O uso do canabidiol no tratamento da doença de Parkinson

RESUMO: A doença de Parkinson (DP) é um transtorno neurodegenerativo caracterizado pela presença de sintomas motores e neurológicos típicos como bradicinesia (movimentos com lentidão), tremores e rigidez de membros, além de sintomas neuropsiquiátricos como transtornos psicóticos, do humor e do sono, tendo impacto significativo na qualidade de vida do paciente. Os principais fármacos atualmente utilizados no tratamento da DP são responsáveis por efeitos adversos graves no paciente, necessitando de um tratamento alternativo, fazendo com que a terapia com canabinóides ganhe espaço na comunidade científica. O canabidiol (CBD) é um composto com amplo efeito farmacológico para diversas neuropatologias, incluindo a DP, devido às suas propriedades antioxidantes, anti-excitotóxicas, anti-inflamatórias e neuroprotetoras. Estudos acerca do CBD vêm demonstrando a sua eficácia no tratamento de doenças neurodegenerativas, ultrapassando as barreiras do preconceito que esse fármaco ainda possui. Discutir a viabilidade do uso do CBD no tratamento da DP. Trata-se de um estudo descritivo, baseado em uma revisão integrativa de literatura. A questão norteadora da pesquisa foi: qual a viabilidade do uso do CBD como tratamento para a DP? Para responder, foi realizada uma busca por pesquisas realizadas entre 2015 a 2020, nas bases de dados, PubMed e SciELO, utilizando os descritores: “Canabidiol” and “Doença de Parkinson” and “Neuropatologia”. A DP é caracterizada pela morte de neurônios dopaminérgicos do Sistema Nervoso, levando à deficiência de dopamina e à um distúrbio do movimento. Seu tratamento é feito com precursores de dopamina, entretanto seus efeitos adversos são graves e muito prevalentes nos pacientes com DP. Todavia, com relação ao tratamento com CBD, em vários estudos caso-controle controlados por placebo, duplos-cego e randomizados foi utilizada uma dose entre 150-400mg/dia e demonstrou reduzir significativamente os sintomas psicóticos e os sintomas gerais dos pacientes (bradicinesia, tremores e rigidez muscular). Ademais, foi constatada uma melhora na mobilidade, na cognição, no bem-estar emocional, no desconforto corporal e na qualidade do sono em relação ao placebo. Os autores sugerem que esse efeito pode estar relacionado às propriedades ansiolíticas e antidepressivas do CBD. A melhor conduta terapêutica do CBD é em associação com o fármaco habitual, já que uma das características mais importantes dessa droga é a sua neuroproteção dos efeitos adversos causados pelo tratamento mais usado atualmente. Obtendo melhora na qualidade de vida dos pacientes com DP, especialmente em relação às atividades diárias exercidas pelo paciente e ao estigma associado à essa doença, o CBD é um fármaco muito promissor, tendo resultados muito favoráveis nos ensaios clínicos. Suas neuropropriedades garantem uma maior tolerabilidade ao tratamento convencional e no futuro projeta-se o seu grande uso como tratamento para a DP. &nbsp

CD44 Expression Profile Varies According to Maturational Subtypes and Molecular Profiles of Pediatric T-Cell Lymphoblastic Leukemia

CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in N/KRAS, NOTCH1, FBXW7 as well as STIL-TAL1 and TLX3 rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1–1272), T-ALL was relatively low, with MFI 43.2 (1.9–1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1aneg) had a lower CD44 expression, MFI 57.5 (2.7–866.3), whereas mCD3/TCRγδpos cases had higher expressions, MFI 99.9 (16.4–866.3). NOTCH1mut and STIL-TAL1 were associated with low CD44 expression, whereas N/KRASmut and FBXW7mut cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations (p = 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL

Atualizações sobre os distúrbios e as complicações do período pós-parto: Updates on disorders and complications of the postpartum period

Os cuidados pós-parto devem se concentrar na identificação de mulheres em risco de morbidade e mortalidade significativas a curto prazo, o período pós-parto, também conhecido como puerpério, refere-se ao período após o parto em que as alterações fisiológicas maternas relacionadas à gravidez retornam ao estado não grávido, os numerosos distúrbios e complicações podem ocorrer no pós-parto imediato ou após a alta da maternidade. Uma variedade de eventos adversos pode ocorrer após o parto, incluindo retenção urinária, hemorroidas, incontinência, neuropatia, morbidade relacionada à anestesia e vários tipos de infecções. Os distúrbios que podem se apresentar após a alta ou a visita inicial pós-parto incluem disfunção sexual, problemas de saúde mental, tireoidite, preocupações com a amamentação e disfunções relacionadas com controle do peso

ABORDAGENS ABERTAS E LAPAROSCÓPICA PARA REPARO DE HÉRNIA INGUINAL: UMA REVISÃO ABRANGENTE.

An inguinal hernia is a protrusion of an intestinal loop or, more rarely, some other abdominal viscera, due to an alteration in the fascia of the abdominal wall. The clinical manifestations can vary from an asymptomatic condition to signs of peritonitis secondary to intestinal strangulation in more serious cases. There are a number of factors involved in the choice of treatment: age, type of hernia and associated symptoms. In view of this, the aim of this study was to provide a comprehensive overview of open and laparoscopic techniques for repairing inguinal hernias. An integrative review of the current literature was carried out by searching the SciELO, PubMed and BVS databases.  The descriptors used to find the related studies were "Inguinal hernia" and "Surgical management". As a result, it was observed that the Lichtenstein technique is still the most widely adopted and consists of an inguinotomy, using polypropylene mesh sutured over the transverse fascia. While the laparoscopic approach to inguinal hernias is a minimally invasive surgery and has been the technique of choice for some surgeons due to the overwhelmingly positive results.A hérnia inguinal se trata de uma protusão de uma alça intestinal ou, de modo mais raro, de alguma outra víscera abdominal, decorrente de uma alteração na fáscia da parede abdominal. As manifestações clínicas podem variar de um quadro assintomático até sinais de peritonite secundária ao estrangulamento intestinal, em casos mais graves. Para a escolha do tratamento, existem alguns fatores envolvidos: idade, tipo de hérnia e sintomas associados. Diante disso, o objetivo do presente estudo foi abordar, de modo abrangente, as técnicas abertas e laparoscópicas de reparo da hérnia inguinal. Foi realizada uma revisão integrativa da literatura atual por meio de buscas das bases de dado SciELO, PubMed e BVS.  Os descritores utilizados para encontrar os estudos relacionados foram “Hérnia inguinal” e “Manejo Cirúrgico”. Como resultado, foi observado que A técnica de Lichtenstein ainda é a mais adotada e consiste em uma inguinotomia, com uso de tela de polipropileno suturada sobre a fáscia transversal. Enquanto a abordagem laparoscópica das hérnias inguinais é uma cirurgia minimamente invasiva e tem sido a técnica de escolha por alguns cirurgiões diande dos resultados marjoritariamente positivos

Pediatric Acute Promyelocytic Leukemia: Epidemiology, Molecular Features, and Importance of GST-Theta 1 in Chemotherapy Response and Outcome.

Previous studies have suggested a variation in the incidence of acute promyelocytic leukemia (APL) among the geographic regions with relatively higher percentages in the Latin American population. We aimed to explore the population burden of pediatric APL, gathering information from the population-based cancer registry (PBCR) and the diagnosis of APL obtained through incident cases from a hospital-based cohort. The homozygous deletion in glutathione S-transferases (GSTs) leads to a loss of enzyme detoxification activity, possibly affecting the treatment response. Mutations in the RAS pathway genes are also considered to be a key component of the disease both in the pathogenesis and in the outcomes. We have assessed mutations in a RAS-MAP kinase pathway (FLT3, PTPN11, and K-/NRAS) and GST variant predisposition risk in the outcome. Out of the 805 children and adolescents with acute myeloid leukemia (AML) who are registered in the PBCR, 35 (4.3%) were APL cases. The age-adjusted incidence rate (AAIR) was 0.03 per 100,000 person-years. One-hundred and sixty-three patients with APL were studied out of 931 AML cases (17.5%) from a hospital-based cohort. Mutations in FLT3, KRAS, and NRAS accounted for 52.1% of the cases. Patients with APL presented a 5-year probability of the overall survival (OS) of 67.3 ± 5.8%. A GST-theta 1 (GSTT1) null genotype conferred adverse prognosis, with an estimated hazard ratio of 2.8, 95% confidence interval (CI) 1.2-6.9. We speculate that the GSTT1 polymorphism is associated with therapeutics and would allow better OS of patients with APL with a GSTT1 null genotype

Chronic infection by atypical Toxoplasma gondii strain induces disturbance in microglia population and altered behaviour in mice

Toxoplasma gondii chronic infection is characterized by the establishment of tissue cysts in the brain and increased levels of IFN-γ, which can lead to brain circuitry interference and consequently abnormal behaviour in mice. In this sense, the study presented here sought to investigate the impact of chronic infection by two T. gondii strains in the brain of infection-resistant mice, as a model for studying the involvement of chronic neuroinflammation with the development of behavioural alterations. For that, male BALB/c mice were divided into three groups: non-infected (Ni), infected with T. gondii ME49 clonal strain (ME49), and infected with TgCkBrRN2 atypical strain (CK2). Mice were monitored for 60 days to establish the chronic infection and then submitted to behavioural assessment. The enzyme-linked immunosorbent assay was used for measurement of specific IgG in the blood and levels of inflammatory cytokines and neurotrophic factors in the brain, and the cell's immunophenotype was determined by multiparametric flow cytometry. Mice infected with ME49 clonal strain displayed hyperlocomotor activity and memory deficit, although no signs of depressive- and/or anxiety-like behaviour were detected; on the other hand, chronic infection with CK2 atypical strain induced anxiety- and depressive-like behaviour. During chronic infection by CK2 atypical strain, mice displayed a higher number of T. gondii brain tissue cysts and inflammatory infiltrate, composed mainly of CD3+ T lymphocytes and Ly6Chi inflammatory monocytes, compared to mice infected with the ME49 clonal strain. Infected mice presented a marked decrease of microglia population compared to non-infected group. Chronic infection with CK2 strain produced elevated levels of IFN-γ and TNF-ɑ in the brain, decreased NGF levels in the prefrontal cortex and striatum, and altered levels of fractalkine (CX3CL1) in the prefrontal cortex and hippocampus. The persistent inflammation and the disturbance in the cerebral homeostasis may contribute to altered behaviour in mice, as the levels of IFN-γ were shown to be correlated with the behavioural parameters assessed here. Considering the high incidence and life-long persistence of T. gondii infection, this approach can be considered a suitable model for studying the impact of chronic infections in the brain and how it impacts in behavioural responses

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans—anteaters, sloths, and armadillos—have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n = 5,941), and Cyclopes sp. have the fewest (n = 240). The armadillo species with the most data is Dasypus novemcinctus (n = 11,588), and the fewest data are recorded for Calyptophractus retusus (n = 33). With regard to sloth species, Bradypus variegatus has the most records (n = 962), and Bradypus pygmaeus has the fewest (n = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data

Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora