Acute symptomatic seizures in patients with recurrent ischemic stroke: A multicentric study.

OBJECTIVE: Epileptic seizures occur frequently after stroke due to changes in brain function and structure, and up to around 10% of stroke patients experience stroke recurrence in the first year. We aimed to establish the risk of acute symptomatic seizures in patients with recurrent stroke. METHODS: Retrospective cohort study including consecutive admissions to a Stroke Unit due to acute ischemic stroke, during a 5-year period. Additional inclusion of patients admitted to two centers in different countries to corroborate findings (confirmatory cohort). We aimed to compare acute symptomatic seizure incidence in patients with and without previous stroke. Patients with history of epilepsy were excluded. Logistic regression modeling was performed to identify predictors in middle cerebral artery (MCA) stroke. RESULTS: We included 1473 patients (1085 with MCA stroke), of which 117 had a recurrent ischemic stroke (84 with MCA stroke). Patients with recurrent stroke had a seizure risk during hospital stay similar to that of patients with a first-ever stroke (5.1% vs. 4.5%, OR 1.15, 95% CI .48-2.71, p = .75). Risk of acute symptomatic seizures was also similar (5.0% vs. 4.1, OR 1.22, 95% CI .29-5.27, p = .78). Older age, female sex, and hemorrhagic transformation were predictors of seizures in patients with a first MCA ischemic stroke, but not in recurrent stroke patients. Electrographic characteristics were similar between the two groups in patients who had an electroencephalogram (46 with first stroke, 5 with recurrent stroke). The low rate of seizures (1.5%) in the confirmatory cohort (n = 198) precluded full comparison with the initial cohort. Nevertheless, the rate of seizures was not higher in stroke recurrence. SIGNIFICANCE: History of previous stroke was not associated with an increased risk of acute symptomatic seizures during hospital stay. Larger, prospective studies, with prospective electrophysiological evaluation, are needed to explore the impact of stroke recurrence on seizure risk.

Competency in invasion science: addressing stagnation challenges by promoting innovation and creative thinking.

In today's ever-evolving scientific landscape, invasion science faces a plethora of challenges, such as terminological inconsistency and the rapidly growing literature corpus with few or incomplete syntheses of knowledge, which may be perceived as a stagnation in scientific progress. We explore the concept of 'competency', which is extensively debated across disciplines such as psychology, philosophy, and linguistics. Traditionally, it is associated with attributes that enable superior performance and continuous ingenuity. We propose that the concept of competency can be applied to invasion science as the ability to creatively and critically engage with global challenges. For example, competency may help develop innovative strategies for understanding and managing the multifaceted, unprecedented challenges posed by the spread and impacts of non-native species, as well as identifying novel avenues of inquiry for management. Despite notable advancements and the exponential increase in scholarly publications, invasion science still encounters obstacles such as insufficient interdisciplinary collaboration paralleled by a lack of groundbreaking or actionable scientific advancements. To enhance competency in invasion science, a paradigm shift is needed. This shift entails fostering interdisciplinary collaboration, nurturing creative and critical thinking, and establishing a stable and supportive environment for early career researchers, thereby promoting the emergence of competency and innovation. Embracing perspectives from practitioners and decision makers, alongside diverse disciplines beyond traditional ecological frameworks, can further add novel insights and innovative methodologies into invasion science. Invasion science must also address the ethical implications of its practices and engage the public in awareness and education programs. Such initiatives can encourage a more holistic understanding of invasions, attracting and cultivating competent minds capable of thinking beyond conventional paradigms and contributing to the advancement of the field in a rapidly changing world.

Prenatal Exposure to Herbicide 2,4-Dichlorophenoxyacetic Acid (2,4D) Exacerbates Zika Virus Neurotoxicity In Vitro and In Vivo.

Zika virus (ZIKV) infection during pregnancy can lead to a set of congenital malformations known as Congenital ZIKV syndrome (CZS), whose main feature is microcephaly. The geographic distribution of CZS in Brazil during the 2015-2017 outbreak was asymmetrical, with a higher prevalence in the Northeast and Central-West regions of the country, despite the ubiquitous distribution of the vector Aedes aegypti, indicating that environmental factors could influence ZIKV vertical transmission and/or severity. Here we investigate the involvement of the most used agrochemicals in Brazil with CZS. First, we exposed human neuroblastoma SK-N-AS cells to the 15 frequently used agrochemical molecules or derivative metabolites able to cross the blood-brain barrier. We found that a derived metabolite from a widely used herbicide in the Central-West region, 2,4-dichlorophenoxyacetic acid (2,4D), exacerbates ZIKV neurotoxic effects in vitro. We validate this observation by demonstrating vertical transmission leading to microcephaly in the offspring of immunocompetent C57BL/6J mice exposed to water contaminated with 0.025 mg/L of 2,4D. Newborn mice whose dams were exposed to 2,4D and infected with ZIKV presented a smaller brain area and cortical plate size compared to the control. Also, embryos from animals facing the co-insult of ZIKV and 2,4D exposition presented higher Caspase 3 positive cells in the cortex, fewer CTIP2+ neurons and proliferative cells at the ventricular zone, and a higher viral load. This phenotype is followed by placental alterations, such as vessel congestion, and apoptosis in the labyrinth and decidua. We also observed a mild spatial correlation between CZS prevalence and 2,4D use in Brazil's North and Central-West regions, with R2 = 0.4 and 0.46, respectively. Our results suggest that 2,4D exposition facilitates maternal vertical transmission of ZIKV, exacerbating CZS, possibly contributing to the high prevalence of this syndrome in Brazil's Central-West region compared to other regions.

Mitochondrial RNA cytosolic leakage drives the SASP.

Senescent cells secrete proinflammatory factors known as the senescence-associated secretory phenotype (SASP), contributing to tissue dysfunction and aging. Mitochondrial dysfunction is a key feature of senescence, influencing SASP via mitochondrial DNA (mtDNA) release and cGAS/STING pathway activation. Here, we demonstrate that mitochondrial RNA (mtRNA) also accumulates in the cytosol of senescent cells, activating RNA sensors RIG-I and MDA5, leading to MAVS aggregation and SASP induction. Inhibition of these RNA sensors significantly reduces SASP factors. Furthermore, BAX and BAK plays a key role in mtRNA leakage during senescence, and their deletion diminishes SASP expression in vitro and in a mouse model of Metabolic Dysfunction Associated Steatohepatitis (MASH). These findings highlight mtRNA's role in SASP regulation and its potential as a therapeutic target for mitigating age-related inflammation.

Molecular Epidemiology of Western Equine Encephalitis Virus, South America, 2023-2024.

Western equine encephalitis virus (WEEV) is a mosquitoborne virus that reemerged in December 2023 in Argentina and Uruguay, causing a major outbreak. We investigated the outbreak using epidemiologic, entomological, and genomic analyses, focusing on WEEV circulation near the Argentina‒Uruguay border in Rio Grande do Sul state, Brazil. During November 2023‒April 2024, the outbreak in Argentina and Uruguay resulted in 217 human cases, 12 of which were fatal, and 2,548 equine cases. We determined cases on the basis of laboratory and clinical epidemiologic criteria. We characterized 3 fatal equine cases caused by a novel WEEV lineage identified through a nearly complete coding sequence analysis, which we propose as lineage C. Our findings highlight the importance of continued surveillance and equine vaccination to control future WEEV outbreaks in South America.

Unveiling the impact of circulating tumor cells: Two decades of discovery and clinical advancements in solid tumors.

Circulating tumor cells (CTCs) enumeration and molecular profiling hold promise in revolutionizing the management of solid tumors. Their understanding has evolved significantly over the past two decades, encompassing pivotal biological discoveries and clinical studies across various malignancies. While for some tumor types, such as breast, prostate, and colorectal cancer, CTCs are ready to enter clinical practice, for others, additional research is required. CTCs serve as versatile biomarkers, offering insights into tumor biology, metastatic progression, and treatment response. This review summarizes the latest advancements in CTC research and highlights future directions of investigation. Special attention is given to concurrent evaluations of CTCs and other circulating biomarkers, particularly circulating tumor DNA. Multi-analyte assessment holds the potential to unlock the full clinical capabilities of liquid biopsy. In conclusion, CTCs represent a transformative biomarker in precision oncology, offering extraordinary opportunities to translate scientific discoveries into tangible improvements in patient care.

Evaluación de la capacidad funcional en actividades básicas de la vida diaria de adultos mayores residentes en hogares de Asunción, Paraguay

Introducción: El envejecimiento poblacional y el aumento de enfermedades crónicas han incrementado la prevalencia de discapacidad en adultos mayores. Evaluar la capacidad funcional en actividades básicas de la vida diaria (ABVD) es esencial para mantener la independencia y calidad de vida. Este estudio se enfocó en evaluar la capacidad funcional de adultos mayores en ABVD en el ámbito familiar de Asunción en el año 2023. Materiales y métodos: Se realizó un estudio observacional, descriptivo, de corte transversal, en noviembre del 2023, con 91 adultos mayores (≥65 años) de Asunción, en hogares familiares. Se aplicaron encuestas mediante Google Formulario y se utilizó el Índice de Barthel para medir la capacidad funcional. El muestreo fue no probabilístico por bola de nieve. Se empleó estadística descriptiva e inferencial, con un nivel de significancia de p≤0,05. Se respetaron los aspectos éticos de la investigación. Resultados: Participaron 91 adultos mayores, con una edad promedio de 79 años±8,2. El 62,6% fueron mujeres y 41,8% del grupo de edad de 75 a 84 años. Según el Índice de Barthel, el 59,3% necesita ayuda para cortar alimentos y el 34,1% depende de otra persona para la higiene personal. El 28,6% tiene incontinencia en deposiciones y el 30,8% en micción. La puntuación promedio del Índice de Barthel fue 68,5±33,9, indicando dependencia leve en el 61,5% de los participantes. El 77% de los adultos mayores reciben cuidados de un familiar. Conclusión: Un alto porcentaje de los adultos mayores mostró algún grado de dependencia, especialmente en actividades de alimentación e higiene. La edad avanzada y el sexo femenino se asociaron con mayores niveles de dependencia. La mayoría de los adultos mayores dependieron de familiares para su cuidado, destacando la necesidad de fortalecer las redes de apoyo y capacitar a los cuidadores informales.

Introduction: Population aging and the increase in chronic diseases have raised the prevalence of disability in older adults. Evaluating functional capacity in basic activities of daily living (BADL) is essential to maintaining independence and quality of life. This study focused on evaluating the functional capacity of older adults in BADL within the family setting of Asunción in 2023. Material and methods: An observational, descriptive, cross-sectional study was conducted in November 2023, with 91 older adults (≥65 years) from Asunción, in family homes. Surveys were administered via Google Forms, and the Barthel Index was used to measure functional capacity. The sampling was non-probabilistic snowball sampling. Descriptive and inferential statistics were employed, with a significance level of p≤0.05. Ethical aspects of the research were respected. Results: Ninety-one older adults participated, with an average age of 79 years±8.2. Of these, 62.6% were women and 41.8% were in the age group of 75 to 84 years. According to the Barthel Index, 59.3% needed help cutting food, and 34.1% depended on another person for personal hygiene. Additionally, 28.6% had bowel incontinence, and 30.8% had urinary incontinence. The average Barthel Index score was 68.5±3.9, indicating mild dependence in 61.5% of participants. Furthermore, 77% of older adults received care from a family member. Conclusion: A high percentage of older adults showed some degree of dependence, especially in activities related to feeding and hygiene. Advanced age and female sex were associated with higher levels of dependence. Most older adults relied on family members for care, highlighting the need to strengthen support networks and train informal caregivers.

Bovine Alphaherpesvirus 1, Bovine Alphaherpesvirus 5 and Bubaline Alphaherpesvirus 1 in Palatine Tonsils from Water Buffaloes in Northern Brazil and Possible Links with the Origin of Bovine Alphaherpesvirus Type 5.

