Portuguese League Against Epilepsy

BackgroundIn 2022, nearly 20 million new cancer cases and 9.7 million deaths occurred globally. Europe, comprising under 10% of the world’s population, accounted for over 22% of cases and 20% of deaths, reflecting an aging population, lifestyle risk factors, and extensive screening. With 40% of cancers preventable through modifiable risk factor interventions, effective prevention is essential. The European Code Against Cancer provides evidence-based guidelines that drive health initiatives across Europe. Supported by Europe’s Beating Cancer Plan and the EU4Health program, the EU Mobile App for Cancer Prevention was developed to disseminate these recommendations. However, its effectiveness depends on usability across populations with varying digital and health literacy; this study evaluates the app’s usability among diverse European populations.ObjectiveThis study aimed to identify enablers, barriers, and user requirements for the use and maintenance of the English version of the EU Mobile App for Cancer Prevention, focusing on how usability varied across individuals with different levels of digital health literacy and diverse sociodemographic backgrounds. In addition, user feedback on mock wireframes—visual representations of the app’s interface and functionality—was gathered to evaluate usability and ease of use, providing insights for tailoring the app design to a broader population.MethodsWe conducted a mixed methods study in 7 European countries with 76 adults aged 19‐84 years recruited via purposive quota sampling. Participants completed quantitative usability testing using mock wireframes to perform 10 predefined tasks simulating core app functionalities (eg, profile setup and health goal tracking). We recorded task completion time, success rates, self-reported confidence, and perceived difficulty. Digital health literacy was assessed using the eHealth Literacy Scale (eHEALS) scale. Qualitative data were collected through focus group discussions guided by a semistructured interview guide, and transcripts were analyzed via thematic content analysis. Statistical analyses included descriptive statistics and 1-way ANOVA to explore group differences.ResultsOverall task completion rates ranged from 75% to 98%, with a median of 86%, indicating general usability. However, usability varied by age, education, and digital health literacy: younger participants and those with higher education and literacy levels reported greater confidence and lower difficulty, whereas older adults and lower-literacy users experienced more challenges. Qualitative analysis identified key themes affecting usability: the need for accessibility (multilingual support and simple language), user-centric design (age-friendly interfaces and intuitive navigation), ethical concerns (data privacy and security), and motivational features (gamification and personalized health goals).ConclusionThe app is generally usable across diverse populations but requires streamlined interfaces and design adaptations to accommodate varying digital health literacy. Ensuring robust data privacy practices is essential for fostering user trust, and integrating motivational elements may enhance sustained engagement. Future work will involve piloting the finalized app to evaluate its real-world uptake and impact on cancer prevention behaviors.

Background: Somatic symptoms of stress are a major concern among the general population, given their severity and overall burden. Objectives: This pilot randomized controlled study (RCT) aimed to assess the effectiveness of frequency-specific microcurrent (FSM) therapy alone (experimental group 1 [EG1]) and combined with a relaxation intervention (experimental group 2 [EG2]), compared to a relaxation intervention alone (active control group [ACG]) and combined with placebo (passive control group [PCG]), to determine the need for a future definitive RCT. Methods: Participants with clinically significant levels of stress were recruited and assessed at three moments (i.e., baseline assessment [T0], at the end of six sessions [T1], and at the end of 12 sessions [T2]) on somatic symptoms and satisfaction with life (primary outcomes), perceived stress, emotional distress, emotional states, and emotion regulation (secondary outcomes). A total of 85 participants completed T0, of whom 58 were randomized into four groups. Results: Using linear mixed models, differences between groups revealed that the participants receiving FSM therapy reported fewer somatic symptoms and negative emotions than those who received relaxation, at T1. Within-group analysis showed that somatic symptoms and satisfaction with life significantly improved after six or twelve sessions of FSM therapy as well as after relaxation. There were also significant improvements in perceived stress, emotional distress, emotion regulation, and emotional states (negative emotions, self-efficacy, and serenity), after six and/or 12 sessions of FSM therapy or relaxation. Conclusions: The results suggest that FSM may be a promising treatment for addressing somatic complaints and negative emotional states, supporting the implementation of a definitive RCT.

