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- The Role of Immunogenetics in the Host-Parasite Interaction of Chagas Disease: Implications for Personalized MedicinePublication . Hassnain, Muhammad; Bukhari, Syeda Mahnoor; Bibi, Tahira; Waheed, Syeda Fakhra; Botelho, Monica C.; Ahmad, WaqasChagas disease, caused by the protozoan parasite Trypanosoma cruzi, continues to be a significant global health issue, especially in Latin America, with increasing international prevalence due to migration. Despite advancements in diagnosis and treatment, it remains a neglected tropical disease characterized by significant morbidity and mortality, mainly influenced by the complex interaction between parasite diversity and host immune responses. Importantly, the remarkable genetic diversity of T. cruzi lineages also contributes to clinical heterogeneity, influencing immune evasion, therapeutic responses, and vaccine feasibility. This review analyzes the impact of immunogenetics on host-parasite interactions in Chagas disease and explores its implications for personalized therapy approaches. Recent research, particularly over the last decade, has indicated that processes including antigenic variation, extracellular vesicle-mediated regulation, and disruption of host signaling pathways facilitate parasite persistence. Host genetic variables significantly influence susceptibility, disease development, and treatment outcomes, including changes in Human Leukocyte Antigen (HLA) genes, cytokine gene polymorphisms, and immunogenetic determinants of cardiac pathology. These findings underscore the potential of immunogenetic markers as tools for prognosis and as targets for personalized therapies. However, there are still considerable research deficiencies. Inadequate comprehension of gene-environment interactions, lack of representation of varied populations, and inconsistencies in study design limit the use of immunogenetic findings in therapeutic settings. At present, the concept of personalized medicine in Chagas disease remains largely aspirational, better understood as a framework for precision public health or stratified interventions guided by host immunogenetic and parasite lineage data. Addressing these issues necessitates comprehensive genomic research, mechanistic investigations of host-parasite interactions, and clinical validation of genetic markers. This study emphasizes the necessity of incorporating immunogenetics into personalized patient management strategies based on existing evidence. This integration has the potential to improve diagnosis, enhance treatment efficacy, and inform preventive interventions, thereby advancing personalized therapy for Chagas disease.
- Cross-sectional study on protective antibodies against influenza A virus subtypes and cross-protection against influenza A(H3N2) subclade K, Portugal, August 2025Publication . Guiomar, Raquel; Henriques, Camila; Pereira da Silva, Susana; Gomes, Licínia; Dias, Daniela; Verdasca, Nuno; Portuguese Laboratory Network for the Diagnosis of Influenza and Respiratory Viruses; Nunes, Baltazar; Rodrigues, Ana PaulaThe 2025/26 season was marked by co-circulation of influenza A subtypes, with the first detection of A(H3N2) subclade K in September 2025. In August 2025 in Portugal, 14.8% (95% CI: 12.2-17.8) of 886 persons tested had cross-protective antibodies against this subclade. The overall seroprevalence against circulating A(H1N1)pdm09 strains was 28.1% (95% CI: 24.4-32.0). These data highlight the presence of previous cross-reactive antibodies and the possible advantage of vaccination in the extent of detectable antibodies against influenza viruses.
- Rapid drug resistance prediction in positive clinical samples using an extensive targeted next-generation sequencing panelPublication . Rosendal, Ebba; Isidro, Joana; Carneiro, Sofia; Gomes, João Paulo; Macedo, RitaTuberculosis (TB) remains a global health challenge, exacerbated by the emergence of drug-resistant strains. Most methods for drug susceptibility testing (DST) are culture-dependent and time consuming, possibly delaying optimal TB-treatment. This study aimed to develop an extensive targeted next-generation sequencing (tNGS) approach for rapid genotypic DST directly from clinical samples. We designed a tNGS panel comprising 30 amplicons targeting 19 genomic regions associated with resistance to 20 antibiotics. This method was applied to 71 smear-positive (0-3+) pulmonary TB clinical samples collected at the Portuguese National Reference Laboratory. DNA was extracted and amplified using multiplex PCRs, followed by sequencing on Oxford Nanopore Technologies MinION platform. Sequencing data were using TB-Profiler and the tNGS results compared to phenotypic DST and whole genome sequencing (WGS) data from corresponding isolates. The tNGS demonstrated high concordance with both phenotypic and WGS-based DST across different sample types and smear positivity levels. For first-line drugs, tNGS showed 88% categorical agreement (CA) with pDST, increasing to 97% when excluding undetermined results. Compared to WGS across all analysed antibiotics, tNGS achieved 92% CA, increasing to >99% when excluding undetermined results. Validation of the tNGS panel showed 90% (1,895/2,076) of amplicons reaching >10x coverage at all analysed positions and 43 (61%) samples with all complete amplicons above this threshold. Non-specific amplification of contaminant bacterial DNA was minimal, with most mapped off-target reads being of human origin. This method enables comprehensive resistance prediction directly from clinical samples and signifies an important development in TB diagnostics and resistance monitoring.
- In vitro and in vivo assessment of nanoceria biocompatibility for their safe use in nervous system applicationsPublication . Fernández-Bertólez, Natalia; Martínez, Luisa; Ramos-Pan, Lucía; Touzani, Assia; Costa, Carla; Laffon, Blanca; Valdiglesias, VanessaNanoceria, or cerium dioxide nanoparticles (CeO NP), are increasingly employed in a number of industrial and commercial applications. Hence, the environmental presence of these nanoparticles is growing progressively, enhancing the global concern on their potential health effects. Recent studies suggest that nanoceria may also have promising biomedical applications particularly in neurodegenerative and brain-related pathologies, but studies addressing their toxicity, and specifically on the nervous system, are still scarce, and their potential adverse effects and action mechanism are not totally understood yet. The objective of this work was to assess the biological behaviour of CeO NP in vitro in human nervous systems cells, and in vivo in Drosophila melanogaster to characterize their safety for exposed individuals and verify their suitability to be further employed in diagnosis and treatment of nervous system disorders. Cell cycle alterations, late apoptosis rate and DNA damage (comet and γH2AX assays), were determined in neuronal SH-SY5Y and glial A172 cells treated with nanoceria. Moreover, the survival rate, morphological changes and behavioural alterations were analysed in D. melanogaster individuals chronically exposed to CeO NP. The results obtained from the in vitro assessment showed that the nanoceria generally presented a good biocompatibility with scarce cyto- or genotoxic effects, essentially depending the exposure time and cell type, and being restricted to the longer exposure periods. Nevertheless, decrease in adult size and alterations observed in the larval crawling in the in vivo assays highlight the need of further investigations before establishing clinical uses of nanoceria.
- Two cinnamic acid derivatives as inhibitors of Pseudomonas aeruginosa las and pqs quorum-sensing systems: Impact on biofilm formation and virulence factorsPublication . Leitão, Miguel M.; Gonçalves, Ariana S.C.; Sousa, Sérgio F; Borges, Fernanda; Simões, Manuel; Borges, AnabelaIntroduction: Quorum sensing (QS) is a bacterial communication mechanism that regulates gene expression, playing a crucial role in various physiological processes. Interfering with this signalling pathway is a promising strategy to control bacterial pathogenicity and virulence. Objectives: This study evaluated the potential of two cinnamic acid derivatives, ferulic and sinapic acids, to inhibit the las and pqs systems in Pseudomonas aeruginosa. Their effects on biofilm architecture, virulence factor production and bacterial motility were also investigated. Methods: Bioreporter strains and bioluminescence-based assays were used to evaluate the modulation of QS-activity by cinnamic acid-type phenolic acids. In addition, in silico docking analysis was performed to validate the binding interactions of the cinnamic acid derivatives with QS-receptors. The biofilm architecture was analysed by optical coherence tomography, and virulence factors production (pyoverdine, pyocyanin, total proteases, lipases, gelatinases and siderophores) and motility were measured by absorbance measurement and plate agar method. Results: Ferulic and sinapic acids at 1000 µg mL-1 inhibited the las and pqs systems by 90 % and 80 %, respectively. The N-3-oxododecanoyl-homoserine lactone production was reduced by 70 % (6.25 µg mL-¹). In silico analysis demonstrated that cinnamic acid derivatives exhibited comparable interactions and higher docking scores than reference ligands and inhibitors. Biofilm thickness decreased from 96 µm to 11 µm, and virulence factors and swarming motility were significantly impaired. The comparable anti-QS activity of cinnamic acid derivatives suggests that the additional methoxy group in sinapic acid does not directly contribute to its anti-QS effect. Conclusion: Ferulic and sinapic acids compromised the biofilm architecture and virulence of P. aeruginosa through QS inhibition.
