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Anatomical education is pivotal for medical students, and innovative technologies like augmented reality (AR) are transforming the field. This study aimed to enhance the interactive features of the "AEducAR" prototype, an AR tool developed by the University of Bologna, and explore its impact on human anatomy learning process in 130 second-year medical students at the International School of Medicine and Surgery of the University of Bologna. An interdisciplinary team of anatomists, maxillofacial surgeons, biomedical engineers, and educational scientists collaborated to ensure a comprehensive understanding of the study's objectives. Students used the updated version of "AEducAR," named "AEducAR 2.0," to study three anatomical topics, specifically the orbit zone, facial bones, and mimic muscles. "AEducAR 2.0" offered two learning activities: one explorative and one interactive. Following each activity, students took a test to assess learning outcomes. Students also completed an anonymous questionnaire to provide background information and offer their perceptions of the activity. Additionally, 10 students participated in interviews for further insights. The results demonstrated that "AEducAR 2.0" effectively facilitated learning and students' engagement. Students totalized high scores in both quizzes and declared to have appreciated the interactive features that were implemented. Moreover, interviews shed light on the interesting topic of blended learning. In particular, the present study suggests that incorporating AR into medical education alongside traditional methods might prove advantageous for students' academic and future professional endeavors. In this light, this study contributes to the growing research emphasizing the potential role of AR in shaping the future of medical education.

Osteoarthritis (OA) is one of the most common disabling pathologies, characterized by joint pain and reduced function, significantly worsening the quality of life. Even if important progresses have been made in OA research, little is yet known about the precise cellular and molecular mechanisms underlying OA. Understanding dysregulated signaling networks and their crosstalk in OA may offer a strong opportunity for the development of combined targeted therapies. Hence, this review highlights the recent findings on the main pathways involved in OA development, including Wnt, Notch, Hedgehog, MAPK, AMPK, and JAK/STAT, providing insights on current targeted therapies in OA patients’ management. The translational potential of this article: The identification of key signaling pathways involved in OA development and the investigation of their signaling crosstalk could pave the way for more effective treatments and improved management of OA patients in the future.

Abstract Most of the patients affected by neuronopathic forms of Mucopolysaccharidosis type II (MPS II), a rare lysosomal storage disorder caused by defects in iduronate-2-sulfatase (IDS) activity, exhibit early neurological defects associated with white matter lesions and progressive behavioural abnormalities. While neuronal degeneration has been largely described in experimental models and human patients, more subtle neuronal pathogenic defects remain still underexplored. In this work, we discovered that the axon guidance receptor Deleted in Colorectal Cancer (Dcc) is significantly dysregulated in the brain of ids mutant zebrafish since embryonic stages. In addition, thanks to the establishment of neuronal-enriched primary cell cultures, we identified defective proteasomal degradation as one of the main pathways underlying Dcc upregulation in ids mutant conditions. Furthermore, ids mutant fish-derived primary neurons displayed higher levels of polyubiquitinated proteins and P62, suggesting a wider defect in protein degradation. Finally, we show that ids mutant larvae display an atypical response to anxiety-inducing stimuli, hence mimicking one of the characteristic features of MPS II patients. Our study provides an additional relevant frame to MPS II pathogenesis, supporting the concept that multiple developmental defects concur with early childhood behavioural abnormalities.

AbstractBackground Colorectal cancer (CRC) screening uptake in many countries has been low and further impacted by the COVID-19 pandemic. General Practitioners (GPs) are key facilitators, however research on their impact on organised CRC screening is still limited.Objectives To evaluate the effectiveness of tailored talks with GPs to increase population uptake of the long-established CRC screening programme in Ancona province, Italy.Methods In this prospective cohort study, one-to-one tailored talks were organised in January 2020 between the GPs of one county of the province (with GPs from other counties as controls) and the screening programme physician-in-chief to discuss the deployment and effectiveness of organised screening. Data was extracted from the National Healthcare System datasets and linear regression was used to assess the potential predictors of CRC screening uptake.Results The mean CRC screening uptake remained stable from 39.9% in 2018–19 to 40.8% in 2020–21 in the 22 GPs of the intervention county, whereas it statistically significantly decreased from 38.7% to 34.7% in the 232 control GPs. In multivariate analyses, belonging to the intervention county was associated with an improved uptake compared to the control counties (+5.1%; 95% Confidence Intervals – CI: 2.0%; 8.1%).Conclusion Persons cared for by GPs who received a tailored talk with a cancer screening specialist avoided a drop in CRC screening adherence, which characterised all other Italian screening programmes during the COVID-19 emergency. If future randomised trials confirm the impact of tailored talks, they may be incorporated into existing strategies to improve population CRC screening uptake.

