Use of NSAIDS compared to paracetamol as potential risk factors for asthma

Introduction: Use of paracetamol has been associated with an increased risk of asthma in several epidemiological studies. In contrast, it has been suggested that non-steroidal anti-inflammatory drugs (NSAIDs) might be protective (Kanabar, Clin Ther 2007), but data relating to these drugs are scarce. Methods: Prevalence of asthma and intake of analgesics in the past 2 years were assessed by questionnaire in 2008 in young adults (≥;16 years) diagnosed with cancer between 1976 and 2003 (Swiss Childhood Cancer Survivor Study). In a multivariate logistic regression we analysed the association between asthma and intake of paracetamol only, NSAIDs only or their combination, adjusting for age, sex, cancer diagnosis, cancer therapy and time since diagnosis. Results: Of the 1293 participants (response rate 68%), 83 (6%) reported asthma and 845 (65%) intake of analgesics in the past 2 years. Of these, 257 (29%) took paracetamol only, 224 (25%) NSAIDs only, 312 (35%) a combination of both and 52 (6%) other analgesics. Adjusted Odds ratios for asthma were 2.2 (95% CI 1.0-4.7; p = 0.04), 1.9 (0.9-4.3; p = 0.12) and 2.9 (1.4-6.1; p <0.01) in those using paracetamol only, NSAIDs only or their combination respectively. Conclusion: These cross-sectional data in a selected population do not support a protective effect of NSAIDs against asthma, neither taken alone nor in combination with paracetamol. All analgesics were positively associated with reported asthma episodes in the past two years. This can be explained by reverse causation, with intake of analgesics being a result rather than a cause of asthma events. Randomised controlled trials in unselected populations are needed to clarify the direction of causation.

Analyse des modifications de la chromatine impliquées dans l'effet barrière de CTF1 aux télomères humains

