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The purpose of the present study was to detect demographic and clinical factors associated with lifetime suicide attempts in Bipolar Disorder (BD). A total of 1673 bipolar patients from different psychiatric departments were compared according to the lifetime presence of suicide attempts on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (presence of suicide attempts) at the univariate analyses, preliminary multiple logistic regression analyses were realized. A final multivariable logistic regression was then performed, considering the presence of lifetime suicide attempts as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. The final multivariable logistic regression analysis showed that an earlier age at first contact with psychiatric services (odds ratio [OR] = 0.97, p < 0.01), the presence of psychotic symptoms (OR = 1.56, p < 0.01) or hospitalizations (OR = 1.73, p < 0.01) in the last year, the attribution of symptoms to a psychiatric disorder (no versus yes: OR = 0.71, partly versus yes OR = 0.60, p < 0.01), and the administration of psychoeducation in the last year (OR = 1.49, p < 0.01) were all factors associated with lifetime suicide attempts in patients affected by BD. In addition, female patients resulted to have an increased association with life-long suicidal behavior compared to males (OR: 1.02, p < 0.01). Several clinical factors showed complex associations with lifetime suicide attempts in bipolar patients. These patients, therefore, require strict clinical monitoring for their predisposition to a less symptom stabilization. Future research will have to investigate the best management strategies to improve the prognosis of bipolar subjects presenting suicidal behavior.

Background: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. Methods: in order to evaluate the long-term effects on the incidence of major adverse events, on the symptom burden, on the quality of life and the mean life expectancy and on the left ventricular (LV) function, we performed a clinical and echocardiographic evaluation together with an assessment using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Heart Failure Model (SHFM) at 10-years follow-up, in the patients cohorts enrolled in the RIGENERA trial. Results: thirty-two patients were eligible for the prospective clinical and echocardiography analyses. A significant reduction in adverse LV remodeling was observed in G-CSF group compared to controls, 9% vs. 48% (p = 0.030). The New York Heart Association (NYHA) functional class was lower in G-CSF group vs. controls (p = 0.040), with lower burden of symptoms and higher quality of life (p = 0.049). The mean life expectancy was significantly higher in G-CSF group compared to controls (15 ± 4 years vs. 12 ± 4 years, p = 0.046. No difference was found in the incidence of major adverse events. Conclusions: this longest available follow-up on G-CSF treatment in patients with severe acute myocardial infarction (AMI) showed that this treatment was safe and associated with a reduction of adverse LV remodeling and higher quality of life, in comparison with standard-of-care treatment.

Heart failure and acute myocardial infarction are conditions that are associated with high morbidity and mortality. Significant dysfunction of the heart muscle can occur as the consequence of end-stage chronic cardiovascular diseases or acute ischemic events that are marked by large infarction area and significant tissue necrosis. Despite the remarkable improvement of conventional treatments, a substantial proportion of patients still develops severe heart failure that can only be resolved by heart transplantation or mechanical device implantation. Therefore, novel approaches based on stem-cell therapy can directly modify the disease process and alter its prognosis. The ability of the stem-cells to modify and repair the injured myocardium is a challenging but intriguing concept that can potentially replace expensive and invasive methods of treatment that are associated with increased risks and significant financial costs. In that sense, granulocyte colony-stimulating factor (G-CSF) seems as an attractive treatment approach. Based on the series of pre-clinical experiments and a limited amount of clinical data, it was demonstrated that G-CSF agents possess the ability to mobilize stem-cells from bone marrow and induce their differentiation into cardiomyocytes or endothelial cells when brought into contact with injured regions of the myocardium. However, clinical benefits of G-CSF use in damaged myocardium remain unclear and are the topic of expert discussion. The main goal of this review is to present relevant and up-to-date evidence on G-CSF therapy use in pre-clinical models and in humans and to provide a rationale for its potential clinical applications in the future.

The regenerative effects of cardiac ckit+stem cells (ckit+CSCs) in acute myocardial infarction (MI) have been studied extensively, but how these cells exert a protective effect on cardiomyocytes is not well known. Growing evidences suggest that in adult stem cells injury triggers inflammatory signaling pathways which control tissue repair and regeneration. Aim of the present study was to determine the mechanisms underlying the cardioprotective effects of ckit+CSCs following transplantation in a murine model of MI. Following isolation and in vitro expansion, cardiac ckit+CSCs were subjected to normoxic and hypoxic conditions and assessed at different time points. These cells adapted to hypoxia as showed by the activation of HIF-1a and the expression of a number of genes, such as VEGF, GLUT1, EPO, HKII and, importantly, of alarmin receptors, such as RAGE, P2X7R, TLR2 and TLR4. Activation of these receptors determined an NFkB-dependent inflammatory and reparative gene response (IRR). Importantly, hypoxic ckit+CSCs increased the secretion of the survival growth factors IGF-1 and HGF. To verify whether activation of the IRR in a hypoxic microenvironment could exert a beneficial effect in vivo, autologous ckit+CSCs were transplanted into mouse heart following MI. Interestingly, transplantation of ckit+CSCs lowered apoptotic rates and induced autophagy in the peri-infarct area; further, it reduced hypertrophy and fibrosis and, most importantly, improved cardiac function. ckit+CSCs are able to adapt to a hypoxic environment and activate an inflammatory and reparative response that could account, at least in part, for a protective effect on stressed cardiomyocytes following transplantation in the infarcted heart.

A ready source of autologous myogenic cells is of vital importance for drug screening and functional genetic studies in Duchenne Muscular Dystrophy (DMD), a rare disease caused by a variety of dystrophin gene mutations. As stem cells (SCs) can be easily and non-invasively obtained from urine specimens, we set out to determine whether they could be myogenic-induced and useful in DMD research. To this end, we isolated stem cells from the urine of two healthy donors and one patient with DMD, and performed surface-marker characterization, myogenic differentiation (MyoD), and then transfection with antisense oligoribonucletoides to test for exon skipping and protein restoration. We demonstrated that native urine-derived stem cells express the full-length dystrophin transcript, and that the dystrophin mutation was retained in DMD patient cells, although the dystrophin protein was detected solely in control cells following myogenic transformation according to the phenotype. Notably, we also showed that treatment with antisense oligoribonucleotide against dystrophin exon 44 induced skipping in both native and MyoD-transformed urine-derived stem cells in DMD, with a therapeutic transcript-reframing effect, as well as visible protein restoration in the latter. Hence MyoD-transformed cells may be a good myogenic model for studying dystrophin gene expression, and native urine stem cells could be used to study the dystrophin transcript, and both diagnostic procedures and splicing modulation therapies in both patients and controls, without invasive and costly collection methods. New, bankable bioproducts from urine stem cells, useful for pre-screening studies and therapeutic applications alike, are also foreseeable following further, more in-depth characterisation.

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The efficacy of bypass surgery in patients with ischemic cardiomyopathy is not easily predictable; preoperative clinical conditions may be similar, but the outcome may differ significantly. We hypothesized that the growth reserve of cardiac stem cells (CSCs) and circulating cytokines promoting CSC activation are critical determinants of ventricular remodeling in this patient population.