles of both the sexes (female and male). For this purpose, Critical Discourse Analysis (CDA) through the three-dimensional model of Norman Fairclough was applied to analyze the relationship between powerful (dominating, controlling) and powerless (feeble, submissive) social groups. The present research explored identities from Punjab Textbook Board (PTB) textbooks of the middle/elementary level to identify and comprehend gender ideology. The study focused on the textual aspects that contribute to the construction of conventional images and stereotypical behavior regarding gender ideology in children at their fledgling stage of life. The research concluded that females were disregarded and excluded from the textbooks and the textbooks portrayed a diminished image of women; whereas, the males were shown as authoritative and dominating in all the socially prestigious fields like, working and earning. The present study, thus, maintained that domination and power had gone with the male members of the society; whereas, the females were publicized as feeble and submissive, working and serving at home, and maintaining their domestic and conjugal images in the textbooks. Moreover, the research recommended the revision of educational policies, curriculum, and textbooks to impart a balanced worldview to children so that socially and emotionally balanced individuals may be developed through education.

Distortion product otoacoustic emissions (DPOAEs) are composed of distortion and reflection components. Much is known about the influence of the stimulus frequency ratio (f 2 /f 1 ) on the overall/composite DPOAE level. However, the influence of f 2 /f 1 on individual DPOAE components is not as well examined. The goals of this pilot study were to systematically evaluate the effects of f 2 /f 1 on DPOAE components in clinically normal-hearing young adult ears. To extend the limited reports in the literature, this examination was carried out over an extended frequency range using two stimulus-level combinations.DPOAEs were recorded from seven normal-hearing, young adult ears for f 2 frequencies between 0.75 and 16 kHz over a range of f 2 /f 1 using two stimulus-level combinations. The distortion (DPOAE D ) and reflection (DPOAE R ) components were separated using an inverse fast Fourier transform algorithm. Optimal ratios for the composite DPOAE and DPOAE components were determined from smoothed versions of level versus ratio functions in each case.The optimal ratio for the composite DPOAE level increased with stimulus level and decreased as a function of frequency above 1 kHz. The optimal ratios for the DPOAE components followed a similar trend, decreasing with increasing frequency. The optimal ratio for DPOAE D was generally higher than that for DPOAE R . The overall level for DPOAE D was greater than that of DPOAE R , both decreasing with increasing frequency. DPOAE R , but not DPOAE D , became unrecordable above the noise floor at the higher frequencies.DPOAE components behave similarly but not identically as a function of f 2 /f 1 . The ear canal DPOAE is generally dominated by DPOAE D . The behavior of DPOAE D as a function of f 2 /f 1 is entirely consistent with known properties of cochlear mechanics. The behavior of DPOAE R is more variable across ears, perhaps reflective of the increased number of parameters that influence its final form. Attempting to use an f 2 /f 1 that would allow a greater bias of the ear canal DPOAE toward one component or the other does not appear to be practical.

Introduction: Ectopic pregnancy is the commonest gynecological emergencies. If not treated timely, it places major morbidity upon future fertility and family. Ectopic pregnancy presents a major health problem for women of childbearing age. The increased incidence of ectopic pregnancy has been partially attributed to improved ability in making an earlier diagnosis. Anything that hampers the migration of the embryo to the endometrial cavity could predispose women to ectopic gestation. The most logical explanation for the increasing frequency of EPs is previous pelvic infection; however, most patients presenting with an EP have no identifiable risk factor. Objective: To determine the frequency of fertility outcome (intrauterine pregnancy and extrauterine pregnancy) in patients having history of ectopic pregnancy. Materials and Methods: A total of 92 patients having history of ectopic pregnancy were included in the study in a consecutive manner and assessed for fertility outcome in terms of extrauterine or intrauterine pregnancy. The study utilized descriptive cross sectional study design. The study settings was department of gynecology, Lady Reading Hospital, Peshawar. The study duration was from 1st January 2019 to 31st December 2020. Results: The mean age of the sample was 30.3 + 6.1 years. The mean parity of the sample was 2.1 + 1.5, mean BMI was 26.4 + 3.5kg/m2 and mean gestational age at presentation was 6.7 + 2.1 weeks. With regards to fertility outcome, 39.1% women had extrauterine pregnancy and 60.9% had intrauterine pregnancy. Extrauterine pregnancy though less than intrauterine is still a significant problem in the study’s population with previous history of ectopic pregnancy. Recommendation: The study recommend more research projects particularly interventional studies for proper management of ectopic pregnancy and reduce the burden of extrauterine pregnancies so that even with history of ectopic pregnancy, term delivery can be assured.

