Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo

Human umbilical cord blood (CB) has attracted much attention as a reservoir for functional hematopoietic stem and progenitor cells, and, recently, as a source of blood-borne fibroblasts (CB-BFs). Previously, we demonstrated that bone marrow stromal cell (BMSC) and CB-BF pellet cultures make cartilage in vitro. Furthermore, upon in vivo transplantation, BMSC pellets remodelled into miniature bone/marrow organoids. Using this in vivo model, we asked whether CB-BF populations that express characteristics of the hematopoietic stem cell (HSC) niche contain precursors that reform the niche. CB ossicles were regularly observed upon transplantation. Compared with BM ossicles, CB ossicles showed a predominance of red marrow over yellow marrow, as demonstrated by histomorphological analyses and the number of hematopoietic cells isolated within ossicles. Marrow cavities from CB and BM ossicles included donor-derived CD146-expressing osteoprogenitors and host-derived mature hematopoietic cells, clonogenic lineage-committed progenitors and HSCs. Furthermore, human CD34+ cells transplanted into ossicle-bearing mice engrafted and maintained human HSCs in the niche. Our data indicate that CB- BFs are able to recapitulate the conditions by which the bone marrow microenvironment is formed and establish complete HSC niches, which are functionally supportive of hematopoietic tissue

Establishment of bone marrow and hematopoietic niches in vivo by reversion of chondrocyte differentiation of human bone marrow stromal cells

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Métodos para Evaluar la Exposición a Contaminantes Plásticos en Procellariiformes: Revisión y Estandarización de Protocolos

A presença de resíduos antropogênicos em águas oceânicas e sua ingestão por aves marinhas tem sido alvo de um crescente número de estudos. Os Procellariiformes são particularmente suscetíveis à ingestão de plástico, uma vez que se alimentam preferencialmente de pequenas presas na superfície da água, onde os plásticos tendem a flutuar e se acumular. Após revisão bibliográfica e aplicação prática de técnicas em campo e laboratório, apresentamos um protocolo padronizado de amostragem para a avaliação da ingestão de plásticos por Procellariiformes que inclui recomendações para opções de tipos e fontes de amostras, além de adaptações à coleta para atender a diversos objetivos de pesquisa. As amostras podem ser coletadas de animais mortos oriundos da captura incidental em atividades de pesca; encalhes de praia; aves mortas nas colônias ou centros de reabilitação; animais vivos em colônias ou centros de reabilitação; ou amostragem não invasiva por meio das fezes, bolos alimentares e ovos não eclodidos. Além disso, sugerimos tipos de análises possíveis, materiais necessários e rotinas de limpeza para evitar a contaminação durante a coleta e processamento. O uso de protocolos padronizados aumenta a consistência, comparabilidade e a reprodutibilidade, permitindo comparações entre estudos em escalas temporais e espaciais diferenciadas.The presence of anthropogenic debris in oceanic waters and their ingestion by seabirds has been the subject of a growing number of studies. Procellariiformes are particularly susceptible to plastic ingestion, since they feed preferably on small prey on the waters’ surface, where plastics tend to float and accumulate. Following an extensive literature review and practical application of techniques in the field and laboratory by the authors, we present a set of guidelines for sampling Procellariiformes to assess plastic ingestion. The guidelines suggest several sample type and sample source options, offering ways to approach different research objectives and overcome logistics constraints. Samples may be collected from dead beach-cast birds or those caught incidentally by fisheries. It is also possible to collect samples from live or dead animals in their breeding sites, rehabilitation centers, or noninvasively through feces, boluses and non-hatched eggs. In addition, we recommend analysis methods, necessary materials and cleaning routines to avoid contamination during collection and processing. The use of standardized protocols increases consistency and repeatability, allowing comparisons between investigations for a number of species, as well as the detection of large-scale spatiotemporal patterns.Los estudios sobre la presencia de residuos antropogénicos en el mar y su ingesta por aves marinas se han incrementado en las últimas décadas. Los Procellariiformes son particularmente susceptibles a la ingesta de plásticos debido a que se alimentan preferentemente de presas sobre la superficie del mar, donde los plásticos tienden a flotar y acumularse. Luego de una extensa revisión bibliográfica y la aplicación práctica de técnicas en el laboratorio y el campo, presentamos protocolos estandarizados para la colecta de muestras para evaluar la ingesta de plásticos en Procellariiformes. Estos protocolos sugieren una variedad de tipos y fuentes de muestras y metodologías de colecta de acuerdo a diferentes objetivos de investigación. Las muestras pueden ser colectadas de aves muertas encontradas en la playa o capturadas incidentalmente en pesquerías; de aves vivas o muertas en colonias reproductivas y centros de rehabilitación; o de manera no-invasiva en el caso de fecas, bolos y huevos no eclosionados. Además, recomendamos métodos de análisis, insumos necesarios y rutinas de limpieza para evitar la contaminación durante la colecta y procesamiento de muestras. La implementación de protocolos estandarizados para la colecta y el análisis de muestras favorece la consistencia y repetibilidad de los estudios, permitiendo la comparación de los resultados y la detección de patrones espacio-temporales a gran escala.Fil: Gallo, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentina. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Oficina de Senasa. Centro Regional Patagonia Sur.; ArgentinaFil: Uhart, Marcela María. University of California at Davis; Estados UnidosFil: Pereira, Alice. Projeto Albatroz; BrasilFil: Pereira Serafini, Patricia. Centro Nacional de Pesquisa e Conservação de Aves Silvestres; Brasil. Instituto Chico Mendes de Conservação da Biodiversidade; Brasi

