Influência dos fatores culturais na relação entre indivíduos portadores de fissura de lábio e/ou palato e a sociedade

O conhecimento do desenvolvimento embriológico é um fator importante na desmistificação dos pacientes portadores de fissuras de lábio e/ou palato. Uma mudança de pensamento deve começar no ambiente familiar e se estender por toda a sociedade, para que não haja preconceitos. A falta de conhecimento do assunto associado aos aspectos culturais, durante anos, resultou em infanticídios indiscriminados, além de outros maus-tratos. Torna-se necessário a formulação de ações no sentido de conscientizar a população de que essa malformação é uma deficiência tratável e de que a criança portadora desta necessita de um apoio maior. Palavras-chaves: fissura, fatores culturais, contexto histórico, relação médico-paciente. SUMMARY The knowledge of embryological development is an important factor in the demystification of patients with cleft lip and/or palate. A change of thinking must begin with the family and spread throughout society, so there is no prejudice. The lack of knowledge of the subject associated with the cultural aspects, for years, has resulted in indiscriminate infanticide, and other abuses. It is necessary to formulate actions to raise awareness that this abnormality is a treatable disorder and that the child with this needs greater support. Keywords: cleft, cultural factors, historical context, doctor-pacient relashionship

Discovery of mating in the major African livestock pathogen Trypanosoma congolense

The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen

Application of hardwood biochar as a reactive capping mat to stabilize mercury derived from contaminated floodplain soil and riverbank sediments

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.scitotenv.2018.10.213 © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Hardwood biochar (pyrolyzed at 700 °C), a potential candidate for Hg removal, has been proposed for use as reactive capping mats along groundwater discharge zones or riverbanks to control release of Hg from contaminated riverbank sediments. Frequent flooding and drainage in fluvial settings can influence the effectiveness of remediation systems in contaminated riverbank sediments and floodplain soils. This study evaluated the effectiveness of Hg removal using hardwood biochar under hydrogeochemical conditions representative of those present within a reactive capping mat installed in a fluvial setting. Two sets of treatment columns, containing 50% v.v biochar and quartz sand, were subjected to 100 weekly wetting/drying cycles that included dry air, water-saturated air, and drainage using leachate derived from two source columns as input solutions: 1. Passing simulated acid rain water through floodplain soil, 2. Passing river water through riverbank sediment. In both treatment columns, >80% of the Hg was retained on the biochar without promoting Hg methylation and the release of other unintended dissolved constituents (including N, P, DOC). Results from solidphase extraction analyses suggest that Hg accumulated near the air/biochar-sand interface (0–2 cm) in the treatment columns at low loadings but was present at greater depths at higher loadings. Results of micro X-ray fluorescence (μ-XRF) mapping and micro X-ray absorption near edge structure (μ-XANES) for the biochar collected at depths 0–2 cm in treatment columns suggest retention of Hg-bearing particles derived from riverbank sediment and floodplain soil within the pore structure of the biochar. Sulfur K-edge XANES analysis of the unused biochar and the biochar after treatment suggest formation of Hg complexes on the biochar surface. These results indicate that hardwood biochar is potentially an effective media for application in reactive mats for controlling Hg discharging from contaminated riverbank sediments.Natural Sciences and Engineering Research Council of CanadaE. I. du Pont de Nemours and Company CanadaOntario Research Fun

Assessment of a Novel VEGF Targeted Agent Using Patient-Derived Tumor Tissue Xenograft Models of Colon Carcinoma with Lymphatic and Hepatic Metastases

The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Gene therapy for the treatment of Niemann-Pick disease type C1: Comparison of AAV9 to a novel serotype, AAV-PHP.B

[no abstract

Gene therapy for the treatment of Niemann-Pick disease type C1: Comparison of AAV9 to a novel serotype, AAV-PHP.B

[no abstract

GTPBP1 resolves paused ribosomes to maintain neuronal homeostasis.

Ribosome-associated quality control pathways respond to defects in translational elongation to recycle arrested ribosomes and degrade aberrant polypeptides and mRNAs. Loss of a tRNA gene leads to ribosomal pausing that is resolved by the translational GTPase GTPBP2, and in its absence causes neuron death. Here, we show that loss of the homologous protein GTPBP1 during tRNA deficiency in the mouse brain also leads to codon-specific ribosome pausing and neurodegeneration, suggesting that these non-redundant GTPases function in the same pathway to mitigate ribosome pausing. As observed in Gtpbp2-/- mice (Ishimura et al., 2016), GCN2-mediated activation of the integrated stress response (ISR) was apparent in the Gtpbp1-/- brain. We observed decreased mTORC1 signaling which increased neuronal death, whereas ISR activation was neuroprotective. Our data demonstrate that GTPBP1 functions as an important quality control mechanism during translation elongation and suggest that translational signaling pathways intricately interact to regulate neuronal homeostasis during defective elongation