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- An overview of the recent advances in antimicrobial resistancePublication . Oliveira, Manuela; Antunes, Wilson; Mota, Salete; Carvalho, Áurea Madureira; Oliveira, Ricardo Jorge Dinis; Silva,Diana Dias daAntimicrobial resistance (AMR), frequently considered a major global public health threat, requires a comprehensive understanding of its emergence, mechanisms, advances, and implications. AMR’s epidemiological landscape is characterized by its widespread prevalence and constantly evolving patterns, with multidrug-resistant organisms (MDROs) creating new challenges every day. The most common mechanisms underlying AMR (i.e., genetic mutations, horizontal gene transfer, and selective pressure) contribute to the emergence and dissemination of new resistant strains. Therefore, mitigation strategies (e.g., antibiotic stewardship programs—ASPs—and infection prevention and control strategies—IPCs) emphasize the importance of responsible antimicrobial use and surveillance. A One Health approach (i.e., the interconnectedness of human, animal, and environmental health) highlights the necessity for interdisciplinary collaboration and holistic strategies in combating AMR. Advancements in novel therapeutics (e.g., alternative antimicrobial agents and vaccines) offer promising avenues in addressing AMR challenges. Policy interventions at the international and national levels also promote ASPs aiming to regulate antimicrobial use. Despite all of the observed progress, AMR remains a pressing concern, demanding sustained efforts to address emerging threats and promote antimicrobial sustainability. Future research must prioritize innovative approaches and address the complex socioecological dynamics underlying AMR. This manuscript is a comprehensive resource for researchers, policymakers, and healthcare professionals seeking to navigate the complex AMR landscape and develop effective strategies for its mitigation.
- Beer with probiotics: Benefits and challenges of their incorporationPublication . Santos, Diana; Barreiros, Luisa; Jesus, Ângelo; Silva, Ana Luísa; Martins, João Paulo; Oliveira, Ana Isabel; Pinho, Cláudia; Jesus, Ângelo; Oliveira, Ana Isabel; Barreiros, LuisaBeer is considered one of the most consumed beverages worldwide and a potential vehicle for probiotics. However, there are several technical challenges to overcome during the production and storage of beers, as probiotics must remain viable until the moment of consumption. Therefore, this work aims to discuss how the incorporation of probiotics improves or adds value to beer and which variables influence the viability of the process. This is a narrative review of the literature with research in the PubMed, Web of Science, and b-on databases for articles related to the incorporation of probiotics in beer and the variables that influence the process. The results demonstrated that the incorporation of probiotics into beer faces technical challenges such as probiotic selection, pH, the presence of alcohol, and beer’s production and storage temperatures. However, strategies such as immobilizing probiotics in alginate, alginate–silica, and durian husk powder, fermentation with the yeast Saccharomyces cerevisiae var. boulardii, and co-fermentation with probiotics permit us to overcome these barriers. Thus, incorporating probiotics into beer brings added value, potentially increasing antioxidant activity and phenolic compound content and providing unique flavors and aromas. Nevertheless, strict control of the technical conditions involved is necessary to ensure probiotic viability and the health benefits they confer.
- Mexican calea (Calea zacatechichi Schltdl.) interferes with cholinergic and dopaminergic pathways and causes neuroglial toxicityPublication . Garcia, Maria Rita; Gil-Izquierdo, Ángel; Ferreres, Federico; Andrade, Paula B.; Mineiro, Tiago; Seabra, Vítor; Videira, Romeu A.; Silva, Diana Dias da; Gomes, Nelson G.M.; Dias da Silva, Diana CristinaThe use of “Mexican calea” (Calea zacatechichi Schltdl.) in ritualistic ceremonies, due to its dream-inducing effects, was until recently limited to indigenous communities in Mexico. However, the plant has recently gained popularity in Western societies being commonly used in recreational settings. Despite the traditional and recreational uses, mechanisms underlying its reported oneirogenic effects remain unknown, with no data available on its neurotoxic profile. The scarcity of toxicological data and the unknown role of major neurotransmitter systems in the dream-inducing properties of the plant prompted us to investigate which neurotransmitters might be affected upon its consumption, as well as the potential cytotoxic effects on neurons and microglial cells. Furthermore, we aimed to explore a relationship between the recorded effects and specific constituents. Effects on cholinergic and monoaminergic pathways were investigated using enzymatic assays, with the latter also being conducted in neuronal SH-SY5Y cells along with the impact on glutamate-induced excitotoxicity. Investigation of the neurotoxic profile was approached in neuronal SH-SY5Y and microglial BV-2 cells, evaluating effects on metabolic performance and membrane integrity using MTT and LDH leakage assays, respectively. Potential interference with oxidative stress was monitored by assessing free radical's levels, as well as 5-lipoxygenase mediated lipid peroxidation. Phenolic constituents were identified through HPLC-DAD-ESI(Ion Trap)MSn analysis. Based on the significant inhibition upon acetylcholinesterase (p < 0.05) and tyrosinase (IC50 = 60.87 ± 7.3 μg/mL; p < 0.05), the aqueous extract obtained from the aerial parts of C. zacatechichi interferes with the cholinergic and dopaminergic systems, but has no impact against monoamine oxidase A. Additionally, a notable cytotoxic effect was observed in SH-SY5Y and BV-2 cells at concentrations as low as 125 and 500 μg/mL (p < 0.05), respectively, LDH leakage suggesting apoptosis may occur at these concentrations, with necroptosis observed at higher ones. Despite the neurocytotoxic profile, these effects appear to be independent of radical stress, as the C. zacatechichi extract scavenged nitric oxide and superoxide radicals at concentrations as low as 62.5 μg/mL, significantly inhibiting also 5-lipoxygenase (IC50 = 72.60 ± 7.3 μg/mL; p < 0.05). Qualitative and quantitative analysis using HPLC-DAD-ESI(Ion Trap)MSn enabled the identification of 28 constituents, with 24 of them being previously unreported in this species. These include a series of dicaffeoylquinic, caffeoylpentoside, and feruloylquinic acids, along with 8 flavonols not previously known to occur in the species, mainly 3-O-monoglycosylated derivatives of quercetin, kaempferol, and isorhamnetin. Our findings regarding the neuroglial toxicity elicited by C. zacatechichi emphasize the necessity for a thorough elucidation of the plant's toxicity profile. Additionally, evidence is provided that the aerial parts of the plant inhibit both acetylcholinesterase and tyrosinase, potentially linking its psychopharmacological effects to the cholinergic and dopaminergic systems, with an apparent contribution from specific phenolic constituents previously unknown to occur in the species. Collectively, our results lay the groundwork for a regulatory framework on the consumption of C. zacatechichi in recreational settings and contribute to elucidating previous contradictory findings regarding the mechanisms underlying the dream-inducing effects of the plant.
- Ensuring safety in cytotoxic drug preparation: A systematic review of guidelines addressing education for pharmacy professionalsPublication . Moreira, Fernando; Jesus, Ângelo; Pinho, Cláudia; Santos, Marlene; Serdoura, Mélanie; Cruz, Agostinho; Moreira, Fernando; Jesus, Ângelo; Pinho, Cláudia; Santos, Marlene; Cruz, AgostinhoChemotherapy preparation involves the use of specific techniques and equipment, given the need to maintain preparation sterility and its strict prescribed composition, and avoid occupational exposure to cytotoxic agents. This study aims to identify the most relevant contents for pharmacy professionals' education and training programs and to elucidate the evaluation procedure these professionals should follow when handling cytotoxics. We adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in conducting and reporting this systematic review. We conducted a literature search in PubMed, Cochrane, and LILACS to identify guidelines on cytotoxic drug preparation published between 2004 and 2024. Inclusion criteria included guidelines written in English, Spanish, or Portuguese that addressed the education, training, and/or evaluation of pharmacy professionals involved in handling cytotoxic drugs. We excluded guidelines developed for other health professionals (e.g. nurses) and guidelines exclusively addressing the manipulation of oral dosage forms. Citation searching was also performed to avoid search biases. Three researchers independently selected 20 guidelines that met the inclusion criteria, out of 3781 unique references identified. Four appraisers assessed the guidelines using the AGREE-II tool. Recommendations for training in cytotoxic drug handling generally included pre-initiation and periodic assessment. Personal protective equipment and engineering controls use, spill management, and aseptic technique were the most frequently mentioned specific training contents. We have developed a training proposal based on the guidelines, with four training levels that address the specific identified content. Each level presents potential competency assessment strategies. Included publications frequently recognized that conducting educational programs before and during the preparation of cytotoxic drugs was important and the combination of theoretical and practical learning seems of the utmost relevance. The development or update of guidelines in this area should prioritize their effective applicability to facilitate their implementation.
