Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy.

Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1). Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs) and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding mechanisms of respiratory deficiency should guide pharmaceutical and clinical research towards better therapy for the respiratory deficits associated with DM1.

Functional sphere profiling reveals the complexity of neuroblastoma tumor-initiating cell model.

Neuroblastoma (NB) is a neural crest-derived childhood tumor characterized by a remarkable phenotypic diversity, ranging from spontaneous regression to fatal metastatic disease. Although the cancer stem cell (CSC) model provides a trail to characterize the cells responsible for tumor onset, the NB tumor-initiating cell (TIC) has not been identified. In this study, the relevance of the CSC model in NB was investigated by taking advantage of typical functional stem cell characteristics. A predictive association was established between self-renewal, as assessed by serial sphere formation, and clinical aggressiveness in primary tumors. Moreover, cell subsets gradually selected during serial sphere culture harbored increased in vivo tumorigenicity, only highlighted in an orthotopic microenvironment. A microarray time course analysis of serial spheres passages from metastatic cells allowed us to specifically "profile" the NB stem cell-like phenotype and to identify CD133, ABC transporter, and WNT and NOTCH genes as spheres markers. On the basis of combined sphere markers expression, at least two distinct tumorigenic cell subpopulations were identified, also shown to preexist in primary NB. However, sphere markers-mediated cell sorting of parental tumor failed to recapitulate the TIC phenotype in the orthotopic model, highlighting the complexity of the CSC model. Our data support the NB stem-like cells as a dynamic and heterogeneous cell population strongly dependent on microenvironmental signals and add novel candidate genes as potential therapeutic targets in the control of high-risk NB.

Les débuts de la communication à trois. Interactions visuelles triadiques entre père, mère et bébé

Plusieurs auteurs ont montré que les échanges visuels entre des mères dépressives ou psychotiques et leur bébé présentent de multiples perturbations : dans cet article, les auteurs proposent une étude exploratoire portant sur les échanges visuels père-mère- bébé (9-18 semaines) dans deux groupes de familles, un groupe suivi pour des difficultés du post-partum et un groupe témoin. Les observations sont réalisées dans le cadre d'un jeu à trois structuré selon diverses modalités d'interaction (un parent joue avec l'enfant en présence de l'autre parent / les deux parents jouent conjointement avec le bébé). Les variables retenues concernent d'une part le niveau d'attention visuelle conjointe des partenaires, d'autre part l'évolution de cette attention visuelle au cours du jeu. Les résultats révèlent que les échanges visuels sont plus intenses dans les familles fonctionnelles, ce qui semble indiquer que l'engagement visuel triadique établi par les partenaires peut être représentatif du fonctionnement de la triade à un moment donné de son développement. D'autre part, l'analyse de l'évolution de l'engagement visuel au travers des différents contextes de jeu amène les auteurs à proposer l'hypothèse d'une « alliance triadique » établie conjointement par les trois partenaires et formant la matrice de leurs échanges dyadiques et triadiques. De façon plus générale, les auteurs supposent que l'établissement de cette alliance joue un rôle déterminant pour le développement et l'autonomisa- tion du bébé au sein de sa famille. Disorders in the visual interaction between depressive or psychotic mothers and their baby have been widely described : in this paper, the authors propose an exploratory study of father-mother-infant visual interaction (infants are 9-18 weeks old) in two groups of families, voluntary families and families in therapy for post-par turn disorders. The observations are gathered during a three-partner play, involving different kinds of triadic interaction (one parent plays with the infant, the other parent being « only present » / both parents play together with the child). The analyses have focused on the amount of visual attention shared by the partners and on the evolution of visual interaction during the game. Results show that triadic interaction is more intense in functional triads, which means that shared visual attention may be representative of the more general functioning of the family at a definite stage of its development. Furthermore, considering the sequential organization of visual interaction throughout the game led the authors to the construct of a « triadic alliance », jointly established by the three partners and providing a matrix for their dyadic and triadic interaction. On a more general level, such an alliance could play an important role for the development and the autonomy of the baby within his j her family.

Contribution à l'élaboration de mécanismes de détection, de contrôle et de lutte contre le blanchiment d'argent au regard de l'usage des technologies de l'information et de la communication "cas de l'Algérie"

Résumé : Désormais, la lutte contre le blanchiment d'argent constitue une priorité pour les Etats et les gouvernements dans le but, d'une part, de préserver l'économie et l'intégrité des places financières et, d'autre part, de priver les organisations criminelles des ressources financières. Dans ce contexte, la préoccupation majeure des autorités algériennes en charge de la lutte contre ce phénomène est de mettre en place un dispositif capable de détecter les mécanismes de blanchiment, d'en évaluer la menace et sur la base de cette connaissance, de définir et de déployer les moyens de riposte les plus efficaces et efficients. Mais nous constatons que mener des enquêtes de blanchiment en conséquence à un crime sous-jacent a montré ses limites en matière d'établissement de preuves, d'élucidation d'affaires et de recouvrement des avoirs. Par ailleurs, nous pensons qu'il serait plus judicieux de mettre en place en amont un contrôle «systématique» des flux financiers et des opérations inhabituelles et/ou suspectes et de là, identifier d'éventuelles opérations de blanchiment, sans forcément connaître le crime initial, en veillant au maintien de l'équilibre entre le «tout sécuritaire» orienté vers la surveillance accrue des flux et la préservation de la vie privée et des libertés individuelles. Notre thèse apporte un regard critique sur le dispositif actuel de lutte contre le blanchiment existant en Algérie que nous évaluons et sur lequel nous relevons plusieurs lacunes. Pour répondre aux problèmes identifiés nous proposons des solutions stratégiques, organisationnelles, méthodologiques et technologiques intégrées dans un cadre opérationnel cohérent au niveau national et international.

Identification of case complexity and increased health care utilization in patients with rheumatoid arthritis.

OBJECTIVES: To document biopsychosocial profiles of patients with rheumatoid arthritis (RA) by means of the INTERMED and to correlate the results with conventional methods of disease assessment and health care utilization. METHODS: Patients with RA (n = 75) were evaluated with the INTERMED, an instrument for assessing case complexity and care needs. Based on their INTERMED scores, patients were compared with regard to severity of illness, functional status, and health care utilization. RESULTS: In cluster analysis, a 2-cluster solution emerged, with about half of the patients characterized as complex. Complex patients scoring especially high in the psychosocial domain of the INTERMED were disabled significantly more often and took more psychotropic drugs. Although the 2 patient groups did not differ in severity of illness and functional status, complex patients rated their illness as more severe on subjective measures and on most items of the Medical Outcomes Study Short Form 36. Complex patients showed increased health care utilization despite a similar biologic profile. CONCLUSIONS: The INTERMED identified complex patients with increased health care utilization, provided meaningful and comprehensive patient information, and proved to be easy to implement and advantageous compared with conventional methods of disease assessment. Intervention studies will have to demonstrate whether management strategies based on INTERMED profiles can improve treatment response and outcome of complex patients.

Clinician characteristics, communication, and patient outcome in oncology: a systematic review.

OBJECTIVE: The aim of this study was to review the literature on clinician characteristics influencing patient-clinician communication or patient outcome in oncology. METHODS: Studies investigating the association of clinician characteristics with quality of communication and with outcome for adult cancer patients were systematically searched in MEDLINE, PSYINFO, PUBMED, EMBASE, CINHAL, Web of Science and The Cochrane Library up to November 2012. We used the preferred reporting items for systematic reviews and meta-analyses statement to guide our review. Articles were extracted independently by two of the authors using predefined criteria. RESULTS: Twenty seven articles met the inclusion criteria. Clinician characteristics included a variety of sociodemographic, relational, and personal characteristics. A positive impact on quality of communication and/or patient outcome was reported for communication skills training, an external locus of control, empathy, a socioemotional approach, shared decision-making style, higher anxiety, and defensiveness. A negative impact was reported for increased level of fatigue and burnout and expression of worry. Professional experience of clinicians was not related to communication and/or to patient outcome, and divergent results were reported for clinician gender, age, stress, posture, and confidence or self-efficacy. CONCLUSIONS: Various clinician characteristics have different effects on quality of communication and/or patient outcome. Research is needed to investigate the pathways leading to effective communication between clinicians and patients. Copyright © 2013 John Wiley & Sons, Ltd.

Communication during brief intervention, intention to change, and outcome.

OBJECTIVES: To explore the relationship between patient's intention to change regarding future alcohol consumption following brief alcohol intervention (BAI) and changes in alcohol consumption 12-months later and the communication characteristics between patient and counselor during BAI. DESIGN, SETTING AND SUBJECTS: Data from 367 patients (experimental arm) of a pragmatic randomized controlled trial were used to assess the effectiveness of BAI among hazardous drinkers attending an Emergency Department (Lausanne University Hospital, Lausanne, Switzerland). Alcohol outcome measures at baseline and 12 months follow-up included usual number of drinks per week, monthly frequency of heavy episodic drinking (5 or more standard drinks for men; 4 or more for women), and the Alcohol Use Disorders Identification Test (AUDIT) score. In addition, the communication characteristics between patient and counselor were analyzed via tape recordings using the Motivational Interviewing Skill Code (MISC) from 97 participants. Patient readiness and importance to change on a 10-point Likert scale (readiness/importance to change ruler) was asked during BAI, and patient intention to change alcohol consumption (yes/no) was asked at the last step. Differences in alcohol outcome at follow-up between the 367 patients who did or did not have an intention to change consumption at baseline were compared, as were differences between these two groups in communication characteristics for the 97 who completed tape recordings. RESULTS: Patients with an intention to decrease alcohol consumption reduced alcohol use and related problems more often, and reported higher levels of importance and readiness to change than did their counterparts. Analyses of MISC-coded data showed a significantly higher use of MI-consistent skills among those with a moderation intention, but no group differences on the 8 other counselor communication skills measures were found. Analyses of patient speech during the intervention indicated that those with an intention to change their alcohol consumption significantly more often self-explored personal ambivalence towards alcohol, expressed more intensely their ability, commitment, desire, need and reason to change their alcohol use than did those in the no decrease group. CONCLUSIONS: The intention expressed by hazardous drinkers when concluding BAI is associated with both patient change talk during BAI and drinking outcome 12 months later, but is mainly independent of counselor communication skills. This intention may be an important clinical indicator of which hazardous drinkers are most likely to improve after BAI.

Transitions in social complexity along elevational gradients reveal a combined impact of season length and development time on social evolution.

Eusociality is taxonomically rare, yet associated with great ecological success. Surprisingly, studies of environmental conditions favouring eusociality are often contradictory. Harsh conditions associated with increasing altitude and latitude seem to favour increased sociality in bumblebees and ants, but the reverse pattern is found in halictid bees and polistine wasps. Here, we compare the life histories and distributions of populations of 176 species of Hymenoptera from the Swiss Alps. We show that differences in altitudinal distributions and development times among social forms can explain these contrasting patterns: highly social taxa develop more quickly than intermediate social taxa, and are thus able to complete the reproductive cycle in shorter seasons at higher elevations. This dual impact of altitude and development time on sociality illustrates that ecological constraints can elicit dynamic shifts in behaviour, and helps explain the complex distribution of sociality across ecological gradients.

GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics.

Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10(-13), r(2) = 8.9%, β = -0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with-but is statistically distinct from-the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10(-37), r(2) = 23.2%, β = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perception.