Treatments for Tourette syndrome in children and young adults: A systematic review

Introduction: Tourette's Syndrome (TS) is a neurodevelopmental disorder characterized by motor and / or vocal tics for more than 12 months. TS affects about 0.8% of pediatric patients and is associated with great functional impairment and psychological distress. The present study aims to list and compare the effectiveness of therapies used in children and young people with TS. Methods: PubMed / MEDLINE, Cochrane Library, ScienceDirect, SciELO and Lilacs were used from September 2020 to April 2021 to search for randomized clinical trials with pharmacological, behavioral, physical or alternative interventions for tics in children and young people with ST. Results: 13 clinical trials were included, of which six pharmacological, six behavioral and one of other conformation. The global score on the Yale Global Tic Severity Scale showed evidence in favor of Habit Reversal Training (HRT) and Comprehensive Behavioral Intervention for Tics (CBIT). Evidence from two studies suggests that antipsychotic medications improve tic scores. Evidence from other interventions has shown no conclusive benefit. Conclusions: The present study identified benefits with the use of antipsychotics. The study also found that HRT and CBIT showed improvement in reducing the severity of tics, in addition to not having any adverse effects. These therapies showed significant clinical improvement, but there is no comparison between the use of these isolated approaches in relation to their use associated with medications. In view of the different forms of therapy, further studies are needed to identify the effectiveness and the profile of adverse effects of these interventions

Development of electrochemical genosensors for the CYPC*2 gene polymorphism detection

Pharmacogenetic studies search for heritable genetic polymorphisms that influence responses to drug therapy. Pharmacogenetics has many possible applications in cardiovascular pharmacotherapy including screening for polymorphisms to choose agents with the greatest potential for efficacy and least risk of toxicity. Pharmacogenetics also informs dose adaptations for specific drugs in patients with aberrant metabolism. Cardiovascular diseases (CVD) are considered one of the leading causes of death worldwide. To prevent cardiovascular complications and further loss of life oral anticoagulants (e.g., warfarin) are frequently prescribed to patients. Nevertheless, warfarin therapeutic agent presents narrow therapeutic windows with well-documented health risks. Some of these dose-responses are a result of specific single-nucleotide polymorphism (SNP) genetic variations present in a patient´s DNA. Among them, determined SNP in the cytochrome P4502C9 (CYP2C9), namely the CYP2C9*2, gene has been identified as dose-response altering SNP. Therefore, the need for a rapid, selective, low-cost and in real time detection device is crucial before prescribing any anticoagulant. In this work an analytical approach based on electrochemical genosensor technique is under development to create a low-cost genotyping platform able to genotype SNPs related with the therapeutic response of warfarin. Analyzing public databases, two specific 71 bp DNA probes, one with adenine (TA) and other with guanine (TG) SNP genetic variation were selected and designed. The design of this electrochemical genosensor consists of ssDNA immobilization onto gold surfaces that act as the SNPs complementary probes. The hybridization reaction is performed in a sandwich format of the complementary ssDNA, using an enzymatic scheme to amplify the electrochemical signal. The electrochemical signal was performed by using chronoamperometric technique.info:eu-repo/semantics/publishedVersio

VKORC1 gene polymorphism as cardiovascular biomarker: Detection by electrochemical genosensors

