Fundação de Amparo à Pesquisa do Estado de São Paulo

This article reconstructs Hans Kelsen’s critique of sovereignty, arguing that his Pure Theory of Law demonstrates the concept is both inherently contradictory and normatively irrelevant. Kelsen’s critique first exposes the logical paradox of positing any sovereign entity above the law. Second, it refutes the dualist separation of national and international law as equally contradictory. Ultimately, the article shows that even within a coherent monist model, the choice of primacy (national or international) does not alter the substance of legal norms, rendering the concept of sovereignty theoretically irrelevant for jurisprudence.

Schistosomiasis affects nearly 250 million people, primarilyinlow-income regions. Aligned with the Sustainable Development Goals,the WHO roadmap highlights the urgent need for new therapeutic alternativesto praziquantel, the only available drug for schistosomiasis treatment.Natural products, including γ-lactones from Annonaceae species,have shown promising anthelmintic activity. The present work aimedto investigate the anthelmintic potential of the natural acetogenin3-hydroxy-4-methylene-2-(n-eicos-11′-yn-19′-enyl)­but-2-enolide(HMB) isolated from Porcelia macrocarpa seeds, againstSchistosoma mansoni. HMB was characterized by NMR and ESI-HRMS analysis, andits toxicity was assessed using mammalian cell lines and Caenorhabditis elegans. HMB exhibited schistosomicidalactivity in vitro (EC50 = 19.3–24.6μg/mL) with no detectable toxicity. in vivo, a single oral dose of 400 mg/kg resulted in a 92.9% reduction inworm burden, which exceeded the 88.2% reduction achieved with praziquantel.Additionally, a 94–100% reduction in egg burden was achieved.Remarkably, the efficacy of HMB was maintained at lower doses. Forexample, a 65% reduction in worm burden was achieved at 100 mg/kg,whereas praziquantel achieved only 15% at the same dose. Therefore,HMB from P. macrocarpa exhibits potentantischistosomal efficacy in vivo, supporting theirfurther development as promising candidates for schistosomiasis therapy.

This article presents a Brazilian Portuguese translation of book 2 of Quintus of Smyrna’s Posthomerica, a Greek epic from the 3rd century CE that narrates in 14 books the events of the Trojan War occurring between the Iliad and the Odyssey. Book 2 recounts the episode traditionally called the “Aethiopis”, which recounts the arrival of Memnon and his Ethiopian warriors to aid the Trojans and take Hector’s place as the bulwark of Priam’s army. This is the second hero who presents himself as a new hope for the Trojans in the Posthomerica, since he is anteceded by Penthesilea, the Amazon queen who dies in book 1. The fate of Memnon is not different from that of the heroine: after killing Antilochus, Nestor’s son, he attracts the fury of Achilles upon himself, who ends up killing him after a relentless duel.

Background: The retina plays a vital role in vision, and its impairment can cause significant visual deficits. Current retinal disease treatments range from conventional anti-inflammatory drugs to advanced anti-VEGF therapies and monoclonal antibodies. TnP, a novel synthetic peptide in preclinical development, has demonstrated therapeutic potential in chronic inflammatory conditions such as multiple sclerosis and asthma due to its immunomodulatory properties. Using zebrafish—which share significant genetic homology with humans—we investigated TnP’s effects on retinopathy models mimicking diabetic retinopathy (DR) through either cobalt chloride (CoCl2)-induced hypoxia or light-induced retinal damage (LIRD). Methods: We employed two retinal injury models (CoCl2-induced hypoxia and LIRD) and subjected them to TnP treatment, assessing the outcomes through visual–motor response testing and histological examination. Results: CoCl2 exposure impaired swimming activity, while light damage reduced the movement distance. Both models induced distinct retinal morphological changes. Although TnP failed to reverse most injury effects, it specifically restored the inner plexiform layer (IPL)’s thickness. Conclusions: Our findings suggest that TnP may enhance neuronal plasticity by promoting cell proliferation and synaptic connectivity. While showing promise as a therapeutic candidate for retinal and neurodegenerative disorders, TnP might achieve optimal efficacy when combined with complementary treatments.

Neuronal Ceroid Lipofuscinosis 11 (CLN11) is an ultra-rare subtype of adult-onset Neuronal Ceroid Lipofuscinosis. Its phenotype is variable and not fully known. A 21-year-old man was evaluated in our neurogenetic outpatient clinic for early onset complex phenotype, including learning difficulties, cerebellar ataxia, cone-rod dystrophy, epilepsy, and dystonia. The patient was submitted to neurological and neuropsychological assessment, neuro-ophthalmological tests, brain MRI, EEG and whole exome sequencing. A homozygous frameshift variant (NM_002087.4: c.768_769dup; p.Gln257Profs*27) was found. Distinct type descriptions, as in this case, increase the clinical spectrum of the disease.

Objetivo: verificar o efeito do treino de habilidades e dos cenários simulados realizados de forma subsequente ou tardia na motivação para aprendizagem de estudantes de medicina. Método: estudo experimental pré e pós-teste com grupo controle e intervenção. Participaram 50 estudantes do segundo ano de medicina, randomizados em dois grupos: grupo controle (exposição dialogada, treino de habilidades e cenários simulados após 12h) e grupo intervenção (exposição dialogada, treino de habilidades e cenários simulados após 21 dias). A Escala de Motivação Situacional foi utilizada para análise. Resultados: todos os estudantes apresentaram aumento na motivação. No grupo controle, a motivação intrínseca aumentou antes e após o cenário simulado (p=0,011). No grupo intervenção, a motivação intrínseca aumentou antes e após o treino de habilidades (p=0,013), antes e após o cenário simulado (p=0,024) e após o treino de habilidades comparado ao cenário simulado (p=0,011), com redução da amotivação (p=0,035). Conclusão: o treino de habilidades e os cenários simulados aumentam a motivação dos estudantes. Contudo, é necessário compreender melhor os impactos dos diferentes intervalos entre as atividades.

The microbiota stability, diversity, and composition are pillars for an efficient and beneficial symbiotic relationship between its host and itself. Microbial dysbiosis, a condition where a homeostatic bacterial community is disturbed by acute or chronic events, is a predisposition for many diseases, including local and systemic inflammation that leads to metabolic syndrome, diabetes, and some types of cancers. Classical dysbiosis occurs in the large intestine. During this period, pathogenic strains can multiply, taking advantage of the compromised environment. This overgrowth triggers an exaggerated inflammatory response from the human immune system due to the weakened integrity of the intestinal barrier. Such inflammation can also directly influence higher polyp formation and/or tumorigenesis. Prebiotics can be instrumental in preventing or correcting dysbiosis. Prebiotics are molecules capable of serving as substrates for fermentation processes by gut microorganisms. This can promote returning the intestinal environment to homeostasis. Effective prebiotics are generally specific oligo- and polysaccharides, such as FOS or inulin. However, the direct effects of prebiotics on intestinal epithelial and immune cells must also be taken into consideration. This interaction happens with diverse prebiotic nondigestible carbohydrates, and they can inhibit or decrease the inflammatory response. The present work aims to elucidate and describe the different types of prebiotics, their influence, and their functionalities for health, primarily focusing on their ability to reduce and control inflammation in the intestinal epithelial barrier, gut, and systemic environments.