Cryopreserved cGMP-compliant human pluripotent stem cell-derived hepatic progenitors rescue mice from acute liver failure through rapid paracrine effects on liver cells.

Background: Liver transplantation remains the only curative treatment for end-stage liver diseases. Unfortunately, there is a drastic organ donor shortage. Hepatocyte transplantation emerged as a viable alternative to liver transplantation.

Regenerative cell therapy for the treatment of hyperbilirubinemic Gunn rats with fresh and frozen human induced pluripotent stem cells-derived hepatic stem cells.

Pluripotent stem cells have been investigated as a renewable source of therapeutic hepatic cells, in order to overcome the lack of transplantable donor hepatocytes. Whereas different studies were able to correct hepatic defects in animal models, they focused on the most mature phenotype of hepatocyte-like cells (HLCs) derived from pluripotent stem cells and needed freshly prepared cells, which limits clinical applications of HLCs. Here, we report the production of hepatic stem cells (pHSCs) from human-induced pluripotent stem cells (hiPSCs) in xeno-free, feeder-free, and chemically defined conditions using as extracellular matrix a recombinant laminin instead of Matrigel, an undefined animal-derived matrix.

Expansion of human primary hepatocytes in vitro through their amplification as liver progenitors in a 3D organoid system.

Despite decades of investigation on the proliferation of adult human primary hepatocytes, their expansion in vitro still remains challenging. To later be able to consider hepatocytes as a cell therapy alternative or bridge to liver transplantation, dramatically impeded by a shortage in liver donors, the first step is having an almost unlimited source of these cells. The banking of transplantable hepatocytes also implies a protocol for their expansion that can be compatible with large-scale production.

[Pulmonary nocardiosis with cerebral abscesses mimicking metastatic lung cancer: Three cases and a review of literature].

Nocardiosis is an infectious disease with wide range of clinical features, which can eventually lead to death. The agent responsible belongs to the genus Nocardia that includes about fifty different species. Nocardiosis occurs mainly in immunocompromised hosts.

RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1.

With the goal of identifying splicing alterations in myotonic dystrophy 1 (DM1) tissues that may yield insights into targets or mechanisms, we have surveyed mis-splicing events in three systems using a RT-PCR screening and validation platform. First, a transgenic mouse model expressing CUG-repeats identified splicing alterations shared with other mouse models of DM1. Second, using cell cultures from human embryonic muscle, we noted that DM1-associated splicing alterations were significantly enriched in cytoskeleton (e.

Prediction of hydration free energies for the SAMPL4 diverse set of compounds using molecular dynamics simulations with the OPLS-AA force field.

All-atom molecular dynamics computer simulations were used to blindly predict the hydration free energies of a range of small molecules as part of the SAMPL4 challenge. Compounds were parametrized on the basis of the OPLS-AA force field using three different protocols for deriving partial charges: (1) using existing OPLS-AA atom types and charges with minor adjustments of partial charges on equivalent connecting atoms and derivation of new parameters for a number of distinct chemical groups (N-alkyl imidazole, nitrate) that were not present in the published force field; (2) calculation of quantum mechanical charges via geometry optimization, followed by electrostatic potential (ESP) fitting, using Jaguar at the LMP2/cc-pVTZ(-F) level; and (3) via geometry optimization and CHelpG charges (Gaussian09 at the HF/6-31G* level), followed by two-stage RESP fitting. The absolute hydration free energy was computed by an established protocol including alchemical free energy perturbation with thermodynamic integration.

Risk factors for acute decompensation of chronic kidney disease in hospitalized patients in the nephrology department: a case-control study.

Objective: To investigate risk factors for acute kidney injury (AKI) in hospitalized patients with chronic kidney disease (CKD) a case-control study was conducted in the Nephrology Department of Hedi Chaker University Hospital in Sfax, Tunisia, for a 1-year period.

Methods: All patients with baseline renal insufficiency hospitalized for AKI were considered as cases. They were compared with control patients with CKD.

