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Capsicum has been an important part of diet since centuries and has been widely used traditionally for ailments. The objective of the present analysis was to determine the diuretic and antidiarrheal potentials of four variations of Capsicum annum L. fruits available in local market of Karachi, Pakistan. It belongs to family Solanaceae and extracts were prepared in 95% ethanol and was given in doses of 200 and 400mg/kg and the activity was correlated with commonly used diuretics and anti-diarrheal further reinforcing its conventional use. Fruits extracts were evaluated for anti-diarrheal properties in castor-oil induced diarrhea to confirm its activity. The diuretic activity of the 95% ethanolic extracts of Capsicum annum L. was assessed based on diuresis of 24 hr. collected through metabolic cage. Urinary excretion of water and electrolytes (Na+ and K+) is significantly increased by the standard diuretic drug furosemide, which is comparable with the extract. The anti-diarrheal effects of 95% ethanolic extracts of Capsicum annum L. were examined by castor oil induced diarrhea and all varieties of Capsicum annum L. significantly inhibited the number of defecations.

The superconducting analogue to the semiconducting diode, the Josephson diode, has long been sought with multiple avenues to realization being proposed by theorists 1-3 . Showing magnetic-field-free, single-directional superconductivity with Josephson coupling, it would serve as the building block for next-generation superconducting circuit technology. Here we realized the Josephson diode by fabricating an inversion symmetry breaking van der Waals heterostructure of NbSe 2 /Nb 3 Br 8 /NbSe 2 . We demonstrate that even without a magnetic field, the junction can be superconducting with a positive current while being resistive with a negative current. The ΔI c behaviour (the difference between positive and negative critical currents) with magnetic field is symmetric and Josephson coupling is proved through the Fraunhofer pattern. Also, stable half-wave rectification of a square-wave excitation was achieved with a very low switching current density, high rectification ratio and high robustness. This non-reciprocal behaviour strongly violates the known Josephson relations and opens the door to discover new mechanisms and physical phenomena through integration of quantum materials with Josephson junctions, and provides new avenues for superconducting quantum devices., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

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Current-induced control of magnetization in ferromagnets using spin-orbit torque (SOT) has drawn attention as a new mechanism for fast and energy efficient magnetic memory devices. Energy-efficient spintronic devices require a spin-current source with a large SOT efficiency (ξ) and electrical conductivity (σ), and an efficient spin injection across a transparent interface. Herein, single crystals of the van der Waals (vdW) topological semimetal WTe 2  and vdW ferromagnet Fe 3 GeTe 2 are used to satisfy the requirements in their all-vdW-heterostructure with an atomically sharp interface. The results exhibit values of ξ ≈ 4.6 and σ ≈ 2.25 × 10 5  Ω -1 m -1 for WTe 2 . Moreover, the significantly reduced switching current density of 3.90 × 10 6 A cm -2 at 150 K is obtained, which is an order of magnitude smaller than those of conventional heavy-metal/ferromagnet thin films. These findings highlight that engineering vdW-type topological materials and magnets offers a promising route to energy-efficient magnetization control in SOT-based spintronics., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

In ferromagnetic semiconductors, the coupling of magnetic ordering with semiconductor character accelerates the quantum computing. The structural stability, Curie temperature (T c ), spin polarization, half magnetic ferromagnetism and transport properties of ZnX 2 Se 4 (X = Ti, V, Cr) chalcogenides for spintronic and thermoelectric applications are studied here by density functional theory (DFT). The highest value of T c is perceived for ZnCr 2 Se 4 . The band structures in both spin channels confirmed half metallic ferromagnetic behavior, which is approved by integer magnetic moments (2, 3, 4) μ B of Ti, V and Cr based spinels. The HM behavior is further measured by computing crystal field energy ΔE crystal , exchange energies Δ x ( d ), Δ x ( pd ) and exchange constants (N o α and N o β). The thermoelectric properties are addressed in terms of electrical conductivity, thermal conductivity, Seebeck coefficient and power factor in within a temperature range 0-400 K. The positive Seebeck coefficient shows p-type character and the PF is highest for ZnTi2Se4 (1.2 × 10 11 W/mK 2 ) among studied compounds.

Background and Aims: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date., Approach and Results: This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] μmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 μmol/L (P = 0.05) tended to be associated with improved NLS., Conclusions: Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS., (© The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

The aim of study was to evaluate the analgesic and anti-inflammatory activity of four different colored (green, yellow, orange and red) sweet bell peppers (Capsicum annuum L.) available in the local market of Karachi Pakistan. Their 95% ethanol extracts at 200 and 400 mg/kg were prepared and compared with commonly used analgesic (aspirin) and anti-inflammatory agents supporting its traditional use. The analgesic effects of 95% ethanol extracts of Capsicum annum L. were investigated by acetic acid induced writhing, tail immersion and hot plate test. The anti-inflammatory activities were observed using carrageenan-induced edema of hind paw in rats. Animals were divided into 10 groups (n=7): (1) Control (2) CAG 200 (3) CAG 400 (4) CAR 200 (5) CAR 400 (6) CAO 200 (7) CAO 400 (8) CAY 200 (9) CAY 400 and (10) Standard. All the extracts were given orally. Acute toxicity was also determined by increasing the dose till 3000 mg/kg, which showed no evidence of mortality. All extracts of Capsicum significantly increased the hot plate pain threshold, moreover remarkably reduced the carrageenan-induced rat paw edema. Results obtained were compared with corresponding control group revealed that the fresh fruits extract of all four kinds of bell pepper (200 mg/kg and 400mg/kg) possess anti-inflammatory and pain suppressing activities possibly mediated via PG synthesis inhibition.

This article focuses on the output feedback control of single-link flexible-joint robot manipulators (SFJRMs) with matched disturbances and parametric uncertainties. Formally, four sensing elements are required to design the controller for single-link manipulators. We have designed a robust control technique for the semiglobal stabilization problem of the angular position of the link in the SFJRM system, with the availability of only a position sensing device. The sliding mode control (SMC) based output feedback controller is devised for SFJRM dynamics. The nonlinear model of SFJRM is considered to estimate the unknown states utilizing the high-gain observer (HGO). It is shown that the output under SMC using HGO-based estimated states coincides with that using original states when the gains of HGO are sufficiently high. Finally, the results are presented showing that the designed control technique works well when the SFJRM model is uncertain and matched perturbations are expected.

Background: Dietary fiber has played a consistent role in weight management, with efficacy potentially attributed to increased viscous fiber consumption., Purpose: To summarize the effects of viscous fiber on body weight and other anthropometric parameters, along with a calorie-deficient diet, through a systematic review and meta-analysis., Methods: MEDLINE, EMBASE, and the Cochrane library were searched through July 24, 2019 for randomized controlled trials that assessed the effect of viscous fiber supplementation as part of a restricted calorie diet for ≥ 4 weeks relative to comparator diets. Data were pooled using the generic inverse-variance method with random-effects models and expressed as mean differences with 95% confidence intervals. Inter-study heterogeneity was assessed using Cochran's Q and quantified with I 2 . The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall certainty of evidence., Results: Findings from 15 studies (n = 1347) showed viscous fiber supplementation significantly decreased body weight (- 0.81 kg [- 1.20, - 0.41]; p < 0.0001), BMI (- 0.25 kg/m 2 [- 0.46, - 0.05]; p = 0.01), and body fat (- 1.39% [- 2.61, - 0.17]; p = 0.03), compared to control. No effect on waist circumference was found. The certainty of evidence was graded as "moderate" for body weight, BMI, and body fat based on downgrades for imprecision. Waist circumference was graded "low" for downgrades of inconsistency and imprecision., Conclusion: Viscous fiber within a calorie-restricted diet significantly improved body weight and other markers of adiposity in overweight adults and those with additional risk factors for cardiovascular disease. This trial is registered at www.clinicaltrials.gov as NCT03257449., Registration: ClinicalTrials.gov identifier: NCT03257449.

Td-WTe 2 (non-centrosymmetric and orthorhombic), a type-II Weyl semimetal, is expected to have higher-order topological phases with topologically protected, helical one-dimensional hinge states when its Weyl points are annihilated. However, the detection of these hinge states is difficult due to the semimetallic behaviour of the bulk. In this study, we have spatially resolved the hinge states by analysing the magnetic field interference of the supercurrent in Nb-WTe 2 -Nb proximity Josephson junctions. The Josephson current along the a axis of the WTe 2 crystal, but not along the b axis, showed a sharp enhancement at the edges of the junction, and the amount of enhanced Josephson current was comparable to the upper limits of a single one-dimensional helical channel. Our experimental observations suggest a higher-order topological phase in WTe 2 and its corresponding anisotropic topological hinge states, in agreement with theoretical calculations. Our work paves the way for the study of hinge states in topological transition-metal dichalcogenides and analogous phases.

The anomalous Hall effect (AHE) is one of the most fundamental phenomena in physics. In the highly conductive regime, ferromagnetic metals have been the focus of past research. Here, we report a giant extrinsic AHE in KV 3 Sb 5 , an exfoliable, highly conductive semimetal with Dirac quasiparticles and a vanadium Kagome net. Even without report of long range magnetic order, the anomalous Hall conductivity reaches 15,507 Ω -1 cm -1 with an anomalous Hall ratio of ≈ 1.8%; an order of magnitude larger than Fe. Defying theoretical expectations, KV 3 Sb 5 shows enhanced skew scattering that scales quadratically, not linearly, with the longitudinal conductivity, possibly arising from the combination of highly conductive Dirac quasiparticles with a frustrated magnetic sublattice. This allows the possibility of reaching an anomalous Hall angle of 90° in metals. This observation raises fundamental questions about AHEs and opens new frontiers for AHE and spin Hall effect exploration, particularly in metallic frustrated magnets., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Understanding the electronic transport properties of layered, van der Waals transition metal halides (TMHs) and chalcogenides is a highly active research topic today. Of particular interest is the evolution of those properties with changing thickness as the 2D limit is approached. Here, we present the electrical conductivity of exfoliated single crystals of the TMH, cluster magnet, Nb 3 Cl 8 , over a wide range of thicknesses both with and without hexagonal boron nitride (hBN) encapsulation. The conductivity is found to increase by more than three orders of magnitude when the thickness is decreased from 280 µm to 5 nm, at 300 K. At low temperatures and below ∼50 nm, the conductance becomes thickness independent, implying surface conduction is dominating. Temperature dependent conductivity measurements indicate Nb 3 Cl 8 is an insulator, however, the effective activation energy decreases from a bulk value of 310 meV to 140 meV by 5 nm. X-ray photoelectron spectroscopy (XPS) shows mild surface oxidation in devices without hBN capping, however, no significant difference in transport is observed when compared to the capped devices, implying the thickness dependent transport behavior is intrinsic to the material. A conduction mechanism comprised of a higher conductivity surface channel in parallel with a lower conductivity interlayer channel is discussed.

Background & Aims: Mutations in ABCB11 can cause deficiency of the bile salt export pump (BSEP), leading to cholestasis and end-stage liver disease. Owing to the rarity of the disease, the associations between genotype and natural history, or outcomes following surgical biliary diversion (SBD), remain elusive. We aimed to determine these associations by assembling the largest genetically defined cohort of patients with severe BSEP deficiency to date., Methods: This multicentre, retrospective cohort study included 264 patients with homozygous or compound heterozygous pathological ABCB11 mutations. Patients were categorized according to genotypic severity (BSEP1, BSEP2, BSEP3). The predicted residual BSEP transport function decreased with each category., Results: Genotype severity was strongly associated with native liver survival (NLS, BSEP1 median 20.4 years; BSEP2, 7.0 years; BSEP3, 3.5 years; p <0.001). At 15 years of age, the proportion of patients with hepatocellular carcinoma was 4% in BSEP1, 7% in BSEP2 and 34% in BSEP3 (p = 0.001). SBD was associated with significantly increased NLS (hazard ratio 0.50; 95% CI 0.27-0.94: p = 0.03) in BSEP1 and BSEP2. A serum bile acid concentration below 102 μmol/L or a decrease of at least 75%, each shortly after SBD, reliably predicted NLS of ≥15 years following SBD (each p <0.001)., Conclusions: The genotype of severe BSEP deficiency strongly predicts long-term NLS, the risk of developing hepatocellular carcinoma, and the chance that SBD will increase NLS. Serum bile acid parameters shortly after SBD can predict long-term NLS., Lay Summary: This study presents data from the largest genetically defined cohort of patients with severe bile salt export pump deficiency to date. The genotype of patients with severe bile salt export pump deficiency is associated with clinical outcomes and the success of therapeutic interventions. Therefore, genotypic data should be used to guide personalized clinical care throughout childhood and adulthood in patients with this disease., Competing Interests: Conflicts of interest Daan B.E. van Wessel: [nothing to disclose], Richard J. Thompson [consultancy for Shire, Albireo, Mirum, Horizon Pharmaceuticals, Sana Biotechnology, GenerationBio, Retrophin and Qing Bile Therapeutics], Emmanuel M. Gonzales [Consultant for CTRS and Mirum Pharmaceuticals], Irena Jankowska [nothing to disclose], Tassos Grammatikopoulos [nothing to disclose], Agustina Kadaristiana [nothing to disclose], Patryk Lipiński [nothing to disclose], Piotr Czubkowski [nothing to disclose], Nathalie Rock [nothing to disclose] Emmanuel Jacquemin [nothing to disclose], Anne Spraul [nothing to disclose], Etienne M. Sokal [founder and CSMO of Promethera Biosciences], Mohammad Shagrani [nothing to disclose], Dieter Broering [nothing to disclose], Talal Algoufi [nothing to disclose], Nejat Mazhar [nothing to disclose], Emanuele Nicastro [nothing to disclose] Deirdre Kelly [Consultant for Albireo], Gabriela Nebbia [nothing to disclose], Henrik Arnell [consultant for Albireo and Mirum Pharmaceuticals], Björn Fischler [has attended one advisory board meeting with Albireo in 2016], Jan Hulscher [nothing to disclose], Daniele Serranti [nothing to disclose], Cigdem Arikan [nothing to disclose], Esra Polat [nothing to disclose], Dominique Debray [consultant for Alexion pharmaceuticals], Florence Lacaille [nothing to disclose], Cristina Goncalves [nothing to disclose], Loreto Hierro [nothing to disclose], Gema Muñoz Bartolo [nothing to disclose], Yael Mozer-Glassberg [nothing to disclose], Amer Azaz [nothing to disclose], Jernej Brecelj [nothing to disclose], Antal Dezsőfi [nothing to disclose], Pier Luigi Calvo [nothing to disclose], Enke Grabhorn [nothing to disclose], Ekkehard Sturm [nothing to disclose] Wendy van der Woerd [nothing to disclose], Binita Kamath [consultant for Mirum Pharmaceuticals, Shire and DCI], Jian-She Wang [nothing to disclose], Liting Li [nothing to disclose], Özlem Durmaz [nothing to disclose], Zerrin Onal [nothing to disclose], Ton Bunt [nothing to disclose], Bettina Hansen [consultant for Mirum Pharmaceuticals, Albireo AB, Chemomab, Calliditas, Intercept, Cyma Bay, unrestricted grants from Cyma bay, Intercept, Mirum and Albireo], Henkjan J. Verkade [Consultant for Danone/Nutricia Research, Ausnutria BV, Albireo AB, GMP+Orphan, Mirum Pharmaceuticals, Intercept and Vivet]. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. All rights reserved.)

Background: The role of dietary fiber in obesity management remains debatable. Evidence suggests that intake of viscous fiber may have the potential to facilitate weight loss., Objective: We aimed to summarize and quantify the effects of viscous fiber on body weight, BMI, waist circumference, and body fat, independent of calorie restriction, through a systematic review and meta-analysis of randomized controlled trials., Methods: Trials ≥4 wk in duration that assessed the effect of viscous fiber supplemented to an ad libitum diet along with comparator diets were included. MEDLINE, EMBASE, and the Cochrane library were searched through 24 July, 2019. Two independent reviewers extracted relevant data. Data were pooled using the generic inverse variance method and random-effects models and expressed as mean differences with 95% CIs. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall certainty of evidence was explored using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach., Results: Findings from 62 trials (n = 3877) showed that viscous fiber reduced mean body weight (-0.33 kg; 95% CI: -0.51, -0.14 kg; P = 0.004), BMI (in kg/m2) (-0.28; 95% CI: -0.42, -0.14; P = 0.0001), and waist circumference (-0.63 cm; 95% CI: -1.11, -0.16 cm; P = 0.008), with no change in body fat (-0.78%; 95% CI: -1.56%, 0.00%; P = 0.05) when consumed with an ad libitum diet. Greater reductions in body weight were observed in overweight individuals and those with diabetes and metabolic syndrome. The certainty of evidence was graded moderate for body weight, high for waist circumference and body fat, and low for BMI., Conclusions: Dietary viscous fiber modestly yet significantly improved body weight and other parameters of adiposity independently of calorie restriction. Future trials are warranted to address the inconsistency and imprecision identified through GRADE and to determine long-term weight-loss sustainability.This systematic review and meta-analysis was registered at clinicaltrials.gov as NCT03257449., (Copyright © The Author(s) 2020.)

Objective: Evidence from randomized controlled trials (RCTs) suggests that viscous dietary fiber may offer beneficial effects on glycemic control and, thus, an improved cardiovascular disease risk profile. Our purpose was to conduct a systematic review and meta-analysis of RCTs to synthesize the therapeutic effect of viscous fiber supplementation on glycemic control in type 2 diabetes., Research Design and Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through 15 June 2018. We included RCTs ≥3 weeks in duration that assessed the effects of viscous fiber on markers of glycemic control in type 2 diabetes. Two independent reviewers extracted data. Data were pooled using the generic inverse variance method and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified ( I 2 statistic). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall certainty of the evidence., Results: We identified 28 eligible trial comparisons ( n = 1,394). Viscous fiber at a median dose of ∼13.1 g/day significantly reduced HbA 1c (MD -0.58% [95% CI -0.88, -0.28]; P = 0.0002), fasting blood glucose (MD -0.82 mmol/L [95% CI -1.32, -0.31]; P = 0.001), and HOMA-insulin resistance (IR) (MD -1.89 [95% CI -3.45, -0.33]; P = 0.02) compared with control and in addition to standard of care. The certainty of evidence was graded moderate for HbA 1c , fasting glucose, fasting insulin, and HOMA-IR and low for fructosamine., Conclusions: Viscous fiber supplements improve conventional markers of glycemic control beyond usual care and should be considered in the management of type 2 diabetes., (© 2019 by the American Diabetes Association.)

This paper presents the design and analysis of a multi degree of freedom (DOF) electro-thermally actuated non-resonant MEMS gyroscope with a 3-DOF drive mode and 1-DOF sense mode system. The 3-DOF drive mode system consists of three masses coupled together using suspension beams. The 1-DOF system consists of a single mass whose motion is decoupled from the drive mode using a decoupling frame. The gyroscope is designed to be operated in the flat region between the first two resonant peaks in drive mode, thus minimizing the effect of environmental and fabrication process variations on device performance. The high gain in the flat operational region is achieved by tuning the suspension beams stiffness. A detailed analytical model, considering the dynamics of both the electro-thermal actuator and multi-mass system, is developed. A parametric optimization is carried out, considering the microfabrication process constraints of the Metal Multi-User MEMS Processes (MetalMUMPs), to achieve high gain. The stiffness of suspension beams is optimized such that the sense mode resonant frequency lies in the flat region between the first two resonant peaks in the drive mode. The results acquired through the developed analytical model are verified with the help of 3D finite element method (FEM)-based simulations. The first three resonant frequencies in the drive mode are designed to be 2.51 kHz, 3.68 kHz, and 5.77 kHz, respectively. The sense mode resonant frequency is designed to be 3.13 kHz. At an actuation voltage of 0.2 V, the dynamically amplified drive mode gain in the sense mass is obtained to be 18.6 µm. With this gain, a capacitive change of 28.11 &nbsp; f F and 862.13 &nbsp; f F is achieved corresponding to the sense mode amplitude of 0.15 &nbsp; μ m and 4.5 &nbsp; μ m at atmospheric air pressure and in a vacuum, respectively.

Anterior cruciate ligament injuries are very commonly encountered during routine MRI reporting and various signs have been described for their identification. However, the diagnosis of isolated bundle tears is difficult using MRI, thus can be easily overlooked, especially isolated tear of posterolateral bundle. We present a case of a young male with "Gap" and "Footprint" signs on MRI knee joint, which are considered highly specific of posterolateral ACL bundle tear.

Objective and Background: Inhibition of acetylcholinesterase (AChE) has gained much importance since the discovery of the involvement of peripheral anionic site as an allosteric regulator of AChE. Characterized by the formation of β-amyloid plaques, Alzheimer's disease (AD) is currently one of the leading causes of death across the world. Progression in this neurodegenerative disorder causes deficit in the cholinergic activity that leads towards cognitive decline. Therapeutic interventions in AD are largely focused upon AChE inhibitors designed essentially to prevent the loss of cholinergic function. The multifactorial AD pathology calls for Multitarget-directed ligands (MTDLs) to follow up on various components of the disease. Considering this approach, other related AD targets were also selected. Structure-based virtual screening was relied upon for the identification of lead compounds with anti-AD effect., Method: Several chemoinformatics approaches were used in this study, reporting four multi-target inhibitors: MCULE-7149246649-0-1, MCULE-6730554226-0-4, MCULE-1176268617-0-6 and MCULE-8592892575-0-1 with high binding energies that indicate better AChE inhibitory activity. Additional in-silico analysis hypothesized the abundant presence of aromatic interactions to be pivotal for interaction of selected compounds to the acetyl-cholinesterase. Additionally, we presented an alternative approach to determine protein-ligand stability by calculating the Gibbs-free energy change over time. Furthermore, this allows to rank potential hits for further in-vitro testing., Results and Conclusion: With no predicted indication of adverse effects on humans, this study unravels four active multi-target inhibitors against AChE with promising affinities and good ADMET profile for the potential use in AD treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Advanced cholestatic liver disease is a leading referral to pediatric liver transplant centers. Recent advances in the genetic classification of this group of disorders promise a highly personalized management although the genetic heterogeneity also poses a diagnostic challenge. Using a next-generation sequencing-based multi-gene panel, we performed retrospective analysis of 98 pediatric patients who presented with advanced cholestatic liver disease. A likely causal mutation was identified in the majority (61%), spanning many genes including ones that have only rarely been reported to cause cholestatic liver disease, e.g. TJP2 and VIPAS39. We find no evidence to support mono-allelic phenotypic expression in the carrier parents despite the severe nature of the respective mutations, and no evidence of oligogenicity. The high-carrier frequency of the founder mutations identified in our cohort (1 in 87) suggests a minimum incidence of 1:7246, an alarmingly high disease burden that calls for the primary prevention through carrier screening., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Patient's perception of their illness influences their healthcare decisions. The objectives of this study were to explore patient's own beliefs about their illness (Schizophrenia) and perceived social support, and its impact on their attitudes toward pharmacological treatment in Lahore, Pakistan., Methods: This study was conducted at Mayo Hospital Lahore from March to September 2016. Hundred individuals suffering from Schizophrenia completed four questionnaires; a socio-demographic questionnaire, the Illness Perception Questionnaire for Schizophrenia(IPQ-S), Drug attitude Inventory-10 (DAI) and Multidimensional Scale of Perceived Social Support (PSS)., Results: Stress, family problems, lack of friends & financial worries were endorsed strongly by patients as cause of their mental illness. Ambiguity regarding their mental illness duration and personal control was observed. Patients' perceived significant negative consequences, negative emotional response, as well as had poor understanding of their mental illness and treatment effectiveness. Statistically significant gender differences in treatment control and illness coherence subscales of IPQS were observed. Drug attitude inventory was positively correlated with Treatment control subscale (p < .01) and negatively correlated with Illness coherence subscale of IPQS (p < .05). The negative consequences subscale and perceived social support was negatively correlated (p < .01)., Conclusion: Patient's perception about their own illness is predictor of their drug taking attitude and perceived social support. Study results should help to develop new interventions to correct inaccurate beliefs in patients with schizophrenia to improve illness outcome.

