Saccamoeba lacustris, sp. nov. (Amoebozoa: Lobosea: Hartmannellidae), a new lobose amoeba, parasitized by the novel chlamydia 'Candidatus Metachlamydia lacustris' (Chlamydiae: Parachlamydiaceae).

An amoeba isolated from an aquatic biotope, identified morphologically as Saccamoeba limax, was found harbouring mutualistic rod-shaped gram-negative bacteria. During their cultivation on agar plates, a coinfection also by lysis-inducing chlamydia-like organisms was found in some subpopulations of that amoeba. .Here we provide a molecular-based identification of both the amoeba host and the two bacterial endosymbionts. Analysis of the 18S rRNA gene revealed that this strain is the sister-group to Glaeseria, for which we proposed the name Saccamoeba lacustris. The rod-shaped endosymbiont was identified as a member of Variovorax paradoxus group (Comamonadaceae, Beta-Proteobacteria). No growth on bacteriological agars was recorded, hence this symbiont might be strictly intracellular. The chlamydia-like parasite was unable to infect Acanthamoeba and other amoebae in coculture, showing high host specificity. Phylogenetic analysis based on the 16S rDNA indicated that it is a new member of the family Parachlamydiaceae (order Chlamydiales), for which we proposed the name 'Candidatus Metachlamydia lacustris'.

Eosinophile Ösophagitis : Die Sicht des Gastroenterologen [Eosinophilic esophagitis : The gastroenterologist's perspective].

Eosinophilic esophagitis is characterized by symptoms of esophageal dysfunction and eosinophil-predominant esophageal inflammation. Eosinophilic inflammation in other parts of the gastrointestinal tract is absent and several differential diagnoses for esophageal eosinophilia have to be excluded before diagnosing eosinophilic esophagitis. Most patients are male and have concomitant atopic disorders. Therapeutic options are based on drugs, diet and dilation.

In vitro susceptibility of Actinobaculum schaalii to 12 antimicrobial agents and molecular analysis of fluoroquinolone resistance.

OBJECTIVES: To assess the in vitro susceptibility of Actinobaculum schaalii to 12 antimicrobial agents as well as to dissect the genetic basis of fluoroquinolone resistance. METHODS: Forty-eight human clinical isolates of A. schaalii collected in Switzerland and France were studied. Each isolate was identified by 16S rRNA sequencing. MICs of amoxicillin, ceftriaxone, gentamicin, vancomycin, clindamycin, linezolid, ciprofloxacin, levofloxacin, moxifloxacin, co-trimoxazole, nitrofurantoin and metronidazole were determined using the Etest method. Interpretation of results was made according to EUCAST clinical breakpoints. The quinolone-resistance-determining regions (QRDRs) of gyrA and parC genes were also identified and sequence analysis was performed for all 48 strains. RESULTS: All isolates were susceptible to amoxicillin, ceftriaxone, gentamicin, clindamycin (except three), vancomycin, linezolid and nitrofurantoin, whereas 100% and 85% were resistant to ciprofloxacin/metronidazole and co-trimoxazole, respectively. Greater than or equal to 90% of isolates were susceptible to the other tested fluoroquinolones, and only one strain was highly resistant to levofloxacin (MIC ?32 mg/L) and moxifloxacin (MIC 8 mg/L). All isolates that were susceptible or low-level resistant to levofloxacin/moxifloxacin (n?=?47) showed identical GyrA and ParC amino acid QRDR sequences. In contrast, the isolate exhibiting high-level resistance to levofloxacin and moxifloxacin possessed a unique mutation in GyrA, Ala83Val (Escherichia coli numbering), whereas no mutation was present in ParC. CONCLUSIONS: When an infection caused by A. schaalii is suspected, there is a risk of clinical failure by treating with ciprofloxacin or co-trimoxazole, and ?-lactams should be preferred. In addition, acquired resistance to fluoroquinolones more active against Gram-positive bacteria is possible.

Alimentation et hypertension artérielle: au-delà du sel de table [Nutrition and hypertension: more than table salt].

The role of dietary sodium intake in the development, and its impact on the treatment, of hypertension are well recognized. However, many other nutritional compounds have been shown, or are believed, to influence blood pressure. Some compounds, such as caffeine and fructose, may raise arterial blood pressure, whereas others might lower arterial blood pressure, for example garlic, dark chocolate, fibers and potassium. In this article, we review several alimentary compounds and their (hypothesized) mechanisms of action, as well as the available evidence supporting a role of these compounds in the "non pharmacological" treatment and prevention of hypertension.

