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Although pulsed field ablation (PFA) is generally considered safe, the mechanisms underlying both symptomatic and silent embolic events remain unclear. This study aimed to investigate the timing, number, size, and characteristics of microembolic signals (MESs) during each step of the pentaspline PFA procedure using real-time carotid Doppler monitoring. MESs were assessed during ablation procedures in 32 patients, including 27 who underwent pulmonary vein (PV) isolation with the pentaspline PFA system and 5 control patients who received radiofrequency ablation limited to the right atrium. The PFA group showed significantly more MESs than the control group. MESs were detected throughout the PFA procedure, with the highest counts observed during PFA delivery to the right PVs. Bubble signals were seen in all procedural steps. In contrast, high-intensity transient signals, which are mainly composed of solid components, were more common during PFA energy delivery. All 303 overcurrent errors-events in which energy delivery is stopped owing to overcurrent detection-occurred during basket-type PFA applications and were associated with a marked increase in MESs. Basket-configuration energy delivery resulted in a significantly higher number of MESs than the flower configuration, particularly in the right PVs. The size of MESs was significantly larger during PFA energy delivery than during catheter or sheath manipulation. This study demonstrated the characteristic timing, frequency, and morphology of MESs during pentaspline PFA procedures, providing insights that may help reduce embolic risks in future practice.

We conducted a multicenter, observational, post-marketing, real-world cohort study in Romania that included all patients with MS (PwMS) who completed at least one cycle of CLD with at least three months of follow-up as of September 2024. Demographic variables and MS clinical characteristics regarding each patient were recorded. No Evidence of Disease Activity (NEDA-3) was assessed at one and two years after CLD initiation. The primary outcome was the proportion and characteristics of PwMS achieving NEDA-3 at 12 and 24 months after CLD initiation and the identification of predictors of failure in achieving NEDA-3. A total of 348 PwMS cases were included, of which CLD was the first DMT option in 129 (37.1%). At one year, 76.74% of the patients with complete available data fulfilled all criteria, achieving NEDA-3 status, with similar proportions between previously DMT-treated PwMS and naïve PwMS. In the univariate analysis, the onset of long-tract involvement, as compared to infratentorial (OR = 6.32, p = 0.01), and the number of Gd-enhancing lesions (OR = 1.12, p = 0.02), were significantly associated with increased odds of not achieving NEDA-3 at one year. In the multivariate model, long tracts (OR = 10.28, p = 0.006), higher baseline EDSS (OR = 1.39, p = 0.01), and longer disease duration (OR = 0.92, p = 0.04) were independent predictors. The initiation of CLD treatment was associated with achieving NEDA-3 at one year in >70% of cases. CLD demonstrated an improvement in MS control, irrespective of the patients' demographics, RMS history, or prior DMT exposure. CLD treatment has a favorable safety profile and a high level of patient adherence.

To probe the formation mechanism of N-despropyl ropinirole, an oxidative degradant in ropinirole hydrochloride extended-release tablets. Forced degradation studies were employed to investigate the mechanism by treating ropinirole API with H2O2 and AIBN, respectively, and the samples analyzed by high resolution LC-QTOF-MS. Meanwhile, the samples from the forced degradation of the extended-release tablets were analyzed by GC-QTOF-MS. The proposed mechanism was supported by an H218O isotope experiment. Lastly, API-excipient compatibility studies were conducted to evaluate the impact of the excipients on the formation of N-despropyl ropinirole. The growth trend of N-despropyl ropinirole in the accelerated stability study was similar to that observed in the forced degradation of ropinirole hydrochloride treated with AIBN, but vastly different from that observed in the forced degradation with H2O2. The forced degradation using isotope labelled H218O showed that 18O was incorporated into propionaldehyde, the volatile co-degradant in the formation of N-despropyl ropinirole. The API-excipient compatibility studies indicated that N-despropyl ropinirole was formed gradually in the presence of CMC-Na and HPMC, respectively. Degradation of ropinirole in the ropinirole hydrochloride extended-release tablets is most likely to proceed via a free radical-mediated oxidative pathway, rather than a nucleophilic oxidative pathway. The forced degradation experiment using H218O is consistent with the proposed free radical-mediated degradation mechanism. The source of the free radicals seems to originate from the two excipients, CMC-Na and HPMC. The results obtained in the current study would be quite beneficial for further improvement of the drug product in terms of controlling its major degradation pathway.

The increased prevalence of multidrug-resistant (MDR) pathogens and biofilm-associated infections underscores the urgent need for alternative antimicrobial strategies. In this study, MDR testing revealed lower resistance in Gram-positive bacteria (Staphylococcus pasteuri, Listeria monocytogenes, and Bacillus cereus; 69–77%) than in Gram-negative strains (Proteus mirabilis, Pseudomonas aeruginosa, and Escherichia coli; 83–92%). Magnetite nanoparticles (Fe3O4NPs) and selenium nanoparticles (SeNPs) were synthesized via a green chemical reduction using L-ascorbic acid, followed by their conjugation with Salvia officinalis (SaO) aqueous extract to enhance stability and biological activities. TEM, DLS, XRD, and FT-IR analyses confirmed the nanoscale crystalline structure of the synthesized metal nanoparticles (MNPs) and the successful integration of SaO phytoconstituents into the nanocomposites. Phytochemical characterization further revealed variable adhesion and retention of SaO bioactive compounds within the two nanocomposites. The MIC values of SaO-Fe3O4NPs (0.03–1) and SaO-SeNPs (0.03–0.5 µg/mL) were not only dramatically lower than the SaO extract (125–500 µg/mL) and MNPs (0.5–25 µg/mL), but also comparable to or even exceeded meropenem (0.25–2 µg/mL). Vigorous antibacterial activity validated by TEM, revealing extracellular and intracellular deformations, in accordance with the growth curve inhibition patterns. The nanocomposites also demonstrated potent antibiofilm activity, achieving 32.5–59.5% inhibition with SaO-Fe₃O₄NPs and 30.2–56.7% with SaO-SeNPs, surpassing meropenem, which exhibited maximum inhibition values of 32.5–47.6%.