- Systematic review of the uses of Cortaderia selloana (Poaceae), an invasive plantPublication . Teixeira, Jéssica; Sousa, Mariana; Cruz, Agostinho; Cruz, AgostinhoCortaderia selloana, commonly known as Pampas Grass, manifests as an invasive plant across numerous countries with predominant studies focused on its control measures (physical, biological, and chemical approaches). Native to South America, this perennial tussock grass negatively impacts economic, environmental, and human health. This study aims to explore the diverse uses of Cortaderia selloana in geographical, cultural and ecological contexts, to provide insights into its applications, and to contribute to socio-economic and ecological understanding. This study comprises a systematic literature review based on the PRISMA 2020 guidelines. The search was conducted in EBSCOhost, ScienceDirect and Web of Science using the search question “("Cortaderia selloana") AND ("use" OR "purpose") NOT (“control”)”. Two researchers independently reviewed the titles and abstracts, applying predefined inclusion and exclusion criteria and extracting data on various aspects covered in the selected studies. A total of 88 articles were retrieved of which 16 were included in this systematic review. This study described diverse applications attributed to Cortaderia selloana, including wastewater treatment, composite synthesis, traditional medicine, bioremediation, biorefining, product development in the automobile industry and decoration. The utilization of this invasive species demonstrated socio-economic and environmental benefits, providing a novel perspective on transforming something harmful into a resource with various applications. Furthermore, the necessity for more research is emphasized, to enhance understanding of known applications and explore new potential uses. This study's main limitation is that it only includes peer-reviewed articles from selected databases. This research provides valuable insights into the diverse uses of Cortaderia selloana across geographical, cultural, and ecological contexts. These findings underscore the importance of considering both the beneficial applications and the challenges posed by this invasive species in order to inform balanced and sustainable management practices.
- Warfarin pharmacogenomics: Designing electrochemical DNA-based sensors to detect CYP2C9*2 gene variationPublication . Barbosa, Tiago; Morais, Stephanie L.; Pereira, Eduarda; Magalhães, Júlia M. C. S.; Domingues, Valentina F.; Ferreira-Fernandes, Hygor; Pinto, Giovanny; Santos, Marlene; Barroso, Maria Fátima; Santos, MarleneThe CYP2C9 enzyme is involved in the metabolism of warfarin. The CYP2C9 gene harbors several single-nucleotide polymorphisms (SNPs), including CYP2C9*2 (rs1799853), which is known to affect warfarin’s therapeutic response. So, it is important to develop analytical tools capable of genotyping these SNPs to adjust warfarin’s therapeutic outcomes. In this work, an electrochemical DNA-based sensor was constructed and optimized for the detection of the CYP2C9*2 polymorphism. Methods: Using bioinformatic database platforms, two 71 base pair DNA target probes with the polymorphic variants A and G were chosen and designed. A DNA-based sensor was composed by mercaptohexanol and the CYP2C9*2 DNA capture probe in a self-assembled monolayer connected to screen-printed gold electrodes. Two independent hybridization events of the CYP2C9*2 allele were designed using complementary fluorescein-labeled DNA signaling to improve selectivity and avoid secondary structures. Three human samples with the homozygous variant (G/G) and non-variant (A/A) and heterozygous (G/A) genotypes were amplified by PCR and then applied to the developed genosensor. Results: Chronoamperometry measurements were performed for both polymorphic probes. A calibration curve in the 0.25 to 2.50 nM (LOD of 13 pM) and another in the 0.15 to 5.00 nM range (LOD of 22.6 pM) were obtained for the homozygous non-variant and variant probes, respectively. This innovative tool was capable of identifying the hybridization reaction between two complementary strands of immobilized DNA, representing a genotyping alternative to the classical PCR methodology. Conclusions: The developed electrochemical DNA-based sensor was able to discriminate two synthetic SNP target sequences (Target-A and Target-G) and detect, with specificity, the three patients’ genotypes (G/G, G/A, and A/A). This tool is therefore a promising, sensitive, and cost-effective analytical way to determine and discriminate an individual’s genotype and predict the appropriate warfarin dose.
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseasesPublication . Rojo, Ana I.; Buttari, Brigitta; Cadenas, Susana; Carlos, Ana Rita; Cuadrado, Antonio; Falcão, Ana Sofia; López, Manuela G.; Georgiev, Milen I.; Grochot-Przeczek, Anna; Gumeni, Sentiljana; Jimenez-Villegas, José; Horbanczuk, Jarosław Olav; Konu, Ozlen; Lastres-Becker, Isabel; Levonen, Anna-Liisa; Maksimova, Viktorija; Michaeloudes, Charalambos; Mihaylova, Liliya V.; Mickael, Michel Edwar; Milisav, Irina; Miova, Biljana; Rada, Patricia; Santos, Marlene; Seabra, Miguel C.; Strac, Dubravka Svob; Tenreiro, Sandra; Trougakos, Ioannis P.; Dinkova-Kostova, Albena T.Non-communicable chronic diseases (NCDs) are most commonly characterized by agerelated loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.
