Mesangiogenic Progenitor Cells Derived from One Novel CD64brightCD31brightCD14neg Population in Human Adult Bone Marrow

Mesenchymal Stromal Cells (MSCs) have been the object of extensive research for decades, due to their intrinsic clinical value. Nonetheless, the unambiguous identification of a unique in vivo MSC progenitor is still lacking, and the hypothesis that these multipotent cells could possibly arise from different in vivo precursors has been gaining consensus in the last years. We identified a novel multipotent cell population in human adult bone marrow that we firstly named Mesodermal Progenitor Cells (MPCs) for the ability to differentiate toward the mesenchymal lineage while still retaining angiogenic potential. Despite extensive characterization, MPCs positioning within the differentiation pathway and whether they can be ascribed as possible distinctive progenitor of the MSC lineage is still unclear. Here we describe the ex vivo isolation of one novel bone marrow sub-population (Pop#8) with the ability to generate MPCs. Multicolor flow cytometry in combination with either FACS or MACS cell sorting were applied to characterize Pop#8 as CD64brightCD31brightCD14neg. We defined Pop#8 properties in culture, including the potential of Pop#8-derived MPCs to differentiate into MSCs. Gene expression data were suggestive of Pop#8 in vivo involvement in HSC niche constitution/maintenance. Pop#8 resulted over three logs more frequent than other putative MSC progenitors, corroborating the idea that most of the controversies regarding culture expanded MSCs could be the consequence of different culture conditions which select or promote particular sub-populations of precursors

Constitutive Expression of Pluripotency-Associated Genes in Mesodermal Progenitor Cells (MPCs)

Background: We recently characterized a progenitor of mesodermal lineage (MPCs) from the human bone marrow of adults or umbilical cord blood. These cells are progenitors able to differentiate toward mesenchymal, endothelial and cardiomyogenic lineages. Here we present an extensive molecular characterization of MPCs, from bone marrow samples, including 39 genes involved in stem cell machinery, differentiation and cell cycle regulation. Methodology/Principal Findings: MPCs are cytofluorimetrically characterized and quantitative RT-PCR was performed to evaluate the gene expression profile, comparing it with MSCs and hESCs lines. Immunofluorescence and dot-blot analysis confirm qRT-PCR data. MPCs exhibit an increased expression of OCT4, NANOG, SALL4, FBX15, SPP1 and to a lesser extent c-MYC and KLF4, but lack LIN28 and SOX2. MPCs highly express SOX15. Conclusions/Significance: MPCs express many pluripotency-associated genes and show a peculiar Oct-4 molecular circuit. Understanding this unique molecular mechanism could lead to identifying MPCs as feasible, long telomeres, target cells for reprogramming with no up-regulation of the p53 pathway. Furthermore MPCs are easily and inexpensively harvested fro

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

Multicenter Observational Retrospective Study on Febrile Events in Patients with Acute Myeloid Leukemia Treated with Cpx-351 in "Real-Life": The SEIFEM Experience

: In the present study, we aimed to evaluate the absolute risk of infection in the real-life setting of AML patients treated with CPX-351. The study included all patients with AML from 30 Italian hematology centers of the SEIFEM group who received CPX-351 from July 2018 to June 2021. There were 200 patients included. Overall, 336 CPX-351 courses were counted: all 200 patients received the first induction cycle, 18 patients (5%) received a second CPX-351 induction, while 86 patients (26%) proceeded with the first CPX-351 consolidation cycle, and 32 patients (10%) received a second CPX-351 consolidation. A total of 249 febrile events were recorded: 193 during the first or second induction, and 56 after the first or second consolidation. After the diagnostic work-up, 92 events (37%) were classified as febrile neutropenia of unknown origin (FUO), 118 (47%) were classifiable as microbiologically documented infections, and 39 (17%) were classifiable as clinically documented infections. The overall 30-day mortality rate was 14% (28/200). The attributable mortality-infection rate was 6% (15/249). A lack of response to the CPX-351 treatment was the only factor significantly associated with mortality in the multivariate analysis [p-value: 0.004, OR 0.05, 95% CI 0.01-0.39]. Our study confirms the good safety profile of CPX-351 in a real-life setting, with an incidence of infectious complications comparable to that of the pivotal studies; despite prolonged neutropenia, the incidence of fungal infections was low, as was infection-related mortality

Mesodermal Progenitor Cells (MPCs) Differentiate into Mesenchymal Stromal Cells (MSCs) by Activation of Wnt5/Calmodulin Signalling Pathway

