A grounded theory study on the influence of sleep on Parkinson’s symptoms

Contains fulltext : 167717.pdf (publisher's version ) (Open Access)BACKGROUND: Upon awaking, many Parkinson's patients experience an improved mobility, a phenomenon known as 'sleep benefit'. Despite the potential clinical relevance, no objective correlates of sleep benefit exist. The discrepancy between the patients' subjective experience of improvement in absence of objective changes is striking, and raises questions about the nature of sleep benefit. We aimed to clarify what patients reporting subjective sleep benefit, actually experience when waking up. Furthermore, we searched for factors associated with subjective sleep benefit. METHODS: Using a standardized topic list, we interviewed 14 Parkinson patients with unambiguous subjective sleep benefit, selected from a larger questionnaire-based cohort. A grounded theory approach was used to analyse the data. RESULTS: A subset of the participants described a temporary decrease in their Parkinson motor symptoms after sleep. Others did experience beneficial effects which were, however, non-specific for Parkinson's disease (e.g. feeling 'rested'). The last group misinterpreted the selection questionnaire and did not meet the definition of sleep benefit for various reasons. There were no general sleep-related factors that influenced the presence of sleep benefit. Factors mentioned to influence functioning at awakening were mostly stress related. CONCLUSIONS: The group of participants convincingly reporting sleep benefit in the selection questionnaire appeared to be very heterogeneous, with only a portion of them describing sleep benefit on motor symptoms. The group of participants actually experiencing motor sleep benefit may be much smaller than reported in the literature so far. Future studies should employ careful inclusion criteria, which could be based on our reported data

Unequal Effects of Myosin 5B Mutations in Liver and Intestine Determine the Clinical Presentation of Low-Gamma-Glutamyltransferase Cholestasis

Mutations in the MYO5B gene cause in some patients low gamma-glutamyltransferase (low-GGT) cholestatic liver disease (CLD) and in other patients microvillus inclusion disease (MVID, a congenital diarrheal and malabsorption disorder). Overlap of symptoms occurs but more MVID patients present cholestasis than CLD patients present diarrhea. Clinical observations indicate that MYO5B mutations can cause but also protect against CLD. This complicates family counseling and therapeutic decisions. Here we have reviewed the literature on MYO5B mutations in relation to CLD. It appears that variations in the clinical presentation of low-GGT CLD can be attributed to the coincident expression but unequal effects of MYO5B mutations in hepatocytes versus enterocytes, two cell types that jointly constitute the core of the enterohepatic circulation. Therefore, contrasting other low-GGT CLDs, those associated with MYO5B mutations should be viewed as a disease of the enterohepatic circulation rather than solely of the liver

Model-Based Evaluation of Methods for Respiratory Sinus Arrhythmia Estimation

OBJECTIVE: Respiratory sinus arrhythmia (RSA) refers to heart rate oscillations synchronous with respiration, and it is one of the major representations of cardiorespiratory coupling. Its strength has been suggested as a biomarker to monitor different conditions and diseases. Some approaches have been proposed to quantify the RSA, but it is unclear which one performs best in specific scenarios. The main objective of this study is to compare seven state-of-the-art methods for RSA quantification using data generated with a model proposed to simulate and control the RSA. These methods are also compared and evaluated on a real-life application, for their ability to capture changes in cardiorespiratory coupling during sleep. METHODS: A simulation model is used to create a dataset of heart rate variability and respiratory signals with controlled RSA, which is used to compare the RSA estimation approaches. To compare the methods objectively in a real-life application, regression models trained on the simulated data are used to map the estimates to the same measurement scale. RESULTS AND CONCLUSION: RSA estimates based on cross entropy, time-frequency coherence and subspace projections showed the best performance on simulated data. In addition, these estimates captured the expected trends in the changes in cardiorespiratory coupling during sleep similarly. SIGNIFICANCE: An objective comparison of methods for RSA quantification is presented to guide future analyses. Also, the proposed simulation model can be used to compare existing and newly proposed RSA estimates. It is freely accessible online

Tissue of origin, but not XCI state, influences germ cell differentiation from human pluripotent stem cells

Stem cells & developmental biolog

Model-Based Evaluation of Methods for Respiratory Sinus Arrhythmia Estimation

Objective: Respiratory sinus arrhythmia (RSA) refers to heart rate oscillations synchronous with respiration, and it is one of the major representations of cardiorespiratory coupling. Its strength has been suggested as a biomarker to monitor different conditions and diseases. Some approaches have been proposed to quantify the RSA, but it is unclear which one performs best in specific scenarios. The main objective of this study is to compare seven state-of-the-art methods for RSA quantification using data generated with a model proposed to simulate and control the RSA. These methods are also compared and evaluated on a real-life application, for their ability to capture changes in cardiorespiratory coupling during sleep. Methods: A simulation model is used to create a dataset of heart rate variability and respiratory signals with controlled RSA, which is used to compare the RSA estimation approaches. To compare the methods objectively in a real-life application, regression models trained on the simulated data are used to map the estimates to the same measurement scale. Results and conclusion: RSA estimates based on cross entropy, time-frequency coherence and subspace projections showed the best performance on simulated data. In addition, these estimates captured the expected trends in the changes in cardiorespiratory coupling during sleep similarly. Significance: An objective comparison of methods for RSA quantification is presented to guide future analyses. Also, the proposed simulation model can be used to compare existing and newly proposed RSA estimates. It is freely accessible online