Introduction: The World Health Organization declared the COVID-19 epidemic an international public health emergency on January 30th, 2020. Many patients required ICU admission for advanced respiratory support, including high flow nasal oxygen, and non‐invasive, and invasive mechanical ventilation. Lower Ct values may be associated with disease severity Objective: To observe the Cycle threshold (Ct) value and outcome of the COVID-19 patients admitted in Intensive Care Unit (ICU). Methods: Nasopharyngeal/ oropharyngeal samples were collected via swabs from suspected COVID-19-positive patients admitted to Corona ICU of Teaching Hospital, Dera Ghazi Khan (DG Khan). Samples were proceeded for RNA extraction and amplification and were declared positive on basis of the S-shaped amplification curve at FAM (ORF1) and ROX channel, and a Ct value of ≤40. Results: Out of 59 ICU admissions, 17 were females and 42 males. The highest percentage of mortality was observed in the 60 and above years of age group (78.98%). Ct values were lower in patients who expired as compared to the patients who were discharged (mean 21.052 vs 23.739). Conclusion: Males were more frequently admitted to ICU for management of severe infection by COVID-19 than females. Mortality is associated with increasing age. Cycle threshold (Ct) values were lower in patients who expired than those who recovered Keywords: Cycle threshold, RT-PCR, COVID-19, ICU

Distortion product otoacoustic emission (DPOAE) levels plotted as a function of stimulus frequency ratio demonstrate a bandpass shape. This bandpass shape is narrower at higher frequencies compared to lower frequencies and thus has been thought to be related to cochlear mechanical tuning. However, the frequency- and level-dependence of these functions above 8 kHz is largely unknown. Furthermore, how tuning estimates from these functions are related to behavioral tuning is not fully understood. From experiment 1, we report DPOAE level ratio functions (LRF) from seven normal-hearing, young-adults for f(2) = 0.75-16 kHz and two stimulus levels of 62/52 and 52/37 dB FPL. We found that LRFs became narrower as a function of increasing frequency and decreasing level. Tuning estimates from these functions increased as expected from 1-8 kHz. In experiment 2, we compared tuning estimates from DPOAE LRF to behavioral tuning in 24 normal-hearing, young adults for 1 and 4 kHz and found that behavioral tuning generally predicted DPOAE LRF estimated tuning. Our findings suggest that DPOAE LRFs generally reflect the tuning profile consistent with basilar membrane, neural, and behavioral tuning. However, further investigations are warranted to fully determine the use of DPOAE LRF as a clinical measure of cochlear tuning.

Chronic exposure to environmental carcinogens like tobacco smoke and smokeless tobacco increases the CYP1A1 gene expression. The CYP1A1 gene polymorphisms and overexpression have been linked to oral cancer. Non-synonymous polymorphism in the gene coding region affects the structural stability and function of the CYP1A1 protein due to the substitution of amino acids. We screened all the 1693 polymorphisms reported for the CYP1A1 gene and filtered down to 25 Non-synonymous SNPs (nsSNPs) that are relevant in cancer. Further, we investigated all 25 SNPs using various in silico methods, to predict whether any of these SNPs cause changes in the structure and possible function of the protein. Among the three substitutions, the T461N (rs1799814), I462F (rs1048943) were found to be deleterious and functionally significant, whereas I462V (rs1048943), reported as functionally significant in some populations, but observed as a tolerated neutral variant by in silico analysis. Furthermore, by molecular dynamics simulation, it was observed that T461N and I462F variants lead to structural changes when compared to the native protein and I462V variants. Eventually, these nsSNPs in CYP1A1 would provide prior information for identifying the functionally valid SNPs as a genetic risk factor and may be targeted for cancer prevention studies and therapies.