Warfarin is an anticoagulant generally used to prevent cardiovascular diseases. Since of the low therapeutic index of warfarin and frequent complications of prevention or treatment, significant differences in individual doses of warfarin are needed to achieve prophylactic and therapeutic ranges. Recent studies have been reporting that genetic variants of vitamin K epoxide reductase complex (VKORC1) influence the response to warfarin and doses [9]. So, the genetic and pharmacogenetic information of the major cardiovascular diseases plays an important role in the identification of the cardiovascular risk factors and in the diagnosis and treatment of these conditions. This work addresses the development of a disposable electrochemical genosensor able of detecting single nucleotide polymorphism (SNP) in the VKORC1 gene. Analysing public databases, two specific 52 bp DNA probes, one with adenine (TA) and another with guanine (TG) SNP genetic variation were selected and selected and designed. The genosensor methodology implied the immobilization of a mixed self-assembled monolayer (SAM) linear VKORC1 DNA-capture probe and mercaptohexanol (MCH) onto screen-printed gold electrodes (SPGE). To improve the genosensor´s selectivity and avoid strong secondary structures, that could hinder the hybridization efficiency, a sandwich format of the VKORC1 allele was designed using a complementary fluorescein isothiocyanate-labelled signaling DNA probe and enzymatic amplification of the electrochemical signal. Preliminary studies indicate that differences in the electrochemical answers were obtained depending of the hybridization reaction format. In fact, higher electrochemical intensities were measured when the hybridization reaction was performed with a complementary DNA (without SNPs). These results suggested that the sensor is able to discriminate between the complementary DNA and single base mismatch targets having a great potential for the DNA polymorphism analysis.info:eu-repo/semantics/publishedVersio

EL IMPACTO Y LAS CONSECUENCIAS DE LA HIPERTENSIÓN ARTERIAL EN EL ACV

O acidente vascular cerebral (AVC) é uma das complicações de maior impacto no mundo, devido a sua prevalência, morbidade e mortalidade, e na maioria dos casos há presença de fatores cardiovasculares, como a hipertensão arterial, que é o seu principal fator de risco modificável, podendo causar diferentes tipos de AVC, como infarto, hemorragia, AVCs grandes ou lacunares e as demências vasculares. O objetivo deste estudo foi analisar e discutir os impactos da hipertensão arterial e os seus fatores de risco que possam levar a um quadro de acidente vascular cerebral. Metodologia: Realizou-se uma revisão de literatura com busca sistemática, com objetivo de coletar e analisar informações atuais sobre esta temática, de forma que contribuiu para um direcionamento clínico, no qual foi utilizada a estratégia do acrônimo PICO. Resultados e discussão: Foram levantadas evidências que contribuíram no direcionamento clínico referente à influência da hipertensão arterial sistêmica no quadro de AVC em indivíduos acima de 50 anos.El accidente cerebrovascular (ACV) es una de las complicaciones más impactantes del mundo, debido a su prevalencia, morbilidad y mortalidad, y en la mayoría de los casos existe la presencia de factores cardiovasculares, como la hipertensión arterial, que es su principal factor de riesgo modificable, que puede causar diferentes tipos de ictus, como infarto, hemorragia, accidentes cerebrovasculares grandes o lacunares y demencias vasculares. El objetivo de este artículo fue analizar y discutir los impactos de la hipertensión y sus factores de riesgo que pueden conducir al accidente cerebrovascular. Metodología: Se realizó una revisión de la literatura con una búsqueda sistemática, con el objetivo de recolectar y analizar información actual sobre este tema, de manera que contribuyera a una dirección clínica, en la que se utilizó la estrategia del acrónimo PICO. Resultados y discusión: Se recogieron evidencias que contribuyeron a la dirección clínica con respecto a la influencia de la hipertensión arterial sistémica en el accidente cerebrovascular en individuos mayores de 50 años.Cerebrovascular accident (CVA) is one of the most impactful complications in the world, due to its prevalence, morbidity and mortality, and in most cases there is the presence of cardiovascular factors, such as arterial hypertension, which is its main modifiable risk factor, which can cause different types of stroke, such as infarction, hemorrhage, large or lacunar strokes and vascular dementias. The objective of this article was to analyze and discuss the impacts of hypertension and its risk factors that may lead to stroke. Methodology: A literature review was carried out with a systematic search, with the objective of collecting and analyzing current information on this theme, in a way that contributed to a clinical direction, in which the strategy of the acronym PICO was used. Results and discussion: Evidence was collected that contributed to the clinical direction regarding the influence of systemic arterial hypertension on stroke in individuals over 50 years of age.O acidente vascular cerebral (AVC) é uma das complicações de maior impacto no mundo, devido a sua prevalência, morbidade e mortalidade, e na maioria dos casos há presença de fatores cardiovasculares, como a hipertensão arterial, que é o seu principal fator de risco modificável, podendo causar diferentes tipos de AVC, como infarto, hemorragia, AVCs grandes ou lacunares e as demências vasculares. O objetivo deste estudo foi analisar e discutir os impactos da hipertensão arterial e os seus fatores de risco que possam levar a um quadro de acidente vascular cerebral. Metodologia: Realizou-se uma revisão de literatura com busca sistemática, com objetivo de coletar e analisar informações atuais sobre esta temática, de forma que contribuiu para um direcionamento clínico, no qual foi utilizada a estratégia do acrônimo PICO. Resultados e discussão: Foram levantadas evidências que contribuíram no direcionamento clínico referente à influência da hipertensão arterial sistêmica no quadro de AVC em indivíduos acima de 50 anos

INCLUSÃO DE CRIANÇAS COM AUTISMO NA ESCOLA: UMA REVISÃO NARRATIVA

Since 2013, the Autism Spectrum Disorder (ASD) is understood as the disorder that embraces the set of other conditions such as Asperger Syndrome, Autistic Disorder, Childhood Disintegrative Disorder (Heller's Syndrome), Rett's Disorder and Atypical Autism. Knowing the need for integration and the school challenges, the present study shows the importance of inserting autistic children in everyday classes of the regular school network, demonstrating how this insertion might possibly be done, through the contact of children with and without the disorder, highlighting the benefits of exchanging experiences and cooperating with each other. Therefore, aspects of autistic types and degrees are also briefly reviewed since it is known to be challenging for any individuals involved during this process: the difficulty of social interaction, eye contact and often social isolation on the part of the autistic plus stereotyped behaviors, prejudiced and bullying practices of classmates reflect in a prism of complexity that can result in fear and refusal on the part of parents when considering education of their children in the school environment.Desde 2013, se entiende por Trastorno del Espectro Autista (TEA) el trastorno que engloba el conjunto de otras condiciones como el Síndrome de Asperger, el Trastorno Autista, el Trastorno Desintegrativo Infantil (Síndrome de Heller), el Trastorno de Rett y el Autismo Atípico. Conociendo la necesidad de integración y los desafíos escolares, el presente estudio muestra la importancia de la inserción de niños autistas en las clases cotidianas de la red escolar regular, demostrando cómo esa inserción puede ser posible, a través del contacto de niños con y sin el trastorno, destacando los beneficios de intercambiar experiencias y cooperar entre sí. Por lo tanto, también se revisan brevemente los aspectos de los tipos y grados de autismo, ya que se sabe que es un desafío para cualquier persona involucrada durante este proceso: la dificultad de la interacción social, el contacto visual y, a menudo, el aislamiento social por parte de los autistas más los comportamientos estereotipados, los prejuicios y las prácticas de bullying de los compañeros se reflejan en un prisma de complejidad que puede resultar en miedo y rechazo por parte de los padres al considerar la educación de sus hijos en el ámbito escolar.Desde 2013, o Transtorno do Espectro Autista (TEA) é entendido como o transtorno que engloba o conjunto de outras condições como a Síndrome de Asperger, o Transtorno Autista, o Transtorno Desintegrativo da Infância (Síndrome de Heller), o Transtorno de Rett e o Autismo Atípico. Sabendo da necessidade de integração e dos desafios escolares, o presente estudo buscou mostrar a importância da inserção de crianças autistas em classes cotidianas da rede regular de ensino, demonstrando também como possivelmente essa inserção pode ser feita, através do contato de crianças com e sem o transtorno, evidenciando os benefícios de troca de experiências e de cooperação entre si. Por isso, também são brevemente revisados os aspectos de tipos e graus autistas uma vez que é sabidamente desafiador para quaisquer indivíduos envolvidos durante esse processo: a dificuldade de interação social, de contato visual e de muitas vezes isolamento social por parte do autista acrescido de comportamentos estereotipados, preconceituosos e práticas de bullying dos colegas de classe refletem em um prisma de complexidade que pode resultar em medo e recusa por parte dos pais ao cogitarem educação dos seus filhos em âmbito escolarDesde 2013, o Transtorno do Espectro Autista (TEA) é entendido como o transtorno que engloba o conjunto de outras condições como a Síndrome de Asperger, o Transtorno Autista, o Transtorno Desintegrativo da Infância (Síndrome de Heller), o Transtorno de Rett e o Autismo Atípico. Sabendo da necessidade de integração e dos desafios escolares, o presente estudo buscou mostrar a importância da inserção de crianças autistas em classes cotidianas da rede regular de ensino, demonstrando também como possivelmente essa inserção pode ser feita, através do contato de crianças com e sem o transtorno, evidenciando os benefícios de troca de experiências e de cooperação entre si. Por isso, também são brevemente revisados os aspectos de tipos e graus autistas uma vez que é sabidamente desafiador para quaisquer indivíduos envolvidos durante esse processo: a dificuldade de interação social, de contato visual e de muitas vezes isolamento social por parte do autista acrescido de comportamentos estereotipados, preconceituosos e práticas de bullying dos colegas de classe refletem em um prisma de complexidade que pode resultar em medo e recusa por parte dos pais ao cogitarem educação dos seus filhos em âmbito escola

Copper nanoparticles stabilized with cashew gum: Antimicrobial activity and cytotoxicity against 4T1 mouse mammary tumor cell line

Copper nanoparticles stabilized with cashew (CG-CuNPs) were synthesized by reduction reaction using ascorbic acid and sodium borohydride, using the cashew gum (CG) as a natural polymer stabilizer. Dynamic light scattering, atomic force microscopy, Fourier-transform infrared spectroscopy, UV-Vis spectrophotometry, and x-ray diffraction were used to characterize the nanoparticles (CG-CuNPs), and copper was quantified by electrochemical measurement. The UV-vis spectra of the CG-CuNPs confirmed the formation of nanoparticles by appearance of a surface plasmon band at 580 nm after 24 h of reaction. The Fourier-transform infrared spectrum of CG-CuNPs showed the peak at 1704 cm−1 from cashew gum, confirming the presence of the gum in the nanoparticles. The average size of CG-CuNPs by dynamic light scattering and atomic force microscopy was around 10 nm, indicating small, approximately spherical particles. Antimicrobial assays showed that CG-CuNPs had activity against Staphylococcus aureus ATCC 29213 with a minimal inhibitory concentration of 0.64 mM. The cytotoxicity assay on BALB/c murine macrophages showed lower cytotoxic effects for CG-CuNPs than CuSO4·5H2O. Viability cell assays for CG-CuNPs at (0.250 mM) inhibited by 70% the growth of 4T1 LUC (4T1 mouse mammary tumor cell line) and NIH 3T3 cells (murine fibroblast cells) over a 24-h period. Therefore, CG-CuNPs can be used as an antimicrobial agent with lower cytotoxic effects than the CuSO4·5H2O precursor.The author would like to thank at UCM for performingDPV, USP by X-ray diffraction experiment, REQUIMTE/LAQV for FTIR, UnB and UFPI for the cytotoxicityassays, as well as at UFPI for help with DLS, UV-Vis,AFM, and microbiological experiments. This work was supported by Project 400398/2014-1—Desenvolvimento de Nanopartículas Estabilizadas com Goma de Cajueiro para Aplicações Biotecnologicas, financed by CNPq. AlexandraPlácido is grateful to FCT by her grant SFRH/BD/97995/2013, financed by POPH-QREN-Tipologia 4.1-Formação Avançada, subsidized by Fundo Social Europeu and Ministério da Ciência, Tecnologia e Ensino Superior.info:eu-repo/semantics/publishedVersio

Identification of Eschweilenol C in derivative of Terminalia fagifolia Mart. and green synthesis of bioactive and biocompatible silver nanoparticles

A green synthetic route was developed to prepare silver nanoparticles (AgNPs) in aqueous solution for biological applications. Eschweilenol C, a compound derivative ellagic acid was identified as the main constituent of the aqueous fraction of the ethanolic extract of Terminalia fagifolia Mart. by NMR analysis. In the green synthesis, the ethanolic extract of T. fagifolia and its aqueous fraction were used to promote silver reduction and nanoparticle stabilization. The synthesized AgNPs presented a spherical or polygonal morphology shape by TEM analysis and AgNPs showed high levels of antioxidant and considerable antibacterial and antifungal activities. Synthesized nanoparticles presented significant antioxidant activity by sequestration of DPPH and ABTS radicals, in addition to iron reduction (FRAP assay) and measurement of antioxidant capacity in ORAC units, in addition, AgNP synthesized with the aqueous fraction also demonstrated antioxidant potential in microglial cells. Gram-positive and Gram-negative bacteria were susceptible to growth inhibition by the nanoparticles, among which the AgNPs formed by the ethanolic extract was the most effective. The data obtained by AFM images suggested that AgNPs could lead to the lysis of bacteria and subsequent death. The antifungal assays showed high efficiency against yeasts and dermatophytes. This work represents the first description of antifungal activity by AgNPs against Fonsecaea pedrosoi, the etiologic agent of chromoblastomycosis. In relation to biocompatibility, the AgNPs induced lower haemolysis than AgNO3.We thank Herbert Kogler and Reinhard Wimmer for the identification of Eschweilenol C. The NMR laboratory at Aalborg University is supported by the Obel Family, SparNord and Carlsberg foundations.The authors are grateful to Carla Eiras (LIMAV/CT/UFPI) and to FCT and EU for financial support through project UID/QUI/50006/2013– POCI-01-0145-FEDER-007265 from COMPETE and projectNORTE-01-0145-FEDER-000011 from COMPETE. Thanks to Andreia Pinto for help with the TEM measurements at Instituto de Medicina Molecular (IMM). This work was supported by the Histology and Comparative Pathology Laboratory of the IMMinfo:eu-repo/semantics/publishedVersio

Novel ocellatin peptides mitigate LPS-induced ROS formation and NF-kB activation in microglia and hippocampal neurons

© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per-mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVVDILKGAAKDLAGHLASKV, with monoisotopic masses of [M + H]± = 1563.8 Da and [M + H]± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and NF-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. Furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. These functional properties suggest possible to neuromodulatory therapeutic applications.Alexandra Plácido is a recipient of a post-doctoral grant from the project FCT (PTDC/BII-BIO/31158/2017). Renato Socodato and Camila Cabral Portugal hold postdoctoral fellowships from FCT (Refs: SFRH/BPD/91833/2012 and FRH/BPD/91962/2012, respectively). This work was funded through project UID/QUI/50006/2013-POCI/01/0145/FEDER/007265 (LAQV/REQUIMTE) with financial support from FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT 2020info:eu-repo/semantics/publishedVersio

Lipidomic Analysis Reveals Serum Alteration of Plasmalogens in Patients Infected With ZIKA Virus

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the Flavivirus genus of the Flaviviridae family. Since the large outbreaks in French Polynesia in 2013–2014 and in Brazil in 2015, ZIKV has been considered a new public health threat. Similar to other related flavivirus, ZIKV is associated with mild and self-limiting symptoms such as rash, pruritus, prostration, headache, arthralgia, myalgia, conjunctivitis, lower back pain and, when present, a short-term low grade fever. In addition, ZIKV has been implicated in neurological complications such as neonatal microcephaly and Guillain–Barré syndrome in adults. Herein, serum lipidomic analysis was used to identify possible alterations in lipid metabolism triggered by ZIKV infection. Patients who presented virus-like symptoms such as fever, arthralgia, headache, exanthema, myalgia and pruritus were selected as the control group. Our study reveals increased levels of several phosphatidylethanolamine (PE) lipid species in the serum of ZIKV patients, the majority of them plasmenyl-phosphatidylethanolamine (pPE) (or plasmalogens) linked to polyunsaturated fatty acids. Constituting up to 20% of total phospholipids in humans, plasmalogens linked to polyunsaturated fatty acids are particularly enriched in neural membranes of the brain. The biosynthesis of plasmalogens requires functional peroxisomes, which are important sites for viral replication, including ZIKV. Thus, increased levels of plasmalogens in serum of ZIKV infected subjects suggest a link between ZIKV life cycle and peroxisomes. Our data provide important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV