Role of major histocompatibility complex class II expression by non-hematopoietic cells in autoimmune and inflammatory disorders: facts and fiction.

It is well established that interactions between CD4(+) T cells and major histocompatibility complex class II (MHCII) positive antigen-presenting cells (APCs) of hematopoietic origin play key roles in both the maintenance of tolerance and the initiation and development of autoimmune and inflammatory disorders. In sharp contrast, despite nearly three decades of intensive research, the functional relevance of MHCII expression by non-hematopoietic tissue-resident cells has remained obscure. The widespread assumption that MHCII expression by non-hematopoietic APCs has an impact on autoimmune and inflammatory diseases has in most instances neither been confirmed nor excluded by indisputable in vivo data. Here we review and put into perspective conflicting in vitro and in vivo results on the putative impact of MHCII expression by non-hematopoietic APCs-in both target organs and secondary lymphoid tissues-on the initiation and development of representative autoimmune and inflammatory disorders. Emphasis will be placed on the lacunar status of our knowledge in this field. We also discuss new mouse models-developed on the basis of our understanding of the molecular mechanisms that regulate MHCII expression-that constitute valuable tools for filling the severe gaps in our knowledge on the functions of non-hematopoietic APCs in inflammatory conditions.

Fourth cranial nerve palsy and brown syndrome: two interrelated congenital cranial dysinnervation disorders?

Based on neuroimaging data showing absence of the trochlear nerve, congenital superior oblique palsy is now classified as a congenital cranial dysinnervation disorder. A similar absence of the abducens nerve is accompanied by misinnervation to the lateral rectus muscle from a branch of oculomotor nerve in the Duane retraction syndrome. This similarity raises the question of whether some cases of Brown syndrome could arise from a similar synkinesis between the inferior and superior oblique muscles in the setting of congenital superior oblique palsy. This hypothesis has gained support from the confluence of evidence from a number of independent studies. Using Duane syndrome as a model, we critically review the accumulating evidence that some cases of Brown syndrome are ultimately attributable to dysgenesis of the trochlear nerve.

Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. METHODS: We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. RESULTS: Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) -0.20 days, 95% CI -0.94, 0.53, p&#8202;=&#8202;0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p&#8202;=&#8202;0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I2 for subgroup analysis 64%, p&#8202;=&#8202;0.04). CONCLUSIONS: No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation.

Constructive thinking skills and impulsivity dimensions in conduct and substance use disorders: differences and relationships in an adolescents' sample.

Impact of conduct disorder (CD) and substance use disorder (SUD) on constructive thinking skills and impulsivity was explored. 71 offending adolescents were assessed for CD and SUD. Furthermore, the constructive thinking inventory, the immediate and delayed memory tasks and the UPPS impulsive behaviour scale were administered. Results showed that youths with CD, independently from SUD, presented higher personality impulsivity (urgency) and altered constructive thinking skills (categorical thinking and personal superstitious thinking). Furthermore, trait-impulsivity explained variation in constructive thinking skills. The implications of these results were discussed.

Impact on assertivity of a social skills training with adolescents suffering from psychotic or anxiety/mood disorders: An exploratory study

During adolescence numerous of important social abilities are acquired within interactions with peers. Severe psychiatric disorders interfere with the acquisition of these social skills. For example, due to excessive shyness, adolescents with psychiatric disorders may not experiment positive social interactions. Social skills training (SKT) may help adolescents to remediate to these diffi culties. This exploratory study aims to assess the SKT's effect on assertivity, in a population of adolescents presenting psychiatric disorder and attending a day care unit for adolescents. The SKT, delivered in group, deals with different themes such as contact, conversation, problem solving, confl ict, fail, success, learning, effort, separation, breakdown, and project. In this context, 38 adolescents (19 suffering from anxiety / mood disorder and 19 suffering from psychotic disorder) rate their level of assertivity before and after a SKT with the Rathus assertivity scale. This scale allows to differentiate between inhibited, assertive and assertiveaggressive adolescents. Results showed a general improvement on assertivity after the SKT. More specifi cally, adolescents suffering from anxiety disorder and the 'inhibited' adolescents showed the higher benefi t from the SKT. Thus, two hours per week of SKT seems to enhance social abilities in a population with severe psychiatric disorders. More specifi - cally, adolescents with anxiety / mood disorders reported more benefi ts of the SKT on their assertivity. Nevertheless, adolescents with psychotic disorders did not report strong benefi ts from the SKT despite the improvement observed at a clinical level. This observation raises questions about the usefulness of self-reported questionnaire to measure such benefi t for adolescents with psychosis.

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.

Occupational exposure to beryllium in Switzerland : exposed workers and occupations at risk

Introduction: Beryllium (Be) is increasingly used in various industrial applications. Occupational exposure to Be may lead to chronic beryllium disease (CBD), a pulmonary granulomatous disorder closely similar to sarcoidosis, which develop in 1 to 15% of exposed workers. Although Switzerland is one of the major Be importers worldwide, little information is available about occurrence of exposure and the number of workers exposed in this country. Objectives: 1) evaluate the number of workers potentially exposed to Be in Switzerland; 2) construct a screening tool to allow potential Be exposure detection in a clinical setting. Methods: After identification of industrial sectors involving beryllium exposure based on expert reports and scientific literature, an estimation of the number of workers employed in these relevant industries was made using data from the Swiss federal population census and registries of economic activities. A second analysis was performed to estimate the fraction of workers really exposed to Be in each industrial sector. This adjustment was made according to the results of a French survey (INRS, Institut National de Recherche et de S��curit��) conducted by questionnaire addressed to 4500 companies in relevant industries on their use of beryllium and other issues such as percentage of employees really exposed. These realistic data were used to develop a self-administrated screening questionnaire allowed to identify patients with possible Be exposure. Results: In Switzerland, the number of workers employed in industries using Be was nearly 150 000. The estimated number of workers exposed to beryllium in these industries ranged from 2000 to 4000. Relevant sectors were: microengineering, precision turning, watchmaking and metal waste treatment and recycling. The validation of the self-administrated questionnaire containing a list of jobs and leisure activities associated with potential Be exposure is in progress within the framework of a national study. Conclusions: The number of workers potentially exposed to Be in Switzerland is rather high compared to estimations for other industrialized countries and might constitute an underestimated occupational health problem. Undetected Be exposure in patients with sarcoidosis may occur and result in misdiagnosis. Once validated, the self-administrated questionnaire could be used by clinicians to screen for Be exposure in patients with granulomatous lung disorders.

Nicotinamide phosphoribosyltransferase as a target in inflammation- related disorders.

NAD(+) biosynthesis through nicotinamide phosphoribosyltransferase (NAMPT) holds potential as a target for the treatment of inflammatory disorders due to NAD(+)'s role in immune cell signaling and metabolism. In addition to its activity as an enzyme, NAMPT is also secreted in the extracellular space where it acts as a pro-inflammatory and proangiogenic cytokine. NAMPT inhibition with FK866 has anti-inflammatory activity in different models of immune disorders and it prevents ischemia-reperfusion-induced heart damage by dampening the production of neutrophil chemoattractants. NAMPT blockade with a neutralizing antibody has beneficial effects in an acute lung injury model. Last, but not least, the anticancer activity of NAMPT inhibitors may also reflect, at least in part, their ability to modify the cancer microenvironment through their anti-inflammatory properties. Overall, NAMPT inhibition holds potential for the treatment of inflammation-related disorders and the development of effective and safe NAMPT inhibitors remains an area of strong interest in pharmaceutical research.

Manifestations neurologiques des troubles musculosquelettiques [Neurological manifestations in musculoskeletal disorders].

Musculoskeletal disorders are a crossroad among diverse specialties: neurology, rehabilitation, orthopedics, occupational medicine and psycho-traumatology. They are integrated into occupational medicine and encompass overuse syndromes, repeated micro-trauma and focal compressive neuropathies linked with professional or sports' activity. Neurological manifestations are omnipresent. Yet, their importance is not always recognized despite frequent resort to neurologists specialized in peripheral nervous system disorders and neurophysiology, as well as, to behavioral cognition specialists. Therapeutic approaches require preventive and work organization measures, neurophysiologic investigations and imaging in expert hands, and conservative treatment with physiotherapy, with or without paraneural and intra-articular injections.

The Beck Cognitive Insight Scale in outpatients with psychotic disorders: further evidence from a French-speaking sample.

OBJECTIVE: The Beck Cognitive Insight Scale (BCIS) evaluates patients' self-report of their ability to detect and correct misinterpretation. Our study aims to confirm the factor structure and the convergent validity of the original scale in a French-speaking environment. METHOD: Outpatients (n = 158) suffering from schizophrenia or schizoaffective disorders fulfilled the BCIS. The 51 patients in Montpellier were equally assessed with the Positive and Negative Syndrome Scale (PANSS) by a psychiatrist who was blind of the BCIS scores. RESULTS: The fit indices of the confirmatory factor analysis validated the 2-factor solution reported by the developers of the scale with inpatients, and in another study with middle-aged and older outpatients. The BCIS composite index was significantly negatively correlated with the clinical insight item of the PANSS. CONCLUSIONS: The French translation of the BCIS appears to have acceptable psychometric properties and gives additional support to the scale, as well as cross-cultural validity for its use with outpatients suffering from schizophrenia or schizoaffective disorders. The correlation between clinical and composite index of cognitive insight underlines the multidimensional nature of clinical insight. Cognitive insight does not recover clinical insight but is a potential target for developing psychological treatments that will improve clinical insight.

Prevalence and correlates of DSM-5 bipolar and related disorders and hyperthymic personality in the community.

BACKGROUND: To 1) establish the lifetime and 12-month prevalence of DSM-5 bipolar and related disorders including the new algorithmically defined conditions grouped within Other Specified Bipolar and Related Disorders (OSBARD) as well as hyperthymic personality in a randomly selected community sample, and 2) determine the clinical relevance of the OSBARD category in terms of sociodemographic characteristics, course, comorbidity and treatment patterns by comparing the subjects of this category to those with bipolar-I (BP-I), bipolar-II (BP-II), major depressive disorder (MDD), and those with no history of mood disorders. METHODS: The semi-structured Diagnostic Interview for Genetic Studies was administered by masterslevel psychologists to a random sample of an urban area (n=3'719). RESULTS: The lifetime prevalence was 1.0% for BP-I, 0.8% for BP-II, 1.0% for OSBARD and 3% for hyperthymic personality. Subjects with OSBARD were more severely affected than subjects without a history of mood disorders regarding almost all clinical correlates. Compared to those with MDD, they also revealed an elevated risk of suicidal attempts, lower global functioning, more treatment seeking and more lifetime comorbidity including anxiety, substance use and impulse-control disorders. However, they did not differ from subjects with BP-II. LIMITATIONS: Small sample sizes for bipolar and related disorders and potential inaccurate recall of symptoms. CONCLUSIONS: The modifications of diagnostic criteria for manic/hypomanic episodes according to the DSM-5 only marginally affect the prevalence estimates for BP-I and BP-II. The new DSM-5 OSBARD category is associated with significant clinical burden, is hardly distinct from BP-II with respect to clinical correlates and deserves similar clinical attention.

Development of mental disorders one year after exposure to psychosocial stressors; a cohort study in primary care patients with a physical complaint.

