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Background: Three-dimensional cell culture systems hold great promise for bridging the gap between in vitro cell-based model systems and small animal models to study tissue biology and disease. Among 3D cell culture systems, stem-cell-derived spheroids have attracted significant interest as a strategy to better mimic in vivo conditions. Cardiac stem cell/progenitor (CSC)-derived spheroids (CSs) provide a relevant platform for cardiac regeneration. Methods: We compared three different cell culture scaffold-free systems, (i) ultra-low attachment plates, (ii) hanging drops (both requiring a 2D/3D switch), and (iii) agarose micro-molds (entirely 3D), for CSC-derived CS formation and their cardiomyocyte commitment in vitro. Results: The switch from a 2D to a 3D culture microenvironment per se guides cell plasticity and myogenic differentiation within CS and is necessary for robust cardiomyocyte differentiation. On the contrary, 2D monolayer CSC cultures show a significant reduced cardiomyocyte differentiation potential compared to 3D CS culture. Forced aggregation into spheroids using hanging drop improves CS myogenic differentiation when compared to ultra-low attachment plates. Performing CS formation and myogenic differentiation exclusively in 3D culture using agarose micro-molds maximizes the cardiomyocyte yield. Conclusions: A 3D culture system instructs CS myogenic differentiation, thus representing a valid model that can be used to study adult cardiac regenerative biology.

There is an increasing interest in understanding the connection between the immune and cardiovascular systems, which are highly integrated and communicate through finely regulated cross-talking mechanisms. Recent evidence has demonstrated that the immune system does indeed have a key role in the response to cardiac injury and in cardiac regeneration. Among the immune cells, macrophages appear to have a prominent role in this context, with different subtypes described so far that each have a specific influence on cardiac remodeling and repair. Similarly, there are significant differences in how the innate and adaptive immune systems affect the response to cardiac damage. Understanding all these mechanisms may have relevant clinical implications. Several studies have already demonstrated that stem cell-based therapies support myocardial repair. However, the exact role that cardiac macrophages and their modulation may have in this setting is still unclear. The current need to decipher the dual role of immunity in boosting both heart injury and repair is due, at least for a significant part, to unresolved questions related to the complexity of cardiac macrophage phenotypes. The aim of this review is to provide an overview on the role of the immune system, and of macrophages in particular, in the response to cardiac injury and to outline, through the modulation of the immune response, potential novel therapeutic strategies for cardiac regeneration.

Abstract Background Long non-coding RNAs (lncRNAs) represent a diverse class of RNAs involved in the regulation of various physiological and pathological cellular processes, including transcription, intracellular trafficking, and chromosome remodeling. LncRNAs deregulation was linked to the development and progression of various cancer types, such as acute leukemias. In this context, lncRNAs were also evaluated as a novel class of biomarkers for cancer diagnosis and prognosis. Here, we analyzed TEX41 in childhood B cell acute lymphoid leukemia (B-ALL). Methods Total RNA was extracted from pediatric B-ALL patients (at diagnosis and after induction of therapy) and from healthy subjects. Total RNA was also extracted from different leukemia cell line models. The expression level of TEX41 was evaluated by q-RT-PCR. Also, the dataset deposited by St. Jude Children’s Research Hospital was consulted. Furthermore, the silencing of TEX41 in RS4;11 cell line was obtained by 2′-Deoxy, 2′Fluroarabino Nucleic Acids (2′F-ANAs) Oligonucleotides, and the effect on cell proliferation was evaluated. Cell cycle progression and its regulators were analyzed by flow cytometry and immunoblotting. Results We exploited the St Jude Cloud database and found that TEX41 is a lncRNA primarily expressed in the case of B-ALL (n = 79) while its expression levels are low/absent for T-cell ALL (n = 25) and acute myeloid leukemia (n = 38). The association of TEX41 with B-ALL was confirmed by real-time PCR assays. TEX41 disclosed increased expression levels in bone marrow from patients with B-ALL at diagnosis, while its expression levels became low or absent when retested in Bone Marrow cells of the same patient after 1 month of induction therapy. Also, silencing experiments performed on RS4;11 cells showed that TEX41 downregulation impaired in vitro leukemic cell growth determining their arrest in the G2-M phase and the deregulation of cell cycle proteins. Conclusions Our findings highlight that TEX41 is an upregulated lncRNA in the case of B-ALL and this feature makes it a novel potential biomarker for the diagnosis of this leukemia subtype in pediatric patients. Finally, TEX41 expression seems to be critical for leukemic proliferation, indeed, silencing experiments targeting TEX41 mRNA in the RS4;11 cell line hampered in vitro cell growth and cell cycle progression, by inducing G2-M arrest as confirmed propidium iodide staining and by the upregulation of p53 and p21 proteins.

