Decision-making in pediatrics: a practical algorithm to evaluate complementary and alternative medicine for children.

We herein present a preliminary practical algorithm for evaluating complementary and alternative medicine (CAM) for children which relies on basic bioethical principles and considers the influence of CAM on global child healthcare. CAM is currently involved in almost all sectors of pediatric care and frequently represents a challenge to the pediatrician. The aim of this article is to provide a decision-making tool to assist the physician, especially as it remains difficult to keep up-to-date with the latest developments in the field. The reasonable application of our algorithm together with common sense should enable the pediatrician to decide whether pediatric (P)-CAM represents potential harm to the patient, and allow ethically sound counseling. In conclusion, we propose a pragmatic algorithm designed to evaluate P-CAM, briefly explain the underlying rationale and give a concrete clinical example.

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

Myocardite : l'attitude reste pragmatique! [Myocarditis: practical approach]

Le terme de « myocardite » est utilisé pour décrire une inflammation non spécifique du muscle cardiaque. Cette inflammation, qui est le plus souvent d'origine infectieuse, peut également être d'origine toxique ou immunologique. Elle peut être associée ou non à une péricardite. Le tableau clinique est habituellement bénin, mais la myocardite peut se compliquer d'une mort subite ou d'un choc cardiogénique rapidement progressif nécessitant une assistance circulatoire ou une transplantation. Dans près de 25% des cas, l'inflammation peut devenir chronique et le cours clinique peut alors évoluer vers celui d'une insuffisance cardiaque globale sur cardiomyopathie dilatée. Après avoir présenté un cas, nous passons en revue les aspects épidémiologiques, diagnostiques et thérapeutiques de cette entité pour laquelle les données fondées sur les preuves sont étonnamment peu nombreuses. Ces éléments justifient le bien-fondé de l'attitude pragmatique qui est généralement adoptée.

Prognostic relevance of Masaoka and Müller-Hermelink classification in patients with thymic tumors.

BACKGROUND: To compare the prognostic relevance of Masaoka and Müller-Hermelink classifications. METHODS: We treated 71 patients with thymic tumors at our institution between 1980 and 1997. Complete follow-up was achieved in 69 patients (97%) with a mean follow up-time of 8.3 years (range, 9 months to 17 years). RESULTS: Masaoka stage I was found in 31 patients (44.9%), stage II in 17 (24.6%), stage III in 19 (27.6%), and stage IV in 2 (2.9%). The 10-year overall survival rate was 83.5% for stage I, 100% for stage IIa, 58% for stage IIb, 44% for stage III, and 0% for stage IV. The disease-free survival rates were 100%, 70%, 40%, 38%, and 0%, respectively. Histologic classification according to Müller-Hermelink found medullary tumors in 7 patients (10.1%), mixed in 18 (26.1%), organoid in 14 (20.3%), cortical in 11 (15.9%), well-differentiated thymic carcinoma in 14 (20.3%), and endocrine carcinoma in 5 (7.3%), with 10-year overall survival rates of 100%, 75%, 92%, 87.5%, 30%, and 0%, respectively, and 10-year disease-free survival rates of 100%, 100%, 77%, 75%, 37%, and 0%, respectively. Medullary, mixed, and well-differentiated organoid tumors were correlated with stage I and II, and well-differentiated thymic carcinoma and endocrine carcinoma with stage III and IV (p < 0.001). Multivariate analysis showed age, gender, myasthenia gravis, and postoperative adjuvant therapy not to be significant predictors of overall and disease-free survival after complete resection, whereas the Müller-Hermelink and Masaoka classifications were independent significant predictors for overall (p < 0.05) and disease-free survival (p < 0.004; p < 0.0001). CONCLUSIONS: The consideration of staging and histology in thymic tumors has the potential to improve recurrence prediction and patient selection for combined treatment modalities.

High-altitude exposure in patients with cardiovascular disease: risk assessment and practical recommendations.