Au/ZrO2 catalysts (1.5 wt% Au loading) undergone to a final calcination at different temperature (423, 573, 773 and 923 K) to opportunely modulate the Au size were proven to be highly active and selective in furfural oxidative esterification to methyl-2-furoate. The catalysts were tested according to previously optimized reaction conditions, employing O2 as benign oxidant and without any base co-catalyst. The strong dependence of the catalytic activity on the Au size was previously ascribed to the presence of Au clusters able to dissociate O2 and producing atomic O that can activate methanol. However, despite the absence of clusters, also the catalysts containing larger Au nanoparticles were active, even if conversion and selectivity were remarkably lower if compared to the other samples. The nature and the role of Au active sites exposed at the surface of clusters and nanoparticles were then investigated by HR-TEM, CO chemisorption and FTIR spectroscopy of adsorbed CO, molecular oxygen, methanol and furfural to establish structure-activity relationships. Metal nanoparticles can activate oxygen and form superoxo species and atomic O, whereas experiments performed on the pre-hydrated samples revealed that Au perimeter sites at the metal-support interface play a key role in methanol activation during furfural oxidative esterification.

The TAK-003 dengue vaccine was licensed in Europe in December 2022, and the official recommendations from most EU countries are still under formulation. To support policymakers, we performed a meta-analysis to quantify TAK-003’s immunogenicity, efficacy and safety among seronegative and seropositive populations after the administration of one or two vaccine doses. We included trials retrieved from MEDLINE, Scopus and ClinicalTrials.gov. The outcomes were the rates of seroconversion, virologically confirmed dengue fever and serious adverse events after each vaccine dose. Data were combined using random-effect proportion or head-to-head meta-analyses. We retrieved a total of 19 datasets, including >20,000 participants. TAK-003 showed an excellent safety profile, and the immunogenicity after two doses against the four DENV serotypes was ≥90% among both adults and children/adolescents who were either seronegative or seropositive at baseline. A single dose was able to elicit a high immunogenic response among adults (≥70%) and children/adolescents (≥90%). The primary two-dose immunization course halved the risk of all types of virologically confirmed dengue fever among seropositive children/adolescents, but seronegative minors were only protected against the diseases caused by DENV-1 and DENV-2. Overall, the results support the use of TAK-003 for the prevention of dengue fever in the pediatric population of endemic countries. Uncertainties remain on the use of a single vaccine dose in non-endemic countries.

Abstract We evaluated the presence of Ehrlichia spp. in unfed capybara ticks, Amblyomma dubitatum, and explored its association with capybaras density, ticks density and environmental variables. We observed that in the Iberá wetlands ecoregion A. dubitatum is infected by "Candidatus Ehrlichia hydrochoerus” and in a lesser extent with an Ehrlichia species closely related to Ehrlichia chaffeensis. The frequency of "Ca. Ehrlichia hydrochoerus" presence in A. dubitatum was not associated with vector abundance, but the probability of finding "Ca. Ehrlichia hydrochoerus"-infected ticks increased when the density of capybaras was low two months before. We hypothesize that when the density of capybaras decreases, A. dubitatum immature stages may seek out alternative hosts one of which could exhibit high realized reservoir competence for "Ca. Ehrlichia hydrochoerus", leading to an increased prevalence of this ehrlichiae in questing A. dubitatum. High minimum temperatures and high cumulative rainfall in the time period previous to tick collection (15 to 60 days) were positively correlated with the prevalence of "Ca. Ehrlichia hydrochoerus" infection in A. dubitatum. Our results suggest that a combination of factors (both biological and abiotic) could raise the risk of human exposure to tick-borne Ehrlichia in the Iberá wetlands ecoregion.

Pericytes are multipotent cells embedded within the vascular system, primarily surrounding capillaries and microvessels where they closely interact with endothelial cells. These cells are known for their intriguing properties due to their heterogeneity in tissue distribution, origin, and multifunctional capabilities. Specifically, pericytes are essential in regulating blood flow, promoting angiogenesis, and supporting tissue homeostasis and regeneration. These multifaceted roles draw on pericytes’ remarkable ability to respond to biochemical cues, interact with neighboring cells, and adapt to changing environmental conditions. This review aims to summarize existing knowledge on pericytes, emphasizing their versatility and involvement in vascular integrity and tissue health. In particular, a comprehensive view of the major signaling pathways, such as PDGFβ/ PDGFRβ, TGF-β, FOXO and VEGF, along with their downstream targets, which coordinate the behavior of pericytes in preserving vascular integrity and promoting tissue regeneration, will be discussed. In this light, a deeper understanding of the complex signaling networks defining the phenotype of pericytes in healthy tissues is crucial for the development of targeted therapies in vascular and degenerative diseases.

A considerable effort has been spent in the past decades to develop targeted therapies for the treatment of demyelinating diseases, such as multiple sclerosis (MS). Among drugs with free radical scavenging activity and oligodendrocyte protecting effects, Edaravone (Radicava) has recently received increasing attention because of being able to enhance remyelination in experimental in vitro and in vivo disease models. While its beneficial effects are greatly supported by experimental evidence, there is a current paucity of information regarding its mechanism of action and main molecular targets. By using high-throughput RNA-seq and biochemical experiments in murine oligodendrocyte progenitors and SH-SY5Y neuroblastoma cells combined with molecular docking and molecular dynamics simulation, we here provide evidence that Edaravone triggers the activation of aryl hydrocarbon receptor (AHR) signaling by eliciting AHR nuclear translocation and the transcriptional-mediated induction of key cytoprotective gene expression. We also show that an Edaravone-dependent AHR signaling transduction occurs in the zebrafish experimental model, associated with a downstream upregulation of the NRF2 signaling pathway. We finally demonstrate that its rapid cytoprotective and antioxidant actions boost increased expression of the promyelinating Olig2 protein as well as of an Olig2:GFP transgene in vivo. We therefore shed light on a still undescribed potential mechanism of action for this drug, providing further support to its therapeutic potential in the context of debilitating demyelinating conditions.

In the last three decades, the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A considerable amount of interest has been raised about nuclear inositol lipids, mainly because of their role in signaling acting. Here, we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling, both in physiological and pathological conditions.

Abstract Multiple complex intracellular cascades contributing to Hunter syndrome (mucopolysaccharidosis type II) pathogenesis have been recognized and documented in the past years. However, the hierarchy of early cellular abnormalities leading to irreversible neuronal damage is far from being completely understood. To tackle this issue, we have generated two novel iduronate-2-sulfatase (IDS) loss of function human neuronal cell lines by means of genome editing. We show that both neuronal cell lines exhibit no enzymatic activity and increased GAG storage despite a completely different genotype. At a cellular level, they display reduced differentiation, significantly decreased LAMP1 and RAB7 protein levels, impaired lysosomal acidification and increased lipid storage. Moreover, one of the two clones is characterized by a marked decrease of the autophagic marker p62, while none of the two mutants exhibit marked oxidative stress and mitochondrial morphological changes. Based on our preliminary findings, we hypothesize that neuronal differentiation might be significantly affected by IDS functional impairment.

Roma 2 Local Health Authority (ASL) developed a strategy to control the COVID-19 epidemic in Hard-to-reach (HTR) migrant communities, addressing both the containment of clusters in informal settlements and access to COVID-19 vaccination. The strategy was based on a strong collaboration of different services across the ASL and with Non-Governmental Organizations (NGOs). NGOs were involved in the active surveillance, reporting of COVID-19 suspected cases to the ASL and information to the communities. Health interventions (e.g., COVID-19 tests, contact tracing, vaccination) were offered in outreach in HTR communities’ life places. From April 2020 to February 2021, 15 outbreaks were controlled, for a total of over 4,500 persons reached, and 265 COVID-19 cases identified. From July to November 2021, vaccinations were offered in outreach or with dedicated sessions, reaching 1,398 people. This intervention model may lay the foundations for the design of public health strategies, not only aimed at HTR populations.

