Scientia, Dipòsit d’Informació Digital del Departament de Salut
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Heterogeneity of cognitive progression and clinical predictors in Parkinson’s disease–subjective cognitive decline
Get PDFCognitive complaints; Cognitive decline; Parkinson’s diseaseQueixes cognitives; Declivi cognitiu; Malaltia de ParkinsonQuejas cognitivas; Deterioro cognitivo; Enfermedad de ParkinsonOpen Access Funding provided by Universitat Autonoma de Barcelona
ERK1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility
Get PDFMAP kinases; Cell motility; Scaffold proteinsQuinasas MAP; Motilidad celular; Proteínas de andamiajeQuinases MAP; Motilitat cel·lular; Proteïnes de bastidaERK1/2 mitogen-activated protein kinases (ERK) are key regulators of basic cellular processes, including proliferation, survival, and migration. Upon phosphorylation, ERK becomes activated and a portion of it dimerizes. The importance of ERK activation in specific cellular events is generally well documented, but the role played by dimerization is largely unknown. Here, we demonstrate that impeding ERK dimerization precludes cellular movement by interfering with the molecular machinery that executes the rearrangements of the actin cytoskeleton. We also show that a constitutively dimeric ERK mutant can drive cell motility per se, demonstrating that ERK dimerization is both necessary and sufficient for inducing cellular migration. Importantly, we unveil that the scaffold protein kinase suppressor of Ras 1 (KSR1) is a critical element for endowing external agonists, acting through tyrosine kinase receptors, with the capacity to induce ERK dimerization and, subsequently, to unleash cellular motion. In agreement, clinical data disclose that high KSR1 expression levels correlate with greater metastatic potential and adverse evolution of mammary tumors. Overall, our results portray both ERK dimerization and KSR1 as essential factors for the regulation of cell motility and mammary tumor dissemination.We are indebted to Dr D. Engelberg for providing reagents. PC lab is supported by grant PID2021-126288OB-I00 and PDC2022-133569-I00 from the Spanish Ministry of Science (MICIU/AEI/FEDER, UE); CIBERONC (CB16/12/00436) from the Instituto de Salud Carlos III (ISCIII); and a grant from ASPLA S.A “Encintalo en Rosa” Initiative. BC is funded by grants from Ministerio de Innovación, Ciencia y Universidades, MICIU PID2020/112760RB-100 and La Fundació d'Estudis i Recerca Oncològica (FERO, BFERO2021.03). JA is supported by CIBERONC; Breast Cancer Research Foundation (BCRF-23-008) and Instituto de Salud Carlos III (ISCIII) (PI22/00001). AK is supported by the Wellcome Trust (Multiuser Equipment Grant, 208402/Z/17/Z). DF-V is a CIBERONC predoctoral fellow (JCSTF2105526)
Recomanacions de prevenció i control de la legionel·losi en cas d'aturada i reobertura d'instal·lacions de risc
Get PDFLegionel·la; Risc; Instal·lacionsLegionela; Riesgo; InstalacionesLegionella; Risk; InstallationsAquest document aborda les consideracions que cal tenir en compte, en cas d’aturada d’instal·lacions amb risc de dispersió de Legionella, per prevenir la proliferació del bacteri i evitar la possible aparició de casos o brots de legionel·losi en la reobertura.Este documento aborda las consideraciones que deben tenerse en cuenta, en caso de parada de instalaciones con riesgo de dispersión de Legionella, para prevenir la proliferación de la bacteria y evitar la posible aparición de casos o brotes de legionelosis en la reapertura.This document addresses the considerations to be taken into account in the event of a shutdown of installations with a risk of Legionella dispersion, in order to prevent the proliferation of the bacterium and avoid the potential occurrence of cases or outbreaks of legionellosis upon reopening
Estadística de la interrupció voluntària de l'embaràs a Catalunya, 2023
Get PDFAvortament legal; CatalunyaLegal abortion; CataloniaAborto legal; CataluñaL’Estadística d’Interrupció Voluntària de l’Embaràs (IVE) de Catalunya conté informació sociodemogràfica i de les característiques de la intervenció de les IVE realitzades en tots els centres sanitaris públics i privats autoritzats.
Tots els centres autoritzats han de proporcionar les dades sobre les IVE realitzades, d’acord amb l’Ordre de 10 de desembre de 1986 del Departament de Salut, per la qual es disposa el procediment de recollida de dades relatives a les interrupcions voluntàries d’embaràs dutes a terme de conformitat amb la Llei orgànica 9/1985, de 5 de juliol.The Statistics on Voluntary Interruption of Pregnancy in Catalonia contains sociodemographic information and the characteristics of the intervention carried out in all public and private health centers authorized.
All authorized centers must provide the data on the interventions carried out, in accordance with the Order of December 10, 1986 of the Department of Health, which provides for the procedure for collecting data related to voluntary interruptions of pregnancy carried out in accordance with Organic Law 9/1985 of 5 July.La Estadística de Interrupción Voluntaria del Embarazo (IVE) de Cataluña contiene información sociodemográfica y de las características de la intervención de las IVE realizadas en todos los centros sanitarios públicos y privados autorizados.
Todos los centros autorizados deben proporcionar los datos sobre las IVE realizadas, de acuerdo con la Orden de 10 de diciembre de 1986 del Departamento de Salud, por la que se dispone el procedimiento de recogida de datos relativos a las interrupciones voluntarias de embarazo llevadas a cabo de conformidad con la Ley orgánica 9/1985, de 5 de julio
Results Centre: advances in the evaluation and transparency of the Catalanhealth system
Get PDFIndicadors; Qualitat assistencial; Resultats de salutIndicadores; Calidad asistencial; Resultados de saludIndicators; Quality of care; Health outcomesEs descriu l’experiència renovada de la Central de Resultats del sistema sanitari català, que s’ha desenvolupat sobre una plataforma tecnològica interactiva amb la visualització de 257 indicadors en sis àmbits i noves eines per a la interpretació dels resultats, així com la possibilitat de descarregar les dades. Els indicadors es mostren des d’una doble perspectiva d’anàlisi: la territorial (segons la residència de la persona) i la del centre d’atenció (segons el lloc on ha estat atesa); a més de la seva evolució temporal (del 2017 al 2023). Les dades es visualitzen mitjançant taules, gràfics i mapes, i s’acompanyen de fitxes tècniques i informes que resumeixen i contextualitzen els resultats, guies d’ajuda a la navegació i un cercador d’indicadors. La plataforma dona continuïtat a les dades publicades anteriorment, i la seva nova visualització i eines de suport en faciliten el monitoratge i la comparació dels resultats per a una millora contínua de l’assistència.Se describe la experiencia renovada de la Central de Resultados del sistema sanitario catalán, que se hadesarrollado sobre una plataforma tecnológica interactiva con la visualización de 257 indicadores en seisámbitos y nuevas herramientas para la interpretación de los resultados, y con la posibilidad de descargarlos datos. Los indicadores se muestran desde una doble perspectiva de análisis: la territorial (según laresidencia de la persona) y la de centro de atención (según el lugar donde ha sido atendida); ademásde su evolución temporal (2017 a 2023). Los datos se visualizan a través de tablas, gráficos y mapas,y se acompa˜nan de fichas técnicas e informes que resumen y contextualizan los resultados, guías deayuda a la navegación y un buscador de indicadores. La plataforma da continuidad a los datos publicadosanteriormente, y su nueva visualización y herramientas de soporte facilitan el monitoreo y la comparaciónde los resultados para una mejora continua de la asistencia.This paper describes the renewed experience of the Results Centre of the Catalan health system. Thistool is based on an interactive platform that allows the visualisation of 257 indicators in six areas. Italso incorporates new functionalities for the interpretation of the results and data download. Theseindicators are shown from a dual perspective of analysis: territorial (according to the person’s residence)and health care centre (according to the place where the care has been provided); also including theirevolution over time (from 2017 to 2023). The data are visualised through tables, graphs and maps. Theyare accompanied by fact sheets and reports that summarise and contextualise the results, and also providenavigation guides and a search engine for indicators. The platform provides continuity with previouslypublished data, while its new visualisation capabilities and supporting tools facilitate the monitoring andbenchmarking of results for continuous improvement of healthcare
Gender differences in ADHD and impulsivity among alcohol or alcohol- and cocaine-dependent patients
Get PDFAlcohol; Gender differences; ImpulsivityAlcohol; Gender differences; ImpulsivityAlcohol; Diferències de gènere; ImpulsivitatBackground: Impulsivity plays a fundamental role in the realm of addiction as is considered a risk factor for addiction. Moreover, it influences the age of onset, severity, and therapeutic management of addictions. The aim of this study was to explore measures of impulsivity in a cohort of male and female diagnosed with Alcohol Use Disorder (AUD) and contrast these findings with those from a group with Alcohol and Cocaine Use Disorder (ACUD).
