Targeted and Self-Adjuvated Nanoglycovaccine Candidate for Cancer Immunotherapy.

Advanced-stage solid primary tumors and metastases often express mucin 16 (MUC16), carrying immature glycans such as the Tn antigen, resulting in specific glycoproteoforms not found in healthy human tissues. This presents a valuable approach for designing targeted therapeutics, including cancer glycovaccines, which could potentially promote antigen recognition and foster the immune response to control disease spread and prevent relapse. In this study, we describe an adjuvant-free poly(lactic-co-glycolic acid) (PLGA)-based nanoglycoantigen delivery approach that outperforms conventional methods by eliminating the need for protein carriers while exhibiting targeted and adjuvant properties. To achieve this, we synthesized a library of MUC16-Tn glycoepitopes through single-pot enzymatic glycosylation, which were then stably engrafted onto the surface of PLGA nanoparticles, generating multivalent constructs that better represent cancer molecular heterogeneity. These glycoconstructs demonstrated affinity for Macrophage Galactose-type Lectin (MGL) receptor, known to be highly expressed by immature antigen-presenting cells, enabling precise targeting of immune cells. Moreover, the glycopeptide-grafted nanovaccine candidate displayed minimal cytotoxicity and induced the activation of dendritic cells in vitro, even in the absence of an adjuvant. In vivo, the formulated nanovaccine candidate was also nontoxic and elicited the production of IgG specifically targeting MUC16 and MUC16-Tn glycoproteoforms in cancer cells and tumors, offering potential for precise cancer targeting, including targeted immunotherapies.

Predictores pronósticos de desarrollo neurológico en recién nacidos a término con crisis neonatales / Neurodevelopmental outcome predictors of term newborns with neonatal seizures

Introducción: El peso específico de las crisis neonatales en el pronóstico neurológico de recién nacidos a término no se conoce bien, por lo que el objetivo del estudio era describir predictores pronósticos en crisis neonatales. Sujetos y métodos: Estudio observacional prospectivo de recién nacidos a término con crisis clínicas en un centro terciario (2009-2018). Pronóstico adverso se definió como muerte, retraso global del desarrollo, parálisis cerebral o epilepsia. Se analizaron las características perinatales, la etiología, los hallazgos electroencefalográficos, la neuroimagen y los tratamientos antiepilépticos siguiendo un modelo de regresión logística. Resultados: Se incluyó a un total de 102 recién nacidos (52 de los cuales tenían desarrollo normal). Se registraron 12 fallecimientos. En el grupo de supervivientes, 38 niños tuvieron un pronóstico desfavorable (28 con retraso global del desarrollo, 27 con parálisis cerebral, 21 con epilepsia). De las variables pronósticas identificadas en el análisis univariante, las complicaciones perinatales, el inicio de las crisis en el primer día de vida, la actividad basal anormal moderada a grave, un patrón anormal en el electroencefalograma de amplitud integrada y la respuesta al tratamiento continuaron mostrándose como independientemente asociadas a pronóstico adverso después de aplicar un modelo de regresión logística. Conclusiones: Existen datos contradictorios sobre marcadores subrogados en crisis neonatales. Aparte de confirmar el valor predictivo de variables previamente descritas, se halló que la monitorización con electroencefalograma de amplitud integrada constituye una prometedora herramienta diagnóstica. En el futuro, se debería extender su utilización en el abordaje de estos pacientes, lo que sería de vital importancia para un diagnóstico y un tratamiento precoces

Introduction: The concrete burden of neonatal seizures in neurodevelopmental outcome of term newborns is still unknown in literature. The aim of this study was to describe prognostic predictors in neonatal seizures. Subjects and methods: Observational prospective study of term neonates with clinical seizures from a tertiary center (2009-2018). Adverse outcome was determined as death, global developmental delay, cerebral palsy or epilepsy. Perinatal characteristics, etiology, electrographic features, neuroimaging and antiepileptic treatment were analyzed in a logistic regression model. Results: A total of 102 newborns were included (52 infants with normal outcome). Twelve fatalities were registered. In the survival group, 38 children had an adverse outcome (28 global developmental delay, 27 cerebral palsy, 21 epilepsy). From the prognostic variables identified in univariate analysis, perinatal complications, seizure onset in the first day of life, moderate to severe abnormal background activity, abnormal amplitude-integrated EEG pattern, and treatment response remained independently associated with adverse outcome after a logistic regression model. Conclusions: There is conflicting data about surrogate markers in neonatal seizures. Aside from confirming the predictive value of previously described variables, we observed that amplitude-integrated EEG monitoring is a forthcoming prognostic tool. Future approaches may include a wider use of amplitude-integrated EEG monitoring, being crucial for timely seizure identification and prompt treatment

Variante faringo-cérvico-braquial da síndrome de Guillain-Barré:uma causa rara de disfunção bulbar aguda em crianças / Pharyngeal-cervical-brachial variant of Guillain-Barré syndrome:a rare cause of acute bulbar dysfunction in children

Aims: To report a case of pharyngeal-cervical-brachial variant of Guillain-Barré syndrome, which is characterized by rapidly progressivebulbar palsy with upper limb, neck and oropharyngeal involvement. It is a rare disorder in childhood and most cases have been described inadolescents.Case Description: A seven year-old-boy presented with dysarthria, hoarseness, dysphagia, facial diplegia and bilateral progressive upperlimb weakness. These symptoms started two weeks after a gastrointestinal infection. Nerve conduction studies were compatible with an acutedemyelinating polyneuropathy in the upper extremities. Anti-ganglioside antibodies in the serum (anti-GT1a, GD1a, GQ1b) were positiveand Campylobacter jejuni was isolated from stools. The patient was treated with intravenous immunoglobulin and needed ventilatory supportduring the first 12 days of admission. He was discharged at day 15 showing improvement of his neurological deficits. He fully recovered aftereleven months of follow-up.Conclusions: Although pharyngeal-cervical-brachial variant of Guillain-Barré syndrome is uncommon in children, it should be consideredin a child with acute bulbar dysfunction because a timely diagnosis allows the early institution of therapeutic measures that can be lifesaving.

Objetivos: Relatar um caso da variante faringo-cervico-braquial da síndrome de Guillain-Barré, que se caracteriza por paralisia bulbarrapidamente progressiva com envolvimento dos membros superiores, pescoço e região orofaríngea. É um diagnóstico raro na criança, ocorrendoa maioria dos casos em adolescentes.Descrição do Caso: Um menino de sete anos de idade iniciou com queixas de disartria, disfonia, disfagia, diplegia facial e fraqueza muscularprogressiva dos membros superiores. Estes sintomas surgiram duas semanas após uma infeção gastrointestinal. Os estudos eletrofisiológicosforam compatíveis com polineuropatia aguda desmielinizante nos membros superiores. Os anticorpos anti-gangliosídeo no plasma(anti-GT1a, GD1a, GQ1b) foram positivos e Campylobacter jejuni foi isolado nas fezes. O paciente foi tratado com imunoglobulina endovenosae necessitou de suporte ventilatório durante os primeiros 12 dias. Teve alta no 15º dia com melhora dos sintomas neurológicos. Recuperou-setotalmente após 11 meses de seguimento.Conclusões: Apesar da variante faringo-cervico-braquial ser pouco frequente em idade pediátrica, é um diagnóstico que deve ser consideradoperante uma criança com disfunção bulbar aguda, pois a identificação precoce permite instituir rapidamente medidas terapêuticas que podemevitar a morte.