Decoding social intentions in human prehensile actions: Insights from a combined kinematics-fMRI study

Consistent evidence suggests that the way we reach and grasp an object is modulated not only by object properties (e.g., size, shape, texture, fragility and weight), but also by the types of intention driving the action, among which the intention to interact with another agent (i.e., social intention). Action observation studies ascribe the neural substrate of this `intentional' component to the putative mirror neuron (pMNS) and the mentalizing (MS) systems. How social intentions are translated into executed actions, however, has yet to be addressed. We conducted a kinematic and a functional Magnetic Resonance Imaging (fMRI) study considering a reach-to-grasp movement performed towards the same object positioned at the same location but with different intentions: passing it to another person (social condition) or putting it on a concave base (individual condition). Kinematics showed that individual and social intentions are characterized by different profiles, with a slower movement at the level of both the reaching (i.e., arm movement) and the grasping (i.e., hand aperture) components. fMRI results showed that: (i) distinct voxel pattern activity for the social and the individual condition are present within the pMNS and the MS during action execution; (ii) decoding accuracies of regions belonging to the pMNS and the MS are correlated, suggesting that these two systems could interact for the generation of appropriate motor commands. Results are discussed in terms of motor simulation and inferential processes as part of a hierarchical generative model for action intention understanding and generation of appropriate motor commands

Avaliação de impacto de política de defesa da concorrência:

Contextualização: O artigo analisa o Programa de Leniência da Comissão Europeia e do CADE, destacando seus efeitos positivos e negativos, com base nos conceitos de eficácia e efetividade. Objetivo: O artigo busca empreender uma análise crítica do Programa de Leniência da Comissão Europeia e do CADE. Método: A investigação crítica conduzida pelo artigo utilizou dados empíricos e qualitativos, além de publicações da OCDE, para a verificação do nível de eficácia e efetividade de cada Programa de Leniência. Conclusões: É apresentada uma análise sobre os principais desafios a serem enfrentados na Europa para melhorar o desempenho de sua política de Leniência, como a inflação da Leniência, o uso estratégico da Leniência e os efeitos da Leniência na esfera cível. Em relação ao Brasil, são realizados apontamentos críticos. Conclui-se que os programas de Leniência têm potencial para se tornar um mecanismo de dissuasão mais poderoso a partir do enfrentamento de tais desafios

Decoding social intentions in human prehensile actions : insights from a combined kinematics-fMRI study

Funding: This work was supported by a grant from the MIUR (N. 287713), the FP7: REWIRE project, by Progetto Strategico, Universitaà di Padova (N. 2010XPMFW4) to UC and by SIR grant (Scientific Independence of Young Researchers—N. RBSI141QKX) to LS.Consistent evidence suggests that the way we reach and grasp an object is modulated not only by object properties (e.g., size, shape, texture, fragility and weight), but also by the types of intention driving the action, among which the intention to interact with another agent (i.e., social intention). Action observation studies ascribe the neural substrate of this ‘intentional’ component to the putative mirror neuron (pMNS) and the mentalizing (MS) systems. How social intentions are translated into executed actions, however, has yet to be addressed. We conducted a kinematic and a functional Magnetic Resonance Imaging (fMRI) study considering a reach-to-grasp movement performed towards the same object positioned at the same location but with different intentions: passing it to another person (social condition) or putting it on a concave base (individual condition). Kinematics showed that individual and social intentions are characterized by different profiles, with a slower movement at the level of both the reaching (i.e., arm movement) and the grasping (i.e., hand aperture) components. fMRI results showed that: (i) distinct voxel pattern activity for the social and the individual condition are present within the pMNS and the MS during action execution; (ii) decoding accuracies of regions belonging to the pMNS and the MS are correlated, suggesting that these two systems could interact for the generation of appropriate motor commands. Results are discussed in terms of motor simulation and inferential processes as part of a hierarchical generative model for action intention understanding and generation of appropriate motor commands.Publisher PDFPeer reviewe

Systemic Candidiasis and TLR2 Agonist Exposure Impact the Antifungal Response of Hematopoietic Stem and Progenitor Cells

We have previously demonstrated that Candida albicans induces differentiation of hematopoietic stem and progenitor cells (HSPCs) toward the myeloid lineage both in vitro and in vivo in a TLR2- and Dectin-1-dependent manner, giving rise to functional macrophages. In this work, we used an ex vivo model to investigate the functional consequences for macrophages derived from HSPCs in vivo-exposed to Pam3CSK4 (a TLR2 agonist) or C. albicans infection. Short in vivo treatment of mice with Pam3CSK4 results in a tolerized phenotype of ex vivo HSPC-derived macrophages, whereas an extended Pam3CSK4 treatment confers a trained phenotype. Early during candidiasis, HSPCs give rise to macrophages trained in their response to Pam3CSK4 and with an increased fungicidal activity; however, as the infection progresses to higher fungal burden, HSPC-derived macrophages become tolerized, while their fungicidal capacity is maintained. These results demonstrate that memory-like innate immune responses, already described for monocytes and macrophages, also take place in HSPCs. Interestingly, extended Pam3CSK4 treatment leads to an expansion of spleen HSPCs and myeloid cells, and drastically reduces the fungal burden in the kidney and spleen during systemic C. albicans infection. This protection against tissue invasion is abrogated by immunodepletion of HSPCs, suggesting their protective role against infection in this model. In addition, HSPCs produce in vitro cytokines and chemokines in response to C. albicans and Pam3CSK4, and these secretomes are capable of inducing myeloid differentiation of HSPCs and modulating peritoneal macrophage cytokine responses. Taken together, these data assign an active role for HSPCs in sensing pathogens during infection and in contributing to host protection by diverse mechanisms

