The economic burden of alcohol dependence in europe.

AIMS: To determine the economic burden pertaining to alcohol dependence in Europe. METHODS: Database searching was combined with grey literature searching to identify costs and resource use in Europe relating to alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) or the World Health Organisation's International Classification of Diseases (ICD-10). Searches combined MeSH headings for both economic terms and terms pertaining to alcohol dependence. Relevant outcomes included direct healthcare costs and indirect societal costs. Main resource use outcomes included hospitalization and drug costs. RESULTS: Compared with the number of studies of the burden of alcohol use disorders in general, relatively few focussed specifically on alcohol dependence. Twenty-two studies of variable quality were eligible for inclusion. The direct costs of alcohol dependence in Europe were substantial, the treatment costs for a single alcohol-dependent patient lying within the range euro1591-euro7702 per hospitalization and the annual total direct costs accounting for 0.04-0.31% of an individual country's gross domestic product (GDP). These costs were driven primarily by hospitalization; in contrast, the annual drug costs for alcohol dependence were low. The indirect costs were more substantial than the direct costs, accounting for up to 0.64% of GDP per country annually. Alcohol dependence may be more costly in terms of health costs per patient than alcohol abuse. CONCLUSIONS: This review confirms that alcohol dependence represents a significant burden for European healthcare systems and society. Difficulties in comparing across cost-of-illness studies in this disease area, however, prevent specific estimation of the economic burden.

Integrating sexuality into gynaecological consultations: gynaecologists' perspectives

There are currently few studies exploring doctors' personal perspectives on integrating sexuality into medical consultations. This study focuses on the views of gynaecologists on introducing, or not introducing, sexuality into their work. A total of 30 semistructured interviews were conducted with gynaecologists in the French-speaking part of Switzerland. The thematic content analysis and computer-assisted lexical analysis (Alceste) on the interview transcripts highlighted four categories: perceptions and description of sexuality, patient's sexological history, training in sexology and perceived difficulties. It is observed that, above all, the 'medical dimension' characterises gynaecologists' perceptions. Of greater interest is our observation of disparities in gynaecologists' discussion of their practice, which is often the product of lay knowledge based on common sense and/or personal experience. Finally, the decision to integrate questions relating to sexuality seems to depend on non-medical factors such as the personal experience, interest or gender of the doctor.

Strategic Adaptation in Function of Chronicity of Schizophrenic Symptoms During A Fluency Task: An fMRI Study

Background: Language processing abnormalities and executive difficulties are hallmark features of schizophrenia. The objective of this study is to assess the blood oxygenation level-dependent (BOLD) response at two different stages of the illness (i.e. comparison between adolescents and adults with schizophrenic symptoms) during a fluency task.Methods: BOLD responses during a covert verbal fluency task were compared between 11 psychotic adolescents with schizophrenic symptoms (mean age 16,9 years) and 14 adults with schizophrenia (mean age 33,4 years). fMRI data were analyzed with standard routine of spm5.Results: First, expected activation's network was found for both groups, separately. Secondly, adolescents showed greater activation in left rolandic opercule (BA 48), left angular (BA 39) and right hippocampus compared to adults. Thirdly, adults demonstrated greater activation in presupplementary motor area (BA 6) and in precentral area (BA 4) compared to adolescents.Conclusions: The adolescents seemed to recruit a verbal network (Broca and Wernicke) and memory abilities to perform a fluency task. In contrast, adults seemed to recruit more executive function abilities to perform a similar task. Despite the evolution of schizophrenia, which is known to have a deleterious influence on the prefrontal cortex development, adult patients seemed to be able to recruit such areas to perform a verbal fluency / executive function task.

Relaxed selection is a precursor to the evolution of phenotypic plasticity.

Phenotypic plasticity allows organisms to produce alternative phenotypes under different conditions and represents one of the most important ways by which organisms adaptively respond to the environment. However, the relationship between phenotypic plasticity and molecular evolution remains poorly understood. We addressed this issue by investigating the evolution of genes associated with phenotypically plastic castes, sexes, and developmental stages of the fire ant Solenopsis invicta. We first determined if genes associated with phenotypic plasticity in S. invicta evolved at a rapid rate, as predicted under theoretical models. We found that genes differentially expressed between S. invicta castes, sexes, and developmental stages all exhibited elevated rates of evolution compared with ubiquitously expressed genes. We next investigated the evolutionary history of genes associated with the production of castes. Surprisingly, we found that orthologs of caste-biased genes in S. invicta and the social bee Apis mellifera evolved rapidly in lineages without castes. Thus, in contrast to some theoretical predictions, our results suggest that rapid rates of molecular evolution may not arise primarily as a consequence of phenotypic plasticity. Instead, genes evolving under relaxed purifying selection may more readily adopt new forms of biased expression during the evolution of alternate phenotypes. These results suggest that relaxed selective constraint on protein-coding genes is an important and underappreciated element in the evolutionary origin of phenotypic plasticity.

c-Myc controls the development of CD8alphaalpha TCRalphabeta intestinal intraepithelial lymphocytes from thymic precursors by regulating IL-15-dependent survival.

The murine gut epithelium contains a large population of thymus-derived intraepithelial lymphocytes (IELs), including both conventional CD4(+) and CD8alphabeta(+) T cells (expressing T-cell receptor alphabeta [TCRalphabeta]) and unconventional CD8alphaalpha(+) T cells (expressing either TCRalphabeta or TCRgammadelta). Whereas conventional IELs are widely accepted to arise from recirculation of activated CD4(+) and CD8alphabeta(+) T cells from the secondary lymphoid organs to the gut, the origin and developmental pathway of unconventional CD8alphaalpha IELs remain controversial. We show here that CD4-Cre-mediated inactivation of c-Myc, a broadly expressed transcription factor with a wide range of biologic activities, selectively impairs the development of CD8alphaalpha TCRalphabeta IELs. In the absence of c-Myc, CD4(-) CD8(-) TCRalphabeta(+) thymic precursors of CD8alphaalpha TCRalphabeta IELs are present but fail to develop on adoptive transfer in immunoincompetent hosts. Residual c-Myc-deficient CD8alphaalpha TCRalphabeta IEL display reduced proliferation and increased apoptosis, which correlate with significantly decreased expression of interleukin-15 receptor subunits and lower levels of the antiapoptotic protein Bcl-2. Transgenic overexpression of human BCL-2 resulted in a pronounced rescue of CD8alphaalpha TCRalphabeta IEL in c-Myc-deficient mice. Taken together, our data support a model in which c-Myc controls the development of CD8alphaalpha TCRalphabeta IELs from thymic precursors by regulating interleukin-15 receptor expression and consequently Bcl-2-dependent survival.

The role of epilepsy in early language development in a child with a congenital lesion in the right hemisphere

Early epilepsy is known to worsen the developmental prognosis of young children with a congenital focal brain lesion, but its direct role is often very difficult to delineate from the other variables. This requires prolonged periods of follow-up with simultaneous serial electrophysiological and developmental assessments which are rarely obtained. We studied a male infant with a right prenatal infarct in the territory of the right middle cerebral artery resulting in a left spastic hemiparesis, and an epileptic disorder (infantile spasms with transient right hemihypsarrhythmia and focal seizures) from the age of 7 months until the age of 4 years. Pregnancy and delivery were normal. A dissociated delay of early language acquisition affecting mainly comprehension without any autistic features was documented. This delay was much more severe than usually expected in children with early focal lesions, and its evolution, with catch-up to normal, was correlated with the active phase of the epilepsy. We postulate that the epilepsy specifically amplified a pattern of delayed language emergence, mainly affecting lexical comprehension, reported in children with early right hemisphere damage.

Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology.

Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors that belong to the steroid/thyroid/retinoic acid receptor superfamily. All their characterized target genes encode proteins that participate in lipid homeostasis. The recent finding that antidiabetic thiazolidinediones and adipogenic prostanoids are ligands of one of the PPARs reveals a novel signaling pathway that directly links these compounds to processes involved in glucose homeostasis and lipid metabolism including adipocyte differentiation. A detailed understanding of this pathway could designate PPARs as targets for the development of novel efficient treatments for several metabolic disorders.

