Transportin 1 accumulates specifically with FET proteins but no other transportin cargos in FTLD-FUS and is absent in FUS inclusions in ALS with FUS mutations

Accumulation of the DNA/RNA binding protein fused in sarcoma (FUS) as inclusions in neurons and glia is the pathological hallmark of amyotrophic lateral sclerosis patients with mutations in FUS (ALS-FUS) as well as in several subtypes of frontotemporal lobar degeneration (FTLD-FUS), which are not associated with FUS mutations. Despite some overlap in the phenotype and neuropathology of FTLD-FUS and ALS-FUS, significant differences of potential pathomechanistic relevance were recently identified in the protein composition of inclusions in these conditions. While ALS-FUS showed only accumulation of FUS, inclusions in FTLD-FUS revealed co-accumulation of all members of the FET protein family, that include FUS, Ewing's sarcoma (EWS) and TATA-binding protein-associated factor 15 (TAF15) suggesting a more complex disturbance of transportin-mediated nuclear import of proteins in FTLD-FUS compared to ALS-FUS. To gain more insight into the mechanisms of inclusion body formation, we investigated the role of Transportin 1 (Trn1) as well as 13 additional cargo proteins of Transportin in the spectrum of FUS-opathies by immunohistochemistry and biochemically. FUS-positive inclusions in six ALS-FUS cases including four different mutations did not label for Trn1. In sharp contrast, the FET-positive pathology in all FTLD-FUS subtypes was also strongly labeled for Trn1 and often associated with a reduction in the normal nuclear staining of Trn1 in inclusion bearing cells, while no biochemical changes of Trn1 were detectable in FTLD-FUS. Notably, despite the dramatic changes in the subcellular distribution of Trn1 in FTLD-FUS, alterations of its cargo proteins were restricted to FET proteins and no changes in the normal physiological staining of 13 additional Trn1 targets, such as hnRNPA1, PAPBN1 and Sam68, were observed in FTLD-FUS. These data imply a specific dysfunction in the interaction between Trn1 and FET proteins in the inclusion body formation in FTLD-FUS. Moreover, the absence of Trn1 in ALS-FUS provides further evidence that ALS-FUS and FTLD-FUS have different underlying pathomechanism

CARÁCTER MULTIDIMENSIONAL DE LA GRAVEDAD DE LOS TRASTORNOS ASOCIADOS A SUSTANCIAS PSICOACTIVAS POR EL ADDICTION SEVERITY INDEX-6

Objetivo: caracterizar a gravidade dos transtornos relacionados a substâncias nas pessoas em tratamento nos Centros de Atenção Psicossocial Álcool e outras Drogas.Método: estudo transversal, realizado em três Centros de Atenção Psicossocial Álcool e outras Drogas III, em Curitiba-Paraná, com 137 pessoas com transtornos relacionados a substâncias. Os dados foram coletados entre abril e novembro de 2018, mediante a aplicação do instrumento Addiction Severity Index sexta versão, e analisados descritivamente a partir de frequências absolutas e relativas, média e desvio padrão.Resultados: do total da amostra, 89,1% (122) eram do sexo masculino; as subescalas de maior gravidade foram Família/crianças 57,8 (± 8,6), Álcool 52,8 (±10,9) e Família/problemas sociais 51,0 (±8,9).Conclusão: O uso de substâncias psicoativas afeta as relações familiares e sociais e o álcool, uma substância lícita, de fácil acesso, está presente na vida das pessoas desde a infância, acabando por ter maior frequência entre todas as faixas etárias.Objective: to characterize the severity of substance-related disorders in patients undergoing treatment at the Psychosocial Care Centers for Alcohol and other Drugs.Method: a transversal study conducted in three Psychosocial Care Centers for Alcohol and other Drugs III, in Curitiba-Paraná, with 137 people with substance-related disorders. Data were collected from April to November of 2018, using the Addiction Severity Index sixth version, and analyzed descriptively using absolute and relative frequencies, mean and standard deviation.Results: out of the entire sample, 89.1% (122) were male; the most severe subscales were Family/children 57.8 (± 8.6), Alcohol 52.8 (± 10.9) and Family/social problems 51.0 (± 8.9).Conclusion: The use of psychoactive substances affects family and social relatedness, and alcohol, a legal substance, easily accessible, has been present in people’s lives since childhood, ending up being more frequent among all age groups.Objetivo: caracterizar la gravedad de los trastornos asociados a sustancias en las personas entratamiento en los Centros de Atención Psicosocial Alcohol y otras Drogas.Método: estudio transversal, que se realizó en tres Centros de Atención Psicosocial Alcohol yotras Drogas III, en Curitiba-Paraná, con 137 personas con trastornos asociados a sustancias.Se obtuvieron los dados entre abril y noviembre de 2018, por medio de aplicación delinstrumento Addiction Severity Index sexta versión, analizándolos de modo descriptivo apartir de frecuencias absolutas y relativas, promedio y desviación estándar.Resultados: del total de la muestra, 89,1% (122) eran del sexo masculino; las sub escalas demayor gravedad fueron Familia/niños 57,8 (± 8,6), Alcohol 52,8 (±10,9) y Familia/problemassociales 51,0 (±8,9).Conclusión: El uso de sustancias psicoactivas afecta las relaciones familiares y sociales y elalcohol, una substancia lícita, de fácil acceso, está presente en la vida de las personas desdela infancia, presentando mayor frecuencia entre todas las franjas etarias

FET proteins TAF15 and EWS are selective markers that distinguish FTLD with FUS pathology from amyotrophic lateral sclerosis with FUS mutations

Accumulation of the DNA/RNA binding protein fused in sarcoma as cytoplasmic inclusions in neurons and glial cells is the pathological hallmark of all patients with amyotrophic lateral sclerosis with mutations in FUS as well as in several subtypes of frontotemporal lobar degeneration, which are not associated with FUS mutations. The mechanisms leading to inclusion formation and fused in sarcoma-associated neurodegeneration are only poorly understood. Because fused in sarcoma belongs to a family of proteins known as FET, which also includes Ewing's sarcoma and TATA-binding protein-associated factor 15, we investigated the potential involvement of these other FET protein family members in the pathogenesis of fused in sarcoma proteinopathies. Immunohistochemical analysis of FET proteins revealed a striking difference among the various conditions, with pathology in amyotrophic lateral sclerosis with FUS mutations being labelled exclusively for fused in sarcoma, whereas fused in sarcoma-positive inclusions in subtypes of frontotemporal lobar degeneration also consistently immunostained for TATA-binding protein-associated factor 15 and variably for Ewing's sarcoma. Immunoblot analysis of proteins extracted from post-mortem tissue of frontotemporal lobar degeneration with fused in sarcoma pathology demonstrated a relative shift of all FET proteins towards insoluble protein fractions, while genetic analysis of the TATA-binding protein-associated factor 15 and Ewing's sarcoma gene did not identify any pathogenic variants. Cell culture experiments replicated the findings of amyotrophic lateral sclerosis with FUS mutations by confirming the absence of TATA-binding protein-associated factor 15 and Ewing's sarcoma alterations upon expression of mutant fused in sarcoma. In contrast, all endogenous FET proteins were recruited into cytoplasmic stress granules upon general inhibition of Transportin-mediated nuclear import, mimicking the findings in frontotemporal lobar degeneration with fused in sarcoma pathology. These results allow a separation of fused in sarcoma proteinopathies caused by FUS mutations from those without a known genetic cause based on neuropathological features. More importantly, our data imply different pathological processes underlying inclusion formation and cell death between both conditions; the pathogenesis in amyotrophic lateral sclerosis with FUS mutations appears to be more restricted to dysfunction of fused in sarcoma, while a more global and complex dysregulation of all FET proteins is involved in the subtypes of frontotemporal lobar degeneration with fused in sarcoma patholog

Ideação suicida em pacientes com transtornos relacionados a substâncias

Objective: to characterize suicidal ideation during life in patients with substance-related disorders. Methodology: observational and cross-sectional study carried out in three Psychosocial Care Centers for Alcohol and Other Drugs III with a total of 137 participants. Data collection occurred through the application of two instruments: Columbia Suicide Severity Rating Scale and Addiction Severity Index – Version 6. The data were analyzed descriptively and expressed as absolute and relative frequencies, mean and standard deviation. Results: 112 (81.8%) participants reported suicidal ideation at some point in their lives. Of these, 55 (49.1%) had a plan and intention to carry it out, 40 (35.8%) had daily thoughts and many times a day and 56 (49.9%) lasting up to eight hours or more, 78 participants (69.6%) considered suicidal ideation certainly as a means of ending suffering. Conclusion: a high frequency of suicidal ideation during life was observed in patients with substance-related disorders, with varying severity and intensity according to sociodemographic, economic and clinical aspects. These results can support professional practice in mental health, enabling the development of preventive strategies.Objetivo: caracterizar a ideação suicida durante a vida em pacientes com transtornos relacionados a substâncias. Metodologia: estudo observacional e transversal realizado em três Centros de Atenção Psicossocial Álcool e outras Drogas III, com 137 participantes. A coleta de dados ocorreu mediante aplicação de dois instrumentos: Columbia Suicide Severity Rating Scale e Addiction Severity Index – Version 6. Os dados foram analisados descritivamente, expressos por frequências absolutas e relativas, média e desvio padrão. Resultados: 112 (81,8%) participantes relataram ideação suicida alguma vez na vida. Desse total, 55 (49,1%) tinham plano e intenção de executálo, 40 (35,8%) apresentavam pensamentos diários e muitas vezes ao dia e 56 (49,9%) com duração de até oito horas ou mais, 78 participantes (69,6%) consideravam a ideação suicida certamente como um meio de findar o sofrimento. Conclusão: observou-se elevada frequência de ideação suicida durante a vida em pacientes com transtornos relacionados a substâncias, com variada gravidade e intensidade de acordo com aspectos sociodemográficos, econômicos e clínicos. Esses resultados podem subsidiar a prática profissional em saúde mental, possibilitando o desenvolvimento de estratégias preventivas

Influence of sociodemographic factors on eating motivations - modelling through artificial neural networks (ANN)

This study aimed at investigating the influence of some sociodemographic factors on the eating motivations. A longitudinal study was carried conducted with 11960 participants from 16 countries. Data analysis included t-test for independent samples or ANOVA, and neural network models were also created, to relate the input and output variables. Results showed that factors like age, marital status, country, living environment, level of education or professional area significantly influenced all of the studied types of eating motivations. Neural networks modelling indicated variability in the food choices, but identifying some trends, for example the strongest positive factor determining health motivations was age, while for emotional motivations was living environment, and for economic and availability motivations was gender. On the other hand, country revealed a high positive influence for the social and cultural as well as for environmental and political and also for marketing and commercial motivations.This is the peer-reviewed version of the following article: Guine, R. P. F.; Ferrao, A. C.; Ferreira, M.; Correia, P.; Mendes, M.; Bartkiene, E.; Szucs, V.; Tarcea, M.; Matek-Sarić, M.; Cernelić-Bizjak, M.; Isoldi, K.; EL-Kenawy, A.; Ferreira, V.; Klava, D.; Korzeniowska, M.; Vittadini, E.; Leal, M.; Frez-Munoz, L.; Papageorgiou, M.; Djekić, I. Influence of Sociodemographic Factors on Eating Motivations - Modelling through Artificial Neural Networks (ANN). International Journal of Food Sciences and Nutrition 2020, 71 (5), 614–627. [https://doi.org/10.1080/09637486.2019.1695758]

Advancing One Health:Updated core competencies

International audienceAbstract One Health recognises the interdependence between the health of humans, animals, plants and the environment. With the increasing inclusion of One Health in multiple global health strategies, the One Health workforce must be prepared to protect and sustain the health and well-being of life on the planet. In this paper, a review of past and currently accepted One Health core competencies was conducted, with competence gaps identified. Here, the Network for Ecohealth and One Health (NEOH) propose updated core competencies designed to simplify what can be a complex area, grouping competencies into three main areas of: Skills; Values and Attitudes; and Knowledge and Awareness; with several layers underlying each. These are intentionally applicable to stakeholders from various sectors and across all levels to support capacity-building efforts within the One Health workforce. The updated competencies from NEOH can be used to evaluate and enhance current curricula, create new ones, or inform professional training programs at all levels, including students, university teaching staff, or government officials as well as continual professional development for frontline health practitioners and policy makers. The competencies are aligned with the new definition of One Health developed by the One Health High-Level Expert Panel (OHHLEP), and when supported by subjectspecific expertise, will deliver the transformation needed to prevent and respond to complex global challenges. One Health Impact Statement Within a rapidly changing global environment, the need for practitioners competent in integrated approaches to health has increased substantially. Narrow approaches may not only limit opportunities for global and local solutions but, initiatives that do not consider other disciplines or social, economic and cultural contexts, may result in unforeseen and detrimental consequences. In keeping with principles of One Health, the Network for Ecohealth and One Health (NEOH) competencies entail a collaborative effort between multiple disciplines and sectors. They focus on enabling practitioners, from any background, at any level or scale of involvement, to promote and support a transformation to integrated health approaches. The updated competencies can be layered with existing disciplinary competencies and used to evaluate and enhance current education curricula, create new ones, or inform professional training programs at all levels-including for students, teachers and government officials as well as continual professional development for frontline health practitioners and policymakers. The competencies outlined here are applicable to all professionals and disciplines who may contribute to One Health, and are complimentary to, not a replacement for, any discipline-specific competencies. We believe the NEOH competencies meet the need outlined by the Quadripartite’s (Food and Agriculture Organisation, United Nations Environment Programme, World Health Organisation, World Organisation for Animal Health) Joint Plan of Action on One Health which calls for cross-sectoral competencies

Fine-grain population structure and transmission patterns of Mycobacterium tuberculosis in southern Mozambique, a high TB/HIV burden area

14 paginas, 5 figuras, 2 tablas.Genomic studies of the Mycobacterium tuberculosis complex (MTBC) might shed light on the dynamics of its transmission, especially in high-burden settings, where recent outbreaks are embedded in the complex natural history of the disease. To this end, we conducted a 1 year prospective surveillance-based study in Mozambique. We applied whole-genome sequencing (WGS) to 295 positive cultures. We fully characterized MTBC isolates by phylogenetics and dating evaluation, and carried out a molecular epidemiology analysis to investigate further associations with pre-defined transmission risk factors. The majority of strains (49.5%, 136/275) belonged to lineage (L) 4; 57.8 % of them (159/275) were in genomic transmission clusters (cut-off 5 SNPs), and a strikingly high proportion (45.5%) shared an identical genotype (0 SNP pairwise distance). We found two 'likely endemic' clades, comprising 67 strains, belonging to L1.2, which dated back to the late 19th century and were associated with recent spread among people living with human immunodeficiency virus (PLHIV). We describe for the first time the population structure of MTBC in our region, a high tuberculosis (TB)/HIV burden area. Clustering analysis revealed an unforeseen pattern of spread and high rates of progression to active TB, suggesting weaknesses in TB control activities. The long-term presence of local strains in Mozambique, which were responsible for large transmission among HIV/TB-coinfected patients, calls into question the role of HIV in TB transmission.This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programmes 101001038 (TB-RECONNECT), PID2019-104477RB-I00 from Ministerio de Economía y Competitividad (Spanish Government) (to I.C.). We acknowledge support from the Spanish Ministry of Science, Innovation and Universities through the ‘Centro de Excelencia Severo Ochoa 2019–2023’.Programme (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Programme. B.S receives a pre-doctoral fellowship from the Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia and co-funded by European Social Fund (AGAUR).Peer reviewe