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BACKGROUND: Long COVID-19 syndrome remains a global public health problem, with more than 145 million people affected with multisystemic symptoms. Addressing the requirements of individuals impacted by a syndrome characterised by a complex and variable clinical presentation is of utmost importance. Identifying the variables that can exert influence and understanding their progression is essential for directing treatment strategies aimed at enhancing both independence and quality of life. Therefore, the aim of this study was to analyse the influence of sociodemographic and clinical variables on existence and their relationship with asthenia, anxiety symptoms and low mood. METHODS: An analytical study secondary to an observational cross-sectional descriptive study. RESULTS: Logistic regression showed significant univariate effects on asthenia [sex (p = 0.034); age (p = 0.042); Activities of Daily Living Questionnaire [ADQL (p = 0.002)] [physical functioning (p < 0.001) and general health (p = 0.014)] and multivariate [sex (p = 0.019), adult age (p = 0.01) and physical functioning (p = 0.04)]]; low mood [time of evolution (p = 0.028) and multivariate [time course (p = 0.007), ADLQ (p = 0.011), role physical (p = 0.013) and general health (p = 0.001)]] and anxiety [physical functioning (p = 0.046) and multivariate [physical functioning (p = 0.034), age (p = 0.011), time of evolution (p = 0.001) and ADQL (p = 0.011)]]. CONCLUSIONS: Increased age, gender and longer evolution time seem to favour the prevalence and occurrence of mental health symptoms; greater independence and good physical functioning are protective factors with respect to the occurrence of mental health-related symptoms in patients affected by post-COVID-19 condition.
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BACKGROUND: Metabolomics is a scientific field that relies on the comprehensive analysis of metabolites to provide direct insights into functional processes in biological systems. Metabolomic data provides valuable insights into the functional processes of biological systems, often analyzed through univariate and multivariate approaches, and well as with functional or pathway analysis using different methods such as mummichog. Yet, the integration of results from these sources to aid the interpretation of their biological significance remains challenging. This represents a significant bottleneck limiting the applicability of multivariate analysis of metabolomic data, despite its potential for providing deep biological insights. RESULTS: In this work we propose two straightforward methods to facilitate the interpretation of results from multivariate analysis and functional metabolic analysis using: i) p-values from multivariate tests as input in functional analysis, and ii) cluster-CV to assess the impact on the predictive performance of a multivariate model at the pathway level. Four simulated data sets were analyzed including a data set with no class separation, and three data sets with a statistically significant discrimination between classes by including either univariate, multivariate, or both types of discriminant effects. The data sets were analyzed using univariate tests and OPLS-DA. Furthermore, p-values for each feature estimated by univariate analysis and OPLS-DA were used as input for functional analysis in mummichog. Cluster-CV was then used to assess the effect of detected metabolic pathways on the class separation observed by OPLS-DA. SIGNIFICANCE: Through simulated data, we show how these approaches enhance the interpretation of biological effects driving multivariate models and support the identification of altered pathways not detected by univariate analysis. By providing a deeper understanding of metabolic phenotypes, these methods might improve the biological insights derived from statistical and functional analysis of future or previous studies.
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Metabolômica , Metabolômica/métodos , Análise Multivariada , HumanosRESUMO
BACKGROUND: Critical limb-threatening ischemia (CLTI) constitutes the most severe manifestation of peripheral artery disease, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremities and elevated mortality rates, while they have low options for surgical revascularization due to associated comorbidities. Alternatively, cell-based therapeutic strategies represent an effective and safe approach to promote revascularization. However, the variability seen in several factors such as cell combinations or doses applied, have limited their success in clinical trials, being necessary to reach a consensus regarding the optimal "cellular-cocktail" prior further application into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert their regenerative properties. Herein, we have evaluated, for the first time, the regenerative and vasculogenic potential of a combination of endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs) isolated from adipose-tissue (AT), compared with ECFCs from umbilical cord blood (CB-ECFCs) and AT-MSCs, in a murine model of CLTI. METHODS: Balb-c nude mice (n:32) were distributed in four different groups (n:8/group): control shams, and ischemic mice (after femoral ligation) that received 50 µl of physiological serum alone or a cellular combination of AT-MSCs with either CB-ECFCs or AT-ECFCs. Follow-up of blood flow reperfusion and ischemic symptoms was carried out for 21 days, when mice were sacrificed to evaluate vascular density formation. Moreover, the long-term molecular changes in response to CLTI and both cell combinations were analyzed in a proteomic quantitative approach. RESULTS: AT-MSCs with either AT- or CB-ECFCs, promoted a significant recovery of blood flow in CLTI mice 21 days post-ischemia. Besides, they modulated the inflammatory and necrotic related processes, although the CB group presented the slowest ischemic progression along the assay. Moreover, many proteins involved in the repairing mechanisms promoted by cell treatments were identified. CONCLUSIONS: The combination of AT-MSCs with AT-ECFCs or with CB-ECFCs promoted similar revascularization in CLTI mice, by restoring blood flow levels, together with the modulation of the inflammatory and necrotic processes, and reduction of muscle damage. The protein changes identified are representative of the molecular mechanisms involved in ECFCs and MSCs-induced revascularization (immune response, vascular repair, muscle regeneration, etc.).