Because of the development of modern transportation facilities, an ever rising number of individuals including many patients with preexisting diseases visit high-altitude locations (>2500 m). High-altitude exposure triggers a series of physiologic responses intended to maintain an adequate tissue oxygenation. Even in normal subjects, there is enormous interindividual variability in these responses that may be further amplified by environmental factors such as cold temperature, low humidity, exercise, and stress. These adaptive mechanisms, although generally tolerated by most healthy subjects, may induce major problems in patients with preexisting cardiovascular diseases in which the functional reserves are already limited. Preexposure assessment of patients helps to minimize risk and detect contraindications to high-altitude exposure. Moreover, the great variability and nonpredictability of the adaptive response should encourage physicians counseling such patients to adapt a cautionary approach. Here, we will briefly review how high-altitude adjustments may interfere with and aggravate/decompensate preexisting cardiovascular diseases. Moreover, we will provide practical recommendations on how to investigate and counsel patients with cardiovascular disease desiring to travel to high-altitude locations.

Exercise dose and insulin sensitivity: relevance for diabetes prevention.

PURPOSE: Exercise improves insulin resistance and is a first line for the prevention and treatment of type 2 diabetes. The extent, however, to which these responses are dose dependent is not known. The purpose of this study was to examine whether exercise dose was associated with improvements in insulin sensitivity after 4 months of exercise training in previously sedentary adults. METHODS: Fifty-five healthy volunteers participated in a 16-wk supervised endurance exercise intervention with a pre/postintervention design. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp, peak oxygen uptake by a graded exercise test, and body composition by dual-energy x-ray absorptiometry. The exercise intervention consisted of three to five sessions per week with a minimum of three sessions supervised. A ramped exercise prescription protocol was used to achieve 75% of peak HR for 45 min per session. Exercise dose, expressed as average kilocalories expended per week, was computed as the product of exercise intensity, duration and frequency. RESULTS: Improved insulin sensitivity was significantly related to exercise dose in a graded dose-response relationship. No evidence of threshold or maximal dose-response effect was observed. Age and gender did not influence this dose-response relationship. Exercise intensity was also significantly related to improvements in insulin sensitivity, whereas frequency was not. CONCLUSIONS: This study identifies a graded dose-response relationship between exercise dose and improvements in insulin sensitivity. The implication of this observation is of importance for the adaptation of exercise prescription in clinical situations.

Evidential relevance in scene to offender transfer cases: development and analysis of a likelihood ratio for offence level propositions

The present paper focuses on the analysis and discussion of a likelihood ratio (LR) development for propositions at a hierarchical level known in the context as 'offence level'. Existing literature on the topic has considered LR developments for so-called offender to scene transfer cases. These settings involve-in their simplest form-a single stain found on a crime scene, but with possible uncertainty about the degree to which that stain is relevant (i.e. that it has been left by the offender). Extensions to multiple stains or multiple offenders have also been reported. The purpose of this paper is to discuss a development of a LR for offence level propositions when case settings involve potential transfer in the opposite direction, i.e. victim/scene to offender transfer. This setting has previously not yet been considered. The rationale behind the proposed LR is illustrated through graphical probability models (i.e. Bayesian networks). The role of various uncertain parameters is investigated through sensitivity analyses as well as simulations.

Cellular perspectives on the glutamate-monoamine interactions in limbic lobe structures and their relevance for some psychiatric disorders.

Dopaminergic, serotonergic and noradrenergic nuclei form the trimonoamine modulating system (TMMS). This system modulates emotional/motivational activities mediated by the limbic circuitry, where glutamate is the major excitatory neurotransmitter. Two main concepts are the basis of this review. First, since 1950 and the discovery of the antipsychotic activity of the dopamine D2 receptor antagonist chlorpromazine, it appears that drugs that can modulate the TMMS possess therapeutic psychiatric properties. Second, the concept of glutamate/trimonoamine imbalance in the cortico-striato-thalamo-cortical loop that has been so successful in explaining the pathophysiology of Parkinson disease has been applied in the pathophysiology of schizophrenia. This review will focus on the complex interactions between the fast synaptic glutamatergic transmission and the TMMS in specific parts of the limbic lobe and we will try to link these interactions to some psychiatric disorders, mainly depression, schizophrenia and drug addiction.

Variants : The Journal of the European Society for Textual Scholarship

This volume is the 10th issue of Variants . In keeping with the mission of the European Society for Textual Scholarship, the articles are richly interdisciplinary and transnational. They bring to bear a wide range of topics and disciplines on the field of textual scholarship: historical linguistics, digital scholarly editing, classical philology, Dutch, English, Finnish and Swedish Literature, publishing traditions in Japan, book history, cultural history and folklore. The questions that are explored - what texts are worth editing? what is the nature of the relationship between text, work, document and book? what is a critical digital edition? - all return to fundamental issues that have been at the heart of the editorial discipline for decades. With refreshing insight they assess the increasingly hybrid nature of the theoretical considerations and practical methodologies employed by textual scholars, while reasserting the relevance and need for producing scholarly editions, whether in print or digital, and continuing advanced research in bibliographical codes, textual transmissions, genetic dossiers, the fluidity of texts and other such subjects that connect textual scholarship with broader investigations into our nations' literary culture and written heritage.

