High-throughput platforms for the screening of new therapeutic targets for neurodegenerative diseases

Despite the recent progress in the understanding of neurodegenerative disorders, a lack of solid fundamental knowledge on the etiology of many of the major neurodegenerative diseases has made it difficult to obtain effective therapies to treat these conditions. Scientists have been looking to carry out more-human-relevant studies, with strong statistical power, to overcome the limitations of preclinical animal models that have contributed to the failure of numerous therapeutics in clinical trials. Here, we identify currently existing platforms to mimic central nervous system tissues, healthy and diseased, mainly focusing on cell-based platforms and discussing their strengths and limitations in the context of the high-throughput screening of new therapeutic targets and drugs.This work had the financial support of Fundação para a Ciência e Tecnologia ( FCT ) through National Funds and, when applicable, co-financed by the FEDER through the PT2020 Partnership Agreement under the 4293 Unit I&D. D.N. Rocha acknowledges FCT for her PhD grant

Volatility leveraging in heart rate: Health vs disease

Heart Rate Variability (HRV) data exhibit long memory and time-varying conditional variance (volatility). These characteristics are well captured using Fractionally Integrated AutoRegressive Moving Average (ARFIMA) models with Generalised AutoRegressive Conditional Heteroscedastic (GARCH) errors, which are an extension of the AR models usual in the analysis of HRV. GARCHmod-els assume that volatility depends only on the magnitude of the shocks and not on their sign, meaning that positive and negative shocks have a symmetric effect on volatility. However, HRV recordings indicate further dependence of volatility on the lagged shocks. This work considers Exponential GARCH (EGARCH) models which assume that positive and negative shocks have an asymmetric effect (leverage effect) on the volatility, thus better copping with complex characteristics of HRV. ARFIMA-EGARCH models, combined with adaptive segmentation, are applied to 24 h HRV recordings of 30 subjects from the Noltisalis database: 10 healthy, 10 patients suffering from congestive heart failure and 10 heart transplanted patients. Overall, the results for the leverage parameter indicate that volatility responds asymmetrically to values of HRV under and over the mean. Moreover, decreased leverage parameter values for sick subjects, suggest that these models allow to discriminate between the different groups. © 2016 CCAL

Modeling volatility in heat rate variability

Modeling Heart Rate Variability (HRV) data has become important for clinical applications and as a research tool. These data exhibit long memory and time-varying conditional variance (volatility). In HRV, volatility is traditionally estimated by recursive least squares combined with short memory AutoRegressive (AR) models. This work considers a parametric approach based on long memory Fractionally Integrated AutoRegressive Moving Average (ARFIMA) models with heteroscedastic errors. To model the heteroscedasticity nonlinear Generalized Autoregressive Conditionally Heteroscedastic (GARCH) and Exponential Generalized Autoregressive Conditionally Heteroscedastic (EGARCH) models are considered. The latter are necessary to model empirical characteristics of conditional volatility such as clustering and asymmetry in the response, usually called leverage in time series literature. The ARFIMA-EGARCH models are used to capture and remove long memory and characterize conditional volatility in 24 hour HRV recordings from the Noltisalis database. © 2016 IEEE

CIDP na Idade Pediátrica - Desafio Diagnóstico

Introdução: A polirradiculoneuropatia desmielinizante inflamatória crónica (CIDP) é uma patologia auto-imune caracterizada pela desmielinização dos nervos periféricos e raízes espinhais, rara na idade pediátrica. Apresenta-se de forma progressiva ou mais raramente recorrente, tornando-se por vezes difícil o seu diagnóstico e o diagnóstico diferencial com Síndrome de Guillain-Barré. Caso Clínico: Criança de 3 anos, com quadro de dor nos membros superiores e inferiores, proximal, simétrica, de agravamento nocturno, associada a recusa ou dificuldade no início da marcha e com 5 dias de evolução, sem outra sintomatologia acompanhante. Refere 2 episódios semelhantes nos 6 meses precedentes, com resolução espontânea em alguns dias. Nas 4 semanas prévias ao actual episódio, apresentou uma gastroenterite aguda sem agente isolado. Objectivamente salienta-se ausência de sinais inflamatórios locais, dor à mobilização dos membros (com possível sinal de Lasègue), diminuição da força muscular (grau 4) proximal e distal nos membros superiores e inferiores, tremor postural e intencional nos membros superiores, reflexos miotáticos presentes nos membros superiores mas ausentes nos inferiores e instabilidade na marcha. Não havia história de exposição a drogas ou tóxicos nem história familiar de neuropatia. Avaliação analítica para doenças auto-imunes e ecografias articulares não revelaram alterações. O estudo electromiográfico (EMG) demonstrou aumento das latências distais, com diminuição das velocidades de condução e atraso/dispersão das ondas F em múltiplos nervos. A análise do LCR revelou dissociação albumino-citológica. Estudo etiológico do LCR, sangue e fezes com resultados negativos. Em D9 de doença pela persistência das queixas álgicas, repetiu o EMG demonstrando agravamento da polineuropatia. Fez Imunoglobulina intravenosa (0,4 g/Kg/dia) durante 5 dias, com melhoria progressiva da sintomatologia e recuperação parcial da capacidade funcional. Discussão: O diagnóstico de CIDP baseia-se em elementos clínicos (interpretamos como episódios recorrentes de neuropatia num período de cerca de 6 meses, embora a nossa observação da criança seja apenas a actual) e no estudo electrofisiológico (reúne critérios de diagnóstico). Está planeada biópsia de nervo para confirmação diagnóstica embora nem todas as guidelines considerem necessária esta investigação. É importante diagnosticar precocemente a CIDP de forma a instituir a terapêutica mais adequada, determinante para o prognóstico

Hypertensive Disorders during Pregnancy and Risk of Bronchopulmonary Dysplasia in Very Preterm Infants.

 It is not yet fully known whether hypertensive disorders (HTD) during pregnancy impose an increased risk of development of bronchopulmonary dysplasia (BPD) in preterm newborn infants. OBJECTIVE:  To test the hypothesis that preeclampsia and other HTD are associated with the development of BPD in preterm infants. MATERIALS AND METHODS:  Data on mothers and preterm infants with gestational age 24 to 30 weeks were prospectively analyzed in 11 Portuguese level III centers. Statistical analysis was performed using IBM SPSS statistics 23. RESULTS:  A total of 494 preterm infants from 410 mothers were enrolled, and 119 (28%) of the 425 babies, still alive at 36 weeks, developed BPD. The association between chronic arterial hypertension, chronic arterial hypertension with superimposed preeclampsia, and gestational hypertension in mothers and BPD in preterm infants was not significant (p = 0.115; p = 0.248; p = 0.060, respectively). The association between preeclampsia-eclampsia and BPD was significant (p = 0.007). The multivariate analysis revealed an association between preeclampsia-eclampsia and BPD (odds ratio [OR] = 4.6; 95% confidence interval [CI] 1.529-13.819; p = 0.007) and a protective effect for BPD when preeclampsia occurred superimposed on chronic arterial hypertension in mothers (OR = 0.077; 95%CI 0.009-0.632; p = 0.017). CONCLUSION:  The results of this study support the association of preeclampsia in mothers with BPD in preterm babies and suggest that chronic hypertension may be protective for preterm babies.info:eu-repo/semantics/publishedVersio

Heart Rate Variability during Plateau Waves of Intracranial Pressure: a pilot descriptive study

This study aims to describe heart rate variability during the first episode of plateau waves of intracranial pressure (ICP) in Traumatic Brain Injury (TBI) in order to characterize and identify at bedside this cerebrovascular phenomenon. The general behavior of the heart rate variability (HRV) spectral measures expressed in the medians across patients is concordant with an increased HRV in the latter part of the baseline and plateau wave, followed by a decrease after the event and a new increase during the recovery. In low and high frequency bands the same increase is more marked in the parametric analysis. Interpretation of HRV may help clinicians to better identify the plateau waves and allow earlier management

A Case of IFAP Syndrome with Severe Atopic Dermatitis

Introduction. The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia. Case Report. A three-month-old Caucasian, male patient was observed with noncicatricial universal alopecia and persistent eczema from birth. He had dystrophic nails, spiky follicular hyperkeratosis, and photophobia which became apparent at the first year of life. Short stature and psychomotor developmental delay were also noticed. Histopathological examination of skin biopsy on left thigh showed epidermis with irregular acanthosis, lamellar orthokeratotic hyperkeratosis, and hair follicles fulfilled by parakeratotic hyperkeratosis. The chromosomal study showed a karyotype 46, XY. Total IgE was 374 IU/mL. One missense mutation c.1360G>C (p.Ala454Pro) in hemizygosity was detected on the MBTPS2 gene thus confirming the diagnosis of IFAP syndrome. Conclusions. We describe a boy with a typical clinical presentation of IFAP syndrome and severe atopic manifestations. A novel missense mutation c.1360G>C (p.Ala454Pro) in MBTPS2 gene was observed. The phenotypic expression of disease is quantitatively related to a reduced function of a key cellular regulatory system affecting cholesterol and endoplasmic reticulum homeostasis. It can cause epithelial disturbance with failure in differentiation of epidermal structures and abnormal skin permeability barrier. However, no correlation phenotype/genotype could be established

Immunological Reconstitution Inflammatory Syndrome and Thrombotic Microangiopathy: Severe Complications in a Child With Acquired Immunodeficiency Syndrome

Some patients with human immunodeficiency virus (HIV) infection deteriorate shortly after starting highly active antiretroviral therapy (HAART), the so-called immunological reconstitution inflammatory syndrome (IRIS).1 Although having a spontaneous resolution in many instances, it can be fatal.1 Worse prognosis is seen in younger children, severe immunosuppression and central nervous system IRIS, or infections with specific agents, namely, Criptococcus.2 Hemophagocytic lymphohistiocytosis (HLH) has also been described in children with HIV infection, in the context of an immunological system dysregulation.3 Thrombotic microangiopathy (TMA) became rare with the introduction of HAART, being mostly associated with advanced disease.4 HIV-associated TMA has specific clinical aspects as well as a worse prognosis than idiopathic or congenital TMA.4-9 The authors present the case of a 10-month-old boy with advanced HIV infection who developed IRIS complicated with HLH and TMA during the course of his treatment.info:eu-repo/semantics/publishedVersio

Some historical aspects of the periodic classification of the chemical elements.

A history of the periodic table of the elements is presented, from the first tentative classifications, passing through Meyer and Mendeleev, up to recent speculations on super-heavy elements still to be synthesized. Many of the discussions and discoveries related to chemical elements and their proper periodic classification are also presented.20110311