Objective: The aim of this study is to compare the efficacy of manual vacuum aspiration and conventional evacuation and curettage in early pregnancy loss. Study Design: Randomized control trial. Place and Duration: Study was conducted at department of obstetrics and gynecology Lady Reading Hospital Peshawar from 1st January 2019 to 31st August 2020. Methods patients were early pregnancy loss (12 weeks or lesser gestational age) were enrolled. Patients were divided into two groups by lottery method. Group A were the patients who had conventional evacuation and curettage treatment. Group B were patient in which MVA was used. Patient’s demographics were recorded after taking written consent. Gestational age was calculated from first day of last menstrual cycle and by ultrasound. Cervical ripening was done by (misoprostol 400mcg) two hours before procedure. Procedure was carried out under aseptic measures. Complete uterine evacuation by either procedure was assessed by ultrasound after procedure and complications were noted data was analysed by SPSS. Results: mean age in Group A was 29 years with SD ± 8.65 while mean age in Group B mean age was 30 years with SD ±7.62. Group B (Manual Vacuum Aspiration) was effective in 96% patients while Group A(Conventional Evacuation and Curettage) was effective in 89% patients. complications were fewer in MVA as compared to conventional evacuation and curettage.

This paper discusses the basic elements of a narrative by analyzing the short story "The Happy Prince" written by Oscar Wilde. The study, evaluation, and understanding of narrative are called narratology. Here in this paper, the narrative pattern of a short story is analyzed to elaborate narratology and its usage in narrative analysis. In the narrative analysis, the main focus is on the art of characterization, plot construction, narrative pattern of story, point of view and speech, thought presentation to make this short story more comprehensive and understandable for its readers. Special observation is made by representing some dialogues from the source text "The Happy Prince" by Oscar Wilde. In narratology the ideas of its main proponents such as Aristotle, Gerard Genette and Vladimir Propp are applied on source text to articulate the desired upshot. The aim to conduct this research is to illustrate narratology, narrative patterns and its application on literary text for its readers especially for the teachers and learners so that they can better interpret any narrative piece of writing.

Objective: to record the rate of low birth weight in pregnant women with vitamin D deficiency Methodology: We enrolled 120 pregnant women having

Purpose The phase delay of stimulus frequency otoacoustic emissions (SFOAEs) has been proposed as a noninvasive, objective, and fast source for estimating cochlear mechanical tuning. However, the implementation of SFOAEs clinically has been thwarted by the gaps in understanding of the stability of SFOAE delay-based tuning estimates and their relationship to behavioral measures of tuning. Therefore, the goals of this study were (a) to investigate the relationship between delay-based tuning estimates from SFOAEs and simultaneously masked psychophysical tuning curves (PTCs) and (b) to assess the across- and within-session repeatability of tuning estimates from behavioral and OAE measures. Method Three sets of behavioral and OAE measurements were collected in 24 normal-hearing, young adults for two probe frequencies, 1 and 4 kHz. For each participant, delay-based tuning estimates were derived from the phase gradient of SFOAEs. SFOAE-based and behavioral estimates of tuning obtained using the fast-swept PTC paradigm were compared within and across sessions. Results In general, tuning estimates were sharper at 4 kHz compared to 1 kHz for both PTCs and SFOAEs. Statistical analyses revealed a significant correlation between SFOAE delay-based tuning and PTCs at 4 kHz, but not 1 kHz. Lastly, SFOAE delay-based tuning estimates showed better intra- and intersession repeatability compared to PTCs. Conclusions SFOAE phase-gradient delays reflect aspects of cochlear mechanical tuning, in that a frequency dependence similar to that of basilar membrane tuning was observed. Furthermore, the significant correlation with PTCs at 4 kHz and the high repeatability of SFOAE-based tuning measures offer promise of an objective, nonbehavioral assay of tuning in human ears.

Background\ud Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage.\ud \ud Methods\ud In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283.\ud \ud Findings\ud Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group.\ud \ud Interpretation\ud Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset.\ud \ud Funding\ud London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.