Mesenchymal Stromal Cells (MSCs) remain poorly characterized because of the absence of manifest physical, phenotypic, and functional properties in cultured cell populations. Despite considerable research on MSCs and their clinical application, the biology of these cells is not fully clarified and data on signalling activation during mesenchymal differentiation and proliferation are controversial. The role of Wnt pathways is still debated, partly due to culture heterogeneity and methodological inconsistencies. Recently, we described a new bone marrow cell population isolated from MSC cultures that we named Mesodermal Progenitor Cells (MPCs) for their mesenchymal and endothelial differentiation potential. An optimized culture method allowed the isolation from human adult bone marrow of a highly pure population of MPCs (more than 97%), that showed the distinctive SSEA-4+CD105+CD90(neg) phenotype and not expressing MSCA-1 antigen. Under these selective culture conditions the percentage of MSCs (SSEA-4(neg)CD105+CD90(bright) and MSCA-1+), in the primary cultures, resulted lower than 2%.We demonstrate that MPCs differentiate to MSCs through an SSEA-4+CD105+CD90(bright) early intermediate precursor. Differentiation paralleled the activation of Wnt5/Calmodulin signalling by autocrine/paracrine intense secretion of Wnt5a and Wnt5b (p<0.05 vs uncondictioned media), which was later silenced in late MSCs (SSEA-4(neg)). We found the inhibition of this pathway by calmidazolium chloride specifically blocked mesenchymal induction (ID₅₀ =  0.5 µM, p<0.01), while endothelial differentiation was unaffected.The present study describes two different putative progenitors (early and late MSCs) that, together with already described MPCs, could be co-isolated and expanded in different percentages depending on the culture conditions. These results suggest that some modifications to the widely accepted MSC nomenclature are required

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Vara Cível da Infância e Juventude de Belo Horizonte: Cotidiano do trabalho e judicialização das relações familiares

O artigo discute os resultados de entrevistas com o juiz, assessores do gabinete e técnicos da Vara Cível da Infância e Juventude de Belo Horizonte. O estudo pretende captar a lógica em uso pelos agentes que produzem e reproduzem o sistema judicial por meio de suas práticas cotidianas, compreendendo as representações e os significados a respeito do trabalho que realizam e dos desafios e dificuldades enfrentados. A interpretação revelou a tensão entre lógica social/substantiva e lógica jurídica/formal e aponta para a importância do aprofundamento analítico do processo de judicialização das relações familiares em curso. The article Child and Juvenile District Court of Belo Horizonte: The Daily Work Routine and the Judicial­ization of Family Relationships discusses the results of interviews conducted with the judge, court assistants and technicians of the Child and Juvenile District Court of Belo Horizonte. The study intends to capture the logic used by the agents who produce and reproduce the ju­dicial system through their everyday practices, including the representations and meanings in relation to the work they execute and the challenges and difficulties they face. The interpretation revealed the tension between the so­cial/substantive logic and the legal/formal logic and indi­cates the importance of deeper analysis into the ongoing process of judicialization of family relationships.Keywords: Child and Juvenile District Court, judicial work, protective measures, child and juvenile law, judicialization</p

A subjetividade como reflexividade e pluralidade: notas sobre a centralidade do sujeito nos processos sociais

Este ensaio maneja o referencial teórico que fundamenta uma concepção do sujeito como agente reflexivo e plural. Nossa intenção é apresentar alguns autores e correntes que têm contribuído para a formulação e compreensão da pluralidade e reflexividade do sujeito. A partir de uma discussão bibliográfica, tomaremos aspectos das pesquisas de vários autores como evidência de que – quaisquer que sejam as linhas teóricas dos autores citados – vários estudiosos têm apontado para a reflexividade e pluralidade constitutivas do ator social. Concluímos que (a) das pluralidades múltiplas presentes na sociedade contemporânea, pode-se derivar a pluralidade dos processos de subjetivação atinentes aos sujeitos sociais; e que (b) diversos autores apontam para a centralidade desse sujeito reflexivo nos processos sociais nos quais ele se insere

A psicologia social sociológica: percursos, rumos e contemporaneidade de uma tradição teórico-metodológica

http://dx.doi.org/10.5007/1807-1384.2016v13n3p101The article aims to accomplish the task of revisiting the story of a sociological tradition that was born and developed as a social psychology directed to the study of individuals in interaction and posits a concept of "subject" as a capable and reflective agent, which at all times invents and reinvents himself, peopling the social settings, forming and transforming social reality. The tradition of sociological social psychology begins in France with Tarde and Le Bon and was institutionalized in the United States, consisting of the effective model of sociology practiced in its early years there.http://dx.doi.org/10.5007/1807-1384.2016v13n3p101O artigo pretende realizar a tarefa de revisitar a história de uma tradição sociológica que nasceu e se desenvolveu enquanto psicologia social direcionada ao estudo dos indivíduos em interação e que postula uma concepção do “sujeito” como agente capaz e reflexivo, que em todo tempo inventa e reinventa a si mesmo, povoando os cenários sociais, formando e transformando a realidade social. A tradição da psicologia social sociológica inicia-se na França com Tarde e Le Bon e foi institucionalizada nos Estados Unidos, consistindo no efetivo modelo de sociologia praticada em seus primeiros anos naquele país. Dessa tradição fazem parte a Escola de Chicago e o Interacionismo Simbólico.http://dx.doi.org/10.5007/1807-1384.2016v13n3p101En este artículo se pretende llevar a cabo la tarea de revisar la historia de una tradición sociológica que nació y se desarrolló como una psicología social dirigido al estudio de los individuos en interacción y postula un concepto de "sujeto" como agente capaz y reflexivo, que en todo momento inventa y se reinventa, poblando los escenarios sociales, la formación y la transformación de la realidad social. La tradición de la psicología social sociológica comienza en Francia con Tarde y Le Bon y se institucionalizó en los Estados Unidos, constituyéndose en el modelo eficaz de la sociología practicada en sus primeros años en ese ípas. De esta tradición son parte de la Escuela de Chicago y el Interaccionismo Simbólico