A measure of dysfunctional eating-related cognitions in people with psychotic disorders.

Obesity and binge eating disorder are common in individuals with psychotic disorders. Eating and weight-related cognitions are known to influence eating behaviors. The study was designed to assess the psychometric properties of the Mizes Anorectic Cognitions Questionnaire (MAC-R) in patients with psychotic disorders. Binge eating disorder (BED), body mass index (BMI), the MAC-R and the three factor eating questionnaire (TFEQ) were assessed in 125 patients with a diagnosis of schizophrenia or schizoaffective disorder. Whereas the MAC-R has not acceptable psychometric properties, a brief version of the MAC-R (BMAC) has good psychometrical properties and is correlated with TFEQ and BMI. Binge eating disorder is also correlated to the Rigid Weight Regulation and Fear of Weight Gain subscale. The BMAC is a useful brief measure to assess eating and weight related cognitions in people with psychotic disorders.

De l'invalide à l'adunatos: réflexions sur l'invalidité et le trouble somatoforme douloureux [From disability to the adunatos: some thoughts on disability and somatoform pain disorder].

Disability, especially if related to a psychiatric disorder, such as somatoform pain disorder, is characterized by medical, psychological, relational, social and societal, as well as financial and political aspects. This manuscript, part of a PhD thesis which reflects on a possible dialogue between an ancient text and the modern conceptualization of disability, tries to address the phenomenological, historical and political dimensions of disability.

CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1.

Cytotoxic T cells that are present in tumors and capable of recognizing tumor epitopes are nevertheless generally impotent in eliciting tumor rejection. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8(+) T-cell dysfunction may reveal effective strategies for immune therapy. The inhibitory receptors PD-1 and Tim-3 are known to negatively regulate CD8(+) T-cell responses directed against the well-characterized tumor antigen NY-ESO-1. Here, we report that the upregulation of the inhibitory molecule BTLA also plays a critical role in restricting NY-ESO-1-specific CD8(+) T-cell expansion and function in melanoma. BTLA-expressing PD-1(+)Tim-3(-) CD8(+) T cells represented the largest subset of NY-ESO-1-specific CD8(+) T cells in patients with melanoma. These cells were partially dysfunctional, producing less IFN-γ than BTLA(-) T cells but more IFN-γ, TNF, and interleukin-2 than the highly dysfunctional subset expressing all three receptors. Expression of BTLA did not increase with higher T-cell dysfunction or upon cognate antigen stimulation, as it does with PD-1, suggesting that BTLA upregulation occurs independently of functional exhaustion driven by high antigen load. Added with PD-1 and Tim-3 blockades, BTLA blockade enhanced the expansion, proliferation, and cytokine production of NY-ESO-1-specific CD8(+) T cells. Collectively, our findings indicate that targeting BTLA along with the PD-1 and Tim-3 pathways is critical to reverse an important mechanism of immune escape in patients with advanced melanoma.

Diabète et conduite: réflexions et atelier pratique [Diabetes and driving: thoughts and educational perspectives].

In Switzerland over 200'000 people with diagnosed diabetes drive a car. Their physicians endorse many roles: usual medical care as well as informing properly about driving recommandations and handling the legal issues behing the licensing procedure. Ability to drive can be impaired in three ways: hypogylcemia, diabetes complications and hyperglycemia. Hypoglycemia is the main risk factor of vehicle accident for diabetic drivers and frequent while driving. However few accidents are reported due to hypoglycemia. Swiss medical guidelines about diabetes and driving mention the requested conditions, but practically how should we do? We sought to answear by creating a specific educationnal program focused on hypoglycemia management. Building patient knowledges through experiences is the main goal of the course diabetes and driving.

Brain dysfunctions, psychopathologies, and body image distortions

The major features in eating disorders are a preoccupation with food and its consumption and body dissatisfaction. Diagnostic manuals provide clusters of criteria according to which affected individuals can be categorized into one or other group of eating disorder. Yet, when considering the high proportion of comorbidities and ignoring the content of the symptoms (food, body), the major features seem to yield obsessional-compulsive, addictive, and impulsive qualities. In the present article, we review studies from the neuroscientific literature (mainly lesion studies) on eating disorder, obsessive-compulsive disorder, impulse control disorder, and addiction to investigate the possibility of a wider phenotype that can be related to a common brain network. The literature localizes this network to the right frontal lobe and its connectivities. This network, when dysfunctional, might result in a behavior that favors the preoccupation with particular thoughts, behaviors, anxieties, and uncontrollable urges that are accompanied by little scope for ongoing behavioral adjustments (e.g., impulse control). We reason that this network may turn out to be equally involved in understudied mental conditions of dysfunctional body processing such as muscle dysmorphia, body dysmorphic disorder (including esthetic surgery), and xelomelia. We finally consider previous notions of a wider phenotype approach to current diagnostic practice (using DSM), such as the possibility of a model with a reduced number of diagnostic categories and primary and secondary factors, and to etiological models of mental health conditions.

Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome.

Individuals with an inherited deficiency in gonadotropin-releasing hormone (GnRH) have impaired sexual reproduction. Previous genetic linkage studies and sequencing of plausible gene candidates have identified mutations associated with inherited GnRH deficiency, but the small number of affected families and limited success in validating candidates have impeded genetic diagnoses for most patients. Using a combination of exome sequencing and computational modeling, we have identified a shared point mutation in semaphorin 3E (SEMA3E) in 2 brothers with Kallmann syndrome (KS), which causes inherited GnRH deficiency. Recombinant wild-type SEMA3E protected maturing GnRH neurons from cell death by triggering a plexin D1-dependent (PLXND1-dependent) activation of PI3K-mediated survival signaling. In contrast, recombinant SEMA3E carrying the KS-associated mutation did not protect GnRH neurons from death. In murine models, lack of either SEMA3E or PLXND1 increased apoptosis of GnRH neurons in the developing brain, reducing innervation of the adult median eminence by GnRH-positive neurites. GnRH neuron deficiency in male mice was accompanied by impaired testes growth, a characteristic feature of KS. Together, these results identify SEMA3E as an essential gene for GnRH neuron development, uncover a neurotrophic function for SEMA3E in the developing brain, and elucidate SEMA3E/PLXND1/PI3K signaling as a mechanism that prevents GnRH neuron deficiency.