Hypertriglyceridemia (hTG) is a lipid disorder, resulting from an elevation in triglyceride levels, with a strong genetic component. It constitutes a significant risk factor for coronary artery disease (CAD), a leading cause of death worldwide. In this study, we performed a common variant association study for hTG in ethnic Saudi Arabs. We genotyped 5501 individuals in a two-phase experiment using Affymetrix Axiom ® Genome-Wide CEU 1 Array (Affymetrix, Santa Cruz, CA) that contains a total of 587,352 single nucleotide polymorphisms (SNPs). The lead variant was the rs1558861 [1.99 (1.73-2.30); p = 7.37 × 10 -22 ], residing on chromosome (chr) 11 at the apolipoprotein A-I/A-5 (APOA1/APOA5) locus. The rs780094 [1.34 (1.21-1.49); p = 8.57 × 10 -8 ] on chr 2 at the glucokinase regulatory protein (GCKR) locus was similarly significantly associated, while the rs10911205 [1.29 (1.16-1.44); p = 3.52 × 10 -6 ] on chr1 at the laminin subunit gamma-1 (LAMC1) locus showed suggestive association with disease. Furthermore, the rs17145738 [0.68 (0.60-0.77); p = 6.69 × 10 -9 ] on chr7 at the carbohydrate-responsive element-binding protein-encoding (MLXIPL) gene locus displayed significant protective characteristics, while another variant rs6982502 [0.76 (0.68-0.84); p = 5.31 × 10 -7 ] on chr8 showed similar but weaker properties. These findings were replicated in 317 cases vs 1415 controls from the same ethnic Arab population. Our study identified several variants across the human genome that are associated with hTG in ethnic Arabs., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Magnetoresistance (MR), the change of a material's electrical resistance in response to an applied magnetic field, is a technologically important property that has been the topic of intense study for more than a quarter century. We report the observation of an unusual "butterfly"-shaped titanic angular magnetoresistance (AMR) in the nonmagnetic Dirac material, ZrSiS, which we find to be the most conducting sulfide known, with a 2-K resistivity as low as 48(4) nΩ⋅cm. The MR in ZrSiS is large and positive, reaching nearly 1.8 × 10 5 percent at 9 T and 2 K at a 45° angle between the applied current ( I || a ) and the applied field (90° is H || c ). Approaching 90°, a "dip" is seen in the AMR, which, by analyzing Shubnikov de Haas oscillations at different angles, we find to coincide with a very sharp topological phase transition unlike any seen in other known Dirac/Weyl materials. We find that ZrSiS has a combination of two-dimensional (2D) and 3D Dirac pockets comprising its Fermi surface and that the combination of high-mobility carriers and multiple pockets in ZrSiS allows for large property changes to occur as a function of angle between applied fields. This makes it a promising platform to study the physics stemming from the coexistence of 2D and 3D Dirac electrons as well as opens the door to creating devices focused on switching between different parts of the Fermi surface and different topological states.

The genetic susceptibility to acquiring low high density lipoprotein-cholesterol (LHDLC) levels is not completely elucidated yet. In this study, we performed a common variant association study for harboring this trait in ethnic Arabs. We employed the Affymetrix high-density Axiom Genome-Wide ASI Array (Asian population) providing a coverage of 598,000 single nucleotide variations (SNPs) to genotype 5495 individuals in a two-phase study involving discovery and validation sets of experiments. The rs1800775 [1.31 (1.22-1.42); p = 3.41E-12] in the CETP gene and rs359027 [1.26 (1.16-1.36); p = 2.55E-08] in the LMCD1 gene were significantly associated with LHDLC levels. Furthermore, rs3104435 [1.26 (1.15-1.38); p = 1.19E-06] at the MATN1 locus, rs9835344 [1.16 (1.08-1.26); p = 8.75E-06] in the CNTN6 gene, rs1559997 [1.3 (1.14-1.47); p = 9.48E-06] in the SDS gene and rs1670273 [1.2 (1.1-1.31); p = 4.81E-06] in the DMN/SYNM gene exhibited suggestive association with the disorder. Seven other variants including rs1147169 in the PLCL1 gene, rs10248618 in the DNAH11, rs476155 in the GLIS3, rs7024300 in the ABCA1, intergenic rs10836699, rs11603691 in P2RX3 and rs750134 in CORO1C gene exhibited borderline protective properties. Validation and joint meta-analysis resulted in rs1800775, rs3104435 and rs359027 retaining their predisposing properties, while rs10836699 and rs11603691 showed protective properties. Our data show several predisposing variants across the genome for LHDLC levels in ethnic Arabs., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Materials harbouring exotic quasiparticles, such as massless Dirac and Weyl fermions, have garnered much attention from physics and material science communities due to their exceptional physical properties such as ultra-high mobility and extremely large magnetoresistances. Here, we show that the highly stable, non-toxic and earth-abundant material, ZrSiS, has an electronic band structure that hosts several Dirac cones that form a Fermi surface with a diamond-shaped line of Dirac nodes. We also show that the square Si lattice in ZrSiS is an excellent template for realizing new types of two-dimensional Dirac cones recently predicted by Young and Kane. Finally, we find that the energy range of the linearly dispersed bands is as high as 2 eV above and below the Fermi level; much larger than of other known Dirac materials. This makes ZrSiS a very promising candidate to study Dirac electrons, as well as the properties of lines of Dirac nodes.

Transition metal dichalcogenides have attracted research interest over the last few decades due to their interesting structural chemistry, unusual electronic properties, rich intercalation chemistry and wide spectrum of potential applications. Despite the fact that the majority of related research focuses on semiconducting transition-metal dichalcogenides (for example, MoS2), recently discovered unexpected properties of WTe2 are provoking strong interest in semimetallic transition metal dichalcogenides featuring large magnetoresistance, pressure-driven superconductivity and Weyl semimetal states. We investigate the sister compound of WTe2, MoTe2, predicted to be a Weyl semimetal and a quantum spin Hall insulator in bulk and monolayer form, respectively. We find that bulk MoTe2 exhibits superconductivity with a transition temperature of 0.10 K. Application of external pressure dramatically enhances the transition temperature up to maximum value of 8.2 K at 11.7 GPa. The observed dome-shaped superconductivity phase diagram provides insights into the interplay between superconductivity and topological physics.

The data shows results acquired in a large cohort of 5668 ethnic Arabs involved in a common variants association study for coronary artery disease (CAD) and myocardial infarction (MI) using the Affymetrix Axiom Genotyping platform ("A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs" Wakil et al. (2015) [1] ). Several loci were described that conferred risk for CAD or MI, some of which were validated in an independent set of samples. Principal Component (PCA) analysis suggested that the Saudi Cohort was close to the CEU and TSI populations, thus pointing to similarity with European populations.

Background: Multiple loci have been identified for coronary artery disease (CAD) by genome-wide association studies (GWAS), but no such studies on CAD incidence has been reported yet for any Middle Eastern population., Methods: In this study, we performed a GWAS for CAD and myocardial infarction (MI) incidence in 5668 Saudis of Arab descent using the Affymetrix Axiom Genotyping platform., Results: We describe SNPs at 16 loci that showed significant (P < 5 × 10(-8)) or suggestive GWAS association (P < 1 × 10(-5)) with CAD or MI, in the ethnic Saudi Arab population. Among the four variants reaching GWAS significance in the present study, the rs10738607&#95;G [0.78(0.71-0.85); p = 2.17E-08] in CDNK2A/B gene was associated with CAD. Two other SNPs on the same gene, rs10757274&#95;G [0.79(0.73-0.86); p = 2.98E-08] and rs1333045&#95;C [0.79(0.73-0.86); p = 1.15E-08] as well as the rs9982601&#95;T [1.38(1.23-1.55); p = 3.49E-08] on KCNE2 were associated with MI. These variants have been previously described in other populations. Several SNPs, including the rs7421388 (PLCL1) and rs12541758 (TRPA1) displaying a suggestive GWAS association (P < 1 × 10(-5)) with CAD as well as rs41411047 (RNF13), rs32793 (PDZD2) and rs4739066 (YTHDF3), similarly showing weak association with MI, were confirmed in an independent dataset. Furthermore, our estimation of heritability of CAD and MI based on observed genome-wide sharing in unrelated Saudi Arabs was approximately 33% and 44%, respectively., Conclusions: Our study has identified susceptibility variants for CAD/MI in ethnic Arabs. These findings provide further insights into pathways contributing to the susceptibility for CAD and will enable more comprehensive genetic studies of these diseases in Middle East populations., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Alexander disease, less commoniy known as fibrinoid leukodystrophy is an extremely rare, non- familial, progressive, lethal leukodystrophy which is characterized predominantly by abnormalities of white matter in bilateral frontal regions. It usually presents early within first 2 years of life with clinical features of macrocephaly, recurrent seizures and psychomotor retardation. Diagnosis of this white matter disorder is possible with certain features seen on magnetic resonance imaging (MRI), even without the need for histological confirmation. Our case is a one year old male infant who presented with repeated episodes of focal seizures to the paediatrician. He was referred for an MRI and subsequently based on typical MRI findings the diagnosis of Alexander disease was made.

Despite their rigorous training, studies have shown that physicians experience higher rates of mental illness, substance abuse, and suicide compared to the general population. An online questionnaire was sent to a random sample of physicians across Canada to assess physicians' knowledge of the incidence of mental illness among physicians and their attitudes towards disclosure and treatment in a hypothetical situation where one developed a mental illness. We received 139 responses reflecting mostly primary care physicians and nonsurgical specialists. The majority of respondents underestimated the incidence of mental illness in physicians. The most important factors influencing respondent's will to disclose their illness included career implications, professional integrity, and social stigma. Preference for selecting mental health treatment services, as either outpatients or inpatients, was mostly influenced by quality of care and confidentiality, with lower importance of convenience and social stigma. Results from this study suggest that the attitudes of physicians towards becoming mentally ill are complex and may be affected by the individual's previous diagnosis of mental illness and the presence of a family member with a history of mental illness. Other factors include the individual's medical specialty and level of experience. As mental illness is common among physicians, one must be conscious of these when offering treatment options.

Dirac and Weyl semimetals are 3D analogues of graphene in which crystalline symmetry protects the nodes against gap formation. Na3Bi and Cd3As2 were predicted to be Dirac semimetals, and recently confirmed to be so by photoemission experiments. Several novel transport properties in a magnetic field have been proposed for Dirac semimetals. Here, we report a property of Cd3As2 that was unpredicted, namely a remarkable protection mechanism that strongly suppresses backscattering in zero magnetic field. In single crystals, the protection results in ultrahigh mobility, 9 × 10(6) cm(2) V(-1) s(-1) at 5 K. Suppression of backscattering results in a transport lifetime 10(4) times longer than the quantum lifetime. The lifting of this protection by the applied magnetic field leads to a very large magnetoresistance. We discuss how this may relate to changes to the Fermi surface induced by the applied magnetic field.

Congenital diaphragmatic hernia is a very common intrathoracic fetal anomaly with Morgagni hernia typically seen on right side anteriorly and Bochdalek hernia on left side posteriorly, because of the protective effects of liver and heart on either side respectively. Hiatal hernias range from herniation of a small portion of stomach into thoracic cavity to herniation of entire stomach into the left thoracic cavity. Very rarely the herniated stomach has been reported in the right thoracic cavity. Early diagnosis and treatment of all diaphragmatic hernias is essential to reduce the associated morbidity and mortality. We present a very rare and interesting case of an 18 months old baby girl with reverse scenarios. She had a large hiatal hernia with right intrathoracic stomach along with a left sided Morgagni hernia in combination.

Magnetoresistance is the change in a material's electrical resistance in response to an applied magnetic field. Materials with large magnetoresistance have found use as magnetic sensors, in magnetic memory, and in hard drives at room temperature, and their rarity has motivated many fundamental studies in materials physics at low temperatures. Here we report the observation of an extremely large positive magnetoresistance at low temperatures in the non-magnetic layered transition-metal dichalcogenide WTe2: 452,700 per cent at 4.5 kelvins in a magnetic field of 14.7 teslas, and 13 million per cent at 0.53 kelvins in a magnetic field of 60 teslas. In contrast with other materials, there is no saturation of the magnetoresistance value even at very high applied fields. Determination of the origin and consequences of this effect, and the fabrication of thin films, nanostructures and devices based on the extremely large positive magnetoresistance of WTe2, will represent a significant new direction in the study of magnetoresistivity.