- Extrapulmonary manifestations of SARS-CoV-2 infection and COVID-19 vaccine adverse effectsPublication . Botelho, Monica Catarina; Poma, Anello Marcello; Wu, JianNo abstract available
- An overview of work-related stress assessmentPublication . Lavreysen, Olivia; Bakusic, Jelena; Abatzi, Thalia-Anthi; Geerts, Annelien; Mateusen, Mies; Bashkin, Osnat; Koscec Bjelajac, Adrijana; Dopelt, Keren; du Prel, Jean-Baptist; Franic, Zrinka; Guseva Canu, Irina; Kiran, Sibel; Merisalu, Eda; Pereira, Cristiana Costa; Roquelaure, Yves; Godderis, LodeObjective: Work-related stress (WRS) is associated with the development of various health issues and long-term absence from the workplace. Adequate measurement of WRS is essential to assess its prevalence, risks, and effectiveness of preventive interventions. The aim of this review was to provide an overview of different categories of WRS assessment: 1) self-assessment, 2) external assessment, and 3) biomarkers. Methods: The databases MEDLINE, PsycINFO, EMBASE, CINAHL, and Web of Science have been searched until July 2024 for studies comprising self-assessment or external assessment of WRS, and WRS biomarkers. The self-assessment studies were further evaluated following the COSMIN guidelines. Results: In this review, a total of 15,749 articles were screened. The final analysis included 53 studies on self-assessment of WRS, 33 articles on external assessment of WRS and 167 articles on stress biomarkers. Within self-assessment studies, four instruments were included in the analysis: Job Content Questionnaire, Effort Reward Imbalance Questionnaire, Copenhagen Psychosocial Questionnaire II and the Demand-Control-Support Questionnaire. The studies applying external assessment used job-exposure matrices, work register data, ethnography, digital tools, and external observation. The identified WRS biomarkers were associated with the sympathetic adrenal medullary axis, the hypothalamic pituitary adrenal axis, immune response and inflammation, and haemostatic, metabolic and (epi)genetic biomarkers. Conclusion: The available evidence does not support the claim that there is a singular golden standard for assessing WRS. Inclusion of objective parameters and the interaction with subjective parameters and biological markers has to be studied to receive a broader view of WRS.
- New insights on antibacterial mode of action of blue-light photoactivated berberine and curcumin-antibiotic combinations against Staphylococcus aureusPublication . Gonçalves, Ariana S.C.; Fernandes, José R.; Saavedra, Maria José; Guimarães, Nuno M.; Pereira, Cristiana; Simões, Manuel; Borges, AnabelaAntimicrobial photodynamic inactivation (aPDI), using photosensitisers in combination with antibiotics, is a promising multi-target strategy to address antibiotic resistance, particularly in wound infections. This study aimed to elucidate the antibacterial mode of action of combinations of berberine (Ber) or curcumin (Cur) with selected antibiotics (Ber-Ab or Cur-Ab) under blue light irradiation (420 nm) against Staphylococcus aureus, including methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains. Multiple physiological parameters were assessed using complementary assays (fluorometry, epifluorescence microscopy, flame emission and atomic absorption spectroscopy, zeta potential, flow cytometry, and the plate agar method) to examine the effect on ROS production, membrane integrity, DNA damage, motility and virulence factors of S. aureus. Results indicated that blue light photoactivated Ber-Ab and Cur-Ab combinations led to substantial ROS generation, even at low concentrations, causing oxidative stress that severely impacted bacterial membrane integrity (approximately 90 % in MRSA and 40 % in MSSA). Membrane destabilization was further confirmed by elevated intercellular potassium release (≈ 2.00 and 2.40 µg/mL in MRSA and MSSA, respectively). Furthermore, significant DNA damage was observed in both strains (≈ 50 %). aPDI treatment with blue light also reduced S. aureus pathogenicity by impairing motility and inhibiting key virulence factors such as proteases, lipases, and gelatinases, all of which play key roles in the infectious process. Overall, Ber-Ab combinations demonstrated the highest efficacy across all parameters tested, highlighting for the first time the multi-target therapeutic potential of this phytochemical-based aPDI strategy to combat antibiotic-resistant S. aureus infections and improve wound infection treatment outcomes.
- Association between cognitive reserve proxies and frailty phenotype: data from UK BiobankPublication . Lorenzo-López, Laura; Cibeira, Nuria; Hemadeh, Ali; López-López, Rocío; Lema-Arranz, Carlota; Maseda, Ana; Fernández-Bertólez, Natalia; Costa, Solange; Pásaro, Eduardo; Valdiglesias, Vanessa; Millán-Calenti, José C; Laffon, BlancaA potential protective role of cognitive reserve proxies against frailty has been suggested in older adults. We explored the cross-sectional association between cognitive reserve indicators and frailty phenotype. Data were obtained from the UK Biobank. We included 31,975 dementia-free participants aged ≥ 60 years (50.7% females, 2.2% frail) who completed a web-based cognitive assessment (fluid intelligence, working memory, visuospatial attention and processing speed, and executive functioning). Frailty was defined according to the Fried's phenotype (unintentional weight loss, exhaustion, low physical activity, slowness, and weakness). Participants meeting three or more criteria were classified as frail. Cognitive performance was compared between nonfrail and frail groups, and regression models were employed to analyze the associations between cognitive reserve proxies (education, skill level of occupation, social support, and multiple deprivation index (MDI)) and the likelihood of frailty. Frail and nonfrail groups significantly differed on cognitive function, with frail individuals demonstrating poorer performance on all cognitive functions (all p < .05) except fluid intelligence. Regression analysis showed that, after adjusting for age and sex, a lower educational level (odds ratio (OR) .797, 95% confidence interval (CI) .673-.944, p = .009), having maintained occupations with low cognitive requirements (OR .790, 95% CI .668-.936, p = .006), having less social support (OR .755, 95% CI .631-.903, p = .002), and living in a region with a high rate of multiple deprivation (OR 1.025, 95% CI 1.019-1.031, p < .001), significantly increased the probability of experiencing frailty. Our findings support the relationship between declined cognitive functions and frailty emphasizing the importance of implementing public health measures to enhance cognitive reserve.
- Association of inflammatory biomarkers with physical and cognitive frailty in a Spanish population of older adultsPublication . Lema-Arranz, Carlota; Hemadeh, Ali; Fernández-Bertólez, Natalia; Cibeira, Nuria; López-López, Rocío; Costa, Solange; Millán-Calenti, José Carlos; Lorenzo-López, Laura; Valdiglesias, Vanessa; Laffon, BlancaFrailty is a multifactorial geriatric syndrome characterized by increased vulnerability to stressors and associated with a higher risk of adverse health outcomes. Chronic low-grade inflammation has been proposed as a key pathophysiological mechanism underlying physical frailty, although its role in cognitive frailty remains undefined. In this cross-sectional study, we assessed the relationship between frailty status, both physical and cognitive, and plasma concentrations of six inflammatory biomarkers-C-reactive protein (CRP), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α), soluble TNF-α receptor type II (sTNF-RII), high-temperature requirement serine protease A1 (HTRA1), and growth differentiation factor 15 (GDF15)-in a cohort of Spanish older adults (N = 150, ≥ 65 years old), classified according to Fried's frailty phenotype and frailty index. The results showed notable differences between frailty phenotype and frailty index, and highlighted CRP, TNF-α, sTNF-RII, and GDF15 as key biomarkers significantly associated with physical frailty status, with CRP and TNF-α also discriminating pre-frail individuals. sTNF-RII stood out for its high predictive capacity, while GDF15 added value as an indicator of sustained cellular stress. Regarding cognitive frailty, CRP, TNF-α, and GDF15 displayed significant associations with this condition. sTNF-RII and HTRA1, scarcely studied in this context, showed promising and significant associations (specific for cognitive frailty in the case of HTRA1) that justify their inclusion in future research aimed at better understanding the inflammatory mechanisms involved in cognitive frailty.