FCB2-Artigos (em revistas ou actas indexadas)
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- Analysis of TERT association with clinical outcome in meningiomas: a multi-institutional cohort study.Publication . Gui, Chloe; Wang, Justin Z.; Patil, Vikas; Landry, Alexander P.; Castelo-Branco, Pedro; Singh, Olivia; Tabori, Uri; Aldape, Kenneth; Behling, Felix; Barnholtz-Sloan, Jill S.; Horbinski, Craig; Tabatabai, Ghazaleh; Ajisebutu, Andrew; Liu, Jeff; Patel, Zeel; Yakubov, Rebeca; Kaloti, Ramneet; Ellenbogen, Yosef; Wilson, Christopher; Cohen-Gadol, Aaron; Tatagiba, Marcos; Holland, Eric C.; Sloan, Andrew E.; Chotai, Silky; Chambless, Lola B.; Gao, Andrew; Makarenko, Serge; Yip, Stephen; Nassiri, Farshad; Zadeh, GelarehBackground TERT promoter mutation is a rare biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival. Although high TERT expression is characteristic of tumours with TERT promoter mutations, it has also been observed in tumours with wildtype TERT promoters. This study aimed to investigate the prevalence and prognostic association of TERT expression in meningiomas.
- Association of acute COVID-19 severity and long COVID fatigue and quality of life: prospective cohort multicenter observational studyPublication . Pires, Ligia; Marreiros, Ana; Saraiva, Cátia; Reis, Cláudia; Neves, Djamila; Guerreiro, Cláudia; Tomé, José Boleo; Luz, Maria Inês; Pereira, Margarida Isabel; Barroso, Ana Sofia; Ferreira, Jorge; Gonzalez, Lucía Méndez; Moniri, Armin; Drummond, Marta; Berger-Estilita, JoanaLong COVID, or post-COVID-19 condition, is characterized by symptoms persisting beyond 12 weeks after severe acute respiratory syndrome coronavirus 2 infection, affecting individuals regardless of acute disease severity. Fatigue – often linked with depression and anxiety – is among its most debilitating manifestations. However, the associations between fatigue subtypes (physical vs mental), mental health symptoms, and acute disease severity on long-term health-related quality of life (HRQoL) remain unclear. This study examines the relationships between long COVID fatigue, depression, anxiety, acute disease severity, and HRQoL in a post-COVID-19 cohort. This prospective observational cohort study was conducted across 5 Portuguese hospitals between November 2020 and June 2022. Adults (≥18 years) with confirmed severe acute respiratory syndrome coronavirus 2 infection ≥6 months prior and fulfilling World Health Organization criteria for long COVID were included. Acute Coronavirus disease 2019 (COVID-19) severity was classified per World Health Organization definitions. The sampling strategy included patients across the severity spectrum. At 3 months postinfection (T1), patients received physician-led clinical assessments. At 6 months (T2), they attended in-person follow-up visits, completing standardized forms and validated questionnaires assessing post-acute sequelae. Fatigue was reported both binarily (yes/no) and via the chalder fatigue scale (11-item version). Anxiety and depression were assessed using the hospital anxiety and depression scale; post-traumatic stress disorder symptoms with the 14-item post-traumatic stress scale; and HRQoL with the EuroQol-5 dimensions. Descriptive statistics, analysis of variance, chi-square, and correlation analyses (Pearson’s or Spearman’s) were used to evaluate associations. Analyses were performed using SPSS (v27; IBM Corp., Amonk). Among 208 patients, fatigue was significantly associated with anxiety and depression (P < .001). Physical fatigue correlated more strongly with depression (r = 0.65, P < .001) and anxiety (r = 0.58, P < .001) than mental fatigue (r = 0.50 and R = 0.48, respectively; P < .001). Surprisingly, severe acute COVID-19 cases reported lower fatigue (CFQ: 13.3 ± 8.4) than mild (17.7 ± 7.2) or moderate (17.4 ± 8.0) cases (P < .005), and higher HRQoL (EuroQol visual analog scale: 74.3 ± 20.3, P = .002). Anxiety symptoms were more common in mild cases (P < .001); post-traumatic stress disorder symptoms did not differ by severity. Long COVID fatigue – especially physical – is strongly linked to depression and anxiety. Mild/moderate acute COVID-19 cases show greater fatigue and lower HRQoL than severe cases, highlighting the need for tailored long-term care regardless of initial severity.
