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https://www.readbyqxmd.com/read/29660027/the-6-hydroxychromanol-derivative-sul-109-ameliorates-renal-injury-after-deep-hypothermia-and-rewarming-in-rats
#1
Pieter C Vogelaar, Maurits Roorda, Edwin L de Vrij, Martin C Houwertjes, Maaike Goris, Hjalmar Bouma, Adrianus C van der Graaf, Guido Krenning, Robert H Henning
Background: Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats...
April 11, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29655949/incidence-and-predictors-of-6-months-mortality-after-an-acute-heart-failure-event-in-rural-uganda-the-mbarara-heart-failure-registry-mahfer
#2
Fardous Charles Abeya, Boniface Amanee Elias Lumori, Suzan Joan Akello, Brian H Annex, Andrew J Buda, Samson Okello
OBJECTIVE: We sought to estimate the incidence and predictors of all-cause mortality 6 months after heart failure hospitalization in Uganda. METHODS: Mbarara Heart Failure Registry is a cohort of patients hospitalized with a clinical diagnosis of heart failure at Mbarara Regional Referral Hospital, Uganda. We measured serum electrolytes, cardiac markers, and echocardiograms. All participants were followed until death or end of 6 months. We used Fine and Gray models to estimate the incidence and predictors all-cause mortality...
March 29, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29599092/cardiorenal-syndrome-as-predictor-of-in-hospital-mortality-in-st-segment-elevation-myocardial-infarction
#3
Ailed Elena Rodríguez-Jiménez, Tessa Negrín-Valdés, Hugo Cruz-Inerarity, Pedro Javier Machural-de la Torre
INTRODUCTION: Cardiorenal syndrome includes numerous conditions affecting the heart and kidney, and is a strong predictor of cardiovascular mortality. METHOD: An analysis was performed on 157 consecutive patients admitted to the Coronary Care Unit of the Camilo Cienfuegos Hospital due to an ST-segment elevation myocardial infarction and heart failure, from January 2013 to December 2016. An analysis was made of the presence of cardiorenal syndrome and its relationship with epidemiological, clinical, and analytical variables, as well as complementary explorations...
March 26, 2018: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/29597053/associations-with-and-prognostic-and-discriminatory-role-of-n-terminal-pro-b-type-natriuretic-peptide-in-heart-failure-with-preserved-vs-mid-range-vs-reduced-ejection-fraction
#4
Gianluigi Savarese, Nicola Orsini, Camilla Hage, Ulf Dahlström, Ola Vedin, Giuseppe M C Rosano, Lars H Lund
BACKGROUND: Aim was to characterize N-terminal pro-B-type natriuretic peptide (NT-proBNP) in terms of determinants of levels and of its prognostic and discriminatory role in heart failure with mid-range (HFmrEF) vs. preserved (HFpEF) and reduced (HFrEF) ejection fraction. METHODS AND RESULTS: In 9,847 out-patients with HFpEF (n=1,811;18%), HFmrEF (n=2,122;22%) and HFrEF (n=5,914;60%) enrolled in the Swedish Heart Failure Registry, median NT-proBNP was 1,428, 1,540 and 2,288 pg/ml, respectively...
March 26, 2018: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/29580660/ckd-self-management-phenotypes-and-associations-with-clinical-outcomes
#5
Sarah J Schrauben, Jesse Y Hsu, Sylvia E Rosas, Bernard G Jaar, Xiaoming Zhang, Rajat Deo, Georges Saab, Jing Chen, Swati Lederer, Radhika Kanthety, L Lee Hamm, Ana C Ricardo, James P Lash, Harold I Feldman, Amanda H Anderson
BACKGROUND: To slow chronic kidney disease (CKD) progression and its complications, patients need to engage in self-management behaviors. The objective of this study was to classify CKD self-management behaviors into phenotypes and assess the association of these phenotypes with clinical outcomes. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Adults with mild to moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study...