Five-membered cyclic organic carbonates (COC) are of interest for their ability to modify the surface properties of smectites and enhance the hydraulic resistance of bentonites to saline leachates. The mechanism of interaction of glycerol carbonate (GC) and several other hydroxyl containing cyclic organic carbonates (generally having progressively greater molecular masses) with sodium montmorillonite (Na + -Mt) was studied using powder X-ray diffraction and infrared spectroscopy. The 001 reflection for GC/Na + -Mt intercalates varied with the amount COC added, and the measured d 001 value increased from 1.29 nm to as large as 2.22 nm at equal-mass coverage of the COC to Na + -Mt. In general, when intercalated, the cyclic carbonyl (C O) stretch and the fundamental hydroxyl (O–H) stretch bands of COC derivatives were red-shifted with respect to these bands for neat COC, indicating strong ion-dipole interaction of the carbonyl group with interlayer Na + , and H-bonding of the OH group with both interlayer water and Mt surfaces. A stable and highly ordered intercalate was produced at a 1:1 mass loading with Mt in which about 6 GC molecules per unit cell (~ 7 molecules per Na + ion) replaced most of the interlayer water.

Nanocomposites of sodium smectite with polyether- and polystyrene-containing pendant cyclic carbonates offer a novel approach to improving hydraulic barrier properties of Na-smectite liners to saline leachates. The cyclic carbonate polyethers were prepared by cationic ring opening polymerization of a cyclic carbonate-containing epoxide, whilst polystyrene polymers having pendant cyclic carbonate groups were obtained from radical photopolymerization of styrene. Na-smectite nanocomposites of these polymers were formed via clay in situ polymerization and solution intercalation methods. X-ray diffraction (XRD) and FT-IR analysis confirmed that the polyether can be intercalated within the layers of smectite via in situ as well as solution intercalation of the pre-formed polymer. The cyclic carbonate polyether nanocomposite was more resistant to leaching in 3M aqueous sodium chloride than its respective cyclic carbonate. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 2421–2429

Objective:The aim of this research was the assessment of the pattern of substance abuse in patients visiting to the current hospital. Place and Duration of Study: This research was carried out from Feburary to October 2018 in Lahore, Pakistan. Materials and Methods:Adult patients were approached who were visiting Outdoor Patient Department, indoor and emergency. The size of the sample was consisted over 400 patient and non-probability convenience sampling technique was used. Inclusion criteria was that the patients actively using and were dependent on any type of substance of abuse as per the criteria of ICD-10. Informed written consent was obtained from the participants. Exclusion criteria was that patients suffering from acute physical disease require urgent and emergency care, in delirium or unconscious and they were not made part of the study. The collection of data was on a sheet and SPSS version 21 was used for analysing the data. Results:The sample group was consisted of 400 patients and out of them 350 patients were males and 50 patients were female. Patients belonging to low economic status were 49.1%. Patients belonging from rural areas were 25.1% whereas patients from urban areas were 62.1% and homeless were 30%. Among them the jobless were 91.3%. Patients with family history of drug abuse were 31%. Poly substances abusers were 50%. Heroin and opium abusers were 28.1%, injections were 8%, cannabis were 19%, benzodiazepines were 7.5% and others were 2%. Conclusion:Mostly patients visiting hospital were jobless male and belonged to urban area of low economic status. Patients having family history of drug abuse were 1/5th. Substance abusers were 50. Heroin and opium abusers were 28.1%, injections were 8%, cannabis were 19%, benzodiazepines were 7.5% and others were 2%.

When measured as a function of primary frequency ratio r = f(2)/f(1), using a constant f(2), distortion product otoacoustic emission (DPOAE) response demonstrates a bandpass shape, previously interpreted as the evidence for a cochlear “second filter.” In this study, an alternate, interference-based explanation, previously advanced in variants, is forwarded on the basis of experimental data along with numerical and analytical solutions of nonlinear and linear cochlear models. The decrease of the DPOAE response with increasing and decreasing ratios is explained by a diminishing “overlap” generation region and the onset of negative interference among wavelets of different phase, respectively. In this paper, the additional quantitative hypothesis is made that negative interference becomes the dominant effect when the spatial width of the generation (overlap) region exceeds half a wavelength of the DPOAE wavelets. Therefore, r is predicted to be optimal when this condition is matched. Additionally, the minimum on the low-ratio side of the DPOAE curve is predicted to occur as the overlap region width equals one wavelength. As the width of the overlap region depends on both tuning and ratio, while wavelength depends on tuning only, an experimental method for estimating tuning from either the width of the pass band or the optimal ratio of the DPOAE vs. ratio curve has been theoretically formulated and evaluated using numerical simulations. A linear model without the possibility of nonlinear suppression is shown to reasonably approximate data from human subjects at low ratios reinforcing the relevance of the proposed negative interference effect. The different dependence of the distortion and reflection DPOAE components on r as well as the nonmonotonic behavior of the distortion component observed at very low ratios are also in agreement with this interpretation.

