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Hingorani A

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https://www.readbyqxmd.com/read/28500271/causal-associations-of-adiposity-and-body-fat-distribution-with-coronary-heart-disease-stroke-subtypes-and-type-2-diabetes-a-mendelian-randomization-analysis
#1
Caroline Dale, Ghazaleh Fatemifar, Tom Palmer, Jonathan White, David Prieto-Merino, Delilah Zabaneh, Jorgen E L Engmann, Tina Shah, Andrew Wong, Helen R Warren, Stela McLachlan, Stella Trompet, Max Moldovan, Richard W Morris, Reecha Sofat, Meena Kumari, Elina Hyppönen, Barbara J Jefferis, Tom R Gaunt, Yoav Ben-Shlomo, Ang Zhou, Aleksandra Gentry-Maharaj, Andy Ryan, Renée de Mutsert, Raymond Noordam, Mark J Caulfield, J Wouter Jukema, Bradford B Worrall, Patricia B Munroe, Usha Menon, Chris Power, Diana Kuh, Debbie A Lawlor, Steve E Humphries, Dennis O Mook-Kanamori, George Davey Smith, Naveed Sattar, Mika Kivimaki, Jacqueline F Price, Frank Dudbridge, Aroon D Hingorani, Michael V Holmes, Juan-Pablo Casas
Background -Implications of different adiposity measures on cardiovascular disease aetiology remain unclear. In this paper we quantify and contrast causal associations of central adiposity (waist:hip ratio adjusted for BMI (WHRadjBMI)) and general adiposity (body mass index (BMI)) with cardiometabolic disease. Methods -97 independent single nucleotide polymorphisms (SNPs) for BMI and 49 SNPs for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with CHD data from CARDIoGRAMplusC4D (combined total 66,842 cases), stroke from METASTROKE (12,389 ischaemic stroke cases), type 2 diabetes (T2D) from DIAGRAM (34,840 cases), and lipids from GLGC (213,500 participants) consortia...
May 12, 2017: Circulation
https://www.readbyqxmd.com/read/28459559/photostable-ratiometric-pdot-probe-for-in-vitro-and-in-vivo-imaging-of-hypochlorous-acid
#2
Li Wu, I-Che Wu, Christopher C DuFort, Markus A Carlson, Xu Wu, Lei Chen, Chun-Ting Kuo, Yuling Qin, Jiangbo Yu, Sunil R Hingorani, Daniel T Chiu
Developing probes for the detection of reactive oxygen species (ROS), a hallmark of many pathophysiological process, is imperative to both understanding the precise roles of ROS in many life-threatening diseases and optimizing therapeutic interventions. We herein report an all-in-one fluorescent semiconducting polymer based far-red to near-infrared (NIR) Pdot nanoprobe for the ratiometric detection of hypochlorous acid (HOCl). The fabrication takes the advantage of flexible polymer design by incorporating target-sensitive and target-inert fluorophores into a single conjugated polymer to avoid leakage or differential photobleaching problems existed in other nanoprobes...
May 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28456096/identifying-low-density-lipoprotein-cholesterol-associated-variants-in-the-annexin-a2-anxa2-gene
#3
Roaa Hani Fairoozy, Jackie Cooper, Jon White, Claudia Giambartolomei, Lasse Folkersen, S Goya Wannamethee, Barbara J Jefferis, Peter Whincup, Yoav Ben-Shlomo, Meena Kumari, Mika Kivimaki, Andrew Wong, Rebecca Hardy, Diana Kuh, Tom R Gaunt, J P Casas, Stela McLachlan, Jackie F Price, Aroon Hingorani, Anders Franco-Cereceda, Thomas Grewal, Anastasia Z Kalea, Steve E Humphries
BACKGROUND AND AIMS: Annexin-A2 (AnxA2) is an endogenous inhibitor of proprotein convertase subtilisin/kexin type-9 (PCSK9). The repeat-one (R1) domain of AnxA2 binds to PCSK9, blocking its ability to promote degradation of low-density lipoprotein cholesterol-receptors (LDL-R) and thereby regulate low-density lipoprotein cholesterol (LDL-C) levels. Here we identify variants in ANXA2 influencing LDL-C levels and we determine the molecular mechanisms of their effects. RESULTS: The ANXA2 single nucleotide polymorphism (SNP) genotype-phenotype association was examined using the Second-Northwick-Park Heart Study (NPHSII) (n∼2700) and the UCL-LSHTM-Edinburgh-Bristol (UCLEB) consortium (n∼14,600)...
