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- The 24-Hour Activity Checklist for Cerebral Palsy: Translation, Content Validity and Test-Retest Reliability of Portuguese VersionsPublication . Vila-Nova, Fabio; Sá, Cristina; Leite, Hércules Ribeiro; Cadete, Ana; Folha, Teresa; Longo, Egmar; Martins, Maria Elisabete; Oliveira, RaulBackground: The importance of 24-h movement behaviour, including sleep, physical activity (PA) and sedentary behaviour (SB), has gained prominence due to its significant impact on the health and development of children, including those with cerebral palsy (CP). The 24-h activity checklist for CP, a tool developed in the Netherlands to monitor the activity in CP paediatric population, requires translation and cultural adaptation to Portuguese for use in Brazil and Portugal. Methods: This cross-sectional methodological study involved translating and culturally adapting the 24-h activity checklist for CP into Brazilian Portuguese (BP) and European Portuguese (EP) languages. The process included forward translation, synthesis and backward translation, expert panel evaluation and pretesting. Brazilian and Portuguese experts appraised content validity, assessed by the individual item (I-CVI) and scale level content validity index scores (S-CVI/Ave). Sixty parents of children with CP participated in the test-retest analysis, reported with the Intraclass Correlation Coefficients (ICCs). Results: I-CVI scores were higher than 0.78 for both versions. S-CVI/Ave scores were considered excellent for BP (0.91) and EP version (1.0). Expert's appraisal results in the inclusion of a question about sleep-related time indicators and the split of sleep, PA, and screen time questions for weekdays and weekends. Brazilian and Portuguese parents of children with CP reported understanding on instructions, questions, and answer options. The ICC values range from 0.81 to 0.99 and 0.6 to 0.98, for BP and EP, respectively. Conclusions: The BP and EP versions of 24-h activity checklist for CP demonstrated good content validity and test-retest reliability, supporting its use in Brazil and Portugal. This tool can contribute to improving communication between families and healthcare professionals to monitor and develop tailored interventions for healthy movement behaviours in children with CP.
- A 30-year experience in neuro-Behçet diseasePublication . Silva, Lénia; Silva, Isabel Fonseca; Fonseca, Tomás; Pinto, Luísa Serpa; Leal, Bárbara; Pinho e Costa, Paulo; Igreja, Liliana; Moreira, Bruno; Santos, Ernestina; Vasconcelos, Carlos; Marinho, António; Correia, João AraújoBackground: Behçet disease (BD) is a systemic vasculitis affecting multiple organs with a wide range of severity. Neuro-Behçet (NBD) is a severe form, characterized by high morbidity, disability, and mortality rates. Methods: Retrospective analysis (1993-2023) of neurological involvement in BD patients at a tertiary center. Results: Of 296 BD patients, 93(31.4 %) underwent neurological evaluation. Definite NBD was identified in 30(10.1 %), probable NBD in 2(0.5 %) and "other neurological symptoms in BD" in 26(8.6 %) patients. The definite NBD group (median age: 36 years, 50 % female) had 44 neurological attacks: 24(55 %) parenchymatous and 20(45 %) non-parenchymatous. The most common syndromes were brainstem (27.3 %) and multifocal (25.6 %), with ataxia being the most frequent sign (40.9 %). One-third had a relapsing course. NBD onset concurred with BD diagnosis in 50 % of cases, followed in 30 %, and preceded in 20 %. Brain MRI revealed predominant involvement of the brainstem and diencephalic regions. The HLA-B*51 allele was more prevalent in definite NBD versus BD patients (53.8 % vs 31.2 %, p = 0.036). Treatments included corticosteroids (70.5 %), cyclophosphamide (15.9 %), infliximab (9.1 %), and conventional synthetic disease-modifying antirheumatic drugs (13.6 %). Better outcomes were achieved with cyclophosphamide and infliximab. The probable NBD and "other neurological symptoms in BD" groups (median age: 37 years) were mostly female (92.9 %). Headache (85 %) and cognitive complaints (23 %) were common symptoms.
- Acute flaccid myelitis in Europe between 2016 and 2023: indicating the need for better registrationPublication . Helfferich, Jelte; Calvo, Cristina; Alpeter, Ekkehardt; Andrés, Cristina; Antón, Andrés; Aubart, Melodie; Bova, Stefania Maria; Cabrerizo, Maria; von Eije, Karin; Fabiola, Stollar; Felipe, Ana; Iordanova, Ralitsa; Thomsen, Marianne Kragh; Knudsen, Per Kristian; van Loenen, Freek; Lopez, Noemi; Mirand, Audrey; Molenkamp, Richard; Midgley, Sofie; Neves, Raquel; Glomb, Lubomira Nikolaeva; Øverbø, Joakim; Öztürk, Gülten; Palminha, Paula; Viekilde Pfeiffer, Helle Cecilie; Prochazka, Birgit; Ribeiro, Carlos; Rodesch, Martine; Schuffenecker, Isabelle; Shetty, Jay; Siegert, Sandy; Solberg, Silje Lae; Sulik, Artur; Türkdoğan, Dilşad; Ünver, Olcay; Verweij, Jaco; Vila, Jorgina; Vuorinen, Tytti; Wickström, Ronny; Fischer, Thea K.; Harvala, Heli; Benschop, Kimberley S.M.Background: Acute flaccid myelitis (AFM) is a rare polio-like condition affecting mainly children and characterised by severe, often persistent, weakness. It is one of several causes of acute flaccid paralysis (AFP), which manifests as acute onset of limb weakness and reduced muscle tone. Some non-polio enteroviruses (EV), such as EV-D68 may cause AFM. Little is known about AFM incidence in Europe.AimWe aimed to better understand AFM incidence, aetiology and current surveillance policies in Europe.MethodsIn 28 countries, members of the European non-polio enterovirus network (ENPEN) and a newly established AFM network of clinicians under ENPEN received a survey asking them how AFM surveillance was performed in their countries in 2016-2023 and the numbers of AFM cases including those diagnosed with EV-D68 infection during this period.ResultsSurveillance information was obtained for 16 countries. In eight countries, AFP surveillance initiated for poliomyelitis eradication was still ongoing, while non-polio AFM cases were only systematically reported in Norway. The survey revealed 130 AFM cases for 14 countries, with 48 (37%) EV-D68-laboratory-confirmed. Among the AFM cases, 70% (n = 91) occurred in 2016, 2018 and 2022, when EV-D68 circulation increased.ConclusionsThis report provides some indication of AFM case numbers in Europe since 2016. However, as 15 of 16 countries with AFM monitoring information lacked structural AFM surveillance, numbers should be interpreted with caution. Knowing AFM incidence matters to determine its impact and detect future outbreaks. Thus, the newly established clinical network will develop a European AFM repository.
- Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical studyPublication . Febra, Claúdia; Saraiva, Joana; Vaz, Fátima; Soares, Nelson; Penque, PenqueBackground: Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE. Methods: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was D-glutamine and D-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3',5'-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68). Conclusions: Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.
- Adapting to COVID-19: Insights from Portuguese residents' home-based lifePublication . Aguiar, Ana; Soares, Patricia; Barbosa, Pedro; Duarte, Raquel; Pinto, MartaBackground: The COVID-19 pandemic led to widespread lockdowns and remote work and educational practices that have impacted the lives of many families. Objective: We aimed to investigate how parents and caregivers altered their routines due to online schooling and teleworking, exploring their association with increased anxiety and depression symptoms. Methods: We conducted an online cross-sectional study and collected data through snowball sampling. We asked questions about age, gender, dwelling area, educational level, and marital status, as well as an open-ended question about teleworking and homeschooling - "Did your routine change due to your children being forced to stay home and take online classes? If so, please explain how it has influenced your personal and professional life, both positively and negatively". Thematic analysis was used to analyse the responses. Results: A total of 181 respondents, primarily women (72.4%), averaging 36.6 years old, holding bachelor's degrees (44.2%), were included. About 78.5% reported routine adjustments. Four salient themes emerged: 1) Perceived changes in professional and personal life, 2) Perceived changes in learning methods, 3) Mental health issues and 4) Perceived advantages of working from home with children at online school. Regarding mental health, 25.4% exhibited symptoms of anxiety, and 7.7% displayed depression symptoms, predominantly linked (80%) to the pandemic's impact. Conclusion: Family routines were disrupted, causing stress. In future crises, policymakers, public health experts, and researchers must acknowledge these challenges to mitigate negative consequences. Simultaneously, they should focus on strategies that enhance the positive aspects of restrictive measures and related policies.