Evaluation of an interprofessional education intervention in partnership with patient educators

Background and aim of the work: Patient involvement in interprofessional education is a novel approach to building collaborative and empathic skills in students. However, this area of teaching is lacking in rigorous studies. The project aimed to evaluate whether an interprofessional education intervention in partnership with patient educators (IPE-PE) would increase readiness for interprofessional learning and empathy in health sciences students. Methods: This is the report of a didactic innovation project. Participants included 310 undergraduate health sciences students who took part in an IPE-PE intervention. Data were collected before and after the training, using the Readiness for Interprofessional Learning Scale (RIPLS) and the Jefferson Scale of Empathy-Health Professions Student version ( JSE-HPS). Only at the end of the intervention, a data collection form was administered to explore the value of the patient educator in the training and to investigate the socio-demographic variables. Results: The mean age of participants was 21±3.2 SD years and 76% were female. The Wilcoxon signed-rank test showed significant changes from before to after the IPE-PE in the RIPLS total score (m=42.7±5.8 SD vs 44.62±5.9 SD, z=-4.168, P<0.001) and in the JSE-HPS total score (m=112.7±12.5 SD vs 116.03±12.8 SD, z=-4.052, P<0.001). Conclusions: Our students reported that IPE-PE had helped them to become more effective healthcare team members, to think positively about other professionals, and to gain an empathic understanding of the perspective of the person being cared for. The results of the project confirm that the intervention promoted the development of empathy, fostering a better understanding of the patient-centred perspective

Stabilire connessioni. Vi raccontiamo “Ampio Spettro*”. Un progetto per contrastare l’antibiotico resistenza

