188 research outputs found
Parkinson’s Disease Subtypes: Critical Appraisal and Recommendations
No full textBackground: In Parkinson’s disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this heterogeneity with potential contribution for the knowledge of disease pathophysiology, natural history and therapeutic development. There have been many studies of PD subtypes but their impact remains unclear with limited application in research or clinical practice. Objective: To critically evaluate PD subtyping systems. Methods: We conducted a systematic review of PD subtypes, assessing the characteristics of the studies reporting a subtyping system for the first time. We completed a critical appraisal of their methodologic quality and clinical applicability using standardized checklists. Results: We included 38 studies. The majority were cross-sectional (n = 26, 68.4%), used a data-driven approach (n = 25, 65.8%), and non-clinical biomarkers were rarely used (n = 5, 13.1%). Motor characteristics were the domain most commonly reported to differentiate PD subtypes. Most of the studies did not achieve the top rating across items of a Methodologic Quality checklist. In a Clinical Applicability Checklist, the clinical importance of differences between subtypes, potential treatment implications and applicability to the general population were rated poorly, and subtype stability over time and prognostic value were largely unknown. Conclusion: Subtyping studies undertaken to date have significant methodologic shortcomings and most have questionable clinical applicability and unknown biological relevance. The clinical and biological signature of PD may be unique to the individual, rendering PD resistant to meaningful cluster solutions. New approaches that acknowledge the individual-level heterogeneity and that are more aligned with personalized medicine are needed
Bloemhof der doorluchtige voorbeelden, daer in door ware, vreemde en deftige geschiedenissen, leeringen en eygenschappen, alles dat de mensch tot nut en vermaek verstrekken kan, te bemerken is : uit de schriften van Philippus Camerarius, Michiel de Montanje en andere schrijvers getrokken en vertaelt /
No full textSignatures: *⁴ A-3A⁴.T.p. vignette and 6 emblematic engravings by Jan Swelinck, taken from Zacharias Heyns' Emblemata of 1625. See Landwehr.Landwehr, J. Emblem books in the Low Countries,Mode of access: Internet.Binding: vellum, lapped foredges. Author, title & date written at head of spine
Peripheral mitochondrial function correlates with clinical severity in idiopathic Parkinson disease
No full textPeripheral mitochondrial function correlates with clinical severity in idiopathic Parkinson’s disease
No full textBackground: Parkinson’s disease is an intractable disorder with heterogeneous clinical presentation that may reflect different underlying pathogenic mechanisms. Surrogate indicators of pathogenic processes correlating with clinical measures may assist in better patient stratification. Mitochondrial function, which is impaired in and central to PD pathogenesis, may represent one such surrogate indicator. Methods: Mitochondrial function was assessed by respirometry experiment in fibroblasts derived from idiopathic patients (n = 47) in normal conditions and in experimental settings that do not permit glycolysis and therefore force energy production through mitochondrial function. Respiratory parameters and clinical measures were correlated with bivariate analysis. Machine-learning-based classification and regression trees were used to classify patients on the basis of biochemical and clinical measures. The effects of mitochondrial respiration on α-synuclein stress were assessed monitoring the protein phosphorylation in permitting versus restrictive glycolysis conditions. Results: Bioenergetic properties in peripheral fibroblasts correlate with clinical measures in idiopathic patients, and the correlation is stronger with predominantly nondopaminergic signs. Bioenergetic analysis under metabolic stress, in which energy is produced solely by mitochondria, shows that patients’ fibroblasts can augment respiration, therefore indicating that mitochondrial defects are reversible. Forcing energy production through mitochondria, however, favors α-synuclein stress in different cellular experimental systems. Machine-learning-based classification identified different groups of patients in which increasing disease severity parallels higher mitochondrial respiration. Conclusion: The suppression of mitochondrial activity in PD may be an adaptive strategy to cope with concomitant pathogenic factors. Moreover, mitochondrial measures in fibroblasts are potential peripheral biomarkers to follow disease progression
Transitioning from Subtyping to Precision Medicine in Parkinson's Disease: A Purpose‐Driven Approach
No full textAbstract
The International Parkinson and Movement Disorder Society (MDS) created a task force (TF) to provide a critical overview of the Parkinson's disease (PD) subtyping field and develop a guidance on future research in PD subtypes. Based on a literature review, we previously concluded that PD subtyping requires an ultimate alignment with principles of precision medicine, and consequently novel approaches were needed to describe heterogeneity at the individual patient level. In this manuscript, we present a novel purpose‐driven framework for subtype research as a guidance to clinicians and researchers when proposing to develop, evaluate, or use PD subtypes. Using a formal consensus methodology, we determined that the key purposes of PD subtyping are: (1) to predict disease progression, for both the development of therapies (use in clinical trials) and prognosis counseling, (2) to predict response to treatments, and (3) to identify therapeutic targets for disease modification. For each purpose, we describe the desired product and the research required for its development. Given the current state of knowledge and data resources, we see purpose‐driven subtyping as a pragmatic and necessary step on the way to precision medicine. © 2024 The Authors.
