Scientia, Dipòsit d’Informació Digital del Departament de Salut
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Donar òrgans és donar vida [cartell]
No full textDonació d'òrgans i teixits; Trasplantaments; DivulgacióDonación de órganos y tejidos; Trasplantes; DivulgaciónOrgan and tissue donation; Transplants; OutreachPromotional poster for organ donation and the option to donate through the "La Meva Salut" application with an image of José Corbacho.Cartel promocional de la donación de órganos y la opción de donar a través de la aplicación “La Meva Salut” con la imagen de José Corbacho.Cartell promocional de la donació d'òrgans i l'opció de fer-se donant a través de l'aplicació "La Meva Salut" amb la imatge de l'artista José Corbacho
Bi-allelic pathogenic variants in TRMT1 disrupt tRNA modification and induce a neurodevelopmental disorder
Full text linkNeurodevelopmental disorder; tRNA modification; ZebrafishTrastorno del neurodesarrollo; Modificación de ARNt; Pez cebraTrastorn del neurodesenvolupament; Modificació de tRNA; Peix zebraThe post-transcriptional modification of tRNAs plays a crucial role in tRNA structure and function. Pathogenic variants in tRNA-modification enzymes have been implicated in a wide range of human neurodevelopmental and neurological disorders. However, the molecular basis for many of these disorders remains unknown. Here, we describe a comprehensive cohort of 43 individuals from 31 unrelated families with bi-allelic variants in tRNA methyltransferase 1 (TRMT1). These individuals present with a neurodevelopmental disorder universally characterized by developmental delay and intellectual disability, accompanied by variable behavioral abnormalities, epilepsy, and facial dysmorphism. The identified variants include ultra-rare TRMT1 variants, comprising missense and predicted loss-of-function variants, which segregate with the observed clinical pathology. Our findings reveal that several variants lead to mis-splicing and a consequent loss of TRMT1 protein accumulation. Moreover, cells derived from individuals harboring TRMT1 variants exhibit a deficiency in tRNA modifications catalyzed by TRMT1. Molecular analysis reveals distinct regions of TRMT1 required for tRNA-modification activity and binding. Notably, depletion of Trmt1 protein in zebrafish is sufficient to induce developmental and behavioral phenotypes along with gene-expression changes associated with disrupted cell cycle, immune response, and neurodegenerative disorders. Altogether, these findings demonstrate that loss of TRMT1-catalyzed tRNA modifications leads to intellectual disability and provides insight into the molecular underpinnings of tRNA-modification deficiency caused by pathogenic TRMT1 variants.The authors thank the affected individuals and their families for their support of this study. One of the authors of this publication (Z.T.) is a member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability, ERN-ITHACA (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516). B.V. is a member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA) (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516). The research in this paper was supported by NIH GM141038 to D.F. Studies performed in the lab of G.K.V. was funded by NIH/ORIP R24OD034438. The clinic-genetic research was funded in part by the Wellcome Trust (WT093205MA and WT104033AIA). This study was funded by the Medical Research Council (MR/S01165X/1, MR/S005021/1, and G0601943), The National Institute for Health Research University College London Hospitals Biomedical Research Centre, Rosetrees Trust, Ataxia UK, Multiple System Atrophy Trust, Brain Research United Kingdom, Sparks Great Ormond Street Hospital Charity, Muscular Dystrophy United Kingdom (MDUK), Muscular Dystrophy Association (MDA USA), and the King Baudouin Foundation. S.E. and H.H. were supported by an MRC strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) MR/S005021/1. B.V. was supported by the Deutsche Forschungsgemeinschaft (DFG) DFG VO 2138/7-1 grant 469177153. J.S. is supported by Cancer Research UK and University College London. A.F. and S.C. were supported by Health & Care Research Wales, Epilepsy Research UK, and Swansea University PhD funding
OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle development
Full text linkExon inclusion; Muscle development; Neuromuscular diseasesInclusión de exones; Desarrollo muscular; Enfermedades neuromuscularesInclusió d'exons; Desenvolupament muscular; Malalties neuromuscularsBackground
Highly expressed in skeletal muscles, the gene Obscurin (i.e. OBSCN) has 121 non-overlapping exons and codes for some of the largest known mRNAs in the human genome. Furthermore, it plays an essential role in muscle development and function. Mutations in OBSCN are associated with several hypertrophic cardiomyopathies and muscular disorders. OBSCN undergoes extensive and complex alternative splicing, which is the main reason that its splicing regulation associated with skeletal and cardiac muscle development has not previously been thoroughly studied.
Methods
We analyzed RNA-Seq data from skeletal and cardiac muscles extracted from 44 postnatal individuals and six fetuses. We applied the intron/exon level splicing analysis software IntEREst to study the splicing of OBSCN in the studied samples. The differential splicing analysis was adjusted for batch effects. Our comparisons revealed the splicing variations in OBSCN between the human skeletal and cardiac muscle, as well as between post-natal muscle (skeletal and cardiac) and the pre-natal equivalent muscle.
Results
We detected several splicing regulations located in the 5’end, 3’ end, and the middle of OBSCN that are associated with human cardiac or skeletal muscle development. Many of these alternative splicing events have not previously been reported. Our results also suggest that many of these muscle-development associated splicing events may be regulated by BUB3.
Conclusions
We conclude that the splicing of OBSCN is extensively regulated during the human skeletal/cardiac muscle development. We developed an interactive visualization tool that can be used by clinicians and researchers to study the inclusion of specific OBSCN exons in pre- and postnatal cardiac and skeletal muscles and access the statistics for the differential inclusion of the exons across the studied sample groups. The OBSCN exon inclusion map related to the human cardiac and skeletal muscle development is available at http://psivis.it.helsinki.fi:3838/OBSCN_PSIVIS/. These findings are essential for an accurate pre- and postnatal clinical interpretation of the OBSCN exonic variants.Open Access funding provided by University of Helsinki (including Helsinki University Central Hospital). We would like to acknowledge that our research was supported by Magnus Ehrnrooth foundation (AO), Samfundet Folkhälsan i Svenska Finland (MS, BU), Jane and Aatos Erkko foundation (PH), Academy of Finland (MS, BU), European Joint Program on Rare Diseases (BU, FM), Sydäntutkimussäätiö (MS), CoMPaSS-NMD (funded by the European Union under Grant Agreement n° 101080874) and Instituto de Salud Carlos III, Spain (project number AC19/00048 to FM). Open access was funded by Helsinki University Library
Endoscopic retrograde cholangiopancreatography training conditions, results from a pan-European survey: Between vision and reality
Full text linkFormació avançada en endoscòpia; Educació en endoscòpia; Formació estructuradaAdvanced endoscopy training; Endoscopy education; Structured trainingFormación avanzada en endoscopia; Educación en endoscopia; Formación estructuradaBackground: Endoscopic retrograde cholangiopancreatography (ERCP) still has a relatively high complication rate, underscoring the importance of high‐quality training. Despite existing guidelines, real‐world data on training conditions remain limited. This pan‐European survey aims to systematically explore the perceptions surrounding ERCP training.
Methods: A survey was distributed through the friends of United European Gastroenterology (UEG) Young Talent Group network to physicians working in a UEG member or associated states who regularly performed ERCPs.
Results: Of 1035 respondents from 35 countries, 649 were eligible for analysis: 228 trainees, 225 trainers, and 196 individuals who regularly performed ERCP but were neither trainees nor trainers. The mean age was 43 years, with 72.1% identifying as male, 27.6% as female, and 0.3% as non‐binary. The majority (80.1%) agreed that a structured training regiment is desirable. However, only 13.7% of trainees and 28.4% of trainers reported having such a structured program in their institutions. Most respondents (79.7%) supported the concept of concentrating training in centers meeting specific quality metrics, with 64.1% suggesting a threshold of 200 annual ERCPs as a prerequisite. This threshold revealed that 36.4% of trainees pursued training in lower volume centers performing <200 ERCPs annually. As many as 70.1% of trainees performed <50 annual ERCPs, whereas only 5.0% of trainers performed <50 ERCPs annually. A low individual trainee caseload (<50 ERCPs annually) was more common in lower‐volume centers than in higher‐volume centers (82.9% vs. 63.4%).