- Addressing Critical Fungal Pathogens Under a One Health Perspective: Key Insights from the Portuguese Association of Medical MycologyPublication . Sabino, Raquel; Antunes, Francisco; Araujo, Ricardo; Bezerra, A. R.; Brandão, João; Carneiro, Carla; Carvalho, Agostinho; Carvalho, D.; Conceição, I.C.; Cota-Medeiros, Fábio; Cruz, C.; Duarte, Elsa Leclerc; Holum, S.; Matos, O.; Maltez, F.; Mendonça, Alexandre; Moura, G.; Pereira, A.; Fortuna R., Celia; Teixeira, Pedro; de Valdoleiros, Sofia R.; Verissímo, Cristina; Viegas, Carla; Portuguese Association of Medical Mycology (ASPOMM); CarneiroFungal infections have emerged as a significant public health concern, especially with the increasing incidence of severe mycoses caused by pathogens such as Aspergillus fumigatus, Candida auris, Candida albicans, and Cryptococcus neoformans. These fungi, listed as critical priorities by the World Health Organization, pose a heightened risk due to rising antifungal resistance and their severe impact on immunocompromised individuals. This article, coordinated by the Portuguese Association of Medical Mycology, highlights the importance of adopting a One Health perspective to address fungal threats comprehensively. Drawing on interdisciplinary collaboration, the association aims to foster greater awareness, improve diagnostic capabilities, and stimulate research and public health policies in Portugal but also at global level. The paper outlines key strategies for surveillance, prevention, and innovation in fungal diagnostics and therapeutics. Moreover, it emphasizes the urgent need for national coordination and international cooperation in managing fungal infections, advocating for integrative approaches that link human, animal, and environmental health. By presenting aconsolidated overview of current challenges and future priorities, this work seeks to enhance preparedness and response mechanisms in the face of escalating fungal threats.
- Advancements in risk stratification and management strategies in primary cardiovascular preventionPublication . Barkas, Fotios; Sener, Yusuf Ziya; Golforoush, Pelin Arabacilar; Kheirkhah, Azin; Rodriguez-Sanchez, Elena; Novak, Jan; Apellaniz-Ruiz, Maria; Akyea, Ralph Kwame; Bianconi, Vanessa; Ceasovschih, Alexandr; Chee, Ying Jie; Cherska, Mariia; Chora, Joana Rita; D'Oria, Mario; Demikhova, Nadiia; Kocyigit Burunkaya, Duygu; Rimbert, Antoine; Macchi, Chiara; Rathod, Krishnaraj; Roth, Lynn; Sukhorukov, Vasily; Stoica, Svetlana; Scicali, Roberto; Storozhenko, Tatyana; Uzokov, Jamol; Lupo, Maria Giovanna; van der Vorst, Emiel P.C.; Porsch, FlorentinaAtherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for advancements in risk ssessment and management strategies. Although significant progress has been made ecently, identifying and managing apparently healthy individuals at a higher risk of developing atherosclerosis and those with subclinical atherosclerosis still poses significant challenges. Traditional risk assessment tools have limitations in accurately predicting future events and fail to encompass the complexity of the atherosclerosis trajectory. In this review, we describe novel approaches in biomarkers, genetics, advanced imaging techniques, and artificial intelligence that have emerged to address this gap. Moreover, polygenic risk scores and imaging modalities such as coronary artery calcium scoring, and coronary computed tomography angiography offer promising avenues for enhancing primary cardiovascular risk stratification and personalised intervention strategies. On the other hand, interventions aiming against atherosclerosis development or promoting plaque regression have gained attention in primary ASCVD prevention. Therefore, the potential role of drugs like statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, omega-3 fatty acids, antihypertensive agents, as well as glucose-lowering and anti-inflammatory drugs are also discussed. Since findings regarding the efficacy of these interventions vary, further research is still required to elucidate their mechanisms of action, optimize treatment regimens, and determine their long-term effects on ASCVD outcomes. In conclusion, advancements in strategies addressing atherosclerosis prevention and plaque regression present promising avenues for enhancing primary ASCVD prevention through personalised approaches tailored to individual risk profiles. Nevertheless, ongoing research efforts are imperative to refine these strategies further and maximise their effectiveness in safeguarding cardiovascular health.
- Aeromonas spp. in Freshwater Bodies: Antimicrobial Resistance and Biofilm AssemblyPublication . Nascimento, Maria; Rodrigues, João; Matias, Rui; Jordão, LuisaAeromonas spp. are environmental bacteria able to infect animals and humans. Here, we aim to evaluate the role of biofilms in Aeromonas persistence in freshwater. Aeromonas were isolated from water and biofilm samples and identified by Vitek-MS and 16S rRNA sequencing. Antibiotic susceptibility profiles were determined according to EUCAST, and a crystal violet assay was used to assess biofilm assembly. MTT and the enumeration of colony-forming units were used to evaluate biofilm and planktonic Aeromonas susceptibility to chlorination, respectively. Identification at the species level was challenging, suggesting the need to improve the used methodologies. Five different Aeromonas species (A. salmonicida, A. hydrophila, A. media, A. popoffii and A. veronii) were identified from water, and one species was identified from biofilms (A. veronii). A. veronnii and A. salmonicida presented resistance to different antibiotics, whith the highest resistance rate observed for A. salmonicida (multiple antibiotic resistance index of 0.25). Of the 21 isolates, 11 were biofilm producers, and 10 of them were strong biofilm producers (SBPs). The SBPs presented increased tolerance to chlorine disinfection when compared with their planktonic counterparts. In order to elucidate the mechanisms underlying biofilm tolerance to chlorine and support the importance of preventing biofilm assembly in water reservoirs, further research is required.