Comment on "Which Patients with Obesity Are at Risk for Renal Disease?"

n/

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy

The Life Span Determinant p66Shc Localizes to Mitochondria Where It Associates with Mitochondrial Heat Shock Protein 70 and Regulates Trans-membrane Potential

P66Shc regulates life span in mammals and is a critical component of the apoptotic response to oxidative stress. It functions as a downstream target of the tumor suppressor p53 and is indispensable for the ability of oxidative stress-activated p53 to induce apoptosis. The molecular mechanisms underlying the apoptogenic effect of p66Shc are unknown. Here we report the following three findings. (i) The apoptosome can be properly activated in vitro in the absence of p66Shc only if purified cytochrome c is supplied. (ii) Cytochrome c release after oxidative signals is impaired in the absence of p66Shc. (iii) p66Shc induces the collapse of the mitochondrial trans-membrane potential after oxidative stress. Furthermore, we showed that a fraction of cytosolic p66Shc localizes within mitochondria where it forms a complex with mitochondrial Hsp70. Treatment of cells with ultraviolet radiation induced the dissociation of this complex and the release of monomeric p66Shc. We propose that p66Shc regulates the mitochondrial pathway of apoptosis by inducing mitochondrial damage after dissociation from an inhibitory protein complex. Genetic and biochemical evidence suggests that mitochondria regulate life span through their effects on the energetic metabolism (mitochondrial theory of aging). Our data suggest that mitochondrial regulation of apoptosis might also contribute to life span determination

Epidemiology, management, and outcome of carbapenem-resistant Klebsiella pneumoniae bloodstream infections in hospitals within the same endemic metropolitan area

In the last decade, carbapenem-resistant Klebsiella pneumoniae (CR-Kp) has become endemic in several countries, including Italy. In the present study, we assessed the differences in epidemiology, management, and mortality of CR-Kp bloodstream infection (BSI) in the three main adult acute-care hospitals of the metropolitan area of Genoa, Italy.From January 2013 to December 2014, all patients with CR-Kp BSI were identified through the computerized microbiology laboratory databases of the three hospitals. The primary endpoints of the study were incidence and characteristics of CR-Kp BSI in hospitals within the same endemic metropolitan area. Secondary endpoints were characteristics of CR-Kp BSI in hospitals with and without internal infectious diseases consultants (IDCs) and 15-day mortality.During the study period, the incidence of healthcare-associated CR-Kp BSI in the entire study population was 1.35 episodes per 10,000 patient-days, with substantial differences between the three hospitals. Patients admitted to the two hospital with internal IDCs were more likely to receive post-susceptibility test combined therapy including carbapenems (77% vs. 26%, p <. 0.001), adequate post-susceptibility test therapies (86% vs. 52%, p <. 0.001), and post-susceptibility therapies prescribed by an infectious diseases specialist (84% vs. 14%, p <. 0.001). Overall, the crude 15-days mortality was 26%. In the final multivariable model, only septic shock at BSI presentation was unfavorably and independently associated with 15-days mortality (odds ratio [OR] 6.7, 95% confidence intervals [CI] 2.6-17.6, p <. 0.001), while a protective effect was observed for post-susceptibility test combined therapies including a carbapenem (OR 0.11, 95% CI 0.03-0.43, p = 0.002).Mortality of CR-Kp remains high. Differences in the incidence of CR-Kp BSI were detected between acute-care centers within the same endemic metropolitan area. Efforts should be made to improve the collaboration and coordination between centers, to prevent further diffusion of CR-Kp

Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma

The molecular pathways which promote lung cancer cell features have been broadly explored, leading to significant improvement in prognostic and diagnostic strategies. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have dramatically altered the treatment approach for patients with metastatic non-small cell lung cancer (NSCLC). Latest investigations by using next-generation sequencing (NGS) have shown that other oncogenic driver mutations, believed mutually exclusive for decades, could coexist in EGFR-mutated NSCLC patients. However, the exact clinical and pathological role of concomitant genomic aberrations needs to be investigated. In this systematic review, we aimed to summarize the recent data on the oncogenic role of concurrent genomic alterations, by specifically evaluating the characteristics, the pathological significance, and their potential impact on the treatment approach

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p < 0.001) and younger (p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p < 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes