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FCB2-Artigos (em revistas ou actas indexadas)

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Now showing 1 - 10 of 856
  • Polyoxometalates’ progress for the treatment of Alzheimer’s disease
    Publication . Aureliano, Manuel; Mateus, João; Rijo, David Manjua
    Alzheimer’s disease (AD) signifies a devastating impact on the quality of life of patients and their families. At a biomolecular level, AD is characterized by the deposition of extracellular plaques of β-amyloid (Aβ), affecting language, spatial navigation, recognition abilities and memory. Among the selected 30 articles about polyoxometalates (POMs) and AD published from 2011 to 2025, pure POMs, hybrid POMs and POM nanoparticles can be found. The majority of POMs are polyoxotungstates (62%), the Keggin-type SiW11O39 being the most studied in AD. The main effect described is the inhibition of Aβ aggregates. Other effects include reversing the neurotoxicity induced by Aβ aggregates, decreasing ROS production and neuroinflammation, restoring memory and sequestering Zn2+ and Cu2+, among others, features that are well known to be associated with the pathology of AD. POMs have also shown the ability to induce the disaggregation of Aβ fibrils, particularly after irradiation, and to inhibit acetylcholinesterase activity at an nM range. Putting it all together, this review highlights a predominant trend in the exploration of POMs to act directly at the level of the formation and/or disaggregation of Aβ aggregates in the treatment of AD.
  • Polypharmacy and the use of potentially inappropriate medications in elderly people in nursing homes: a cross-sectional study
    Publication . Fest, Giulia; Costa, Lara; Pinto, Ezequiel; Leitao, Helena; Nascimento, Tânia
    Polypharmacy and the use of potentially inappropriate medications (PIM) are prevalent issues among institutionalized older adults, contributing to adverse drug events and decreased quality of life. This study aimed to describe the sociodemographic and clinical characteristics associated with polypharmacy and the use of PIM in elderly people in nursing homes. A cross-sectional descriptive study was conducted among 151 residents aged ≥ 65 years. Data was extracted from institutional records. The mean age of participants was 86.48 ± 8.00 years; 71.5% were female. Excessive polypharmacy was observed in 49.7% of residents. The mean number of medications was 9.66 ± 4.18, with nervous system drugs being the most prescribed (3.73 ± 2.31). PDDIs were detected in 94% of the sample and PIMs were present in 82.8% of residents. The most common PIMs were proton pump inhibitors (ATC A) and anxiolytics (ATC N). Binary logistic regression identified two independent predictors for PIMs: the total number of medications (AOR = 1.259) and the use of ATC A (Alimentary tract and metabolism) medications (AOR = 2.315). Conversely, age and sex were not significant predictors. The study reveals a critical prevalence of excessive polypharmacy, PIM use, and PDDIs among institutionalized elderly in the Algarve. These findings underscore the urgent need for systematic, multidisciplinary medication reviews in Portuguese nursing homes to promote safer and more rational prescribing practices.
  • IL-6 and Surgical Outcomes in Carotid Endarterectomy: A Systematic Review.
    Publication . Rocha-Melo-Sousa, Antónia; Brazuna, Márcio; Tavares, Carmen; Guduru, Sai; Fragão-Marques, Mariana; Rocha-Neves, João
    Interleukin-6 (IL-6) is a key inflammatory cytokine implicated in atherosclerotic plaque progression and carotid vulnerability. Although elevated IL-6 levels have been linked to cerebrovascular risk, its prognostic value in patients undergoing carotid endarterectomy (CEA) remains undefined. This systematic review aimed to investigate the available evidence on the relationship between IL-6 levels, surgical outcomes and mechanistic evidence in CEA patients. The review followed the PRISMA statement and AMSTAR-2 critical appraisal guidelines, with the protocol registered on PROSPERO (CRD420251120023). PubMed/MEDLINE, Scopus, and Web of Science were systematically searched up to July 2025 using the terms "interleukin-6" and "carotid endarterectomy". Original studies in humans assessing IL-6 in relation to clinical outcomes after CEA or mechanistic evidence were included without language or date restrictions. Study quality was evaluated using the Cochrane Risk of Bias 2 and NHLBI tools, and evidence certainty was appraised using the GRADE framework. Given the heterogeneity of studies, only a qualitative synthesis was performed. : From 1232 records identified, 13 studies encompassing 1396 patients met the inclusion criteria. Most were prospective observational cohorts, with a mean participant age of 68.52 years and 81.16% male predominance. Perioperative stroke and mortality rates were uniformly low (≤2%), consistent with contemporary registry data. Across studies, elevated IL-6 levels-whether systemic or plaque-derived-were consistently associated with symptomatic carotid disease, plaque vulnerability, and adverse long-term outcomes. However, not all studies presented quantitative data on IL-6 levels, limiting the ability to draw definitive prognostic conclusions. : Current evidence supports a mechanistic link between IL-6-mediated inflammation and carotid plaque instability, yet robust clinical validation in surgical populations is lacking. Future large-scale, prospective studies incorporating IL-6 measurement are warranted to establish its prognostic utility, guide anti-inflammatory therapeutic strategies, and refine postoperative risk stratification in patients undergoing CEA.
