The role of TAU protein in the pathophysiology of frontotemporal dementia

CONTEXTO: Sob a denominação demência frontotemporal (DFT) enquadram-se importantes síndromes demenciais de natureza degenerativa progressiva que acometem os lobos frontais e temporais em ambos os hemisférios. As DFTs podem ser agrupadas, segundo seus aspectos clínicos dominantes, em variante frontal, afasia progressiva não fluente e demência semântica. A proteína Tau tem papel importante na patogenia desses transtornos, e anormalidades conformacionais estão presentes em até 50% dos casos de DFT esporádica. Do ponto de vista neuropatológico, as DFTs podem ser classificadas em Tau negativas e Tau positivas, estas últimas também classificadas entre as tauopatias. OBJETIVO: Neste trabalho será revisto o papel da proteína Tau na patogenia das DFTs. MÉTODOS: Busca simples no Scielo e na Pubmed por meio das palavras-chave: "tauopatias", "demência frontotemporal" e "proteína Tau". Foram revisados os artigos publicados a partir de 2000, e artigos anteriores de maior relevância, identificados a partir das referências estudadas. RESULTADOS: Dentre os trabalhos incluídos nesta análise, 12 abordam as tauopatias, sendo dez originais e sete de revisão. Foram identificados 20 artigos sobre DFT, sendo 16 artigos originais e quatro de revisão. CONCLUSÃO: A proteína Tau tem papel fundamental na patogenia das DFTs e outras doenças neurodegenerativas. O conhecimento desses mecanismos fisiopatológicos é o passo inicial para o desenvolvimento de estratégias terapêuticas.BACKGROUND: Frontotemporal dementia (FTD) represents an important group of neurodegenerative diseases, affecting temporal and frontal lobes of both hemispheres. FTD can be divided into three clinical subsyndromes: frontal variant, non-fluent progressive aphasia, and semantic dementia. Abnormalities of the metabolism of Tau protein are present in the physiopathology of FTD, and is found in approximately 50% of sporadic cases, supporting the classification of the FTDs into Tau-negative and Tau-positive subtypes, the latter also called "Tauopathies". OBJECTIVE: To review the role of Tau in the pathophysiology of FTD. METHODS: Review of the literature on FTD published in the Pubmed and Scielo databases since the year 2000, using the keywords: Tau, Tauopathies, frontotemporal dementia. Relevant references previously published, as indicated in the reference list of selected articles, were also included. RESULTS: Through electronic search we identified 12 articles addressing Tauopathies (ten containing original data and seven reviews), and 20 articles (16 with original data and four reviews) on FTDs. CONCLUSIONS: There is consistent evidence in the literature to support the notion that Tau protein plays a crucial role in the pathogenesis of FTDs and other neurodegenerative dementias, and the knowledge on these mechanisms is necessary for the development of more specific therapies

The end of fascism?

When did fascism end? Did it end in July 1943, with the fall of Mussolini from power, or in April 1945, with Liberation Day? The argument of this article is that fascism was not simply a historical experience but a political form that attempted to transcend Italy's social and political fractures with fantasies and unrealistic but nevertheless captivating expectations. Its hypnotic contagious power cast a mimetic spell that can be continuously reloaded: by blurring the boundaries between truth and lies; by exploiting crowd irrationality; by establishing boundaries between outsiders and insiders; by perpetuating negative sentiments of hostility, fear and envy within society; and by manipulating time. The argument, therefore, is that fascism has never ended, not merely in the sense of political and cultural continuity, but in the deeper sense of immanency within the body politic of Italy's democracy. As such, it is meaningless to wonder whether fascism might come back. It is here and now, in the only form that current historical circumstances allow it to exist - and yet it might be countered by a process of rejection that individuals and political communities can and should exercise in their everyday life, adopting the political form generated by the Resistance.Il principale argomento di questo articolo & egrave; che il fascismo non fu semplicemente un'esperienza storica ma una forma politica che tent & ograve; di trascendere le fratture sociali e politiche dell'Italia con fantasie e aspettative irrealistiche, ma comunque accattivanti, che sono state poi nel tempo riattivate e imitate e che possono essere ancora riattivate e imitate nel futuro. Da questo punto di vista, il fascismo non & egrave; mai finito, non solo nei termini di continuit & agrave; politica e culturale, ma nel senso pi & ugrave; profondo di immanenza all'interno del corpo politico della democrazia italiana. Tuttavia, il processo mimetico che garantisce la sopravvivenza del fascismo pu & ograve; essere contrastato da un processo di rifiuto che individui e comunit & agrave; politiche possono e devono attivamente esercitare nella vita quotidiana a partire dalla forma politica inaugurata nella storia d'Italia dalla Resistenza

An Alumni survey of the School of Social Work, Portland State University

The alumni survey conducted at Portland State University School of Social Work by second year students had two purposes. One purpose was to fulfill the research practicum requirements of a Masters of Social Work degree by providing experience in the area of applied survey research. The other was to provide a data base for future alumni research at the school

The Italian Resistance: historical junctures and new perspectives

This introduction to this special issue of Modern Italy explores how the emphasis on fascism in recent scholarship and public discourse risks its mythification and cultural rehabilitation, and urges a rebalancing of historiography to highlight the pivotal role of the Italian Resistance in shaping Italy's democratic identity. Marking the eightieth anniversary of Italy's liberation and the thirtieth anniversary of Modern Italy, the issue examines lesser-known aspects of the Resistance, such as marginal groups, gendered experiences and transnational perspectives. Contributions include studies on Roma Resistance fighters, the Catholic underground press, American soldiers of Italian descent, and women in the Liberal Party. The articles emphasise the liminality and creative potential of the Resistance as a transformative period that redefined political and cultural identities

Effects of a multidisciplinar cognitive rehabilitation program for patients with mild Alzheimer's disease

OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatry symptoms in patients with mild Alzheimer's disease. METHOD: The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer's patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer's patients in waiting lists for future intervention. INTERVENTION: Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing), physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings. MEASUREMENTS: The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer's disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments. RESULTS: Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer's subjects. The treatment was also beneficial for the patients' quality of life. CONCLUSION: This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer's patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield adjunct and clinically relevant benefits in dementia treatment

Effects of Stress on Lactate Levels and Other Physiological Variables During Exercise

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How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins?

Variations on the statement "the variant surface glycoprotein (VSG) coat that covers the external face of the mammalian bloodstream form of Trypanosoma brucei acts a physical barrier" appear regularly in research articles and reviews. The concept of the impenetrable VSG coat is an attractive one, as it provides a clear model for understanding how a trypanosome population persists; each successive VSG protects the plasma membrane and is immunologically distinct from previous VSGs. What is the evidence that the VSG coat is an impenetrable barrier, and how do antibodies and other extracellular proteins interact with it? In this review, the nature of the extracellular surface of the bloodstream form trypanosome is described, and past experiments that investigated binding of antibodies and lectins to trypanosomes are analysed using knowledge of VSG sequence and structure that was unavailable when the experiments were performed. Epitopes for some VSG monoclonal antibodies are mapped as far as possible from previous experimental data, onto models of VSG structures. The binding of lectins to some, but not to other, VSGs is revisited with more recent knowledge of the location and nature of N-linked oligosaccharides. The conclusions are: (i) Much of the variation observed in earlier experiments can be explained by the identity of the individual VSGs. (ii) Much of an individual VSG is accessible to antibodies, and the barrier that prevents access to the cell surface is probably at the base of the VSG N-terminal domain, approximately 5 nm from the plasma membrane. This second conclusion highlights a gap in our understanding of how the VSG coat works, as several plasma membrane proteins with large extracellular domains are very unlikely to be hidden from host antibodies by VSG.The authors’ lab is funded by the Wellcome Trust (093008/Z10/Z) and the Medical Research Council (MR/L008246/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It was first available from PLOS via http://dx.doi.org/10.1371/journal.ppat.100525

Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

Pulmonary tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb), is a major world health problem. The production of reactive nitrogen species (RNS) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. Nevertheless, the protective role of RNS during Mtb infection remains controversial. Here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pathogenesis. We found that recognition of Mycobacterium marinum, a close relative of Mtb, was sufficient to induce a nitrosative defense mechanism in a manner dependent on MyD88, the central adaptor protein in Toll like receptor (TLR) mediated pathogen recognition. However, this host response was attenuated by mycobacteria via a virulence mechanism independent of the well-characterized RD1 virulence locus. Our results indicate a mechanism of pathogenic mycobacteria to circumvent host defense in vivo. Shifting the balance of host-pathogen interactions in favor of the host by targeting this virulence mechanism may help to alleviate the problem of infection with Mtb strains that are resistant to multiple drug treatments

Using a virtual environment to assess cognition in the elderly

YesEarly diagnosis of Alzheimer’s disease (AD) is essential if treatments are to be administered at an earlier point in time before neurons degenerate to a stage beyond repair. In order for early detection to occur tools used to detect the disorder must be sensitive to the earliest of cognitive impairments. Virtual reality (VR) technology offers opportunities to provide products which attempt to mimic daily life situations, as much as is possible, within the computational environment. This may be useful for the detection of cognitive difficulties. We develop a virtual simulation designed to assess visuospatial memory in order to investigate cognitive function in a group of healthy elderly participants and those with a mild cognitive impairment. Participants were required to guide themselves along a virtual path to reach a virtual destination which they were required to remember. The preliminary results indicate that this virtual simulation has the potential to be used for detection of early AD since significant correlations of scores on the virtual environment with existing neuropsychological tests were found. Furthermore, the test discriminated between healthy elderly participants and those with a mild cognitive impairment (MCI)

The impact of physical activity on fatigue and quality of life in lung cancer patients: a randomised controlled trial protocol

Background: People with lung cancer have substantial symptom burden and more unmet needs than the general cancer population. Physical activity (PA) has been shown to positively influence quality of life (QOL), fatigue and daily functioning in the curative treatment of people with breast and colorectal cancers and lung diseases, as well as in palliative settings. A randomised controlled trial (RCT) is needed to determine if lung cancer patients benefit from structured PA intervention. The Physical Activity in Lung Cancer (PAL) trial is designed to evaluate the impact of a 2-month PA intervention on fatigue and QOL in patients with non-resectable lung cancer. Biological mechanisms will also be studied.Methods/design: A multi-centre RCT with patients randomised to usual care or a 2-month PA programme, involving supervised PA sessions including a behavioural change component and home-based PA. QOL questionnaires, disease and functional status and body composition will be assessed at baseline, 2, 4 and 6 months follow-up. The primary endpoint is comparative levels of fatigue between the 2 arms. Secondary endpoints include: QOL, functional abilities and physical function. Exploratory endpoints include: anxiety, depression, distress, dyspnoea, PA behaviour, fitness, hospitalisations, survival, cytokines and insulin-like growth factor levels.Discussion: This study will provide high-level evidence of the effect of PA programmes on cancer-related fatigue and QOL in patients with advanced lung cancer. If positive, the study has the potential to change care for people with cancer using a simple, inexpensive intervention to improve their QOL and help them maintain independent function for as long as possible.Trial registration: Australian New Zealand Clinical Trials Registry No. ACTRN12609000971235. © 2012 Dhillon et al.; licensee BioMed Central Ltd