UNLABELLED Phenytoin (PHT) and Carbamazepine (CBZ) are excellent sodium channel blockers administered in clinical treatment of epileptic seizures. However, the narrow therapeutic range and limited pharmacokinetics of these drugs have raised serious concerns in the proper management of epilepsy. To overcome this, the present study attempts to identify a candidate molecule with superior pharmacological profile than PHT and CBZ through In silico approaches. PHT and CBZ served as query small molecules for Tanimoto based similarity search with a threshold of 95% against PubChem database. Aided by MolDock algorithm, high affinity similar compound against each query was retrieved. PHT and CBZ and their respective similar were further tested for toxicity profiles, LC 50 values and biological activity. Compounds, NSC403438 and AGN-PC-0BPCBP respectively similar to PHT and CBZ demonstrated higher affinity to sodium channel protein than their respective leads. Of particular relevance, NSC403438 demonstrated highest binding affinity bestowed with least toxicity, better LC 50 values and optimal bioactivity. NSC403438 was further mapped for its structure based pharmacophoric features. In the study, we report NSC403438 as potential sodium channel blocker as a better candidate than PHT and CBZ which can be put forth for pharmacodynamic and pharmacokinetic studies. ABBREVIATIONS AEDs - Antiepileptic drugs, BLAST - Basic Local Alignment Search Tool, CBZ - Carbamazepine, GEFS+ - Generalized Epilepsy with Febrile Seizures Plus, GPCR - G Protein Coupled Receptor, Nav - Sodium channel with specific voltage conduction, PDB - Protein Data Bank, PHT - Phenytoin, PIR - Protein Information resources, SAVES - Structural Analysis and Verification Server, VGSC - Voltage-gated Sodium channels.

A green methodology exploring the scope of diurethane synthesis from diols and urea in the presence of a homogeneous catalyst is described. Past reactions of diurethanes have relied heavily on environmentally corrosive reagents such as phosgene. Prior to this work, we have utilized metal glycerolates as homogeneous catalysts in the glycerolysis of urea. Here we explore the synthetic scope of this system with a variety of diols. The conversion to diurethanes is proposed to proceed via an intermediate zinc bound isocyanate ligand, which rearranges to form the terminal urethane in the case of 1,3- and higher diols in good selectivity and yields. With butane 1,2,4-triol the selectivity is exclusively for the 5-membered carbonate, suggesting that the proximity of the second hydroxyl group is critical in forming the ring.

Inappropriate activation of the Hh signaling pathway has been implicated in the development of several types of cancers including prostate, lung, pancreas, breast, brain and skin. Present study identified the binding affinities of eight established inhibitors viz., Cyclopamine, Saridegib, Itraconazole, LDE-225, TAK-441, BMS-833923 (XL139), PF-04449913 and Vismodegib targeting SMO receptor - a candidate protein involved in hedgehog pathway and sought to identify the best amongst the established inhibitors through by molecular docking. Exelxis® BMS 833923 (XL 139) demonstrated superior binding affinity aided by MolDock scoring docking algorithm. Further BMS 833923 (XL 139) was evaluated for pharmacophoric features which revealed appreciable ligand receptor interactions.

Introduction: Oxidative stress resulting from excessive generation of Reactive Oxygen Species (ROS) plays a significant role in neurodegeneration associated with seizures/epilepsy. Aim: To evaluate oxidative stress markers and antioxidant enzymes in Genetic Generalised Epilepsy (GGE) and to know the extent of oxidative stress induced by Anti-Epileptic Drugs (AEDs) with the time duration of treatment. Materials and Methods: In this case-control study, 310 GGE patients (male:female=203:107), who were on AED treatment (n=235) and 75 untreated patients (male:female=49:26) along with 310 age and sex matched healthy controls were recruited. Oxidative stress markers such as Nitric Oxide (NO), Malondialdehyde (MDA) and antioxidant enzyme activities namely Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Catalase (CAT) were measured spectrophotometrically. Results: Significantly higher levels of serum NO, MDA and low levels of plasma Total Antioxidant Capacity (TAC) were found in patients as compared to controls (p5 years compared to other groups (≤ 1 year and 1-≤ 5 years) (p=0.02, p=0.01, p=0.001, p=0.01 and p=0.05 respectively). Further, significant increase in the levels of NO, MDA and decreased activities of SOD, CAT were found in treated patients compared to untreated patients (p

The idiopathic generalized epilepsy (IGE) is a neurological disorder which accounts for approximately 30% of all epilepsy cases. Patients identified with IGE syndromes have pharmacoresponsive epilepsies without abnormal neurological symptoms, structural brain lesions and are of unknown origin. A genetic etiology to IGEs has been proposed. Gamma amino butyric acid (GABA), a major inhibitory neurotransmitter acts by binding to transmembrane GABAA and GABAB receptors of both pre- and postsynaptic neurons. Synapsin II (SynII), a neuron specific phosphoprotein plays a major role in synaptogenesis and neurotransmitter release. The present study was carried out with an aim to evaluate the association of GABRA6 (rs3219151) TC and Syn II (rs37733634) AG gene polymorphisms with IGE. Molecular analysis revealed that the frequency of 'CC' genotype and 'C'allele of GABRA6 (rs3219151) TC gene polymorphism was significantly higher in IGE patients compared to healthy controls [CC vs. TT, χ2=26; p0.001; Odds ratio=3.6 (95% CI; 2.1-5.9); C vs T, χ2=24.7; p0.001; Odds ratio=1.78 (95% CI; 1.4-2.2)]. The frequency of 'GG' genotype and 'G' allele of the intronic polymorphism AG in Syn II gene was also found to be significantly associated with the disease when compared to controls [GG vs AA, χ2=64.52; p0.001; Odds ratio=7.37 (95% CI; 4.4-12.3); G vs. A, χ2=65.78; p0.001; Odds ratio=2.57 (95% CI; 2.0-3.2)]. The generalized multifactor dimensionality reduction method was employed to detect gene-gene interactions. The gene-gene interaction at two loci involving GABRA6 and Syn II revealed a significant association [χ2=36.6, p0.001, Odds ratio=3.17 (95% CI; 2.2-4.6)] with IGE. Therefore, the present study clearly indicates that both GABRA6 (rs3219151) TC and Syn II (rs37733634) AG polymorphisms are important risk factors for the development of IGE in the South Indian population from Andhra Pradesh. The gene-gene interaction studies demonstrated significant interactive effects of these two loci in the development of the disease.

Certain minerals and trace elements are essential for the development of healthy nervous system. Altered serum levels of these elements may lead to the development of various diseases including epilepsy. The present study was designed to evaluate the association of serum calcium, magnesium, zinc and copper in the development of genetic generalized epilepsy [GGE; erstwhile known as idiopathic generalized epilepsy (IGE)] as well as idiopathic intractable epilepsy (IIE), in which seizures persist despite treatment with at least two or three antiepileptic drugs tolerated at reasonable dosage. 200 GGE patients and equal number of healthy controls were recruited for study with their written informed consent. The patients were further divided into responders and non-responders based on their response to antiepileptic drugs. Copper and zinc levels were assayed by atomic absorption spectrophotometer whereas calcium and magnesium were analyzed by Human Star 600 fully automated biochemistry analyzer. The patients with GGE had significant low levels of calcium, magnesium and zinc (1.85 ± 0.33, 0.69 ± 0.13 mmol/L and 11.33 ± 3.32 µmol/L respectively) and the corresponding values for controls were 2.27 ± 0.22, 0.89 ± 0.15, 12.71 ± 3.24 (p