- Ten-year analgesic utilization patterns and economic implications in PortugalPublication . Duarte, Nuno; Martins, João Paulo; García-Pedraza, Jose-Ángel; Santos, MarleneThis study evaluated the 10-year consumption and economic patterns of classical analgesics, adjuvants and opioids in Portugal (2012-2022), and conducted a comparative analysis between Portugal, Spain and Denmark to explore the consumption patterns among these countries for 2022. Data on sales and national health service (NHS) costs were obtained from the Portuguese National Authority of Medicines and Health Products. Sales data were converted to defined daily dose (DDD) per 1000 inhabitants per day according to the Anatomical Therapeutic Chemical (ATC) classification/DDD methodology, while comparisons between Spain and Denmark were evaluated with the chi-square test, when appropriate. The findings reveal that classical analgesics use in Portugal remained stable during the period 2012-2022, with ibuprofen being the most consumed. Adjuvants, specifically gabapentinoids, experienced an 84% increase in use, primarily attributed to pregabalin. Weak opioids, led by tramadol, witnessed a 117% rise in use, while strong opioid use, led by tapentadol, increased by 618%. Portugal presented the lowest overall opioid consumption when compared to Denmark and Spain in 2022. Economic trends indicated a heightened NHS expenditure on analgesics, primarily driven by increased opioid use. Notwithstanding, there was no significant burden on relative expenditure over the 10-year period. Portugal presented a major increase in both weak and strong opioid prescriptions, aligning with the trends for Spain and Denmark. The development and approval of generic medicines and vigilant market monitoring are imperative strategies for managing the escalated costs resulting from heightened consumption, particularly concerning opioids.
- Microcarrier-based fluorescent yeast estrogen screen assay for fast determination of endocrine disrupting compoundsPublication . Gregório, Bruno J.R.; Ramos, Inês I.; Marques, Sara S.; Barreiros, Luísa; Magalhães, Luís M.; Schneider, Rudolf J.; Segundo, Marcela A.The presence of endocrine-disrupting compounds (EDCs) in water poses a significant threat to human and animal health, as recognized by regulatory agencies throughout the world. The Yeast Estrogen Screen (YES) assay is an excellent method to evaluate the presence of these compounds in water due to its simplicity and capacity to assess the bioaccessible forms/fractions of these compounds. In the presence of a compound with estrogenic activity, Saccharomyces cerevisiae cells, containing a lacZ reporter gene encoding the enzyme β-galactosidase, are induced, the enzyme is synthesised, and released to the extracellular medium. In this work, a YES-based approach encompassing the use of a lacZ reporter gene modified strain of S. cerevisiae, microcarriers as solid support, and a fluorescent substrate, fluorescein di-β-d-galactopyranoside, is proposed, allowing for the assessment of EDCs’ presence after only 2 h of incubation. The proposed method provided an EC50 of 0.17 ± 0.03 nM and an LLOQ of 0.03 nM, expressed as 17β-estradiol. The assessment of different EDCs provided EC50 values between 0.16 and 1.2 × 103 nM. After application to wastewaters, similar results were obtained for EDCs screening, much faster, compared to the conventional 45 h spectrophotometric procedure using a commercial kit, showing potential for onsite high-throughput screening of environmental contamination.
- Interações medicamentosas potenciais: uma análise exploratória em farmácia comunitáriaPublication . Fernandes, Daniela; Jesus, ÂngeloInterações medicamentosas (IMs) podem ser descritas como a influência farmacológica de um fármaco sobre outro, quando administrados em combinação. Com o avanço da tecnologia farmacêutica, aumentam os fármacos disponíveis, aumentando também as possibilidades da ocorrência de interações entre medicamentos, já que a administração simultânea de dois ou mais medicamentos para um mesmo paciente se tornou uma prática comum. Analisar e classificar as interações medicamentosas potenciais (IMPs) do tipo fármaco-fármaco em prescrições de utentes com dislipidémia e/ou diabetes mellitus; determinar quais as IMPs mais prevalentes; determinar quais os fármacos mais associados a IMs; identificar todas as IMPs major, minor e moderadas na amostra. Este estudo avaliou informação recolhida a partir de 101 prescrições de utentes com dislipidémia e/ou diabetes no distrito do Porto e Braga. Posteriormente, as informações relativas a cada um dos grupos da amostra foram analisadas com recurso à base de dados IBM Micromedex Complete Drug Interactions. Finalmente, foi feito o tratamento estatístico descritivo dos dados. Resultados: Em 101 prescrições, existem 116 potenciais interações medicamentosas no total, 32 Major e 84 Moderadas. Existem IMPs em 50 (ou 49,5%) das prescrições e em 24 das prescrições, (ou 23,8%) existe potencial para IMP major. Perante estes resultados, urge encontrar soluções que se foquem nas potenciais reações adversas ao medicamento (RAMs) provocados por IMs, de modo a aumentar a segurança dos utentes e da própria comunidade e melhorar a saúde pública.