A gap seems to exist between clinical guidelines and the prescribing practices of General Practitioners with respect to the use of antibiotics. This is true especially in patients presenting with symptoms and signs of upper respiratory tract infections. The Broad-Spectrum project was established to ad- dress this issue: at the one hand, different research methods are applied to understand the determi- nants of inappropriate prescriptions of antibiotics; at the other hand, a nationwide distance learning course will be distributed among Italian General Practitioners with the aim of changing the actual prescribing habits of physicians, contemporarily addressing uncertainties faced by clinicians when planning their daily work during the COVID-19 pandemic. Further aims of the project are to spread a culture of research and evidence-based teaching among the younger generations of General Practitioners, and to create a group of young professionals trained in medical research and teaching.We want to tell the story of this non-profit experience, carried out by a group of young doctors in training in General Practice - which was characterized by the continuous construction of connections: connections between clinicians and the academy and other institutions and associations such as the National Institute of Health, the Local Medical Boards, the Regional Health Trust of Sardinia and the Italian Society of Medical Education (SIPeM), between research and training, between the communi- cative and clinical aspects General Practice. Two features of this project are valuable. The first is that the identification of problems was done by the involved professionals who sought the methodological and institutional collaboration of others in the healthcare system to collect and analyse data perceived as important for daily practice with patients. The second is the choice of a training that is not flattened on a formalization of traditional teaching but is aimed to foster a change in everyday practice through reflection and independent thinking on the basis of context-specific evidence.Partendo dall’osservazione della distanza esistente tra le indicazioni delle linee guida e la pratica prescrit- tiva dei medici rispetto all’utilizzo degli antibiotici in persone che presentano sintomi/segni da infezioni di grado lieve è stato messo a punto un progetto su due assi: un asse di ricerca che andasse a studiare le cause profonde del problema dell’inappropriata prescrizione di antibiotici e un asse formativo che avesse l’obiettivo di modificare le abitudini prescrittive dei medici. Ciò cercando contemporaneamente di dipanare le grandi incertezze che i clinici devono affrontare quotidianamente nella loro pratica durante la pandemia da COVID-19. Altri obiettivi sono stati diffondere una cultura della ricerca tra le giovani generazioni dei medici di medi- cina generale, e creare un gruppo di giovani professionisti che apprendessero i rudimenti della formazione nel progettare e attuare il percorso formativo stesso. Vogliamo narrare la storia di quest’esperienza no profit, voluta e portata avanti da un gruppo piccolo di giovani medici in formazione in Medicina Generale -che è stata caratterizzata dalla costruzione continua di connessioni: connessioni tra l’area professionale e l’accademia e altre istituzioni come l’Istituto Superiore di Sanità, la ATS Sardegna e SIPeM, tra ricerca e formazione, tra gli aspetti comunicativi del lavoro del medico e quelli clinici. Di pregio in questo progetto due aspetti: il primo è l’individuazione dei problemi sul campo da parte dei professionisti coinvolti e che possano avvalersi, nella raccolta e nell’analisi dei dati, del contributo meto- dologico di istituzioni indipendenti. Il secondo la scelta di una formazione che non sia appiattita su una formalizzazione di didattica tradizionale ma sia rivolta al cambiamento e alla costruzione di un professio- nista capace di riflessione e pensiero indipendente, che lavori sempre sulla base di evidenze contesto specifiche

AML alters bone marrow stromal cell osteogenic commitment via Notch signaling

IntroductionAcute myeloid leukemia (AML) is a highly heterogeneous malignancy caused by various genetic alterations and characterized by the accumulation of immature myeloid blasts in the bone marrow (BM). This abnormal growth of AML cells disrupts normal hematopoiesis and alters the BM microenvironment components, establishing a niche supportive of leukemogenesis. Bone marrow stromal cells (BMSCs) play a pivotal role in giving rise to essential elements of the BM niche, including adipocytes and osteogenic cells. Animal models have shown that the BM microenvironment is significantly remodeled by AML cells, which skew BMSCs toward an ineffective osteogenic differentiation with an accumulation of osteoprogenitors. However, little is known about the mechanisms by which AML cells affect osteogenesis.MethodsWe studied the effect of AML cells on the osteogenic commitment of normal BMSCs, using a 2D co-culture system.ResultsWe found that AML cell lines and primary blasts, but not normal hematopoietic CD34+ cells, induced in BMSCs an ineffective osteogenic commitment, with an increase of the early-osteogenic marker tissue non-specific alkaline phosphatase (TNAP) in the absence of the late-osteogenic gene up-regulation. Moreover, the direct interaction of AML cells and BMSCs was indispensable in influencing osteogenic differentiation. Mechanistic studies identified a role for AML-mediated Notch activation in BMSCs contributing to their ineffective osteogenic commitment. Inhibition of Notch using a γ-secretase inhibitor strongly influenced Notch signaling in BMSCs and abrogated the AML-induced TNAP up-regulation.DiscussionTogether, our data support the hypothesis that AML infiltration produces a leukemia-supportive pre-osteoblast-rich niche in the BM, which can be partially ascribed to AML-induced activation of Notch signaling in BMSCs

The effects of primary care monitoring strategies on COVID-19 related hospitalisation and mortality: a retrospective electronic medical records review in a northern Italian province, the MAGMA study

