Brain structural trajectories in youth at familial risk for schizophrenia or bipolar disorder according to development of psychosis spectrum symptoms.

BACKGROUND: The evaluation of child and adolescent offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) may help understand changes taking place in the brain in individuals at heightened risk for disease during a key developmental period. METHODS: One hundred twenty-eight individuals (33 SzO and 46 BpO, considered jointly as 'Familial High Risk' (FHR), and 49 controls) aged 6-17 years underwent clinical, cognitive and neuroimaging assessment at baseline, 2- and 4-year follow-up. Twenty FHR participants (11 SzO and 9 BpO) developed psychotic spectrum symptoms during follow-up, while 59 FHR participants did not. Magnetic resonance imaging was performed on a 3Tesla scanner; cortical surface reconstruction was applied to measure cortical thickness, surface area and grey matter volume. RESULTS: FHR participants who developed psychotic spectrum symptoms over time showed greater time-related mean cortical thinning than those who did not and than controls. By subgroups, this effect was present in both BpO and SzO in the occipital cortex. At baseline, FHR participants who developed psychotic spectrum symptoms over time had smaller total surface area and grey matter volume than those who did not and than controls. Over time, all FHR participants showed less longitudinal decrease in surface area than controls. In those who developed psychotic spectrum symptoms over time, this effect was driven by BpO, while in those who did not, this was due to SzO, who also showed less grey matter volume reduction. CONCLUSION: The emergence of psychotic spectrum symptoms in FHR was indexed by smaller cross-sectional surface area and progressive cortical thinning. Relative preservation of surface area over time may signal different processes according to familial risk. These findings lay the foundation for future studies aimed at stratification of FHR youth.

Infliximab therapy reverses the increase of allograft inflammatory factor-1 in serum and colonic mucosa of rats with inflammatory bowel disease.

OBJECTIVE: Our purpose was to study the molecular basis of infliximab (IFX) effect on colon mucosa in a colitis model and to identify new biomarkers of mucosal healing. METHODS: Healthy rats and rats which were subjected to experimental colitis induced by dextran sulfate sodium, with or without IFX treatment (in the short- and long-term), were studied along with forty-seven IBD patients. Colon mucosal integrity by periodic acid Schiff (PAS) staining, intestinal damage by immunohistochemistry (proliferating cell nuclear antigen, ß-catenin, E-cadherin, phosphotyrosine, p-p38, allograft inflammatory factor-1 (AIF-1) and colonic mucosal apoptosis by TUNEL staining were evaluated in rats while serum and colon AIF-1 levels were determined in IBD patients. RESULTS: In rats with colitis, IFX reestablished the epithelial barrier integrity, recovered mucus production and decreased colon inflammation, as verified by reduced serum and colon AIF-1 levels; colon and serum AIF-1 levels were also lower in inactive IBD patients compare to active ones. P38 activation after IFX treatment tended to induce differentiation/proliferation of epithelial cells along the colonic crypt-villous axis. CONCLUSIONS: These findings support AIF-1 as a new biomarker of mucosal healing in experimental colitis and suggest that p38 activation is involved in the mucosal healing intracellular mechanism induced by IFX treatment.

Untreated highly viraemic pregnant women from Asia or sub-Saharan Africa often transmit hepatitis B virus despite serovaccination to newborns.

BACKGROUND & AIMS: Mother-to-child (MTC) hepatitis B virus (HBV) transmission has been mainly studied in Asia. The geographical origins of women and HBV genotypes differ in Europe. The aims were to determine the rate and risk factors of MTC HBV transmission from women with high HBV DNA loads in a maternity hospital in Paris, France. METHODS: Retrospective study of HIV-negative, HBs Ag-positive pregnant women with HBV DNA loads above 5 Log10 I.U/ml who were not given lamivudine or tenofovirDF during pregnancy between 2004 and 2011. RESULTS: Among 11 417 pregnant women, 437 (4%) showed a positive HBs Ag. Among these women, 52 had HBV DNA loads above 5 Log10 I.U/ml: 41, 10 and 1 born in Asia, sub-Saharan Africa and Europe respectively. Among the 52 women, 40 were eligible for the analysis: no antiviral therapy during pregnancy; children over 9 months old. Twenty-eight (70%) women were assessed, corresponding to 41 childbirths. Eleven children (27%) had positive HBs Ag, 14 (34%) had positive HBc and HBs Ab, 16 (39%) had positive HBs Ab only. The risk of having positive HBs Ag, according to maternal HBV DNA loads, was 14% for HBV DNA loads less or equal to 8 Log10 I.U/ml, 42% for HBV DNA loads over 8 Log10 I.U/ml, P = 0.04, but not related to the women's origin, HBV genotype. CONCLUSIONS: This study confirms that serovaccination does not fully protect newborns from MTC HBV transmission, when maternal HBV DNA loads exceed 5 Log10 I.U/ml, regardless of the women's origin or HBV genotype.