- Air pollution mixture complexity and its effect on PM2.5-related mortality: A multicountry time-series study in 264 citiesPublication . Masselot, Pierre; Kan, Haidong; Kharol, Shailesh K; Bell, Michelle L.; Sera, Francesco; Lavigne, Eric; Breitner, Susanne; das Neves Pereira da Silva, Susana; Burnett, Richard T.; Gasparrini, Antonio; Brook, Jeffrey R.; MCC Collaborative Research NetworkBackground: Fine particulate matter (PM2.5) occurs within a mixture of other pollutant gases that interact and impact its composition and toxicity. To characterize the local toxicity of PM2.5, it is useful to have an index that accounts for the whole pollutant mix, including gaseous pollutants. We consider a recently proposed pollutant mixture complexity index (PMCI) to evaluate to which extent it relates to PM2.5 toxicity. Methods: The PMCI is constructed as an index spanning seven different pollutants, relative to the PM2.5 levels. We consider a standard two-stage analysis using data from 264 cities in the Northern Hemisphere. The first stage estimates the city-specific relative risks between daily PM2.5 and all-cause mortality, which are then pooled into a second-stage meta-regression model with which we estimate the effect modification from the PMCI. Results: We estimate a relative excess risk of 1.0042 (95% confidence interval: 1.0023, 1.0061) for an interquartile range increase (from 1.09 to 1.95) of the PMCI. The PMCI predicts a substantial part of within-country relative risk heterogeneity with much less between-country heterogeneity explained. The Akaike information criterion and Bayesian information criterion of the main model are lower than those of alternative meta-regression models considering the oxidative capacity of PM2.5 or its composition. Conclusions: The PMCI represents an efficient and simple predictor of local PM2.5-related mortality, providing evidence that PM2.5 toxicity depends on the surrounding gaseous pollutant mix. With the advent of remote sensing for pollutants, the PMCI can provide a useful index to track air quality.
- Alkyl deoxyglycoside-polymyxin combinations against critical priority carbapenem-resistant gram-negative bacteriaPublication . Matos, Ana M. de; Calado, Patrícia; Miranda, Mónica; Almeida, Rita; Rauter, Amélia P.; Oliveira, M. Conceição; Manageiro, Vera; Caniça, ManuelaThe escalating antimicrobial resistance crisis urges the development of new antibacterial treatments with innovative mechanisms of action, particularly against the critical priority carbapenem-resistant Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA) and Enterobacteriaceae (CRE). Membrane-disrupting dodecyl deoxyglycosides have been reported for their interesting phosphatidylethanolamine-associated bactericidal activity against Gram-positive strains; however, their inability to penetrate the Gram-negative outer membrane (OM) renders them useless against the most challenging pathogens. Aiming to repurpose alkyl deoxyglycosides against Gram-negative bacteria, this study investigates the antimicrobial effects of five reference compounds with different deoxygenation patterns or anomeric configurations in combination with polymyxins as adjuvants for enhanced OM permeability. The generation of the lead 4,6-dideoxy scaffold was optimized through a simultaneous dideoxygenation step and applied to the synthesis of a novel alkyl 4,6-dideoxy C-glycoside 5, herein reported for the first time. When combined with subtherapeutic colistin concentrations, most glycosides demonstrated potent antimicrobial activity against several multidrug-resistant clinical isolates of CRAB, CRE and CRPA exhibiting distinct carbapenem resistance mechanisms, together with acceptable cytotoxicity against human HEK-293T and Caco-2 cells. The novel 4,6-dideoxy C-glycoside 5 emerged as the most promising prototype structure for further development (MIC 3.1 μg/mL when combined with colistin 0.5 μg/mL against CRPA or 0.25 μg/mL against several CRE and CRAB strains), highlighting the potential of C-glycosylation for an improved bioactive profile. This study is the first to show the potential of IM-targeting carbohydrate-based compounds for the treatment of infections caused by MDR Gram-negative pathogens of clinical importance.