Introdução: O linfoma de Hodgkin (LH) caracteriza-se como um tumor originado no sistema linfático, oriundo da transformação clonal de células B em malignas, podendo se disseminar pelo sistema linforreticular. O diagnóstico é realizado por meio de exames laboratoriais, da biópsia de gânglios linfáticos e da medula óssea. O tratamento de primeira linha se dá pelo uso da Bleomicina, antibiótico glicopeptídico com atividade antitumoral, entretanto, tal fármaco possui efeitos adversos importantes que devem ser relatados, dentre eles a dermatite flagelada (DF), uma forma peculiar de hiperpigmentação de aspecto linear resultante do processo inflamatório. Objetivo: Relatar o caso de uma paciente portadora de linfoma de Hodgkin com evolução para dermatite flagelada consequente ao tratamento com bleomicina. Material e métodos: Trata-se de uma análise descritiva de um relato de caso e revisão bibliográfica a partir das bases de dados PubMed, Biblioteca Eletrônica Científica Online (SciELO) e protocolos do Ministério da Saúde. Relato de caso: Paciente feminina de 35 anos, diagnosticada com linfoma de hodgkin em tratamento inicial com protocolo ABVD, relata que após primeiro ciclo utilizando bleomicina surgiram lesões hipercrômicas e hiperqueratóticas, com espessura de pele aumentada nas extremidades, em mãos e pés. Relata que após tocar a mão em algum local inicia-se um prurido, com evolução com uma lesão escurecida, elucidando um diagnóstico de dermatite flagelada por bleomicina. Apresentou melhora das lesões com tratamento à base de dexametasona tópica e ureia 10%. Aos exames, PET-CT indisponível na unidade e com TC interin com massa mediastinal. Foi mantido o uso de bleomicina e realizado 4 ciclos para o tratamento do linfoma. Paciente com melhora dos sintomas e com plano para realizar exames complementares e acompanhamento com hematologista. Discussão: O metabolismo da Bleomicina, fármaco utilizado para o tratamento do LH, é realizado pela enzima hidrolase responsável pela produção de radicais livres que rompem as cadeias de DNA das células cancerígenas gerando morte celular. O acúmulo de hidrolases produz uma resposta inflamatória intensa que pode resultar em reações adversas como estomatite, mucosite, anorexia, pneumonite intersticial aguda ou crônica, fibrose pulmonar, hiperqueratose, alopecia, alterações do leito ungueal e a dermatite flagelada. Sob esse viés, a DF apesar de pouco documentada, é uma forma peculiar de hiperpigmentação de aspecto linear, que geralmente acomete tronco, dorso, superfície palmar e plantar. Conclusão: Tendo em vista os argumentos supracitados, conclui-se que a bleomicina é considerada uma droga citostática com potencial desencadeador de efeitos adversos, incluindo dermatite flagelada, sendo assim, é indubitável a necessidade de reconhecimento precoce de possíveis efeitos adversos da bleomicina, para instituição terapêutica adequada, afim de favorecer a continuidade da terapia antitumoral.

Abstract Background miRNAs are small non-coding RNAs that regulate gene expression and are linked to cancer development and progression. miRNA profiles are currently studied as new prognostic factors or therapeutic perspectives. Among hematological cancers, myelodysplastic syndromes at higher risk of evolution into acute myeloid leukemia are treated with hypomethylating agents, like azacitidine, alone or in combination with other drugs, such as lenalidomide. Recent data showed that, during azacitidine and lenalidomide therapy, the concurrent acquisition of specific point mutations affecting inositide signalling pathways is associated with lack or loss of response to therapy. As these molecules are implicated in epigenetic processes, possibly involving miRNA regulation, and in leukemic progression, through the regulation of proliferation, differentiation and apoptosis, here we performed a new miRNA expression analysis of 26 high-risk patients with myelodysplastic syndromes treated with azacitidine and lenalidomide at baseline and during therapy. miRNA array data were processed, and bioinformatic results were correlated with clinical outcome to investigate the translational relevance of selected miRNAs, while the relationship between selected miRNAs and specific molecules was experimentally tested and proven. Results Patients’ overall response rate was 76.9% (20/26 cases): complete remission (5/26, 19.2%), partial remission (1/26, 3.8%), marrow complete remission (2/26, 7.7%), hematologic improvement (6/26, 23.1%), hematologic improvement with marrow complete remission (6/26, 23.1%), whereas 6/26 patients (23.1%) had a stable disease. miRNA paired analysis showed a statistically significant up-regulation of miR-192-5p after 4 cycles of therapy (vs baseline), that was confirmed by real-time PCR analyses, along with an involvement of BCL2, that was proven to be a miR-192-5p target in hematopoietic cells by luciferase assays. Furthermore, Kaplan–Meier analyses showed a significant correlation between high levels of miR-192-5p after 4 cycles of therapy and overall survival or leukemia-free survival, that was stronger in responders, as compared with patients early losing response and non-responders. Conclusions This study shows that high levels of miR-192-5p are associated with higher overall survival and leukemia-free survival in myelodysplastic syndromes responding to azacitidine and lenalidomide. Moreover, miR-192-5p specifically targets and inhibits BCL2, possibly regulating proliferation and apoptosis and leading to the identification of new therapeutic targets.

Influenza is a significant public health concern, with Italy being profoundly impacted annually. Despite extensive vaccination campaigns and cooperative initiatives between the Public Health Departments of Local Healthcare Authorities and family physicians, low vaccine uptake rates persist. This study builds upon the OBVIOUS project, providing an updated picture of influenza vaccine uptake in Italy through a representative sample. A cross-sectional computer-assisted web interviewing (CAWI) survey of 10,001 Italian citizens was conducted between 31 March and 5 June 2023. Our findings underscore the negative impact of a lack of awareness that a person is in a priority group for influenza vaccination (−26.1 percentage points in vaccine uptake) and the profound influence of social circles on vaccination decisions (−5 percentage points when unfavorable). Medical professionals played a pivotal role, with recommendations from family doctors significantly promoting vaccine uptake (+20.2 percentage points). Age, chronic conditions, and socio-demographic factors also influenced vaccination behaviors. For children, parental negative perceptions regarding the flu (−10.4 percentage points) and vaccine safety (−23.4 percentage points) were crucial determinants. The present study emphasizes the need for a comprehensive approach addressing awareness, societal beliefs, and tailored medical advice to enhance vaccination rates and protect public health in Italy.

One of the main aims of the Italian National Healthcare Outcomes Program (Programma Nazionale Esiti, PNE) is the identification of the hospitals with the lowest performance, leading them to improve their quality. In order to evaluate PNE impact for a subset of outcome indicators, we evaluated whether the performance of the hospitals with the lowest scores in 2016 had significantly improved after five years. The eight indicators measured the risk-adjusted likelihood of the death of each patient (adjusted relative risk—RR) 30 days after the admission for acute myocardial infarction, congestive heart failure, stroke, chronic obstructive pulmonary disease, chronic kidney disease, femur fracture or lung and colon cancer. In 2016, the PNE identified 288 hospitals with a very low performance in at least one of the selected indicators. Overall, 51.0% (n = 147) of these hospitals showed some degree of improvement in 2021, and 27.4% of them improved so much that the death risk of their patients fell below the national mean value. In 34.7% of the hospitals, however, the patients still carried a mean risk of death >30% higher than the average Italian patient with the same disease. Only 38.5% of the hospitals in Southern Italy improved the scores of the selected indicators, versus 68.0% in Northern and Central Italy. Multivariate analyses, adjusting for the baseline performance in 2016, confirmed univariate results and showed a significantly lower likelihood of improvement with increasing hospital volume. Despite the overall methodological validity of the PNE system, current Italian policies and actions aimed at translating hospital quality scores into effective organizational changes need to be reinforced with a special focus on larger southern regions.

Lamin B1 is an essential protein of the nuclear lamina that plays a crucial role in nuclear function and organization. It has been demonstrated that lamin B1 is essential for organogenesis and particularly brain development. The important role of lamin B1 in physiological brain development and aging has only recently been at the epicenter of attention and is yet to be fully elucidated. Regarding the development of brain, glial cells that have long been considered as supporting cells to neurons have overturned this representation and current findings have displayed their active roles in neurogenesis and cerebral development. Although lamin B1 has increased levels during the differentiation of the brain cells, during aging these levels drop leading to senescent phenotypes and inciting neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. On the other hand, overexpression of lamin B1 leads to the adult-onset neurodegenerative disease known as Autosomal Dominant Leukodystrophy. This review aims at highlighting the importance of balancing lamin B1 levels in glial cells and neurons from brain development to aging.

BackgroundThe optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin pregnancies with short cervical length at ultrasound or cervical dilatation at physical examination might be associated with a reduced risk of PTB. However, such evidence is based mainly on small studies thus questioning the robustness of these findings. The aim of this systematic review was to determine the role of cervical cerclage in preventing PTB and adverse maternal or perinatal outcomes in twin pregnancies.Methods and findingsKey databases searched and date of last search: MEDLINE, Embase, and CINAHL were searched electronically on 20 April 2023. Eligibility criteria: Inclusion criteria were observational studies assessing the risk of PTB among twin pregnancies undergoing cerclage versus no cerclage and randomized trials in which twin pregnancies were allocated to cerclage for the prevention of PTB or to a control group (e.g., placebo or treatment as usual). The primary outcome was PTB ConclusionsEmergency cerclage for cervical dilation or short cervical length