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BackgroundMedical simulations have emerged as a valuable tool in anatomical-medical training, allowing healthcare professionals to gain hands-on experience in a controlled and safe environment. One such simulation platform is SimLife®, which uses the Pulse for Practice (P4P) system to enable realistic restoration of airflow (“re-ventilation”) and blood flow (“revascularization”) in bodies donated to science.ObjectiveThis study aimed to evaluate the feasibility of introducing SimLife® technology in Italy. Additionally, it assessed the impact of this technology across various medical specialties, utilizing a minimal number of donated bodies.MethodsThe study utilized the existing body donation program and dissection rooms at the Anatomy Center of the University of Bologna. 62 participants from 13 medical specialties performed simulations using the SimLife® P4P platform. Post-simulation, structured interviews were used to collect data on the interventions performed, participant perceptions of the technology’s usefulness, enjoyment, and willingness to repeat the experience, as well as critical issues encountered.ResultsKey findings include that 86% of participants rated SimLife® technology as extremely useful for post-lauream training, while 84% found it highly beneficial for team-building activities. A total of 31 interventions were successfully performed across various anatomical regions, with participants reporting high satisfaction and a strong willingness to repeat the simulation experience.ConclusionThe findings support the effectiveness of SimLife® technology for body donor re-ventilation and revascularization, reinforcing its value for medical training across various specialties.

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.

Background: Oral and implant surgery represent highly specialized fields within dentistry that require a deep understanding of complex anatomical structures, together with practical hands-on experience. The present review examines common trends in oral and implant surgery training, focusing on how traditional methods like donated body dissection coexist with different and modern educational tools, and highlights the pros and cons of the different approaches in order to optimize training outcomes. Methods: A systematic literature search was carried out using the databases PubMed and Cochrane Library including the last 10 years of published articles about training in oral surgery and implantology. Starting from a total of 1319 studies, 47 were included to be carefully evaluated, and 20 studies were finally selected for this narrative review. The studies utilize methodologies such as randomized controlled trials (RCTs), cross-sectional surveys, case–control studies, and systematic reviews. The results were thematically organized, highlighting key quantitative outcomes and drawing connections between the different educational approaches. Results: From the narrative review, it emerged that oral and implant surgery training requires a careful balance between traditional methods, such as donated human body dissection, and modern technological advancements like virtual simulations and synthetic models. While animal and synthetic models have specific uses, their application remains limited in replicating the full complexity of human anatomy. These last technologies offer flexibility and expanded access to education but do not substitute for the hands-on experience gained through donated human body dissection. Conclusions: As educational institutions continue to evolve their training programs, ensuring access to human body dissection remains of paramount importance. Combining the strengths of both traditional and modern approaches may help optimize oral and implant surgery education, enhancing student preparedness without overlooking the critical value of direct anatomical experience.

Variants in CRYAB can lead to desmin-related (cardio-)myopathy (DRM), a genetic muscle disorder with no curative treatment available. We introduced a homozygous CRYAB c.358G > A (p.Arg120Gly) mutation, which is established for the study of DRM in mice, into a donor human induced pluripotent stem cell (hiPSC) line. Control and mutant hiPSCs were tested for karyotype integrity and pluripotency marker expression. HiPSCs could be differentiated into endoderm, ectoderm and cardiomyocytes as a mesodermal derivative in vitro. CRYABhom hiPSC-derived cardiomyocytes developed intracellular CRYAB aggregates, which is a hallmark of DRM. This newly created mutant can be utilized to study DRM and cardiac proteinopathy in a human context.

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.

Abstract Lamin A, a main constituent of the nuclear lamina, is involved in mechanosignaling and cell migration through dynamic interactions with the LINC complex, formed by the nuclear envelope proteins SUN1, SUN2 and the nesprins. Here, we investigated lamin A role in Ewing Sarcoma (EWS), an aggressive bone tumor affecting children and young adults. In patients affected by EWS, we found a significant inverse correlation between LMNA gene expression and tumor aggressiveness. Accordingly, in experimental in vitro models, low lamin A expression correlated with enhanced cell migration and invasiveness and, in vivo, with an increased metastatic load. At the molecular level, this condition was linked to altered expression and anchorage of nuclear envelope proteins and increased nuclear retention of YAP/TAZ, a mechanosignaling effector. Conversely, overexpression of lamin A rescued LINC complex organization, thus reducing YAP/TAZ nuclear recruitment and preventing cell invasiveness. These effects were also obtained through modulation of lamin A maturation by a statin-based pharmacological treatment that further elicited a more differentiated phenotype in EWS cells. These results demonstrate that drugs inducing nuclear envelope remodeling could be exploited to improve therapeutic strategies for EWS.

Polyphosphoinositides (PPIns) are signalling messengers representing less than five per cent of the total phospholipid concentration within the cell. Despite their low concentration, these lipids are critical regulators of various cellular processes, including cell cycle, differentiation, gene transcription, apoptosis and motility. PPIns are generated by the phosphorylation of the inositol head group of phosphatidylinositol (PtdIns). Different pools of PPIns are found at distinct subcellular compartments, which are regulated by an array of kinases, phosphatases and phospholipases. Six of the seven PPIns species have been found in the nucleus, including the nuclear envelope, the nucleoplasm and the nucleolus. The identification and characterisation of PPIns interactor and effector proteins in the nucleus have led to increasing interest in the role of PPIns in nuclear signalling. However, the regulation and functions of PPIns in the nucleus are complex and are still being elucidated. This review summarises our current understanding of the localisation, biogenesis and physiological functions of the different PPIns species in the nucleus.

Abstract Patients with late‐stage Kellgren‐Lawrence knee osteoarthritis received a single intra‐articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells (BM‐MSCs) in a phase I/IIa trial to assess safety and efficacy using a broad toolset of analytical methods. Besides safety, outcomes included patient‐reported outcome measures (PROMs): Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); contrast‐enhanced magnetic resonance imaging (MRI) for cartilage morphology (Whole Organ MRI Scores [WORMS]), collagen content (T2 scores), and synovitis; and inflammation and cartilage turnover biomarkers, all over 12 months. BM‐MSCs were characterized by a panel of anti‐inflammatory markers to predict clinical efficacy. There were no serious adverse events, although four patients had minor, transient adverse events. There were significant overall improvements in KOOS pain, symptoms, quality of life, and WOMAC stiffness relative to baseline; the 50 million dose achieved clinically relevant improvements across most PROMs. WORMS and T2 scores did not change relative to baseline. However, cartilage catabolic biomarkers and MRI synovitis were significantly lower at higher doses. Pro‐inflammatory monocytes/macrophages and interleukin 12 levels decreased in the synovial fluid after MSC injection. The panel of BM‐MSC anti‐inflammatory markers was strongly predictive of PROMs over 12 months. Autologous BM‐MSCs are safe and result in significant improvements in PROMs at 12 months. Our analytical tools provide important insights into BM‐MSC dosing and BM‐MSC reduction of synovial inflammation and cartilage degradation and provide a highly predictive donor selection criterion that will be critical in translating MSC therapy for osteoarthritis. Stem Cells Translational Medicine 2019;8:746&757

Polyphosphoinositides (PPIns) and their modulating enzymes are involved in regulating many important cellular functions including proliferation, differentiation or gene expression, and their deregulation is involved in human diseases such as metabolic syndromes, neurodegenerative disorders and cancer, including Acute Myeloid Leukemia (AML). Given that PPIns regulating enzymes are highly druggable targets, several studies have recently highlighted the potential of targeting them in AML. For instance many inhibitors targeting the PI3K pathway are in various stages of clinical development and more recently other novel enzymes such as PIP4K2A have been implicated as AML targets. PPIns have distinct subcellular organelle profiles, in part driven by the specific localisation of enzymes that metabolise them. In particular, in the nucleus, PPIns are regulated in response to various extracellular and intracellular pathways and interact with specific nuclear proteins to control epigenetic cell state. While AML does not normally manifest with as many mutations as other cancers, it does appear in large part to be a disease of dysregulation of epigenetic signalling and many novel therapeutics are aimed at reprogramming AML cells toward a differentiated cell state or to one that is responsive to alternative successful but limited AML therapies such as ATRA. Here, we propose that by combining bioinformatic analysis with inhibition of PPIns pathways, especially within the nucleus, we might discover new combination therapies aimed at reprogramming transcriptional output to attenuate uncontrolled AML cell growth. Furthermore, we outline how different part of a PPIns signalling unit might be targeted to control selective outputs that might engender more specific and therefore less toxic inhibitory outcomes.

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.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by peripheral blood cytopenia and abnormal myeloproliferation, as well as a variable risk of evolution into acute myeloid leukemia (AML). The nucleus is a highly organized organelle with several distinct domains where nuclear inositides localize to mediate essential cellular events. Nuclear inositides play a critical role in the modulation of erythropoiesis or myelopoiesis. Here, we briefly review the nuclear structure, the localization of inositides and their metabolic enzymes in subnuclear compartments, and the molecular aspects of nuclear inositides in MDS.