Antiepileptic drug (AED) treatment in epilepsy is often compromised by the unpredictability of efficacy and inter-individual variability among patients, which at least in part is the result of genetic variation. The idea to determine an individual's response to a prescribed medicine came into inception around 29 years ago. Pharmacogenetics is used to predict the drug response and efficacy, as well as potential adverse effects. We investigated the functional significance of the C3435T polymorphism of the MDR1 gene in a South Indian population. The patients were divided into responders and non-responders based on their clinical outcome and AED response. The risk of drug resistance was significantly higher in patients bearing TT genotype in comparison to carriers of the homozygous CC genotype [TT vs. CC, χ(2)=12.52; p=0.001, Odds ratio=2.34 (95% CI: 1.942-11.32)]. We suggest that the influence of the C3435T polymorphism in predicting the drug-resistance in epilepsy, might be significant and further investigations focusing on carbamazepine and phenytoin, in various ethnic populations are necessary to clarify the effect of C3435T polymorphism on the multidrug resistance in epilepsy patients.

Hyperthermostable alkaline lipase fromBacillus sonorensis4R was purified and characterized. The enzyme production was carried out at 80°C and 9.0 pH in glucose-tween inorganic salt broth under static conditions for 96 h. Lipase was purified by anion exchange chromatography by 12.15 fold with a yield of 1.98%. The molecular weight of lipase was found to be 21.87 KDa by SDS-PAGE. The enzyme activity was optimal at 80°C witht1/2of 150 min and at 90°C, 100°C, 110°C, and 120°C; the respective values were 121.59 min, 90.01 min, 70.01 min, and 50 min. The enzyme was highly activated by Mg andt1/2values at 80°C were increased from 150 min to 180 min when magnesium and mannitol were added in combination. The activation energy calculated from Arrhenius plot was 31.102 KJ/mol. At 80–120°C, values ofΔHandΔGwere in the range of 28.16–27.83 KJ/mol and 102.79 KJ/mol to 111.66 KJ/mol, respectively. Lipase activity was highest at 9.0 pH and stable for 2 hours at this pH at 80°C. Pretreatment of lipase with MgSO4and CaSO4stimulated enzyme activity by 249.94% and 30.2%, respectively. The enzyme activity was greatly reduced by CoCl2, CdCl2, HgCl2, CuCl2, Pb(NO3)2, PMSF, orlistat, oleic acid, iodine, EDTA, and urea.

A 59-year-old white alcoholic female was transferred to ER by ambulance at 04:52 a.m. for lethargy, disorientation, weakness, falls, and headache for few days. She was only drinking alcohol for few days but not eating. She had history of hypertension, and she was taking Lorazepam 2 mg thrice daily, Ramipril 2.5 mg once daily and Hydrochlorothiazide 12.5 mg once daily. Her initial vital signs by paramedics revealed BP of 124/56 mmHg, pulse of 75 bpm, and temperature of 36.7 C. Her weight was 60 kg, and her height was 161 cm. Her Glasgow Coma Scale was 13/15. On examination, the patient was confused, only oriented to place and had slurred speech and multiple bruises of different ages. Her pupils were 5 mm, equal and reactive to light. No other significant findings were found. Initial laboratory results are shown in Table 1. Intravenous fluids were started as first line of 1 L of Normal Saline with 40 mEq of KCl at 100 mL/h and second line of 250 mL of Normal Saline with 40 mEq of KCl at 50 mL/h. Head CT scan was negative for acute hemorrhage, infarct, or edema. Thiamine 100 mg IVP was given, and third IV line was then initiated with 1 L of Saline with 40 mEq of KCl at 100 mL/h. Her blood pressure suddenly dropped to 82/44 mmHg, so a bolus of Normal Saline 500 mL was given, and her blood pressure improved to 152/87 mmHg within 15 min. She was transferred to ICU where she additionally received IV magnesium sulfate, oral potassium chloride, and oral sodium phosphate replacements. Serial blood chemistry tests were done, and IV fluid types and rates were adjusted accordingly. During the first day, she excreted a large amount of diluted urine which could be secondary to a quick decrease in serum vasopressin level when her A. G. Tarakji Aleppo University, Aleppo, Syria