The structure of Cd3As2, a high-mobility semimetal reported to host electrons that act as Dirac particles, is reinvestigated by single-crystal X-ray diffraction. It is found to be centrosymmetric rather than noncentrosymmetric as previously reported. It has a distorted superstructure of the antifluorite (M2X) structure type with a tetragonal unit cell of a = 12.633(3) and c = 25.427(7) Å in the centrosymmetric I41/acd space group. The antifluorite superstructure can be envisioned as consisting of distorted Cd6□2 cubes (where □ = an empty cube vertex) in parallel columns, stacked with opposing chirality. Electronic structure calculations performed using the experimentally determined centrosymmetric structure are similar to those performed with the inversion symmetry absent but with the important implication that Cd3As2 is a three-dimensional (3D)-Dirac semimetal with no spin splitting; all bands are spin degenerate and there is a 4-fold degenerate bulk Dirac point at the Fermi energy along Γ-Z in the Brillouin zone. This makes Cd3As2 a 3D electronic analogue of graphene. Scanning tunneling microscopy experiments identify a 2 × 2 surface reconstruction in the (112) cleavage plane of single crystals; needle crystals grow with a [110] long axis direction.

We examined the role of hepatic nuclear factor-1 alpha (HNF1a) gene polymorphism on coronary artery disease (CAD) traits in 4631 Saudi angiographed individuals (2419 CAD versus 2212 controls) using TaqMan assay on ABI Prism 7900HT sequence detection system. Following adjustment for confounders, the rs2259820&#95;CC (1.19 (1.01-1.42); P = 0.041), rs2464196&#95;TT (1.19 (1.00-1.40); P = 0.045), and rs2259816&#95;T (1.13 (1.01-1.26); P = 0.031) were associated with MI. The rs2259820&#95;T (1.14 (1.03-1.26); P = 0.011) and rs2464196&#95;C (1.12 (1.02-1.24); P = 0.024) were associated with type 2 diabetes mellitus (T2DM), while the rs2393791&#95;T (1.14 (1.01-1.28); P = 0.032), rs7310409&#95;G (1.16 (1.03-1.30); P = 0.013), and rs2464196&#95;AG+GG (1.25 (1.05-1.49); P = 0.012) were implicated in hypertension. Hypertriglyceridemia was linked to the rs2393791&#95;T (1.14 (1.02-1.27); P = 0.018), rs7310409&#95;G (1.12 (1.01-1.25); P = 0.031), rs1169310&#95;G (1.15 (1.04-1.28); P = 0.010), and rs1169313&#95;CT+TT (1.24 (1.06-1.45); P = 0.008) and high low density lipoprotein-cholesterol levels were associated with rs2259820&#95;T (1.23 (1.07-1.41); P = 0.004), rs2464196&#95;T (1.22 (1.06-1.39); P = 0.004), and rs2259816&#95;T (1.18 (1.02-1.36); P = 0.023). A 7-mer haplotype CATATAC (χ(2) = 7.50; P = 0.0062), constructed from the studied SNPs, was associated with MI, and CATATA implicated in T2DM (χ(2) = 3.94; P = 0.047). Hypertriglyceridemia was linked to TGCGGG (χ(2) = 4.26; P = 0.039), and obesity to ACGGGT (χ(2) = 5.04; P = 0.025). Our results suggest that the HNF1a is a common susceptibility gene for MI, T2DM, hypertension, and dyslipidemia.

Background: Adiponectin Q is a hormone that modulates several metabolic processes and contributes to the suppression of biochemical pathways leading to metabolic syndrome. Hence, polymorphic changes in the adiponectin Q (ADIPOQ) gene are likely to contribute to metabolic disorders, and consequently lead to atherosclerosis. In the present study, we performed a population-based association study for 8 SNPs in 4646 Saudi individuals (2339 CAD cases versus angiographed 2307 controls) by real-time PCR., Methods: Linkage analysis was done by the Affymetrix Gene Chip array, sequencing by the MegaBACE DNA analysis system and genotyping accomplished by TaqMan chemistry with the Applied Biosystem real-time Prism 7900HT Sequence Detection System., Results: The rs2241766 (TG + GG) [Odds ratio(95% Confidence Interval = 1.35(1.01-1.72); p = 0.015] and rs9842733A > T [1.48(1.01-2.07); p = 0.042] were associated with hypertension [HTN; 3541 cases vs 1101 controls), following adjustment for the presence of other cardiovascular risk traits. The rs2241766 (TG + GG) was further implicated in harbouring of low high density lipoprotein levels (LHDL; 1353 versus 2156 controls) [1.35(1.10-1.67); p = 0.005], but lost its association with obesity after the adjustment for confounders. Besides, low high density lipoprotein was also linked with rs6444174 (TC + CC) [1.28(1.05-1.59)]. On the other hand, while initial univariate logistic regression analysis pointed to rs1063537 C > T (p = 0.010), rs2082940 C > T (p = 0.035) and rs1063539 G > C (p = 0.035) as being associated with myocardial infarction, significance levels of these relationships were diminished following adjustment for the influence of confounding covariates. Interestingly, haplotyping showed that an 8-mer haplotype GTGCCTCA and several of its derivatives constructed from the studied SNPs were commonly implicated in MI (χ² = 4.12; p = 0.042), HTN (χ² = 6.40; p = 0.011) and OBS (χ² = 5.18; p = 0.023)., Conclusion: These results demonstrate that the ADIPOQ 3'UTR harbours common susceptibility variants for metabolic risk traits and CAD, pointing to the importance of this region in atherosclerosis disease pathways.