Resumo: Descreve-se a construção de um instrumento para medida de atitudes de estudantes de Medicina frente a seis aspectos relevantes ao exercício da profissão: 1) aspectos psicológicos e emocionais presentes em doenças orgânicas e mentais; 2) situações relacionadas à morte; 3) atenção primária à saúde; 4) doença mental; 5) contribuição do médico ao avanço científico da Medicina; 6) outros aspectos da atuação médica. Desenvolveu-se uma escala do tipo Likert, com cinco opções de respostas, cuja versão final contém 52 itens. Os procedimentos para validação aparente e de conteúdo do instrumento, bem como a análise fatorial dos dados de sua aplicação preliminar a um total de 196 estudantes de Medicina, permitam eliminar itens inadequados e comprovar que a escala é dotada de alta consistência interna (coeficiente alfa de Cronbach = 0,86). O trabalho desenvolvidos resultou, portanto, na definição de um instrumento com índices adequadas de validade e de fidedignidade para a medida das atitudes de estudantes de Medicina. Aplicação futuras desta escala poderão trazer subsídios para melhor compreensão do processo da formação médica, bem como fundamentar discussões que levem a seu aprimoramento.

Summary: Heart failure secondary to cardiomyocyte loss and/or dysfunction is the number one killer worldwide. The field of myocardial regeneration with its far-reaching primary goal of cardiac remuscularization and its hard-to-accomplish translation from bench to bedside, has been filled with ups and downs, steps forward and steps backward, controversies galore and, unfortunately, scientific scandals. Despite the present morass in which cardiac remuscularization is stuck in, the search for clinically effective regenerative approaches remains keenly active. Starting with a concise overview of the still highly debated regenerative capacity of the adult mammalian heart, we focus on the main interventions, that have reached or are close to clinical use, critically discussing key findings, successes, and failures. Finally, some promising and innovative approaches for myocardial repair/regeneration still at the pre-clinical stage are discussed to offer a holistic view on the future of myocardial repair/regeneration for the prevention/management of heart failure in the clinical scenario. Funding: This research was funded by Grants from the Ministry of University and Research PRIN2015 2015ZTT5KB_004; PRIN2017NKB2N4_005; PON-AIM – 1829805-2.

AimsHuman epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression.Methods and ResultsWe enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (P < 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P < 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent with microbial DNA sequences.ConclusionsOur study revealed a unique immune signature of the epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 complex, in acute coronary syndrome patients at their first event, paving the way for epitope-driven therapeutic strategies.

Abstract Background The determination of CA 15-3 is useful for monitoring breast cancer patients. Several retrospective studies determined CA 15-3 levels in frozen samples to evaluate the sensitivity and specificity of novel biomarkers in relation to breast cancer; however, freeze-thaw cycles, as well as preanalytical variables before sample storage, are not always reported. Here, we analyzed the current scientific literature to identify possible critical aspects related to CA 15-3 determination in frozen-stored human serum/plasma samples. Methods We obtained data from 4 different bibliographic databases: Web of Science, Embase, PubMed, and Cochrane Library. We followed the PRISMA guidelines to screen and select the eligible articles discussed in the final revision. Results Initially, 674 scientific papers were evaluated, and after the application of the screening and eligibility criteria, 18 studies were included in the qualitative synthesis. The analysis reported an important level of heterogeneity concerning the preanalytical phase before sample storage. Conclusion Although advances in healthcare have been achieved using certified workflows in medical diagnostics, standardized preanalytical processes are not always applied when referring to frozen-stored biosamples. Biobanks will guarantee the best possible conditions for the storage of human biological samples to be used in clinical research. The use of certified bioresources will favor the optimal development and introduction of new disease biomarkers.

Appropriate dilated cardiomyopathy (DCM) animal models are highly desirable considering the pathophysiological and clinical heterogeneity of DCM. Genetically modified mice are the most widely and intensively utilized research animals for DCM. However, to translate discoveries from basic science into new and personalized medical applications, research in non-genetically based DCM models remains a key issue. Here, we characterized a mouse model of non-ischemic DCM induced by a stepwise pharmacologic regime of Isoproterenol (ISO) high dose bolus followed by a low dose systemic injection of the chemotherapy agent, 5-Fluorouracil (5-FU). C57BL/6J mice were injected with ISO and, 3 days after, were randomly assigned to saline or 5-FU. Echocardiography and a strain analysis show that ISO + 5FU in mice induces progressive left ventricular (LV) dilation and reduced systolic function, along with diastolic dysfunction and a persistent global cardiac contractility depression through 56 days. While mice treated with ISO alone recover anatomically and functionally, ISO + 5-FU causes persistent cardiomyocyte death, ensuing in cardiomyocyte hypertrophy through 56 days. ISO + 5-FU-dependent damage was accompanied by significant myocardial disarray and fibrosis along with exaggerated oxidative stress, tissue inflammation and premature cell senescence accumulation. In conclusions, a combination of ISO + 5FU produces anatomical, histological and functional cardiac alterations typical of DCM, representing a widely available, affordable, and reproducible mouse model of this cardiomyopathy.