Hub proteins in interaction networks involved in signaling pathways are known to have more disordered residues than non-hubs. Since the signaling mechanisms involving PPI are regulated by phosphorylation, disordered interfaces could be thought to be extremely phosphorylated. In the present study we sought to map the phosphorylated sites onto disordered regions on interacting proteins-Interactomes and non-interacting proteins-Negatomes. Dataset of non-interacting protein included 784 proteins retrieved from Negatome database 2.0. 2252 interacting proteins were retrieved from “GeneMania”. Intrinsically disordered regions were predicted with “Disopred” program. The binding interfaces were defined by “PDBePISA” server, while, phosphorylation sites were derived from “NetPhos” program. All phosphorylation sites were mapped onto protein structures using alignments calculated by the MUSCLE program. As anticipated, the extent of phosphorylation in interactomes were significantly higher in disordered regions to its ordered counter parts (p=0.04). Insights revealed that the disordered regions in negatome were sparse in comparison to those in interactomes (p

The 1-(4-Fluorobenzoyl)-3-(isomeric fluorophenyl)thioureas (1–3) were prepared by the reaction of 4-fluorobenzoyl isothiocyanate produced in situ with isomeric fluoroanilines in dry acetonitrile in good yields. The novel compounds were characterized by multinuclear (1H and 13C) NMR, elemental analyses and FTIR spectroscopy techniques. Structural and conformational properties of compounds 1–3 have been analyzed using a combined approach including X-ray diffraction, vibrational spectra and theoretical calculation methods. The carbonyl and thiourea groups are almost planar and the conformation adopted by the C S and the C O double bonds is antiperiplanar, in a conformation which is stabilized by intramolecular N H⋯O hydrogen bond. Crystal packing shows molecules connected by intermolecular N H⋯S C hydrogen bonds to form centrosymmetric dimers.

The title thiourea was synthesized by reaction of 3,4,5-trimethoxybenzoyl isothiocyante with 3-fluoroaniline. The 3,4,5-trimethoxybenzoyl isothiocyante was produced in situ by reaction of 3,4,5-trimethoxybenzoyl chloride with ammonium thiocyanate in dry acetonitrile. The structure was confirmed by the spectroscopic, elemental analysis and single crystal X-ray diffraction data. It crystallizes in the monoclinic space group P21/c with unit cell dimensions a = 13.0966(9), b = 16.6460(13), c = 7.8448(5), β = 106.721(5)°, V 1637.9(2) ų, Z = 4.

The synthesis of several 2-(substituted fluorobenzoylimino)-3-(substituted fluorophenyl)-4-methyl-1,3-thiazolines ( 2a–t ) was carried out by base-catalyzed cyclization of corresponding 1-(fluorobenzoyl)-3-(fluorophenyl)thioureas ( 1a–t ) with 2-bromoacetone in aqueous medium. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. All synthesized compounds were evaluated for in vitro antibacterial activity using Gram-positive bacteria ( Staphylococcus aureus , Bacillus subtilis ) and Gram-negative bacteria ( Escherichia coli , Pseudomonas aeruginosa ). The minimum inhibitory concentration (MIC) was determined for the most active compounds. In vitro antifungal activity was also determined against the five fungal species ( Rhizopus oryzae , Fusarium oxysporum , Aspergillus terreus , A. niger and A. fumigatus ).

A series of 2-, 3-, and 4-substituted (fluorobenzoylimino)-3-aryl-4-methyl-1,3-thiazolines (2a–j) were synthesized in good yields by the base-catalyzed cyclization of corresponding 1-(fluorobenzoyl)-3-(fluorophenyl)thioureas (1a–j) with α-bromoacetone in water. Compared to the reactions in conventional nonaqueous solvents under inert anhydrous conditions, the aqueous medium provides a much cleaner, more efficient, and simpler method for synthesis.

The base catalyzed intramolecular nucleophilic cyclization of 1-(2-haloaroyl)-3-aryl thioureas (1a-i), in the presence of DMF afforded the 1-aryl-2-thioxo-2,3-dihydro-1H-quinazolin-4-ones (2a-i). The structures were confirmed by spectroscopic data, elemental analyses and in case of the 2c by single crystal X-ray diffraction data. The mechanistic studies support an intramolecular nucleophilic substitution (SNAr mechanism) rather than intramolecular aromatic substitution (SRN1 mechanism).