Association between the practice of fitness-related exercises and body image dissatisfaction in adolescents from Curitiba (PR), Brazil / Associação entre a prática de exercícios físicos relacionados ao fitness e insatisfação com a imagem corporal em adolescentes de Curitiba (PR), Brasil

ABSTRACT Objective: The aim of this study was to analyze the association between participation in fitness-related exercises (FRE) and body image dissatisfaction (BID) in adolescents and evaluate the interaction between physical exercise and nutritional status in this association. Methods: A cross-sectional study was conducted in 2015 involving 799 adolescents (10-16 years old) from 14 public schools in Curitiba (PR), Brazil. BID was assessed using the Body Shape Questionnaire and the Silhouette Scale. The FRE was classified as "does not practice," "practices ≤300 min/week," and "practices >300 min/week" by the Physical Activity Questionnaire for Adolescents. Poisson and multinomial logistic regressions, adjusted for sex, sexual maturation, and nutritional status analyzed the association of FRE and BID. Results: The BID prevalence was 28.3%; 52.4% of the adolescents wanted to reduce their silhouettes; and 48.7% did not practice FRE. Adolescents who practiced FRE >300 min/week had a 28% higher prevalence for some level of BID (PR 1.28; 95%CI 1.08-1.52) and a 46% lower chance of wanting to reduce silhouettes (OR 0.54; 95%CI 0.35-0.82), compared to nonpractitioners. There was no interaction between FRE and nutritional status in association with BID. Conclusions: The adolescents who practice FRE >300 min/week are likely to have some level of BID and are less likely to report the desire to increase their silhouettes, regardless of their nutritional status.

RESUMO Objetivo: Analisar a associação entre a participação em exercícios físicos relacionados ao fitness (EFRF) e a insatisfação com a imagem corporal (IIC) em adolescentes e avaliar a interação entre os exercícios físicos e o estado nutricional nesta associação. Métodos: Estudo transversal realizado em 2015 com 799 adolescentes (10 a 16 anos) de 14 escolas públicas de Curitiba (PR), Brasil. A IIC foi avaliada por meio do Body Shape Questionnaire e da Escala de Silhuetas. A participação em EFRF foi avaliada pelo Questionário de Atividade Física para Adolescentes e classificada em "não pratica", "pratica ≤300 minutos/semana" e "pratica >300 minutos/semana". As regressões de Poisson e logística multinomial, ajustadas por sexo, maturação sexual e estado nutricional, analisaram a associação entre EFRF e IIC. Resultados: A prevalência de IIC foi de 28,3%; 52,4% dos adolescentes queriam reduzir a silhueta e 48,7% não praticavam a EFRF. Adolescentes que praticavam EFRF >300 minutos/semana tiveram prevalência 28% maior para algum nível de IIC (razão de prevalência — RP 1,28; intervalo de confiança de 95% — IC95% 1,08-1,52) e chance 46% menor de querer reduzir silhuetas (OR 0,54; 95IC% 0,35-0,82), comparados aos não praticantes. Não houve interação entre os EFRF e o estado nutricional na associação com IIC. Conclusões: Os adolescentes que praticam EFRF >300 minutos/semana estão mais propensos a apresentar algum nível de IIC e têm menores chances de reportar o desejo de aumentar silhuetas, independentemente do estado nutricional.

Natural resources used in the traditional medicine of the Marinaú community, Caxiuanã forest, Brazil.

Background: The diversity of Conservation Units in Brazil, ranging from Strict Protection areas like National Parks to Sustainable Use areas such as National Forests, supports the coexistence of human populations with extensive traditional knowledge of local natural resources. This traditional and local knowledge plays a crucial role in their subsistence and has significant potential to contribute to bioprospecting initiatives, as well as to enhance research and strategies for biological conservation. The São Sebastião de Marinaú community, situated within the Caxiuanã National Forest, offers valuable opportunities for ethnobiological studies. Methods: The field study was carried out with 48 informants from the São Sebastião de Marinaú Community, Caxiuanã National Forest (CNF), Brazil, a Sustainable Use Conservation Unit. It involved participant observation, semi-structured interviews, and guided tours. Indices of Use Value (UV), Fidelity Level (FL), and Consensus Factor (ICF) indicated plant species with therapeutic potential. Results: A total of 944 uses associated with 154 plants and 21 animals were reported. Statistical tests pointed out that factors such as gender and age are not determinants in the richness of known plants among the residents. The plants are distributed among 59 botanical families and 126 genera. They predominantly use species native to Brazil (69%), among which 47 are endemic to the Amazon. The medicines are prepared mainly by decoction of leaves and bark. According to UV, veronica (Dalbergia monetaria L.f.) was the most important. The animals used are all vertebrates, and paca (Cuniculus paca Linnaeus, 1766,) was the most cited. Bile and lard are the parts most used in the recipes. They mentioned 116 diseases, especially those of the digestive system. The ceruzeiro (Allantoma lineata (Mart. ex O.Berg) Miers) had a high consensus of local use, and no additional studies on this species exist. Conclusion: This study underscores the vital role of traditional communities in sustainable conservation units, as their involvement is crucial for preserving plant and animal species essential to local traditional medicine. Such research also promotes the recognition of non-timber products as valuable raw materials with potential applications in the chemical and pharmaceutical industries. Additionally, mapping the occurrence and use of species in vulnerable conditions aids in developing effective conservation strategies for these resources.