Herpesviruses are significant pathogens of ruminants. In water buffaloes (Bubalus bubalis), however, herpesviruses have not been thoroughly studied. Although bubaline alphaherpesvirus 1 (BuAHV1) and bovine alphaherpesvirus 1 (BoAHV1) have already been recovered from water buffaloes, to date, no reports on the occurrence of bovine alphaherpesvirus 5 (BoAHV5) in these animals have been published. Therefore, the aim of this study was to search for BuAHV1, BoAHV1, and BoAHV5 in palatine tonsils of apparently healthy water buffaloes from the Pará state, Northern Brazil. Tissue samples of tonsils (n = 293) were screened by a nested PCR (nPCR) targeting a region of UL44 (gC coding gene), followed by sequencing, to detect and differentiate between the viral types. Viral genome segments were detected in 18 out of 293 (6.1%) of the palatine tonsil samples. Two animals carried genomes of BoAHV1 only, eleven animals carried BoAHV5 genomes only, and four animals carried BuAHV1 only. Another animal had both BoAHV1 and BoAHV5 genomes in its tonsils. No infectious virus could be recovered from any of the samples. The BuAHV1 sequences identified here were more closely related to BuAHV1 genomes identified in India. Phylogenetic analyses suggested a closer relationship between the recovered BoAHV5 and BuAHV1 genomes. Therefore, evidence is provided here to confirm that not only BoAHV1 and BuAHV1, but also BoAHV5, can infect water buffaloes. This report highlights (i) the first detection of BoAHV5 in water buffaloes and (ii) the occurrence of coinfections with BoAHV1 and BoAHV5 in that species. Such findings and the similarity of BoAHV5 to Indian herpesvirus genomes suggest that the origin of type 5 may be linked to recombinations between bovine and bubaline herpesviruses within bubalines, since the scenario for generation of recombinants in buffaloes is potentially present.

Toxoplasma gondii and Neospora caninum in invasive wild boars (Sus scrofa) and hunting dogs from Brazil.

The wild boar, an impactful invasive species in Brazil, is subject to population control activities, which often include the use of hunting dogs. Hunters commonly consume wild boar meat, which is also used to feed their dogs, posing a risk of Toxoplasma gondii infection for humans and both T. gondii and Neospora caninum for dogs. The study aimed to investigate the prevalence of infection in wild boars (n = 127) and hunting dogs (n = 73) from São Paulo, Rio Grande do Sul, and Paraná states. We employed histopathological, serological (indirect fluorescent antibody test), and molecular techniques (endpoint polymerase chain reaction). Histopathology slides of wild boar tissue (central nervous system, heart, skeletal muscle, liver, spleen, kidney, gastrointestinal tract, pancreas, lymph nodes, and thyroid) sections revealed no T. gondii or N. caninum cysts (0/47). Antibodies anti-T. gondii were detected in 35/108 (32.4%) and anti-N. caninum in 45/108 (41.7%) wild boars. Only 2/18 (11.1%) wild boar tissue homogenate samples tested positive for T. gondii on endpoint PCR. Hunting dogs showed antibodies against T. gondii in 62/73 (85%) and against N. caninum in 31/73 (42%). The presence of antibodies against T. gondii and N. caninum in wild boars and hunting dogs, along with T. gondii DNA detection in wild boars, indicates the circulation of these parasites. Educating hunters on preventing these foodborne diseases, including zoonotic risks, is crucial.

The virome of bubaline (Bubalus bubalis) tonsils reveals an unreported bubaline polyomavirus.

Water buffalo (Bubalus bubalis) farming is increasing in many regions of the world due to the species' ability to thrive in environments where bovine cattle would struggle. Despite water buffaloes being known for their resistance to diseases, there is a lack of data about the diversity of the microbiome of the species. In this study, we examined the virome diversity in palatine tonsils collected from animals from the island of Marajó, northern Pará state, Brazil, which harbors the largest bubaline flock in the country. Tonsil fragments from 60 clinically healthy bubalines were randomly selected from a sample of 293 animals. The samples were purified, extracted, and randomly amplified with phi29 DNA polymerase. After amplification, the products were purified and sequenced. Circular DNA viruses were predominant in the tonsils' virome. Sequences of genome segments representative of members of the genera Alphapolyomavirus (including a previously unreported bubaline polyomavirus genome) and Gemycircularvirus were identified, along with other not yet classified circular virus genomes. As the animals were clinically healthy at the time of sampling, such viruses likely constitute part of the normal tonsillar virome of water buffaloes inhabiting the Ilha do Marajó biome.

Extrafacial lentigo maligna: A progression model and enhanced diagnostic techniques using dermatoscopy and reflectance confocal microscopy.

Lentigo maligna (LM) is a subtype of lentiginous melanoma confined to the epidermis, which is associated with chronic sun exposure. Its clinical, dermatoscopic, and histopathological diagnosis can be challenging, particularly in the early and advanced stages, requiring appropriate clinicopathological correlation. This article reviews the clinical presentation, diagnosis through noninvasive methods (dermoscopy and confocal microscopy), and provides insights for diagnosis of extrafacial LM through the presentation of four representative clinical cases from different phases of a theoretical-practical progression model. Recognizing these lesions is crucial, as once they invade the dermis, they can behave like any other type of melanoma.