  • Unraveling the potential of gasotransmitters as neurogenic and neuroprotective molecules: focus on Alzheimer's and Parkinson's diseases.
    Publication . Simao, Sonia; Filipa Santos, Daniela; Teixeira, Mariana; Agostinho, Rafaela R.; Rodrigues, Joana; Vitorino, Marta; Araújo, Inês M.
    Alzheimer's disease and Parkinson's disease are the two most prevalent neurodegenerative disorders worldwide, both characterized by progressive neuronal loss. Despite distinct pathophysiological features, they share cellular dysfunctions such as abnormal protein aggregation, oxidative stress, and neuroinflammation, research into which might be beneficial for developing novel therapeutic strategies that could tackle both conditions. This review highlights the emerging role of the gasotransmitters nitric oxide, carbon monoxide and hydrogen sulfide as modulators of adult neurogenesis and neuroprotection in Alzheimer's disease and Parkinson's disease. We have gathered recent evidence demonstrating that these endogenous gases exert anti-inflammatory, antioxidant, and anti-apoptotic effects, and, critically, promote neurogenesis - suggesting a dual neuroprotective and neuroregenerative therapeutic potential. The unique physicochemical features of these gasotransmitters, including their ability to cross the blood-brain barrier and diffuse rapidly throughout the neural tissue, further support their suitability as candidates for innovative neuroregenerative treatments. While clinical translation remains challenging, harnessing the neurogenic and neuroprotective actions of these gasotransmitters may offer transformative avenues for addressing the increasing burden of Alzheimer's disease and Parkinson's disease.
  • Assessing the impact of different feedback mechanisms on suture skills acquisition: a mixed methods study using phenomenological and quantitative analysis
    Publication . Gonçalves, Nuno Silva; Collares, Carlos; Pêgo, José Miguel
    BACKGROUND: Even though suture skills are recognized as important for medical graduates, they are often underdeveloped due to reduced surgical exposure, limited feedback opportunities, and constraints on teaching resources. While various feedback strategies exist to support skill acquisition, comparative evidence on their effectiveness from the learner’s perspective is limited. OBJECTIVE: To assess the impact of 3 feedback modalities: video review alone, video review with structured self-assessment, and video review with expert feedback, on the acquisition of basic suture skills among medical students, using both quantitative and qualitative methods. METHODS: Sixty-eight students were randomly assigned to 3 feedback groups (A: video only, B: video + structured self-assessment, and C: video + expert feedback). Each performed a basic suture task (Part A), received group-specific feedback, and repeated the task (Part B). Performances were video-recorded and rated by blinded assessors using a 15-item checklist and a global score. Additionally, thirteen participants from group C completed semi-structured interviews on their feedback experience. RESULTS: The mean global score rose from 3.24 to 3.52 in Group A, 3.46 to 3.63 in Group B, and 3.51 to 3.76 in Group C. ANOVA showed no significant differences between groups (F(2,65) = 0.669, p = 0.516, hp2 = 0.020). Qualitative findings indicated that expert feedback, particularly when combined with video review, significantly enhanced motivation, confidence, and clarity. Group C participants described shifting from “fear of performing sutures” to “confidence,” attributing this to the personalized, emotionally supportive feedback. CONCLUSION: Although performance outcomes were similar across feedback types, expert feedback offered unique emotional and cognitive benefits. These findings support the integration of structured, learner-centered feedback in surgical training, combining scalability with pedagogical value.
