Dysregulation of Neuronal Nicotinic Acetylcholine Receptor–Cholesterol Crosstalk in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a set of complex neurodevelopmental diseases that include impaired social interaction, delayed and disordered language, repetitive or stereotypic behavior, restricted range of interests, and altered sensory processing. The underlying causes of the core symptoms remain unclear, as are the factors that trigger their onset. Given the complexity and heterogeneity of the clinical phenotypes, a constellation of genetic, epigenetic, environmental, and immunological factors may be involved. The lack of appropriate biomarkers for the evaluation of neurodevelopmental disorders makes it difficult to assess the contribution of early alterations in neurochemical processes and neuroanatomical and neurodevelopmental factors to ASD. Abnormalities in the cholinergic system in various regions of the brain and cerebellum are observed in ASD, and recently altered cholesterol metabolism has been implicated at the initial stages of the disease. Given the multiple effects of the neutral lipid cholesterol on the paradigm rapid ligand-gated ion channel, the nicotinic acetylcholine receptor, we explore in this review the possibility that the dysregulation of nicotinic receptor-cholesterol crosstalk plays a role in some of the neurological alterations observed in ASD.

Principais técnicas fisioterápicas em cães: Revisão de literatura

É crescente na medicina veterinária as técnicas e especialidades voltadas ao aprimoramento e prestação de serviços que objetivam o bem-estar animal e qualidade de vida. Nesse sentido, a reabilitação animal busca a recuperação e reestabelecimento das funções do animal, ou de forma que fique mais próxima das condições normais, seja promovendo analgesia, resolução da inflamação, a melhoria na locomoção, bem como a redução do desconforto. A fisioterapia, por sua vez, é uma especialidade que desenvolve várias técnicas, podendo ser utilizada para promover tanto a estimulação local como generalizada. Pode também ser empregada como método conservador ou, ainda, ser associada à métodos cirúrgicos. Apresentamos de maneira geral e sintetizada, conceitos, técnicas e a importância da reabilitação física animal, por meio de uma revisão bibliográfica, buscando realizar uma abordagem voltada às alterações ortopédicas, neurológicas e doenças degenerativas e/ou crônicas. Para isso, foi realizada uma revisão de literatura em bases de dados e livros, publicados entre 2000 a 2020, tanto em língua inglesa como portuguesa, com os seguintes descritores: cães, medicina veterinária, reabilitação, fisioterapia, fisiatria, controle da dor, ortopedia, medicina veterinária integrativa. A fisioterapia demonstra-se benéfica no tratamento e prevenção de patologias ortopédicas, neurológicas e também no controle da obesidade canina. Várias técnicas e equipamentos podem ser empregados, sendo o protocolo terapêutico individual, devendo sempre ser elaborado com base nas necessidades e limitações de cada paciente. Para isso, é imprescindível que o médico veterinário fisiatra tenha pleno conhecimento das técnicas de reabilitação. Palavras-chave: Reabilitação, ortopedia, atrofia, medicina integrativa Abstract It is growing in veterinary medicine the techniques and specialties focused on the improvement and provision of services that aim to promote the welfare and quality of life of the animal. In this sense, animal rehabilitation seeks the recovery and reestablishment of the animal's functions, or in a way that is closer to normal conditions, by either promoting pain relief, reducing inflammation, improving locomotion, as well as reducing discomfort. Physiotherapy, in turn, is a specialty that develops various techniques, and can be used to promote both local and generalized stimulation. It can also be used as a conservative method or, still, be associated with surgical treatment. We present, in a general and synthesized way, concepts, techniques, and the importance of animal physical rehabilitation, by means of a bibliographic review, trying to make an approach focused on orthopedic and neurological alterations, and degenerative and/or chronic diseases. For this, we conducted a literature review in databases and books, published between 2000 and 2020, both in English and Portuguese, with the following descriptors: dogs, veterinary medicine, rehabilitation, physiotherapy, physiatry, pain control, orthopedics, integrative veterinary medicine. Physiotherapy has proven beneficial in the treatment and prevention of orthopedic and neurological pathologies, and also in the control of canine obesity. Several techniques and equipment can be used, and the therapeutic protocol is individual, and should always be prepared based on the needs and limitations of each patient. For this, it is essential that the veterinary physiatrist has full knowledge of rehabilitation techniques. Keywords: Rehabilitation, orthopedics, atrophy, integrative medicine