Characterization of a bacteriocin produced by Lactobacillus sakei R1333 isolated from smoked salmon.

Strain R1333, isolated from commercially available smoked salmon, was identified as Lactobacillus sakei based on biochemical tests, sugar fermentation reactions (API 50 CHL), PCR with species-specific primers and sequencing of the 16S rRNA gene. Strain R1333 produces a 3811 kDa class IIa bacteriocin, active against Streptococcus caprinus, Streptococcus macedonicus, Streptococcus spp., L.

Anxious and depressive symptoms in Parkinson's disease: the French cross-sectionnal DoPaMiP study.

Anxiety has been less extensively studied than depression in Parkinson's disease (PD). The DoPaMiP survey allowed assessing simultaneously anxiety and depressive symptoms in PD and comparing correlations of both symptoms with clinical and therapeutic features of the disease. Cross sectional survey conducted prospectively in 450 ambulatory nondemented PD patients and 98 patients with other disorders than PD.

Inappropriate medication use and risk of falls--a prospective study in a large community-dwelling elderly cohort.

Background: Explicit criteria for determining potentially inappropriate medication consumption in elderly were elaborated by Beers et al. These lists have been used worldwide to evaluate medical prescriptions but there is little epidemiologic evidence demonstrating negative consequences of inappropriate medication use. It has been reported that some drugs could increase the risk of falls, which are a frequent and serious problem in elderly population.

Determinants of glycopeptides consumption in hospitals.

The aim of this study was to describe consumption of glycopeptides and to study factors associated with their use in 47 French hospitals. Consumption of glycopeptides for systemic use (defined daily doses per 1,000 patient-days: DDD/1,000 PD and per 100 admissions), number of methicillin-resistant Staphylococcus aureus (MRSA) (percentage and incidence per 1,000 patient-days), and number of venous central lines and hospital characteristics (size, length of stay, number of beds: total and for each hospital inpatient areas and antibiotic policies) were recorded from January, 2002, through December, 2002. Multiple linear regression was performed to check for hospital characteristics.

Hepatitis B vaccination and first central nervous system demyelinating events: reanalysis of a case-control study using the self-controlled case series method.

The hypothesis that hepatitis B vaccination is a risk factor for multiple sclerosis has been discussed at length. The data from an earlier case-control study were reanalyzed using the self-controlled case series method. Using the matched cases from the case-control study, we found a relative incidence of 1.

Channelling of COX-2 inhibitors to patients at higher gastrointestinal risk but not at lower cardiovascular risk: the Cox2 inhibitors and tNSAIDs description of users (CADEUS) study.

Purpose: To describe the characteristics of users of cyclo-oxygenase (COX)-2 inhibitors and traditional nonselective non-steroidal anti-inflammatory drugs (tNSAIDs) in France.

Methods: Between 1 August 2003 and 31 July 2004, patients who received at least one dispensing of celecoxib, rofecoxib or tNSAIDs were randomly sampled with a 1:1:2 target ratio within the French National Healthcare Insurance database. Patients and prescribers were asked to fill a questionnaire on socio-demographic characteristics, NSAID indication and use and previous medical history.

[Relationship between antibiotic policies and antibiotic consumption in hospitals].

Objective: The authors had for aim to study the relationship between antibiotic policies and antibiotic consumption in hospitals.

Design: A component analysis was used to summarize the various measures of the antibiotic policies developed by hospitals. Antibiotics consumption was expressed as a number of Daily Defined Doses per 1,000 patient-days.

The CADEUS study: methods and logistics.

Purpose: At the request of the French Health authorities, a study called CADEUS (COX-2 inhibitors and NSAIDs: description of users) aimed to describe the users of cyclo-oxygenase (COX)-2 inhibitors and traditional non-selective non-steroidal anti-inflammatory drugs (tNSAIDs). We report here the methodology, logistics and study design performances.

Methods: CADEUS is a cohort study designed to include 40,000 patients randomly sampled monthly in the French National Healthcare Insurance database, who received at least one dispensation of celecoxib, rofecoxib or tNSAIDs (1:1:2), from September 2003 to August 2004.

Impact of hospitalisation in an acute medical geriatric unit on potentially inappropriate medication use.

Background And Objective: Potentially inappropriate medication use is a major safety issue in the elderly and may cause a substantial proportion of drug-related hospital admissions. Hospitalisation could result in a change in the quantity and type of drugs, but its effect on potentially inappropriate drug use is still unknown. The aim of this study was to estimate the potentially inappropriate medication prevalence in patients > or =70 years of age at admission to and at discharge from an acute medical geriatric unit, and to identify the factors associated with no longer being a potentially inappropriate drug user at hospital discharge.

Evaluation of statistical association measures for the automatic signal generation in pharmacovigilance.

Pharmacovigilance aims at detecting the adverse effects of marketed drugs. It is generally based on the spontaneous reporting of events thought to be the adverse effects of drugs. Spontaneous Reporting Systems (SRSs) supply huge databases that pharmacovigilance experts cannot exhaustively exploit without data mining tools.

[Psychotropic drug use and mental psychiatric disorders in France; results of the general population ESEMeD/MHEDEA 2000 epidemiological study].

Introduction: The use of psychotropic drugs is high in France and has increased over the last two decades. To date, no national study evaluating psychotropic drug use in the context of the diagnosis of psychiatric disorders has been performed. Such data has now been generated in the ESEMeD/MHEDEA 2000 study, which has allowed comparison of the situation in France with that in five other European countries (Germany, Belgium, Spain, the Netherlands and Italy).

[Antidepressant adverse effects in the elderly: analysis of spontaneous reports in France].

The prescription of antidepressants in the elderly has changed since the marketing of new antidepressants such as selective serotonin reuptake inhibitors (SSRIs). We analysed the adverse effects associated with antidepressants in subjects aged > or =75 years reported to the pharmacovigilance centres in France. Among the 2381 cases recorded between 1985 and 2001, the distribution of adverse effects may reflect sales figures: 1040 for SSRIs (44%), 586 for tricyclic and related antidepressants (25%), 46 for monoamine oxidase inhibitors (2%) and 654 for other antidepressants (27%).

NSAID use profiles derived from reimbursement data in France.

Because extrapolation of adverse event rates from clinical trials to the general population relies on the assumption of similar drug-usage patterns, we have studied usage patterns for nonsteroidal anti-inflammatory drugs (NSAIDs) from the National Health Insurance claims database. Reimbursement patterns of NSAIDs and analgesics were studied in a cohort of 232 users, half selected from authorisations of reimbursed spa cures, and the other half - strictly matched according to age and gender - who had redeemed at study onset at least one prescription for NSAIDs, analgesics or other antirheumatic drugs. Drug utilisation was measured as the total number of defined daily doses (DDD) bought over the 9-month study period.

Patterns and correlates of benzodiazepine use in the French general population.

Objective: To investigate the prevalence of current use of benzodiazepines (BZDs) and related drugs in the French general population and factors associated with this use.

Methods: National cross-sectional telephone survey conducted between 25 April 2001 and 8 May 2001 in a representative sample of non-institutionalized adults of BZD use and duration, prescriber specialty, socio-demographic data and mood and anxiety disorders, using a structured diagnostic interview.

Results: The prevalence of current use of BZD was 7.

Differences between clinical trials and postmarketing use.

Aims: Clinical trials constitute the gold standard to assess the efficacy and safety of new medicines. However, because they are conducted in standardized conditions far from the real world of prescription and use, discrepancies in patient selection or treatment conditions may alter both the effectiveness and risks. On the basis of three examples, our objectives were to study the differences between the characteristics of treated populations and treatment patterns in clinical trials and in postmarketing settings and to discuss the potential consequences on actual efficacy and safety.