The study of deformation signals associated with seismicity in alluvial plain areas is a challenging topic that, however, is increasingly studied thanks to the great aid given by remote sensing techniques that exploit Synthetic Aperture Radar (SAR) data. This study focuses on the determination of the deformation field within the Emilia-Romagna Region (northern Italy), in the area comprising Modena, Reggio Emilia, and Parma cities. SAR data acquired along both orbits during the Sentinel-1 and Cosmo-SkyMed satellite missions were processed with the Small Baseline Subset interferometric technique from June 2012, after the serious seismic swarm of May 2012, to January 2022, just before the two earthquakes occurred in February 2022. The results, validated with Global Navigation Satellite System measurements, do not highlight displacements correlated with the seismicity but, thanks to their high spatial resolution, it was possible to discriminate areas affected by noticeable subsidence phenomena: (i) the highly industrialized areas located north of the municipalities of Reggio Emilia and Modena cities and (ii) a sector of the high-speed railway sited north of the Reggio Emilia city centre, close to the Reggio Emilia AV Mediopadana station. Here we show that, at least since 2012, the latter area is affected by subsidence which can be related to the secondary consolidation process of the fine soils loaded by the railway embankment. The piezometric level analysis also suggests that the lowering of the groundwater table could accelerate the subsidence rate, affecting the stability of infrastructures in highly populated and industrialized areas.

In this work, the shallow geothermal heat-exchange potential of a coastal plain in southern Italy, the Sant’Eufemia plain (Calabria region), was evaluated. Stratigraphic and hydrogeological data and thermophysical properties of the main geological formations of the area have been averaged over the first 100 m of subsoil to define the thermal conductivity, the specific heat extraction rates of the ground and the geothermal potential of the area (MWh·y−1) for both cooling and heating modes. The investigation revealed that the crystalline bedrock and the saturated conditions of the sedimentary infill mainly control the heat-exchange potential. The range of the geothermal potential in the investigated Sant’Eufemia plain is 3.61–10.56 MWh·y−1 and 3.72–11.47 MWh·y−1 for heating and cooling purposes, respectively. The average depth drilled to supply a standard domestic power demand of 5.0 kW is ~90 m for heating and ~81 m for cooling modes. The different depth also drives the final drilling costs, which range from EUR 3200 to 8700 for the heating mode and from EUR 2800 to 7800 for the cooling mode. Finally, the mean values of drilling depth and costs for both heating and cooling modes are provided for the main municipalities and strategic sites.

Background: Paediatric acute B-cell lymphoblastic leukaemia is the most common cancer of the paediatric age. Although the advancement of scientific and technological knowledge has ensured a huge step forward in the management of this disease, there are 15%–20% cases of recurrence leading to serious complications for the patient and sometimes even death. It is therefore necessary to identify new and increasingly personalised biomarkers capable of predicting the degree of risk of B-ALL in order to allow the correct management of paediatric leukaemia patients. Methods: Starting from our previously published results, we validate the expression level of LINC00958 in a cohort of 33 B-ALL and 9 T-ALL childhood patients, using in-silico public datasets as support. Expression levels of LINC00958 in B-ALL patients stratified by risk (high risk vs. standard/medium risk) and who relapsed 3 years after the first leukaemia diagnosis were also evaluated. Results: We identified the lncRNA LINC00958 as a biomarker of B-ALL, capable of discriminating B-ALL from T-ALL and healthy subjects. Furthermore, we associated LINC00958 expression levels with the disease risk classification (high risk and standard risk). Finally, we show that LINC00958 can be used as a predictor of relapses in patients who are usually stratified as standard risk and thus not always targeted for marrow transplantation. Conclusions: Our results open the way to new diagnostic perspectives that can be directly used in clinical practice for a better management of B-ALL paediatric patients. [ABSTRACT FROM AUTHOR]

