FCB2-Artigos (em revistas ou actas indexadas)
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- Longitudinal variation of correlations between different components of assessment within a medical schoolPublication . Sousa, Rita Matos; Collares, Carlos; Pereira, Vítor HugoAn assessment program should be inclusive and ensure that the various components of medical knowledge, clinical skills, and professionalism are assessed. The level and the variation over time in the strength of the correlation between these components of assessment is still a matter of study. Based on the meaningful learning theory and the integrated learning theory, we hypothesize that these components increase their connections during the medical school course. MethodsThis is a retrospective cohort study that analyzed data collected for a 10-year period in one medical school. We included students from the 3rd to 6th year of medical school from 2011 to 2021. Three assessment components were addressed: Knowledge, Clinical Skills, and Professionalism. For data analysis, Pearson correlation coefficients (R) and R2 were calculated to study the correlation between variables and a z-test on Fisher's r-to-z was used to determine the differences between correlation coefficients.Results949 medical students were included in the study. The correlation between Clinical Skills and Professionalism showed a medium to strong association (Pearson's R ranging from 0.485 to 0.734), while the correlation between Knowledge and Professionalism was weaker but exhibited a steady evolution with Pearson's R fluctuating between 0.075 and 0.218. The Knowledge and Clinical Skills correlation became statistically significant from 2013 onwards and peaking at Pearson's R of 0.440 for the cohort spanning 2016-2019. We also revealed a strengthening of correlations between Professionalism and Clinical Skills from the beginning to the end of clinical training, but not with the knowledge component. Conclusions This analysis contributes to our understanding of the dynamics of correlations of different assessment components within an institution and provides a framework for how they interact and influence each other. Trial registration. This study was not a clinical trial, but a retrospective observational study, without health care interventions. Nevertheless, we provide herein the number of the study as submitted to the Ethics committee - CEICVS 146/2021.
- Zebrafish Avatar-test forecasts clinical response to chemotherapy in patients with colorectal cancerPublication . Costa, Bruna; Estrada, Marta F.; Gomes, António; Fernandez, Laura M.; Azevedo, José M.; Póvoa, Vanda; Fontes, Márcia; Alves, António; Galzerano, António; Castillo-Martin, Mireia; Herrando, Ignacio; Brandão, Shermann; Carneiro, Carla; Nunes, Vítor; Carvalho, Carlos; Parvaiz, Amjad; Marreiros, Ana; Fior, RitaCancer patients often undergo rounds of trial-and-error to find the most effective treatment because there is no test in the clinical practice for predicting therapy response. Here, we conduct a clinical study to validate the zebrafish patient-derived xenograft model (zAvatar) as a fast predictive platform for personalized treatment in colorectal cancer. zAvatars are generated with patient tumor cells, treated exactly with the same therapy as their corresponding patient and analyzed at single-cell resolution. By individually comparing the clinical responses of 55 patients with their zAvatar-test, we develop a decision tree model integrating tumor stage, zAvatar-apoptosis, and zAvatar-metastatic potential. This model accurately forecasts patient progression with 91% accuracy. Importantly, patients with a sensitive zAvatar-test exhibit longer progression-free survival compared to those with a resistant test. We propose the zAvatar-test as a rapid approach to guide clinical decisions, optimizing treatment options and improving the survival of cancer patients.
- Identification of novel DNA methylation prognostic biomarkers for AML with normal cytogeneticsPublication . Cardoso, Cândida; Pestana, Daniel; Gokuladhas, Sreemol; Marreiros, Ana; Justin M. O'Sullivan; Binnie, Alexandra; Teotónio Fernandes, Mónica Alexandra; Castelo-Branco, PedroPURPOSE AML is a hematologic cancer that is clinically heterogeneous, with a wide range of clinical outcomes. DNA methylation changes are a hallmark of AML but are not routinely used as a criterion for risk stratification. The aim of this study was to explore DNA methylation markers that could risk stratify patients with cytogenetically normal AML (CN-AML), currently classified as intermediate-risk.MATERIALS AND METHODSDNA methylation profiles in whole blood samples from 77 patients with CN-AML in The Cancer Genome Atlas (LAML cohort) were analyzed. Individual 5'-cytosine-phosphate-guanine-3' (CpG) sites were assessed for their ability to predict overall survival. The output was validated using DNA methylation profiles from bone marrow samples of 79 patients with CN-AML in a separate data set from the Gene Expression Omnibus.RESULTSIn the training set, using DNA methylation data derived from the 450K array, we identified 2,549 CpG sites that could potentially distinguish patients with CN-AML with an adverse prognosis (intermediate-poor) from those with a more favorable prognosis (intermediate-favorable) independent of age. Of these, 25 CpGs showed consistent prognostic potential across both the 450K and 27K array platforms. In a separate validation data set, nine of these 25 CpGs exhibited statistically significant differences in 2-year survival. These nine validated CpGs formed the basis for a combined prognostic biomarker panel, which includes an 8-CpG Somatic Panel and the methylation status of cg23947872. This panel displayed strong predictive ability for 2-year survival, 2-year progression-free survival, and complete remission in the validation cohort.CONCLUSIONThis study highlights DNA methylation profiling as a promising approach to enhance risk stratification in patients with CN-AML, potentially offering a pathway to more personalized treatment strategies.
- Oxidative stress and aging: synergies for age related diseasesPublication . Filipa Santos, Daniela; Simao, Sonia; Nóbrega, Clévio; Bragança, José; Castelo-Branco, Pedro; Pombinho de Araújo, Inês Maria; ALFA Score ConsortiumAging is characterized by a progressive decline in physiological function and underlies several disabilities, including the increased sensitivity of cells and tissues to undergo pathological oxidative stress. In recent years, efforts have been made to better understand the relationship between age and oxidative stress and further develop therapeutic strategies to minimize the impact of both events on age-related diseases. In this work, we review the impact of the oxidant and antioxidant systems during aging and disease development and discuss the crosstalk of oxidative stress and other aging processes, with a focus on studies conducted in elderly populations.
- Knowledge attainment, learning approaches, and self-perceived study burnout among European veterinary studentsPublication . Iivanainen, Antti; Wandall, Jakob; Parpala, Anna; Nevgi, Anne; Keto-Timonen, Riikka; Tipold, Andrea; Schaper, Elisabeth; van Haeften, Theo; Pihl, Tina Holberg; Press, Charles McLean; Holm, Peter; Collares, CarlosThis study investigates the relationship between approaches to learning, self-perceived study burnout, and the level of knowledge among veterinary students. Veterinary educational programs are under regular development and would benefit greatly from detailed feedback on students' knowledge, proficiency, influencing factors, and coping mechanisms.Methods The VetRepos consortium developed and calibrated an item repository testing knowledge across the entire veterinary curriculum. Two hundred forty-eight students from seven European veterinary institutions took the VetRepos test, comprising a subset of the repository. They also responded to a questionnaire assessing deep and unreflective learning approaches and self-perceived study burnout, represented by exhaustion and cynicism. Structural equation modeling analyzed the relationship between these latent traits and the VetRepos test score.Results The model failed the exact-fit test but was retained based on global fit indices, inter-item residual correlations, and standardized residual covariances. Root Mean Square Error of Approximation with robust standard errors and scaled test statistic was 0.049 (95% confidence interval 0.033-0.071), scaled and robust Comparative Fit Index 0.95 (0.90-0.98), and scaled Standardized Root Mean Square Residual 0.056 (0.049-0.071). Measurement invariance across study years was not violated (Delta CFI = 0.00, chi 2 = 3.78, Delta df = 4, p = 0.44), but it could not be confirmed between genders or universities. The VetRepos test score regressed on the study year [standardized regression coefficient = 0.68 (0.62-0.73)], showed a negative regression on the unreflective learning approach [-0.25 (-0.47 to -0.03)], and a positive regression on the deep approach [0.16 (0.03-0.28)]. No direct association with perceived burnout was observed; however, a significant, medium-sized association was found between the unreflective approach and self-perceived study burnout. No significant differences in learning approaches or perceived burnout were found between study years.Discussion The most important source of variance in VetRepos test scores, unrelated to the study year, was the learning approach. The association between the VetRepos test score and self-perceived burnout was indirect. Future research should complement this cross-sectional approach with longitudinal and person-oriented studies, further investigating the relationship between study burnout and learning approaches.
- Drug-associated acute kidney disease – data from a world pharmacovigilance databasePublication . Baptista, Alexandre; Marreiros, Ana; Macedo, Ana; Coelho, AndréBackground Drugs are a frequent cause of nephrotoxicity, especially in the context of acute kidney disease (AKD), with a significant number of cases being drug-associated. The WHO's VigiBase is a powerful tool for identifying drugs described and associated with the development of AKD. Methods We retrieved data from the period 1968 to 2022 regarding notifications of adverse drug reactions (ADR). The extracted medications were evaluated for their nephrotoxicity based on the bibliographic score (BS) developed through pre-selected references. The main medications involved were classified as 'non-nephrotoxic', 'potentially nephrotoxic', and 'nephrotoxic'. We utilized the IC025 and reporting odds ratio (ROR) disproportionality indexes to study the relationship between medications and the odds of being included in an AKD notification. Results During the period, a total of 33,932,051 notifications were obtained, revealing 435,677 cases related to drug-associated AKD following MedDRA term filtering, predominantly affecting males aged 45-64. We identified 8,991 active ingredients or suspected combinations associated with AKD development, with the ATC class A - Alimentary Tract and Metabolism being the most frequently described. Among the medications most strongly associated with this phenotype, classes J and N stood out. Among the most notable medications collected, 8.3% were classified as "non-nephrotoxic," 16.7% as "potentially nephrotoxic," and 75% as "known nephrotoxic." Notable active ingredients included cobicistat + elvitegravir + emtricitabine + tenofovir disoproxil (IC025 8.7; ROR 786.96), inotersen (IC025 7.7; ROR 604.57), emtricitabine + tenofovir disoproxil (IC025 7.9; ROR 432.36), esomeprazole (IC025 6.8; ROR 184.23), and pantoprazole (IC025 6.3; ROR 109.86), with proton pump inhibitors dominating the top four positions among the most frequently involved medications. Conclusion AKD is a frequent adverse reaction in VigiBase, with a significantly high reported mortality rate. Evaluation of the notifications revealed medications with a high disproportionality index and a strong association with AKD. We also highlight the potential nephrotoxic role of less suspected medications. This study emphasizes the need to consider AKD as a condition potentially associated with iatrogenic etiology, highlighting various medications and their respective involvement in the various possible manifestations of AKD.
- Potentially inappropriate medication: a pilot study in institutionalized older adultsPublication . Andrade, Amanda de Oliveira; Nascimento, Tânia; Cabrita, Catarina; Leitao, Helena; Pinto, EzequielInstitutionalized older adults often face complex medication regimens, increasing their risk of adverse drug events due to polypharmacy, overprescribing, medication interactions, or the use of Potentially Inappropriate Medications (PIM). However, data on medication use and associated risks in this population remain scarce. This pilot study aimed to characterize the sociodemographic, clinical and pharmacotherapeutic profiles, and the use of PIM among institutionalized elders residing in Residential Structures for Elderly People (ERPI) in the Faro municipality, located in the Portuguese region of the Algarve. We conducted a cross-sectional study in a non-randomized sample of 96 participants (mean age: 86.6 ± 7.86 years) where trained researchers reviewed medication profiles and identified potentially inappropriate medications using the EU(7)-PIM list. Over 90% of participants exhibited polypharmacy (≥5 medications), with an average of 9.1 ± 4.15 medications per person. About 92% had potential drug interactions, including major and moderate interactions. More than 86% used at least one potentially inappropriate medication, most commonly central nervous system drugs. This pilot study demonstrates that institutionalized older adults may be at high risk of potential medication-related problems. Implementing comprehensive medication review programs and promoting adapted prescribing practices are crucial to optimize medication use and improve the well-being of this vulnerable population.
- Camptothecin-loaded mesoporous silica nanoparticles functionalized with CpG oligodeoxynucleotide as a new approach for skin cancer treatmentPublication . Qureshi, Munibah; Viegas, Cláudia; Duarte, Sofia O.D.; Girardi, Michael; Shehzad, Adeeb; Fonte, PedroThe therapeutic efficacy of camptothecin (CPT), a potent antitumor alkaloid, is hindered by its hydrophobic nature and instability, limiting its clinical use in treating cutaneous squamous cell carcinoma (SCC). This study introduces a novel nano drug delivery system (NDDS) utilizing functionalized mesoporous silica nanoparticles (FMSNs) for efficient CPT delivery. The FMSNs were loaded with CPT and subsequently coated with chitosan (CS) for enhanced stability and bioadhesion. Importantly, CpG oligodeoxynucleotide (CpG ODN) was attached onto the CS-coated FMSNs to leverage the immunostimulatory properties of CpG ODN, augmenting the chemotherapy's efficacy. The final formulation FMSN-CPT-CS-CpG displayed an average size of 241 nm and PDI of 0.316 with an encapsulation efficiency of 95 %. Comprehensive in vitro and in vivo analyses, including B16F10 cells and DMBA/TPA-induced SCC murine model, demonstrated that the FMSN-CPT-CS-CpG formulation significantly enhanced cytotoxicity against B16F10 cells and induced complete regression in 40 % of the in vivo subjects, surpassing the efficacy of standard CPT and FMSN-CPT treatments. This study highlights the potential of combining chemotherapeutic and immunotherapeutic agents in an NDDS for targeted, efficient skin cancer treatment.
- Editorial: the role of thyroid hormones in vertebrate development, volume IIPublication . Campinho, Marco António; Sachs, Laurent M.The thyroid hormone is an important signaling molecule system involved in vertebrate development, acting at the embryonic and post-embryonic levels (1). Although this has long been established, a detailed understanding of the thyroid hormone’s developmental action still needs to be fully understood. The present Frontiers in Endocrinology Research Topic aims to close this knowledge gap by bringing together a collection of papers addressing what is known and the challenges ahead on the role of thyroid hormones in vertebrate development, from teleosts to humans. The published manuscripts highlight the pivotal action of thyroid hormones in vertebrate neurodevelopment (Lee at al.; Ng et al.; O’Shaughnessy et al.; Richard et al.; Silva and Campinho; Valcárcel-Hernández et al.), post natal development in amphibians (8–10) and how thyroid disorders can affect human development (Ru et al.; SeyedAlinaghi et al.).
- Spatio-temporal dynamics of early somite segmentation in the chicken embryoPublication . Maia-Fernandes, Ana C; Martins, Ana; Borralho Martins, Nísia; Pais de Azevedo, Tomás; Magno, Ramiro; dos Santos Duarte, Guilhermina Isabel; Andrade, Raquel; MDuring vertebrate embryo development, the body is progressively segmented along the anterior-posterior (A-P) axis early in development. The rate of somite formation is controlled by the somitogenesis embryo clock (EC), which was first described as gene expression oscillations of hairy1 (hes4) in the presomitic mesoderm of chick embryos with 15-20 somites. Here, the EC displays the same periodicity as somite formation, 90 min, whereas the posterior-most somites (44-52) only arise every 150 minutes, matched by a corresponding slower pace of the EC. Evidence suggests that the rostral-most somites are formed faster, however, their periodicity and the EC expression dynamics in these early stages are unknown. In this study, we used time-lapse imaging of chicken embryos from primitive streak to somitogenesis stages with high temporal resolution (3-minute intervals). We measured the length between the anterior-most and the last formed somitic clefts in each captured frame and developed a simple algorithm to automatically infer both the length and time of formation of each somite. We found that the occipital somites (up to somite 5) form at an average rate of 75 minutes, while somites 6 onwards are formed approximately every 90 minutes. We also assessed the expression dynamics of hairy1 using half-embryo explants cultured for different periods of time. This showed that EC hairy1 expression is highly dynamic prior to somitogenesis and assumes a clear oscillatory behaviour as the first somites are formed. Importantly, using ex ovo culture and live-imaging techniques, we showed that the hairy1 expression pattern recapitulates with the formation of each new pair of somites, indicating that somite segmentation is coupled with EC oscillations since the onset of somitogenesis.