Gender influences the detection of spatial working memory deficits in bipolar disorder.

Objective: Despite evidence that gender may influence neurocognitive functioning, few studies have examined its effects in bipolar disorder (BD) a priori. The aim of this study was to examine how gender influences executive-type functions, which are potentially useful as endophenotypes for BD. Methods: The performance of 26 euthymic patients(12 males, 14 females) with DSM-IV BD (20 BD type I and six BD type II) was compared to that of 26 controls (12 males, 14 females) on tests of executive function. Controls were matched to patients on an individual basis for sex, age and premorbid IQ. Tests assessed spatial working memory (SWM), planning, attentional set-shifting and verbal fluency. Results: Overall, patients showed deficits in SWM strategy (p < 0.001) and made more SWM errors relative to controls (p < 0.001). These deficits were more apparent in male-only comparisons (both p < 0.001) than in female-only comparisons (both p < 0.05). When examined in isolation, male controls were significantly better at performing the SWM task than female controls (both p < 0.05). This pattern was not observed in the patient cohort: male patients had poorer strategy scores than female patients (p < 0.05), but made a similar number of SWM errors. Conclusions: These findings provide evidence that gender can influence the detection of SWM deficits in the euthymic phase of BD, as the sex-related disequilibrium in SWM identified in healthy controls was disrupted in BD. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.

The myeloproliferative disorder-associated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3

The somatic JAK2 valine-to-phenylalanine (V617F) mutation has been detected in up to 90% of patients with polycythemia and in a sizeable proportion of patients with other myeloproliferative disorders such as essential thrombocythemia and idiopathic myelofibrosis. Suppressor of cytokine signaling 3 (SOCS3) is known to be a strong negative regulator of erythropoietin (EPO) signaling through interaction with both the EPO receptor (EPOR) and JAK2. We report here that JAK2 V617F cannot be regulated and that its activation is actually potentiated in the presence of SOCS3. Instead of acting as a suppressor, SOCS3 enhanced the proliferation of cells expressing both JAK2 V617F and EPOR. Additionally, although SOCS1 and SOCS2 are degraded in the presence of JAK2 V617F, turnover of SOCS3 is inhibited by the JAK2 mutant kinase and this correlated with marked tyrosine phosphorylation of SOCS3 protein. We also observed constitutive tyrosine phosphorylation of SOCS3 in peripheral blood mononuclear cells (PBMCs) derived from patients homozygous for the JAK2 V617F mutant. These findings suggest that the JAK2 V617F has overcome normal SOCS regulation by hyperphosphorylating SOCS3, rendering it unable to inhibit the mutant kinase. Thus, JAK2 V617F may even exploit SOCS3 to potentiate its myeloproliferative capacity.

El uso de la musicoterapia para la mejora de la comunicación de niños con Trastorno del Espectro Autista en Aulas Abiertas Especializadas

Los beneficios que aporta la musicoterapia en alumnos con Trastorno del Espectro Autista, han sido demostrados profusamente por los distintos autores, si bien carecemos de literatura suficiente sobre su utilización en las Aulas Abiertas Especializadas en colegios ordinarios (Aulas TEA). En este sentido, el objetivo del trabajo, ha consistido en analizar qué mejoras aporta la musicoterapia al desarrollo de la comunicación en los alumnos con Trastorno del Espectro Autista dentro de las Aulas Abiertas de los CEIPs de Castilla-La Mancha y la Comunidad Autónoma de Madrid. Para ello, se ha realizado una amplia revisión documental de fuentes de referencia y se ha entrevistado a los docentes responsables de las Aulas Abiertas Especializadas que utilizan actividades de musicoterapia como recurso en el aula. Se concluye el artículo manifestando, en primer lugar, la escasa integración de la musicoterapia en las aulas TEA (menos del 20% de los centros). En aquellas aulas que sí se programa con actividades de musicoterapia, los beneficios que ésta aporta se ven reflejados en un incremento claro de la intención comunicativa en los alumnos. Además, a la hora de planificar las actividades se tiene muy en cuenta conocer las preferencias y la historia musical del niño. No obstante, existen factores que impiden el aprovechamiento total de las posibilidades terapéuticas de la musicoterapia debido, especialmente a: a) una escasa formación del profesorado y b) un espacio inadecuado para poner en práctica una sesión de musicoterapia.

Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells.

Mutant mice where tyrosine 136 of linker for activation of T cells (LAT) was replaced with a phenylalanine (Lat(Y136F) mice) develop a fast-onset lymphoproliferative disorder involving polyclonal CD4 T cells that produce massive amounts of Th2 cytokines and trigger severe inflammation and autoantibodies. We analyzed whether the Lat(Y136F) pathology constitutes a bona fide autoimmune disorder dependent on TCR specificity. Using adoptive transfer experiments, we demonstrated that the expansion and uncontrolled Th2-effector function of Lat(Y136F) CD4 cells are not triggered by an MHC class II-driven, autoreactive process. Using Foxp3EGFP reporter mice, we further showed that nonfunctional Foxp3(+) regulatory T cells are present in Lat(Y136F) mice and that pathogenic Lat(Y136F) CD4 T cells were capable of escaping the control of infused wild-type Foxp3(+) regulatory T cells. These results argue against a scenario where the Lat(Y136F) pathology is primarily due to a lack of functional Foxp3(+) regulatory T cells and suggest that a defect intrinsic to Lat(Y136F) CD4 T cells leads to a state of TCR-independent hyperactivity. This abnormal status confers Lat(Y136F) CD4 T cells with the ability to trigger the production of Abs and of autoantibodies in a TCR-independent, quasi-mitogenic fashion. Therefore, despite the presence of autoantibodies causative of severe systemic disease, the pathological conditions observed in Lat(Y136F) mice unfold in an Ag-independent manner and thus do not qualify as a genuine autoimmune disorder.