BACKGROUND: Mental disorders, common in primary care, are often associated with physical complaints. While exposure to psychosocial stressors and development or presence of principal mental disorders (i.e. depression, anxiety and somatoform disorders defined as multisomatoforme disorders) is commonly correlated, temporal association remains unproven. The study explores the onset of such disorders after exposure to psychosocial stressors in a cohort of primary care patients with at least one physical symptom. METHOD: The cohort study SODA (SOmatization, Depression and Anxiety) was conducted by 21 private-practice GPs and three fellow physicians in a Swiss academic primary care centre. GPs included patients via randomized daily identifiers. Depression, anxiety or somatoform disorders were identified by the full Patient Health Questionnaire (PHQ), a validated procedure to identify mental disorders based on DSM-IV criteria. The PHQ was also used to investigate exposure to psychosocial stressors (before the index consultation and during follow up) and the onset of principal mental disorders after one year of follow up. RESULTS: From November 2004 to July 2005, 1020 patients were screened for inclusion. 627 were eligible and 482 completed the PHQ one year later and were included in the analysis (77%). At one year, prevalence of principal mental disorders was 30/153 (19.6% CI95% 13.6; 26.8) for those initially exposed to a major psychosocial stressor and 26/329 (7.9% CI95% 5.2; 11.4) for those not. Stronger association exists between psychosocial stressors and depression (RR&#8201;=&#8201;2.4) or anxiety (RR&#8201;=&#8201;3.5) than multisomatoforme disorders (RR&#8201;=&#8201;1.8). Patients who are "bothered a lot" (subjective distress) by a stressor are therefore 2.5 times (CI95% 1.5; 4.0) more likely to experience a mental disorder at one year. A history of psychiatric comorbidities or psychological treatment was not a confounding factor for developing a principal mental disorder after exposure to psychosocial stressors. CONCLUSION: This primary care study shows that patients with physical complaints exposed to psychosocial stressors had a higher risk for developing mental disorders one year later. This temporal association opens the field for further research in preventive care for mental diseases in primary care patients.

Associations of serum uric acid and SLC2A9 variant with depressive and anxiety disorders: a population-based study

Background: Limited information exists regarding the association between serum uric acid (SUA) and psychiatric disorders. We explored the relationship between SUA and subtypes of major depressive disorder (MDD) and specific anxiety disorders. Additionally, we examined the association of SLC2A9 rs6855911 variant with anxiety disorders. Methods: We conducted a cross-sectional analysis on 3,716 individuals aged 35-66 years previously selected for the population-based CoLaus survey and who agreed to undergo further psychiatric evaluation. SUA was measured using uricase-PAP method. The French translation of the semi-structured Diagnostic Interview for Genetic Studies was used to establish lifetime and current diagnoses of depression and anxiety disorders according to the DSM-IV criteria. Results: Men reported significantly higher levels of SUA compared to women (357��}74 &#956;mol/L vs. 263��}64 &#956;mol/L). The prevalence of lifetime and current MDD was 44% and 18% respectively while the corresponding estimates for any anxiety disorders were 18% and 10% respectively. A quadratic hockey-stick shaped curve explained the relationship between SUA and social phobia better than a linear trend. However, with regards to the other specific anxiety disorders and other subtypes of MDD, there was no consistent pattern of association. Further analyses using SLC2A9 rs6855911 variant, known to be strongly associated with SUA, supported the quadratic relationship observed between SUA phenotype and social phobia. Conclusions: A quadratic relationship between SUA and social phobia was observed consistent with a protective effect of moderately elevated SUA on social phobia, which disappears at higher concentrations. Further studies are needed to confirm our observations.

Evaluer les troubles de la marche des personnes ��g��es au cabinet [Assessment of gait disorders in older people]

Gait disorders are frequent and important to assess in older people because they provide unique diagnostic and prognostic information. Gait disorders can be regarded as a marker of frailty because they are associated with several adverse consequences, including falls, cognitive disorders, functional decline, institutionalization, hospitalization, and death. Using structured instruments, gait assessment could be performed in primary care practice to classify the level of sensorimotor deficit and provide the necessary information to decide how to best intervene to improve gait performances, prevent falls as well as functional decline.