Resumo: Por quatro anos consecutivos, avaliaram-se as atitudes de formandos em Medicina frente a aspectos relevantes ao exercício dessa profissão. Como as turmas avaliadas correspondiam a dois diferentes currículos, foi avaliado o possível efeito de uma reformulação curricular sobre as atitudes dos estudantes. Empregou-se escala do tipo Likert validada e testada, com 52 itens agrupados em seis fatores. Não houve diferenças consideráveis entre as quatro turmas, o que permitiu agrupar os resultados dos quatro anos em um conjunto único de 317 graduandos. Os resultados revelaram atitudes predominantemente positivas frente a 1) aspectos emocionais em doenças orgânicas; 2) atenção primária à saúde; 3) outros aspectos da atuação médica na comunidade. Foram detectadas atitudes indefinidas ou conflitantes frente a ;4) morte ;5) doença mental; 6) contribuição do médico ao avanço científico de Medicina. Não houve diferenças significativas entre as turmas correspondentes aos dois currículos de graduação. Concluiu-se que os graduandos em Medicina apresentam atitudes positivas frente a três dois seis aspectos abordados, o que indica consecução dos correspondentes objetivos educacionais. A ausência de diferenças entre os graduandos das duas estruturas curriculares sugere que as tendências atitudinais detectadas refletem valores mais arraigados na cultura da instituição. A ausência de atitudes claramente positivas frente a alguns dos aspectos avaliados segura a necessidade de intervenções educacionais específicas.

Patients with severe iron deficiency, malabsorption or intolerance to oral iron are frequently treated with intravenous iron replacement. We report the case of a 42-year-old woman with non-erosive oligoarticular arthritis with antiparietal cell antibodies and iron deficiency anemia secondary to menorrhagia and unresponsive to oral iron preparations. She was treated with an intravenous infusion of ferric gluconate. After the first infusion of 125 mg (in 250 mL saline), she developed transient pain in her knee and wrist joints. When the dose was subsequently halved, the patient showed no adverse symptoms in the next four infusions and had normalized hemoglobin levels and iron indices. However, after a subsequent 125 mg ferric gluconate infusion she developed severe leg pain, muscular and joint stiffness, and functional impairment of her hands, right foot, and ankle. Laboratory tests showed a progressive increase in creatine kinase, transaminase, and C-reactive protein that normalized several days after the infusion. Although rhabdomyolysis is not reported among endovenous iron-induced adverse events, our findings suggest that intravenous iron infusions might have increased free iron generation promoting oxidative joint and muscular injury, which would explain the joint pain and stiffness, and rhabdomyolysis. Greater attention should be paid to the more frequent cases of myalgia occurring after iron infusion, which may underlie a rhabdomyolytic event requiring clinical observation.

Resumo: Avaliou-se a eficácia de um novo currículo introduzido na Faculdade de Medicina de Ribeirão Preto (Universidade de São Paulo) com base no desempenho dos graduandos em provas objetivas que abrangeram os domínios cognitivo, psicomotor e afetivo. A avaliação foi aplicada durante seis anos a 222 formando do antigo currículo e 261 graduandos do novo currículo. Todos se submeteram a um prova de conhecimentos médicos gerais (testes de múltipla escolha) e à avaliação de atitudes (escala psicométrica). Grupos de 18 a 20 estudantes foram sorteados para provas práticas de competências clínicas (pacientes reais e “padronizados”) e psicomotoras (manequins e animais anestesiados), realizadas por exames clínico objetivo estruturado (OSCE). Habilidades cognitivas complexas foram avaliadas com a técnica patient management problem. Os resultados mostraram melhora significativa do desempenho, associada ao novo currículo, nas provas de conhecimentos e de competências psicomotoras. Porém, com relação às habilidades cognitivas complexas, o antigo currículo foi superior em muitos aspectos. Não houve diferenças significativas entre os dois currículos na maioria das competências clínicas testadas e em nenhum dos aspectos avaliados com a escala de atitudes.

Biomimetic apatites exhibit a high reactivity allowing ion substitutions to modulate their in vivo response. We developed a novel approach combining several bioactive ions in a spatially controlled way in view of subsequent releases to address the sequence of events occurring after implantation, including potential microorganisms’ colonization. Innovative micron-sized core-shell particles were designed with an external shell enriched with an antibacterial ion and an internal core substituted with a pro-angiogenic or osteogenic ion. After developing the proof of concept, two ions were particularly considered, Ag+ in the outer shell and Cu2+ in the inner core. In vitro evaluations confirmed the cytocompatibility through Ag-/Cu-substituting and the antibacterial properties provided by Ag+. Then, these multifunctional “smart” particles were embedded in a polymeric matrix by freeze-casting to prepare 3D porous scaffolds for bone engineering. This approach envisions the development of a new generation of scaffolds with tailored sequential properties for optimal bone regeneration.