HYPONATREMIAAS A PROGNOSTIC FACTOR IN COVID-19

Introduction: Hyponatremia has already been described in sever acute respiratory syndrome (SARS) which was associated with poor outcome. This is also seen in sars-cov-2 for the most part with moderate to severe infection. Thus, hyponatremia can be taken as a prognostic factor. Severe hyponatremia has long been recognized as a direct cause of death or permanent neurological alterations. Patients with Coronavirus disease 2019 (COVID-19), caused by SARS-COV2 infection, can develop a potentially fatal rapid-onset pneumonia. Aim:To describe the impact of hyponatremia on COVID-19 patient outcome. Material and methods:It is a retrospective study on the patient admitted in Peerless Hospital and diagnosed COVID 19 positive, conrmed by RTPCR or Gene – X pert. Data of the serum sodium concentrations of patients with COVID19 infection after admission and analysed the relationship between the serum sodium and severity of the illness and its outcome. 320 participants were taken. Result: In our study, 131(40.9%) COVID-19 patients were in Hyponatremic and 189(59.1%) COVID-19 patients were in Normonatremic group. High Systolic blood pressure, High Diastolic blood pressure, low SPO2 and high Respiratory rate was observed in Hyponatremic COVID-19 patients which were statistically signicant. 272 (85.0%) patients were Alive and 48 (15.0%) patients were Death. Conclusion: Our study showed an independent relationship between 131 Hyponatremic COVID-19 patients at admission and transfer to ICU, use of mechanic ventilation or death. Our results support the test sodium in hospitalized COVID-19 patients as another bedside screening tool for early identication of patients at high risk of poor outcome.

Catatonic syndrome as the presentation of encephalitis in association with COVID-19

COVID-19 has shown different neurological manifestations even sometimes there are the initial or the main presentation.The following case report is about a middle-aged woman who, over 3 days, developed fever, clinical neurological alterations (stupor, muteness, fixed gaze and catatonia), cerebrospinal fluid (16 lymphocytes) and an electroencephalogram (EEG) (4–6 Hz generalised activity) with characteristics of encephalitis. A serum IgG, IgM, nasopharyngeal swab PCR for SARS-CoV-2. The patient responded positively to support measures, symptomatic and corticosteroid treatment. At discharge, the patient was independent and improved considerably.We report the presence of catatonia as a possible and atypical manifestation of encephalitis in association with COVID-19.

PREJUÍZOS DO DIAGNÓSTICO TARDIO EM HANSENÍASE: UMA REVISÃO INTEGRATIVA/ IMPAIRMENTS OF DELAY IN DIAGNOSIS OF LEPROSY: AN INTEGRATIVE REVIEW

RESUMO Introdução: A hanseníase é uma doença crônica infectocontagiosa com período de incubação prolongado. Pode se apresentar com alterações cutâneas, neurológicas e até levar a incapacidades e deformidades. Apresenta caráter hiperendêmico no Tocantins. Objetivo: Fazer uma revisão da literatura em periódicos nacionais a respeito dos prejuízos de um diagnóstico tardio em Hanseníase. Metodologia: Trata-se de uma revisão integrativa com a pesquisa dos artigos obtidos através de bases de dados da Biblioteca Virtual em Saúde (BVS). Foram selecionados trabalhos de 2015 a 2019 e 27 publicações foram incluídas no estudo. Resultados e Discussão: A demora do reconhecimento da doença aumenta as chances de incapacidades. Ainda é uma patologia estigmatizante, na qual os seus portadores sofrem preconceitos, podendo levar a sintomas depressivos. Considerações Finais: As incapacidades e as deformidades geradas se associam a demora do seu reconhecimento, além do potencial para prejuízos biopsicossociais que diminuem a qualidade de vida da população afetada. Palavras-Chave: Hanseníase; Diagnóstico; Pessoas com Deficiência. ABSTRACT: Introduction: Leprosy is a chronic disease with infectious character, with extended incubation period. It may present cutaneous, neurological alterations that can lead to disabilities and deformities. With a hyperendemic character in Tocantins. Objective: Make an integrative review of literature in national periodics concerning harms of a delay diagnosis in leprosy. Method: This is an integrative review with articles search through the virtual health library (BVS). Also Occured from december 2019 to February 2020. Publications from 2015 to 2019, 27 publications were included in the study. Results and discussions: The delay of acknowledgement the leprosy may increase the chance of disabilities. It also continue as a stigmatizing pathology that the affected suffers prejudices and may lead to depressives symptoms. Conclusions: The disabilities and desformities generated are associated with the delay of his acknowlegdment, and furthermore the potencial for biopshycosocial harms that lower the life quality of the affected population. Keywords: Leprosy; Diagnosis; Disabled Persons.

