Hospital healthcare flows: A longitudinal clustering approach of acute coronary syndrome in women over 45 years.

Acute coronary syndrome (ACS) in women is a growing public health issue and a death leading cause. We explored whether the hospital healthcare trajectory was characterizable using a longitudinal clustering approach in women with ACS. From the 2009-2014 French nationwide hospital database, we extracted spatio-temporal patterns in ACS patient trajectories, by replacing the spatiality by their hospitalization cause.

Sequential Pattern Mining to Predict Medical In-Hospital Mortality from Administrative Data: Application to Acute Coronary Syndrome.

Prediction of a medical outcome based on a trajectory of care has generated a lot of interest in medical research. In sequence prediction modeling, models based on machine learning (ML) techniques have proven their efficiency compared to other models. In addition, reducing model complexity is a challenge.

Prediction of In-Hospital Mortality from Administrative Data: A Sequential Pattern Mining Approach.

Study of trajectory of care is attractive for predicting medical outcome. Models based on machine learning (ML) techniques have proven their efficiency for sequence prediction modeling compared to other models. Introducing pattern mining techniques contributed to reduce model complexity.

Hospital burden of coronary artery disease: Trends of myocardial infarction and/or percutaneous coronary interventions in France 2009-2014.

Background: Currently, cardiovascular disease (CVD) is widely acknowledged to be the first leading cause of fatality in the world with 31% of all deaths worldwide and is predicted to remain as such in 2030. Furthermore, CVD is also a major cause of morbidity in adults worldwide. Among these diseases, the coronary artery disease (CAD) is the most common cause, accounting for over 40% of CVD deaths.

PaFloChar: An Innovating Approach to Characterise Patient Flows in Myocardial Infarction.

A better knowledge of patient flows would improve decision making in health planning. In this article, we propose a method to characterise patients flows and also to highlight profiles of care pathways considering times and costs. From medico-administrative data, we extracted spatio-temporal patterns.

Short-term administration of the glucagon receptor antagonist LY2409021 lowers blood glucose in healthy people and in those with type 2 diabetes.

Aim: To describe the clinical effects of single and multiple doses of a potent, selective, orally administered, small-molecule antagonist of the human glucagon receptor, LY2409021, in healthy subjects and in patients with type 2 diabetes.

Methods: LY2409021 was administered in dose-escalation studies to healthy subjects (n = 23) and patients with type 2 diabetes (n = 9) as single doses (Study 1) and daily to patients with type 2 diabetes (n = 47) for 28 days (Study 2). Safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) assessments were made after single doses and in patients receiving once-daily doses of LY2409021 (5, 30, 60 or 90 mg) for 28 days.

Therapeutic potential of retinoid x receptor modulators for the treatment of the metabolic syndrome.

The increasing prevalence of obesity is a fundamental contributor to the growing prevalence of the metabolic syndrome. Rexinoids, a class of compounds that selectively bind and activate RXR, are being studied as a potential option for the treatment of metabolic syndrome. These compounds have glucose-lowering, insulin-sensitizing, and antiobesity effects in animal models of insulin resistance and type 2 diabetes.

A single-center, randomized, double-blind, three-way crossover study examining postchallenge glucose responses to human insulin 70/30 and insulin lispro fixed mixtures 75/25 and 50/50 in patients with type 2 diabetes mellitus.

Objective: The aim of this study was to test the ability of human insulin 70/30, insulin lispro mixture 75/25 (75% neutral protamine lispro [NPL], 25% insulin lispro), and insulin lispro mixture 50/50 (50% NPL, 50% insulin lispro) to control postprandial glucose (PPG) concentrations in patients with type 2 diabetes mellitus (DM).

Methods: This single-center, randomized, double-blind, 3-way crossover study was conducted at the Diabetes and Glandular Disease Research Center, San Antonio, Texas. We measured serum glucose responses after a standardized breakfast test meal (500 kcal; 50% carbohydrate, 34% fat, 16% protein) in patients with type 2 DM receiving a single preprandial dose of human insulin 70/30, insulin lispro 75/25, or insulin lispro 50/50 by SC injection.

Global effects of vitamin A deficiency on gene expression in rat liver: evidence for hypoandrogenism.

Vitamin A (retinol) metabolites are ligands for transcription factors that regulate many genes. The liver is the main storage depot for retinol and plays a role in vitamin A homeostasis. To better understand the effects of vitamin A deficiency on liver gene expression, we produced retinol deficiency in male rats by feeding a diet low in retinol for 53 days after weaning and examined the effects on gene expression in liver using Affymetrix oligonucleotide microarrays.

A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia.

Objective: Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone.

Regulation of NAD(P)H:quininone oxidoreductase by glucocorticoids.

Previous studies in neonatal and adolescent rats as well as adrenalectomized rats have demonstrated that glucocorticoids regulate the expression of the rat NAD(P)H:quinone oxidoreductase gene (QOR). We used primary cultures of rat adult hepatocytes to document that added glucorticoids repress both the basal and 1,2-benzanthracene-induced expression of QOR mRNA by 65-70%. QOR enzyme activity and protein were concomitantly suppressed as well.

Identification of a retinoid receptor response element in the human aldehyde dehydrogenase-2 promoter.

Background: The human aldehyde dehydrogenase-2 promoter contains sites that bind members of the nuclear receptor family, and one (designated FP330-3') is predicted to bind retinoic acid receptors.

Methods: Binding of retinoid receptors to the FP330-3' oligonucleotide duplex and point mutations thereof was assayed using electrophoretic mobility shift assays. The function of the promoter element was determined in transfection assays.

Peroxisome proliferator-activated receptors (PPAR) and the mitochondrial aldehyde dehydrogenase (ALDH2) promoter in vitro and in vivo.

Background: The aldehyde dehydrogenase 2 (ALDH2) promoter contains a nuclear receptor response element (NRRE) that represents an overlapping direct repeat-1 (DR-1) and -5 (DR-5) element. Because DR-1 elements are preferred binding sites for peroxisome proliferator-activated receptors (PPARs), we tested the hypothesis that PPARs regulate ALDH2 expression.

Methods: We examined the ability of PPAR isoforms to bind to the ALDH2 NRRE in electrophoretic mobility shift assays, their ability to activate the transcription of promoter-reporter constructs containing this NRRE, the effect of PPAR ligands on ALDH2 expression in liver, and the role of the PPARalpha on the expression of ALDH2 by using PPARalpha-null mice.

Regulation of the rat glutathione S-transferase A2 gene by glucocorticoids: involvement of both the glucocorticoid and pregnane X receptors.

Glucocorticoids regulate the rat glutathione S-transferase A2 (GSTA2) gene in a biphasic manner in cultured hepatocytes that repress gene expression at low concentration (10--100 nM) but induce gene expression at high concentration (>1 microM). High concentrations of the glucocorticoid receptor (GR) antagonist RU38486 (5--10 microM) also induced the expression of GSTA2. These effects were reproduced in HepG2 cells transfected with a luciferase reporter containing 1.

Effects of vitamin A deficiency on rat liver alcohol dehydrogenase expression and alcohol elimination rate in rats.

Background: Vitamin A has been suggested to regulate the expression of liver alcohol dehydrogenase (ADH) in humans. There are few studies on the ability of retinoic acid to affect ADH expression in vivo and none on its effects on alcohol metabolic rate.

Methods: Male Sprague Dawley rats were used for isolation of hepatocytes or were rendered vitamin A deficient by feeding a deficient diet for 7 weeks.

The transcriptional and DNA binding activity of peroxisome proliferator-activated receptor alpha is inhibited by ethanol metabolism. A novel mechanism for the development of ethanol-induced fatty liver.

Fatty acids are ligands for the peroxisome proliferator-activated receptor alpha (PPAR alpha). Fatty acid levels are increased in liver during the metabolism of ethanol and might be expected to activate PPAR alpha. However, ethanol inhibited PPAR alpha activation of a reporter gene in H4IIEC3 hepatoma cells expressing alcohol-metabolizing enzymes but not in CV-1 cells, which lack these enzymes.

The retinoid X receptor response element in the human aldehyde dehydrogenase 2 promoter is antagonized by the chicken ovalbumin upstream promoter family of orphan receptors.

Two tandem sites in the aldehyde dehydrogenase 2 promoter (designated FP330-5' and FP330-3') that bind members of the nuclear receptor superfamily were recently identified. Antibodies against apolipoprotein regulatory protein (ARP-1) altered DNA-protein interactions in electrophoretic mobility shift assays using oligonucleotides representing either promoter site and rat liver or cultured cell nuclear extracts. In vitro-translated chicken ovalbumin upstream promoter transcription factor (COUP-TFI), ARP-1, or ErbA-related protein 2 (Ear2) bound both sites.

An A/G polymorphism in the promoter of mitochondrial aldehyde dehydrogenase (ALDH2): effects of the sequence variant on transcription factor binding and promoter strength.

Introduction: The strong protective effect of the ALDH2*2 mutation on risk of alcoholism suggests that other mutations that reduce mitochondrial aldehyde dehydrogenase (ALDH) activity in the liver might also deter drinking. This study describes a polymorphic locus found in the promoter of the ALDH2 gene that affects expression of reporter constructs.

Methods: Polymerase chain reaction (PCR)-based sequencing was used to search for polymorphisms.

The negative regulation of the rat aldehyde dehydrogenase 3 gene by glucocorticoids: involvement of a single imperfect palindromic glucocorticoid responsive element.

Glucocorticoids repressed the polycyclic aromatic hydrocarbon-dependent induction of Class 3 aldehyde dehydrogenase (ALDH3) enzyme activity and mRNA levels in isolated rat hepatocytes by more than 50 to 80%, with a concentration-dependence consistent with the involvement of the glucocorticoid receptor (GR). No consistent effect on the low basal transcription rate was observed. This effect of glucocorticoids (GC) on polycyclic aromatic hydrocarbon induction was effectively antagonized at the mRNA and protein level by the GR antagonist RU38486.

Hormonal regulation of hepatic enzymes involved in foreign compound metabolism.

The regulation of hepatic P450s has been the focus of numerous studies because of the importance of these proteins in endocrinology, oncology, and toxicology, as well as drug development. Considerable evidence exists demonstrating that many hepatic P450s are regulated by developmental, sex, or hormonal factors in addition to receptors that interact with foreign chemicals. The focus of work in our laboratory has been on the effects of steroid hormones, especially glucocorticoids, on expression of genes regulated by the Ah receptor.

Regulation of the Ah gene battery via Ah receptor-dependent and independent processes in cultured adult rat hepatocytes.

A number of genes under the control of the arylhydrocarbon (Ah) receptor were tested for the effects of glucocorticoids on their expression in cultured primary rat hepatocytes. Treatment of cultured hepatocytes with 1.0 microM dexamethasone potentiated the induction (2- to 3-fold) of cytochrome P4501A1, glutathione S-transferase Ya subunit (GSTYa), and UDP-glucuronosyltransferase gene expression by polycyclic aromatic hydrocarbons (PAH), whereas the glucocorticoid agonist suppressed PAH induction of NAD(P)H:quinone oxidoreductase (QOR) subunit and aldehyde dehydrogenase 3C gene expression by 60-80%.