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- Safeguarding patients, relatives, and nurses: A screening approach for detecting 5-FU residues on elastomeric infusion pumps using HPLC-DADPublication . Cardoso, Andreia; Jesus, Ângelo; Barreiros, Luísa; Carvalho, Daniel; Sá, Maria dos Anjos; Carvalho, Susana; Correia, Patrícia; Moreira, Fernando; Moreira, Fernando; Correia, Patrícia Carla dos Santos ; Barreiros, Luisa; Jesus, ÂngeloThe leakage of 5-fluorouracil (5-FU) from elastomeric infusion pumps used in cancer therapy poses a potential risk of unintentional exposure to multiple individuals, including patients’ relatives and healthcare professionals, and may also compromise the accurate administration of 5-FU dosages to patients. This study aimed to develop, validate, and apply an analytical method to detect and quantify 5-FU residues on the external surfaces of infusion pumps. A high-performance liquid chromatography with diode-array detection (HPLC-DAD) method was optimized for the quantification of 5-FU contamination across different components of the infusion pump, including the hard casing, infusion tubing, and catheter connection port. A mobile phase containing 5% acetic acid was used to obtain more efficient separation of 5-FU and the detection was performed at 260 nm. The method was evaluated for linearity, sensitivity, precision, accuracy, selectivity, robustness, and stability. The method demonstrated linearity within the range of 0.150 to 3.000 µg/cm2, with limits of detection and quantification of 0.05 µg/cm2 and 0.14 µg/cm2, respectively. Relative standard deviations ranged from 1.8% to 12.7%, and accuracy exceeded 85%. In real sample analysis, detectable residues were found around the catheter connection port. This screening-oriented method addresses an existing gap, as previous contamination reports were based solely on self-reported user observations. The detection of 5-FU residues highlights the critical need for safe handling practices and the consistent use of personal protective equipment (PPE) to protect healthcare workers, especially nursing staff involved in the removal of the infusion pumps, after treatment.
- Factors influencing the prescription of first-line treatment for type 2 diabetes mellitus: a systematic reviewPublication . Moreira, Helena Silva; Moreira, Fernando; Jesus, Ângelo; Soares, Matilde Monteiro; Santos, Paulo; Moreira, FernandoUnderstanding prescribing patterns for type 2 diabetes mellitus, a complex condition affecting over 10% of the global adult population, can optimise prescribing practices, guide policymakers in promoting evidence-based medicine, and help tailor first-line treatments to individual characteristics or specific subgroups, improving patient outcomes. This study aimed to identify factors influencing the prescription and non-prescription of metformin, the recommended first-line therapy in Western guidelines, and to evaluate whether these prescribing patterns align with evidence-based recommendations. It also explores factors associated with initial combination therapy, a more recent and controversial approach compared to stepwise therapy. We conducted a systematic search in PubMed, Scopus, and Web of Science on 25 August 2023, without language or time restrictions, to identify observational analytical studies assessing factors associated with the initiation of metformin or combination therapy in adults with type 2 diabetes mellitus who were naïve to antidiabetic medications. Studies involving pregnant or breastfeeding women were excluded. A narrative synthesis was conducted. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklists (PROSPERO registration number CRD42023438313). Thirty studies were included, evaluating 105 variables, most of which (62%) were assessed in one study. The 25 variables using combination therapy as the outcome were mostly (72%) evaluated also in one study. Initial metformin prescription was strongly and positively associated with younger age, lower glycated haemoglobin levels, higher body mass index, and absence of renal impairment. Initial combination therapy was associated with higher HbA1c levels and a lower burden of comorbidities. Findings also highlighted a discrepancy between clinical practice and evidence-based recommendations. However, concerns were raised regarding both the internal and external validity of the included studies. Our systematic review, which offers insights into real-world clinical practices, indicated that there is a misalignment between clinical practices and evidence-based recommendations, supporting the need for interventions in this field.
- Nano versus bulk: Evaluating the toxicity of lanthanum, yttrium, and cerium oxides on Enchytraeus crypticusPublication . Santos, Joana; Neca, Inês; Capitão, Ana; Nogueira, João; Santos, José A. S.; Pinto, Edgar; Barreto, Angela; Silva, Ana L. Daniel da; Maria, Vera L.; Pinto, EdgarConsidering the increase in demand for rare earth elements (REEs) and their accumulation in soil ecosystems, it is crucial to understand their toxicity. However, the impact of lanthanum, yttrium and cerium oxides (La2O3, Y2O3 and CeO2, respectively) on soil organisms remains insufficiently studied. This study aims to unravel the effects of La2O3, Y2O3 and CeO2 nanoparticles (NPs) and their corresponding bulk forms (0, 156, 313, 625, 1250 and 2500 mg/kg) on the terrestrial species Enchytraeus crypticus. The effects on survival, reproduction (21 days (d)), avoidance behavior (2 d) and DNA integrity (2 and 7 d) of E. crypticus were evaluated. No significant effects on survival were observed. For La2O3, the bulk form affected more endpoints than the NPs, inducing avoidance behavior (1250 mg/kg) and DNA damage (1250 mg/kg - 2 d; 2500 mg/kg - 7 d). The Y2O3 NPs demonstrated higher toxicity than the bulk form: decreased reproduction (≥ 1250 mg/kg); induced avoidance behavior (≥ 625 mg/kg) and DNA damage (≥ 156 mg/kg - 2 d; 2500 mg/kg - 7 d). For CeO2, both forms exhibited similar toxicity, decreasing reproduction (625 mg/kg for bulk and 2500 mg/kg for NPs) and inducing DNA damage at all tested concentrations for both forms. REEs oxides toxicity was influenced by the REEs type and concentration, exposure time and material form, suggesting different modes of action. This study highlights the distinct responses of E. crypticus after exposure to REEs oxides and shows that REEs exposure may differently affect soil organisms, emphasizing the importance of risk assessment.
- Evaluation of the potential of annatto seed powder to reduce the formation of heterocyclic amines in charcoal-grilled and pan-fried beef pattiesPublication . Gonçalves, Thaís de Moura Neves; Braga, Anna Rafaela Cavalcante; Pinto, Edgar; Viegas, Olga; Mesquita, Leonardo M. de Souza; Ferreira, Isabel Maria Pinto Leite Viegas Oliveira; García-Jares, Carmen; De Rosso, Veridiana Vera; Domene, Semíramis Martins Álvares; Pinto, EdgarVarious strategies are being explored to reduce the formation of undesirable compounds during the thermal processing of foods. This study investigates the impact of incorporating annatto seed powder (Bixa orellana L.) into beef patties to reduce the formation of heterocyclic amines (HAs) during charcoal-grilling and pan-frying. A three-level full factorial design was used to assess the effect of both annatto seed powder concentration and cooking times on HAs formation. The results showed that HA formation increased with longer cooking times and decreased with higher concentrations of annatto seed powder. A significant reduction in HA content was observed in both charcoal-grilled and pan-fried beef patties when annatto seed powder was added, with a particularly notable 91 % reduction at the 1 % addition level. These findings demonstrate that the addition of annatto seed powder is a highly effective strategy for reducing HA formation in beef patties. Chemical compounds studied in this article: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (PubChem CID: 62275); 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) (PubChem CID: 104739); 2amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx) (PubChem CID: 104855); 2-amino-1-methyl-6phenylimidazo[4,5-b]pyridine (PhIP) (PubChem CID: 1530); 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (TrpP-1) (PubChem CID: 5284474); 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) (PubChem CID: 5284476); 2-amino-9H-pyrido[2,3-b]indole (A α (MeA α C) (PubChem CID: 62805); 2-amino-3-methyl-9H-pyrido[2,3-b]indole C) (PubChem CID: 62244); Bixin (PubChem CID: 5281226).