The main cause of morbidity and mortality in diabetes mellitus (DM) is cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here, we compared these two models for their effects on cardiac structure, function and transcriptome. Different doses of STZ and diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and nonobese sex- and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR and RNA-seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM affected left ventricular function and myocardial performance differently. T1DM displayed exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis, along with increased cardiac oxidative stress, CM DNA damage and senescence, when compared to T2DM in mice. T1DM and T2DM affected the whole cardiac transcriptome differently. In conclusion, the STZ-induced T1DM and T2DM mouse models showed significant differences in cardiac remodeling, function and the whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.

Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases sharing common risk factors, such as obesity, hyperinsulinemia, and inflammation, with underlying mechanisms including endothelial dysfunction, inflammation, oxidative stress, and metabolic alterations. Cardiovascular benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors observed in diabetic and non-diabetic patients are also related to their cardiac-specific, SGLT-independent mechanisms, in addition to the metabolic and hemodynamic effects. In search of the possible underlying mechanisms, a research campaign has been launched proposing varied mechanisms of action that include intracellular ion homeostasis, autophagy, cell death, and inflammatory processes. Moreover, the research focus was widened toward cellular targets other than cardiomyocytes. At the moment, intracellular sodium level reduction is the most explored mechanism of direct cardiac effects of SGLT2 inhibitors that mediate the benefits in heart failure in addition to glucose excretion and diuresis. The restoration of cardiac Na+ levels with consequent positive effects on Ca2+ handling can directly translate into improved contractility and relaxation of cardiomyocytes and have antiarrhythmic effects. In this review, we summarize clinical trials, studies on human cells, and animal models, that provide a vast array of data in support of repurposing this class of antidiabetic drugs.

Current bioinformatics workflows for PIWI-interacting RNA (piRNA) analysis focus primarily on germline-derived piRNAs and piRNA-clusters. Frequently, they suffer from outdated piRNA databases, questionable quantification methods, and lack of reproducibility. Often, pipelines specific to miRNA analysis are used for the piRNA research in silico. Furthermore, the absence of a well-established database for piRNA annotation, as for miRNA, leads to uniformity issues between studies and generates confusion for data analysts and biologists. For these reasons, we have developed WIND ( Workflow for p IRNAs a Nd beyon D), a bioinformatics workflow that addresses the crucial issue of piRNA annotation, thereby allowing a reliable analysis of small RNA sequencing data for the identification of piRNAs and other small non-coding RNAs (sncRNAs) that in the past have been incorrectly classified as piRNAs. WIND allows the creation of a comprehensive annotation track of sncRNAs combining information available in RNAcentral, with piRNA sequences from piRNABank, the first database dedicated to piRNA annotation. WIND was built with Docker containers for reproducibility and integrates widely used bioinformatics tools for sequence alignment and quantification. In addition, it includes Bioconductor packages for exploratory data and differential expression analysis. Moreover, WIND implements a 'dual' approach for the evaluation of sncRNAs expression level quantifying the aligned reads to the annotated genome and carrying out an alignment-free transcript quantification using reads mapped to the transcriptome. Therefore, a broader range of piRNAs can be annotated, improving their quantification and easing the subsequent downstream analysis. WIND performance has been tested with several small RNA-seq datasets, demonstrating how our approach can be a useful and comprehensive resource to analyse piRNAs and other classes of sncRNAs.

Abstract Background Vascular Ehlers–Danlos syndrome (vEDS) is a heritable connective tissue disorder caused by defects in the type III collagen protein. It is generally considered the most severe form of Ehlers–Danlos syndrome (EDS) due to an increased risk of spontaneous artery or organ rupture. vEDS has an extremely heterogeneous presentation and muscle rupture is considered a minor diagnostic criterium. Methods A patient with a long history of inconclusive examinations and investigations was referred to our unit. The clinical picture was mainly characterized by muscle ruptures, whereas the cardiovascular involvement was limited to mitral regurgitation. We performed a panel analysis of genes associated with inheritable heart diseases using the TruSight Cardio kit (Illumina). A skin biopsy was then performed for functional studies to analyze the different forms of collagen molecules produced in vitro by cutaneous fibroblasts. Results The patient presented the novel variant c.3478A>G (p.Ile1160Val) in COL3A1 (NM_000090.3), whose pathogenicity was supported by biochemical analysis of type III collagen. Conclusion In this report, we describe a case of vEDS with predominant and severe musculoskeletal involvement. Our findings provide insight into genetic variants and clinical expression of vEDS, broadening the clinical scenario of the syndrome.