Cell death during sepsis: integration of disintegration in the inflammatory response to overwhelming infection

Sepsis is a major health problem and a leading cause of death worldwide. In recent years, a crescendo of attention has been directed to the mechanisms of cell death that develop during this disease, since these are viewed as important contributors to the proinflammatory and anti-inflammatory responses associated with poor outcome. Here we discuss mechanisms of cell death evident severe bacterial infection and sepsis including necrosis, apoptosis, pyroptosis, and extracellular trap-associated neutrophil death, with a particular emphasis on lymphocyte apoptosis and its contribution to the immunosuppressed phenotype of late sepsis. Individual bacterial pathogens express virulence factors that modulate cell death pathways and influence the sepsis phenotype. A greater knowledge of cell death pathways in sepsis informs the potential for future therapies designed to ameliorate immune dysfunction in this syndrome

Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling

Following endocytosis into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multiprotein complex that orchestrates cargo retrieval and recycling and, importantly, is biochemically and functionally distinct from the established retromer pathway. We have called this complex 'retriever'; it is a heterotrimer composed of DSCR3, C16orf62 and VPS29, and bears striking similarity to retromer. We establish that retriever associates with the cargo adaptor sorting nexin 17 (SNX17) and couples to CCC (CCDC93, CCDC22, COMMD) and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of α5β1 integrin. Through quantitative proteomic analysis, we identify over 120 cell surface proteins, including numerous integrins, signalling receptors and solute transporters, that require SNX17-retriever to maintain their surface levels. Our\ua0identification of retriever establishes a major endosomal retrieval and recycling pathway

Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression

Postpartum depression (PPD) affects up to 19% of all women after parturition. The non-apeptide oxytocin (OXT) is involved in adjustment to pregnancy, maternal behavior, and bonding. Our aim was to examine the possible association between plasma OXT during pregnancy and the development of PPD symptoms. A total of 74 healthy, pregnant women were included in this prospective study. During the third trimester of pregnancy and within 2 weeks after parturition, PPD symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Blood samples for plasma OXT assessment were collected in the third trimester. Following the literature, participants with postpartum EPDS scores of 10 or more were regarded as being at risk for PPD development (rPPD group). In a logistic regression analysis, plasma OXT was included as a potential predictor for being at risk for PPD. Results were controlled for prepartal EPDS score, sociodemographic and birth-outcome variables. Plasma OXT concentration in mid-pregnancy significantly predicted PPD symptoms at 2 weeks postpartum. Compared with the no-risk-for-PPD group, the rPPD group was characterized by lower plasma OXT concentrations. To our knowledge, this is the first study to show an association between prepartal plasma OXT concentration and postpartal symptoms of PPD in humans. Assuming a causal relationship, enhancing OXT release during pregnancy could serve as a potential target in prepartum PPD prevention, and help to minimize adverse effects of PPD on the mother-child relationship

Factores psicosociales asociados a un alto, medio y bajo riesgo de síntomas depresivos en el posparto inmediato Psychosocial factors associated to low, medium and high risk of depressive symptoms in the immediate postpartum period

OBJETIVOS: evaluar factores psicosociales asociados a síntomas depresivos en el posparto inmediato. MÉTODOS: 45 mujeres puérperas de un hospital público de Buenos Aires, Argentina, fueron entrevistadas entre el 1er y el 3er día posparto, de marzo-diciembre 2010. La Escala de Depresión Posnatal de Edimburgo (EPDS) fue administrada para evaluar síntomas depresivos. La entrevista psicológica perinatal (EPP) fue administrada para detectar variables psicosociales. A partir de los resultados obtenidos en la EPDS, se separó la muestra en tres grupos con diferentes grados de riesgo de sintomatología depresiva: "negativas o de bajo riesgo", "positivas de riesgo medio" y "positivas de alto riesgo". Los puntajes de corte utilizados fueron 9 y 19. RESULTADOS: se encontraron diferencias significativas entre los tres grupos con violencia familiar, migración, historia previa de depresión, presencia de síntomas depresivos durante el embarazo y mayor cantidad de estresores. CONCLUSIONES: el establecimiento de los dos puntajes de corte en la EPDS permite una detección temprana de las mujeres que presentan síntomas depresivos. Se sugiere la utilidad del puntaje de corte de 19 para la detección temprana de mujeres con mayor riesgo de desarrollar depresión posparto.<br>OBJECTIVES: evaluate psychosocial factors associated to depressive symptoms during the immediate postpartum period. METHODS: a total of 45 argentine puerperal women hospitalized in a public maternal hospital of Buenos Aires, Argentina, were interviewed on the 1st and 3rd day postpartum from March to December 2010. Aiming to assess the presence of depressive symptoms, the Edinburgh Postnatal Depression Scale (EPDS) was administrated. The Perinatal Psychological Interview was administrated to explore psychosocial variables. Based on the scores obtained in the EPDS, the sample was separated in three different groups with increasing risk of depressive symptomatology: "negative or low risk", "positive medium risk" and "positive high risk". Cut-off scores were 9 and 19 points. RESULTS: out of the total psychosocial variables analyzed, statistically significant differences were found among the three groups regarding family violence, migration, previous history of depression, depressive symptoms during pregnancy and increasing number of life events. CONCLUSIONS: the setting of two cut-off scores in EPDS allows the early detection of women with depressive symptoms. It is suggested the usefulness of cut-off value of 19 for early detection of women at high risk to developing postpartum depression

Internet-based stress management for women with preterm labour: a case-based experience report

Pregnant women with preterm labour (PTL) in pregnancy often experience increased distress and anxieties regarding both the pregnancy and the child's health. The pathogenesis of PTL is, among other causes, related to the stress-associated activation of the maternal-foetal stress system. In spite of these psychobiological associations, only a few research studies have investigated the potential of psychological stress-reducing interventions. The following paper will present an online anxiety and stress management self-help program for pregnant women with PTL. Structure and content of the program will be illustrated by a case-based experience report. L.B., 32 years (G3, P1), was recruited at gestational week 27 while hospitalized for PTL for 3 weeks. She worked independently through the program for 6 weeks and had regular written contact with a therapist. Processing the program had a positive impact on L.B.'s anxiety and stress levels, as well as on her experienced depressive symptoms and bonding to the foetus. As PTL and the risk of PTB are associated with distress, psychological stress-reducing interventions might be beneficial. This study examines the applicability of an online intervention for pregnant women with PTL. The case report illustrates how adequate low-threshold psychological support could be provided to these women