- Stock structure of the gulf hake urophycis cirrata (Teleostei: Phycidae) in south-western atlantic using Otolith shape and elemental analysesPublication . Santificetur, César; Rossi-Wongtschowski, Carmen Lúcia Del Bianco; Ruperti, André; Almeida, Agostinho; Pinto, Edgar; Correia, Alberto Teodorico; Pinto, EdgarUrophycis cirrata is an important demersal fish species targeted by Brazilian industrial fisheries. With high exploitation rates, its stock(s) is(are) currently deemed fully exploited or overexploited. While basic ecological information, such as length at first maturity, exists, knowledge of its population structure is limited. A sub-sample of 90 sagittal otoliths of U. cirrata juveniles (300–411 mm total length) collected during the Program for Assessment of the Sustainable Potential of Living Resources in the Exclusive Economic Zone (REVIZEE) in 2001/2002 was analyzed. Samples came from the outer continental shelf and upper slope of the southeast-south Brazilian coast, divided into three regions: northern (Cabo São Tomé to São Sebastião), central (São Sebastião to Cabo Santa Marta Grande), and southern (Cabo Santa Marta Grande to Chuí). Otolith shape (elliptic Fourier descriptors) and elemental (element:Ca) signatures were examined using univariate (ANOVA, Tukey) and multivariate (MANOVA, LDFA) statistical methods. An overall reclassification success rate of 86% was achieved using both signatures. However, individuals from the three regions were not fully separable, indicating a single, albeit not homogeneous, population unit for fisheries management. As fish stocks are dynamic, contemporary studies should be conducted to verify whether this population structure persists.
- New methodologies and techniques for biomonitoring pesticide exposure in agricultural workers: A systematic reviewPublication . Moreira, Andreia; Guedes, Joana; Silva, Manuela Vieira da; Vieira da Silva, ManuelaBiomonitoring allows for the assessment of internal exposure to various pesticides and metabolites. Following PRISMA guidelines, this systematic review aims to summarise innovative biomonitoring techniques for assessing pesticide exposure in agricultural workers, their advantages and limitations, and their applicability. The search of the Medline/PubMed, ScienceDirect, Scopus, and Web of Science databases identified 14 articles dealing with new techniques for biomonitoring pesticide exposure in agricultural workers. These new methodologies have identified several biomarkers associated with exposure to organophosphates. Most of the included studies combine and/or improve traditional methods to overcome their limitations. This leads to more sensitive, specific, and precise techniques with lower detection and quantification limits. Therefore, it is necessary to thoroughly analyse and test new biomonitoring methods for assessing pesticide exposure. These techniques can complement qualitative risk assessments and aid in developing strategies to protect public health and the environment.
- Altered NRF2 signalling in systemic redox imbalance: Insights from non-communicable diseasesPublication . Santos, Marlene; Morgenstern, Christina; Santos, MarleneThe balanced activity of the cytoprotective transcription factor NRF2 is central for maintaining redox, metabolic-energetics, and proteome homeostasis, as well as for regulating inflammatory responses, among other functions. Activated NRF2 regulates the expression of hundreds of genes containing antioxidant response elements (AREs) or electrophile response elements (EpRE) in their regulatory regions, often promoting cytoprotection under stress conditions and contributing to defence against various pathologies and non-communicable diseases (NCDs). The products of increased NRF2 activity, detected systemically, may originate from either the white blood cells, the cells of the vasculature or tissue-derived products that could be secreted into biological fluids. Therefore, assessing basal and inducible NRF2 activity in blood or other biofluids is crucial for inferring NRF2 responses in local and often inaccessible tissues. In previous work, we identified a panel of six biomarkers - Glutamate-cysteine ligase catalytic subunit (GCLC), Glutamate-cysteine ligase modifier subunit (GCLM), Haem oxygenase 1 (HMOX1), NAD(P)H quinone dehydrogenase 1 (NQO1), Sulfiredoxin 1 (SRXN1), and Thioredoxin reductase 1 (TXNRD1) - as indicators of NRF2 activity. In the current study, we assess their utility in a clinical setting to measure NRF2 activation in a disease context. Here we discuss findings on how NRF2 activity in accessible human samples can reveal its involvement in various NCDs and its connection to clinical aspects such as diagnosis, disease progression and response to therapy.