Epigenetics is the study of changes in organisms that result from modifications in gene expression rather than alterations in the genetic code itself [...].

Castration Resistant Prostate Cancer (CRPC) is characterized by poor prognosis and limited therapeutic options. AgNPs functionalized with glucose (G-AgNPs) were observed cytotoxic to CRPC cell lines (PC-3 and Du-145) and not LNCaP. This study aims to evaluate AgNPs and G-AgNPs' uptake mechanisms in these cells and understand their role in the selective effect against CRPC cells. Uptake of AgNPs and G-AgNPs was assessed through transmission electron microscopy (TEM). A microRNA (miRNAs) analysis approach was used to uncover the main molecular differences responsible for the endocytic mechanisms' regulation. Caveolin (Cav) 1 and 2 mRNA and protein levels were assessed in the three cell lines. Caveolae-dependent endocytosis was inhibited with genistein or siCav1- and siCav2- in PC-3 and Du-145 and resazurin assay was used to evaluate viability after AgNPs and G-AgNPs administration. Caveolae-dependent endocytosis was induced with Cav1+ and Cav2+ plasmids in LNCaP, resazurin assay was used to evaluate viability after AgNPs and G-AgNPs administration and TEM to assess their location. AgNPs and G-AgNPs were not uptaked by LNCaP. miRNA analysis revealed 37 upregulated and 90 downregulated miRNAs. Functional enrichment analysis of miRNAs' targets resulted in enrichment of terms related to endocytosis and caveolae. We observed that Cav1 and Cav2 are not expressed in LNCaP. Inhibiting caveolae-dependent endocytosis in Du-145 and PC-3 led to a significative reduction of cytotoxic capacity of AgNPs and G-AgNPs and induction of caveolae-dependent endocytosis in LNCaP lead to a significative increase as well as their uptake by cells. This study shows the potential of these AgNPs as a new therapeutic approach directed to CRPC patients, uncovers caveolae-dependent endocytosis as the uptake mechanism of these AgNPs and highlights deregulation of Cav1 and Cav2 expression as a key difference in hormone sensitive and resistant PCa cells which may be responsible for drug resistance.

Background:The criteria for defining outcomes and severity in systemic sclerosis-associated interstitial lung disease (SSc-ILD) are highly heterogeneous. Moreover, little is known about patients’ and physicians’ perspective on the most important aspects to consider when dealing with SSc-ILD.Objectives:his survey aimed to identify which outcomes and severity measures related to SSc-ILD are considered important for patients and physicians, to be further included when defining the long-term treatment goals of SSc-ILD.Methods:An international survey was designed based on a systematic literature review of outcomes and severity measures in SSc-ILD, with combined inputs from both physicians and patients. For physicians, the survey was conducted in English. For patients, the survey was adapted to lay terms and translated into different languages by native speakers (Italian, Portuguese, Spanish, Arabic, Chinese, French, Romanian, Ukrainian, German and Hindi), then spread through SSc patient associations. Survey participants were asked to rate on a scale of 1-10 the importance of each item when considering the outcomes of the treatment and when defining severe SSc-ILD, with higher values representing increasing importance. Items scored in average ≥8 and voted ≥8 by ≥80% of participants were arbitrarily considered as “important”.Results:738 participants completed the surveys, including 388 physicians with experience with SSc-ILD and 350 patients with SSc-ILD. Most physicians were based in Europe (70%), were specialists in rheumatology (76%), working at university hospitals (83%) and having been in practice for more than 5 years (82%). Patients with SSc-ILD were mostly from Europe (46%) and North America (39%), most of them being females (92%), aged over 50 years (63%) and living with SSc for longer than 3 years (75%).Both physicians and patients deemed death, a decline of pulmonary functional tests (PFTs), an increase of ILD extent on high-resolution computed tomography (HRCT) and onset/worsening of dyspnoea as important outcomes to be prevented with treatment (Figure 1A-B). Additionally, hospitalization (both with and without increased outpatient clinic burden), referral to lung transplantation, need to start/increase oxygen supplementation and onset/worsening of pulmonary hypertension secondary to ILD (PH-ILD) were important outcomes for physicians. Conversely, patients also considered lung infections, worsening of physical activity and worsening of psychological well-being important outcomes.Similar trends were noted when asking about items to define severe disease (Figure 1 C-D): while referral to lung transplantation, need for oxygen supplementation, ILD extent on HRCT and dyspnoea were important to both physicians and patients, PFTs and PH-ILD were rated important only by physicians, while lung infections, physical activity and daily activities were highly chosen only by patients.Outcomes and items such as cough, impact of ILD on sexual, social, and working life were not deemed important by any group.Conclusion:The perspectives of patients and physicians partially overlap, when considering the targets of treatment of SSc-ILD and the items contributing to the perceived disease severity. Based on these insights, both stakeholders’ opinion should be included in defining the long-term targets of SSc-ILD treatment, to create an appropriate definition of «progression» to be used as a surrogate outcome in clinical trials and practice.REFERENCES: NIL.Figure 1.Items of importance for physicians, patients or both when assessing severity and outcome in SSc-ILD.Acknowledgements:NIL.Disclosure of Interests:Cosimo Bruni Boehringer Ingelheim, Foundation for Research in Rheumatology (FOREUM), Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC), Scleroderma Research Foundation (SRF), Novartis Foundation for Bio-medical Research, EMDO Foundation. Educational grants from AbbVie and Wellcome Trust., Liubov Petelytska research grant from Swiss National Research Foundation/Scholars at risk, Muriel Elhai congress support from Janssen and AstraZeneca, Ilaria Galetti: None declared, Vera Guimarães: None declared, Qingran Yan: None declared, Sinziana Muraru congress support from AstraZeneca (virtual EULAR congress 2021), Gesa Sauer: None declared, Nada Msabri Gharbi: None declared, Parikshit Sen: None declared, Khadija El Aoufy: None declared, Suzana Jordan: None declared, Oliver Distler 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur and UCB, Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143). Co-founder of CITUS AG., 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur and UCB, Boehringer Ingelheim, Kymera, Mitsubishi Tanabe.

Essential oils are natural compounds used by humans for scientific purposes due to their wide range of properties. Eugenol is mostly present in clove oil, while pulegone is the main constituent of pennyroyal oil. To guarantee the safe use of eugenol and pulegone for both humans and animals, this study addressed, for the first time, the effects of these compounds, at low doses (chronic toxicity) and high doses (acute toxicity), in laboratory animals. Thirty-five FVB/n female mice were randomly assigned to seven groups (n = 5): group I (control, non-additive diet); group II (2.6 mg of eugenol + 2.6 mg of pulegone); group III (5.2 mg of eugenol + 5.2 mg of pulegone); group IV (7.8 mg of eugenol + 7.8 mg of pulegone); group V (7.8 mg of eugenol); group VI (7.8 mg of pulegone); and group VII (1000 mg of eugenol + 1000 mg of pulegone). The compounds were administered in the food. Groups I to VI were integrated into the chronic toxicity study, lasting 28 days, and group VII was used in the acute toxicity study, lasting 7 days. Animals were monitored to assess their general welfare. Water and food intake, as well as body weight, were recorded. On the 29th day, all animals were euthanized by an overdose of ketamine and xylazine, and a complete necropsy was performed. Blood samples were collected directly from the heart for microhematocrit and serum analysis, as well as for comet assay. Organs were collected, weighed, and fixed in formaldehyde for further histological analysis and enzymatic assay. Eugenol and pulegone induced behavioral changes in the animals, namely in the posture, hair appearance and grooming, and in mental status. These compounds also caused a decrease in the animals’ body weight, as well as in the food and water consumption. A mortality rate of 20% was registered in the acute toxicity group. Both compounds modulated the serum levels of triglycerides and alanine aminotransferase. Eugenol and pulegone induced genetic damage in all animals. Eugenol increased the activity of the CAT enzyme. Both compounds increased the GR enzyme at the highest dose. Moreover, pulegone administered as a single compound increased the activity of the GST enzyme. Histopathological analysis revealed inflammatory infiltrates in the lungs of groups II, III, and IV. The results suggest that eugenol and pulegone may exert beneficial or harmful effects, depending on the dose, and if applied alone or in combination.