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The development of obesity is associated with substantial modulation of adipose tissue (AT) structure. The plasticity of the AT is reflected by its remarkable ability to expand or reduce in size throughout the adult lifespan, which is linked to the development of its vasculature. This increase in AT vasculature could be mediated by the differentiation of adipose tissue-derived stem cells (ASCs) into endothelial cells (ECs) and form new microvasculature. We have already shown that microRNA (miRNA)-145 regulates the differentiation of ASCs into EC-like (ECL) cells. Here, we investigated whether ASCs-differentiation into ECs is governed by a miRNAs signature that depends on fat depot location and /or the metabolic condition produced by obesity. Human ASCs, which were obtained from white AT by surgical procedures from lean and obese patients, were induced to differentiate into ECL cells. We have identified that miRNA-29b-3p in both subcutaneous (s)ASCs and visceral ASCs and miRNA-424-5p and miRNA-378a-3p in subcutaneous (s)ASCs are involved in differentiation into EC-like cells. These miRNAs modulate their pro-angiogenic effects on ASCs by targeting FGFR1, NRP2, MAPK1, and TGF-β2, and the MAPK signaling pathway. We show for the first time that miRNA-29b-3p upregulation contributes to ASCs’ differentiation into ECL cells by directly targeting TGFB2 in both sASCs and visceral ASCs. Moreover, our results reveal that, independent of sASCs’ origin (obese/lean), the upregulation of miRNA-378a-3p and the downregulation of miRNA-424-5p inhibit MAPK1 and overexpress FGFR1 and NRP2, respectively. In summary, both the adipose depot location and obesity affect the differentiation of resident ASCs through the expression of specific miRNAs.

La propuesta se enmarca en la asignatura de tercer curso de didáctica II de la educación física del Grado en Ciencias de la Actividad Física y el Deportes de una Universidad de Cataluña. El objetivo es primeramente ofrecer un modelo de formación competencial al alumnado del grado. También, con esta idea competencial, se propone un producto final que ha desarrollado dicho alumnado, con un recurso pedagógico, a modo de repertorio, para docentes consistente en unidades didácticas competenciales para la educación física en secundaria. La metodología se ha basado en el trabajo experimental en el aula y la reflexión del alumnado y figura docente. Los resultados han permitido formar al alumnado, y futuros docentes, en el ámbito de la programación educativa, siguiendo competencial, y que se adapte a la normativa vigente. Además, como producto final, se ofrece un repositorio virtual, a partir de una página web, con 76 unidades didácticas en acceso abierto, para cualquier centro educativo de secundaria, adaptándolo a las particularidades de cada docente, institución y localidad. Se propone que estas metodologías en los grados puedan ampliarse para que el propio estudiante se inicie en la creación y divulgación de propuestas didácticas. Palabras clave: Agenda 2030; formación docente; unidad didáctica; educación física; competencias; biblioteca virtual; inclusión; tecnologías Abstract. The proposal is part of the third-year subject of didactics II of physical education of the Degree in Physical Activity and Sports Sciences of an University of Catalonia. The objective is firstly to offer a model of competency training to the students of the degree. Also, with this competency idea, a final product that has been developed by said students is proposed, with a pedagogical resource, as a repertoire, for teachers consisting of competency teaching units for physical education in secondary school. Methodology has been based on experimental work in the classroom and the reflection of students and teachers. Results have allowed to train students, and future teachers, in the field of educational programming, following a competency idea, and that adapts to current regulations. In addition, as a final product, a virtual repository is offered, based on a web page, with 76 teaching units in open access, for any secondary school, adapting it to the particularities of each teacher, institution and locality. It is proposed that these methodologies in the degrees can be extended so that the student himself begins in the creation and dissemination of didactic proposals. Keywords: 2030 Agenda; teacher training, teaching unit; physical education; skills; virtual library; inclusion; technologies

Los ámbitos de ocupación profesional de los ciclos formativos para la familia de actividades físicas y deportivas son muy amplios. Por todo ello hay que proponer un buen modelo de prácticas externas que se relacionen con las competencias que las titulaciones ofrecen y que el futuro profesional deberá desarrollar. El objetivo de la presente aportación es desarrollar una propuesta de los diferentes espacios de prácticas educativas para el alumnado de ciclos formativos de la familia de actividades físicas y deportivas para obtener experiencias de calidad. La metodología se ha basado en el análisis de expertos en el ámbito de los documentos, decretos y orientaciones que regulan y guían los estudios con la metodología Delphi. Los resultados muestran la posibilidad y necesidad de ofrecer prácticas que potencien el desarrollo de diferentes habilidades, en diferentes ámbitos y ofrezcan aprendizajes globales. La formación profesional dual puede ser una opción pertinente para relacionar alumnado, institución y mundo laboral. Abstract. The fields of professional occupation for the family of physical and sports activities in the training cycles are very wide. For all these reasons, it is necessary to propose a good model of external internships that are related to the competences that the degrees offer. The objective of the proposal is to develop a proposal of the different spaces of educational practices for the students of formative cycles of the family of physical and sports activities to obtain quality experiences. The methodology has been based on the analysis of experts in the field of documents, decrees and guidelines that regulate the studies with Delphi metodology. The results show the possibility and need to offer practices that enhance the development of different skills, in different areas and offer global learning. Dual vocational training can be a relevant option to relate student, institution, and the world of work.

