Migrações e fronteiras no Distrito Federal: a integração linguística como garantia dos direitos humanos

O presente artigo tem como objetivo descrever o projeto acadêmico, em fase de desenvolvimento, de inserção linguística dos imigrantes, oriundos de diversas localidades, que chegam em Brasília. De fato, um dos principais obstáculos encontrados por essa população no momento de sua chegada e nos primeiros contatos com as entidades de assistência é linguístico. Para tanto, busca-se implementar um sistema de comunicação linguisticamente inclusivo, capaz de integrar a população imigrante e refugiada aos sistemas de prestação de serviços públicos nas áreas de saúde, trabalho, Centros de Referência de Assistência Social, Centros de Referência Especializados de Assistência Social, Comitê Nacional para os Refugiados e Polícia Federal, e o Instituto de Migrações e Direitos Humanos, contribuindo assim para a efetivação do exercício dos diretos humanos dessa população. O projeto visa, num primeiro momento, formar e alimentar um banco de intérpretes voluntários e bolsistas, para atender às demandas mais emergenciais. Além disso, trata-se também da criação de um aplicativo capaz de auxiliar a comunicação com diversos recursos linguísticos (bancos terminológicos multilíngues, plataforma multilíngue de informações sobre direitos e deveres dessa população, geolocalizador de intérpretes, etc.). Sugere-se assim que um sistema de comunicação linguisticamente inclusivo, tal como o que visamos implementar, será capaz de facilitar a gestão e eventual integração da população imigrante e refugiada aos sistemas de prestação de serviços públicos. Desenvolvida no âmbito acadêmico, enquanto programa de extensão, essa iniciativa permitirá consolidar pesquisas anteriores, num contexto de ação social que engloba todas as competências desenvolvidas nos cursos oferecidos pelo Departamento de Línguas Estrangeiras e Tradução. Além disso, trata-se de fortalecer a formação profissional dos estudantes e colocar em prática os conhecimentos linguísticos que desenvolvem ao longo de sua formação. Serão também orientados sobre questões ligadas à manutenção dos direitos humanos e aos trânsitos de populações na atualidade

Neuroimaging Biomarkers and Cognitive Function in Non-CNS Cancer and Its Treatment: Current Status and Recommendations for Future Research

Cognitive changes in patients undergoing treatment for non-central nervous system (CNS) cancers have been recognized for several decades, yet the underlying mechanisms are not well understood. Structural, functional and molecular neuroimaging has the potential to help clarify the neural bases of these cognitive abnormalities. Structural magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), MR spectroscopy (MRS), and positron emission tomography (PET) have all been employed in the study of cognitive effects of cancer treatment, with most studies focusing on breast cancer and changes thought to be induced by chemotherapy. Articles in this special issue of Brain Imaging and Behavior are devoted to neuroimaging studies of cognitive changes in patients with non-CNS cancer and include comprehensive critical reviews and novel research findings. The broad conclusions that can be drawn from past studies and the present body of new research is that there are structural and functional changes associated with cancer and various treatments, particularly systemic cytotoxic chemotherapy, although some cognitive and fMRI studies have identified changes at pre-treatment baseline. Recommendations to accelerate progress include well-powered multicenter neuroimaging studies, a better standardized definition of the cognitive phenotype and extension to other cancers. A systems biology framework incorporating multimodality neuroimaging, genetics and other biomarkers will be highly informative regarding individual differences in risk and protective factors and disease- and treatment-related mechanisms. Studies of interventions targeting cognitive changes are also needed. These next steps are expected to identify novel protective strategies and facilitate a more personalized medicine for cancer patients

Town of Jay Annual Report Year Ending June 30, 2014

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Blood and neuroimaging biomarkers of cognitive sequelae in breast cancer patients throughout chemotherapy:A systematic review

Breast cancer treatment can induce alterations in blood-and neuroimaging-based markers. However, an overview of the predictive value of these markers for cognition is lacking for breast cancer survivors. This systematic review summarized studies of the last decade, using the PubMed database, evaluating blood markers, and the association between blood-or structural neuroimaging markers and cognition across the chemotherapy trajectory for primary breast cancer, following PRISMA guidelines. Forty-four studies were included. Differences were observed in all blood marker categories, from on-therapy until years post-chemotherapy. Associations were found between cognitive functioning and (1) blood markers (mainly inflammation-related) during, shortly-, or years post-chemotherapy and (2) white and gray matter metrics in frontal, temporal and parietal brain regions months up until years post-chemotherapy. Preliminary evidence exists for epigenetic and metabolic changes being associated with cognition, only after chemotherapy. This review demonstrated time-dependent associations between specific blood-based and structural neuroimaging markers with cognitive impairment in patients with breast cancer. Future studies are encouraged to include both neuroimaging-and blood markers (e.g. of neuronal integrity, epigenetics and metabolism) to predict long-term cognitive effects of chemotherapy

The impact of mindfulness on functional brain connectivity and peripheral inflammation in breast cancer survivors with cognitive complaints

Simple Summary Cognitive impairment is a common side effect of cancer treatment and impacts the quality of life of cancer survivors. As there is currently no golden standard for the treatment of cancer-related cognitive impairment (CRCI), we investigated the potential of a mindfulness-based intervention to impact the underlying mechanisms of CRCI. Breast cancer survivors with cognitive complaints (n = 117) were randomly assigned to a mindfulness, physical training, or waitlist control group. Resting state functional MRI data and serum blood samples were collected and compared before and after the intervention. We could not identify differences between the groups in resting state functional connectivity. However, the functional organization of attention-, salience- and executive functioning-related neural networks differed between both intervention groups and the waitlist control group. Additionally, physical training could alter therapy-induced immune deregulation. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI. Background: Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a mindfulness-based intervention on brain function and inflammatory profiles in breast cancer survivors with CRCI. Methods: Female breast cancer survivors reporting cognitive complaints (n = 117) were randomly assigned to a mindfulness-based intervention (n = 43), physical training (n = 36), or waitlist control condition (n = 38). Region-of-interest (ROI) and graph theory analyses of resting state functional MRI data were performed to study longitudinal group differences in functional connectivity and organization in the default mode, dorsal attention, salience, and frontoparietal network. Additionally, bead-based immunoassays were used to investigate the differences in inflammatory profiles on serum samples. Measures were collected before, immediately after and three months post-intervention. Results: No ROI-to-ROI functional connectivity changes were identified. Compared to no intervention, graph analysis showed a larger decrease in clustering coefficient after mindfulness and physical training. Additionally, a larger increase in global efficiency after physical training was identified. Furthermore, the physical training group showed a larger decrease in an inflammatory profile compared to no intervention (IL-12p70, IFN-& gamma;, IL-1 & beta;, and IL-8). Conclusion: Both mindfulness and physical training induced changes in the functional organization of networks related to attention, emotion processing, and executive functioning. While both interventions reduced functional segregation, only physical training increased functional integration of the neural network. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI

Neuroinflammation as potential precursor of leukoencephalopathy in early-stage breast cancer patients:A cross-sectional PET-MRI study

BACKGROUND: Although chemotherapy-induced leukoencephalopathy has been described in case and cohort studies, literature remains inconclusive about its prevalence and mechanisms. Therefore, we investigated the presence of leukoencephalopathy after multiagent chemotherapy in women treated for breast cancer and potential underlying neuroinflammatory processes. METHODS: In this exploratory study, 15 chemotherapy-treated and 15 age-matched chemotherapy-naïve patients with early-stage breast cancer, as well as 15 healthy controls underwent simultaneous PET-MR neuroimaging, including T1-weighted MPRAGE, T2-weighted FLAIR and dynamic PET with the 18-kDA translocator protein (TSPO) radioligand [(18)F]DPA-714. Total and regional (juxtacortical, periventricular, deep white matter and infratentorial) lesion burden were compared between the groups with one-way ANOVA. With paired t-tests, [(18)F]DPA-714 volume of distribution [V(T), including partial volume correction (PVC)] in lesioned and normal appearing white matter (NAWM) were compared within subjects, to investigate inflammation. Finally, two general linear models were used to examine the predictive values of neurofilament light-chain (NfL) serum levels on (1) total lesion burden or (2) PVC [(18)F]DPA-714 V(T) of lesions showing elevated inflammation. RESULTS: No significant differences were found in total or localized lesion burden. However, significantly higher (20–45%) TSPO uptake was observed in juxtacortical lesions (p ≤ 0.008, t ≥ 3.90) compared to NAWM in both cancer groups, but only persisted for chemotherapy-treated patients after PVC (p = 0.005, t = 4.30). NfL serum levels were not associated with total lesion volume or tracer uptake in juxtacortical lesions. CONCLUSION: This multimodal neuroimaging study suggests that neuroinflammatory processes could be involved in the development of juxtacortical, but not periventricular or deep white matter, leukoencephalopathy shortly after chemotherapy for early-stage breast cancer

Phase 3 Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC (NCT01780675)

Introduction: To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA). Methods: In a multicenter, randomized phase 3 trial (NCT01780675), patients with SCLC were randomized to standard PCI or HA-PCI of 25 Gy in 10 fractions. Neuropsychological tests were performed at baseline and 4, 8, 12, 18, and 24 months after PCI. The primary end point was total recall on the Hopkins Verbal Learning Test-Revised at 4 months; a decline of at least five points from baseline was considered a failure. Secondary end points included other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival. Results: From April 2013 to March 2018, a total of 168 patients were randomized. The median follow-up time was 26.6 months. In both treatment arms, 70% of the patients had limited disease and baseline characteristics were well balanced. Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms: 29% of patients on PCI and 28% of patients on HA-PCI dropped greater than or equal to five points (p = 1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function, and processing speed did not change significantly different over time between the groups. The overall survival was not significantly different (p = 0.43). The cumulative incidence of brain metastases at 2 years was 20% (95% confidence interval: 12%-29%) for the PCI arm and 16% (95% confidence interval: 7%-24%) for the HA-PCI arm. Conclusions: This randomized phase 3 trial did not find a lower probability of cognitive decline in patients with SCLC receiving HA-PCI compared with conventional PCI. No increase in brain metastases at 2 years was observed in the HA-PCI arm. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved

Atlas of the clinical genetics of human dilated cardiomyopathy

[Abstract] Aim. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results. In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion. This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.Hôpitaux de Paris; PHRC AOM0414

Two-pronged attack: dual inhibition of Plasmodium falciparum M1 and M17 metalloaminopeptidases by a novel series of hydroxamic acid-based inhibitors

Plasmodium parasites, the causative agents of malaria, have developed resistance to most of our current antimalarial therapies, including artemisinin combination therapies which are widely described as our last line of defense. Antimalarial agents with a novel mode of action are urgently required. Two Plasmodium falciparum aminopeptidases, PfA-M1 and PfA-M17, play crucial roles in the erythrocytic stage of infection and have been validated as potential antimalarial targets. Using compound-bound crystal structures of both enzymes, we have used a structure-guided approach to develop a novel series of inhibitors capable of potent inhibition of both PfA-M1 and PfA-M17 activity and parasite growth in culture. Herein we describe the design, synthesis, and evaluation of a series of hydroxamic acid-based inhibitors and demonstrate the compounds to be exciting new leads for the development of novel antimalarial therapeutics