April 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28453187/pcsk9-monoclonal-antibodies-for-the-primary-and-secondary-prevention-of-cardiovascular-disease
#4
REVIEW
Amand F Schmidt, Lucy S Pearce, John T Wilkins, John P Overington, Aroon D Hingorani, Juan P Casas
BACKGROUND: Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for patients who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) may further reduce LDL-C, potentially reducing CVD risk as well...
April 28, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28436317/endoureteral-coil-embolization-of-an-ureteral-arterial-fistula
#5
Pavel Kibrik, Justin Eisenberg, Marc A Bjurlin, Natalie Marks, Anil Hingorani, Enrico Ascher
Background Ureteral arterial fistulas are rare but potentially life threatening. We present a female who developed a ureteral arterial fistula following a right robotic nephrectomy. After several endovascular interventions to control the bleeding had failed, we approached the fistula through the right ureteral stump with coil embolization. Methods Coil embolization of the right ureteral stump was performed. We utilized a 6Fr × 45 cm sheath inserted through one of the cystoscope channels to cannulate the right ureteral orifice...
January 1, 2017: Vascular
https://www.readbyqxmd.com/read/28423765/evaluation-of-machine-learning-methods-to-predict-coronary-artery-disease-using-metabolomic-data
#6
Henrietta Forssen, Riyaz Patel, Natalie Fitzpatrick, Aroon Hingorani, Adam Timmis, Harry Hemingway, Spiros Denaxas
Metabolomic data can potentially enable accurate, non-invasive and low-cost prediction of coronary artery disease. Regression-based analytical approaches however might fail to fully account for interactions between metabolites, rely on a priori selected input features and thus might suffer from poorer accuracy. Supervised machine learning methods can potentially be used in order to fully exploit the dimensionality and richness of the data. In this paper, we systematically implement and evaluate a set of supervised learning methods (L1 regression, random forest classifier) and compare them to traditional regression-based approaches for disease prediction using metabolomic data...
2017: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/28409546/clinical-correlation-with-failure-of-endovenous-therapy-for-leg-swelling
#7
Ahmad Alsheekh, Anil Hingorani, Natalie Marks, Yuriy Ostrozhynskyy, Enrico Ascher
Background The development and use of minimally invasive procedures provide improved options for the management of symptoms of chronic venous insufficiency. While many patients with iliac venous occlusive disease and superficial venous insufficiency improve with combined iliac venous stenting and correction of superficial venous reflux, some patients have symptoms which persist. The goal of this study was to identify clinical factors related to persistent symptoms in patients with leg swelling after treatment of both iliac vein stenting and thermal ablation...
June 2017: Vascular
https://www.readbyqxmd.com/read/28399267/development-of-a-%C3%AE-9-tetrahydrocannabinol-amino-acid-dicarboxylate-prodrug-with-improved-ocular-bioavailability
#8
Goutham R Adelli, Prakash Bhagav, Pranjal Taskar, Tushar Hingorani, Sara Pettaway, Waseem Gul, Mahmoud A ElSohly, Michael A Repka, Soumyajit Majumdar
Purpose: The aim of the present study was to evaluate the utility of the relatively hydrophilic Δ9-tetrahydrocannabinol (THC) prodrugs, mono and di-valine esters (THC-Val and THC-Val-Val) and the amino acid (valine)-dicarboxylic acid (hemisuccinate) ester (THC-Val-HS), with respect to ocular penetration and intraocular pressure (IOP) lowering activity. THC, timolol, and pilocarpine eye drops were used as controls. Methods: THC-Val, THC-Val-Val, and THC-Val-HS were synthesized and chemically characterized...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28356508/the-druggable-genome-and-support-for-target-identification-and-validation-in-drug-development
#9
Chris Finan, Anna Gaulton, Felix A Kruger, R Thomas Lumbers, Tina Shah, Jorgen Engmann, Luana Galver, Ryan Kelley, Anneli Karlsson, Rita Santos, John P Overington, Aroon D Hingorani, Juan P Casas
Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end points) are important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets, and, where there were licensed drugs, to clinical indications...