Only very few educational mobile health applications (MHAs) on oral cancer exists. Based on existing literature, only one of such MHAs (application name: Prayaas) was created specifically for lay persons; unfortunately, the application has been critiqued to be non-inclusive and non-comprehensive. Hence, this study aimed to co-create a more comprehensive and inclusive educational MHA prototype on oral cancer through a participatory action research approach. A three-round modified Delphi technique was employed to engage stakeholders in a participatory action research process. Digital communication experts and individuals with oral cancer risk factors (n = 17) from five countries participated. Round one utilised focus group discussions to define essential application features. Rounds two and three involved iterative evaluations of successive prototypes using a validated questionnaire (Mobile Application Rating Scale). Quantitative data were analysed using descriptive statistics, with consensus defined a priori as a mean score > 2.5 on a 5-point Likert scale—indicating majority agreement on each evaluated item. Stakeholder input across three iterative rounds led to the co-creation of the “Beat Oral Cancer” prototype. Quantitative consensus was achieved across all evaluated domains, including usability, aesthetics, information quality, and perceived impact. The final prototype showed significant improvements: the second version was rated higher than the first in entertainment (+ 0.68), interactivity (+ 0.32), customizability (+ 0.64), and ease of use (+ 0.33). Key inclusive features, such as adjustable text size, were incorporated based on stakeholder feedback. This study successfully co-created a highly comprehensive, stakeholder-informed MHA prototype for oral cancer education via a modified Delphi process. The results demonstrate the value of iterative participatory design in creating digital health tools with high potential for acceptability and usability. This work establishes a methodological precedent for applying the Delphi technique in mobile health co-creation and provides a foundation for future efficacy testing and public deployment.

BACKGROUND: Prescribing and maintaining adherence to high-intensity exercise is challenging in people with Parkinson’s disease (PwPD). Adding cognitive engagement may enhance exercise benefits. Critical heart rate (CHR) offers a promising method to prescribe aerobic intensity and provide feedback during training. However, it is unclear whether this approach achieves higher training loads than self-selected intensity while preserving adherence. AIM: To investigate the feasibility of a walking-based intervention with intensity feedback prescribed using CHR (WB+F) in PwPD. Secondarily, the effects on motor and non-motor outcomes were explored. METHODS:Twenty-four PwPD were invited to participate in a randomized crossover-controlled trial consisting of two 8-week training cycles (WB+F: walking at CHR with intensity feedback; SSS: self-selected speed), separated by a 3-week washout period. Feasibility outcomes included retention, adherence, and compliance. Motor and non-motor outcomes were assessed before and after each training cycle. RESULTS: Retention comprised 10 participants (42% of those enrolled), with adherence rates above 75% in both training conditions (p=0.572). Compliance analyses showed higher values for WB+F compared with SSS for distance covered (p=0.004), rating of perceived exertion (p=0.006), and training load (p=0.002). Cognitive performance improved (p=0.032), and time to complete the 400-m walk test decreased (p=0.043) following WB+F. INTERPRETATION: Despite the promising cognitive and motor outcomes, this feasibility study demonstrated low retention rates, which limit the clinical relevance of the findings. Nevertheless, the compliance results suggest that CHR-based prescription is feasible in PwPD. Future studies should adopt parallel-group designs to ensure larger sample sizes and adequately test the efficacy of the WB+F approach.

A Doença de Alzheimer impõe desafios significativos não apenas aos pacientes, mas também aos seus cuidadores familiares, que frequentemente assumem essa função de forma não planejada e sem preparo prévio. Este estudo teve como objetivo investigar, com base na literatura científica recente, como práticas de humanização e suporte psicossocial podem contribuir para reduzir a sobrecarga emocional e promover saúde integral aos cuidadores de pessoas com Alzheimer. Trata-se de uma revisão integrativa da literatura, com publicações entre 2020 e 2025, nas bases SciELO, LILACS, PubMed, BVS e Google Scholar. Os resultados demonstraram que a sobrecarga física, emocional e social é uma realidade constante entre os cuidadores, agravada pela ausência de apoio institucional. No entanto, intervenções voltadas ao suporte emocional, capacitação, autocuidado e fortalecimento de redes de apoio mostram-se eficazes na melhoria da qualidade de vida desses indivíduos. Conclui-se que humanizar o cuidado é essencial para transformar a vivência do cuidador, exigindo ações conjuntas entre família, profissionais de saúde e políticas públicas.