We have recently shown that in ischemic tissue, the hypoxic endothelial cells (EC) release extracellular microvesicles (EMVs) that are rich in tissue factor (TF). These TF-EMVs induce monocyte (Mo) homing to the ischemic zone, their differentiation into EC-like cells, and the formation of new blood vessels increasing tissue perfusion. In addition to membrane proteins, EMVs contain noncoding RNAs that can modulate cellular signaling pathways in the recipient cells. Here, we have investigated whether miRNA contained into secreted EMVs may be transferred into Mo where they could modulate EC-like cell differentiation and angiogenic responses. Our results indicated that EMVs released from activated ECs contain high levels of miR-126 and that the levels are directly proportional to TF expression in EMVs. Interestingly, miR-126 is transferred to Mo when they are incubated with TF-EMVs. Increased levels of miR-126 in Mo do not promote EC-like cell differentiation but regulate angiogenesis by targeting several components of the VEGF pathway, as SPRED1 and PI3KR2. Our findings reveal that activated ECs secrete EMVs carrying miR-126, which can modulate Mo reprogramming of angiogenic genes.

Vancomycin is used for the treatment of bone and joint infections (BJI), but scarce information is available about its pharmacokinetic/pharmacodynamic (PK/PD) characteristics. We aimed to identify the risk factors associated with the non-achievement of an optimal PK/PD target in the first therapeutic drug monitoring (TDM). Methods: A retrospective study was conducted in a tertiary hospital from January 2020 to January 2022. Patients with BJI and TDM of vancomycin on day 2 of treatment were included. Initial vancomycin fixed doses (1 g every 8 h or 12 h) was decided by the responsible doctors. According to TDM results, dosage adjustments were performed. An AUC24h/MIC < 400 mg × h/L, between 400 and 600 mg × h/L and >600 mg × h/L, were defined as suboptimal, optimal and supratherapeutic, respectively. Patients were grouped into these three categories. Demographic, clinical and PK characteristics were compared between groups. Nephrotoxicity at the end of treatment was assessed. Results: A total of 94 patients were included: 22 (23.4%), 42 (44.7%) and 30 (31.9%) presented an infratherapeutic, optimal and supratherapeutic PK/PD targets, respectively. A younger age and initial vancomycin dose 40 mg/kg/day were associated with overexposure. The nephrotoxicity rate was 22.7%. More than 50% of patients did not achieve an optimal PK/PD. Considering age, baseline serum-creatinine and body weight, TDM is required to readily achieve an optimal and safe exposure.

Abstract Background The composition and function of the adipose tissue covering the heart are poorly known. In this study, we have investigated the epicardial adipose tissue (EAT) covering the cardiac ventricular muscle and the EAT covering the left anterior descending artery (LAD) on the human heart, to identify their resident stem cell functional activity. Methods EAT covering the cardiac ventricular muscle was isolated from the apex (avoiding areas irrigated by major vessels) of the heart (ventricular myocardium adipose tissue (VMAT)) and from the area covering the epicardial arterial sulcus of the LAD (PVAT) in human hearts excised during heart transplant surgery. Adipose stem cells (ASCs) from both adipose tissue depots were immediately isolated and phenotypically characterized by flow cytometry. The different behavior of these ASCs and their released secretome microvesicles (MVs) were investigated by molecular and cellular analysis. Results ASCs from both VMAT (mASCs) and the PVAT (pASCs) were characterized by the expression of CD105, CD44, CD29, CD90, and CD73. The angiogenic-related genes VEGFA, COL18A1, and TF, as well as the miRNA126-3p and miRNA145-5p, were analyzed in both ASC types. Both ASCs were functionally able to form tube-like structures in three-dimensional basement membrane substrates. Interestingly, pASCs showed a higher level of expression of VEGFA and reduced level of COL18A1 than mASCs. Furthermore, MVs released by mASCs significantly induced human microvascular endothelial cell migration. Conclusion Our study indicates for the first time that the resident ASCs in human epicardial adipose tissue display a depot-specific angiogenic function. Additionally, we have demonstrated that resident stem cells are able to regulate microvascular endothelial cell function by the release of MVs.