Eukaryotic genomes are compartmentalized in different structural domains that can affect positively or negatively gene expression. These regions of euchromatin and heterochromatin are characterized by distinct histones marks which can facilitate or repress gene transcription. The chromatin environment represents thus one of the main problems to control gene expression in biotechnological applications or gene therapy, since its expression is affected by the chromatin neighboring its locus of insertion. Some chromatin regions like telomeres are composed of constitutive heterochromatin which leads to the telomeric position effect (TPE) that silences genes adjacent to the telomere. TPE is known to spread by the selfrecruitment of the SIR histone deacetylase complex from the telomere in S.cerevisiae, but the histone marks that are associated to telomeric chromatin in mammalian cells remain mostly unknown. The transcription factor CTF1 has shown antisilencing properties in mammalian cells and also a boundary activity against TPE in yeast cells when fused to the yeast Gal4 DNA binding domain. In the work presented here, we describe a dual-reporter system to assess the boundary activity of proteins such as CTF1 at human telomeres. When located between the two reporter genes, CTF1 shields the telomere distal gene from TPE, while the telomereproximal gene remains silenced by telomeric heterochromatin. The boundary activity of CTF1 is shown to act regardless its function of transcriptional activator, by opposition to the transcriptional activator VP16 which activates indifferently both transgenes. Moreover, this study shows that CTF1 boundary activity is linked to its H3 binding function, as expected from a chromatin remodeler. ChIP experiments showed that histone deacetylation is the main histone modification involved in gene silencing at mammalian cell telomeres. Distinctly to yeast cells, the histone deacetylation signal in human cells extented over a short range along the chromosome. CTF1 may help to block this propagation and therefore to restore histones acetylation level on telomere protected locus. Surprisingly, other histone marks such as trimethyl-H3K9 or trimethyl-H4K20 were found on telomere protected locus, while in another clone, unsilencing of telomere distal transgene was associated with recruitment of the histone variant H2A.Z. Thus, I conclude that CTF1 displays a chromatin boundary function which is independent of its transcriptional activity and therefore exhibit features required for use as chromatin insulator in biotechnological applications. RESUME Les génomes eucaryotes sont compartementalisés en domaines structurels qui peuvent affecter positivement ou négativement l'expression des gènes avoisinants. Ces régions dites d'euchromatine ou d'hétérochromatine sont caractérisées par des modifications posttraductionnelles des histones qui peuvent faciliter ou au contraire inhiber la transcription des gènes qui s'y trouvent. Ainsi, isoler un gène de son environnement chromatinien est problème fréquent lorsqu'il s'agit de contrôler son expression dans le cadre d'applications en biotechnologie ou encore en thérapie génique. Certaines régions de chromatine telles que les télomères sont composées d'hétérochromatine constitutive qui mène au silençage des gènes avoisinants. Cet effet de position télomérique (TPE) est connu dans la levure S.cerevisiae comme se propageant par auto-recrutement du complexe de déacétylation d'histone SIR, alors que peu de modifications de chromatine ont pu être associées à ce phénomène dans les cellules de mammifères. Le facteur de transcription CTF1 a montré des propriétés d'anti-silençage dans les cellules de mammifères, ainsi qu'une activité barrière contre le silençage télomérique dans les cellules de levures lorsqu'il est fusionné au domaine de liaison à l'ADN de la protéine de levure Gal4. Dans le travail présenté ci-après est décrit un système à deux gènes rapporteurs permettant de mesurer l'activité barrière de protéines telles que CTF1 aux télomères humains, et les modifications de chromatine qui y sont associées. Lorsque CTF1 est placé entre les deux gènes rapporteurs, le gène distant du télomère est protégé du silençage qui lui est associé, alors que le gène proche du télomère reste soumis à ce silençage induit par l'hétérochromatine télomérique. L'activité barrière de CTF1 est montrée ici comme agissant indépendamment de son activité transcriptionnelle, par opposition à l'activateur transcriptionnel VP16 qui active indifféremment les deux transgènes. En outre, cette étude appuie l'hypothèse stipulant que CTF1 agisse comme remodeleur chromatinien puisqu'elle démontre que son activité barrière est directement dépendante de son activité de liaison avec l'histone H3. De plus, des expériences d'immuno-précipitation de la chromatine démontrent que la déacétylation des histones est le majeur phénomène intervenant dans le silençage télomérique. Par opposition à la levure, ce signal de déacétylation ne se propage dans les cellules humaines que sur une courte distance le long du chromosome. CTF1 agit ainsi en bloquant cette propagation et en restaurant le niveau d'acétylation des histones sur le locus protégé du télomère. De manière surprenante et inattendue, d'autres modifications d'histones telles que 4 les H3K9 et H4K20 triméthylées sont aussi observées à ce locus, tandis le recrutement du variant H2A.Z peut aussi être suffisant à restaurer l'expression du gène distant du télomère. En terme de cette analyse, CTF1 exhibe ainsi une fonction de barrière chromatinienne qui exclue une activité transcriptionnelle non désirée - propriété qui est requise dans l'établissement des isolateurs visant à permettre le contrôle d'un transgène dans le cadre d'applications en biotechnologies.

Objective results at 1 year of a new ultracongruent postero-stabilized total knee arthroplasty