RNAi-mediated silencing of insulin receptor substrate-4 enhances actinomycin D- and tumor necrosis factor-alpha-induced cell death in hepatocarcinoma cancer cell lines.

Insulin receptor substrate-4 (IRS-4) transmits signals from the insulin-like growth factor receptor (IGF-IR) and the insulin receptor (IR) to the PI3K/AKT and the ERK1/2 pathways. IRS-4 expression increases dramatically after partial hepatectomy and plays an important role in HepG2 hepatoblastoma cell line proliferation/differentiation. In human hepatocarcinoma, IRS-4 overexpression has been associated with tumor development. Herein, we describe the mechanism whereby IRS-4 depletion induced by RNA interference (siRNA) sensitizes HepG2 cells to treatment with actinomycin D (Act D) and combined treatment with Act D plus tumor necrosis factor-alpha (TNF-alpha). Similar results have been obtained in HuH 7 and Chang cell lines. Act D therapy drove the cells to a mitochondrial-dependent apoptotic program involving cytochrome c release, caspase 3 activation, PARP fragmentation and DNA laddering. TNF-alpha amplifies the effect of Act D on HepG2 cell apoptosis increasing c-jun N-terminal kinase (JNK) activity, IkappaB-alpha proteolysis and glutathione depletion. IRS-4 depleted cells that were treated with Act D showed an increase in cytochrome c release and procaspase 3 and PARP proteolysis with respect to control cells. The mechanism involved in IRS-4 action is independent of Akt, IkappaB kinase and JNK. IRS-4 down regulation, however, decreased gamma-glutamylcysteine synthetase content and cell glutathione level in the presence of Act D plus TNF-alpha. These results suggest that IRS-4 protects HepG2 cells from oxidative stress induced by drug treatment.

Resultados de la electrólisis percutánea intratisular en el dolor en el hombro: infraespinoso, un ensayo controlado aleatorio / Résultats de l'Électrolyse Percutanée Intra-tissulaire contre la douleur de l'épaule: Muscle sous-épineux. Une étude contrôlée et randomisée / Results of the Electrolysis Percutaneous Intratissue in the shoulder pain: infraspinatus, A Randomized Controlled Trial

Background: The Electrolysis Percutaneous Intratissue (EPI®) is a novel technique that provokes a local inflammatory process, allowing the phagocytises and affected tissue to repair. Objectives: The work is aimed to: a) verify the effectiveness of the EPI® when there is shoulder pain, b) locate where the EPI® should be applied, c) and find the possible interaction between the trigger points and the tendon pain. Design: Randomized controlled trial. Setting: Institute of Physiotherapy and Sports. Method: A double randomized experimental longitudinal study was conducted on four groups of 10 people aged 34-47 years with pain in the shoulder. In the first study there were three intervention groups and a control group. In the second study, the group with the best results in the first study served as a control group. Measurements: The variables measured were the perceived pain and the restriction for abduction, internal and external rotation. Results: Although the three intervention groups improved respect to the control group when the EPI® was applied, the results show that the EPI® is more effective when it is applied in all detected trigger points and to tendon pain. Conclusions: The EPI® is more effective if applied in the infraspinatus muscle and the tendon than applied only to one of the two structures, when both structures have pain. Limitations: The study could have tested the involvement of different structures and its related biomechanical implications. It could have also considered more variables(AU)

Introducción: la electrólisis percutánea intratisular (EPI®) es una novedosa técnica que provoca un proceso inflamatorio local, que permite la fagocitosis y la reparación del tejido afectado. Objetivos: verificar la efectividad de la EPI® cuando hay dolor del hombro, b) localizar dónde debería ser aplicada la EPI® y C) y determinar la interacción entre los posibles puntos de activación y el dolor del tendón. Diseño: estudio controlado aleatorio. Ubicación: Instituto de Fisioterapia y el Deporte. Método: se realizó un estudio longitudinal experimental aleatorizado doble en cuatro grupos de 10 personas con edades entre 34-47 años que sufrían dolor en el hombro. En el primer estudio hubo tres grupos de intervención y un grupo de control. En el segundo estudio, el grupo que tuvo mejores resultados en el primer estudio sirvió como grupo de control. Mediciones: las variables que se midieron fueron dolor percibido y la restricción de la abducción, rotación interna y rotación externa. Resultados: aunque los tres grupos de intervención mejoraron respecto al grupo de control cuando se aplicó la EPI®, los resultados muestran que la EPI® es más eficaz cuando se aplica en todos los puntos de activación detectados y donde hay dolor en los tendones. Conclusiones: la EPI® es más eficaz si se aplica en el músculo infraespinoso y el tendón que si se aplica solo a una de las dos estructuras, cuando ambas presentan dolor. Limitaciones: el estudio podría haber probado la participación de diferentes estructuras y sus implicaciones biomecánicas relacionadas. Podría también haber tenido en cuenta más variables(AU)

Introduction: L'Électrolyse Percutanée Intra-tissulaire (EPI®) est une nouvelle technique qui produit une réaction inflammatoire locale permettant la régénération tissulaire du tendon, ligament, muscle, etc. Objectifs: Le but de ce travail est de, a) confirmer l'effectivité de l'EPI® lorsqu'il y a une douleur au niveau de l'épaule, b) localiser la région sur laquelle l'EPI® doit être appliqué, et c) trouver la possible interaction entre les points de stimulation et la douleur tendineuse. Dessin: Une étude contrôlée et randomisée. Lieu: Institut de physiothérapie et de sports. Méthode: Une étude randomisée, expérimentale et longitudinale de quatre groupes de 10 personnes, âgées de 34 - 47 ans et atteintes d'une douleur au niveau de l'épaule, a été réalisée. Dans la première étude, il y a eu trois groupes expérimentaux et un groupe témoin. Dans la deuxième étude, le groupe ayant les meilleurs résultats dans la première étude a servi de groupe témoin. Évaluations: Parmi les variables analysées, on peut trouver la perception de la douleur et la limitation de l'adduction et de la rotation interne et externe. Résultats: Quoique les trois groupes expérimentaux ont éprouvé une amélioration vis-à-vis le groupe témoin après l'application de l'EPI®, les résultats ont montré que cette technique est plus effective si elle est appliquée sur tous les points de stimulation détectés et contre la douleur tendineuse. Conclusions: L'EPI® est plus effective si elle est appliquée sur le muscle sous-épineux et les tendons que sur une seule de ces deux structures, quand toutes les deux sont douloureuses. Limitations: L'étude pouvait avoir examiné les différentes structures compromises et leurs implications biomécaniques associées. Elle pouvait avoir aussi considéré beaucoup plus de variables(AU)

Role of insulin receptor substrate-4 in IGF-I-stimulated HEPG2 proliferation.

BACKGROUNDS/AIMS: Insulin receptor substrate-4 (IRS-4) is a scaffold protein that mediates the actions of insulin-like growth factor-I (IGF-I). Its expression increases dramatically after partial hepatectomy (a liver regeneration model). Herein, we report IRS-4 expression in a human hepatoblastoma cell line (HepG2) and IGF-I-dependent IRS-4 tyrosine phosphorylation. METHODS: The role of IRS-4 in HepG2 proliferation was established by RNA interference (siRNA). After 72h of transfection with IRS-4 siRNA, we observed a specific reduction in IRS-4 expression. RESULTS: Depletion of IRS-4 levels decreased ERK phosphorylation, p70S6K phosphorylation and IGF-I-stimulated cell proliferation. Changes in ERK phosphorylation in IRS-4-depleted cells were independent of ras/raf/MEK1/2- and PI3K/Akt-cascades. IRS-4 down-regulation abolished IGF-I-, TPA- and IGF-I plus TPA-stimulated ERK and p70S6K activities. Our results suggest that PKC-epsilon mediates the effect of IRS-4 on ERK activity. Moreover, decreased IRS-4 levels diminished FBS- and IGF-I-stimulated HepG2 growth and cause stress fiber disruption in HepG2 cell line. CONCLUSIONS: Collectively, our data suggest that IRS-4 plays an important role in HepG2 proliferation/differentiation and exerts its actions through ERK and p70S6K activation in a ras/raf/MEK1/2- and PI3Kinase/Akt-independent manner and in a PKC-dependent way.

Insulin receptor substrate-4 signaling in quiescent rat hepatocytes and in regenerating rat liver.

This study was designed to characterize insulin receptor substrate-4 (IRS-4) in isolated rat hepatocytes and to examine its role in liver regeneration. Subcellular fractionation revealed that 85% of IRS-4 is located at isolated hepatocyte plasma membranes. The distribution of IRS-4 among intracellular compartments remained unchanged in insulin-stimulated cells. Two bands corresponding to 145 and 138 kd were observed in immunoblotting experiments. Immunoprecipitation of hepatocyte lysates with a highly specific antibody against IRS-4 led to an insulin and insulin-like growth factor 1 (IGF-1)-dependent increase in phosphotyrosine residues of the 145-kd band. IRS-4 was found to be associated with Src homology 2 (SH2) domain-containing proteins (phosphatidylinositol 3-kinase [PI 3-kinase] and Src homology phosphatase [SHP-2]) and with protein kinase C zeta (PKC zeta). Insulin and IGF-1 elicited a rapid and dose-dependent binding of these 3 proteins to IRS-4. These data suggest that IRS-4 is insulin-/IGF-1-activated by phosphorylation and not by translocation, inducing the recruitment of SH2 domain-containing proteins and PKC zeta to the membrane. To evaluate the possible role of IRS-4 in liver regeneration, we also examined this system after partial hepatectomy (PH). One day after PH, IRS-1 expression increased, consistent with a stimulatory role in the regenerative process, whereas it decreased 7 days after liver resection. This drastic IRS-1 depletion occurred at the expense of increased IRS-2 and IRS-4 expression 7 days after PH. In addition, at this period of time after surgery, the in vivo insulin stimulation of remnant rat livers showed an increase in IRS-4/PI 3-kinase association. Given that 1 and 7 days after PH isolated hepatocytes responded similarly to insulin in terms of induced cell proliferation, a compensatory role is proposed for IRS-2/4 induction. In conclusion, IRS-4 is activated by insulin and IGF-1-like IRS-1 in rat hepatocytes, and the induced expression of IRS-4 is a compensatory mechanism that plays a role in conditions of liver regeneration.

Pretreatment with FK506 up-regulates insulin receptors in regenerating rat liver.

This report examines the effect of FK506 pretreatment on liver insulin receptor expression in partially (70%) hepatectomized rats. FK506 pretreatment led to an increased insulin receptor number 24 hours after hepatectomy, detected by means of insulin binding and cross-linking procedures. This increase was related to enhanced insulin receptor expression determined by in vitro mRNA translation and Western blot techniques. We also tested the functionality of the expressed insulin receptors by [(3)H] thymidine incorporation into DNA in insulin-stimulated hepatocytes. The results show that FK506 pretreatment elicits an increase in the amount of insulin receptor alpha-subunits as measured by Western blot. Maximum alpha-subunit expression recorded 24 hours after surgery was preceded by increased insulin receptor mRNA levels, which were detected 6 hours after hepatectomy. Moreover, in FK506-pretreated rat hepatocytes, obtained from remnant livers 24 hours after partial hepatectomy (PH), the increase in insulin receptor number was associated with improved sensitivity to the hormone. However, in both experimental groups (FK506-pretreated and nonpretreated rats), the sensitivity of hepatocytes toward epidermal growth factor (EGF) showed no significant change, which suggests a specific effect of FK506 on insulin receptor expression. In conclusion, our findings suggest that FK506 pretreatment induces insulin receptor expression in regenerating rat liver and promotes liver regeneration in hepatectomized rats.

Apoyo social, características sociodemográficas y burnout en enfermeras y auxiliares de hospital / Social support, sociodemographic characteristics and burnout syndrome in hospital nurses and nursing auxiliaries

Este estudio explora la relación entre síndrome de burnout (agotamiento emocional, despersonalización y falta de realización personal) y apoyo procedente de la red social: vínculos informales (familia y amigos) y vínculos del lugar de trabajo (supervisores y compañeros). Para la recogida de datos se utilizaron la Multidimensional Support Scale (Winefield HR, Winefield AH, Tiggemann M, 1992) y el Maslach Burnout Inventory (Maslach C, Jackson SE, 1986) en una muestra de enfermeras de un hospital general. Se obtuvieron los siguientes resultados: a) el agotamiento emocional se relacionó positivamente con el apoyo social de los compañeros, y b) la suficiencia con el apoyo de la familia y de los amigos estaba asociada a la realización personal. Para futuras investigaciones se debe considerar la importancia de valorar qué necesidades de apoyo social específicas requieren diferentes vínculos sociales y el rol que los vínculos informales tienen en la prevención del síndrome. Finalmente, se discuten algunas implicaciones que nuestros hallazgos tienen en el diseño y la implementación de programas de prevención (AU)