Inflammation and Vasculitis Related to Brolucizumab.

Background/objectives: To compare the prevalence of intra-ocular inflammation (IOI) between brolucizumab and aflibercept in neovascular age-related macular degeneration (nAMD) after intra-vitreal injections (IVI) and to compare the IOI odds ratios (ORs) of both therapies with the prevalence of septic endophthalmitis after IVI that was previously reported in the literature. Methods: A total of 468 IVI of brolucizumab (117 eyes) were compared with 2884 IVI of aflibercept (305 eyes) regarding IOI and occlusive retinal vasculitis (RV) from December 2021 to June 2023 in this retrospective study. The OR was calculated for both anti-VEGF agents and was compared with the relative risk of septic endophthalmitis after IVI. Results: There were four eyes with unilateral IOI related to brolucizumab (3.42%), one presenting uveitis (0.85%), two vitritis (1.71%) and the last one presenting occlusive RV (0.85%), compared with two eyes presenting unilateral IOI (anterior uveitis, 0.66%) and none with RV from the aflibercept cohort. The incidence of IOI per injection with brolucizumab (0.855%) was significantly higher compared with aflibercept (0.069%, p = 0.004). The OR of IOI related to brolucizumab IVI compared with septic endophthalmitis was 20 times greater (1.49 for aflibercept, p = 0.646, versus 20.15 for brolucizumab, p < 0.001). The OR of RV with brolucizumab compared with septic endophthalmitis was 4.6. Conclusion: Data from our department suggest a much higher risk of IOI and occlusive retinal vasculitis after brolucizumab when compared with aflibercept. The risk of IOI and severe sight-threatening complications related to brolucizumab is greater than the risk of septic endophthalmitis after any IVI.

Laboratory and physiological aspects of substitute metazoan models for in vivo pharmacotoxicological analysis.

New methods are essential to characterize the performance of substitute procedures for detecting therapeutic action(s) of a chemical or key signal of toxicological events. Herein, it was discussed the applications and advantages of using arthropods, worms, and fishes in pharmacological and/or toxicology assessments. First of all, the illusion of similarity covers many differences between humans and mice, remarkably about liver injury and metabolism of xenobiotics. Using invertebrates, especially earthworms (Eisenia fetida), brine shrimps (Artemia salina, Daphnia magna), and insects (Drosophila melanogaster) and vertebrates as small fishes (Oryzias latipes, Pimephales promelas, Danio rerio) has countless advantages, including fewer ethical conflicts, short life cycle, high reproduction rate, simpler to handle, and less complex anatomy. They can be used to find contaminants in organic matters and water and are easier genetically engineered with orthologous-mutated genes to explore specific proteins involved in proliferative and hormonal disturbances, chemotherapy multidrug resistance, and carcinogenicity. As multicellular embryos, larvae, and mature organisms, they can be tested in bigger-sized replication platforms with 24-, 96-, or 384-multiwell plates as cheaper and faster ways to select hit compounds from drug-like libraries to predict acute, subacute or chronic toxicity, pharmacokinetics, and efficacy parameters of pharmaceutical, cosmetic, and personal care products. Meanwhile, sublethal exposures are designed to identify changes in reproduction, body weight, DNA damages, oxidation, and immune defense responses in earthworms and zebrafishes, and swimming behaviors in A. salina and D. rerio. Behavioral parameters also give specificities on sublethal effects that would not be detected in zebrafishes by OECD protocols.

Current management of inherited retinal degenerations in Portugal (IRD-PT survey).

