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- Dose-dependent pharmacological mechanisms within the Neuroscience-based Nomenclature: a new concept to facilitate neuroscience-based prescribingPublication . Zemach, Sasson; Zohar, Joseph; Correll, Christoph U.; Stahl, Stephen M.; Drago, Filippo; Goodwin, Guy M.; Moller, Hans-Jurgen; Uchida, Hiroyuki; Siafis, Spyridon; Santos, Marlene; Blier, Pierre; Santos, MarleneIn this Personal View, we introduce the concept of different dosage different pharmacology (DDDP), which describes how certain psychotropic medications have distinct therapeutic effects at low and high doses due to differing neurobiological mechanisms. Using the Neuroscience-based Nomenclature (NbN) framework, which classifies drugs by pharmacology and modes of action, we identified ten agents demonstrating DDDP in a comprehensive expert-based consensus process: amisulpride, amitriptyline, aripiprazole, brexpiprazole, cariprazine, doxepin, mirtazapine, quetiapine, risperidone, and trazodone. These medications show clearly demarcated dose-dependent effects, with changes in pharmacological action. For example, some drugs show anxiolytic or hypnotic effects at low doses (via histamine H1 or noradrenergic α1 antagonism) and antidepressant effects at high doses (via reuptake inhibition of serotonin or norepinephrine). Understanding these differences supports more rational prescribing (eg, increasing dopamine partial agonist doses beyond the optimal range might reduce efficacy). DDDP, within the NbN framework, offers a neuroscience-based approach to more precise psychopharmacology.
- Integrating PET for tumour hypoxia in radiotherapy planning: Insights from Portuguese radiotherapy and nuclear medicine technologistsPublication . Sousa, Ruben Diogo Oliveira; Faria, Brígida Mónica; Bravo, Isabel; Costa, Pedro; Costa, Pedro; Faria, Brigida MonicaIn the era of personalised medicine, tumour hypoxia (TH) is critical in radiotherapy (RT) response due to its role in tumour resistance. Positron Emission Tomography (PET) enables non-invasive assessment of TH and supports heterogeneous dose-escalation to hypoxic sub-volumes, improving treatment efficacy. This study explores Nuclear Medicine Technologists (NMT) and Radiotherapy Technologists (RTT) perceptions of PET-based TH (PET-TH) assessment and implementation in RT planning in Portugal. We conducted an observational cross-sectional survey of RTTs and NMTs currently working in Portuguese healthcare institutions. Statistical tests were used to assess associations and compare distributions using IBM® SPSS®. A total of 66 participants, 57 (86.4 %) females, with a mean age of 33.68 (±8.13) years, were included: 23 (34.8 %) NMTs and 43 (65.2 %) RTTs. While 65.2 % of NMT departments had PET scans with RT-compatible settings, only 8.7 % had performed PET-TH studies. Among RTTs, 88.4 % reported that their treatment planning systems were compatible with PET/CT fusion, yet only 9.3 % had used PET in RT planning. RTTs received more training in TH (p = 0.006) and rated their knowledge higher than NMTs (p = 0.042). Greater professional experience and higher perceived knowledge were associated with better performance on evaluation items (p = 0.027; p = 0.037). Regardless of institution type, 92.4 % expressed interest in interprofessional collaboration to support individualised planning. The assessed departments possess infrastructures for PET-TH integration, yet clinical implementation remains limited. Knowledge and professional experience are associated with competency. Targeted training for Technologists and interdisciplinary workflows may improve PET-TH adoption. Addressing knowledge and workflow could facilitate PET integration into RT planning and potentially enhance treatment outcomes. Future efforts should focus on interdisciplinary collaboration.
- Effectiveness of an intervention program for informal carers of children admitted to a rehabilitation centrePublication . Morais, Sónia; Pimenta, Rui Esteves; Morais, Carminda; Macedo, Rui; Ribeiro, Inês; Ferreira, Pedro Lopes; Pimenta, Rui; Macedo, RuiHealth literacy improves informal caregivers’ knowledge and ability to provide care. The aim of this study is to analyze the impact of a group-based intervention on the health literacy of informal caregivers of children with special health needs (SHNs). The intervention focuses on movement, hydrotherapy, walking, and relaxation, with three evaluation stages. Participants included 34 informal caregivers of children with SHNs, recruited at a Physical Medicine and Rehabilitation Service. We collected sociodemographic data of the participants and measured their health literacy through the short-form version of the European Health Literacy Survey Questionnaire (HLS-EU-Q16). Around 70% of the participants were female, with a mean age of 41.06 ± 4.98 years, and nearly 85% were married or in a de facto union. About 26% were unemployed, and more than 65% had completed secondary education or higher. The mean scores of the HLS-EU-Q16 were statistically significantly higher throughout the intervention, with differences over the evaluation stages [F(2,56) = 75.55; p < 0.05]. A structured, dynamic, and group-based intervention plan showed improvements in the health literacy of the participants, with an increase in the percentage of participants with sufficient and excellent levels of health literacy at the end of the intervention.
