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Expression of pannexin-1 hemichannels increased during explant culture (p = 0.0027). Extracellular vesicles were most abundantly extruded from the explants during the first 3 h of culture and the temporal pattern of extrusion was unaltered by blocking hemichannels. DISCUSSION We show the mechanism of uptake of nuclear non-viability stains into the syncytiotrophoblast during explant culture is via upregulation of pannexin 1 hemichannels. Contrary to suggestions by some, the production of extracellular vesicles from cultured placental explants is not an in vitro artefact resulting from the apparent death of the syncytiotrophoblast in explant cultures. BACKGROUND Melancholic depression (MD) is a subtype of Major Depression associated with more clinical severity and poorer prognosis that non-melancholic depression (NMD). The differentiation between depression subtypes is still clinical, although the identification of specific biomarkers could be useful for diagnosis and the development of new treatments. Purpose of the present manuscript is to review the biomarkers that have been associated with MD. METHODS We performed a bibliographic research on the main databases (PubMed, Embase, PsycInfo, Isi Web of Knowledge, Medscape, The Cochrane Library), in order to find studies that proposed biological markers for melancholic depression. A total of 14 studies met our inclusion criteria. RESULTS Most of studies focused on immune dysregulation. Subjects with MD show biological abnormalities than healthy controls (HC). MD might be characterized by specific biological changes and it could be associated to more severe abnormalities with respect to NMD; however especially about this latter point the available data are preliminary. LIMITATIONS Most available data have not been replicated; the studies focused on different biomarkers. In addition, many articles report results on a limited sample size. CONCLUSIONS Melancholic depression is a subtype of major depression that seems to be associated with specific alterations of different biological systems. Future studies with larger sample can confirm the results and hypothesis presented in this review. find more V.BACKGROUND Transcranial Magnetic Stimulation (TMS) has emerged as a valid therapeutic option in the treatment of depression, especially in cases of inadequate response to antidepressant agents. Despite the recognized efficacy of this technique, its mechanisms of action are still debated and optimal protocols have not yet been established. METHODS The present review focuses on TMS protocols that either engage the targeted brain circuits or synchronize the stimulation frequency to individual neuronal oscillations to increase the antidepressant efficacy. RESULTS TMS efficacy was found to be enhanced by preliminary or concomitant modulation of the functional state of the targeted brain networks. Conversely, there is not enough evidence of higher efficacy of TMS protocols with individual selection of the stimulation frequency compared to standard ones. LIMITATIONS Most studies included small patient samples. CONCLUSIONS Our results suggest that a good option to enhance rTMS efficacy might be to follow synaptic potentiation and depression rules. V.BACKGROUND Cardiorespiratory fitness (CRF) strongly influences health, but very little is known about the childhood determinants of adult CRF. Our longitudinal study investigated whether childhood psychopathology and socioeconomic status (SES) were related to adult CRF in 1647 Finnish male military conscripts. METHODS Childhood psychopathology was assessed at the age of eight using the Rutter and Children's Depression Inventory questionnaires. Parental education and family structure were used to assess childhood SES. In late adolescence, depressive symptoms were assessed with the Beck Depression Inventory and smoking with a questionnaire. CRF in early adulthood was examined with the Cooper's 12-minute run test. RESULTS General linear models showed that low parental education (p=0.001), depressive symptoms in childhood (p=0.035) and late adolescence, smoking, underweight, and overweight/obesity (all p less then 0.001) independently predicted lower CRF. The interaction between depressive symptoms in childhood and adolescence was significant (p=0.003). In adolescents with depressive symptoms, childhood depressive symptoms (p=0.001) and overweight/obesity (p less then 0.001) predicted lower CRF. In adolescents without depressive symptoms, conduct problems in childhood predicted lower CRF in the initial models, but the effect disappeared after taking into account smoking and body mass index. Mediational analysis confirmed these results. LIMITATIONS We lacked data on physical activity and only studied males at three time-points. CONCLUSIONS Recurrent depression in childhood and adolescence and low SES in childhood predict lower adult CRF. Conduct problems in childhood predict lower CRF, but the effect is mediated by overweight/obesity and smoking. Psychiatric treatment for children and adolescents should promote physical activity, particularly for children with low SES. V.BACKGROUND The concept of melancholia has been associated with psychiatric nosology for centuries. Nevertheless, its definition, relationship to the contemporary concept of Major Depressive Disorder, and clinical implications remain uncertain. METHODS In a total sample of 3211 closely evaluated patient-subjects diagnosed with DSM-5 Major Depressive or Bipolar Disorder and meeting DSM-5 criteria for major depression with melancholic features or not at a European mood disorder center, we matched 1833 for depression severity (baseline HDRS21 score ≥18) and compared rates and ratings of characteristics of interest between the subgroups, using bivariate and multivariate methods. RESULTS Observed prevalence of melancholic features was 35.2% in the 1833 subjects matched for severity, and 21.0% among all 3211 subjects. Diagnosis was highly dependent on depression-severity measured three ways. Very few clinical characteristics differed between melancholic and nonmelancholic subjects matched for illness-severity; more suicidal ideation with melancholic features was a notable exception.

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