Conclusions: The first pan‐European survey investigating ERCP training conditions reveals strong support for structured training and the concentration of training efforts within centers meeting specific quality metrics. Furthermore, this survey exposes the low availability of structured training programs, with many trainees practicing at lower‐volume centers and 71% of all trainees having little hands‐on exposure. These data should motivate to standardize ERCP training conditions further and ultimately improve patient care throughout.Open Access funding enabled and organized by Projekt DEAL
Automatic colon segmentation on T1-FS MR images
Full text linkColon contents; Colon segmentation; Medical image analysisContingut del còlon; Segmentació del còlon; Anàlisi d'imatges mèdiquesContenido del colon; Segmentación del colon; Análisis de imágenes médicasThe volume and distribution of the colonic contents provides valuable insights into the effects of diet on gut microbiotica involving both clinical diagnosis and research. In terms of Magnetic Resonance Imaging modalities, T2-weighted images allow the segmentation of the colon lumen, while fecal and gas contents can be only distinguished on the T1-weighted Fat-Sat modality. However, the manual segmentation of T1-weighted Fat-Sat is challenging, and no automatic segmentation methods are known.
This paper proposed a non-supervised algorithm providing an accurate T1-weighted Fat-Sat colon segmentation via the registration of an existing colon segmentation in T2-weighted modality.
The algorithm consists of two phases. It starts with a registration process based on a classical deformable registration method, followed by a novel Iterative Colon Registration process that utilizes a mesh deformation approach. This approach is guided by a probabilistic model that provides the likelihood of the colon boundary, followed by a shape preservation process of the colon segmentation on T2-weighted images. The iterative process converges to achieve an optimal fit for colon segmentation in T1-weighted Fat-Sat images.
The segmentation algorithm has been tested on multiple datasets (154 scans) and acquisition machines (3) as part of the proof of concept for the proposed methodology. The quantitative evaluation was based on two metrics: the percentage of ground truth labeled feces correctly identified by our proposal (
), and the volume variation between the existing colon segmentation in the T2-weighted modality and the colon segmentation computed in T1-weighted Fat-Sat images.
Quantitative and medical evaluations demonstrated a degree of accuracy, usability, and stability concerning the acquisition hardware, making the algorithm suitable for clinical application and research.This work was supported in part by the projects PID2021-122295OB-I00 (Ministerio de Ciencia e Innovación, Spain), the project PID2021-122136OB-C21 funded by MCIN/AEI/ 10.13039/501100011033 and ERDF “A way of making Europe”, by the EU Horizon 2020 and the Department of Research and Universities of the Government of Catalonia (2021 SGR 01035). Ciberehd is funded by the Instituto de Salud Carlos III, Spain
Multicenter evaluation of the QIAstat-Dx Gastrointestinal Panel 2, a multiplex PCR platform for the diagnosis of acute gastroenteritis
Full text linkDiarrhea; Ggastrointestinal infection; Syndromic testingDiarrea; Infección gastrointestinal; Pruebas sindrómicasDiarrea; Infecció gastrointestinal; Proves sindròmiquesThe QIAstat-Dx Gastrointestinal Panel 2 (GI2 Panel) is a sample-to-answer multiplex PCR instrument that can detect 17 targets in a run time of about 80 minutes. The performance of the QIAstat-Dx GI2 Panel was evaluated by testing 1,939 prospective, 119 prospectively collected and then archived positive clinical samples and 750 retrospective clinical specimens across 13 sites in Europe and the United States. Specimens tested included bulk stool samples preserved in modified Cary-Blair transport medium. For most targets, results were compared to those of the FilmArray GI panel (13/17), and discordant results were adjudicated with a third assay. For the remaining targets (4/17), a composite comparator method was used, which included three comparator assays for each target. Before discordant resolution, the QIAstat-Dx GI2 Panel positive percent agreement (PPA) was 95% or greater for 5/17 targets (Campylobacter, E. coli O157, Cryptosporidium, Cyclospora cayetanensis, and Giardia lamblia) and 90% or greater for 11/17 targets: adenovirus F40/F41, astrovirus, norovirus GI/GII, rotavirus A, Plesiomonas shigelloides, enteropathogenic Escherichia coli, enterotoxigenic E. coli, Salmonella, Yersinia enterocolitica, Shiga-like toxin E. coli (STEC) stx1/stx2, and Shigella/enteroinvasive E. coli. No cases of Entamoeba histolytica were encountered during the clinical study. The negative percent agreement (NPA) was >98.9% for all QIAstat-Dx GI2 Panel targets. The three most common pathogens identified in single and co-infections were enteropathogenic E. coli (9.9%), Campylobacter (5.2%), and norovirus GI/GII (3.1%). In summary, this clinical study examined more than 2,800 samples from Europe and the U.S. using the QIAstat-Dx GI2 Panel and identified 90%-100% PPA and 99% NPA for its 17 targets.IMPORTANCEThe manuscript highlights the significance and impact of the QIAstat-Dx GI2 Panel, a sample-to-answer multiplex PCR instrument capable of detecting 17 targets in approximately 80 minutes. This comprehensive clinical study, conducted across 13 sites in Europe and the United States, evaluated the performance of the panel using over 2,800 clinical samples. The results demonstrate a high accuracy of the QIAstat-Dx GI2 panel, with a PPA equal to or higher than 90% for all targets and an NPA greater than 98.9% for all targets. These findings underscore the reliability and effectiveness of the GI2 panel in the rapid and precise detection of gastrointestinal pathogens, which is crucial for timely diagnosis and treatment of infections
Anterolateral Thigh Flap for Acute/Primary Burn Reconstruction
Full text linkBurn reconstruction; Free flap; MicrosurgeryReconstrucción de quemaduras; Colgajo libre; MicrocirugíaReconstrucció de cremades; Flap lliure; MicrocirurgiaIntroduction: The indication for a free flap in acute burn reconstruction is very specific. It should avoid several complications that are more common in the burned patient population. We propose an anterolateral thigh (ALT) flap as a first option for primary burn reconstruction in microvascular free flap reconstruction in burned patients. Patients and Methods: A retrospective review of all acutely burned patients treated with microvascular ALT free flap reconstruction between the years 2005 and 2022 in the Vall d’Hebron Barcelona Hospital Campus Burn Centre was conducted. Results: We performed 30 ALT flaps for primary burn reconstruction. The majority of patients were male (87.5%), with a mean age of 36.7 years, and 37% of patients were smokers. High-voltage electrical burns were the most common etiology. The mean time between burn injury and microsurgery was 22 days. The main recipient site was the lower limb. The flap survival rate was 96.6%. One patient required a meshed skin graft to cover a defect in the proximal third due to peripheral flap necrosis. One flap experienced mild congestion, which resolved spontaneously. Another flap had a local infection, which resolved with antibiotic therapy and surgical debridement. Conclusions: An ALT flap offers several advantages to a burned patient, provided that the surgical technique and postoperative management described in this study are followed. We propose it as the first option for primary burn reconstruction using free flaps in a burned patient
Recombinant Mycobacterium bovis BCG-Based HIV Vaccine: Failures and Promising Approaches for a Successful Vaccine Strategy
Full text linkHIV; Live-attenuated vaccines; MycobacteriaVIH; Vacunas vivas atenuadas; MicobacteriasVIH; Vacunes vives atenuades; MicobacterisDuring 2022, AIDS claimed a life every minute and about 9.2 million HIV-infected people were not on treatment. In addition, a person living with HIV is estimated to be 20-30 times more susceptible to developing active tuberculosis. Every year, 130,000 infants are newly infected, with vertical transmission being the main cause of pediatric HIV infection. Thus, the development of an effective, safe, and accessible vaccine for neonates and/or adults is an urgent need to prevent or control HIV infection or progression to AIDS. An effective HIV vaccine should induce long-lasting mucosal immunity, broadly neutralizing antibodies, innate immunity, and robust stimulation of CD4+ and CD8+ T-cell responses. Recombinant BCG is a promising live-attenuated bacterial vaccine vector because of its capacity to stimulate T-cell immunity. As a slow-growing microorganism, it provides prolonged low-level antigenic exposure upon infecting macrophages and APCs, potentially stimulating both effector and memory T-cell responses. BCG is considered safe and is currently administered to 80% of infants in countries where it is part of the national immunization program. Additionally, BCG offers several benefits as a live vaccine vehicle since it is cost-effective, easy to mass-produce, and heat stable. It is also well-suited for newborns, as maternal antibodies do not interfere with its efficacy. Furthermore, BCG has a strong safety profile, having been administered to over three billion people as a TB vaccine. In this review, we provide an extensive summary of the literature relating to immunogenicity studies in animal models performed since 2011. Moreover, we provide a comprehensive analysis of the key factors influencing the design of recombinant BCG as a live vaccine vehicle: (i) expression vectors; (ii) selection of HIV immunogen; (iii) promoters to regulate gene expression; (iv) BCG strain and BCG codon optimization; (v) genetic plasmid stability; (vi) influence of preexisting immunity, route, and dose immunization; and (vii) safety profile.This research was funded by the División de Investigación Bogotá (DIB)-Universidad Nacional de Colombia, grants 62267 and 60311 and by Instituto de Salud Carlos III, PI20/00217 and PI24/00576
Presència d’etanol, drogues i psicofàrmacs en víctimes de trànsit: Informe sobre consum problemàtic i conseqüències - 2023
No full textVíctimes de trànsit; Alcohol; EstupefaentsTraffic victims; Alcohol; DrugsVíctimas de tráfico; Alcohol; EstupefacientesDes de l’any 1998, la Subdirecció General de Seguretat Viària del Servei Català de Trànsit elabora l’Anuari estadístic d’accidents de trànsit a Catalunya, 1998 – 2023, amb indicadors provinents de l’anàlisi d’accidents i amb dades sobre la presència d’alcohol i diferents substàncies en accidents amb persones víctimes. Des del 2005 incorpora les observacions del percentatge de persones conductores mortes amb presència d’alcohol i estupefaents. Finalment, des del 2010 recull el percentatge de positius en controls rutinaris d’alcoholèmia, en controls d’accidents i en controls de morts en accident (independentment de si les persones víctimes eren conductores o no)
Notificació d’incidents en la seguretat del pacient en l’hospitalització d’aguts a Catalunya: dades de 2024
Full text linkNotificació; Seguretat del pacient; Hospitalització d’agutsNotification; Patient safety; Acute hospitalizationNotificación; Seguridad del paciente; Hospitalización de agudosL’objectiu és fer un recull dels incidents que en permeti fer una anàlisi i buscar solucions per tal de reduir-ne el nombre i la freqüència amb la finalitat d’augmentar la seguretat del pacient durant l’assistència sanitària. Les dades que s’analitzen a continuació corresponen a l’any 2024, però cal tenir en compte que les notificacions analitzades en aquest informe corresponen únicament a les que els centres han tancat, una vegada revisades pels gestors de l’eina. Per tant, el nombre d’incidents anual depèn del moment en què s’extreuen les dades (en aquest cas, el 3 de juny del 2025)