- 3-Bromopyruvate boosts the effect of chemotherapy in acute myeloid leukemia by a pro-oxidant mechanismPublication . Vieira, Joana Pereira; Preto, Ana; Granja, Sara; Queirós, Odília; Celeiro, Sónia Pires; Ko, Young Hee; Casal, Margarida; Matos, Catarina Barbosa; Baltazar, Fátima; Granja, SaraAcute myeloid leukemia (AML) comprises a diverse group of blood cancers with varying genetic, phenotypic, and clinical traits, making development of targeted therapy challenging. Metabolic reprogramming in AML has been described as relevant for chemotherapy effectiveness. 3-Bromopyruvate (3-BP) is an anticancer agent that undermines energy metabolism of cancer cells. However, the effect of 3-BP in hematologic malignancies, such as AML, needs further investigation. Thus, we aimed to explore 3-BP as a chemo-sensitizing agent in AML. Different approaches of combining 3-BP with classical chemotherapy (daunorubicin and cytarabin) were tested in diverse AML cell lines. Cell sensitivity to the different drug combinations was analyzed by Trypan blue staining. The effect of pre-treatment with a non-toxic concentration of 3-BP was assessed on the AML cell metabolic profile (Western blot and immunofluorescence), mitochondrial activity (cytometry flow), and antioxidant capacity (colorimetric detection kit). KG-1 and MOLM13 cells showed increased sensitivity to chemotherapy (decreased EC 50 values) after exposure to a non-toxic concentration (5 μ M) of 3-BP. In both cell lines, 5 glucose consumption without changing extracellular lactate levels. 5 μ μ M 3-BP decreased M 3-BP treatment increased reactive oxygen species levels and decreased cell antioxidant capacity by depleting reduced glutathione levels in both KG-1 and MOLM13 cells. Our results demonstrate that non-toxic concentrations of 3-BP enhance the effect of classical chemotherapy in AML cells through a pro-oxidant mechanism. These data unveiled a new approach for AML treatment, using 3-BP or other pro-oxidant agents as co-adjuvants of chemotherapy, subsiding chemotherapy- induced side effects.
- MCT1 is a new prognostic biomarker and its therapeutic inhibition boosts response to Temozolomide in human glioblastomaPublication . Gonçalves, Vera Miranda; Gonçalves, Céline S.; Granja, Sara; Castro, Joana Vieira de; Reis, Rui M.; Costa, Bruno M.; Baltazar, Fátima; Granja, SaraGlioblastoma, the brain tumour with highest prevalence and lethality, exhibits a characteristic glycolytic phenotype with increased lactate production. Recently, we reported a MCT1 overexpression in GBMs tumours, being associated to tumour growth and aggressiveness. Thus, we aimed to disclose the role of MCT1 in GBM prognosis and in vivo therapy response. Importantly, MCT1 overexpression is associated with poor prognosis of GBM. Moreover, MCT1 inhibition retards GBM tumour growth and boosts response to temozolomide treatment.