Place des apports oraux en acides gras oméga-3 dans la mucoviscidose [Relevance of omega-3 fatty acid oral supplementation in cystic fibrosis]

Chronic inflammation and fatty acid deficiency, in particular in docosahexaenoic acid (DHA, C22:6-n3), occurring in cystic fibrosis patients, are two convincing arguments urging the use of polyunsaturated fatty acids (PUFA) omega-3 in this population. PUFA omega-3 oral dietary intake position in the cystic fibrosis treatment is however not clear despite many years of clinical research. This review article sets out the reasons that conduct nutritionists to try this approach and reviews the results published until nowadays.

Diagnostic des onychomycose a moisissures et importance pour le traitement [Diagnosis of non dermatophyte onychomycosis ant its relevance for treatment].

PCR methods are reliable and suitable to in situ identify dermatophytes, yeasts and non dermatophyte moulds (NDM) in onychomycosis. Onychomycosis insensitive to standard treatment with topical agents as well as with oral terbinafine or itraconazole revealed Fusarium spp., Acremonium spp. and Aspergillus spp. as infectious agents. However, NDM onychomycosis could be efficiently cured using topical amphotericin B. In conclusion, correct fungal species identification is important in onychomycoses in order to prescribe adequate treatments since dermatophytes and moulds have different sensitivities to antifungal drugs.

Un guide pratique au traitement des gliomes [A practical guide for the management of gliomas]

The management of gliomas in daily clinical practice is challenging. It requires a multidisciplinary and coordinated approach involving neurosurgery, radiotherapy and, finally, chemotherapy. Important progress has been made during the last years with the introduction of a combined treatment associating standard radiotherapy with concomitant chemotherapy using temozolomide, a novel alkylating agent. For the first time in many years a new treatment strategy translated into a significant prolongation of survival. In parallel, molecular markers (e.g. loss of heterozygosity on chromosomes 1p and 19q or methylation of the methyl-guanine methyl transferase [MGMT] gene promoter) allowed for identification of distinct subtypes of glioma or prediction of treatment response. In this "Practical Guide", we describe the daily practice and aim at answering some common questions in the management of patients suffering from glioblastoma, astrocytoma, oligodendroglioma and low grade glioma. The therapeutic options presented here are based on evidences from the literature. In the absence of documented evidence, the empirical choices from our local practice are explained and justified.

A critical analysis of three psychological research programs of doping behaviour

Objectives To consider the various specific substances-taking activities in sport an examination of three psychological models of doping behaviour utilised by researchers is presented in order to evaluate their real and potential impact, and to improve the relevance and efficiency of anti-doping campaigns. Design Adopting the notion of a "research program" (Lakatos, 1978) from the philosophy of science, a range of studies into the psychology of doping behaviour are classified and critically analysed. Method Theoretical and practical parameters of three research programs are critically evaluated (i) cognitive; (ii) drive; and (iii) situated-dynamic. Results The analysis reveals the diversity of theoretical commitments of the research programs and their practical consequences. The «cognitive program» assumes that athletes are accountable for their acts that reflect the endeavour to attain sporting and non-sporting goals. Attitudes, knowledge and rational decisions are understood to be the basis of doping behaviour. The «drive program» characterises the variety of traces and consequences on psychological and somatic states coming from athlete's experience with sport. Doping behaviour here is conceived of as a solution to reduce unconscious psychological and somatic distress. The «situated-dynamic program» considers a broader context of athletes' doping activity and its evolution during a sport career. Doping is considered as emergent and self-organized behaviour, grounded on temporally critical couplings between athletes' actions and situations and the specific dynamics of their development during the sporting life course. Conclusions These hypothetical, theoretical and methodological considerations offer a more nuanced understanding of doping behaviours, making an effective contribution to anti-doping education and research by enabling researchers and policy personnel to become more critically reflective about their explicit and implicit assumptions regarding models of explanations for doping behaviour.