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1.
Notf Rett Med ; 25(6): 401-411, 2022.
Artigo em Alemão | MEDLINE | ID: mdl-35464755

RESUMO

Background: Recent advances in acute stroke therapy have been shown to improve clinical outcome and therefore reduce long-term disability. Acute therapy procedures in stroke have a limited time frame after onset of symptoms; thus, rapid emergency management is critical. The Tyrolean Stroke Pathway was developed to optimize the entire treatment pathway from stroke onset to outpatient rehabilitation. Objectives: The description of the Tyrolean Stroke Pathway as an example to optimize the entire treatment pathway of stroke patients in a central European alpine region with a focus on prehospital management. Materials and methods: In four subprojects from the prehospital phase up to outpatient rehabilitation, the project optimized intersections between different phases of care and evaluated the care processes using quality assurance measures. Results: After implementation, thrombolysis rates doubled and functional outcome of stroke patients after 3 months improved and complications, e.g., pneumonia, declined. Access to rehabilitation improved, particularly because of the establishment of quality assured and funded outpatient rehabilitation. Conclusions: The project showed that a holistic standardized stroke pathway from acute management up to outpatient rehabilitation can be successfully implemented in clinical routine. The project improved the entire health care pathway of stroke patients. The Stroke Action Plan for Europe 2018-2030 recommends to have national plans for stroke that encompass the entire chain of care.

2.
Cell Rep ; 35(2): 108985, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33852843

RESUMO

Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective and lifespan-extending effects of dietary spermidine, a natural autophagy-promoting polyamine. Here, we show that dietary spermidine passes the blood-brain barrier in mice and increases hippocampal eIF5A hypusination and mitochondrial function. Spermidine feeding in aged mice affects behavior in homecage environment tasks, improves spatial learning, and increases hippocampal respiratory competence. In a Drosophila aging model, spermidine boosts mitochondrial respiratory capacity, an effect that requires the autophagy regulator Atg7 and the mitophagy mediators Parkin and Pink1. Neuron-specific Pink1 knockdown abolishes spermidine-induced improvement of olfactory associative learning. This suggests that the maintenance of mitochondrial and autophagic function is essential for enhanced cognition by spermidine feeding. Finally, we show large-scale prospective data linking higher dietary spermidine intake with a reduced risk for cognitive impairment in humans.


Assuntos
Envelhecimento/genética , Proteína 7 Relacionada à Autofagia/genética , Disfunção Cognitiva/genética , Suplementos Nutricionais , Proteínas Quinases/genética , Espermidina/farmacologia , Ubiquitina-Proteína Ligases/genética , Envelhecimento/metabolismo , Animais , Proteína 7 Relacionada à Autofagia/metabolismo , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Cognição/fisiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/prevenção & controle , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Aprendizagem/efeitos dos fármacos , Aprendizagem/fisiologia , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Proteínas Quinases/metabolismo , Transdução de Sinais , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Ubiquitina-Proteína Ligases/metabolismo
3.
Sci Transl Med ; 13(580)2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568522

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD+). Elevating NAD+ by oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction induced by aging (in 2-year-old C57BL/6J mice), hypertension (in Dahl salt-sensitive rats), or cardiometabolic syndrome (in ZSF1 obese rats). This effect was mediated partly through alleviated systemic comorbidities and enhanced myocardial bioenergetics. Simultaneously, nicotinamide directly improved cardiomyocyte passive stiffness and calcium-dependent active relaxation through increased deacetylation of titin and the sarcoplasmic reticulum calcium adenosine triphosphatase 2a, respectively. In a long-term human cohort study, high dietary intake of naturally occurring NAD+ precursors was associated with lower blood pressure and reduced risk of cardiac mortality. Collectively, these results suggest NAD+ precursors, and especially nicotinamide, as potential therapeutic agents to treat diastolic dysfunction and HFpEF in humans.


Assuntos
Insuficiência Cardíaca , Animais , Estudos de Coortes , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Ratos , Ratos Endogâmicos Dahl , Volume Sistólico
4.
Gesundheitswesen ; 82(S 02): S122-S130, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-32193880

RESUMO

AIMS AND OBJECTIVES: Data linkage is of paramount importance in the evaluation of treatment regimens for chronic diseases where different health care sectors are involved. A comprehensive picture of long-term treatment effects and, in particular, the cost-effectiveness ratio of treatment approaches can only be drawn when data from various sources are merged and analyzed together. METHODOLOGICAL PROBLEMS AND CHALLENGES: Regarding post-acute stroke care, the present study gives an example of an exact deterministic data linkage procedure including clinical patient records and claims data of TGKK, the main Tyrolean statutory health insurance fund. Typical problems known from other data linkage projects also emerged in the so-called StrokeCard program conducted at the Medical University of Innsbruck. Distinctive Austrian features (the majority of the Austrian population benefits from a mandatory social insurance system without freedom of choice) facilitated the feasibility of the data linkage procedures. RESULTS: Over the recruitment period 01/2014-12/2015, 540 patients could be assigned to the operative dataset. Of these, 367 patients were part of the StrokeCard group (i. e. the treatment group), and 173 belonged to the usual care group (i. e. the control group); 11 patients did not complete the one-year follow-up period (7 treatment group patients vs. 4 control group patients); 7 of them died during the study (5 treatment group patients vs. 2 control group patients). For all 540 patients, TGKK claims data were available for the time-frames of one year before recruitment and one year after discharge from the University hospital. All data could be used in the health-economic evaluation of the StrokeCard program. CONCLUSIONS: The linking of clinical patient records with data collected by SHI funds opens a window of opportunities for analyses of medical care. Counter-intuitively, Austrian health services research activities have limited experience in data linkage approaches, alhough studies based on the linkage of clinical patient records and claims data are indispensable for the evaluation of complex multi-sectoral treatment schemes. The current project proves the feasibility of data linkage mechanisms in the Austrian context. This should be regarded as an impetus for extending data linkage principles to evaluation studies in the future.


Assuntos
Pesquisa sobre Serviços de Saúde , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Áustria , Alemanha , Humanos , Programas Nacionais de Saúde
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