Background: The muscle Ras (MRAS) gene resides on chromosome 3q22.3 and encodes a member of the membrane-associated Ras small GTPase proteins, which function as signal transducers in multiple processes including cell growth and differentiation. Its role in cardiovascular disease is not fully understood yet. In a preliminary study in heterozygous familial hypercholesterolaemia, we identified a locus linking the early onset of coronary artery disease (CAD) to chromosome 3q.22 and elected to sequence the MRAS gene using the MegaBACE DNA analysis system. In the present study, we investigated the association of seven single-nucleotide polymorphisms (SNPs) at this locus with CAD and its dyslipidaemia-related risk traits in 4,650 Saudi angiographed individuals using TaqMan assays by the Applied Biosystems real-time Prism 7900HT Sequence Detection System., Results: Among the studied SNPs, rs6782181 (p = 0.017) and rs9818870T (p = 0.009) were associated with CAD following adjustment for sex, age and other confounding risk factors. The rs6782181&#95;GG also conferred risk for obesity (1,764 cases vs. 2,586 controls) [1.16(1.03-1.30); p = 0.017], hypercholesterolaemia (1,686 vs. 2,744) [1.23(1.02-1.47); p = 0.019], hypertriglyceridaemia (1,155 vs. 3,496) [1.29(1.01-1.45); p = 0.043] and low high-density lipoprotein-cholesterol (lHDL-chol) levels (1,935 vs. 2,401) [1.15(1.02-1.30); p = 0.023] after adjustment. Additionally, rs253662&#95;(CT+TT) [1.16(1.01-1.32); p = 0.030] was associated with lHDL-chol levels. Interestingly, rs253662 (p = 0.014) and rs6782181 (p = 0.019) were protective against acquiring high low-density lipoprotein-cholesterol (hLDL-chol) levels (p = 0.014), while rs1720819 showed similar effects against CAD (p < 0.0001). More importantly, a 7-mer haplotype, ACCTGAC (χ2 = 7.66; p = 0.0056), constructed from the studied SNPs, its 6-mer derivative CCTGAC (χ2 = 6.90; p = 0.0086) and several other shorter derivatives conferred risk for obesity. hLDL-chol was weakly linked to CTAA (χ2 = 3.79; p = 0.052) and CCT (χ2 = 4.32; p = 0.038), while several other haplotypes were protective against both obesity and hLDL-chol level., Conclusion: Our results demonstrate that the genomic locus for the MRAS gene confers risk for CAD, obesity and dyslipidaemia and point to the possible involvement of other genes or regulatory elements at this locus, rather than changes in the M-Ras protein function, in these events.

Background: Angiotensinogen (AGT) constitutes a central component of the renin-angiotensin system that controls the systemic blood pressure and several other cardiovascular functions and may play an important role in atherosclerosis pathways. In this study, we employed TaqMan genotyping assays to evaluate the role of 8 AGT variants in primary hypertension (HTN), type 2 diabetes mellitus (T2DM), and obesity as a possible trigger of coronary artery disease (CAD) in a population of 4615 angiographed native Saudi individuals., Methods: Linkage analysis was done by using the Affymetrix Gene Chip array, sequencing by using the MegaBACE DNA analysis system and genotyping accomplished by TaqMan chemistry using the Applied Biosystem real-time Prism 7900HT Sequence Detection System., Results: Six variants, rs2067853 GG [Odds ratio(95% Confidence Interval) = 1.44(1.17-1.78); p = 0.001], rs7079 [1.49(1.20-1.85); p < 0.0001], rs699 G [1.19(1.08-1.13); p < 0.0001], rs3789679 A [1.51(1.14-1.99); p = 0.004], rs2148582 GG [1.31(1.11-1.55); p = 0.002] and rs5051 TC + CC [1.32(1.13-1.60); p = 0.001] conferred risk for HTN (3521 cases versus 1094 controls). The rs2067853 (p = 0.042), rs699G (p = 0.007) and rs5051 (p = 0.051) also conferred risk for myocardial infarction (MI; 2982 vs 1633), while rs3789679 A (p < 0.0001) and GA + AA (p < 0.0001) as well as rs4762G (p = 0.019) were associated with obesity (1576 vs 2458). However, while these variants appeared to be also associated with CAD (2323 vs 2292), only the rs7079G (p = 0.035) retained its significant relationship. Interestingly, among the haplotypes constructed from these SNPs, the baseline 8-mer haplotype, GGTGGGGT (χ² = 7.02; p = 0.0081) and another GGCGGAGT (χ² = 5.10; p = 0.024), together with several of their derivatives were associated with HTN. T2DM was associated with two 8-mer haplotypes, GGTAGGAC (χ2 = 5.66; p = 0.017) and ATTGAGAC (χ² = 5.93; p = 0.015), obesity with GGCGGAGT (χ² = 9.49; p = 0.0021) and MI was linked to ATTGGGAC (χ² = 6.68; p = 0.010) and GGTGGGAT (χ² = 4.25; p = 0.039). Furthermore, several causative haplotypes were also shared among the risk traits as well as with CAD., Conclusion: These results point to AGT as independently conferring risk for various cardiovascular traits, and possibly interacting with these traits in events leading to atherosclerosis.

Fibrillar amyloid beta-protein (Abeta) is the principal component of amyloid plaques in the brains of patients with Alzheimer's disease. We have studied the effect of walnut extract on Abeta fibrillization by Thioflavin T fluorescence spectroscopy and electron microscopy. The walnut extract not only inhibited Abeta fibril formation in a concentration and time- dependent manner but it was also able to defibrillize Abeta preformed fibrils. Over 90% inhibition of Abeta fibrillization was observed with 5 microl of methanolic extract of walnut (MEOW) both after 2 and 3 days of incubation. The maximum defibrillization (91.6%) was observed when preformed Abeta fibrils were incubated with 10 microl of MEOW for 2 days. These results suggest that walnuts may reduce the risk or delay the onset of Alzheimer's disease by maintaining Abeta in the soluble form. Further studies showed that anti-amyloidogenic compound in walnut is an organic compound of molecular weight less than 10 kDa, which is neither a lipid nor a protein. Chloroform extract of walnut had no effect on Abeta fibrillization while MEOW and its 10 kDa filtrate inhibited Abeta fibrillization equally. It is proposed that polyphenolic compounds (such as flavonoids) present in walnuts may be responsible for its anti-amyloidogenic activity.