136 research outputs found
kassubek_LANDSCAPE_TAN-18-OR-0090_suppl – Supplemental material for Structural brain signature of cognitive decline in Parkinson’s disease: DTI-based evidence from the LANDSCAPE study
No full textSupplemental material, kassubek_LANDSCAPE_TAN-18-OR-0090_suppl for Structural brain signature of cognitive decline in Parkinson’s disease: DTI-based evidence from the LANDSCAPE study by Martin Gorges, Hans-Peter Müller, Inga Liepelt-Scarfone, Alexander Storch, Richard Dodel, Rüdiger Hilker-Roggendorf, Daniela Berg, Martin S. Kunz, Elke Kalbe, Simon Baudrexel and Jan Kassubek in Therapeutic Advances in Neurological Disorders</p
Costs of Parkinson's Disease and Antiparkinsonian Pharmacotherapy: An Italian Cohort Study
No full textObjective: Antiparkinsonian pharmacotherapy is costly and the determinants of drug costs in Parkinson's disease (PD) have been poorly investigated. The objective of this study was to investigate the costs of PD and antiparkinsonian drugs in an Italian cohort of patients and identify cost-driving factors of drug therapy. Methods: Seventy outpatients with idiopathic PD were recruited in the Department of Neurology, Napoli University, Italy. Data on resource utilization were collected for 6 months using a bottom-up approach. Clinical status was evaluated using the Unified Parkinson's Disease Rating Scale. Direct and indirect costs were calculated from the societal perspective (figures of year 2009). Independent determinants of total costs and costs of antiparkinsonian drugs were identified using multivariate regression analysis. Results: The total costs of PD were EUR 8,640 (95% CI: EUR 6,700-11,240) per patient over a 6-month period. Direct costs accounted for 70% of the total costs. Antiparkinsonian drugs (EUR 1,450; 95% CI: EUR 1,220-1,760) were the primary component of costs paid by the health insurance (39.6%) and one of the most expensive components of the direct costs (24.0%). The highest copayments made by patients were for antiparkinsonian drugs and medical equipment (58%). Independent determinants of the increased costs of antiparkinsonian pharmacotherapy were younger age and occurrence of motor fluctuations. Conclusions: Antiparkinsonian pharmacotherapy is one of the major cost components of PD-related costs for health insurance. It imposes a considerable economic burden on patients and their families as well. Copyright (C) 2010 S. Karger AG, Base
Trim17, novel E3 ubiquitin-ligase, initiates neuronal apoptosis
No full textAccumulating data indicate that the ubiquitin-proteasome system controls apoptosis by regulating the level and the function of key regulatory proteins. In this study, we identified Trim17, a member of the TRIM/RBCC protein family, as one of the critical E3 ubiquitin ligases involved in the control of neuronal apoptosis upstream of mitochondria. We show that expression of Trim17 is increased both at the mRNA and protein level in several in vitro models of transcription-dependent neuronal apoptosis. Expression of Trim17 is controlled by the PI3K/Akt/GSK3 pathway in cerebellar granule neurons (CGN). Moreover, the Trim17 protein is expressed in vivo, in apoptotic neurons that naturally die during post-natal cerebellar development. Overexpression of active Trim17 in primary CGN was sufficient to induce the intrinsic pathway of apoptosis in survival conditions. This pro-apoptotic effect was abolished in Bax(-/-) neurons and depended on the E3 activity of Trim17 conferred by its RING domain. Furthermore, knock-down of endogenous Trim17 and overexpression of dominant-negative mutants of Trim17 blocked trophic factor withdrawal-induced apoptosis both in CGN and in sympathetic neurons. Collectively, our data are the first to assign a cellular function to Trim17 by showing that its E3 activity is both necessary and sufficient for the initiation of neuronal apoptosis. Cell Death and Differentiation (2010) 17, 1928-1941; doi: 10.1038/cdd.2010.73; published online 18 June 201
A Consensus Set of Outcomes for Parkinson's Disease from the International Consortium for Health Outcomes Measurement.
No full textItem does not contain fulltextBACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative condition that is expected to double in prevalence due to demographic shifts. Value-based healthcare is a proposed strategy to improve outcomes and decrease costs. To move towards an actual value-based health care system, condition-specific outcomes that are meaningful to patients are essential. OBJECTIVE: Propose a global consensus standard set of outcome measures for PD. METHODS: Established methods for outcome measure development were applied, as outlined and used previously by the International Consortium for Health Outcomes Measurement (ICHOM). An international group, representing both patients and experts from the fields of neurology, psychiatry, nursing, and existing outcome measurement efforts, was convened. The group participated in six teleconferences over a six-month period, reviewed existing data and practices, and ultimately proposed a standard set of measures by which patients should be tracked, and how often data should be collected. RESULTS: The standard set applies to all cases of idiopathic PD, and includes assessments of motor and non-motor symptoms, ability to work, PD-related health status, and hospital admissions. Baseline demographic and clinical variables are included to enable case mix adjustment. CONCLUSIONS: The Standard Set is now ready for use and pilot testing in the clinical setting. Ultimately, we believe that using the set of outcomes proposed here will allow clinicians and scientists across the world to document, report, and compare PD-related outcomes in a standardized fashion. Such international benchmarks will improve our understanding of the disease course and allow for identification of 'best practices', ultimately leading to better informed treatment decisions
Methods for monitoring and measurement of protein translation in time and space
No full textRegulation of protein translation constitutes a crucial step in control of gene expression. In comparison
to transcriptional regulation, however, translational control has remained a significantly under-studied
layer of gene expression. This trend is now beginning to shift thanks to recent advances in nextgeneration sequencing, proteomics, and microscopy based methodologies which allow accurate
monitoring of protein translation rates, from single target messenger RNA molecules to genome-wide
scale studies. In this review, we summarize these recent advances, and discuss how they are enabling
researchers to study translational regulation in a wide variety of in vitro and in vivo biological systems,
with unprecedented depth and spatiotemporal resolution.The authors are funded by a Medical Research Council (MRC) Career Development Award to F. K. M. (MR/P009417/1)
Predictive response-relevant clustering of expression data provides insights into disease processes
No full textThis article describes and illustrates a novel method of microarray data analysis that couples model-based clustering and binary classification to form clusters of ;response-relevant' genes; that is, genes that are informative when discriminating between the different values of the response. Predictions are subsequently made using an appropriate statistical summary of each gene cluster, which we call the ;meta-covariate' representation of the cluster, in a probit regression model. We first illustrate this method by analysing a leukaemia expression dataset, before focusing closely on the meta-covariate analysis of a renal gene expression dataset in a rat model of salt-sensitive hypertension. We explore the biological insights provided by our analysis of these data. In particular, we identify a highly influential cluster of 13 genes-including three transcription factors (Arntl, Bhlhe41 and Npas2)-that is implicated as being protective against hypertension in response to increased dietary sodium. Functional and canonical pathway analysis of this cluster using Ingenuity Pathway Analysis implicated transcriptional activation and circadian rhythm signalling, respectively. Although we illustrate our method using only expression data, the method is applicable to any high-dimensional datasets
Intensive hunting changes human-wildlife relationships
No full textWildlife alter their behaviors in a trade-off between consuming food and fear of becoming food themselves. The risk allocation hypothesis posits that variation in the scale, intensity and longevity of predation threats can influence the magnitude of antipredator behavioral responses. Hunting by humans represents a threat thought to be perceived by wildlife similar to how they perceive a top predator, although hunting intensity and duration varys widely around the world. Here we evaluate the effects of hunting pressure on wildlife by comparing how two communities of mammals under different management schemes differ in their relative abundance and response to humans. Using camera traps to survey wildlife across disturbance levels (yards, farms, forests) in similar landscapes in southern Germany and southeastern USA, we tested the prediction of the risk allocation hypothesis: that the higher intensity and longevity of hunting in Germany (year round vs 3 months, 4x higher harvest/km(2)/year) would reduce relative abundance of hunted species and result in a larger fear-based response to humans (i.e., more spatial and temporal avoidance). We further evaluated how changes in animal abundance and behavior would result in potential changes to ecological impacts (i.e., herbivory and predation). We found that hunted species were relatively less abundant in Germany and less associated with humans on the landscape (i.e., yards and urban areas), but did not avoid humans temporally in hunted areas while hunted species in the USA showed the opposite pattern. These results are consistent with the risk allocation hypothesis where we would expect more spatial avoidance in response to threats of longer duration (i.e., year-round hunting in Germany vs. 3-month duration in USA) and less spatial avoidance but more temporal avoidance for threats of shorter duration. The expected ecological impacts of mammals in all three habitats were quite different between countries, most strikingly due to the decreases in the relative abundance of hunted species in Germany, particularly deer, with no proportional increase in unhunted species, resulting in American yards facing the potential for 25x more herbivory than German yards. Our results suggest that the duration and intensity of managed hunting can have strong and predictable effects on animal abundance and behavior, with the potential for corresponding changes in the ecological impacts of wildlife. Hunting can be an effective tool for reducing wildlife conflict due to overabundance but may require more intensive harvest than is seen in much of North America
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