- The renin-angiotensin system in healthy human platelets: expressed but inactivePublication . Panosetti, François; Cuenot, François M.; Auguste, Damian S. Saint; Martins Cavaco, Ana Cláudia; Nunes, Allancer D. C.; Lu, Philip H. J.; Magrini, Céline; Molot, Max; Sanglard, Gabriel; Günçü, Rodi; Zouaghi, Yassine; Béguelin, Charles; Lima, Augusto Martins; Stergiopulos, NikolaosPlatelets play a crucial role in arterial thrombus formation, offering potential for new antiplatelet therapies with reduced bleeding risk. Here, we investigated the role of the renin-angiotensin system (RAS) in human platelets and explored its potential link to COVID-19 coagulopathy. Experiments were performed ex vivo on healthy human platelets. The expression of RAS receptors (Mas, MrgD, ACE, ACE2, AT1 and AT2) was evaluated using western blot and immunofluorescence. Platelets were incubated in vitro with either Captopril or different RAS peptides including Alamandine, Angiotensin-I, Angiotensin-II, Angiotensin-(1-7), and Angiotensin-(1-9). Platelet adhesion was measured by spectrophotometry using BCECF fluorescence. Platelet activation and aggregation were analyzed using aggregometry after stimulation with extracellular matrix proteins. ACE and ACE2 activity were assessed using Fluorescent Peptides (FPS). We demonstrated that healthy human platelets express all the tested RAS receptors. However, RAS peptides did not modulate platelet adhesion or aggregation despite a wide range of concentrations tested. ACE activity was detected in platelet lysates, but it was not inhibited by Captopril, while ACE2 activity was undetectable. Our findings suggest that while RAS receptors are expressed in platelets, RAS peptides do not impact platelet function, at least in our experimental setting. COVID-19 coagulopathy may occur independently of the RAS.
- Molecular detection of multiple antimicrobial resistance genes in helicobacter pylori-positive gastric samples from patients undergoing upper gastrointestinal endoscopy with gastric biopsy in Algarve, PortugalPublication . Nunes, Francisco José Viegas Cortez; Aguieiras, Catarina; Calhindro, Mauro; Louro, Ricardo; Peixe, Bruno; Queirós, Patrícia; Castelo-Branco, Pedro; Mateus, Teresa LetraBackground/Objectives: Helicobacter pylori (H. pylori) is a common gastric pathogen linked to gastritis, gastroduodenal ulcers, and gastric cancer. Rising antimicrobial resistance (AMR) poses challenges for effective treatment and has prompted the WHO to classify H. pylori as a high-priority pathogen. This study aimed to detect the prevalence of AMR genes in H. pylori-positive gastric samples from patients in Algarve, Portugal, where regional data is scarce. Methods: Eighteen H. pylori-positive gastric biopsy samples from patients undergoing upper gastrointestinal endoscopy were analyzed. PCR and sequencing were used to identify genes associated with resistance to amoxicillin (Pbp1A), metronidazole (rdxA, frxA), tetracycline (16S rRNA mutation) and clarithromycin (23S rRNA). Sequence identity and homologies were verified using tBLASTx and the Comprehensive Antibiotic Resistance Database (CARD). Results: Out of the 18 H. pylori-positive samples, 16 (88.9%) contained at least one AMR gene. The most frequent genes were rdxA (83.3%) and frxA (66.7%) for metronidazole resistance, and the 16S rRNA mutation (66.7%) for tetracycline. Resistance to amoxicillin and clarithromycin was detected in 27.8% and 16.7% of cases, respectively. Most samples (72.2%) had multiple resistance genes. A significantly strong association was found between female sex and the presence of the rdxA gene (p = 0.043). Conclusions: The study reveals a high prevalence of H. pylori resistance genes in Algarve, particularly against metronidazole and tetracycline. These findings highlight the need for local surveillance and tailored treatment strategies. Further research with larger populations is warranted to assess regional resistance patterns and improve eradication efforts.
- Coding and non-coding RNA expression in NSC34 cells following TDP-43 depletion and mutant TDP-43 M337V expressionPublication . Gbadamosi, Ismail; Binias, Sandra; Gielniewski, Bartłomiej; Magno, Ramiro; dos Santos Duarte, Guilhermina Isabel; Jawaid, AliSeveral neurodegenerative disorders (NDDs), notably amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are characterized by pathological cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP-43) in neurons and glia. Primarily localized in the nucleus under physiological conditions, TDP-43 is a critical regulator of RNA processing and metabolism. Therefore, RNA changes induced by TDP-43 depletion or mutation could play an important role in the pathogenesis of ALS and other TDP-43 related NDDs.To investigate these effects in NSC34 motor neuron-like cells, a commonly used cellular model of ALS, we used RNA interference to knock down TDP-43 and overexpressed the ALS-associated TDP-43 M337V mutation. RNA from both these experiments was enriched for small and large transcripts and subsequently analyzed via next-generation sequencing. The resulting transcriptomics datasets offer a valuable resource for studying the impact of TDP-43 depletion and mutant over-expression in motor neurons. These data enable comprehensive differential expression analyses and functional enrichment studies, identifying cellular pathways affected by TDP43 depletion or mutation. Additionally, the inclusion of non-coding RNAs facilitates the construction of gene regulatory networks, providing insights into the interplay between coding and non-coding RNAs in gene expression regulation under TDP-43 loss-of-function or pathogenic mutation conditions.
- An integrative review of potential diagnostic biomarkers for complex regional pain syndromePublication . Lopes, Revelino; Santos, André; Gomes, Teresa; Ribeiro, Júlia; Rodrigues, Ivone; Paiva, Bruno; Nzwalo, Isa; Catamo Vaz, Deise Haua da Silva; Baco, Jamal; Buque, Helena Agostinho; Botelho, Marta; Pais, Sandra; Nzwalo, HipólitoBackground: Complex regional pain syndrome (CRPS) is a rare, chronic, painful, neurological, debilitating disorder. Despite the substantial impact on quality of life, diagnosis remains challenging due to its complex pathophysiology and subjective clinical criteria. This integrative review aims to synthesize current research on potential diagnostic biomarkers for CRPS. Methods: A systematic search was conducted using the PubMed and Scopus databases to identify relevant studies published until January 2025. Inclusion criteria focused on adult CRPS patients, with studies examining diagnostic or predictive biomarkers. Results: Key findings highlight the role of inflammatory and immune-related biomarkers, such as elevated levels of cytokines (IL-6, TNF-alpha), immune cell infiltration, and specific autoantibodies. Neuropeptides, including substance P and calcitonin gene-related peptide, were associated with pain sensitization in acute phases, though their levels normalized in chronic stages. Additionally, genetic and epigenetic markers, brain imaging, and neurophysiological alterations provided insights into CRPS pathogenesis, emphasizing the dynamic nature of these biomarkers across disease stages. Conclusions: This review underscores the need for further research to integrate these biomarkers into diagnostic frameworks, which could enhance early diagnosis and treatment strategies for CRPS.
- Advanced therapy medicinal products development - from guidelines to medicines in the marketPublication . Frederico, Catarina; Vieira da Conceição, André Filipe; Nóbrega, Clévio; Mendonça, Liliana S.In Europe, Advanced Therapy Medicinal Products (ATMPs) include medicines based on gene therapy, somaticcell therapy, tissue-engineered products, and combined ATMPs. ATMPs constitute an emerging and innovative class of medicines used to treat multiple pathologies and are particularly relevant in pathologies where therapeutic options are limited and require high medical needs. These therapies act, among others, through the insertion of recombinant nucleic acids, including genes, to promote a therapeutic effect and through the restoration of cell functions, and repairing or replacing damaged cells and tissues impaired in pathological conditions. Despite their unique potential, these therapies face challenges related to scientific complexity, production processes, regulatory approval, and market access that hinder their development and availability. Based on official European guidelines, the present review explores the current regulatory framework for the non-clinical and clinical development of advanced therapies. We aimed to discuss the regulations applied to the different types of ATMPs, as well as the challenges associated with their development until these therapies reach the market. Accordingly, topics such as the implementation of proof-of-concept studies to provide evidence supporting the potential clinical effect; biodistribution studies to evaluate tissue distribution and persistence; and toxicology studies to assess potential undesirable effects, integration potential of viral vectors, tumorigenicity, and germline transmission, are discussed. This work also covers some of the ATMPs available to patients on the EU market.
- Comparison of different microalgae biomass typologies used in rotifers enrichment for zebrafish (Danio rerio) larvae nutritionPublication . de Castro, Daniela; Castaldi, Matthew; Martins, Gil; Santos, Tamara; Pereira, Hugo; Diogo, Patrícia; Varela, João; Gavaia, Paulo; Shivendra KumarThe use of enriched rotifers with industrially produced microalgae represents a valuable tool for the enhancement of zebrafishlarval nutrition and increased biological performance. Currently, a monoculture of microalgal species (Nannochloropsis sp.) inform of liquid paste is routinely used for rotifers enrichment for zebrafish larvae feeding; however, the most adequate typology (i.e.,paste or freeze-dried) of the industrially produced microalgal biomass is still controversial. This work aimed to compare the effectsof rotifers enriched with three different industrially produced microalgae species (i.e., Nannochloropsis oceanica, Tetraselmis chui,and Tisochrysis lutea) using paste and freeze-dried powder. Enriched rotifers were provided as feed during larval growth and theimpact on growth and survival was evaluated. The use of enriched rotifers with both paste or freeze-dried microalgae improvedgrowth compared to larvae fed exclusively with commercial microdiet. Larvae fed rotifers enriched with N. oceanica and T. chuiattained higher weight and length both at 15 and 30 days postfertilization (dpf ), while the use of microalgae in paste contributed togreater larvae lengths when compared to freeze-dried. The experimental results in this study revealed that N. oceanica and T. chuiin paste are the most suitable microalgae forms to be used in zebrafish larvae nutrition and in the improvement of enrichmentmethodologies for rotifers.
- The mechanical and perfusion basis of exercise limitation in apical hypertrophic cardiomyopathyPublication . Hughes, Rebecca K.; Malcolmson, James; Prista Monteiro, Ricardo; Torlasco, Camilla; Davies, Rhodri; Lopes, Luis R.; Mohiddin, Saidi; Captur, Gabriella; Moon, James C.; Lloyd, GuyPatients with apical hypertrophic cardiomyopathy (ApHCM) commonly suffer symptoms of chest pain and dyspnea. Apical hypertrophy causes cavity obliteration early in systole, persisting into diastole; generating high pressures and creating basal to apical heterogeny in myocardial deformation across the cardiac cycle.1 Conventional measures of systolic function (eg, ejection fraction [EF]) may be supranormal, but other parameters may be abnormal either globally (global longitudinal strain [GLS]),2 or apically (longitudinal, radial and circumferential strain, including twist).3 Cardiac magnetic resonance (CMR) demonstrated that apical perfusion defects are a universal feature across the phenotypic spectrum.4 Reduced exercise capacity in HCM is widely reported; however, in ApHCM, functional limitation has been little explored, and the underpinning roles for abnormal myocardial mechanics and perfusion abnormalities are unknown. We hypothesized that patients with ApHCM would have functional limitation associated with abnormalities of global/regional myocardial mechanics (strain, twist) and myocardial blood flow (MBF).
- Green surgery: a systematic review of the environmental impact of laparotomy, laparoscopy, and roboticsPublication . Cunha, Miguel F.; Neves, João Cunha; Roseira, Joana; Pellino, Gianluca; Castelo-Branco, PedroSurgery is the most energy-intensive healthcare sector, but data on the environmental impact of abdominal surgical techniques are limited. This systematic review aims to identify the most sustainable approach among open, laparoscopic, and robotic surgeries. We searched MEDLINE, Cochrane, and Web of Science databases (inception to March 2024) for studies on the carbon footprint of abdominal surgery, focusing on carbon dioxide equivalents (CO2e) or CO2 emissions. The Joanna Briggs Institute checklist was used to assess bias. (PROSPERO: 298486). Of 2155 records, eight cohort studies were included, showing low to moderate risk of bias but high heterogeneity. Two studies on hysterectomy found robotic surgery had the highest carbon footprint (12.0-40.3 kgCO2e) compared to laparoscopic (10.7-29.2 kgCO2e) and open surgery (7.1-22.7 kgCO2e). Another study found laparoscopic prostatectomy produced more emissions than robotic surgery (59.7 vs. 47.3 kgCO2e) due to higher disposable devices, surgery time and length of stay. Single-use devices in laparoscopic cholecystectomy emitted more CO2e than hybrid devices (7.194 vs. 1.756 kgCO2e). CO2 used in minimally invasive surgery had negligible environmental effects (0.9 kgCO2e). Qualitative subgroup analyses revealed significant differences between surgery types and measurement methodologies, contributing to data heterogeneity. Minimally invasive surgeries often have higher carbon footprints due to disposable tools and waste. However, one study showed robotic surgery may reduce the overall environmental impact by shortening hospital stays. Due to methodological heterogeneity across studies, definitive conclusions remain limited. Standardized life-cycle assessment methodologies and inclusion of clinical outcomes in future studies are urgently needed to clarify the environmental sustainability of surgical practices.