In Vivo Fate Analysis Reveals the Multipotent and Self-Renewal Features of Embryonic AspM Expressing Cells

Radial Glia (RG) cells constitute the major population of neural progenitors of the mouse developing brain. These cells are located in the ventricular zone (VZ) of the cerebral cortex and during neurogenesis they support the generation of cortical neurons. Later on, during brain maturation, RG cells give raise to glial cells and supply the adult mouse brain of Neural Stem Cells (NSC). Here we used a novel transgenic mouse line expressing the CreERT2 under the control of AspM promoter to monitor the progeny of an early cohort of RG cells during neurogenesis and in the post natal brain. Long term fate mapping experiments demonstrated that AspM-expressing RG cells are multi-potent, as they can generate neurons, astrocytes and oligodendrocytes of the adult mouse brain. Furthermore, AspM descendants give also rise to proliferating progenitors in germinal niches of both developing and post natal brains. In the latter –i.e. the Sub Ventricular Zone- AspM descendants acquired several feature of neural stem cells, including the capability to generate neurospheres in vitro. We also performed the selective killing of these early progenitors by using a Nestin-GFPflox-TK allele. The forebrain specific loss of early AspM expressing cells caused the elimination of most of the proliferating cells of brain, a severe derangement of the ventricular zone architecture, and the impairment of the cortical lamination. We further demonstrated that AspM is expressed by proliferating cells of the adult mouse SVZ that can generate neuroblasts fated to become olfactory bulb neurons

Efficacy of Transcranial Direct Current Stimulation (tDCS) on Balance and Gait in Multiple Sclerosis Patients: A Machine Learning Approach

Transcranial direct current stimulation (tDCS) has emerged as an appealing rehabilitative approach to improve brain function, with promising data on gait and balance in people with multiple sclerosis (MS). However, single variable weights have not yet been adequately assessed. Hence, the aim of this pilot randomized controlled trial was to evaluate the tDCS effects on balance and gait in patients with MS through a machine learning approach. In this pilot randomized controlled trial (RCT), we included people with relapsing–remitting MS and an Expanded Disability Status Scale >1 and <5 that were randomly allocated to two groups—a study group, undergoing a 10-session anodal motor cortex tDCS, and a control group, undergoing a sham treatment. Both groups underwent a specific balance and gait rehabilitative program. We assessed as outcome measures the Berg Balance Scale (BBS), Fall Risk Index and timed up-and-go and 6-min-walking tests at baseline (T0), the end of intervention (T1) and 4 (T2) and 6 weeks after the intervention (T3) with an inertial motion unit. At each time point, we performed a multiple factor analysis through a machine learning approach to allow the analysis of the influence of the balance and gait variables, grouping the participants based on the results. Seventeen MS patients (aged 40.6 ± 14.4 years), 9 in the study group and 8 in the sham group, were included. We reported a significant repeated measures difference between groups for distances covered (6MWT (meters), p < 0.03). At T1, we showed a significant increase in distance (m) with a mean difference (MD) of 37.0 [−59.0, 17.0] (p = 0.003), and in BBS with a MD of 2.0 [−4.0, 3.0] (p = 0.03). At T2, these improvements did not seem to be significantly maintained; however, considering the machine learning analysis, the Silhouette Index of 0.34, with a low cluster overlap trend, confirmed the possible short-term effects (T2), even at 6 weeks. Therefore, this pilot RCT showed that tDCS may provide non-sustained improvements in gait and balance in MS patients. In this scenario, machine learning could suggest evidence of prolonged beneficial effects

Efficacy of Transcranial Direct Current Stimulation (tDCS) on Balance and Gait in Multiple Sclerosis Patients: A Machine Learning Approach

Transcranial direct current stimulation (tDCS) has emerged as an appealing rehabilitative approach to improve brain function, with promising data on gait and balance in people with multiple sclerosis (MS). However, single variable weights have not yet been adequately assessed. Hence, the aim of this pilot randomized controlled trial was to evaluate the tDCS effects on balance and gait in patients with MS through a machine learning approach. In this pilot randomized controlled trial (RCT), we included people with relapsing–remitting MS and an Expanded Disability Status Scale >1 and p p = 0.003), and in BBS with a MD of 2.0 [−4.0, 3.0] (p = 0.03). At T2, these improvements did not seem to be significantly maintained; however, considering the machine learning analysis, the Silhouette Index of 0.34, with a low cluster overlap trend, confirmed the possible short-term effects (T2), even at 6 weeks. Therefore, this pilot RCT showed that tDCS may provide non-sustained improvements in gait and balance in MS patients. In this scenario, machine learning could suggest evidence of prolonged beneficial effects

Circulating non-hematological cells during cardiopulmonary bypass: New findings in cardiac surgery procedures

Background: Several factors have been historically advocated to explain the coagulative and inflammatory disorders following cardiopulmonary bypass (CPB). In this paper, we describe the presence of circulating non-hematological cells, introduced within the bloodstream during CPB. We defined the origin of the cells and tested their impact on coagulation. Methods: We collected peripheral arterial blood samples in twenty consecutive coronary artery bypass graft cases at four different surgical moments and assessed the presence and nature of circulating cells with the use of the CELLSEARCH® Test, immunocytochemistry and immunofluorescence, evaluating the expression of cytokeratin and calretinin. The effect of the circulating non-hematological cells on coagulation was tested in vitro, using the ROTEM assay. Results: A mean of 263.85 ± 57.5 (median 258.5) cells were present in the samples following the suction of blood from the surgical field while all the other samples were negative (zero cells) (p<0.00001). Immunologic tests confirmed the mesothelial origin of the cells. The ROTEM® assay of the blood samples contaminated by the mesothelial cells presented longer clotting times (53.4 ± 8.2 secs 48.3 ± 8.9 sec, p=0.05), longer clot formation times (137.1 ± 31.5 sec vs 111.9 ± 25.2 sec, p=0.009), smaller alfa angle amplitudes (66.7 ± 9.1° vs 71.1 ± 5.1°, p=0.04) and maximum clot firmness times (59.0 ± 5.4 sec vs 61.9 ±4.6 sec, p=0.004) than the controls. Conclusion: The presence of circulating non-hematological cells during CPB with a mesothelial immunophenotype alters in vitro coagulation assays. This finding can help to further understand the pathophysiology of CPB

New indications for the prevention of cardiovascular diseases

Cardiovascular diseases represent the first cause of death and disability in Italy. The main reversible risk factors are high levels of LDL-cholesterol, hypertension, tobacco-smoking, diabetes and/or metabolic syndrome and poor physical activity (at leisure). The prevalence of these risk factors is high in adult Italian population. Cardiovascular diseases prevention should start early in life, with health promotion programs aimed at the acquisition of a healthy lifestyle in communities such as schools and worksites. Besides the "cardiovascular risk score" should be used by general practitioners in order to screen adult population and to lower risk factors levels

Identification of copy number alterations in colon cancer from analysis of amplicon-based Next generation sequencing data

In the publication of this article [1], there is an error in Fig. 7. The minus and plus signals are inverted which impairs understanding of the results described

Aberrant signaling through the HER2-ERK1/2 pathway is predictive of reduced disease-free and overall survival in early stage non-small cell lung cancer (NSCLC) patients

Background: Purpose of this study was to evaluate the contribution of the Extracellular-regulated protein kinase (ERK)-1/2 pathway to oncogenic signaling elicited by the tyrosine kinase receptor HER2 in Non-Small Cell Lung Cancer (NSCLC) and to assess the prognostic value of these oncoproteins in NSCLC patients. Methods: Immunohistochemistry was performed to determine expression and activation of HER2 and ERK1/2 (detected by phosphorylation of Y1248 and T202/Y204, respectively) using Tissue Micro Arrays (TMA) containing matched normal and neoplastic tissues from 132 NSCLC patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of pERK1/2, pHER2 and a combination thereof with clinical-pathological parameters such as age, lymph node status (N), size (T), stage (TNM) and grade. Results: We found that HER2 was overexpressed in 33/120 (27%) and activated in 41/114 (36%) cases; ERK1/2 was activated in 44/102 (43%) cases. A direct association was found between pERK1/2 and pHER2 (23/41; p=0.038). In addition, patients positive for pERK1/2 and for both pHER2 and pERK1/2 showed significantly worse overall survival (OS) and disease-free survival (DFS) compared with negative patients. Univariate and multivariate analysis of patients' survival revealed that positivity for pHER2-pERK1/2 and for pERK1/2 alone were independent prognostic factors of poor survival in NSCLC patients. In particular, this association was significantly important for DFS in stage I+II patients. Conclusion: This study provides evidence that activated ERK1/2 and/or the combined activation of HER2 and ERK1/2 are good indicators of poor prognosis in NSCLC patients, not only in unselected patients but also in early stage disease