Collaboration entre médecin de famille et psychiatre pour les problèmes de santé mentale [Family physicians and psychiatrists' collaborative care for mental health problems].

The burden of disease linked to mental disorders represents more than one-fifth of years lived with disability in the world. Less than half of people suffering from mental disorders are adequately treated. Three quarter of those who receive treatment are followed by primary care. Collaborative care aims to increase the efficiency of direct general practitioner's treatment. Main components are sustainable and individualized consultation-liaison relationship (1/2 day of psychiatrist by 15 days for 10-15 general practitioners), and support of a clinical case manager for complex situations. Collaboration is bidirectional: early or crisis access to specialist care and long-term followup by general practitioner. This model is a challenge for the doctor-patient dual relationship and requires incentives in a public health perspective.

An integrated encyclopedia of DNA elements in the human genome.

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

Role of MyD88 and Toll-like receptors 2 and 4 in the sensing of Parachlamydia acanthamoebae.

Parachlamydia acanthamoebae is a Chlamydia-related organism whose pathogenic role in pneumonia is supported by serological and molecular clinical studies and an experimental mouse model of lung infection. Toll-like receptors (TLRs) play a seminal role in sensing microbial products and initiating innate immune responses. The aim of this study was to investigate the roles of MyD88, TLR2, and TLR4 in the interaction of Parachlamydia with macrophages. Here, we showed that Parachlamydia entered bone-marrow derived macrophages (BMDMs) in a TLR-independent manner but did not multiply intracellularly. Interestingly, compared to live bacteria, heat-inactivated Parachlamydia induced the production of substantial amounts of tumor necrosis factor alpha (TNF), interleukin-6 (IL-6), and IL-12p40 by BMDMs and of TNF and IL-6 by peritoneal macrophages as well as RAW 264.7 and J774 macrophage cell lines. Cytokine production by BMDMs, which was partially inhibited upon trypsin treatment of Parachlamydia, was dependent on MyD88, TLR4, and, to a lesser extent, TLR2. Finally, MyD88(-/-), TLR4(-/-), and TLR2(-/-) mice were as resistant as wild-type mice to lung infection following the intratracheal instillation of Parachlamydia. Thus, in contrast to Chlamydia pneumoniae, Parachlamydia acanthamoebae weakly stimulates macrophages, potentially compensating for its low replication capacity in macrophages by escaping the innate immune surveillance.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.

Les discordances du moi : une lecture critique du débat philosophique contemporain sur l'identité personnelle au regard de la transplantation d'organes

La présente recherche analyse le concept mental d'identité personnelle et en propose une interprétation critique, qui se développe à partir des cas de troubles psychologiques se manifestant chez certains patients transplantés. Nous pensons que l'étude de ces cas offre la possibilité de repenser, et par là critiquer, certains présupposés qui conditionnent le débat philosophique contemporain sur l'identité personnelle de matrice essentiellement analytique. Nous proposons de ce concept mental une interprétation inusuelle, reposant sur une certaine compréhension de l'être (humain), que nous caractérisons par la formule «identité personnelle transductive ». Cette expression véhicule l'idée d'une «ontologie autre » ; autre que l'ontologie classique qui pense l'être comme déterminité, à l'instar d'un individu substantiel, stable et persistant. Nous nous éloignons ainsi de la conception de la déterminité telle qu'elle se développe depuis l'Antiquité grecque, parce que nous croyons que le changement ou le devenir réside dans la nature des choses. Nous avons ainsi essayé de présenter une interprétation de l'être différente, en empruntant à Gilbert Simondon la notion de « transductivité » -dans le sens d'« individuation en progrès »que cet auteur lui attribue. En comparant les témoignages des patients transplantés avec les cas imaginaires de transplantation de cerveau qui dominent les discussions philosophiques, nous avons montré la nécessité de refonder l'ontologie sur laquelle reposent les théories contemporaines de l'identité personnelle. Cette tentative répond à l'exigence de résoudre et tempérer les apories qui se font jour au sein des conceptions déterministes de la personne -soient-elles réductionnistes (à l'instar des partisans du critère de continuité psychologique et physique) ou non réductionnistes (à l'instar des conceptions simples ou Théories de l'ego basées sur une approche à la première personne, où la personne, comprise comme persistance substantielle d'un sujet, se fonde d'elle-même). Au coeur de notre démarche se trouve la notion d'« image du corps », véritable outil d'unification épistémologique et de renouvellement ontologique. Cette notion s'est révélée extrêmement utile non seulement pour comprendre et démêler les composantes qui interviennent dans le surgissement des troubles psychologiques lors des transplantations d'organes, ainsi que la variabilité des réactions individuelles, mais aussi, plus fondamentalement, pour rendre manifeste l'opération de «transduction perpétuée »qui est à la base de l'ontogenèse de l'être humain en tant que personne, donc du moi. La notion d'image du corps nous a donc permis de mettre en évidence ce que l'expérience de la transplantation d'organes bien comprise pourrait ou devrait apporter à la théorie de l'identité personnelle. C'est ainsi que, par approximation, s'est précisée l'idée d'une identité personnelle transductive, où le moi (la personne), étant interprété comme l'aspect subjectif d'une opération d'«individuation perpétuée », se donne sous le signe de la discordance.

The cost effectiveness of pharmacological smoking cessation therapies in developing countries: a case study in the Seychelles

OBJECTIVE: To examine the incremental cost effectiveness of the five first line pharmacological smoking cessation therapies in the Seychelles and other developing countries. DESIGN: A Markov chain cohort simulation. SUBJECTS: Two simulated cohorts of smokers: (1) a reference cohort given physician counselling only; (2) a treatment cohort given counselling plus cessation therapy. INTERVENTION: Addition of each of the five pharmacological cessation therapies to physician provided smoking cessation counselling. MAIN OUTCOME MEASURES: Cost per life-year saved (LYS) associated with the five pharmacotherapies. Effectiveness expressed as odds ratios for quitting associated with pharmacotherapies. Costs based on the additional physician time required and retail prices of the medications. RESULTS: Based on prices for currently available generic medications on the global market, the incremental cost per LYS for a 45 year old in the Seychelles was 599 US dollars for gum and 227 dollars for bupropion. Assuming US treatment prices as a conservative estimate, the incremental cost per LYS was significantly higher, though still favourable in comparison to other common medical interventions: 3712 dollars for nicotine gum, 1982 dollars for nicotine patch, 4597 dollars for nicotine spray, 4291 dollars for nicotine inhaler, and 1324 dollars for bupropion. Cost per LYS increased significantly upon application of higher discount rates, which may be used to reflect relatively high opportunity costs for health expenditures in developing countries with highly constrained resources and high overall mortality. CONCLUSION: Pharmacological cessation therapy can be highly cost effective as compared to other common medical interventions in low mortality, middle income countries, particularly if medications can be procured at low prices.

Diagnostic contribution of cardiac magnetic resonance in patients with acute coronary syndrome and culprit-free angiograms.

BACKGROUND: In spite of robust knowledge about underlying ischemic myocardial damage, acute coronary syndromes (ACS) with culprit-free angiograms raise diagnostic concerns. The present study aimed to evaluate the additional value of cardiac magnetic resonance (CMR) over commonly available non-CMR standard tests, for the differentiation of myocardial injury in patients with ACS and non-obstructed coronary arteries. MATERIAL/METHODS: Patients with ACS, elevated hs-TnT, and a culprit-free angiogram were prospectively enrolled into the study between January 2009 and July 2013. After initial evaluation with standard tests (ECG, echocardiography, hs-TnT) and provisional exclusion of acute myocardial infarction (AMI) in coronary angiogram, patients were referred for CMR with the suspicion of myocarditis or Takotsubo cardiomyopathy (TTC). According to the result of CMR, patients were reclassified as having myocarditis, AMI, TTC, or non-injured myocardium as assessed by late gadolinium enhancement. RESULTS: Out of 5110 patients admitted with ACS, 75 had normal coronary angiograms and entered the study; 69 of them (92%) were suspected for myocarditis and 6 (8%) for TTC. After CMR, 49 patients were finally diagnosed with myocarditis (65%), 3 with TTC (4%), 7 with AMI (9%), and 16 (21%) with non-injured myocardium. The provisional diagnosis was changed or excluded in 23 patients (31%), with a 9% rate of unrecognized AMI. CONCLUSIONS: The study results suggest that the evaluation of patients with ACS and culprit-free angiogram should be complemented by a CMR examination, if available, because the initial work-up with non-CMR tests leads to a significant proportion of misdiagnosed AMI.