Introduction: A new ultra congruent, postero-stabilized total knee arthroplasty (TKA) with a mobile bearing, the FIRST knee prosthesis (Free Insert in Rotation Stabilized in Translation, Symbios SA), was designed and expected to significantly reduce polyethylene wear, to improve the range of motion and the overall stability of the knee while ensuring a physiological ligament balance. Gait analysis has proven to give really objective outcome parameters after lower limb surgery. The goal of our study was to compare the subjective and really objective results of this new TKA with two other widespread models of TKA. Methods: A clinical prospective monocentric cohort study of 100 consecutive patients (47-88 yrs) undergoing a FIRST TKA for primary osteoarthritis is currently being done. Pre- and post-operative follow-ups (6 weeks, 4 months and 1 year) were done with well-recognized subjective evaluations (EQ-5D and WOMAC scores) and semi-objective questionnaires (KSS score and radiography evaluation) as well as with a really objective evaluation using gait parameters from 6 walking trials, performed at different speeds (slow, normal and fast) with an ambulatory gait analysis system (Physilog®, BioAGM CH). The outcomes of the first 32 new TKA after one year of follow-up were compared to the results after 1 year of a randomized controlled clinical trial comparing 29 NexGen® postero-stabilized TKA (Zimmer Inc) with a fixed bearing and 26 NexGen® TKA with a mobile bearing using the same methods. Results: Subjective and semi-objective results were similar for the three types of TKA. As for the really objective parameters, the gait cycle time of the FIRST TKA was statistically significantly shorter at normal speed of walk, as well as double-support periods, as compared to both standard models. The extension (in terms of range of motion when walking) of the operated knee was significantly improved for all three types of walk in favour of the FIRST TKAs compared to both NexGen TKAs. The normal walking speed was significantly higher with faster swing speed and stride lengths for the new TKA. Significantly better coordination scores were observed at normal walking speed for the FIRST TKA as compared to the fixed-bearing TKAs. Conclusion: The FIRST TKAs showed statistically significantly better objective outcomes in terms of gait after one year of follow-up with similar subjective and semi-objective results in comparison with widespread TKA designs. These encouraging short-terms results will have to be confirmed at a 5 years follow-up of the FIRST TKAs.

Changes in D-serine levels and localization during postnatal development of the rat vestibular nuclei.

The patterns of development of the vestibular nuclei (VN) and their main connections involving glutamate neurotransmission offer a good model for studying the function of the glial-derived neuromodulator D-serine in synaptic plasticity. In this study we show that D-serine is present in the VN and we analyzed its distribution and the levels of expression of serine racemase and D-amino acid oxidase (D-AAO) at different stages of postnatal (P) development. From birth to P21, high levels of D-serine were detected in glial cells and processes in all parts of the VN. This period corresponded to high expression of serine racemase and low expression of D-AAO. On the other hand, in the mature VN D-serine displayed very low levels and was mainly localized in neuronal cell bodies and dendrites. This drop of D-serine in adult stages corresponded to an increasing expression of D-AAO at mature stages. High levels of glial D-serine during the first 3 weeks of postnatal development correspond to an intense period of plasticity and synaptogenesis and maturation of VN afferents, suggesting that D-serine could be involved in these phenomena. These results demonstrate for the first time that changes in D-serine levels and distribution occur during postnatal development in the central nervous system. The strong decrease of D-serine levels and the glial-to-neuronal switch suggests that D-serine may have distinct functional roles depending on the developmental stage of the vestibular network.

El discurs polític: la immigració com a pretext

El treball és una d’anàlisi del discurs polític que apareix en els programes electorals dels candidats a les presidencials franceses 2012, centrant l’atenció en el terme immigration. L’objectiu és identificar de quina manera expressen la seva ideologia, concretar les semblances, les divergències i els matisos que determinen en els seus discursos.

Psychological distress in adult survivors of childhood cancer: the Swiss Childhood Cancer Survivor study.