Background: Most symptomatic SARS-CoV-2 infections produce mild to moderate symptoms. Although most patients are managed in the outpatient setting, little is known about the effect of general practitioners' (GP) management strategies on the outcomes of COVID-19 outpatients in Italy. Objectives: Describe the management of Italian GPs of SARS-CoV-2 infected adult patients and explore whether GP active care and monitoring are associated with reducing hospitalisation and death. Methods: Retrospective observational study of SARS-CoV-2 infected adult outpatients managed by GPs in Modena (Italy) from March 2020 to April 2021. Information on management and monitoring strategies, patients' socio-demographic characteristics, comorbidities, and outcomes (hospitalisation and death due to COVID-19) were retrieved through an electronic medical record review and analysed descriptively and through multiple logistic regression. Results: Out of the 5340 patients from 46 GPs included in the study, 3014 (56%) received remote monitoring, and 840 (16%) had at least one home visit. More than 85% of severe or critical patients were actively monitored (73% daily) and 52% were visited at home. Changes over time in patients' therapeutic management were observed in concordance with the guidelines' release. Active daily remote monitoring and home visits were strongly associated with reduced hospitalisation rate (OR 0.52, 95% CI 0.33-0.80 and OR 0.50, 95% CI 0.33-0.78 respectively). Conclusion: GPs effectively managed an increasing number of outpatients during the first waves of the pandemic. Active monitoring and home visits were associated with reduced hospitalisation in COVID-19 outpatients

Effectiveness of patients’ involvement in a medical and nursing pain education programme: a protocol for an open-label randomised controlled trial including qualitative data

Introduction Pain is a multidimensional experience that varies among individuals and has a significant impact on their health. A biopsychosocial approach is recommended for effective pain management; however, health professionals’ education is weak on this issue. Patient involvement is a promising didactic methodology in developing a more holistic perspective, however there is a lack of reliable evidence on this topic. The aim of the present study is to evaluate the effectiveness of patient involvement in pain education in undergraduate medicine and nursing students. Methods and analysis An open-label randomised controlled trial including qualitative data will be conducted. After an introductory lesson, each student will be randomly assigned to the intervention group, which includes an educational session conducted by a patient–partner along with an educator, or to the control group in which the session is exclusively conducted by an educator. Both sessions will be carried out according to the Case-Based Learning approach. Primary outcomes will be students’ knowledge, attitudes, opinions and beliefs about pain management, whereas the secondary outcome will be students’ satisfaction. The Pain Knowledge and Attitudes (PAK) and Chronic Pain Myth Scale (CPMS) will be administered preintervention and postintervention to measure primary outcomes. Students’ satisfaction will be measured by a questionnaire at the end of the session. Two focus groups will be conducted to evaluate non-quantifiable aspects of learning. Ethics and dissemination The protocol of this study was approved by the independent Area Vasta Emilia Nord ethics committee

On the importance of primary and community healthcare in relation to global health and environmental threats:Lessons from the COVID-19 crisis

In the course of the COVID-19 pandemic, it has become clear that primary healthcare systems play a critical role in clinical care, such as patient screening, triage, physical and psychological support and also in promoting good community advice and awareness in coordination with secondary healthcare and preventive care. Because of the role of social and environmental factors in COVID-19 transmission and burden of disease, it is essential to ensure that there is adequate coordination of population-based health services and public health interventions. The COVID-19 pandemic has shown the primary and community healthcare (PCHC) system's weaknesses worldwide. In many instances, PCHC played only a minor role, the emphasis being on hospital and intensive care beds. This was compounded by political failures, in supporting local community resilience. Placing community building, social cohesion and resilience at the forefront of dealing with the COVID-19 crisis can help align solutions that provide a vision of a € planetary health'. This can be achieved by involving local well-being and participation in the face of any pervasive health and environmental crisis, including other epidemics and large-scale ecological crises. This paper proposes that PCHC should take on two critical roles: first, to support local problem-solving efforts and to serve as a partner in innovative approaches to safeguarding community well-being; and second, to understand the local environment and health risks in the context of the global health perspective. We see this as an opportunity of immediate value and broad consequence beyond the control of the COVID-19 pandemic.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality