Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the delivery of bioactives sourced from plants: part II - applications and preclinical advancements.

INTRODUCTION: Numerous purified bioactive compounds, crude extracts, and essential oils have demonstrated potent antioxidant, antimicrobial, anti-inflammatory, and antiviral properties, particularly in vitro or in silico; however, their in vivo applications are hindered by inadequate absorption and distribution in the organism. The incorporation of these phytochemicals into solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) has demonstrated significant advancements and represents a viable approach to improve their bioavailability through different administration routes. AREAS COVERED: This review discusses the potential applications of SLN and NLC, loading bioactive compounds sourced from plants for the treatment of several diseases. An overview of the preclinical developments on the use of these lipid nanoparticles is also provided as well as the requisites to be launched on the market. EXPERT OPINION: Medicinal plants have gained even more value for the pharmaceutical industries and their customers, leading to many studies exploring their therapeutic potential. Several bioactives derived from plants with antiviral, anticancer, neuroprotective, antioxidant, and antiaging properties have been proposed and loaded into lipid nanoparticles. In vitro and invivo studies corroborate the added value of SLN/NLC to improve the bioavailability of several bioactives. Surface modification to increase their stability and target delivery should be considering.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the delivery of bioactives sourced from plants: part I - composition and production methods.

INTRODUCTION: Nanoparticles (NPs) are widely used in the pharmaceutical field to treat various human disorders. Among these, lipid-based NPs (LNPs), including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), are favored for drug/bioactive delivery due to their high stability, biocompatibility, encapsulation efficiency, and sustained/controlled release. These properties make them particularly suitable as carriers of compounds derived from plant sources. AREAS COVERED: This study comprehensively explores updated literature knowledge on SLN and NLC, focusing on their composition and production methods for the specific delivery of drug/bioactive compounds derived from plant sources of interest in pharmaceutical and biomedical fields. EXPERT OPINION: SLN and NLC facilitate the development of more effective natural product-based therapies, aiming to reduce dosage and minimize side effects. These delivery systems align with the consumer demands for safer and more sustainable products, as there are also based on biocompatible and biodegradable raw materials, thereby posing minimal toxicological risks while also meeting regulatory guidelines.

Using behavior and eye-fixations to detect feigned memory impairment.

Background: Detecting invalid cognitive performance is an important clinical challenge in neuropsychological assessment. The aim of this study was to explore behavior and eye-fixations responses during the performance of a computerized version of the Test of Memory Malingering (TOMM-C) under standard vs. feigning conditions. Participants and methods: TOMM-C with eye-tracking recording was performed by 60 healthy individuals (31 with standard instruction - SI; and 29 were instructed to feign memory impairment: 21 Naïve Simulators - NS and 8 Coached Simulators - CS) and 14 patients with Multiple Sclerosis (MS) and memory complaints performed. Number of correct responses, response time, number of fixations, and fixation time in old vs. new stimuli were recorded. Nonparametric tests were applied for group comparison. Results: NS produced fewer correct responses and had longer response times in comparison to SI on all three trials. SI showed more fixations and longer fixation time on previously presented stimuli (i.e., familiarity preference) specially on Trial 1, whereas NS had more fixations and longer fixation time on new stimuli (i.e., novelty preference) specially in the Retention trial. MS patients produced longer response time and had a different fixation pattern than SI subjects. No behavioral or oculomotor difference was observed between NS and CS. Conclusion: Healthy simulators have a distinct behavioral and eye-fixation response pattern, reflecting a novelty preference. Oculomotor measures may be useful to detect exaggeration or fabrication of cognitive dysfunction. Though, its application in clinical populations may be limited.

Assessment of oxidative stress biomarkers in Palaemon varians exposed to deep eutectic systems.

In recent years, there has been extensive research within the scientific community on deep eutectic systems due to their remarkable versatility in solubilizing diverse substances and serving as effective solvents in catalytic processes. While initially regarded as non-toxic, a comprehensive toxicological assessment is essential to comprehend their behavior within organisms. In this study, seven distinct systems, composed of N,N,N-triethyl-N-(2,3-dihydroxypropyl)ammonium chloride (N00Cl) and glycerol-derived ethers with alkyl chains of varying lengths (100, 200, 3F00, 300, 3i00, and 400), in a 1:2 molar ratio were investigated for their aquatic toxicity in shrimp (Palaemon varians). The assessment involved analyzing oxidative stress biomarkers such as glutathione S-transferase, glutathione peroxidase, catalase, superoxide dismutase, total antioxidant capacity (TAC), and lipoperoxidation (MDA content). Results show an odd-even effect for LC50 values being N00Cl-300, the system showing higher values. Regarding oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidant capacity in the organisms has been observed, suggesting significant toxicity to shrimps due to the changes in oxidative stress biomarkers at high concentrations. However, at 100 mg/l all systems can be considered environmentally safe, and no negative impacts are expected on aquatic ecosystems.

Self-sustaining long-term 3D epithelioid cultures reveal drivers of clonal expansion in esophageal epithelium.

Aging epithelia are colonized by somatic mutations, which are subjected to selection influenced by intrinsic and extrinsic factors. The lack of suitable culture systems has slowed the study of this and other long-term biological processes. Here, we describe epithelioids, a facile, cost-effective method of culturing multiple mouse and human epithelia. Esophageal epithelioids self-maintain without passaging for at least 1 year, maintaining a three-dimensional structure with proliferative basal cells that differentiate into suprabasal cells, which eventually shed and retain genomic stability. Live imaging over 5 months showed that epithelioids replicate in vivo cell dynamics. Epithelioids support genetic manipulation and enable the study of mutant cell competition and selection in three-dimensional epithelia, and show how anti-cancer treatments modulate competition between transformed and wild-type cells. Finally, a targeted CRISPR-Cas9 screen shows that epithelioids recapitulate mutant gene selection in aging human esophagus and identifies additional drivers of clonal expansion, resolving the genetic networks underpinning competitive fitness.

Admission and discharge sodium: Chloride ratio in acute heart failure - The importance of electrolytes.

BACKGROUND: Chloride has prognostic implications in heart failure (HF). The sodium:chloride (Na:Cl) ratio gathers information of both ions. OBJECTIVES: To study the prognostic impact of Na:Cl ratio in acute HF. METHODS: We retrospectively analysed patients included in an acute HF cohort in 2009-2010. PRIMARY ENDPOINT: all-cause mortality. FOLLOW-UP: 1-year from admission to study the impact of admission Na:Cl ratio; 1-year post-discharge to study the discharge ratio impact. ROC curves of the association of Na, Cl, and the Na:Cl ratio with 1-year mortality were determined and the AUC compared. The association of Na:Cl ratio with mortality was assessed in multivariate analyses. RESULTS: We studied 616 patients. Median admission Na:Cl ratio = 1.34 (1.31-1.38). During 1-year since admission, 229 patients died, AUC for death-association of admission Na, Cl and Na:Cl ratio = 0.42 (0.38-0.47), 0.39 (0.35-0.44) and 0.58 (0.53-0.63), respectively, with significant difference between Na:Cl ratio curve and the others. When admission Na:Cl ratio ≥ 1.34, the multivariate-adjusted death-risk was 1.41 (1.04-1.89); 1.32 (1.04-1.68), per each 0.1 increase in ratio. In-hospital death rate was 4.1 %, median discharge Na:Cl ratio = 1.40 (1.37-1.45). During 1-year post-discharge, 205 patients (34.9 %) died; AUC for Na, Cl and Na:Cl ratio: 0.45 (0.40-0.50), 0.41 (0.36-0.46) and 0.57 (0.52-0.62), with differences between Na:Cl ratio curve and the others. When discharge Na:Cl ratio ≥ 1.43 (percentile 66.7), the adjusted-HR of death was 1.43 (1.04-1.97), p = 0.03, 1.54 (1.23-1.92) per 0.1 increase. CONCLUSIONS: Elevated Na:Cl ratio is independently associated with all-cause death. Per each 0.1 increase in Na:Cl ratio at admission and discharged, there was a 32 % and 54 % higher risk, respectively.

Polymyositis and Severe Rhabdomyolysis in the Context of Influenza and COVID-19 Vaccination: A Case Report.

Rhabdomyolysis is characterized by muscle breakdown and the release of muscle enzymes into the bloodstream, which can lead to acute kidney injury (AKI) and electrolyte imbalances. This case report details a 52-year-old male who developed severe rhabdomyolysis and polymyositis following influenza and SARS-COV-2 vaccinations. Presenting with severe muscle pain and elevated creatine kinase (CK) levels, the patient's condition was managed with aggressive hydration and supportive care, resulting in significant recovery. While vaccine-related adverse effects such as myositis and rhabdomyolysis are rare, this case underscores the need for vigilance in monitoring post-vaccination complications and highlights the importance of recognizing and promptly treating vaccine-associated inflammatory myopathies to prevent severe complications. The findings contribute to the growing body of literature on vaccine-induced myopathies and emphasize the necessity of a multidisciplinary approach in managing such complex cases.

Nanostructured ZnO thin film to enhance gutta-percha's adhesion to endodontic sealers.

BACKGROUND: Gutta-percha (GP) combined with an endodontic sealer is still the core material most widely used for tridimensional obturation. The sealer acts as a bonding agent between the GP and the root dentinal walls. However, one of the main drawbacks of GP core material is the lack of adhesiveness to the sealer. ZnO thin films have many remarkable features due to their considerable bond strength, good optical quality, and excellent piezoelectric, antibacterial, and antifungal properties, offering many potential applications in various fields. This study aimed to explore the influence of GP surface's functionalization with a nanostructured ZnO thin film on its adhesiveness to endodontic sealers. METHODS: Conventional GP samples were divided randomly into three groups: (a) Untreated GP (control); (b) GP treated with argon plasma (PT); (c) Functionalized GP (PT followed by ZnO thin film deposition). GP's surface functionalization encompassed a multi-step process. First, a low-pressure argon PT was applied to modify the GP surface, followed by a ZnO thin film deposition via magnetron sputtering. The surface morphology was assessed using SEM and water contact angle analysis. Further comprehensive testing included tensile bond strength assessment evaluating Endoresin and AH Plus Bioceramic sealers' adhesion to GP. ANOVA procedures were used for data statistical analysis. RESULTS: The ZnO thin film reproduced the underlying surface topography produced by PT. ZnO thin film deposition decreased the water contact angle compared to the control (p < 0.001). Endoresin showed a statistically higher mean bond strength value than AH Plus Bioceramic (p < 0.001). There was a statistically significant difference between the control and the ZnO-functionalized GP (p = 0.006), with the latter presenting the highest mean bond strength value. CONCLUSIONS: The deposition of a nanostructured ZnO thin film on GP surface induced a shift towards hydrophilicity and an increased GP's adhesion to Endoresin and AH Bioceramic sealers.

Repeated human leukocyte antigens eplets, importance of typing the partner.

INTRODUCTION: Antibody-mediated rejection (AMR) is the most common cause of immune-mediated allograft failure after kidney transplant and impacts allograft survival. Previous sensitization is a major risk factor for development of donor specific antibodies (DSA). AMR can have a wide range of clinical features such as impaired kidney function, proteinuria/hypertension or can be subclinical. HLA molecules have specific regions of antigens binding antibodies called epitopes and eplets are considered essential components responsible for immune recognition. We present a patient with subclinical AMR 1 week post transplantation. CASE REPORT: A 48-year-old, caucasian woman with end-stage kidney disease (ESKD) secondary to autosomal dominant polycystic kidney disease (ADPKD) on peritoneal dialysis was registered in deceased donor waitlist. She was a hypersensitized patient from 3 prior pregnancies with a calculated panel reactive antibody of 93,48%. She was transplanted through kidney paired exchange donation with no evidence of DSA pre transplantation. Surgery and post-op were unremarkable with excellent and immediate graft function. Per protocol DSA levels on the 5th day was DR1 of 3300 MFI, with an increase in MFI by day 13 with 7820 MFI and a new B41 1979MFI. Allograft kidney biopsy findings were diagnostic of AMR and she was treated with immunoglobulin and plasmapheresis. As early onset AMR post transplantation was observed an anamnestic response was hypothesized from a previous exposure to allo-HLA. We decided to type her husband, her son's father, which was presented with DSA. Mismatch eplet analysis revealed a shared 41 T and 67LQ eplets between the donor and husband, responsible for the reactivity and new HLA class I B41 and HLA class II DR1 DSA, respectively. DISCUSSION: Shared eplets between the patient husband and donor was responsible for the alloimmune response and early development of DSAs. This case highlights the importance of early monitoring DSA levels in highly sensitized patients after transplant in order to promptly address and lower inflammatory damage. Mismatch eplet analysis can provide a thorough and precise evaluation of immune compatibility providing a useful technique to immune risk stratification, donor selection and post-transplant immunosuppressive therapy and monitoring.

Comparison of Cytological Adequacy between 23- and 25-Gauge in Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules: A Single-Center Prospective Study.

INTRODUCTION: Approximately 15% of fine-needle aspiration (FNA) of thyroid nodules are considered nondiagnostic. Several factors are potentially involved, including clinical and nodule features but also the gauge (G) of the needle used. However, few studies have compared the cytological adequacy obtained with different gauge needles and the data are controversial. We aimed to evaluate cytological adequacy results using 23- or 25-G needles. METHODS: This study is an observational and prospective study of thyroid nodules submitted to ultrasound-guided FNA. The procedure was performed randomly using 23- or 25-G needles. The samples were reported by different cytopathologists who were blinded to the information of the gauge of the needle used. Statistical analysis was performed to compare cytological adequacy of FNA between the two groups. RESULTS: A total of 177 thyroid nodules were included - 98 (55.4%) using 23-G and 79 (44.6%) using 25-G needles. The 23-G group presented a higher rate of cytological adequacy (69.4% [68/98] vs. 46.8% [37/79], p = 0.002). No differences were found between the two groups regarding patient or nodule characteristics. On logistic regression, 23-G needles correlated with better cytological adequacy (unadjusted OR 2.57 [95% CI: 1.39-4.77]), even after adjusting for nodule dimension, location, and type of cytology (slides +/- additional liquid-based cytology) (adjusted OR 2.44 [95% CI: 1.23-4.84]). CONCLUSION: The gauge of the needle used was found to be an independent predictor of cytological adequacy, with 23-G needles providing more adequate samples. Further investigation is needed to confirm our results in order to stablish the optimal diagnosis technique.

Aldehyde Dehydrogenase 2 (ALDH2): A novel sorafenib target in hepatocellular carcinoma unraveled by the proteome-wide cellular thermal shift assay.

Sorafenib is a multikinase inhibitor indicated for first-line treatment of unresectable hepatocellular carcinoma. Despite its widespread use in the clinic, the existing knowledge of sorafenib mode-of-action remains incomplete. To build upon the current understanding, we used the Cellular Thermal Shift Assay (CETSA) coupled to Mass Spectrometry (CETSA-MS) to monitor compound binding to its target proteins in the cellular context on a proteome-wide scale. Among the potential sorafenib targets, we identified aldehyde dehydrogenase 2 (ALDH2), an enzyme that plays a major role in alcohol metabolism. We validated the interaction of sorafenib with ALDH2 by orthogonal methods using pure recombinant protein, proving that this interaction is not mediated by other cellular components. Moreover, we showed that sorafenib inhibits ALDH2 activity, supporting a functional role for this interaction. Finally, we were able to demonstrate that both ALDH2 protein expression and activity were reduced in sorafenib-resistant cells compared to the parental cell line. Overall, our study allowed the identification of ALDH2 as a novel sorafenib target and sheds light on its potential role in both hepatocellular carcinoma and sorafenib resistance condition.

Proteomic Profiling of Plasma- and Gut-Derived Extracellular Vesicles in Obesity.

Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions, and although they have been associated with obesity comorbidities, their protein cargo in this context remains largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein-folding functions, highlighting the importance of proper folding in maintaining metabolic homeostasis. Previously, we revealed that gut-derived EVs' proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood-derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein PTMs in the intricate mechanisms underlying obesity, shedding light on potential biomarkers and pathways for future research.

[Eating Habits of People with Type 2 Diabetes Mellitus in Portugal: A Cross-Sectional Study]. / Hábitos Alimentares das Pessoas com Diabetes Mellitus Tipo 2 em Portugal: Um Estudo Transversal.

INTRODUCTION: Nutrition is a cornerstone of diabetes mellitus prevention and management; therefore, it is essential to enable patients to adopt healthy eating habits. Previous studies have not yet documented the main errors in the eating habits of Portuguese people with type 2 diabetes mellitus. This study aims to identify the main errors in the eating habits of people living with type 2 diabetes mellitus in Portugal and to evaluate its associations with sociodemographic variables. METHODS: Cross-sectional multicentric study in a convenience sample of people with type 2 diabetes mellitus in Primary Health Care Units. The UK Diabetes and Diet Questionnaire (UKDDQ) - translated and adapted, was applied from July to October 2022. Descriptive and inferential statistical analyses were conducted. RESULTS: Of the 550 participants, 52.2% were female, 68.3% were 65 years or over, 55.8 % had an education level up to the fourth grade, 24.7% had economic deprivation, and the mean time since diagnosis was 10.60 ± 8.13 years. Only 36.2% of the sample had a healthy UKDDQ score. Less than 50% of the sample had healthy scores for the items "high-fiber rice or pasta", "high-fiber bread", "butter, margarine and vegetable oils" and "vegetables and pulses". Only 8.9% of the sample had a healthy consumption of fiber. About 70.4% reported healthy scores for the consumption of "high-added-sugar foods" and 54.7% for "high-saturated fat". A statistically significant weak positive correlation was found between the UKDDQ score and age (ρ = 0.201, p < 0.001) with a more frequent choice of healthy foods with increasing age. Female respondents reported healthier habits, particularly in the consumption of "high-saturated fat" and "high-fiber foods". CONCLUSION: The majority of our sample did not take advantage of the potential benefits of healthy eating habits. The main food groups whose consumption should be emphasized or discouraged were individualized, particularly the need to encourage the consumption of high-fiber foods. Targeted educational actions must focus especially on younger and/or male patients.

Introdução: A nutrição é uma área de intervenção na prevenção e gestão da diabetes mellitus; por isso, é fulcral promover a capacitação da população para a adoção de hábitos alimentares saudáveis. Ainda que existam alguns estudos nesta área, não se conhecem os principais erros nos hábitos alimentares das pessoas com diabetes em Portugal. Os objetivos deste estudo foram identificar os principais erros nos hábitos alimentares das pessoas com diabetes mellitus tipo 2 em Portugal e avaliar a sua relação com variáveis sociodemográficas. Métodos: Estudo transversal multicêntrico, em amostra de conveniência de pessoas com diabetes mellitus tipo 2 seguidas em Unidades de Cuidados de Saúde Primários. Aplicação do UK Diabetes and Diet Questionnaire (UKDDQ) ­ traduzido e adaptado, de julho a outubro de 2022. Análise estatística descritiva e inferencial. Resultados: Amostra de 550 participantes, 52,2% do sexo feminino, 68,3% com 65 anos ou mais, 55,8% com nível de escolaridade igual ou inferior ao 1.º ciclo do ensino básico, 24,7% com insuficiência económica e tempo desde o diagnóstico médio de 10,60 ± 8,13 anos. Apenas 36,2% da amostra obteve um score UKDDQ considerado saudável. Menos de 50% obteve scores saudáveis para os itens "arroz ou massa ricos em fibras", "pão integral", "manteiga, margarina e óleos vegetais" e "vegetais e leguminosas". Somente 8,9% da amostra obteve score saudável para o consumo de fibras. Cerca de 70,4% obteve score saudável para o consumo de açúcares livres e 54,7% para o consumo de ácidos gordos saturados. Verificou-se a existência de uma correlação com significado estatístico positiva fraca entre o score UKDDQ e a idade (ρ = 0,201, p < 0,001), com escolha mais frequente de alimentos saudáveis com o aumentar da idade. As pessoas do sexo feminino reportaram hábitos alimentares mais saudáveis, particularmente no consumo de fibras e ácidos gordos saturados. Conclusão: A maior parte da nossa amostra não usufruiu do potencial efeito positivo de uma alimentação saudável. Individualizam-se grupos de alimentos cujos consumos devem ser enfatizados ou desencorajados, particularmente, a necessidade de incentivar o consumo de alimentos ricos em fibra. Ações educacionais dirigidas devem ter especial foco em pessoas mais jovens e/ou do sexo masculino.

Spontaneous Remission of High-Grade Non-Hodgkin Lymphoma After SARS-CoV-2 Infection: A Case Report.

ABSTRACT: Despite extensive research into COVID-19 since its emergence in late 2019, there is still much not fully understood about its long-term effects. When infected with SARS-CoV-2, cancer patients have been reported to be at higher risk for unfavorable outcomes. Nevertheless, evidence suggests that viruses may exhibit an antitumor effect in some cases, which has recently been anecdotally reported with SARS-CoV-2. We present the case of a patient with a recent high-grade non-Hodgkin lymphoma diagnosis and without any cancer-specific therapy, in whom a complete metabolic response on 2-[ 18 F]FDG PET/CT was observed after COVID-19.

Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts.

There is growing evidence supporting the role of fibroblasts in all stages of atherosclerosis, from the initial phase to fibrous cap and plaque formation. In the arterial wall, as with macrophages and vascular smooth muscle cells, fibroblasts are exposed to a myriad of LDL lipids, including the lipid species formed during the oxidation of their polyunsaturated fatty acids of cholesteryl esters (PUFA-CEs). Recently, our group identified the final oxidation products of the PUFA-CEs, cholesteryl hemiesters (ChE), in tissues from cardiovascular disease patients. Cholesteryl hemiazelate (ChA), the most prevalent lipid of this family, is sufficient to impact lysosome function in macrophages and vascular smooth muscle cells, with consequences for their homeostasis. Here, we show that the lysosomal compartment of ChA-treated fibroblasts also becomes dysfunctional. Indeed, fibroblasts exposed to ChA exhibited a perinuclear accumulation of enlarged lysosomes full of neutral lipids. However, this outcome did not trigger de novo lysosome biogenesis, and only the lysosomal transcription factor E3 (TFE3) was slightly transcriptionally upregulated. As a consequence, autophagy was inhibited, probably via mTORC1 activation, culminating in fibroblasts' apoptosis. Our findings suggest that the impairment of lysosome function and autophagy and the induction of apoptosis in fibroblasts may represent an additional mechanism by which ChA can contribute to the progression of atherosclerosis.

Autism spectrum disorder in a patient with Nicolaides-Baraitser Syndrome: case report.

Nicolaides-Baraitser Syndrome is a rare genetic condition that clinically presents with intellectual disabilities, facial and bone changes, and sparse hair. In Brazil, only one case has been previously reported without genetic confirmation. We present the case of an 8-year-old boy, clinically and genetically diagnosed with Nicolaides-Baraitser Syndrome, who developed autism spectrum disorder characteristics with a formal diagnosis at the age of eight. Diagnosing autism spectrum disorder in patients with intellectual disabilities is a clinical challenge requiring careful evaluation.

Aerobic physical exercise versus dual-task cognitive walking in cognitive rehabilitation of people with stroke: a randomized clinical trial.

Introduction: Stroke is a neurological deficit caused by an acute focal injury to the central nervous system due to vascular injury that can result in loss of neurological function, lasting brain damage, long-term disability and, in some cases, death. The literature reports that aerobic physical exercise, as well as dual-task cognitive walking, are used for the cognitive recovery of people with stroke. We aimed to assess whether aerobic physical exercise influences post-stroke cognitive recovery, namely performance on selective and sustained attention. We tested the hypothesis that post-stroke aerobic physical exercise leads to more significant gains than post-stroke dual-task cognitive walking. Methods: We used a Randomized Clinical Trial, single-blind, parallel group, to verify the existence of differences between two groups. A total of 34 patients with subacute to chronic stroke were divided into two groups to train three times a week for 12 weeks: the aerobic physical exercise (PE) group engaged in 20 min on a treadmill, 20 min on a stationary bicycle and 5 min on a desk bike pedal exerciser per session; the dual-task (DT) gait exercise group walked for 45 min while simultaneously performing cognitive tasks per session. All participants were assessed on cognitive functioning with the Mini-Mental State Examination (MMSE) and d2 Test of Attention before acute interventions and post interventions. We have also applied a Visual Analog Scale to monitor the participants' perceived difficulty, pre-, post-acute, and post-chronic interventions. Participants also responded to a Borg Scale of perceived exertion following the acute and the final session of chronic training. Results: A mixed model ANOVA revealed a significant interaction effect with a large effect size for most of the cognitive variables under study. The variables associated with the d2 Test of Attention showed significant differences between the groups, mainly from T0 to T2. Also for MMSE, an ANOVA revealed a significant interaction effect with significant improvements from T0 to T2. Our results strongly suggest that aerobic physical exercise is more beneficial than dual-task cognitive-gait exercise since in the PE group, cognitive attention scores increase, and cognitive impairment and perception of exertion decrease, compared to the DT group. Conclusion: These findings support that PE provides more significant benefits for patients post-stroke when compared to DT.