Inherited retinal dystrophies/degenerations (IRDs) are the leading cause of visual impairment and incurable familial blindness in the Western world. Given the clinical and genetic heterogeneity, establishing a molecular diagnosis is especially relevant. The aim of this study was to perform the first nationwide survey to understand the prevalence and current management of IRDs in Portugal. A response was obtained from 26 healthcare providers (HCP) (76.5% response rate). Only 4 respondents reported not managing IRD patients. Most HCPs (68.1%) reported managing up to 100 patients, while three currently manage between 501 and 1000 patients. Based on the Portuguese population, an estimated IRD prevalence of 0.031%, i.e., about 1 in 3000 individuals, was calculated. In most HCPs (86.3%), most patients are adults, and non-syndromic retinitis pigmentosa is the most frequent diagnosis. Only 4 HCPs currently use the national, web-based IRD registry (IRD-PT). However, all but one respondent expressed interest in participating in such a registry. Genetic testing is available in 54.5%, with 58.3% HCPs reporting solved rates between 61-80%, but 4 to 9 months to get a genetic test result in 83.4% of cases. Based on this survey, the prevalence of biallelic RPE65-associated disease in Portugal is 0.00031%, i.e., approximately 1:300,000 individuals. Data from this study provide vital background information on national differences in the diagnosis and management of IRD patients. Nationwide implementation of the IRD-PT registry should be encouraged and supported to provide population-based reference data and to identify patients eligible for current and future therapies.

Intravenous Thrombolysis in Patients With Cervical Artery Dissection: A Secondary Analysis of the STOP-CAD Study.

OBJECTIVES: Cervical artery dissection (CeAD) accounts for 25% of ischemic strokes in young adults. This study evaluated the benefits and harms of intravenous thrombolysis (IVT) in patients presenting with spontaneous CeAD and acute ischemic stroke symptoms. METHODS: This analysis used data from the retrospective STOP-CAD study and included patients with spontaneous CeAD who presented within 1 day of acute ischemic stroke symptoms. Patients were dichotomized into those who received IVT and those managed without IVT. We assessed the association between IVT and 90-day functional independence (modified Rankin Scale scores 0-2) and the incidence of symptomatic intracranial hemorrhage (ICH, defined as ICH causing new or worsening neurologic symptoms within 72 hours after CeAD diagnosis). RESULTS: This study included 1,653 patients from the original STOP-CAD cohort of 4,023. The median age was 49 years, and 35.1% were women; 512 (31.0%) received IVT. IVT was associated with 90-day functional independence (adjusted odds ratio [aOR] = 1.67, 95% CI 1.23-2.28, p = 0.001), but not with symptomatic ICH (aOR = 1.52, 95% CI 0.79-2.92, p = 0.215). DISCUSSION: In patients with spontaneous CeAD and suspected ischemic stroke, IVT improved functional outcomes, without increasing symptomatic ICH risk. These findings support current guideline recommendations to consider thrombolysis for otherwise eligible patients with CeAD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IVT significantly increases the probability of 90-day functional independence in patients with CeAD.

Unveiling a Small Bowel Obstruction: A Case of a Neuroendocrine Ileal Tumor.

Neuroendocrine tumors (NETs) are rare, slow-growing tumors originating from the diffuse neuroendocrine cell system, predominantly affecting the digestive tract. Small bowel neuroendocrine tumors (SBNETs) may present with nonspecific symptoms, such as abdominal pain, or with intermittent intestinal obstruction. This case outlines the diagnostic journey of a septuagenarian male with prolonged abdominal symptoms and weight loss. Despite extensive investigation, a definitive cause remained elusive. Recurrent partial intestinal obstruction led to surgical exploration and segmental resection. Pathology confirmed a NET. The case underscores the importance of considering intestinal neoplasia in older patients with recurrent partial small bowel obstruction.

Association between the practice of fitness-related exercises and body image dissatisfaction in adolescents from Curitiba (PR), Brazil.

OBJECTIVE: The aim of this study was to analyze the association between participation in fitness-related exercises (FRE) and body image dissatisfaction (BID) in adolescents and evaluate the interaction between physical exercise and nutritional status in this association. METHODS: A cross-sectional study was conducted in 2015 involving 799 adolescents (10-16 years old) from 14 public schools in Curitiba (PR), Brazil. BID was assessed using the Body Shape Questionnaire and the Silhouette Scale. The FRE was classified as "does not practice," "practices ≤300 min/week," and "practices >300 min/week" by the Physical Activity Questionnaire for Adolescents. Poisson and multinomial logistic regressions, adjusted for sex, sexual maturation, and nutritional status analyzed the association of FRE and BID. RESULTS: The BID prevalence was 28.3%; 52.4% of the adolescents wanted to reduce their silhouettes; and 48.7% did not practice FRE. Adolescents who practiced FRE >300 min/week had a 28% higher prevalence for some level of BID (PR 1.28; 95%CI 1.08-1.52) and a 46% lower chance of wanting to reduce silhouettes (OR 0.54; 95%CI 0.35-0.82), compared to nonpractitioners. There was no interaction between FRE and nutritional status in association with BID. CONCLUSIONS: The adolescents who practice FRE >300 min/week are likely to have some level of BID and are less likely to report the desire to increase their silhouettes, regardless of their nutritional status.

QM/MM Study of the Reaction Mechanism of L-Tyrosine Hydroxylation Catalyzed by the Enzyme CYP76AD1.

We have studied the hydroxylation mechanism of l-Tyr by the heme-dependent enzyme CYP76AD1 from the sugar beet (Beta vulgaris). This enzyme has a promising biotechnological application in modified yeast strains to produce medicinal alkaloids, an alternative to the traditional opium poppy harvest. A generative machine learning software based on AlphaFold was used to build the structure of CYP76AD1 since there are no structural data for this specific enzyme. After model validation, l-Tyr was docked in the active site of CYP76AD1 to assemble the reactive complex, whose catalytic distances remained stable throughout the 100 ns of MD simulation. Subsequent QM/MM calculations elucidated that l-Tyr hydroxylation occurs in two steps: hydrogen abstraction from l-Tyr by CpdI, forming an l-Tyr radical, and subsequent radical rebound, corresponding to a rate-limiting step of 16.0 kcal·mol-1. Our calculations suggest that the hydrogen abstraction step should occur in the doublet state, while the radical rebound should happen in the quartet state. The clarification of the reaction mechanism of CYP76AD1 provides insights into the rational optimization of the biosynthesis of alkaloids to eliminate the use of opium poppy.

Appendiceal Neoplasm: It's Never What It Seems.

Appendiceal neoplasms are a rare and heterogeneous condition with a non-specific clinical presentation, often concealing intricate predicaments; hence they require complex and diverse management. The present case report aims not only to describe a less usual form of presentation and its orientation but also to provide a modest literature review in a rather demanding pathology.

scEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood.

Ageing is the accumulation of changes and decline of function of organisms over time. The concept and biomarkers of biological age have been established, notably DNA methylation-based clocks. The emergence of single-cell DNA methylation profiling methods opens the possibility of studying the biological age of individual cells. Here, we generate a large single-cell DNA methylation and transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages. The number of genes expressed increases with age, but gene-specific changes are small. We next develop scEpiAge, a single-cell DNA methylation age predictor, which can accurately predict age in (very sparse) publicly available datasets, and also in single cells. DNA methylation age distribution is wider than technically expected, indicating epigenetic age heterogeneity and functional differences. Our work provides a foundation for single-cell and sparse data epigenetic age predictors, validates their functionality and highlights epigenetic heterogeneity during ageing.

Allium cepa as a Toxicogenetic Investigational Tool for Plant Extracts: A Systematic Review.

Toxicological studies are important to investigate the genotoxic effects of various substances. Allium cepa can be used as test model for this purpose. This review summarizes the scope and applications for this A. cepa test model. For this, an up-to-date (April 2023) literature search was made in the Science Direct, PubMed, and Web of Science databases to find published evidence on studies performed using A. cepa as a test model. Out of 3,748 studies, 74 fit the inclusion criteria. The results showed that the use of the test model A. cepa contributed considerably to measuring the toxicological potential of plant extracts, proving the efficacy of the test as a potent bioindicator of toxic effects. In addition, 27 studies used more than one test system to verify the toxicological potential of extracts and fractions. Studies have shown that the A. cepa model has the potential to replace other test systems that make use of animals and cell cultures, besides having other advantages such as low cost, ease of execution, and good conditions for the observation of chromosomes. In conclusion, the A. cepa test can be considered one of the potential biomonitoring systems in toxicological studies of crude extracts.

Comparative analysis of the degree of patient satisfaction after breast-conserving surgery with or without oncoplastic surgery: systematic review and meta-analysis.

Introduction: Conservative surgery is the gold standard for the treatment of single and small tumors and, combined with the concept of oncoplastic tumors, brings good aesthetic results while maintaining cancer safety. The objective was to comparatively analyze the degree of satisfaction of patients undergoing breast conserving surgery (BCS), with and without oncoplastic surgery (OPS) using level II OPS techniques. Methods: Review with a search in the databases MEDLINE (by PubMed), EMBASE, Clinical Trials, Scopus, Web of Science, BVS and Oppen gray. The meta-analysis of random effects was performed using the Der Simonian-Laird method considering the odds ratio (OR) with a 95% confidence interval (95% CI). Results: There was no statistically significant difference in the aesthetic outcome between women who underwent OPS and BCS (OR 0.90; 95% CI 0.62-1.30). The staging (OR 1.93; 95% CI 0.97-3.84; I 2 = 15.83%); tumor location [central (OR 1.28; 95% CI 0.06-27.49; I 2 = 17.63%); lower (OR 0.75; 95% CI 0.21-2.65; I 2 = 2.21%); superior (OR 0.67; 95% CI 0.26-1.74; I 2 = 0.00%] and tumor size (OR 8.73; 95% CI -11.82-29.28; I 2 = 93.18%) showed no association with the type of BCS performed, with or without OPS. The degree of satisfaction remains even in cases of extreme oncoplasty. Conclusion: The level of patient satisfaction in relation to BCS was similar to that of the group undergoing OPS, highlighting that OPS allows the patient's satisfaction rate to be maintained even in the case of large or multicentric tumors.

Exploring Molecular Heteroencoders with Latent Space Arithmetic: Atomic Descriptors and Molecular Operators.

A variational heteroencoder based on recurrent neural networks, trained with SMILES linear notations of molecular structures, was used to derive the following atomic descriptors: delta latent space vectors (DLSVs) obtained from the original SMILES of the whole molecule and the SMILES of the same molecule with the target atom replaced. Different replacements were explored, namely, changing the atomic element, replacement with a character of the model vocabulary not used in the training set, or the removal of the target atom from the SMILES. Unsupervised mapping of the DLSV descriptors with t-distributed stochastic neighbor embedding (t-SNE) revealed a remarkable clustering according to the atomic element, hybridization, atomic type, and aromaticity. Atomic DLSV descriptors were used to train machine learning (ML) models to predict 19F NMR chemical shifts. An R2 of up to 0.89 and mean absolute errors of up to 5.5 ppm were obtained for an independent test set of 1046 molecules with random forests or a gradient-boosting regressor. Intermediate representations from a Transformer model yielded comparable results. Furthermore, DLSVs were applied as molecular operators in the latent space: the DLSV of a halogenation (H→F substitution) was summed to the LSVs of 4135 new molecules with no fluorine atom and decoded into SMILES, yielding 99% of valid SMILES, with 75% of the SMILES incorporating fluorine and 56% of the structures incorporating fluorine with no other structural change.

Therapeutic-driven framework for bioequivalence assessment of complex topical generic drug products.

Despite the continuous research on understanding how topical drugs and the skin interact, the development of a topical generic product remains a challenge. Due to their local action effect rather than systemic, establishing suitable frameworks for documenting bioequivalence between reference and test formulations is anything but straightforward. In previous years, clinical endpoint trials were considered the gold standard method to demonstrate bioequivalence between topical products. Nevertheless, significant financial and time resources were required to be allocated owing to the inherent complexity of these studies. To address this problem, regulatory authorities have begun to accept alternative approaches that could lead to a biowaiver, avoiding the need for clinical endpoint trials. These alternatives encompass various in vitro and/or in vivo techniques that have been analysed and the benefits and drawbacks of each method have been considered. Furthermore, other factors like the integration of a quality by design framework to ensure a comprehensive understanding of the product and process quality attributes have also been taken into account. This review delves into international regulatory recommendations for semisolid topical products, with a focus on those established by the European Medicines Agency, as well as the Food and Drug Administration. Both approaches were carefully examined, discussing aspects such as acceptance criteria, sample size, and microstructure evaluation. Additionally, novel and innovative therapeutic-driven approaches based on in vitro disease models for the rapid and effective development of topical generic products are presented.

Identification of radiologic and clinicopathologic variables associated with tumor regression pattern and distribution of cancer cells after short-course radiotherapy and consolidation chemotherapy in patients with rectal cancer.

Background: Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective: To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods: We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results: Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion: The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern.

Synchronous Gastric and Rectal Adenocarcinoma With Complete Response After Total Neoadjuvant Therapy: A Case Report.

Synchronous gastric cancer with another neoplasm is a rare condition, with colorectal cancer being the most frequently associated neoplasm. This article presents a case of a 76-year-old male diagnosed with synchronous gastric and rectal cancer with complete remission of gastric and rectal neoplasms after adjuvant therapy. The patient exhibited symptoms prompting upper and lower endoscopies, revealing gastric and rectal adenocarcinomas, respectively. Staging was performed, and due to the locally advanced nature of both malignancies, the patient underwent total neoadjuvant therapy (TNT) for rectal cancer. The treatment consisted of external radiotherapy and neoadjuvant chemotherapy with oxaliplatin, leucovorin, folinic acid, and fluorouracil (FOLFOX). Remarkably, after seven cycles, a complete clinical response of the rectal neoplasm was achieved. Subsequent surgical resection included simultaneous subtotal gastrectomy and rectal anterior resection, resulting in a complete pathological response for both tumors. To the best of our knowledge, it is among the first cases to report a full pathological response in gastric cancer following TNT intended for rectal cancer.

RIPPLE-VT study: Multicenter prospective evaluation of ventricular tachycardia substrate ablation by targeting scar channels to eliminate latest scar potentials without direct ablation.

BACKGROUND: Recurrent ventricular tachycardia (VT) can be treated by substrate modification of the myocardial scar by catheter ablation during sinus rhythm without VT induction. Better defining this arrhythmic substrate could help improve outcome and reduce ablation burden. OBJECTIVE: The study aimed to limit ablation within postinfarction scar to conduction channels within the scar to reduce VT recurrence. METHODS: Patients undergoing catheter ablation for recurrent implantable cardioverter-defibrillator therapy for postinfarction VT were recruited at 5 centers. Left ventricular maps were collected on CARTO using a Pentaray catheter. Ripple mapping was used to categorize infarct scar potentials (SPs) by timing. Earliest SPs were ablated sequentially until there was loss of the terminal SPs without their direct ablation. The primary outcome measure was sustained VT episodes as documented by device interrogations at 1 year, which was compared with VT episodes in the year before ablation. RESULTS: The study recruited 50 patients (mean left ventricular ejection fraction, 33% ± 9%), and 37 patients (74%) met the channel ablation end point with successful loss of latest SPs without direct ablation. There were 16 recurrences during 1-year follow-up. There was a 90% reduction in VT burden from 30.2 ± 53.9 to 3.1 ± 7.5 (P < .01) per patient, with a concomitant 88% reduction in appropriate shocks from 2.1 ± 2.7 to 0.2 ± 0.9 (P < .01). There were 8 deaths during follow-up. Those who met the channel ablation end point had no significant difference in mortality, recurrence, or VT burden but had a significantly lower ablation burden of 25.7 ± 4.2 minutes vs 39.9 ± 6.1 minutes (P = .001). CONCLUSION: Scar channel ablation is feasible by ripple mapping and can be an alternative to more extensive substrate modification techniques.

Peptide-Hitchhiking for the Development of Nanosystems in Glioblastoma.

Glioblastoma (GBM) remains the epitome of aggressiveness and lethality in the spectrum of brain tumors, primarily due to the blood-brain barrier (BBB) that hinders effective treatment delivery, tumor heterogeneity, and the presence of treatment-resistant stem cells that contribute to tumor recurrence. Nanoparticles (NPs) have been used to overcome these obstacles by attaching targeting ligands to enhance therapeutic efficacy. Among these ligands, peptides stand out due to their ease of synthesis and high selectivity. This article aims to review single and multiligand strategies critically. In addition, it highlights other strategies that integrate the effects of external stimuli, biomimetic approaches, and chemical approaches as nanocatalytic medicine, revealing their significant potential in treating GBM with peptide-functionalized NPs. Alternative routes of parenteral administration, specifically nose-to-brain delivery and local treatment within the resected tumor cavity, are also discussed. Finally, an overview of the significant obstacles and potential strategies to overcome them are discussed to provide a perspective on this promising field of GBM therapy.

Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron-BA.1 variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the United States became increasingly significant. The number of detected introductions varied from 96 and 101 for Alpha and Delta to 39 for Omicron-BA.1. Most of these introductions left a low number of descendants (<10), suggesting a limited impact on the evolution of the pandemic in Galicia. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.