March 24, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29572627/functional-impairment-and-risk-of-mortality-in-patients-on-chronic-hemodialysis-results-of-the-lazio-dialysis-registry
#6
Maurizio Bossola, Claudia Marino, Anteo Di Napoli, Nera Agabiti, Luigi Tazza, Marina Davoli
BACKGROUND: Functional impairment is associated with adverse outcomes in older people, as well as in patients on chronic hemodialysis. The aim of this study was to evaluate if functional impairment represents a risk factor for reduced survival in patients on chronic hemodialysis. METHODS: All incident chronic hemodialysis patients of Lazio, a large region of central Italy, registered in the Dialysis and Transplant Lazio Region Registry (DTLRR) in the period 2008-2013 were considered eligible...
March 23, 2018: Journal of Nephrology
https://www.readbyqxmd.com/read/29540798/application-of-a-genetic-risk-score-to-racially-diverse-type-1-diabetes-populations-demonstrates-the-need-for-diversity-in-risk-modeling
#7
Daniel J Perry, Clive H Wasserfall, Richard A Oram, MacKenzie D Williams, Amanda Posgai, Andrew B Muir, Michael J Haller, Desmond A Schatz, Mark A Wallet, Clayton E Mathews, Mark A Atkinson, Todd M Brusko
Prior studies identified HLA class-II and 57 additional loci as contributors to genetic susceptibility for type 1 diabetes (T1D). We hypothesized that race and/or ethnicity would be contextually important for evaluating genetic risk markers previously identified from Caucasian/European cohorts. We determined the capacity for a combined genetic risk score (GRS) to discriminate disease-risk subgroups in a racially and ethnically diverse cohort from the southeastern U.S. including 637 T1D patients, 46 at-risk relatives having two or more T1D-related autoantibodies (≥2AAb+ ), 790 first-degree relatives (≤1AAb+ ), 68 second-degree relatives (≤1 AAb+ ), and 405 controls...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29534825/prevalent-and-incident-heart-failure-in-cardiovascular-outcome-trials-of-patients-with-type-2-diabetes
#8
REVIEW
Stephen J Greene, Muthiah Vaduganathan, Muhammad Shahzeb Khan, George L Bakris, Matthew R Weir, Jonathan H Seltzer, Naveed Sattar, Darren K McGuire, James L Januzzi, Norman Stockbridge, Javed Butler
Despite multiple examples of glucose-lowering therapies affecting heart failure (HF) risk, ascertainment of HF data in cardiovascular outcome trials of these medications has not been systematically characterized. In this review, large (n >1,000) published phase III and IV cardiovascular outcome trials evaluating glucose-lowering therapies through June 2017 were identified. Data were abstracted from publications, U.S. Food and Drug Administration advisory committee records, and U.S. Food and Drug Administration labeling documents...
March 10, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29521244/synthesis-structural-characterization-and-docking-studies-of-sulfamoyl-phenyl-acid-esters-as-dpp-iv-inhibitors
#9
Reema Abdelkareem Abu Khalaf, Dima Sabbah, Eveen Al-Shalabi, Iyad Al-Sheikh, Ghadeer Albadawi, Ghassan Abu Sheikha
BACKGROUND: Diabetes mellitus is a major worldwide health concern that has several serious complications including retinopathy, neuropathy, nephropathy and macrovascular diseases. OBJECTIVE: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, gliptins, are a new class of antidiabetic agents that potentiates the action of incretins in decreasing the blood glucose levels. METHODS: In the present study, synthesis and characterization of a series of ten N4-sulfonamido-acrylic and phthalamic acid methyl esters (3a-e and 5a-e) were achieved...
March 8, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29521173/fixed-ratio-combination-therapy-for-type-2-diabetes-the-top-ten-things-you-should-know-about-insulin-and-glucagon-like-peptide-1-receptor-agonist-combinations
#10
Ian Blumer, Jeremy H Pettus, Tricia Santos Cavaiola
Many individuals with type 2 diabetes (T2D) will eventually require insulin therapy to help achieve and maintain adequate glycemic control. However, the use of insulin can be associated with adverse effects such as hypoglycemia and weight gain, and in some patients the addition of insulin to treatment regimens is often still insufficient to achieve target glycemic control. Combining basal insulin with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of patients with T2D has been demonstrated to be effective and well tolerated, while mitigating many of the adverse events associated with giving either of these drug classes alone...