- Metabolism-targeted therapy in NSCLC – A new theranostics inhalation approach using lactate functionalized and selenium-chrysin loaded nanoparticles (SeChry@PUREG4-LA24)Publication . Mendes, Cindy; Martins, Filipa; Granja, Sara; Gonçalves, Joana; Barros, Hélio; Casimiro, Teresa; Ricardo, Ana Aguiar; Silva, Fernanda; Abreu, Bruna; Cristovão, Miguel; André, Saudade; Pereira, Sofia A.; Baltazar, Fátima; Marques, Helena Cabral; Gaspar, Maria Manuela; Gonçalves, Luís G.; Bonifácio, Vasco D. B.; Serpa, Jacinta; Granja, SaraLung cancer is one of the most lethal cancers globally, primarily due to delayed diagnosis and lack of specific and effective therapy. Increased lactate production and consumption, along with cysteine metabolic reliance, are features identified in NSCLC in our recent studies. Cancer metabolic remodeling leads to excessive ROS production, triggering oxidative stress, promoting angiogenesis, causing cellular and tissue damage, and contributing to various pathophysiological changes. This study aimed to investigate the therapeutic potential of selenium–chrysin (SeChry), a cysteine metabolism inhibitor, and its delivery targeted at MCT1 by encapsulation in fourth-generation polyurea dendrimers functionalized with lactic acid (PUREG4-LA24), the nanoformulation SeChry@PUREG4-LA24, in NSCLC. We explored the impact of SeChry nanoformulation on cell death mechanisms, including ferroptosis, and its influence on angiogenesis in in vitro and in vivo models. SeChry@PUREG4-LA24 induces cell death through the induction of intracellular ROS and lipid peroxides, resulting in distinct expression patterns of ferroptosis-associated genes across cell lines. Experiments using chicken embryo chorioallantoic membrane (CAM) and mouse orthotopic xenograft models revealed a trend toward decreased tumor growth and angiogenesis with SeChry@PUREG4-LA24 administration. These findings suggest the potential of SeChry@PUREG4-LA24 as an innovative therapeutic approach for NSCLC, highlighting its impact on cell death mechanisms and anti-angiogenic effects.
- Medication review improves pain management and quality of life in chronic pain: a pilot randomized controlled studyPublication . Duarte, Nuno; Martins, João Paulo; García-Domingo, Mónica; A. García-Pedraza, Jose; Santos, Marlene; Santos, Marlene; Oliveira Martins, João Paulo; Duarte, NunoChronic pain is a complex condition that benefits from a multidisciplinary approach. This pilot parallel-group single-blinded randomized controlled study evaluated the feasibility, acceptability and adherence by patients and physicians of pharmacist-led medication review on chronic pain patients. Trends in pain intensity, quality of life and patient satisfaction were examined. Twenty adults were recruited from two primary care units in Porto, Portugal, and randomly assigned to either the medication review (MR) group, (n=10) using the Dader method, or the usual care (UC) group, (n=10) and given general advice, for 16-weeks. Pain intensity decreased by 2.07 (MR group) and increased by 0.52 (UC group), yielding an adjusted mean difference of 2.77 (95% CI, -4.93 to -0.62; p=0.008). Pain relief was reported by 62.5% in the MR group versus 37.5% in UC (p=0.357). The MR group showed significant improvement in physical functioning (p=0.019) and higher treatment satisfaction (p=0.029). The acceptance rate of MR interventions was 71%, which resolved 63% of negative medication outcomes. Acceptability was high (>90% of planned interviews). Conducting pharmacist led MR for chronic pain management in primary care is feasible and well accepted by patients and physicians. Observed trends toward improved pain and QoL warrant confirmation in a larger trial. This pilot trial was registered in clinicaltrials.gov (NCT06997861).
- Development of a sustainable biosensor to detect respiratory infectious diseasesPublication . Nascimento, Ana Margarida; Abreu, Cristina; Silva, M.; Leite, B.; Rouly, S.; Abreu, M. J.; Ferraz, Ricardo; Costa, M.; Prudêncio, Cristina; Parente, E.; Vieira, Mónica; Ferraz, Ricardo; Vieira, Mónica; Prudêncio, CristinaThe Covid-19 pandemic brought the need to use social masks to prevent the spread of the SARS-CoV-2 virus. However, no reliable and fast method were yet established to detect viral particles and to improve the protective ability of social masks. Through color changes, colorimetric biosensors can be used as a rapid and easily approach to detect virus. Gold nanoparticles (AuNP) are known to have excellent optical properties and huge research potential. The new SARS-CoV-2 has the ability of entering human body cells, namely through a second pathway of entry – the sialic acid (SA) receptor. In order to respond to the emergency and to contribute to the diminishing of the spread of SAR-CoV-2, we developed a colorimetric biosensor based on the functionalization AuNP by sialic acid (SA) (SA-AuNP), as a new and effective textile coating layer, to provide a direct indication of the protective capacity of social masks. To do that, AuNPs (10 nm) were functionalized with SA (SA-AuNP), in three different concentrations (50-50, 30-70 and 20-80, respectively) to select the optimal concentration for respiratory virus detection. Fourier-transform infrared spectroscopy (FTIR) and Scanning Electron Microscope with a Transmission Detector (STEM) analyses confirmed SA-AuNPs binding. FTIR results showed a well-established bond, through matches of peaks of SA-AuNPs. Bindings between the compounds were more evident in 50-50 concentration of SA-AuNP. In the 30-70 SA-AuNP the STEM images show some superposition of the nanoparticles and not so evident binding, as in the 20-80 concentration. Still, between these last two concentrations, the 30-70 is the one that shows the best results since it is visible some circular points larger than the others. To achieve the goal, the concentrations 30-70 and 50-50 of SA-AuNP were impregnated (Textile Foulard) in two substrates of different compositions, a cellulosic and a synthetic one. However, in this technique there are many parameters, such as drying time and temperature, which were varied to understand which the best procedure was to obtain the biosensor.
- Betulinic acid and obesity-related disordersPublication . Azevedo, Lara; Ferraz, Ricardo; Vieira, Mónica; Prudêncio, Cristina; Fernandes, Sílvia; Ferraz, Ricardo; Almeida Vieira, Mónica Andreia; Prudêncio, Cristina; Fernandes, SílviaThe obesity epidemic is not just a health issue, it is increasingly driving a shift in the prevalence of chronic diseases, affecting 890 million adults and straining healthcare systems worldwide. Conditions such as type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fatty liver disease, and various cancer types are closely tied to this growing crisis. Betulinic acid has anti-inflammatory, antioxidant and anti-cancer properties and modulates key metabolic pathways such as NF-κB and AMPK signaling. This compound improves insulin sensitivity, reduces hepatic steatosis, mitigates the progression of atherosclerosis and fibrosis, and suppresses inflammatory responses, which are important in treating those obesity-related disorders. Additionally, betulinic acid use in cancer treatment has been explored due to its potential in angiogenesis and metastasis inhibition and promotion of apoptosis. This review spotlights the therapeutic potential of the natural compound betulinic acid in processes such as insulin sensitivity, glucose and lipid metabolism, adiposity, inflammation, oxidative stress, intestinal microbiota, and other mechanisms underlying different obesity-related disorders. Overall, besides strong therapeutic potential of betulinic acid, described limitations such as poor aqueous solubility, limited bioavailability, production and extraction have resulted in scarce clinical data making it premature to draw definitive conclusions regarding its application in clinical practice.
- Environmental and food safety assessment of pre-harvest activities in local small-scale fruit and vegetable farms in northwest Portugal: Hazard identification and compliance with good agricultural practices (GAPs)Publication . Macieira, Ariana; Fernandes, Virgínia Cruz; Brandão, Teresa R. S.; Delerue-Matos, Cristina; Teixeira, Paula; Fernandes, VirgíniaThe popularity of small-scale and local fruit and vegetable production has increased in recent years due to perceived economic, environmental, and social benefits. However, these operations face contamination risks that both consumers and small-scale producers may underestimate. The present study aimed to assess the microbiological and chemical hazards on fruit, vegetables, soil, and water samples from small-scale farms in north-western Portugal during pre-harvest activities. Additionally, the study investigated farmers’ non-compliance with food safety regulations and good agricultural practices (GAPs), exploring how their behaviour might contribute to the identified hazards. A before-and-after analysis of non-compliant behaviours was conducted to determine the impact of training on improving food safety practices. The analysis identified the presence of pathogenic bacteria, pesticides, flame retardant residues, nitrates, and heavy metals. Lead (Pb) concentrations exceeded EU limits in organic carrots from one producer (0.156 ± 0.043 mg/kg) and in chard from another (0.450 ± 0.126 mg/kg). Cadmium (Cd) levels were also above regulatory thresholds in bell peppers (0.023 ± 0.009 mg/kg) and organic tomatoes (0.026 ± 0.015 mg/kg) from two different producers. Elevated levels of heavy metals were detected in irrigation water from two sites, with zinc (Zn) at 0.2503 ± 0.0075 mg/L and Pb at 0.0218 ± 0.0073 mg/L. Among food samples, the most prevalent microorganisms were Pseudomonas spp. (88.2%), Bacillus cereus (76.5%), and aerobic mesophilic bacteria (100%). Phosphorus flame retardants (PFRs), particularly tris(2-butoxyethyl) phosphate (TBEP), were detected in all food and soil samples. Some EU-banned pesticides were detected in food and soil samples, but at levels below the maximum residue limits (MRLs). Chlorpyrifos (35.3%) and p,p’-DDD (23.5%) were the most detected pesticides in food samples. After the training, GAP behaviour improved, particularly that related to hygiene. However, issues related to record-keeping and soil and water analyses persisted, indicating ongoing challenges in achieving full compliance.