March 29, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28349888/screening-for-familial-hypercholesterolaemia-in-childhood-avon-longitudinal-study-of-parents-and-children-alspac
#10
Marta Futema, Jackie A Cooper, Marietta Charakida, Christopher Boustred, Naveed Sattar, John Deanfield, Debbie A Lawlor, Nicholas J Timpson, Steve E Humphries, Aroon D Hingorani
BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is an autosomal-dominant disease with frequency of 1/500 to 1/250 that leads to premature coronary heart disease. New approaches to identify FH mutation-carriers early are needed to prevent premature cardiac deaths. In a cross-sectional study of the Avon Longitudinal Study of Parents and Children (ALSPAC), we evaluated the biochemical thresholds for FH screening in childhood, and modelled a two-stage biochemical and sequencing screening strategy for FH detection...
May 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28330434/is-there-an-effect-of-race-ethnicity-on-early-complications-of-iliac-vein-stenting
#11
Ahmad Alsheekh, Anil Hingorani, Samson Ferm, Pavel Kibric, Afsha Aurshina, Natalie Marks, Enrico Ascher
Background There have been well-documented implications of race/ethnicity on the outcome of various vascular diseases. Little literature has examined the effect of race/ethnicity on venous disease. Iliac vein stenting is an emerging technology in treating chronic venous insufficiency. To further characterize this disease and its treatment, we chose to study the effect of selected clinical factors including race/ethnicity on the early complications of non-thrombotic iliac vein stenting. Methods In this observational study, data analysis was performed for 623 patients with chronic venous insufficiency who underwent iliac vein stenting during the time period from August 2012 to September 2014...
January 1, 2017: Vascular
https://www.readbyqxmd.com/read/28299667/runx3-and-cell-fate-decisions-in-pancreas-cancer
#12
Martin C Whittle, Sunil R Hingorani
The RUNX family transcription factors are critical regulators of development and frequently dysregulated in cancer. RUNX3, the least well characterized of the three family members, has been variously described as a tumor promoter or suppressor, sometimes with conflicting results and opinions in the same cancer and likely reflecting a complex role in oncogenesis. We recently identified RUNX3 expression as a crucial determinant of the predilection for pancreatic ductal adenocarcinoma (PDA) cells to proliferate locally or promulgate throughout the body...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28279251/oral-anticoagulants-for-primary-prevention-treatment-and-secondary-prevention-of-venous-thromboembolic-disease-and-for-prevention-of-stroke-in-atrial-fibrillation-systematic-review-network-meta-analysis-and-cost-effectiveness-analysis
#13
Jonathan Ac Sterne, Pritesh N Bodalia, Peter A Bryden, Philippa A Davies, Jose A López-López, George N Okoli, Howard Hz Thom, Deborah M Caldwell, Sofia Dias, Diane Eaton, Julian Pt Higgins, Will Hollingworth, Chris Salisbury, Jelena Savović, Reecha Sofat, Annya Stephens-Boal, Nicky J Welton, Aroon D Hingorani
BACKGROUND: Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs...
March 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28254179/neutrophil-counts-and-initial-presentation-of-12-cardiovascular-diseases-a-caliber-cohort%C3%A2-study
#14
Anoop Dinesh Shah, Spiros Denaxas, Owen Nicholas, Aroon D Hingorani, Harry Hemingway
BACKGROUND: Neutrophil counts are a ubiquitous measure of inflammation, but previous studies on their association with cardiovascular disease (CVD) were limited by small numbers of patients or a narrow range of endpoints. OBJECTIVES: This study investigated associations of clinically recorded neutrophil counts with initial presentation for a range of CVDs. METHODS: We used linked primary care, hospitalization, disease registry, and mortality data in England...
March 7, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28225386/acute-myocardial-infarction-and-antiphospholipid-antibody-syndrome-a-systematic-review
#15
Salik Nazir, Niranjan Tachamo, Saroj Lohani, Rittu Hingorani, Dilli R Poudel, Anthony Donato
BACKGROUND: Antiphospholipid antibody syndrome (APS) is a disorder associated with both arterial and venous thromboembolic disease, including acute myocardial infarction (AMI). Given that management with anticoagulants is critical and differs from usual AMI care, identification of key discriminators of patients with AMI with APS is important. METHODS: We performed an English-language systematic review of the literature of cases and case series of patients with AMI and APS from inception until 20 March 2016, collecting demographics, investigations, and outcomes...
June 2017: Coronary Artery Disease
https://www.readbyqxmd.com/read/28218913/ligand-promoted-protein-folding-by-biased-kinetic-partitioning
#16
Karan S Hingorani, Matthew C Metcalf, Derrick T Deming, Scott C Garman, Evan T Powers, Lila M Gierasch
Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems...
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28170093/topical-treatments-for-blepharokeratoconjunctivitis-in-children
#17
REVIEW
Michael O'Gallagher, Catey Bunce, Melanie Hingorani, Frank Larkin, Stephen Tuft, Annegret Dahlmann-Noor
BACKGROUND: Blepharokeratoconjunctivitis (BKC) is a type of inflammation of the surface of the eye and eyelids that involves changes of the eyelids, dysfunction of the meibomian glands, and inflammation of the conjunctiva and cornea. Chronic inflammation of the cornea can lead to scarring, vascularisation and opacity. BKC in children can cause significant symptoms including irritation, watering, photophobia and loss of vision from corneal opacity, refractive error or amblyopia.Treatment of BKC is directed towards modification of meibomian gland disease and the bacterial flora of lid margin and conjunctiva, and control of ocular surface inflammation...
February 7, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28135092/evolutionary-covariance-combined-with-molecular-dynamics-predicts-a-framework-for-allostery-in-the-muts-dna-mismatch-repair-protein
#18
Bharat Lakhani, Kelly M Thayer, Manju M Hingorani, David L Beveridge
Mismatch repair (MMR) is an essential, evolutionarily conserved pathway that maintains genome stability by correcting base-pairing errors in DNA. Here we examine the sequence and structure of MutS MMR protein to decipher the amino acid framework underlying its two key activities-recognizing mismatches in DNA and using ATP to initiate repair. Statistical coupling analysis (SCA) identified a network (sector) of coevolved amino acids in the MutS protein family. The potential functional significance of this SCA sector was assessed by performing molecular dynamics (MD) simulations for alanine mutants of the top 5% of 160 residues in the distribution, and control nonsector residues...
March 9, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28007107/patient-reported-outcome-measuring-tools-in-cataract-surgery-clinical-comparison-at%C3%A2-a-tertiary-hospital
#19
Simon S M Fung, Joshua Luis, Badrul Hussain, Catey Bunce, Melanie Hingorani, Joanne Hancox
PURPOSE: To assess the performance of patient-reported outcome measure questionnaires and determine their appropriateness for routine use in cataract patients. SETTING: Moorfields Eye Hospital, London, United Kingdom. DESIGN: Prospective cohort study. METHODS: Patients having cataract surgery between February and March 2013 were recruited. The following 4 questionnaires-Catquest-9SF, EuroQol 5-dimensions questionnaire (EQ-5D) and visual analog scale (EQ-VAS), National Eye Institute Socioemotional Scale (NEI-SES), and short-form Visual Function Index (VF-8R)-were completed preoperatively and 3 weeks and 3 months postoperatively...
December 2016: Journal of Cataract and Refractive Surgery
https://www.readbyqxmd.com/read/27987614/the-bull-s-eye-sign-and-other-suprainguinal-venographic-findings-to-limit-the-use-of-intravascular-ultrasound-in-patients-with-severe-venous-stasis
#20
Enrico Ascher, Justin Eisenberg, Natalie Bauer, Natalie Marks, Anil Hingorani, Syed Rizvi
OBJECTIVE: When assessing the common femoral and suprainguinal veins in patients with venous stasis, it is generally agreed that use of intravascular ultrasound (IVUS) is mandatory. This widely held dogma is reinforced by the fact that extrinsic compression of the iliac veins does not reproduce images consistent with eccentric stenosis as one sees in the arterial system. In an attempt to identify a subgroup of patients where the use of IVUS could be averted, we analyzed and carefully evaluated the images of patients who had both standard contrast venograms and IVUS examinations...
January 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
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