March 9, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29516618/sodium-glucose-co-transporter-2-inhibitors-sglt2is-the-latest-residents-on-the-block-impact-on-glycaemic-control-at-a-general-practice-level-in-england
#11
A H Heald, A A Fryer, S G Anderson, M Livingston, M Lunt, M Davies, Gyc Moreno, R Gadsby, R J Young, M Stedman
AIMS: Despite increasing spend on new Type 2 diabetes mellitus (T2DM) therapies, the proportion of people with T2DM achieving target glycaemia outcomes is declining. Our aim was to determine, using published General Practice level data, how differences in T2DM prescribing patterns relate to glycaemic target achievement levels. METHODS: Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of class of medication in 2015/16 and changes to 2014/15 in medication to proportions achieving target glycaemic control (TGC; glycated haemoglobin A1c (HbA1c) ≤7...
March 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29506779/risks-of-diabetic-foot-syndrome-and-amputation-associated-with-sodium-glucose-co-transporter-2-inhibitors-a-meta-analysis-of-randomized-controlled-trials
#12
D Li, J Yufeng Yang, T Wang, S Shen, H Tang
BACKGROUND: The U.S. Food and Drug Administration recently issued a safety communication requiring new warnings of increased leg and foot amputation risk be added to canagliflozin drug labelling. However, the risk associated with other sodium-glucose co-transporter 2 inhibitors (SGLT2i) remains uncertain. AIM: This meta-analysis aimed to evaluate the potential risks of diabetic foot syndrome (DFS) and amputation associated with SGLT2i. METHODS: Relevant databases were searched from inception to June 14, 2017 to identify randomized controlled trials (RCTs) that evaluated risks of DFS and amputation associated with SGLT2i use...
February 13, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29491518/fast-tracking-in-adult-living-donor-liver-transplantation-a-case-series-of-15-patients
#13
Pooja Bhangui, Prashant Bhangui, Nikunj Gupta, Annu Sarin Jolly, Seema Bhalotra, Nishant Sharma, A S Soin, Vijay Vohra
Background and Aims: Fast tracking (FT) for more efficacious use of resources may be difficult after living donor liver transplantation (LDLT) due to a partial liver graft, complex vascular anastomoses and longer operating time. Our study was aimed at reporting our experience with FT (on table extubation) in LDLT recipients. A secondary objective of our study was to look at defining a subgroup of patients who could be prospectively planned for FT. Methods: We studied the demographics and outcomes of 15 LDLT recipients extubated immediately in the operating suite based on an uneventful intraoperative course, haemodynamic stability after graft reperfusion and improvement of metabolic parameters post-implantation and vascular anastomoses...
February 2018: Indian Journal of Anaesthesia
https://www.readbyqxmd.com/read/29481928/outcomes-and-risk-factors-associated-with-prolonged-intubation-after-evar
#14
Ian C Bostock, Devin S Zarkowsky, Caitlin W Hicks, David H Stone, Mahmoud B Malas, Philip P Goodney
BACKGROUND: Time to discharge has decreased for aortic surgery since the advent of EVAR, partially due to improved perioperative management. We aimed to investigate outcomes and risk factors associated with prolonged intubation following EVAR. METHODS: The VSGNE database was queried to select all patients who underwent elective EVAR between 01/2003 and 12/2014. Patients who were not extubated in the operating room were classified as having prolonged intubation. Patients requiring prolonged intubation were compared to those extubated in the OR using t-test and chi-square statistics...
February 23, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29447733/stroke-risk-in-patients-with-reduced-ejection-fraction-after-myocardial-infarction-without-atrial-fibrillation
#15
João Pedro Ferreira, Nicolas Girerd, John Gregson, Ichraq Latar, Abhinav Sharma, Marc A Pfeffer, John J V McMurray, Azmil H Abdul-Rahim, Bertram Pitt, Kenneth Dickstein, Patrick Rossignol, Faiez Zannad
BACKGROUND: Stroke can occur after myocardial infarction (MI) in the absence of atrial fibrillation (AF). OBJECTIVES: This study sought to identify risk factors (excluding AF) for the occurrence of stroke and to develop a calibrated and validated stroke risk score in patients with MI and heart failure (HF) and/or systolic dysfunction. METHODS: The datasets included in this pooling initiative were derived from 4 trials: CAPRICORN (Effect of Carvedilol on Outcome After Myocardial Infarction in Patients With Left Ventricular Dysfunction), OPTIMAAL (Optimal Trial in Myocardial Infarction With Angiotensin II Antagonist Losartan), VALIANT (Valsartan in Acute Myocardial Infarction Trial), and EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study); EPHESUS was used for external validation...