Movement Disorders
published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Reflex Mechanisms in CRPS-Related Dystonia
No full textThis paper focuses on the pathophysiology of fixed dystonia (i.e., sustained muscle contractions resulting in abnormal postures) in Complex Regional Pain Syndrome from an engineering point of view. Although the mechanisms are still elusive, the evidence implicating involvement of aberrant muscle force feedback is compelling. A neuromuscular model with aberrant muscle force feedback successfully mimicked fixed dystonia while results of several experiments point to involvement of muscle force feedback.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Biomechatronics & Human-Machine Contro
European VAT and the sharing economy
No full textThe past few years have seen the sensational rise of new models of production, distribution and consumption, synthetically referred to as the "sharing economy". The advent of such new economic models, underpinned by digital platforms like Airbnb, Uber, GuestToGuest and BlaBlaCar, poses however several challenges in the legal field. Against this background, the research seeks to assess the practical feasibility to apply a tax, such as the European VAT, which was conceived in the 1960s, to the reality of the sharing economy. In particular, through the help of several interpretative sources and a framework of selected tax principles, the study relates the specifics of the sharing economy to the following EU VAT propositions: the concepts of "taxable persons" and "taxable transactions", the CJEU's doctrine on "composite supplies", the "place of supply" rules, and the attribution to platforms of a "liability for collection and remittance of VAT". Building on such analysis, the author finally formulates a series of recommendations for improving the current EU VAT system.Negli ultimi anni si è assistito alla sensazionale ascesa di nuovi modelli di produzione, distribuzione e consumo, denominati, con un'espressione sintetica, "sharing economy". L'avvento di tali nuovi modelli economici, promosso da piattaforme digitali quali Airbnb, Uber, GuestToGuest e BlaBlaCar, pone tuttavia diverse criticità sul versante giuridico. In tale contesto, la ricerca mira a valutare l'effettiva possibilità di applicare un tributo concepito negli anni '60, quale l'Imposta sul Valore Aggiunto, alla realtà dell'economia della condivisione. In particolare, mediante l'ausilio di diverse fonti interpretative e alcuni principi che regolano la materia tributaria, lo studio pone in relazione le specificità dell'economia della condivisione ai seguenti elementi della normativa europea in campo IVA: i concetti di "soggetti passivi" e "operazioni imponibili", la dottrina elaborata dalla CGUE circa le "operazioni complesse", la normativa in materia di "luogo della prestazione", nonché l'attribuzione alle piattaforme di una "responsabilità per il pagamento dell'IVA". A fronte di tale analisi, l'autore formula infine una serie di raccomandazioni volte a migliorare l'attuale regolamentazione europea in campo IVA.Discipline manageriali, finanziarie e giuridiche per la gestione integrata d'aziend
A Historical Perspective on Rating Scales in PD: The Problems of Evaluating Impairments and Disabilities
No full textRisk factors for hallucinations in Parkinson's disease: Results from a large prospective cohort study
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