PURPOSE: To evaluate the degree of psychological distress in adult childhood cancer survivors in Switzerland and to characterize survivors with significant distress. METHODS: Childhood cancer survivors who were age younger than 16 years when diagnosed between 1976 and 2003, had survived more than 5 years, and were currently age 20 years or older received a postal questionnaire. Psychological distress was assessed using the Brief Symptom Inventory (BSI). Raw scores were transformed into T scores according to the German norm sample, and the proportion of participants being at increased risk for psychological distress was calculated (case rule: T > or = 63). t tests and univariable and multivariable logistic regressions were used for statistical analyses. RESULTS: One thousand seventy-six survivors (63.% of eligible survivors, 71.9% of contacted survivors) returned the questionnaire, 987 with complete data on BSI. Comparison with the norm populations showed lower T scores (T < 50) in the Global Severity Index (GSI; T = 46.2), somatization (T = 47.6), obsessive-compulsive tendencies (T = 46.9), and anxiety (T = 48.4). However, more childhood cancer survivors (especially women) had increased distress for GSI (14.4%), interpersonal sensitivity (16.5%), depression (13.4%), aggression (16.9%), and psychotic tendencies (15.6%) than the expected 10% from the norm population. Caseness was associated with female sex, being a single child, older age at study, and self-reported late effects, especially psychological problems. CONCLUSION: Results show that childhood cancer survivors, on average, have less psychological distress than a norm population but that the proportion of survivors at risk for high psychological distress is disproportionally large. Monitoring psychological distress in childhood cancer survivors may be desirable during routine follow-up, and psychological support should be offered as needed.

Parents - child role reversal in trilogue play: case studies of trajectories from pregnancy to toddlerhood

Role reversal, whereby a child attempts to meet her parent's adult needs for parenting, intimacy, or companionship, has been identified as a risk factor for developmental disturbances. It has been defined from diverse perspectives as a child attachment strategy, a parent - toddler relational disturbance, and a boundary disturbance between parents and child. The recently discovered infant's triangular capacity, namely the sharing of her attention and affects with both parents, allows one to analyse the infant's contribution to early family dynamics. Role reversal was detected in 4 out of 45 father - mother - infant interactions observed in trilogue play from pregnancy to toddlerhood. The developmental trajectories towards role reversal are explored by means of case analyses. Results are compared with cases of problematic triangulation encountered in the same sample. In role reversal, family interactions are rigidly organized around a "two against one" coalition, whereby the normative hierarchy between parents and child is reversed. The child's triangular capacity is overactivated, controlling the tension between her parents by provocation - animation strategies

Savoir, faire ? Les relations chimériques de la psychanalyse avec la psychiatrie publique et l'université en Suisse romande

C'est souvent dans les institutions psychiatriques que le médecin développe les premiers contacts avec la psychanalyse. L'institution entretient pourtant avec la psychanalyse un rapport chimérique que les sociétés de psychanalyse contribuent à pervertir en restant cloîtrées. Telle pourrait être la thèse de Nicolas Despland qui souhaite, par un article qui défriche le problème, ouvrir la discussion pour trouver des solutions qui importent à tous les protagonistes. (Tribune psychanalytique)

Mise en place percutanée de filtres dans la veine cave inférieure en prévention de l'embolie pulmonaire : recommandations

Recommandations conçues dans le cadre d'un Groupe de travail coordonée par Lucia Mazzolai du Service d'angiologie. Membres du Groupe de travail: Angelillo-Scherrer Anne (Service d'hématologie), Burnier Michel ( Service de néphrologie), Demartines Nicolas (Service de chirurgie viscérale), Duchosal Michel (Service d'hématologie), Farron Alain (Service d'orthopédie), Hohlfeld Patrick (Département de gynéco-obstétrique), Hugli Olivier (Service des urgences), Jichlinski Patrice (Service d'urologie), Jolliet Philippe (Service de médecine intensive), Kern Christian (Service d'anesthésiologie), Levivier Marc (Service de neurochirurgie), Leyvraz Serge (Service d'oncologie), Meuli Reto (Service de radiodiagnostic et radiologie interventionnelle), Nicod Laurent (Service de pneumologie), Qanadli Salah (Service de radiodiagnostic et radiologie interventionnelle), Ris Hans-Beat (Service de chirurgie thoracique et vasculaire), Ruchat Patrick (Service de chirurgie cardiovasculaire), Vial Yvan (Service de gynécologie obstétrique), Vogt Pierre (Service de cardiologie), Von Segesser Ludwig (Service de chirurgie cardiovasculaire), Waeber Gerard (Service de médecine interne), Yersin Bertrand (Service des urgences)