February 20, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29438556/physical-performance-trajectories-and-mortality-among-older-mexican-americans
#16
Miriam Mutambudzi, Nai-Wei Chen, Bret Howrey, Marc A Garcia, Kyriakos S Markides
Background: We sought to identify distinct trajectory classes of physical performance in Mexican Americans aged 75 years and older, and to examine whether these trajectories predict mortality. Methods: We used 4 waves of Hispanic Established Populations for Epidemiologic Studies of the Elderly (H-EPESE) data for adults 75 years and older from 2004-5 to 2013. Latent growth curve analysis was used to identify distinct trajectory classes. Multinomial logistic regression analysis was used to examine the association between baseline characteristics and the newly constructed trajectories...
February 9, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29438464/intra-generational-social-mobility-and-changes-in-blood-pressure-longitudinal-analysis-from-the-elsa-brasil-study
#17
J M N Guimarães, R H Griep, P J Clarke, M J M Fonseca, S M Barreto, L Giatti, P A Lotufo, J G Mill, A G Pacheco, D Chor
Background: During the past four decades, the highest worldwide blood pressure (BP) levels have shifted from high-income countries to low- and middle-income countries. We investigated the association of intra-generational social mobility with changes in BP and also with the incidence of hypertension over a 4-year follow-up. Methods: Data for 6529 baseline participants from ELSA-Brasil born between 1938 and 1975 were used. Based on a social mobility matrix, occupational social mobility was defined as the change in occupational social class between participants' first occupation and current occupation (stable high; upward; downward; stable low)...
February 9, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29431870/a-quarter-of-patients-with-type-1-diabetes-have-co-existing-non-islet-autoimmunity-the-findings-of-a-uk-population-based-family-study
#18
Aizhan Kozhakhmetova, Rebecca C Wyatt, Claire Caygill, Claire Williams, Anna E Long, Kyla Chandler, Rachel J Aitken, Janet M Wenzlau, Howard W Davidson, Kathleen M Gillespie, Alistair J K Williams
Individuals with type 1 diabetes (T1D) are at increased risk of coeliac disease (CD), autoimmune thyroiditis and autoimmune gastritis, but the absolute risks are unclear. The aim of this study was to investigate the prevalence of autoantibodies to tissue transglutaminase (TGA), thyroid peroxidase (TPOA), and gastric H+ /K+ -ATPase (ATPA) and their genetic associations in a well-characterised population-based cohort of individuals with T1D from the Bart's-Oxford family study for whom islet autoantibody prevalence data were already available...
February 12, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29415819/a-new-class-of-drugs-for-heart-failure-sglt2-inhibitors-reduce-sympathetic-overactivity
#19
REVIEW
Motoaki Sano
Even in the presence of excess glucose, the proximal renal tubules continue to resorb more glucose. Sodium glucose cotransporter 2 (SGLT2) inhibitors are drugs that control this "greed" (H. Ito, Keio University, Japan). Negative feedback mechanisms maintain homeostasis for various physiological functions. However, there is no negative feedback mechanism for resorption of glucose by the proximal renal tubules. When food was scarce during human evolution, not limiting nutrient reabsorption was advantageous for survival, but the opposite is true in the era of satiation...
February 4, 2018: Journal of Cardiology
https://www.readbyqxmd.com/read/29412819/gut-hormone-polyagonists-for-the-treatment-of-type-2-diabetes
#20
Sara J Brandt, Anna Götz, Matthias H Tschöp, Timo D Müller
Chemical derivatives of the gut-derived peptide hormone glucagon-like peptide 1 (GLP-1) are among the best-in-class pharmacotherapies to treat obesity and type 2 diabetes. However, GLP-1 analogs have modest weight lowering capacity, in the range of 5-10%, and the therapeutic window is hampered by dose-dependent side effects. Over the last few years, a new concept has emerged: combining the beneficial effects of several key metabolic hormones into a single molecular entity. Several unimolecular GLP-1-based polyagonists have shown superior metabolic action compared to GLP-1 monotherapies...
February 2018: Peptides
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