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Tecido Adiposo , Modelos Animais de Doenças , Isquemia , Células-Tronco Mesenquimais , Camundongos Endogâmicos BALB C , Camundongos Nus , Animais , Camundongos , Isquemia/terapia , Isquemia/fisiopatologia , Cordão Umbilical/citologia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Neovascularização Fisiológica , Células Endoteliais , HumanosRESUMO
IMPORTANCE: Assessment of praxis skills is an essential aspect of understanding autistic children's development of play and playfulness. OBJECTIVE: To assess the relationship and influence of ideational praxis skills on play skills and playfulness among autistic children. DESIGN: A cross-sectional study. SETTINGS: Homes, schools, and early care centers across Spain. PARTICIPANTS: Children ages 4 yr 6 mo to 6 yr 11 mo (45 typically developing [TP] and 45 with autism spectrum disorder [ASD]). OUTCOMES AND MEASURES: Student's t tests were used to compare means between the two groups. Pearson's correlation and multiple linear regression were used to determine possible effects of ideational skills on play and playfulness. RESULTS: Scores for the TP group were significantly higher than those of the ASD group on all play dimensions-space management, t(88) = 4.58; material management, t(88) = 5.86; pretense-symbolism, t(88) = 8.12; and participation, t(88) = 7.31-and on the Test of Playfulness (ToP), t(88) = 10.18, and Test of Ideational Praxis (TIP), t(88) = 4.38 (all ps < .001). Multiple linear regression revealed a statistically significant effect of TIP dimensions-space management, F(3, 41) = 4.83, p < .042; material management, F(3.41) = 8.49. p < .001; pretense-symbolism, F(3, 41) = 5.66. p < .002; and participation, F(3.41) = 7.81. p < .001-and on the ToP, F(3, 41) = 5.96. p < .002. CONCLUSIONS AND RELEVANCE: Ideational praxis skills combined with diagnostic information significantly predicted play skills and playfulness, highlighting the influence of ideation on play. Plain-Language Summary: This article provides data supporting the influence of ideational praxis skills on the play skills and playfulness of autistic children. Understanding how ideational praxis skills affect the ability to recognize and act on object affordances might promote greater possibilities for play interactions among autistic children.
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Transtorno do Espectro Autista , Jogos e Brinquedos , Humanos , Estudos Transversais , Masculino , Feminino , Criança , Pré-Escolar , Transtorno do Espectro Autista/reabilitação , Espanha , Transtorno Autístico/reabilitaçãoRESUMO
Bacteria are highly adaptable and grow in diverse niches, where they often interact with eukaryotic organisms. These interactions with different hosts span the entire spectrum from symbiosis to pathogenicity and thus determine the lifestyle of the bacterium. Knowledge of the genetic determinants involved in animal and plant host colonization by pathogenic and mutualistic bacteria is not only crucial to discover new drug targets for disease management but also for developing novel biostimulant strategies. In the last decades, significant progress in genome-wide high-throughput technologies such as transposon insertion sequencing has led to the identification of pathways that enable efficient host colonization. However, the extent to which similar genes play a role in this process in different bacteria is yet unclear. This review highlights the commonalities and specificities of bacterial determinants important for bacteria-host interaction.