Failure to thrive in a girl born into a family affected by familial dysalbuminemic hyperthyroxinemia

Autosomal dominant familial dysalbuminemic hyperthyroxinemia (FDH)is characterized by modified human serum albumin (HSA) inducing asubstantially higher affinity for thyroxine (T4). Histidin or prolinsubstitution on residue R218 produces localized conformationalchanges of HSA creating additional room for T4 binding, leadingto 14-20 fold normal total T4 (TT4) levels. Affected individuals areconsidered euthyroid. Our patient is an 18 months-old swiss girl bornto a mother known for the rare R218P mutation in the HSA gene.She presented with severe failure to thrive (height -2.92 SD, weight-3.6 SD), habitual hip dislocation without anatomical anomaly, latefontanelle closing and protruding ears. Psychomotor development isslightly retarded. Thyroid function testing confirmed extremely high TT4(1446.0 nmol/l) levels, which are similar to her brother's values (1534.4nmol/l and 1757.6 nmol/l respectively). Free T4 seems slightly elevated(26 pmol/l), probably due to methodological reasons. TSH (0.92 mU/l),free T3 (4.4 pmol/l) and thyroxin binding globulin (32 mg/l) are withinthe normal range. Her two half-brothers, affected by the samemutation, are now 18.7 (P1) and 16.6 (P2) years old and wereoriginally described by S. Pannain et al. in 2000. Both werecharacterized by growth retardation (-2.1 and -2.2 SD) before the ageof 4 years. P1 has reached a normal adult height (-0.4 SD) and P2has caught up to normal growth (-0.68 SD) with moderate bonematuration delay. Pubertal development and anterior pituitary functionare adequate. Primary growth and developmental retardation in thefirst years of life with adequate catch-up seem to be a distinctcharacteristic in FDH with R218P mutation. Hip dislocation is typicallyseen in other situations associated to thyroid disorders, like Downsyndrome. These findings might be explained by altered early thyroidhormone utilization in children with FDH.

Interhospital aeromedical transfers: need for a specific training

Introduction: The interhospital aeromedical transfers concern mainly unstable patients presenting with multiple organ failure and among whom the intensity, as well as the difficulty of care are often underestimated. Material and method: Retrospective analysis of 2094 interhospital transfers made by the Rega helicopter of Lausanne between 2003 and 2008, with description of the pathologies, the demographic characteristics, as well as the medical and technical difficulties. Results: Male patient are overrepresented (65 vs 35%), their age being 40-80 years old. On the other hand, we note an important number (10%) of patients less than 10 years. The average time of flight is 13 minutes, with a high rate of night transfers (34%). In 73% of the cases, the transfers concern medical, especially cardiovascular and neurological situations. Trauma and surgical situations account for less than 20%. The transferred patients often require mechanical ventilation (27%), as well as invasive measure of blood pressure (11%), particularly in cases of neurological, pulmonary or cardiac diseases. In 6% of the cases, we note a haemodynamic instability, requiring the use of catecholamines. In 1% a cardiopulmonary resuscitation was initiated during the flight. The overall mortality at 48 hours is about 5%. Conclusions: In spite of relatively brief flights, the complexity and the variety of the pathologies require a specific training for the medical teams involved in the transfers, concerning the aspects of resuscitation, mechanical ventilation, and the knowledge of advanced life support in paediatrics, traumatology and cardiopulmonary intensive care.

Mycobacterium avium subsp. paratuberculosis in an Italian Cohort of Type 1 Diabetes Pediatric Patients.

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne's disease in ruminants. Recent studies have linked MAP to type 1 diabetes (T1D) in the Sardinian population. The aim of this study was to investigate the prevalence of MAP infection in a T1D cohort from continental Italy compared with healthy control subjects. 247 T1D subjects and 110 healthy controls were tested for the presence of MAP. MAP DNA was detected using IS900-specific polymerase chain reaction (PCR). The presence of antibodies towards a MAP antigen, heparin binding hemoagglutinin (HBHA), was detected by ELISA. We demonstrated a higher MAP DNA prevalence in plasma samples from T1D patients and a stronger immune response towards MAP HBHA, compared with healthy control subjects. Moreover, in the recent onset patients, we observed an association between anti-MAP antibodies and HLA DQ2 (DQA1 0201/DQB1 0202). These findings taken together support the hypothesis of MAP as an environmental risk factor for the development of T1D in genetically predisposed subjects, probably involving a mechanism of molecular mimicry between MAP antigens and pancreatic islet β-cells.

Capturing epidermal stemness for regenerative medicine.

The skin is privileged because several skin-derived stem cells (epithelial stem cells from epidermis and its appendages, mesenchymal stem cells from dermis and subcutis, melanocyte stem cells) can be efficiently captured for therapeutic use. Main indications remain the permanent coverage of extensive third degree burns and healing of chronic cutaneous wounds, but recent advances in gene therapy technology open the door to the treatment of disabling inherited skin diseases with genetically corrected keratinocyte stem cells. Therapeutic skin stem cells that were initially cultured in research or hospital laboratories must be produced according strict regulatory guidelines, which ensure patients and medical teams that the medicinal cell products are safe, of constant quality and manufactured according to state-of-the art technology. Nonetheless, it does not warrant clinical efficacy and permanent engraftment of autologous stem cells remains variable. There are many challenges ahead to improve efficacy among which to keep telomere-dependent senescence and telomere-independent senescence (clonal conversion) to a minimum in cell culture and to understand the cellular and molecular mechanisms implicated in engraftment. Finally, medicinal stem cells are expansive to produce and reimbursement of costs by health insurances is a major concern in many countries.

Heavy metal ions are potent inhibitors of protein folding.

Environmental and occupational exposure to heavy metals such as cadmium, mercury and lead results in severe health hazards including prenatal and developmental defects. The deleterious effects of heavy metal ions have hitherto been attributed to their interactions with specific, particularly susceptible native proteins. Here, we report an as yet undescribed mode of heavy metal toxicity. Cd2+, Hg2+ and Pb2+ proved to inhibit very efficiently the spontaneous refolding of chemically denatured proteins by forming high-affinity multidentate complexes with thiol and other functional groups (IC(50) in the nanomolar range). With similar efficacy, the heavy metal ions inhibited the chaperone-assisted refolding of chemically denatured and heat-denatured proteins. Thus, the toxic effects of heavy metal ions may result as well from their interaction with the more readily accessible functional groups of proteins in nascent and other non-native form. The toxic scope of heavy metals seems to be substantially larger than assumed so far.

When is a child with status epilepticus likely to have Dravet syndrome?

PURPOSE: To identify clinical risk factors for Dravet syndrome (DS) in a population of children with status epilepticus (SE). MATERIAL AND METHODS: Children aged between 1 month and 16 years with at least one episode of SE were referred from 6 pediatric neurology centers in Switzerland. SE was defined as a clinical seizure lasting for more than 30min without recovery of normal consciousness. The diagnosis of DS was considered likely in previously healthy patients with seizures of multiple types starting before 1 year and developmental delay on follow-up. The presence of a SCN1A mutation was considered confirmatory for the diagnosis. Data such as gender, age at SE, SE clinical presentation and recurrence, additional seizure types and epilepsy diagnosis were collected. SCN1A analyses were performed in all patients, initially with High Resolution Melting Curve Analysis (HRMCA) and then by direct sequencing on selected samples with an abnormal HRMCA. Clinical and genetic findings were compared between children with DS and those with another diagnosis, and statistical methods were applied for significance analysis. RESULTS: 71 children with SE were included. Ten children had DS, and 61 had another diagnosis. SCN1A mutations were found in 12 of the 71 patients (16.9%; ten with DS, and two with seizures in a Generalized Epilepsy with Febrile Seizures+(GEFS+) context). The median age at first SE was 8 months in patients with DS, and 41 months in those with another epilepsy syndrome (p<0.001). Nine of the 10 DS patients had their initial SE before 18 months. Among the 26 patients aged 18 months or less at initial SE, the risk of DS was significantly increased for patients with two or more episodes (56.3%), as compared with those who had only one episode (0.0%) (p=0.005). CONCLUSION: In a population of children with SE, patients most likely to have DS are those who present their initial SE episode before 18 months, and who present with recurrent SE episodes.