  • Tert expression in meningiomas predicts progression-free survival independent of tert promoter mutation
    Publication . Gui, Chloe; Wang, Justin; Patil, Vikas; Landry, Alexander; Castelo-Branco, Pedro; Singh, Olivia; Tabori, Uri; Aldape, Kenneth; Behling, Felix; Barnholtz-Sloan, Jill; Horbinski, Craig; Tabatabai, Ghazaleh; Ajisebutu, Andrew; Liu, Jeff; Patel, Zeel; Yakubov, Rebeca; Kaloti, Ramneet; Ellenbogen, Yosef; Wilson, Christopher; Cohen-Gadol, Aaron; Tatagiba, Marcos; Sloan, Andrew; Holland, Eric; Chambless, Lola; Gao, Andrew; Chotai, Silky; Makarenko, Serge; Yip, Stephen; Nassiri, Farshad; Zadeh, Gelareh
    While TERT promoter mutation (TPM) has been es¬tablished as a marker of clinically aggressive meningiomas, this alteration is rare and found in less than 5% of all cases. However, a larger subset of meningiomas may exhibit aberrant TERT expression in the absence of TPMs. This study investigated the effect of TERT gene expression on clinical outcome in meningioma patients. METHODS: Clinical and mo¬lecular data were retrospectively collected on 1241 meningiomas, split into a Toronto discovery cohort and a multi-institutional validation co¬hort. Sanger sequencing and bulk RNA sequencing were used to determine TPM status and TERT gene expression. The effect of TERT expression on progression-free survival (PFS) was assessed using Kaplan-Meier and Cox regression analysis. RESULTS: While meningiomas with TPM showed expectedly higher TERT gene expression compared to wildtype (TP-WT) cases (p<0.0001), TERT expression was still detected in 28.7% (157/547) of TP-WT meningiomas. Meningiomas with TERT expression showed sig¬nificantly worse PFS compared to meningiomas without any TERT expres¬sion. In fact, WHO grade 1 meningiomas with TERT expression had PFS outcomes resembling WHO grade 2 meningiomas lacking TERT expression (p=0.59). In turn, WHO grade 2 meningiomas with TERT expression had clinical outcomes similar to WHO grade 3 meningiomas without TERT ex¬pression (p=0.42). Furthermore, the proportion of meningiomas expressing TERT as well as overall TERT expression levels increased with increasing WHO grade. Multivariable analysis showed that TERT expression was sig-nificantly associated with worse PFS even when controlling for other known predictors of clinical outcome including TPM, CDKN2A/B loss, 1p/22q status and WHO grade (HR 1.85 [95% CI 1.33-2.57], p=0.00024). CON¬CLUSION: TERT expression is a novel independent biomarker of outcome for meningiomas identifiable in up to one-third of cases that may be utilized to reclassify tumors to a higher WHO grade.
  • Reinfection incidence following surgical intervention for infected aortic bypass: a meta-analysis
    Publication . Brazuna, Márcio; Costa, Marta Gonçalves; Marreiros, Ana; Andrade, Leonardo Araújo; Andrade, José Paulo; Neves, João Rocha
    Background Infection of vascular grafts after aortic revascularization surgery is a serious complication with high morbid ity and mortality. This systematic review and meta-analysis aims to determine reinfection incidence in patients undergoing surgical intervention for infected aortic bypass grafts and identify key risk factors in the literature. Materials and Methods This systematic review and meta-analysis followed PRISMA guidelines. Three electronic databases, PubMed/MEDLINE, Scopus, and Web of Science were used to search studies published after January 1, 2000, that assessed reinfection rates following surgical intervention for infected aortic bypass grafts. Random-effects meta-analysis was per formed to calculate pooled incidence of major outcomes.Results: Our systematic review included 30 studies with a total of 2,341 patients. Overall reinfection rate was 12.7% (95% CI: 8.6%–16.9%). In terms of morbidity 34.1% had acute kidney injury, 23.8% needed amputation, and 29.4% developed acute limb ischemia. The 30-day mortality rate was 27.8% (95% CI: 13.2%–42.4%).The medical approach to treatment varied significantly, however, the majority involved total removal of the infected prosthesis. The main microorganisms isolated in primary infections were mostly Staphylococcus and Enterococ cus species, with a notable representation of gram-negative bacteria.Conclusion: Reinfection rates after surgical treatment of infected aortic bypass grafts were relatively high and constitute a challenge of high clinical impact. This is further demon strated by the high 30-day mortality rate. The significant variation in treatment approaches observed above also highlights the lack of formalized management protocols. Further studies are needed to determine the best surgical approach and patientrelated risk factors to optimize outcomes in this difficult population.
  • Polypharmacy and the Use of Potentially Inappropriate Medications in Elderly People in Nursing Homes: A Cross-Sectional Study
    Publication . Fest, Giulia; Costa, Lara; Pinto, Ezequiel; Leitao, Helena; Nascimento, Tânia
    Polypharmacy and the use of potentially inappropriate medications (PIM) are prevalent issues among institutionalized older adults, contributing to adverse drug events and decreased quality of life. This study aimed to describe the sociodemographic and clinical characteristics associated with polypharmacy and the use of PIM in elderly people in nursing homes. A cross-sectional descriptive study was conducted among 151 residents aged ≥ 65 years. Data was extracted from institutional records. The mean age of participants was 86.48 ± 8.00 years; 71.5% were female. Excessive polypharmacy was observed in 49.7% of residents. The mean number of medications was 9.66 ± 4.18, with nervous system drugs being the most prescribed (3.73 ± 2.31). PDDIs were detected in 94% of the sample and PIMs were present in 82.8% of residents. The most common PIMs were proton pump inhibitors (ATC A) and anxiolytics (ATC N). Binary logistic regression identified two independent predictors for PIMs: the total number of medications (AOR = 1.259) and the use of ATC A (Alimentary tract and metabolism) medications (AOR = 2.315). Conversely, age and sex were not significant predictors. The study reveals a critical prevalence of excessive polypharmacy, PIM use, and PDDIs among institutionalized elderly in the Algarve. These findings underscore the urgent need for systematic, multidisciplinary medication reviews in Portuguese nursing homes to promote safer and more rational prescribing practices.
  • CRISPR-based functional genomics in pluripotent stem cells
    Publication . Zahedi, Setareh
    The integration of CRISPR-based functional genomics with pluripotent stem cell (PSC) technologies has been recognized as a transformative approach for investigating gene function, modeling human disease, and advancing regenerative medicine. The aim of this review is to provide a comprehensive evaluation of recent developments in CRISPR-Cas platforms, including gene knockouts, base and prime editing, and CRISPR activation or interference (CRISPRa/i), as applied to PSC systems. Studies employing human PSCs, including embryonic stem cells and induced pluripotent stem cells, have been examined to summarize methodologies for genome-wide screening, lineage tracing, and therapeutic engineering. Advances in editing efficiency, delivery strategies, and genomic safety have been reported, while limitations persist in the form of off-target modifications, epigenetic variability, and cell-type-specific responses. Notable applications include the generation of immune-evasive PSC lines, the development of organoid models for physiological and pathological studies, and the implementation of phenotypic screening for disease-relevant traits. Collectively, these technological and methodological advancements have established functional genomics of PSC-CRISPRSPR as a versatile and powerful framework for elucidating fundamental aspects of human biology, dissecting complex traits, and accelerating the translation of discoveries from experimental research to clinical implementation.
  • Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias
    Publication . Nóbrega, Clévio; Marcelo, Adriana; Vieira da Conceição, André Filipe; Encarnação Estevam, Bernardo Alexandre; Rajado, Ana Teresa; Albuquerque Andrade de Matos, Carlos Adriano; Vilhena Catarino Brito, David; Torquato Afonso, Inês; Antunes Codêsso, José Miguel; Koppenol, Rebekah; Costa, Rafael Gomes da; Afonso Reis, Ricardo António; Paulino, Rodrigo; Gomes, Tiago
    Polyglutamine spinocerebellar ataxias (PolyQ SCAs) comprise a group of six inherited rare neurodegenerative diseases. They are caused by abnormal mutation of a CAG tract in six otherwise unrelated genes, leading to a complex cascade of molecular events that culminate in neuronal death. Based on decades of research in these diseases, this review identifies and categorizes the distinctive hallmarks involved in the molecular pathogenesis of PolyQ SCAs. We organized these molecular signatures into three groups: (i) primary hallmarks, which directly refer to the transcription and translation of the abnormally expanded gene and protein, respectively; (ii) secondary hallmarks, which include alterations in pathways and organelles that are implicated in the disease pathogenesis; and iii) end-stage hallmarks, which highlight the final events of the pathogenesis cascade in PolyQ SCAs. This framework is expected to provide a platform for understanding the complex network of molecular mechanisms involved in these diseases and to guide current and future efforts in developing therapies.