Background: Skin local reactions to mRNA COVID-19 vaccines have been linked to the use of vaccine excipients. The aim of the study is to evaluate the role of skin testing excipients in delayed skin reactions due to mRNA COVID-19 vaccines. Methods: Skin testing among a group of healthcare workers with skin reactions due to mRNA vaccines was performed. Patch testing and intradermal testing (IDT) with polyethylene glycol (PEG)-400, PEG-2000, trometamol, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine were performed. Healthcare workers without skin reactions to vaccines were used for skin testing as controls. Results: Thirty-one healthcare workers (from a total of 4315 vaccinated healthcare workers) experienced cutaneous adverse vaccine reactions. Skin testing was performed in sixteen of the healthcare workers (11 delayed large local reactions (DLLR) and 5 widespread reactions). Positive IDT for PEG-2000 1% in DLLR was seen in 10 (90.9%) patients, in comparison with one (16.6%) individual with a delayed widespread reaction. Delayed positive IDT reactions for PEG-2000 1% on day 2 were observed in three (27.3%) patients with DLLR. Patch testing of the excipients was negative. Among 10 controls, only one exhibited a transient positive IDT reaction to PEG-2000 1%. Conclusions: Immediate and delayed reactions to IDT are frequently detected in patients with DLLR. The observation of positive delayed intradermal reactions to PEG disclosed only in patients with DLLR reinforces a possible role of PEG in the development of these reactions. Skin testing of other excipients is of little importance in clinical practice.

INTRODUCCIÓN. Las tradiciones son elementos identitarios de un pueblo, y los juegos de los niños son parte de esta tradición. El objeto de estudio del presente artículo es la cometa. Se realiza a partir de un esbozo histórico, folklórico y lúdico, y el análisis de sus usos y simbolismos de dicho instrumento. MÉTODO. La metodología se ha basado en el análisis de obras de finales del s. XIX e inicios del s. XX que tratan la historia, simbolismo y construcción del juego. Se centra el estudio en la aportación del folklorista Joan Amades, que detalla los diferentes significados y usos de este juguete. Las fuentes secundarias relacionadas con la cometa contextualizan la aportación. A la vez, se ha llevado a cabo una aplicación en el aula, para el posible trabajo competencial, con un grupo de alumnos de ciclos formativos de la familia de actividades físicas. RESULTADOS. La propuesta permite hacer ver al alumnado los juegos existentes en el pasado, la dificultad en su construcción, la práctica y la aplicación al siglo XXI. DISCUSIÓN. Se evidencia que es necesaria una reflexión en torno al pasado y una recuperación de las tradiciones si se quiere mantener la identidad de los pueblos.

BackgroundIn addition to the lack of COVID-19 diagnostic tests for the whole Spanish population, the current strategy is to identify the disease early to limit contagion in the community.AimTo determine clinical factors of a poor prognosis in patients with COVID-19 infection.Design and settingDescriptive, observational, retrospective study in three primary healthcare centres with an assigned population of 100,000.MethodExamination of the medical records of patients with COVID-19 infections confirmed by polymerase chain reaction. Logistic multivariate regression models adjusted for age and sex were constructed to analyse independent predictive factors associated with death, ICU admission and hospitalization.ResultsWe included 322 patients (mean age 56.7 years, 50% female, 115 (35.7%) aged ≥ 65 years): 123 (38.2) were health workers (doctors, nurses, auxiliaries). Predictors of ICU admission or death were greater age (OR = 1.05; 95%CI = 1.03 to 1.07), male sex (OR = 2.94; 95%CI = 1.55 to 5.82), autoimmune disease (OR = 2.82; 95%CI = 1.00 to 7.84), bilateral pulmonary infiltrates (OR = 2.86; 95%CI = 1.41 to 6.13), elevated lactate-dehydrogenase (OR = 2.85; 95%CI = 1.28 to 6.90), elevated D-dimer (OR = 2.85; 95%CI = 1.22 to 6.98) and elevated C-reactive protein (OR = 2.38; 95%CI = 1.22 to 4.68). Myalgia or arthralgia (OR = 0.31; 95%CI = 0.12 to 0.70) was protective factor against ICU admission and death. Predictors of hospitalization were chills (OR = 5.66; 95%CI = 1.68 to 23.49), fever (OR = 3.33; 95%CI = 1.89 to 5.96), dyspnoea (OR = 2.92; 95%CI = 1.62 to 5.42), depression (OR = 6.06; 95%CI = 1.54 to 40.42), lymphopenia (OR = 3.48; 95%CI = 1.67 to 7.40) and elevated C-reactive protein (OR = 3.27; 95%CI = 1.59 to 7.18). Anosmia (OR = 0.42; 95%CI = 0.19 to 0.90) was the only significant protective factor for hospitalization after adjusting for age and sex.ConclusionDetermining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts.

Background: The increase in the incidence of obesity and obesity-related cardiovascular risk factors (CVRFs) over the last decades has brought attention on adipose tissue (AT) pathobiology. The expansion of AT is associated with the development of new vasculature needed to perfuse the tissue; however, not all fat depots have the same ability to induce angiogenesis that requires recruitment of their own endothelial cells. In this study we have investigated the effect of different CVRFs, on the angiogenic capacity of the subcutaneous (SAT) and visceral (VAT) adipose tissue and on the function of their mesenchymal cell reservoir. Methods: A transcriptomic approach was used to compare the different angiogenic and inflammatory profiles of the subcutaneous and visceral fat depots from individuals with obesity, as well as their resident stem cells (ASCs). Influence of other risk factors on fat composition was also measured. Finally, the microvesicles (MVs) released by ASCs were isolated and their regenerative potential analyzed by molecular and cellular methodologies. Results: Obesity decreases the angiogenic capacity of AT. There are differences between SAT and VAT; from the 21 angiogenic-related genes analyzed, only three were decreased in SAT compared with those decreased in VAT. ASCs isolated from both fat depots showed significant differences; there was a significant up-regulation of the VEGF-pathway on visceral derived ASCs. ASCs release MVs that stimulate endothelial cell migration and angiogenic capacity. Conclusions: In patients with obesity, SAT expresses a greater number of angiogenic molecules than VAT, independent of the presence of other CVRFs.

C-reactive protein (CRP) is a short pentraxin mainly found as a pentamer in the circulation, or as non-soluble monomers CRP (mCRP) in tissues, exerting different functions. This review is focused on discussing the role of CRP in cardiovascular disease, including recent advances on the implication of CRP and its forms specifically on the pathogenesis of atherothrombosis and angiogenesis. Besides its role in the humoral innate immune response, CRP contributes to cardiovascular disease progression by recognizing and binding multiple intrinsic ligands. mCRP is not present in the healthy vessel wall but it becomes detectable in the early stages of atherogenesis and accumulates during the progression of atherosclerosis. CRP inhibits endothelial nitric oxide production and contributes to plaque instability by increasing endothelial cell adhesion molecules expression, by promoting monocyte recruitment into the atheromatous plaque and by enzymatically binding to modified low-density lipoprotein. CRP also contributes to thrombosis, but depending on its form it elicits different actions. Pentameric CRP has no involvement in thrombogenesis, whereas mCRP induces platelet activation and thrombus growth. In addition, mCRP has apparently contradictory pro-angiogenic and anti-angiogenic effects determining tissue remodeling in the atherosclerotic plaque and in infarcted tissues. Overall, CRP contributes to cardiovascular disease by several mechanisms that deserve an in-depth analysis.

Atherosclerosis (AT) is a progressive chronic disease involving lipid accumulation, fibrosis, and inflammation in medium and large-sized arteries, and it is the main cause of cardiovascular disease (CVD). AT is caused by dyslipidemia and mediated by both innate and adaptive immune responses. Despite lipid-lowering drugs have shown to decrease the risk of cardiovascular events (CVEs), there is a significant burden of AT-related morbidity and mortality. Identification of subjects at increased risk for CVE as well as discovery of novel therapeutic targets for improved treatment strategies are still unmet clinical needs in CVD. Microvesicles (MVs), small extracellular plasma membrane particles shed by activated and apoptotic cells have been widely linked to the development of CVD. MVs from vascular and resident cells by facilitating exchange of biological information between neighboring cells serve as cellular effectors in the bloodstream and play a key role in all stages of disease progression. This article reviews the current knowledge on the role of MVs in AT and CVD. Attention is focused on novel aspects of MV-mediated regulatory mechanisms from endothelial dysfunction, vascular wall inflammation, oxidative stress, and apoptosis to coagulation and thrombosis in the progression and development of atherothrombosis. MV contribution to vascular remodeling is also discussed, with a particular emphasis on the effect of MVs on the crosstalk between endothelial cells and smooth muscle cells, and their role regulating the active process of AT-driven angiogenesis and neovascularization. This review also highlights the latest findings and main challenges on the potential prognostic, diagnostic, and therapeutic value of cell-derived MVs in CVD. In summary, MVs have emerged as new regulators of biological functions in atherothrombosis and might be instrumental in cardiovascular precision medicine; however, significant efforts are still needed to translate into clinics the latest findings on MV regulation and function.