Unification of multi-species vertebrate anatomy ontologies for comparative biology in Uberon.

BACKGROUND: Elucidating disease and developmental dysfunction requires understanding variation in phenotype. Single-species model organism anatomy ontologies (ssAOs) have been established to represent this variation. Multi-species anatomy ontologies (msAOs; vertebrate skeletal, vertebrate homologous, teleost, amphibian AOs) have been developed to represent 'natural' phenotypic variation across species. Our aim has been to integrate ssAOs and msAOs for various purposes, including establishing links between phenotypic variation and candidate genes. RESULTS: Previously, msAOs contained a mixture of unique and overlapping content. This hampered integration and coordination due to the need to maintain cross-references or inter-ontology equivalence axioms to the ssAOs, or to perform large-scale obsolescence and modular import. Here we present the unification of anatomy ontologies into Uberon, a single ontology resource that enables interoperability among disparate data and research groups. As a consequence, independent development of TAO, VSAO, AAO, and vHOG has been discontinued. CONCLUSIONS: The newly broadened Uberon ontology is a unified cross-taxon resource for metazoans (animals) that has been substantially expanded to include a broad diversity of vertebrate anatomical structures, permitting reasoning across anatomical variation in extinct and extant taxa. Uberon is a core resource that supports single- and cross-species queries for candidate genes using annotations for phenotypes from the systematics, biodiversity, medical, and model organism communities, while also providing entities for logical definitions in the Cell and Gene Ontologies. THE ONTOLOGY RELEASE FILES ASSOCIATED WITH THE ONTOLOGY MERGE DESCRIBED IN THIS MANUSCRIPT ARE AVAILABLE AT: http://purl.obolibrary.org/obo/uberon/releases/2013-02-21/ CURRENT ONTOLOGY RELEASE FILES ARE AVAILABLE ALWAYS AVAILABLE AT: http://purl.obolibrary.org/obo/uberon/releases/

Quelle perception ont les médecins de famille en Suisse de leur rôle dans la prévention et la promotion de la santé? : comprendre les barrières à l'implémentation

Introduction: The importance of health promotion and prevention and the potential of general practitioners (GPs) to conduct individual prevention procedures have been demonstrated in several studies. Clinical recommendations for screening and prevention activities, an important condition for success, are published regularly, but their implementation into daily practice does not necessarily follow. Information is lacking about the actual conditions of how prevention is carried out on a daily basis by Swiss GPs, about their perceptions and needs, their attitudes and the present barriers they face. Such information is essential for the development of new tools and programs targeting better implementation of clinical recommendations for prevention in primary care in Switzerland. Objectives: The objectives of the study were to analyze how Swiss GPs perceive their role in prevention by obtaining information regarding the following issues: What do disease prevention and health promotion mean to them? What are the current incentives and barriers they face? What are their ideas and suggestions to deal with these barriers? What are their needs and expectations regarding prevention guidelines and tools? Methods: We conducted a qualitative research project using focus groups to examine the questions mentioned above. A total of 13 focus groups took place including GPs from eight cantons: five groups in German- speaking Switzerland and eight in French- speaking Switzerland. Each group was composed of 4-11 GPs, making in total 102 participants, who were paid expenses to cover their participation. The sessions were audio-recorded and transcribed verbatim. Data analysis: Content analysis of the transcriptions began by classifying the data according to a typology, the first level of which was developed in line with the structure of the interview guide. This typology was extended by successively regrouping similar statements. Synopsis and interpretation was then performed on each category thus obtained. This research report is based on the results from the French-speaking cantons. Results: Physicians perceive a change in their role as a consequence of changes in society and the health system. They emphasize the importance of a personalized and long lasting relationship between the family doctor and his/her patient; a privileged position allowing them to perform individualized prevention activities, considered to be more effective, as they are appropriate to the specific situation and needs of the patient. They point out their need for training and for better information concerning prevention and health promotion interventions, and stress difficulties arising from the lack of a clear political signal conferring them with a mandate for prevention. -- INTRODUCTION L'importance de la prévention et de la promotion de la santé et le potentiel des médecins de famillea à mettre en oeuvre des mesures individuelles de prévention, de dépistage et de conseils, a été démontrée dans plusieurs études. Régulièrement durant les dernières années, de nombreuses associations médicales ont publié des recommandations cliniques concernant les activités de dépistage et de prévention qui sont une condition essentielle pour le succès, mais ne sont pas forcément appliquées de manière systématique dans la pratique médicale quotidienne. Des contraintes spécifiques contribuent à l'écart entre le désir des médecins de pratiquer une médecine préventive et la réalité d'un cabinet médical. Nous n'avons que peu de données sur les conditions actuelles dans lesquelles la prévention et la promotion de la santé sont réalisées par les médecins de famille suisses dans leur travail quotidien. Des informations précises et représentatives sur leurs perceptions et leurs besoins, leurs attitudes et les contraintes auxquelles ils sont confrontés manquent. Or ces données sont essentielles dans le développement de nouveaux outils et programmes visant une meilleure implémentation des recommandations cliniques dans le domaine de la prévention et la promotion de la santé dans la médecine de famille en Suisse. OBJECTIFS Le développement de concepts pour une prévention systématique ainsi que d'outils adéquats, tout comme l'amélioration des conditions qui permettent une implémentation à grande échelle, implique, avant tout, l'analyse de la perception que les médecins de famille suisses ont de leur rôle dans la prévention. Par conséquent, cette étude a eu pour objectif d'obtenir des informations concernant les questions suivantes : ? Que signifient la prévention et la promotion de la santé pour les médecins de famille suisses ? ? Quelles sont leurs incitations et les barrières rencontrées ? ? Quelles sont leurs idées et leurs suggestions pour faire face à ces contraintes ? ? Quels sont leurs besoins et leurs attentes concernant les outils pour la prévention ? METHODES Nous avons mené un projet de recherche qualitative en utilisant la technique des focus groups pour examiner les questions mentionnées ci-dessus. Une telle technique de collecte de données est particulièrement adaptée à un domaine où l'on connaît mal les perceptions des parties prenantes. Nous avons mené 13 focus groups au total, comprenant des médecins issus de huit cantons: cinq groupes ont eu lieu en Suisse alémanique et huit groupes en Suisse romande. Chaque groupe était composé de 4 à 11 médecins de famille, avec au total 102 participants qui ont été défrayés pour leur participation. Les séances ont été audio-enregistrées et transcrites. ANALYSE DES DONNEES L'analyse du contenu des transcriptions a commencé par la classification des données selon une typologie dont le premier niveau a été développé à partir de la structure de la grille d'entretiens. Cette typologie a été affinée et élargie en regroupant successivement des propos similaires. Une synthèse a été effectuée pour chaque catégorie. Ce rapport est basé sur les résultats de l'analyse des données des cantons francophones. RESULTATS Les médecins perçoivent un changement de leur rôle dans une société et dans un système de santé qui évoluent. Ils soulignent l'importance de la relation personnalisée et durable du médecin de famille avec son patient, atout précieux, qui leur permet de réaliser des activités de prévention individualisées et adaptées à la situation et aux besoins du patient, considérées plus efficaces. Afin de surmonter leur doutes et découragement par rapport aux interventions de prévention, ils pointent la nécessité d'une formation aux nouvelles connaissances en prévention et promotion de la santé et d'une meilleure information aux médecins quant à leur efficacité et importance. Ils montrent le besoin d'un signal clair des politiques par rapport à l'attribution de ce mandat aux médecins de famille et de leur reconnaissance en tant qu'acteur de prévention dans le système de santé.