- Prevenção do Cancro Cervical - O caso angolanoPublication . Andrade, P.; Silva, Regina Augusta; Rocha, Helder; Silva, ReginaO cancro cervical é a principal causa de mortalidade por cancro em Angola, colocando sérios desafios ao sistema de saúde do país. Esta situação resulta de deficiências nas infraestruturas de saúde pública, sensibilização da população e acesso a cuidados de saúde preventivos, apesar da disponibilidade de intervenções com boa relação custo-eficácia, como a vacinação contra o HPV e o rastreio do colo do útero. A implementação de programas de rastreio organizado é desafiante em contextos com poucos recursos, mesmo com a aplicação de métodos de inspeção visual, estes enfrentam limitações na precisão e cobertura diagnóstica. Similarmente, campanhas de vacinação contra o HPV, embora promissoras, são limitadas por barreiras sociogeográficas e logísticas. Esta revisão explora a situação atual da prevenção do cancro cervical em Angola, identificando os principais desafios, como a falta de estudos epidemiológicos, infraestruturas de rastreio e as barreiras socioeconómicas no acesso aos cuidados de saúde. Há ainda um trabalho considerável pela frente para cumprir a estratégia da Organização Mundial de Saúde para 2030 -90% de cobertura vacinal, 70% de rastreio e 90% de tratamento. No entanto, podem ser feitos progressos com a adoção de métodos de rastreio inovadoras que incluam a auto-amostragem e unidades de saúde móveis, expandindo esforços de vacinação e reduzindo obstáculos culturais e logísticos.
- A preliminary assessment of a stool-based microRNA profile for early colorectal cancer screeningPublication . Santos, Daniela A. R.; Eiras, Mariana; Gonzalez-Santos, Miguel; Santos, Marlene; Pereira, Carina; Santos, Lúcio Lara; Dinis-Ribeiro, Mário; Lima, Luís; Santos, MarleneColorectal cancer screening methods are well established worldwide as a fundamental pilar in CRC management, namely through non-invasive faecal occult blood testing. However, the limited sensitivity of faecal occult blood test for detecting precancerous lesions highlights the need to search for alternative tools, such as microRNAs (miRs). The main aim of this study was to identify stoolbased miR profiles for early colorectal cancer detection. A panel with miR-21-5p, miR-199a-5p, and age showed a moderate performance for colorectal cancer detection (sensitivity: 88%). Additionally, miR-451a, miR-21-5p, miR-199a-5p, age, and gender showed high performance for discriminating high-grade dysplasia lesions (sensitivity: 91%). Moreover, when we obtained a positive result in either panel, we achieved a sensitivity of 96% for high-grade dysplasia lesions identification. Finally, when a negative result was obtained in these panels after a positive faecal occult blood test result, we accurately identified individuals without lesions. These findings demonstrate the potential of miR panels as non-invasive biomarkers for colorectal cancer and high-grade dysplasia lesions detection and could constitute a secondary screening method following a positive faecal occult blood test.
- Immunogenicity as a predictor of Influenza vaccine efficacy: A systematic reviewPublication . Martins, André Miguel; Juan, Luis Félix Valero; Santos, Marlene; Martins, João Paulo; Santos, Marlene; Oliveira Martins, João PauloInfluenza represents a significant burden on global public health, and vaccination is the most effective strategy to reduce it. The large investment in vaccination programs and the need for adjustments in vaccine serotypes are important reasons for evaluating the influenza vaccine’s efficacy every year. Establishing a relationship between immunogenicity data and efficacy is also crucial for predicting the efficacy of a vaccine during its development. Antibody response measurement is one of the most common methods for evaluating immunogenicity, particularly in vaccines and biologics. The aim of this systematic review was to define a model that relates the immunogenicity of a given vaccine to its efficacy, based on hemagglutination inhibition titer levels. To achieve this goal, information was gathered from articles linking immunogenicity with the efficacy of the influenza vaccine in the Medline and Scopus databases. Different mathematical models were developed and applied to assess the relationship between HAI titers and the effectiveness of the flu vaccine. This analysis was conducted for the various existing vaccines, for the different influenza virus strains, and for their efficacy in paediatric populations. The r2 obtained ranged from 0.2579 to 0.966, which points to the importance of this immunological factor in the efficacy of the influenza vaccine. Conclusions: The efficacy values for titer level 40 confirm the validity of the data provided by Hobson.