Methodology: A total of 204 patients (153 men and 51 women) underwent evaluation using Adult ADHD Self-Report Scale (ASRS), Barrat Impulsiveness Scale (BIS-11), Zuckerman-Kuhlman Personality Questionnaire (ZKPQ), Visual Analogue Scale (VAS), Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI).
Results: A total of 24.6% of the sample (21.9% AUD group and 32.2% ACUD group) screened positive for ADHD. Differences were observed in Total Impulsivity (T(199) =-2.587, p=.010), with the mean score being higher in the ACUD group. Gender differences were noted with ADHD exhibiting a significant explanatory power for impulsivity (greater than 37%) in women compared to men, where its relevance is minimal. Among women, an inverse relationship was found between impulsivity and activity and sociability, in contrast to men, where the inverse relationship was with intolerance to isolation. Both men and women showed associations between ADHD and elevated levels of anxiety and depression. Study limitations and practical implications are discussed.
Conclusions: Although this is an observational study and should be develop a longitudinal study, we detected that the presence of ADHD in addicted women significantly influences impulsivity and should be systematically assessed due to the differences in the clinical approach.The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research project was supported by Castile and León’s (Spain) Gerencia Regional de Salud (GRS 2187/A/20, GRS 234/A/21, GRS2571/A/22) Scholarships, Delegación del Gobierno para el Plan Nacional sobre Drogas, Ministerio de Sanidad (2022/050) Scholarship and Instituto de Salud Carlos III (RD21/0029): funding by European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR). The scholarships were awarded to CR (Main Researcher) and his research team. The group was funded as a member of the Network of Research In Primary care of Addictions (Red de Investigacion en Atención de Adicciones (RIAPAD)
Applying two approaches to detect unmeasured confounding due to time-varying variables in a self-controlled risk interval design evaluating COVID-19 vaccine safety signals, using myocarditis as a case example
Get PDFCOVID-19 vaccine safety; Pharmacoepidemiology; Quantitative bias analysisSeguridad de la vacuna COVID-19; Farmacoepidemiología; Análisis de sesgo cuantitativoSeguretat de la vacuna COVID-19; Farmacoepidemiologia; Anàlisi de biaix quantitatiuWe test the robustness of the self-controlled risk interval (SCRI) design in a setting where time between doses may introduce time-varying confounding, using both negative control outcomes (NCOs) and quantitative bias analysis (QBA). All vaccinated cases identified from 5 European databases between September 1, 2020, and end of data availability were included. Exposures were doses 1-3 of the Pfizer, Moderna, AstraZeneca, and Janssen COVID-19 vaccines; outcomes were myocarditis and, as the NCO, otitis externa. The SCRI used a 60-day control window and dose-specific 28-day risk windows, stratified by vaccine brand and adjusted for calendar time. The QBA included two scenarios: (1) baseline probability of the confounder was higher in the control window and (2) vice versa. The NCO was not associated with any of the COVID-19 vaccine types or doses except Moderna dose 1 (IRR = 1.09; 95% CI 1.01-1.09). The QBA suggested that even the strongest literature-reported confounder (COVID-19; RR for myocarditis = 18.3) could only explain away part of the observed effect, from IRR = 3 to IRR = 1.40. The SCRI seems robust to unmeasured confounding in the COVID-19 setting, although a strong unmeasured confounder could bias the observed effect upward. Replication of our findings for other safety signals would strengthen this conclusion.This project received support from the European Medicines Agency under the Framework service contract EMA/2018/23/PE
Exploring algorithms to select candidates for non-selective beta-blockers in cirrhosis: A post hoc analysis of the PREDESCI trial
Get PDFDecompensation; Portal hypertension; Spleen stiffnessDescompensación; Hipertensión portal; Rigidez esplénicaDescompensació; Hipertensió portal; Rigidesa esplènicaBackground & Aims
Whether non-invasive tests (NITs) can accurately select patients with cirrhosis requiring non-selective beta-blockers (NSBBs) for clinically significant portal hypertension (CSPH) and prevention of decompensation is unclear. Our aim was to test the performance of NIT-based algorithms for CSPH diagnosis using the prospective PREDESCI cohort. We investigated whether a new algorithm combining NITs with endoscopy could improve performance.
Methods
We included patients with compensated cirrhosis and available liver elastography who were screened during the trial. The performance of models based on liver stiffness measurement (LSM) and platelet count was evaluated. An algorithm considering endoscopy for patients with inconclusive results (the “grey zone”) was then developed and validated in an independent cohort of 195 patients in whom spleen stiffness was also available.
Results
We included 170 patients from the PREDESCI cohort. An LSM ≥25 kPa alone (Baveno VII criteria) or combined with an LSM >20 kPa plus thrombocytopenia (AASLD criteria) ruled-in CSPH with positive predictive values of 88% and 89%, respectively. However, 37%-47% patients fell into the grey zone while at high risk of decompensation or death. Performing endoscopy in inconclusive cases identified patients with varices that, when reclassified as high-risk for CSPH, significantly reduced the grey zone to 22%. In this algorithm, 86% of patients with CSPH were correctly classified as high risk. The diagnostic performance was confirmed in the external validation cohort, where combining Baveno VII criteria with spleen stiffness showed similar accuracy to the model using endoscopy.
Conclusions
Algorithms based only on LSM and platelet count are suboptimal to identify NSBB treatment candidates. Performing endoscopy in patients with indeterminate findings from NITs improved diagnostic performance and risk stratification. Endoscopy may be substituted by spleen stiffness for stratifying risk in the grey zone.
Impact and implications
The PREDESCI trial demonstrated that non-selective beta-blockers prevent decompensation in patients with clinically significant portal hypertension (CSPH). Still, it is unclear whether we can select treatment candidates using non-invasive tests to assess the presence of CSPH without measuring HVPG (hepatic venous pressure gradient). In the prospective cohort of patients screened during the PREDESCI trial, we showed that algorithms based on liver stiffness and platelet count had suboptimal performance, mainly due to a high rate of indeterminate results. Performing endoscopy on patients in the grey zone significantly increased the number correctly characterized as having CSPH and improved the risk stratification for decompensation or death on long-term follow-up. These findings were validated in an independent cohort. In addition, a model using spleen stiffness instead of endoscopy showed similar diagnostic performance in the external validation cohort, suggesting that adequate risk stratification to select treatment candidates can be achieved with a fully non-invasive algorithm.AB, JB, ED, reported receiving grants from the National Institutes of Health (NIH) outside the submitted work. JB was supported in part by the Swiss Liver Foundation
Identification of modifier gene variants overrepresented in familial hypomagnesemia with hypercalciuria and nephrocalcinosis patients with a more aggressive renal phenotype
Get PDFFamilial hypomagnesemia with hypercalciuria and nephrocalcinosis; Renal phenotypeHipomagnesèmia familiar amb hipercalciúria i nefrocalcinosi; Fenotip renalHipomagnesemia familiar con hipercalciuria y nefrocalcinosis; Fenotipo renalFamilial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an ultra-rare autosomal recessive renal tubular disease with an incidence of <1/1.000.000 individuals, caused by loss-of-function mutations in CLDN16 and CLDN19. Our study includes a unique cohort representing all known FHHNC patients in Spain, with 90% harbouring mutations in CLDN19. Of these, 70% carry the p.G20D mutation in homozygosis. Despite this high genetic homogeneity, our FHHNC cohort display a high phenotypic variability, even among siblings harbouring identical mutations. Patients were stratified at the extremes of the renal phenotype according to their estimated glomerular filtration rate annual decline and subjected to whole exome sequencing (WES) aiming to find candidate phenotype-modifier genes. Initial statistical analysis by SKAT-O identified numerous variants, which were then filtered based on P-value <0.01 and kidney expression. A thorough prioritization strategy was then applied by an exhaustive disease knowledge-driven exploitation of data from public databases (Human Protein Atlas, GWAS catalog, GTEx) to further refine candidate genes. Odds ratios were also calculated to identify potential risk variants. This analysis pipeline suggested several gene variants associated with a higher risk of developing a more aggressive renal phenotype. While these findings hint at the existence of genetic modifiers in FHHNC, further research is needed to confirm their role and potential clinical significance. Clinical decisions should not be based on these preliminary findings, and additional cohorts should be studied to validate and expand upon our results. This exploratory study provides a foundation for future investigations into the genetic factors influencing FHHNC progression and may contribute to our understanding of the disease’s variable expressivity potentially enabling the implementation of more tailored therapeutic strategies.This study was funded in part by Fondo Europeo de Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Ciencia e Innovación (PI14/01107, PI18/01107, PI22/01946 to GA); by the Fundación Senefro (SEN2023 to AM); and by donations from the FHHNC patient advocacy group HIPOFAM (to GA and AM). AM research group holds the Quality Mention from the Generalitat de Catalunya (Grant No. 2021 SGR 01600 to AM). CMM is supported by the Miguel Servet program from the Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Ciencia e Innovación (CP18/00116).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Silver Nanoparticles and Antibiotics: A Promising Synergistic Approach to Multidrug-Resistant Infections
Get PDFAntibiotic resistance; Antimicrobial synergy; Silver nanoparticlesResistència als antibiòtics; Sinergia antimicrobiana; Nanopartícules de plataResistencia a los antibióticos; Sinergia antimicrobiana; Nanopartículas de plataThe escalating threat of antibiotic resistance demands innovative strategies against multidrug-resistant (MDR) microorganisms, particularly in hospital settings where such infections represent a major global health challenge. Since the rapid growth of nanotechnology interdisciplinary research and funding programs in the 2000s, silver ions have re-emerged as potent antimicrobial agents, offering a promising complement to conventional therapies. This therapeutic potential is nowadays explored through the use of silver nanoparticles (AgNPs) as sources for silver ions release. Recent studies have shown that controlled silver ion release enhances the efficacy of common antibiotics. This can be attributed to the energetically demanding nature of the bacterial response to silver, which weakens bacterial metabolism and, in turn, overwhelms bacterial defenses and increases antibiotic effectiveness. Herein, historical insights into the use of colloidal silver and AgNPs are combined with a review of recent research on the exploitation of the synergistic effect between AgNPs and antibiotics as a promising strategy against MDR pathogens.This research was funded by the international joint research projects program MCIN/AEI (CONCORD, PCI2019-103436), co-funded by the European Union and Generalitat de Catalunya (2021-SGR-00878). ICN2 is supported by the Severo Ochoa program from Spanish MCIN/AEI (Grant No.: CEX2021-001214-S) and receives funding from the CERCA Programme/Generalitat de Catalunya