Migraine and sleep disorders: a systematic review

Migraine and sleep disorders are common and often burdensome chronic conditions with a high prevalence in the general population, and with considerable socio-economic impact and costs. The existence of a relationship between migraine and sleep disorders has been recognized from centuries by clinicians and epidemiological studies. Nevertheless, the exact nature of this association, the underlying mechanisms and interactions are complex and not completely understood. Recent biochemical and functional imaging studies identified central nervous system structures and neurotransmitters involved in the pathophysiology of migraine and also important for the regulation of normal sleep architecture, suggesting a possible causative role, in the pathogenesis of both disorders, of a dysregulation in these common nervous system pathways. This systematic review summarizes the existing data on migraine and sleep disorders with the aim to evaluate the existence of a causal relationship and to assess the presence of influencing factors. The identification of specific sleep disorders associated with migraine should induce clinicians to systematically assess their presence in migraine patients and to adopt combined treatment strategies

Evaluation of physicians' professional performance: An iterative development and validation study of multisource feedback instruments

Contains fulltext : 107798.pdf (publisher's version ) (Open Access)BACKGROUND: There is a global need to assess physicians' professional performance in actual clinical practice. Valid and reliable instruments are necessary to support these efforts. This study focuses on the reliability and validity, the influences of some sociodemographic biasing factors, associations between self and other evaluations, and the number of evaluations needed for reliable assessment of a physician based on the three instruments used for the multisource assessment of physicians' professional performance in the Netherlands. METHODS: This observational validation study of three instruments underlying multisource feedback (MSF) was set in 26 non-academic hospitals in the Netherlands. In total, 146 hospital-based physicians took part in the study. Each physician's professional performance was assessed by peers (physician colleagues), co-workers (including nurses, secretary assistants and other healthcare professionals) and patients. Physicians also completed a self-evaluation. Ratings of 864 peers, 894 co-workers and 1960 patients on MSF were available. We used principal components analysis and methods of classical test theory to evaluate the factor structure, reliability and validity of instruments. We used Pearson's correlation coefficient and linear mixed models to address other objectives. RESULTS: The peer, co-worker and patient instruments respectively had six factors, three factors and one factor with high internal consistencies (Cronbach's alpha 0.95 - 0.96). It appeared that only 2 percent of variance in the mean ratings could be attributed to biasing factors. Self-ratings were not correlated with peer, co-worker or patient ratings. However, ratings of peers, co-workers and patients were correlated. Five peer evaluations, five co-worker evaluations and 11 patient evaluations are required to achieve reliable results (reliability coefficient >/= 0.70). CONCLUSIONS: The study demonstrated that the three MSF instruments produced reliable and valid data for evaluating physicians' professional performance in the Netherlands. Scores from peers, co-workers and patients were not correlated with self-evaluations. Future research should examine improvement of performance when using MSF

Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation

Recycling endosomes regulate plasma membrane recycling. Recently, recycling endosome-associated proteins have been implicated in the positioning and orientation of the mitotic spindle and cytokinesis. Loss of MYO5B, encoding the recycling endosome-associated myosin Vb, is associated with tumor development and tissue architecture defects in the gastrointestinal tract. Whether loss of MYO5B expression affects mitosis is not known. Here, we demonstrate that loss of MYO5B expression delayed cytokinesis, perturbed mitotic spindle orientation, led to the misorientation of the plane of cell division during the course of mitosis, and resulted in the delamination of epithelial cells. Remarkably, the effects on spindle orientation, but not cytokinesis, were a direct consequence of physical hindrance by giant late endosomes, which were formed in a chloride channel-sensitive manner concomitant with a redistribution of chloride channels from the cell periphery to late endosomes upon loss of MYO5B. Rab7 availability was identified as a limiting factor for the development of giant late endosomes. In accordance, increasing rab7 availability corrected mitotic spindle misorientation and cell delamination in cells lacking MYO5B expression. In conclusion, we identified a novel role for MYO5B in the regulation of late endosome size control and identify the inability to control late endosome size as an unexpected novel mechanism underlying defects in cell division orientation and epithelial architecture. Loss of the recycling endosome-associated motor protein myosin Vb causes the formation of giant late endo-lysosomes; these in turn hinder the orientation of the mitotic spindle and chromosome segregation. Deregulated endosome size thus hampers faithful cell division