Apathy Associated With Impaired Recognition of Happy Facial Expressions in Huntington's Disease.

OBJECTIVES: Previous research has demonstrated an association between emotion recognition and apathy in several neurological conditions involving fronto-striatal pathology, including Parkinson's disease and brain injury. In line with these findings, we aimed to determine whether apathetic participants with early Huntington's disease (HD) were more impaired on an emotion recognition task compared to non-apathetic participants and healthy controls. METHODS: We included 43 participants from the TRACK-HD study who reported apathy on the Problem Behaviours Assessment - short version (PBA-S), 67 participants who reported no apathy, and 107 controls matched for age, sex, and level of education. During their baseline TRACK-HD visit, participants completed a battery of cognitive and psychological tests including an emotion recognition task, the Hospital Depression and Anxiety Scale (HADS) and were assessed on the PBA-S. RESULTS: Compared to the non-apathetic group and the control group, the apathetic group were impaired on the recognition of happy facial expressions, after controlling for depression symptomology on the HADS and general disease progression (Unified Huntington's Disease Rating Scale total motor score). This was despite no difference between the apathetic and non-apathetic group on overall cognitive functioning assessed by a cognitive composite score. CONCLUSIONS: Impairment of the recognition of happy expressions may be part of the clinical picture of apathy in HD. While shared reliance on frontostriatal pathways may broadly explain associations between emotion recognition and apathy found across several patient groups, further work is needed to determine what relationships exist between recognition of specific emotions, distinct subtypes of apathy and underlying neuropathology. (JINS, 2019, 25, 453-461)

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Magnetization Transfer Imaging in Premanifest and Manifest Huntington Disease: A 2-Year Follow-Up

Neurological Motor Disorder

Políticas públicas "na colônia": incidência, significados e implicações para a agricultura familiar na fronteira noroeste, RS

O presente trabalho aborda a incidência das políticas públicas na agricultura familiar na região Fronteira Noroeste do Rio Grande do Sul. A partir de uma abordagem sistêmica e privilegiando o ponto de vista das famílias agricultoras, busca-se desvelar a incidência das políticas públicas “na colônia”, tal como é denominado o “meio rural” pelos agricultores familiares da região. Visando contribuir para a compreensão das políticas públicas no desenvolvimento rural, essa pesquisa teve como objetivo identificar e analisar o conjunto de políticas acessadas pela agricultura familiar na região Fronteira Noroeste do Rio Grande do Sul, considerando o entendimento de agricultores familiares acerca destas e sua interferência em seus sistemas sociais e produtivos. Partindo-se da abordagem de estudo da evolução e diferenciação de sistemas agrários, procedeu-se com as seguintes etapas de operacionalização metodológica: 1) reconstituição da história da agricultura na região; 2) entrevistas com informantes-chave e elaboração de uma tipologia da agricultura familiar; 3) visitas em Unidades de Produção Agrícola (UPAs) e entrevistas com famílias agricultoras; 4) tabulação de dados e análise dos resultados. Foram identificados cinco sistemas agrários na história da região, sendo eles: 1) Sistema Agrário Indígena; 2) Sistema Agrário Jesuítico-Guarani; 3) Sistema Agrário Caboclo; 4) Sistema Agrário Colonial; 5) Sistema Agrário Moderno Agroindustrial. Para a caracterização socioeconômica da agricultura familiar na região Fronteira Noroeste, classificou-se as UPAs em 9 tipos a partir de seus sistemas de produção, os quais foram denominados de: 1) Tipo Leite; 2) Tipo Leite+Fumo; 3) Tipo Leite+Grãos; 4) Tipo Leite+Suínos; 5) Tipo Grãos; 6) Tipo Suínos+Grãos; 7) Tipo Gado de Corte; 8) Tipo Pesca Artesanal; 9) Tipo Hortifruti. . Identificou-se 49 políticas públicas (nas diferentes esferas e níveis) incidentes nas UPAs da agricultura familiar pesquisadas, as quais foram classificadas em oito eixos de incidência: 1) acesso à terra; 2) habitação e eletrificação rural; 3) saúde no rural; 4) educação do campo e formação profissional; 5) sociossistencial; 6) ambiental; 7) produção agrícola e agroindustrial; 8) comercialização. Em média, foi identificada a incidência de 11 políticas públicas por UPA no período de 19 anos considerado (2000 a 2018), sendo que a UPA em que incidiu o maior número de políticas públicas contou com 17 políticas incidentes e na UPA com o menor número de políticas públicas, houve a incidência de apenas 2 políticas. Destacaram-se, pela importância, a linha de crédito do Pronaf Mais Alimentos, o Programa Nacional de Habitação Rural (PNHR) e o Programa Nacional de Crédito Fundiário (PNCF). Constatou-se uma desigual incidência de políticas públicas e diferentes necessidades apontadas pelas famílias em cada um dos tipos de UPAs identificados. Os resultados das entrevistas também apontaram para a necessidade de políticas de garantia de preço, acesso à mercados diferenciados para agricultura familiar, modernização da infraestrutura produtiva, acesso à terra e reconhecimento da pluriatividade na agricultura familiar. Destaca-se a importância de considerar a influência do conjunto de políticas incidentes na agricultura familiar, tanto para a construção de políticas de desenvolvimento rural, quanto na análise, diagnóstico e planejamento de UPAs.The current study addresses the public policies incidence on family farming in the Northwest Frontier region of Rio Grande do Sul. Based on a systemic approach and privileging the farming families' point of view, we sought to reveal the impact of public policies “in the colony”, as the “rural area” is called by family farmers in the region. Aiming to contribute to the understanding of public policies in rural development, this research had as objective to identify the set of policies accessed by family farming in the Northwest Frontier region of Rio Grande do Sul, considering the family farmers understanding about it and their interference in their social and productive systems. Based on the approach of studying the evolution and differentiation of agrarian systems, the following steps of methodological operationalization were carried out: 1) reconstitution of the agriculture's history of the region; 2) interviews with key informants and the elaboration of a family farming typology; 3) visits to Agricultural Production Units and interviews with farming families; 4) data tabulation and results analysis. Five agrarian systems have been identified in the history of the region, namely: 1) Indigenous Agrarian System; 2) Jesuit-Guarani Agrarian System; 3) Caboclo Agrarian System; 4) Colonial Agrarian System; 5) Agroindustrial Modern Agrarian System. For the socioeconomic characterization of family farming in the Fronteira Noroeste region, UPAs were classified into 9 types based on their production systems, which were called: 1) Milk type; 2) Milk + Smoke yype; 3) Milk + Grain type; 4) Milk + Pigs type ; 5) Grain type; 6) Pigs + Grains type; 7) Beef Cattle type; 8) Artisanal fishing type; 9) Vegetable type. 49 public policies were identified (at different levels and levels) in the family farming UPAs surveyed, which were classified into eight areas of incidence: 1) land access; 2) housing and rural electrification; 3) rural health; 4) Countryside education and professional training; 5) socioassistance; 6) environmental; 7) agricultural and agro-industrial production; 8) commercialization. On average, the incidence of 11 public policies per UPA were identified, in a period of 19-year period (2000 to 2018), wherein the UPA with the highest number of public policies accessed 17 policies and the UPA with the lowest number of public policies accessed only two policies. Due to their importance, The Pronaf Mais Alimentos credit line, the National Rural Housing Program (PNHR) and the National Land Credit Program (PNCF) stood out. An unequal incidence of public policies was observed and different needs were pointed out by families in each of the types of UPAs identified. The interviews results also pointed to the need for price guarantee policies, access to differentiated markets for family farming, modernization of the productive infrastructure, access to land and recognition of the pluriactivity in family farming. The importance of considering the influence of the set of policies on family farming is highlighted, both for the construction of rural development policies and for the analysis, diagnosis and planning of UPAs

Early atrophy of pallidum and accumbens nucleus in Huntington's disease

In Huntington's disease (HD) atrophy of the caudate nucleus and putamen has been described many years before clinical manifestation. Volume changes of the pallidum, thalamus, brainstem, accumbens nucleus, hippocampus, and amygdala are less well investigated, or reported with contradicting results. The aim of our study is to provide a more precise view of the specific atrophy of the subcortical grey matter structures in different stages of Huntington's disease, and secondly to investigate how this influences the clinical manifestations. All TRACK-HD subjects underwent standardised T1-weighted 3T MRI scans encompassing 123 manifest HD (stage 1, n = 77; stage 2, n = 46), 120 premanifest HD (close to onset n = 58, far from onset n = 62) and 123 controls. Using FMRIB's FIRST and SIENAX tools the accumbens nucleus, amygdala, brainstem, caudate nucleus, hippocampus, pallidum, putamen, thalamus and whole brain volume were extracted. Results showed that volumes of the caudate nucleus and putamen were reduced in premanifest HD far from predicted onset (> 10.8 years). Atrophy of accumbens nucleus and pallidum was apparent in premanifest HD in the close to onset group (0-10.8 years). All other structures were affected to some degree in the manifest group, although brainstem, thalamus and amygdala were relatively spared. The accumbens nucleus, putamen, pallidum and hippocampus had a strong significant correlation with functional and motor scores. We conclude that volume changes may be a sensitive and reliable measure for early disease detection and in this way serve as a biomarker for Huntington's disease. Besides the caudate nucleus and putamen, the pallidum and the accumbens nucleus show great potential in this respect.Neurological Motor Disorder

Apathy and atrophy of subcortical brain structures in Huntington's disease: A two-year follow-up study

Background: Huntington's disease (HD) is characterized by motor and behavioral symptoms, and cognitive decline. HD gene carriers and their caregivers report the behavioral and cognitive symptoms as the most burdensome. Apathy is the most common behavioral symptom of HD and is related to clinical measures of disease progression, like functional capacity. However, it is unknown whether apathy is directly related to the neurodegenerative processes in HD. Objective: The aim is to investigate whether an association between atrophy of subcortical structures and apathy is present in HD, at baseline and after 2 years follow-up. Method: Volumes of 7 subcortical structures were measured using structural T1 MRI in 171 HD gene carriers of the TRACK-HD study and apathy was assessed with the Problem Behaviors Assessment-Short, at baseline and follow-up visit. At baseline, logistic regression was used to evaluate whether volumes of subcortical brain structures were associated with the presence of apathy. Linear regression was used to assess whether subcortical atrophy was associated with the degree of apathy at baseline and with an increase in severity of apathy over time. Results: At baseline, smaller volume of the thalamus showed a higher probability of the presence of apathy in HD gene carriers, but none of the subcortical structures was associated with the degree of apathy. Over time, no association between atrophy of any subcortical structures and change in degree of apathy was found. Conclusion: The presence of apathy is associated with atrophy of the thalamus in HD, suggesting that apathy has an underlying neural cause and might explain the high incidence of apathy in HD. However, no association was found between atrophy of these subcortical structures and increase in severity of apathy over a 2-year time period. Keywords: Apathy, Huntington's disease, Subcortical structures, Thalamu

The structural correlates of functional deficits in early huntington's disease

Neurological Motor Disorder

Pharmacologic inhibition of hypoxia-inducible factor (HIF)-hydroxylases ameliorates allergic contact dermatitis

Background When an immune cell migrates from the bloodstream to a site of chronic inflammation, it experiences a profound decrease in microenvironmental oxygen levels leading to a state of cellular hypoxia. The hypoxia‐inducible factor‐1α (HIF‐1α) promotes an adaptive transcriptional response to hypoxia and as such is a major regulator of immune cell survival and function. HIF hydroxylases are the family of oxygen‐sensing enzymes primarily responsible for conferring oxygen dependence upon the HIF pathway. Methods Using a mouse model of allergic contact dermatitis (ACD), we tested the effects of treatment with the pharmacologic hydroxylase inhibitor DMOG, which mimics hypoxia, on disease development. Results Re‐exposure of sensitized mice to 2,4‐dinitrofluorobenzene (DNFB) elicited inflammation, edema, chemokine synthesis (including CXCL1 and CCL5) and the recruitment of neutrophils and eosinophils. Intraperitoneal or topical application of the pharmacologic hydroxylase inhibitors dymethyloxalylglycine (DMOG) or JNJ1935 attenuated this inflammatory response. Reduced inflammation was associated with diminished recruitment of neutrophils and eosinophils but not lymphocytes. Finally, hydroxylase inhibition reduced cytokine‐induced chemokine production in cultured primary keratinocytes through attenuation of the JNK pathway. Conclusion These data demonstrate that hydroxylase inhibition attenuates the recruitment of neutrophils to inflamed skin through reduction of chemokine production and increased neutrophilic apoptosis. Thus, pharmacologic inhibition of HIF hydroxylases may be an effective new therapeutic approach in allergic skin inflammation.This work was funded by Science Foundation Ireland grants to Cormac Taylor and Martin Steinhoff and a grant from the European Union (ERACoSYSMed) to Cormac Taylor and Martin Schneider. Moritz Strowitzki receives funding from the German Research Foundation (DFG; STR 1570/1-1) and the Braun Foundation (Braun; BBSTD18/00018).Scopu

Tapping linked to function and structure in premanifest and symptomatic Huntington disease(e–Pub ahead of print)

Objective: Motor signs are functionally disabling features of Huntington disease. Characteristic motor signs define disease manifestation. Their severity and onset are assessed by the Total Motor Score of the Unified Huntington's Disease Rating Scale, a categorical scale limited by interrater variability and insensitivity in premanifest subjects. More objective, reliable, and precise measures are needed which permit clinical trials in premanifest populations. We hypothesized that motor deficits can be objectively quantified by force-transducer-based tapping and correlate with disease burden and brain atrophy.Methods: A total of 123 controls, 120 premanifest, and 123 early symptomatic gene carriers performed a speeded and a metronome tapping task in the multicenter study TRACK-HD. Total Motor Score, CAGrepeat length, and MRIs were obtained. The premanifest group was subdivided into A and B, based on the proximity to estimated disease onset, the manifest group into stages 1 and 2, according to their Total Functional Capacity scores. Analyses were performed centrally and blinded.Results: Tapping variability distinguished between all groups and subgroups in both tasks and correlated with 1) disease burden, 2) clinical motor phenotype, 3) gray and white matter atrophy, and 4) cortical thinning. Speeded tapping was more sensitive to the detection of early changes.Conclusion: Tapping deficits are evident throughout manifest and premanifest stages. Deficits are more pronounced in later stages and correlate with clinical scores as well as regional brain atrophy, which implies a link between structure and function. The ability to track motor phenotype progression with force-transducer-based tapping measures will be tested prospectively in the TRACK-HD study. Neurology (R) 2010;75:2150-216