Adding mechanobiological cell features to finite element analysis of an immediately loaded dental implant.

Finite element analysis (FEA) has been used to analyze the behavior of dental materials, mainly in implantology. However, FEA is a mechanical analysis and few studies have tried to simulate the biological characteristics of the healing process of loaded implants. This study used the rule of mixtures to simulate the biological healing process of immediate implants in an alveolus socket and bone-implant junction interface through FEA. Three-dimensional geometric models of the structures were obtained, and material properties were derived from the literature. The rule of mixtures was used to simulate the healing periods-immediate and early loading, in which the concentration of each cell type, based on in vivo studies, influenced the final elastic moduli. A 100 N occlusal load was simulated in axial and oblique directions. The models were evaluated for maximum and minimum principal strains, and the bone overload was assessed through Frost's mechanostat. There was a higher strain concentration in the healing regions and cortical bone tissue near the cervical portion. The bone overload was higher in the immediate load condition. The method used in this study may help to simulate the biological healing process and could be useful to relate FEA results to clinical practice.

Molecular epidemiology of Western equine encephalitis virus in Brazil, 2023-2024.

During the ongoing western equine encephalitis virus (WEEV) outbreak in South America, we described three fatal cases in horses from Rio Grande do Sul, Brazil. We sequenced WEEV strains and identified a novel lineage causing these cases. Continued surveillance and horse immunization are needed to mitigate the WEEV burden.

Vibrational spectroscopy coupled with machine learning sheds light on the cellular effects induced by rationally designed TLR4 agonists.

In this work, we present the potential of Fourier transform infrared (FTIR) microspectroscopy to compare on whole cells, in an unbiased and untargeted way, the capacity of bacterial lipopolysaccharide (LPS) and two rationally designed molecules (FP20 and FP20Rha) to activate molecular circuits of innate immunity. These compounds are important drug hits in the development of vaccine adjuvants and tumor immunotherapeutics. The biological assays indicated that FP20Rha was more potent than FP20 in inducing cytokine production in cells and in stimulating IgG antibody production post-vaccination in mice. Accordingly, the overall significant IR spectral changes induced by the treatment with LPS and FP20Rha were similar, lipids and glycans signals being the most diagnostic, while the effect of the less potent molecule FP20 on cells resulted to be closer to control untreated cells. We propose here the use of FTIR spectroscopy supported by artificial intelligence (AI) to achieve a more holistic understanding of the cell response to new drug candidates while screening them in cells.

Taming the terminological tempest in invasion science.

Standardised terminology in science is important for clarity of interpretation and communication. In invasion science - a dynamic and rapidly evolving discipline - the proliferation of technical terminology has lacked a standardised framework for its development. The result is a convoluted and inconsistent usage of terminology, with various discrepancies in descriptions of damage and interventions. A standardised framework is therefore needed for a clear, universally applicable, and consistent terminology to promote more effective communication across researchers, stakeholders, and policymakers. Inconsistencies in terminology stem from the exponential increase in scientific publications on the patterns and processes of biological invasions authored by experts from various disciplines and countries since the 1990s, as well as publications by legislators and policymakers focusing on practical applications, regulations, and management of resources. Aligning and standardising terminology across stakeholders remains a challenge in invasion science. Here, we review and evaluate the multiple terms used in invasion science (e.g. 'non-native', 'alien', 'invasive' or 'invader', 'exotic', 'non-indigenous', 'naturalised', 'pest') to propose a more simplified and standardised terminology. The streamlined framework we propose and translate into 28 other languages is based on the terms (i) 'non-native', denoting species transported beyond their natural biogeographic range, (ii) 'established non-native', i.e. those non-native species that have established self-sustaining populations in their new location(s) in the wild, and (iii) 'invasive non-native' - populations of established non-native species that have recently spread or are spreading rapidly in their invaded range actively or passively with or without human mediation. We also highlight the importance of conceptualising 'spread' for classifying invasiveness and 'impact' for management. Finally, we propose a protocol for classifying populations based on (i) dispersal mechanism, (ii) species origin, (iii) population status, and (iv) impact. Collectively and without introducing new terminology, the framework that we present aims to facilitate effective communication and collaboration in invasion science and management of non-native species.

Interferon-induced protein with tetratricopeptide repeats 5 of black fruit bat (Pteropus alecto) displays a broad inhibition of RNA viruses.

Bats are natural host reservoirs and have adapted a unique innate immune system that permits them to host many viruses without exhibiting symptoms. Notably, bat interferon stimulated genes (ISGs) have been shown to play antiviral roles. Interferon induced protein with tetratricopeptide repeats 5 (IFIT5) is a well-characterised ISG in humans with antiviral activities against negative-sense RNA viruses via inhibiting viral transcription. Here, we aim to investigate if Pteropus alecto (pa) IFIT5 (paIFIT5) possess the ability to inhibit negative-sense RNA viruses. Initially, gene syntenic and comparative structural analyses of multiple animals highlighted a high level of similarity between Pteropus alecto and human IFIT5 proteins. Our results showed that paIFIT5 was significantly inducible by viral and dsRNA stimulation. Transient overexpression of paIFIT5 inhibited the replication of vesicular stomatitis virus (VSV). Using minireplicon and transcription reporter assays, we demonstrated the ability of paIFIT5 specifically to inhibit H17N10 polymerase activity. Mechanistically, we noticed that the antiviral potential of paIFIT5 against negative sense RNA viruses was retributed to its interaction with 5'ppp containing RNA. Taken together, these findings highlight the genetic and functional conservation of IFIT5 among mammals.

Dehydrogenation and Transfer Hydrogenation of Alkenones to Phenols and Ketones on Carbon-Supported Noble Metals.

The catalytic dehydrogenation of substituted alkenones on noble metal catalysts supported on carbon (Pt/C, Pd/C, Rh/C, and Ru/C) was investigated in an organic phase under inert conditions. The dehydrogenation and semihydrogenation of the enone starting materials resulted in aromatic compounds (primary products), saturated cyclic ketones (secondary products), and cyclic alcohols (minor products). Pd/C exhibits the highest catalytic activity, followed by Pt/C and Rh/C. Aromatic compounds remain the primary products, even in the presence of hydrogen donors. Joint experimental and theoretical analyses showed that the four catalytic materials stabilize a common dienol intermediate on the metal surfaces, formed by keto-enol tautomerization. This intermediate subsequently forms aromatic products upon dehydrogenation. The binding orientation of the enone reactants on the catalytic surface is strongly metal-dependent, as the M-O bond distance changes substantially according to the metal. The longer M-O bonds (Pt: 2.84 Å > Pd: 2.23 Å > Rh: 2.17 Å > Ru: 2.07 Å) correlate with faster reaction rates and more favorable keto-enol tautomerization, as shorter distances correspond to a more stabilized starting material. Tautomerization is shown to occur via a stepwise surface-assisted pathway. Overall, each of the studied metals exhibits a distinct balance of enthalpy and entropy of activation (ΔH°‡, ΔS°‡), offering unique possibilities in the realm of enone dehydrogenation reactions that can be achieved by suitable selection of catalytic materials.

Endoscopic Submucosal Dissection for Resections Larger than 10 cm: Outcomes from a Portuguese Center.

Background: Endoscopic submucosal dissection (ESD) is a minimally invasive technique for en bloc resection of superficial neoplastic lesions, independent of their size. However, for giant gastrointestinal superficial neoplasia, the risk of invasive cancer is higher, and ESD is typically challenging. Despite the increasing literature on giant resections, data on their efficacy and safety are still lacking. Objective: The aim of this study was to describe ESD outcomes from a Portuguese center, compare them with other international studies, and analyze the possible risk factors influencing outcomes. Methods: We conducted a retrospective single-center review using a prospectively collected database, including patients with rectal ESD resections larger than 10 cm, between January 2016 and December 2021. Clinical, procedural, and pathological data were collected and analyzed. Revision of the literature for comparison with international results was done through PubMed. Data were analyzed and statistical analysis performed, using Microsoft Excel and SPSS, to identify significant risk factors. Results: The study included 15 rectal resections, with a mean diameter of 140.9 mm (range 105-270), corresponding to lesions of 125.9 mm (87-238). The overall en bloc resection rate was 100% (n = 15). According to ESGE criteria, procedure was considered curative in 53.3% (n = 8), non-curative with high risk in 13.3% (n = 2), and local-risk recurrence in 33.3% (n = 5). Adverse events occurred in 26.7% (n = 4): 1 minor perforation and 3 stenosis, most endoscopically managed. For non-curative resections with local-risk recurrence, surveillance without adjuvant therapy was performed in all cases. For high-risk non-curative resections, surgery was performed in 1 patient and adjuvant chemoradiation therapy in another. Follow-up (mean 16 months) demonstrated a recurrence rate of 0%. Statistical analysis revealed resection size ≥20 cm as a risk factor for perforation (p value 0.067), and involvement of ≥90% of the circumference and procedural time ≥4 h as risk factors for stenosis (p value 0.029 and 0.009, respectively). Conclusions: Although challenging, ESD for giant lesions seems effective and safe, with a still relevant rate of complications, which were mostly endoscopically treated. Rigorous characterization of lesions is crucial to predict and avoid complications or the need for therapy escalation.

Background: A dissecao endoscopica da submucosa (DES) e uma tecnica minimamente invasiva para ressecao em bloco de tumores superficiais, independentemente do seu tamanho. No entanto, nas neoplasias superficiais gastrointestinais gigantes, o risco de cancro invasivo esta aumentado e a DES e tipicamente desafiante. Apesar do incremento da literatura acerca de ressecoes gigantes, dados da sua eficacia e seguranca sao ainda escassos. Objetivo: Descricao de outcomes de DES de um centro portugues e comparacao com estudos internacionais. Analise de eventuais fatores de risco influenciando os outcomes. Métodos: Revisao retrospetiva de um centro, usando a sua base de dados prospectivamente colhida, incluindo pacientes com ressecoes rectais por DES maiores que 10 cm, entre janeiro 2016 e dezembro 2021. Dados clinicos, endoscopicos e patologicos foram colhidos e analisados. A literatura foi revista atraves do PubMed, para comparacao com resultados internacionais. A analise dos resultados e estatistica foi realizada, utilizando o Microsoft Excel e SPSS, para a identificacao de fatores de risco com impacto significativo nos outcomes. Resultados: O estudo incluiu um total de 15 ressecoes retais, com uma media de diametros de 140,9 mm (intervalo 105­270), correspondendo a lesoes 125,9 mm (intervalo 87­238). A taxa de ressecao em bloco foi de 100% (n = 15). Segundo os criterios da ESGE, o procedimento foi curativo em 53,3% (n = 8), nao curativo com alto risco em 13,3% (n = 2) e com risco de recorrencia local em 33,3% (n = 5). Eventos adversos ocorreram em 26,7% (n = 4): 1 microperfuracao e 3 estenoses, a maioria geridas endoscopicamente. Os 5 casos nao curativos com risco de recorrencia local ficaram apenas sob vigilancia. Nas resseccoes nao curativas de alto risco, um paciente foi submetido a cirurgia e outro a quimioradioterapia adjuvante. O follow-up (media de 16 meses) demonstrou uma taxa de recorrencia de 0%. A analise estatistica demonstrou o tamanho da resseccao ≥20 cm como fator de risco significativo para perfuracao (p value 0.067); e envolvimento de ≥ 90% da circunferencia do lumen e tempo de procedimento ≥4h como fatores de risco significativos para estenose (p value 0.029 e 0.009, respetivamente). Conclusão: Apesar de desafiante, a DES para lesoes gigantes parece eficaz e segura, com uma taxa de complicacoes importante, possiveis de tratamento endoscopico. A caracterizacao rigorosa destas lesoes e crucial para predizer e evitar complicacoes ou a necessidade de escalada terapeutica.

Novel TLR4-Activating Vaccine Adjuvant Enhances the Production of Enterococcus faecium-binding Antibodies.

Vaccines are one of the greatest achievements of modern medicine. Due to their safer profile, the latest investigations usually focus on subunit vaccines. However, the active component often needs to be coupled with an adjuvant to be effective and properly trigger an immune response. We are developing a new synthetic monosaccharide-based TLR4 agonist, such as glucosamine-derived compounds FP18 and FP20, as a potential vaccine adjuvant. In this study, we present a new FP20 derivative, FP20Hmp, with a hydroxylated ester linked to the glucosamine core. We show that the modification introduced improves the activity of the adjuvant and its solubility. This study presents the synthesis of FP20Hmp, its in vitro characterization, and in vivo activity while coupled with the ovalbumin antigen or in formulation with an enterococcal antigen. We show that FP20Hmp enables increased production of antigen-specific antibodies that bind to the whole bacterium.