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Bactérias , Elementos de DNA Transponíveis , Interações entre Hospedeiro e Microrganismos , Bactérias/genética , Animais , Interações entre Hospedeiro e Microrganismos/genética , Simbiose , Plantas/microbiologia , Interações Hospedeiro-Patógeno/genética , HumanosRESUMO
Both EphB2- and EphB3-deficient mice exhibit profound histological alterations in the thymic epithelial network but few changes in T-cell differentiation, suggesting that this organization would be sufficient to produce functional T lymphocytes. Also, other antigen-presenting cells involved in immunological education could substitute the thymic epithelium. Accordingly, we found an increased frequency of plasmacytoid dendritic cells but not of conventional dendritic cells, medullary fibroblasts or intrathymic B lymphocytes. In addition, there are no lymphoid infiltrates in the organs of mutant mice nor do they contain circulating autoantibodies. Furthermore, attempts to induce arthritic lesions after chicken type II collagen administration fail totally in EphB2-deficient mice whereas all WT and half of the immunized EphB3-/- mice develop a typical collagen-induced arthritis. Our results point out that Th17 cells, IL4-producing Th2 cells and regulatory T cells are key for the induction of disease, but mutant mice appear to have deficits in T cell activation or cell migration properties. EphB2-/- T cells show reduced in vitro proliferative responses to anti-CD3/anti-CD28 antibodies, produce low levels of anti-type II collagen antibodies, and exhibit low proportions of T follicular helper cells. On the contrary, EphB3-/- lymph node cells respond accurately to the different immune stimuli although in lower levels than WT cells but show a significantly reduced migration in in vitro transwell assays, suggesting that no sufficient type II collagen-dependent activated lymphoid cells reached the joints, resulting in reduced arthritic lesions.
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Artrite Experimental , Animais , Camundongos , Colágeno , Colágeno Tipo II , Epitélio , Timo , Receptor EphB3/metabolismoRESUMO
IMPORTANCE: Assuming the care of a family member with a disability or chronic illness constitutes a health risk factor for caregivers, who frequently overlook their own self-care. OBJECTIVE: To analyze the self-care activities (SCAs) among caregivers of a family member with a disability or chronic illness and assess the impact on their satisfaction and quality of life (QoL). DESIGN: Descriptive, cross-sectional, analytic study. SETTING: Community. PARTICIPANTS: Five hundred caregivers of family members with a disability or chronic illness in the city of Zaragoza, Spain. OUTCOMES AND MEASURES: The family caregivers' occupational performance and satisfaction were assessed with the Canadian Occupational Performance Measure, and their QoL was assessed with the World Health Organization-Quality of Life. RESULTS: In total, 32.8% of family caregivers had difficulty in all activities related to self-care, 46.6% had difficulty sleeping and resting, 31.6% had difficulty receiving health-related treatments, and 31.2% had difficulty with physical exercise. Women and younger family caregivers showed greater impairment in self-care. Occupational performance, satisfaction, and QoL worsened as the number of affected activities increased. CONCLUSIONS AND RELEVANCE: Caring for a family member with a disability or chronic illness has a negative impact on the SCAs of caregivers, especially among female caregivers and those of younger age. Caregiving is also associated with lower occupational performance, satisfaction, and QoL. Plain-Language Summary: Caring for a family member with a disability or chronic illness can become a health risk for caregivers, who frequently ignore their own self-care. The study results found that women and younger family caregivers showed a greater decline in self-care. This study provides information to help occupational therapists to work with family caregivers to prevent a decline in their self-care and improve their quality of life.
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Cuidadores , Qualidade de Vida , Humanos , Feminino , Autocuidado , Estudos Transversais , Canadá , Família , Doença CrônicaRESUMO
INTRODUCTION: Ward Clerks are an essential part of the healthcare team, as they provide administrative and organizational support in healthcare institutions. The aim of this study is to determine the training impact of a basic one-hour online course on patient safety for this staff. METHOD: A quasi-experimental before/after study carried out on a population of 170 administrative staff working in the centers of an Occupational Mutual Insurance Company (MC Mutual) who took the patient safety course. A convenience sample of 22 administrative professionals, who agreed to participate, was chosen from this population, which made it possible to reconstruct their knowledge before and after the course, by examination and interview, immediately after the course and at 6 months. RESULTS: Of the 170 professionals participating in the course, 167 (98.2%) completed the initial test and the post-test, with mean scores increasing from 5.7 (P1) to 7.3 (P2) (p<0.05). A total of 22 out of a sample of 42 (52.4%) agreed to participate in the interviews and all three interviews were achieved by 21 (E1), 22 (E2) and 19 (E3) professionals, whose mean scores increased from 5.9 (E1) to 7.2 (E2) and 7.5 (E3) (p<0.05). CONCLUSIONS: The results suggest that the training course was effective. The evaluation by interview 6 months after the course indicates a likely medium to long term effect. The involvement of administrative professionals in the the Company´s patients care is key. Evaluating the impact of an intervention is essential to inform its effectiveness and guide its planning.
Introducción: El personal administrativo es un colectivo esencial. El objetivo de este estudio es analizar el impacto formativo de un curso online básico sobre seguridad del paciente para administrativos. Método: Estudio cuasi experimental antes/después en una población de 170 administrativos/as que prestaban sus servicios en los centros de la Mutua Colaboradora con la Seguridad Social MC Mutual y que realizaron un curso de seguridad del paciente. Se evaluaron los conocimientos adquiridos mediante una prueba al inicio (P1) y al final del curso (P2). Además, se eligió una muestra de conveniencia de 42 administrativos/as para evaluar sus conocimientos mediante entrevista, previos (E1) y posteriores (E2) al curso, y a los 6 meses (E3). Resultados: De los 170 administrativos/as participantes en el curso, 167 (98,2%) completaron la prueba al inicio y final, con puntuaciones medias que incrementaron de 5,7 (P1) a 7,3 (P2) (p<0,05). Aceptaron participar en las entrevistas 22 administrativos/as de una muestra de 42 (52,4%), y se consiguieron las tres entrevistas de 21 (E1), 22 (E2) y 19 (E3) administrativos/as, cuyas puntuaciones medias incrementaron desde 5,9 (E1) a 7,2 (E2) y 7,5 (E3) (p<0,05). Conclusiones: Los resultados sugieren que el curso de formación fue efectivo. La evaluación mediante la entrevista a los seis meses del curso indica un probable efecto a medio-largo plazo. La implicación de los/as profesionales administrativos/as en la atención a los usuarios de la Mutua es clave. La evaluación del impacto de una intervención es esencial para informar sobre su efectividad y orientar su planificación.
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Segurança do Paciente , Previdência Social , Humanos , Fatores de Tempo , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Capacitação em ServiçoRESUMO
Introducción: El personal administrativo es un colectivo esencial. El objetivo de este estudio es analizar el impacto formativo de un curso online básico sobre seguridad del paciente para administrativos. Método: Estudio cuasi experimental antes/después en una población de 170 administrativos/as que prestaban sus servicios en los centros de la Mutua Colaboradora con la Seguridad Social MC Mutual y que realizaron un curso de seguridad del paciente. Se evaluaron los conocimientos adquiridos mediante una prueba al inicio (P1) y al final del curso (P2). Además, se eligió una muestra de conveniencia de 42 administrativos/as para evaluar sus conocimientos mediante entrevista, previos (E1) y posteriores (E2) al curso, y a los 6 meses (E3).Resultados: De los 170 administrativos/as participantes en el curso, 167 (98,2%) completaron la prueba al inicio y final, con puntuaciones medias que incrementaron de 5,7 (P1) a 7,3 (P2) (p<0,05). Aceptaron participar en las entrevistas 22 administrativos/as de una muestra de 42 (52,4%), y se consiguieron las tres entrevistas de 21 (E1), 22 (E2) y 19 (E3) administrativos/as, cuyas puntuaciones medias incrementaron desde 5,9 (E1) a 7,2 (E2) y 7,5 (E3) (p<0,05). Conclusiones: Los resultados sugieren que el curso de formación fue efectivo. La evaluación mediante la entrevista a los seis meses del curso indica un probable efecto a medio-largo plazo. La implicación de los/as profesionales administrativos/as en la atención a los usuarios de la Mutua es clave. La evaluación del impacto de una intervención es esencial para informar sobre su efectividad y orientar su planificación.(AU)
Introduction: Clerical staff are an essential part of the healthcare team, as they provide administrative and organizational support to healthcare institutions. The aim of this study is to determine the impact of a basic one-hour online training course on patient safety for these staff.Method: A quasi-experimental pre/post study carried out in a population of 170 administra-tive staff working in the centers of an Occupational Mutual Insurance Company (MC Mutu-al) who completed the patient safety training. A convenience sample of 22 administrative professionals, who agreed to participate, was chosen from this population, which made it possible to test their knowledge before and after the course, by examination (P1, P2) and interview, immediately after the course and at 6 months (E1, E2, E3).Results: Of the 170 professionals participating in the course, 167 (98.2%) completed the initial test and the post-test, with mean scores increasing from 5.7 (P1) to 7.3 (P2) (p<0.05). A total of 22 out of a sample of 42 (52.4%) agreed to participate in the interviews and all three interviews were completed by 21 (E1), 22 (E2) and 19 (E3) professionals, whose mean scores increased from 5.9 (E1) to 7.2 (E2) and 7.5 (E3) (p<0.05) Conclusions: The results suggest that the training course was effective. The evaluation by interview 6 months after the course indicates a likely medium to long term effect. The involvement of administrative professionals in the company ́s patient care is key. Evaluating the impact of an intervention is essential to inform its effectiveness and guide its plannin.(AU)
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Humanos , Masculino , Feminino , Saúde Ocupacional , Pessoal Administrativo/educação , Educação a Distância , Cursos de Capacitação , Segurança do Paciente , Educação ContinuadaRESUMO
BACKGROUND: Serum transaminases, alkaline phosphatase and bilirubin are common parameters used for DILI diagnosis, classification, and prognosis. However, the relevance of clinical examination, histopathology and drug chemical properties have not been fully investigated. As cholestasis is a frequent and complex DILI manifestation, our goal was to investigate the relevance of clinical features and drug properties to stratify drug-induced cholestasis (DIC) patients, and to develop a prognosis model to identify patients at risk and high-concern drugs. METHODS: DIC-related articles were searched by keywords and Boolean operators in seven databases. Relevant articles were uploaded onto Sysrev, a machine-learning based platform for article review and data extraction. Demographic, clinical, biochemical, and liver histopathological data were collected. Drug properties were obtained from databases or QSAR modelling. Statistical analyses and logistic regressions were performed. RESULTS: Data from 432 DIC patients associated with 52 drugs were collected. Fibrosis strongly associated with fatality, whereas canalicular paucity and ALP associated with chronicity. Drugs causing cholestasis clustered in three major groups. The pure cholestatic pattern divided into two subphenotypes with differences in prognosis, canalicular paucity, fibrosis, ALP and bilirubin. A predictive model of DIC outcome based on non-invasive parameters and drug properties was developed. Results demonstrate that physicochemical (pKa-a) and pharmacokinetic (bioavailability, CYP2C9) attributes impinged on the DIC phenotype and allowed the identification of high-concern drugs. CONCLUSIONS: We identified novel associations among DIC manifestations and disclosed novel DIC subphenotypes with specific clinical and chemical traits. The developed predictive DIC outcome model could facilitate DIC prognosis in clinical practice and drug categorization.
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Colestase , Aprendizado de Máquina , Fenótipo , Humanos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestase/induzido quimicamente , Bases de Dados Factuais , PrognósticoRESUMO
BACKGROUND: Limited data are available on the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). We describe the natural history of pre-existing IBD and de novo IBD after SOT. METHODS: This was a retrospective, multicenter study that included patients with pre-existing IBD at the time of SOT and patients with de novo IBD after SOT. The primary outcome was IBD progression, defined by escalation of medical treatment, surgical therapy, or hospitalization due to refractory IBD. Risk factors were identified using multivariate Cox proportional hazard analysis. RESULTS: A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) were included. Most patients with pre-existing IBD (92.5%) were in remission before SOT. During follow-up, 32% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 (interquartile range, 1.3-4.6) years. In the de novo cohort, 55% of patients had disease progression with a median time to flare of 1.9 (interquartile range, 0.8-3.9) years after diagnosis. In the pre-existing IBD cohort, active IBD at the time of SOT (hazard ratio, 1.80; 95% confidence interval, 1.14-2.84; Pâ =â .012) and the presence of extraintestinal manifestations (hazard ratio, 3.10; 95% confidence interval, 1.47-6.54; Pâ =â .003) were predictive factors for IBD progression. CONCLUSIONS: One-third of patients with pre-existing IBD and about half of patients with de novo IBD have disease progression after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for IBD progression.
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Drug-induced liver injury (DILI) is a serious adverse hepatic event presenting diagnostic and prognostic challenges. The clinical categorization of DILI into hepatocellular, cholestatic, or mixed phenotype is based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values; however, this classification may not capture the full spectrum of DILI subtypes. With this aim, we explored the utility of assessing changes in the plasma metabolomic profiles of 79 DILI patients assessed by the RUCAM (Roussel Uclaf Causality Assessment Method) score to better characterize this condition and compare results obtained with the standard clinical characterization. Through the identification of various metabolites in the plasma (including free and conjugated bile acids and glycerophospholipids), and the integration of this information into predictive models, we were able to evaluate the extent of the hepatocellular or cholestatic phenotype and to assign a numeric value with the contribution of each specific DILI sub-phenotype into the patient's general condition. Additionally, our results showed that metabolomic analysis enabled the monitoring of DILI variability responses to the same drug, the transitions between sub-phenotypes during disease progression, and identified a spectrum of residual DILI metabolic features, which can be overlooked using standard clinical diagnosis during patient follow-up.
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Doença Hepática Induzida por Substâncias e Drogas , Colestase , Humanos , Fatores de Risco , Alanina TransaminaseRESUMO
BACKGROUND: Antibiotic treatment of Mycobacterium abscessus disease is toxic and poorly effective and lacks a firm evidence base. Dual ß-lactam and ß-lactam/ß-lactamase inhibitor combinations may be interesting leads to improve treatment outcomes. OBJECTIVES: To summarize the current preclinical studies on dual ß-lactam and ß-lactam/ß-lactamase inhibitor combinations against M. abscessus. SOURCES: We performed a literature search using the National Center for Biotechnology Information's PubMed interface with additional snowball sampling. CONTENT: Select combinations of ß-lactam antibiotics, as well as ß-lactam/ß-lactamase inhibitor combinations show promising in vitro activity and synergy against M. abscessus. ß-Lactam antibiotics differ in their ability to reach and interfere with their targets and their resistance to the M. abscessus ß-lactamase. The synergy is typically observed for combinations of ß-lactam antibiotics or a ß-lactam antibiotic with a ß-lactamase inhibitor. No additional killing capacity was demonstrated in three-drug combinations of synergistic ß-lactam antibiotics and a ß-lactamase inhibitor. The efficacy of select dual ß-lactam antibiotics and ß-lactam/ß-lactamase inhibitor combinations is retained in intracellular infection assays and mouse models, but no combination has a complete preclinical portfolio. IMPLICATIONS: Future clinical strategies should entail either dual ß-lactam or ß-lactam/ß-lactamase inhibitor combinations. Imipenem-ceftaroline and an all-oral tebipenem-avibactam combination are promising leads but still require a complete preclinical portfolio, target product profiles as well as clinical trial confirmation.
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Antibacterianos , Sinergismo Farmacológico , Quimioterapia Combinada , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Inibidores de beta-Lactamases , beta-Lactamas , Mycobacterium abscessus/efeitos dos fármacos , beta-Lactamas/uso terapêutico , beta-Lactamas/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Inibidores de beta-Lactamases/uso terapêutico , Inibidores de beta-Lactamases/farmacologia , Humanos , Resultado do Tratamento , Animais , Testes de Sensibilidade MicrobianaRESUMO
The combination of hydrogels and magnetic nanoparticles, scarcely explored to date, offers a wide range of possibilities for innovative therapies. Herein, we have designed hybrid 3D matrices integrating natural polymers, such as collagen, chitosan (CHI) and hyaluronic acid (HA), to provide soft and flexible 3D networks mimicking the extracellular matrix of natural tissues, and iron oxide nanoparticles (IONPs) that deliver localized heat when exposed to an alternating magnetic field (AMF). First, colloidally stable nanoparticles with a hydrodynamic radius of â¼20 nm were synthesized and coated with either CHI (NPCHI) or HA (NPHA). Then, collagen hydrogels were homogeneously loaded with these coated-IONPs resulting in soft (E0 â¼ 2.6 kPa), biodegradable and magnetically responsive matrices. Polymer-coated IONPs in suspension preserved primary neural cell viability and neural differentiation even at the highest dose (0.1 mg Fe/mL), regardless of the coating, even boosting neuronal interconnectivity at lower doses. Magnetic hydrogels maintained high neural cell viability and sustained the formation of highly interconnected and differentiated neuronal networks. Interestingly, those hydrogels loaded with the highest dose of NPHA (0.25 mgFe/mg polymer) significantly impaired non-neuronal differentiation with respect to those with NPCHI. When evaluated under AMF, cell viability slightly diminished in comparison with control hydrogels magnetically stimulated, but not compared to their counterparts without stimulation. Neuronal differentiation under AMF was only affected on collagen hydrogels with the highest dose of NPHA, while non-neuronal differentiation regained control values. Taken together, NPCHI-loaded hydrogels displayed a superior performance, maybe benefited from their higher nanomechanical fluidity. STATEMENT OF SIGNIFICANCE: Hydrogels and magnetic nanoparticles are undoubtedly useful biomaterials for biomedical applications. Nonetheless, the combination of both has been scarcely explored to date. In this study, we have designed hybrid 3D matrices integrating both components as promising magnetically responsive platforms for neural therapeutics. The resulting collagen scaffolds were soft (E0 â¼ 2.6 kPa) and biodegradable hydrogels with capacity to respond to external magnetic stimuli. Primary neural cells proved to grow on these substrates, preserving high viability and neuronal differentiation percentages even under the application of a high-frequency alternating magnetic field. Importantly, those hydrogels loaded with chitosan-coated iron oxide nanoparticles displayed a superior performance, likely related to their higher nanomechanical fluidity.
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Quitosana , Hidrogéis , Hidrogéis/farmacologia , Quitosana/farmacologia , Colágeno/farmacologia , Ácido Hialurônico/farmacologia , Técnicas de Cultura de Células , Fenômenos MagnéticosRESUMO
BACKGROUND AND AIMS: Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) requires histology. In this study, a magnetic resonance imaging (MRI) score was developed and validated to identify MASH in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Secondarily, a screening strategy for MASH diagnosis was investigated. METHODS: This prospective multicentre study included 317 patients with biopsy-proven MASLD and contemporaneous MRI. The discovery cohort (Spain, Portugal) included 194 patients. NAFLD activity score (NAS) and fibrosis were assessed with the NASH-CRN histologic system. MASH was defined by the presence of steatosis, lobular inflammation, and ballooning, with NAS ≥4 with or without fibrosis. An MRI-based composite biomarker of Proton Density Fat Fraction and waist circumference (MR-MASH score) was developed. Findings were afterwards validated in an independent cohort (United States, Spain) with different MRI protocols. RESULTS: In the derivation cohort, 51% (n = 99) had MASH. The MR-MASH score identified MASH with an AUC = .88 (95% CI .83-.93) and strongly correlated with NAS (r = .69). The MRI score lower cut-off corresponded to 88% sensitivity with 86% NPV, while the upper cut-off corresponded to 92% specificity with 87% PPV. MR-MASH was validated with an AUC = .86 (95% CI .77-.92), 91% sensitivity (lower cut-off) and 87% specificity (upper cut-off). A two-step screening strategy with sequential MR-MASH examination performed in patients with indeterminate-high FIB-4 or transient elastography showed an 83-84% PPV to identify MASH. The AUC of MR-MASH was significantly higher than that of the FAST score (p < .001). CONCLUSIONS: The MR-MASH score has clinical utility in the identification and management of patients with MASH at risk of progression.
Assuntos
Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Estudos Prospectivos , Imageamento por Ressonância Magnética , Fibrose , Biópsia , Biomarcadores/metabolismo , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/metabolismoRESUMO
PURPOSE: To characterize the resistance mechanisms affecting the cefepime-taniborbactam combination in a collection of carbapenemase-producing Enterobacterales (CPE) and carbapenem-resistant Pseudomonas spp. (predominantly P. aeruginosa; CRPA) clinical isolates. METHODS: CPE (n = 247) and CRPA (n = 170) isolates were prospectively collected from patients admitted to 8 Spanish hospitals. Susceptibility to cefepime-taniborbactam and comparators was determined by broth microdilution. Cefepime-taniborbactam was the most active agent, inhibiting 97.6% of CPE and 67.1% of CRPA (MICs ≤ 8/4 mg/L). All isolates with cefepime-taniborbactam MIC > 8/4 mg/L (5 CPE and 52 CRPA) and a subset with MIC ≤ 8/4 mg/L (23 CPE and 24 CRPA) were characterized by whole genome sequencing. RESULTS: A reduced cefepime-taniborbactam activity was found in two KPC-ST307-Klebsiella pneumoniae isolates with altered porins [KPC-62-K. pneumoniae (OmpA, OmpR/EnvZ), KPC-150-K. pneumoniae (OmpK35, OmpK36)] and one each ST133-VIM-1-Enterobacter hormaechei with altered OmpD, OmpR, and OmpC; IMP-8-ST24-Enterobacter asburiae; and NDM-5-Escherichia coli with an YRIN-inserted PBP3 and a mutated PBP2. Among the P. aeruginosa (68/76), elevated cefepime-taniborbactam MICs were mostly associated with GES-5-ST235, OXA-2+VIM-2-ST235, and OXA-2+VIM-20-ST175 isolates also carrying mutations in PBP3, efflux pump (mexR, mexZ) and AmpC (mpl) regulators, and non-carbapenemase-ST175 isolates with AmpD-T139M and PBP3-R504C mutations. Overall, accumulation of these mutations was frequently detected among non-carbapenemase producers. CONCLUSIONS: The reduced cefepime-taniborbactam activity among the minority of isolates with elevated cefepime-taniborbactam MICs is not only due to IMP carbapenemases but also to the accumulation of multiple resistance mechanisms, including PBP and porin mutations in CPE and chromosomal mutations leading to efflux pumps up-regulation, AmpC overexpression, and PBP modifications in P. aeruginosa.
Assuntos
Antibacterianos , Proteínas de Bactérias , Ácidos Borínicos , Carbapenêmicos , Ácidos Carboxílicos , Humanos , Cefepima/farmacologia , Carbapenêmicos/farmacologia , Antibacterianos/farmacologia , Pseudomonas/genética , Espanha/epidemiologia , beta-Lactamases/genética , Pseudomonas aeruginosa/genética , Testes de Sensibilidade MicrobianaRESUMO
Existing literature on executive coaching has shown beneficial outcomes for leaders. Indeed, executive coaching can positively affect an individual's psychological well-being and quality of work life. However, while burnout among leaders is on the rise, to our knowledge no prior study has investigated the influence of executive coaching on the dimensions of burnout and engagement concurrently. Therefore, the aim of the current study is to examine if an executive coaching intervention has positive effects on managerial burnout and engagement. We implemented a ten-week coaching intervention for leaders, where questionnaire data were collected at two time points. Participants (N = 92; Mage = 42; 64% male) were randomly assigned to an intervention or a wait-list control group. Self-reported levels of engagement and burnout were collected at the start of the study protocol (T1) and at the end (T2). Coaching sessions for the intervention group were one hour once per week. The control group did not receive coaching. Repeated measures ANOVAs examined the extent to which the intervention influences the leader's engagement and burnout. Analyses revealed that all three dimensions of burnout significantly decreased for the intervention group over time while vigor increased. Findings did not reveal an increase in dedication and absorption. Consistent with prior literature, this study supports that executive coaching can improve a leader's well-being. Specifically, this study shows that an executive coaching intervention can decrease burnout symptoms and increase vigor in leaders. Adding a follow-up survey to the design would allow for further exploration of the intervention on engagement.
RESUMO
Diabetes mellitus (DM) constitutes a chronic metabolic disease characterized by elevated levels of blood glucose which can also lead to the so-called diabetic vascular complications (DVCs), responsible for most of the morbidity, hospitalizations and death registered in these patients. Currently, different approaches to prevent or reduce DM and its DVCs have focused on reducing blood sugar levels, cholesterol management or even changes in lifestyle habits. However, even the strictest glycaemic control strategies are not always sufficient to prevent the development of DVCs, which reflects the need to identify reliable biomarkers capable of predicting further vascular complications in diabetic patients. Endothelial progenitor cells (EPCs), widely known for their potential applications in cell therapy due to their regenerative properties, may be used as differential markers in DVCs, considering that the number and functionality of these cells are affected under the pathological environments related to DM. Besides, drugs commonly used with DM patients may influence the level or behaviour of EPCs as a pleiotropic effect that could finally be decisive in the prognosis of the disease. In the current review, we have analysed the relationship between diabetes and DVCs, focusing on the potential use of EPCs as biomarkers of diabetes progression towards the development of major vascular complications. Moreover, the effects of different drugs on the number and function of EPCs have been also addressed.
Assuntos
Diabetes Mellitus , Angiopatias Diabéticas , Células Progenitoras Endoteliais , Humanos , Células Progenitoras Endoteliais/metabolismo , Diabetes Mellitus/metabolismo , Angiopatias Diabéticas/metabolismo , Glicemia/metabolismo , Biomarcadores/metabolismoRESUMO
BACKGROUND: In 2021, the Spanish Ministry of Health launched the CIBERPOSTCOVID project to establish what post COVID was. The present study reports the level of agreement among stakeholders on post COVID and its clinical and diagnostic characteristics in the Spanish health system. METHODS: The agreement on post COVID among clinicians, public health managers, researchers and patients' representatives was explored in a real-time, asynchronous online Delphi. In a two-wave consensus, respondents rated from 1 (total disagreement) to 6 (total agreement) 67 statements related to terminology, duration, etiology, symptoms, impact on quality of life, severity, elements to facilitate diagnosis, applicability in the pediatric population, and risk factors. Consensus was reached when 70 % of ratings for a statement were 5 or 6, with an interquartile range equal or less than 1. FINDINGS: A total of 333 professionals and patients participated in this eDelphi study. There was agreement that post COVID was "a set of multi-organic symptoms that persist or fluctuate after acute COVID-19 infection and are not attributable to other causes" with a minimum duration of 3 months. The highest levels of agreement were found in the most frequent symptoms and its impacts on everyday activities. Aspects related to the diagnostic process and the measurement of its severity reached a lower level of consensus. There was agreement on the need to rule out previous health problems and assess severity using validated functional scales. However, no agreement was reached on the risk factors or specific features in the pediatric population. INTERPRETATION: This policy-based consensus study has allowed the characterization of post COVID generating collective intelligence and has contributed to an operational definition applicable in clinical practice, health services management and useful for research purposes in Spain and abroad. Agreements are consistent with existing evidence and reference institutions at European and international level.