La sindrome di Chediak-Higashi a esordio tardivo

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder caused by mutations in the CHS1/LYST gene, encoding for LYST protein, involved in lysosomal trafficking. It is characterized by recurrent bacterial infections, oculocutaneous albinism, silver hair, haematological and neurological alterations and a possible evolution towards the socalled accelerated phase (haemophagocytic lymphohistiocytosis). It is classified in a classic form, with infantile onset, lethal if bone marrow transplantation is not promptly performed, and in an atypical form, with adolescent/adult onset, for which a more conservative approach may be possible. The paper describes a case of hypertrophic-hyperplastic gingivopathy associated with leuko-neutropenia. The evaluation of the bone marrow smear raised the suspicion of CHS and the analysis of the clinical history highlighted the presence of suggestive criteria for atypical CHS. The genetic investigation confirmed the diagnosis.

Neurological Alterations and Testicular Damages in Aging Induced by D-Galactose and Neuro and Testicular Protective Effects of Combinations of Chitosan Nanoparticles, Resveratrol and Quercetin in Male Mice

Aging is a neurological disease that is afforded by incidence of oxidative stress. Chitosan has received global interests due to its wide medical uses. Quercetin (Q) is a bioflavonoid and widely distributed in vegetables and fruits. Resveratrol is considered as a potent antioxidant and is a component of a wide range of foods. The using of either chitosan nanopartciles (CH-NPs), querectin (Q), and resveratrol (RV) to reduce the oxidative stress and biochemical alterations on brain and testicular tissues induced by D-galactose (DG) (100 mg/Kg) were the aim of the present study. This study investigated the probable protective effects of CH-NPs in two doses (140,280 mg/Kg), Q (20 mg/Kg) and RV (20 mg/Kg), against DG induced aging and neurological alterations. Brain antioxidant capacity as malonaldehyde (MDA), catalase (CAT), and glutathione reductase (GRx), as well as histopathological damages of the brain and testicular tissues were measured. The DG treated group had significantly elevated the oxidative stress markers by 96% and 91.4% in brain and testicular tissues respectively and lower significantly the antioxidant enzyme activities of both brain and testicular tissues than those of the control group by 86.95%, 69.27%, 83.07%, and 69.43%. Groups of DG that treated with a combination of CH-NPs in two doses, Q and RV, the levels of oxidative stress marker declined significantly by 68.70%, 76.64% in brain tissues and by 74.07% and 76.61% in testicular tissues, and the enzymatic antioxidants increased significantly by 75.55%, 79.24%, 62.32%, and 61.97% as compared to the DG group. The present results indicate that CH-NPs, Q, and RV have protective effects against DG-induced brain and testis tissue damage at the biochemical and histopathological levels. Mechanisms of this protective effect of used compounds against neurological and testicular toxicity may be due to the enhanced brain and testis antioxidant capacities.

Clinical, anatomopathological, and immunohistochemical findings of a transitional cell carcinoma from nasal cavity, frontal and ethmoidal sinus with meningoencephalic invasion in a dog

Background: Primary neoplasms of the nasal cavity and sinuses are uncommon in domestic animals, most of which are of epithelial origin, being adenocarcinoma the most common tumor diagnosed in this region. Some malignant nasal cavity neoplasms may invade the brain causing clinical neurological signs, as well as purulent nasal secretion and epistaxis. Case Description: A case of neoplasm is reported in a 14-year-old pincher presenting dyspnea, epistaxis, and neurological alterations. Necropsy revealed the presence of a mass in the oral cavity vestibule, and another in the whole nasal cavity with invasion of the cribiform plate, meninges and brain. Squamous cells carcinoma was diagnosed in the oral cavity and transitional carcinoma in the nasal cavity. The immunohistochemistry confirmed that the brain infiltration was of the same origin as the nasal cavity neoplasm. Conclusion: The present report describes a rare case of transitional carcinoma of the nasal cavity as well as the frontal and ethmoidal sinuses with brain invasion, confirmed by immunohistochemistry. It is extremely important for veterinarians to include neoplasms in their differential diagnoses, when these animals show chronic respiratory signs and neurological alterations that do not improve with appropriate treatment, always associating with complementary exams, for correct diagnosis establishment and prognosis formulation.

Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals

SummaryNeurons draw on alternative splicing for their increased transcriptomic complexity throughout animal phylogeny. To delve into the mechanisms controlling the assembly and evolution of this regulatory layer, we characterized the neuronal microexon program in Drosophila and compared it with that of mammals. We found that in Drosophila, this splicing program is restricted to neurons by the post-transcriptional processing of the enhancer of microexons (eMIC) domain in Srrm234 by Elav and Fne. eMIC deficiency or misexpression leads to widespread neurological alterations largely emerging from impaired neuronal activity, as revealed by a combination of neuronal imaging experiments and cell-type-specific rescues. These defects are associated with the genome-wide skipping of short neural exons, which are strongly enriched in ion channels. Remarkably, we found no overlap of eMIC-regulated exons between flies and mice, illustrating how ancient post-transcriptional programs can evolve independently in different phyla to impact distinct cellular modules while maintaining cell-type specificity.