Síndrome de Dravet − experiência de uma Unidade de Neuropediatria

Introduction: Dravet syndrome (DS) is a rare and complex genetic epilepsy syndrome. The first seizures are generally induced by fever in the first year of life of a previously healthy child, and the condition is typically associated with impaired psychomotor development. The authors present a clinical review of DS patients followed at a Neuropediatric Unit of a level III Pediatric Hospital. Material and methods: Retrospective study of pediatric patients with DS followed at a Neuropediatric Unit between 2001 and 2019. Results: Twenty-two patients were diagnosed and followed in this institution. The median (interquartile range [IQR]) age at first seizure was 4.5 (4-5.75) months, which was described as generalized tonic-clonic, focal seizure, or focal to bilateral tonic-clonic seizure, and 95% of patients had fever during this first episode. Neuroimaging and first electroencephalogram (EEG) were normal in all patients. SCN1A gene mutations were detected in 21 (95%) patients. All patients underwent multiple antiepileptic drug (AED) regimens. Psychomotor development was delayed in 20 (91%) patients, and 13 (59%) presented ataxia. At the end of follow-up, the median (IQR) age was 19 (8-23) years, with no reported deaths. Discussion: The characteristics of the first DS seizures are crucial for diagnosis, which can be supported by genetic sequencing, with most patients presenting an SCN1A gene mutation. Neuroimaging and EEG are typically normal at disease onset, but most patients present EEG abnormalities over time. Seizure management can be challenging, requiring a combination of multiple AEDs. Conclusion: DS is a progressive disease associated with poor cognitive and motor skill outcomes, resulting in great morbidity. Early diagnosis can help avoid unnecessary studies, optimize the therapeutic strategy, allow genetic counseling, and improve long-term outcomes.info:eu-repo/semantics/publishedVersio

Efficient deep-red light-emitting electrochemical cells based on a perylenediimide-iridium-complex dyad

A two-layer light-emitting electrochemical cell device based on a new perylenediimide-iridium-complex dyad is presented emitting in the deep-red region with high external quantum efficiencies (3.27%).Costa Riquelme, Ruben Dario, [email protected] ; Orti Guillen, Enrique, [email protected] ; Bolink, Henk, [email protected] ; Gierschner, Johannes, [email protected]

An orally active formulation of angiotensin-(1-7) produces an antithrombotic effect

INTRODUCTION AND OBJECTIVE: The heptapeptide angiotensin-(1-7) is a component of the renin-angiotensin system, which promotes many beneficial cardiovascular effects, including antithrombotic activity. We have recently shown that the antithrombotic effect of angiotensin-(1-7) involves receptor Mas-mediated NO-release from platelets. Here, we describe an orally active formulation based on angiotensin-(1-7) inclusion in cyclodextrin [Ang-(1-7)- CyD] as an antithrombotic agent. Cyclodextrins are pharmaceutical tools that are used to enhance drug stability, absorption across biological barriers and gastric protection. METHOD: To test the antithrombotic effect of Ang-(1-7)-CyD, thrombus formation was induced in the abdominal vena cava of spontaneously hypertensive rats that were pretreated either acutely or chronically with Ang-(1-7)-CyD. Male Mas-knockout and wild-type mice were used to verify the role of the Mas receptor on the effect of Ang-(1-7)-CyD. RESULTS: Acute or chronic oral treatment with Ang-(1-7)-CyD promoted an antithrombotic effect (measured by thrombus weight; all values are, respectively, untreated vs. treated animals) in spontaneously hypertensive rats (acute: 2.86 + 0.43 mg vs. 1.14 + 0.40 mg; chronic: 4.27 + 1.03 mg vs. 1.39 + 0.68 mg). This effect was abolished in Mas-knockout mice (thrombus weight in Mas wild-type: 0.76 + 0.10 mg vs. 0.37 + 0.02 mg; thrombus weight in Mas-knockout: 0.96 + 0.11 mg vs. 0.87 + 0.14 mg). Furthermore, the antithrombotic effect of Ang-(1-7)-CyD was associated with an increase in the plasma level of Angiotensin-(1-7). CONCLUSION: These results show for the first time that the oral formulation Ang-(1-7)-CyD has biological activity and produces a Mas-dependent antithrombotic effect

Dimers and the Critical Ising Model on Lattices of genus>1

We study the partition function of both Close-Packed Dimers and the Critical Ising Model on a square lattice embedded on a genus two surface. Using numerical and analytical methods we show that the determinants of the Kasteleyn adjacency matrices have a dependence on the boundary conditions that, for large lattice size, can be expressed in terms of genus two theta functions. The period matrix characterizing the continuum limit of the lattice is computed using a discrete holomorphic structure. These results relate in a direct way the lattice combinatorics with conformal field theory, providing new insight to the lattice regularization of conformal field theories on higher genus Riemann Surfaces.Comment: 44 pages, eps figures included; typos corrected, figure and comments added to section

REGISTRO DE MUTAÇÃO MARROM EM QUERO-QUERO (Vanellus chilensis Molina, 1782), NO CENTRO-OESTE DO BRASIL

Chromatic mutations (aberrant plumage) in birds are not uncommon to register in the wild, but should be reported. Here we present a new case of chromatic mutation in Southern Lapwing (Vanellus chilensis), which present brown mutation. We believe this is the first case reported in a journal indexed in this aberration pattern for V. chilensis, given that the known cases are individuals with leucism and dilution. It is important to report cases of aberrant plumage in birds, focusing on future studies, serving as a basis for bringing together all the cases mentioned for regional and/or national lists, reporting the respective cases of mutations and affected species.Mutações cromáticas (plumagens aberrantes) em aves, não são incomuns de se registrar na natureza, mas devem ser divulgados. Apresentamos aqui um novo caso de mutação cromática em quero-quero (Vanellus chilensis), que apresenta mutação marrom. Acreditamos ser o primeiro caso divulgado em revista indexada nesse padrão de aberração para V. chilensis, tendo em vista que os casos conhecidos são de indivíduos com leucismo e diluição. É importante divulgar os casos de plumagens aberrantes em aves, com enfoque de estudos futuros, servindo de base para reunir todos os casos mencionados visando a elaboração de listas regionais e/ou nacionais, reportando os respectivos casos de mutações e espécies afetadas

Beyond Genetic Factors in Familial Amyloidotic Polyneuropathy: Protein Glycation and the Loss of Fibrinogen's Chaperone Activity

Familial amyloidotic polyneuropathy (FAP) is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR). This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease