Shaping bursting by electrical coupling and noise

Gap-junctional coupling is an important way of communication between neurons and other excitable cells. Strong electrical coupling synchronizes activity across cell ensembles. Surprisingly, in the presence of noise synchronous oscillations generated by an electrically coupled network may differ qualitatively from the oscillations produced by uncoupled individual cells forming the network. A prominent example of such behavior is the synchronized bursting in islets of Langerhans formed by pancreatic \beta-cells, which in isolation are known to exhibit irregular spiking. At the heart of this intriguing phenomenon lies denoising, a remarkable ability of electrical coupling to diminish the effects of noise acting on individual cells. In this paper, we derive quantitative estimates characterizing denoising in electrically coupled networks of conductance-based models of square wave bursting cells. Our analysis reveals the interplay of the intrinsic properties of the individual cells and network topology and their respective contributions to this important effect. In particular, we show that networks on graphs with large algebraic connectivity or small total effective resistance are better equipped for implementing denoising. As a by-product of the analysis of denoising, we analytically estimate the rate with which trajectories converge to the synchronization subspace and the stability of the latter to random perturbations. These estimates reveal the role of the network topology in synchronization. The analysis is complemented by numerical simulations of electrically coupled conductance-based networks. Taken together, these results explain the mechanisms underlying synchronization and denoising in an important class of biological models

Thermography imaging during static and controlled thermoregulation in complex regional pain syndrome type 1: diagnostic value and involvement of the central sympathetic system

BACKGROUND: Complex Regional Pain Syndrome type 1 (CRPS1) is a clinical diagnosis based on criteria describing symptoms of the disease. The main aim of the present study was to compare the sensitivity and specificity of calculation methods used to assess thermographic images (infrared imaging) obtained during temperature provocation. The secondary objective was to obtain information about the involvement of the sympathetic system in CRPS1. METHODS: We studied 12 patients in whom CRPS1 was diagnosed according to the criteria of Bruehl. High and low whole body cooling and warming induced and reduced sympathetic vasoconstrictor activity. The degree of vasoconstrictor activity in both hands was monitored using a videothermograph. The sensitivity and specificity of the calculation methods used to assess the thermographic images were calculated. RESULTS: The temperature difference between the hands in the CRPS patients increases significantly when the sympathetic system is provoked. At both the maximum and minimum vasoconstriction no significant differences were found in fingertip temperatures between both hands. CONCLUSION: The majority of CRPS1 patients do not show maximal obtainable temperature differences between the involved and contralateral extremity at room temperature (static measurement). During cold and warm temperature challenges this temperature difference increases significantly. As a result a higher sensitivity and specificity could be achieved in the diagnosis of CRPS1. These findings suggest that the sympathetic efferent system is involved in CRPS1

Quality of Life in Oncological Patients with Oropharyngeal Dysphagia: Validity and Reliability of the Dutch Version of the MD Anderson Dysphagia Inventory and the Deglutition Handicap Index

Quality of life is an important outcome measurement in objectifying the current health status or therapy effects in patients with oropharyngeal dysphagia. In this study, the validity and reliability of the Dutch version of the Deglutition Handicap Index (DHI) and the MD Anderson Dysphagia Inventory (MDADI) have been determined for oncological patients with oropharyngeal dysphagia. At Maastricht University Medical Center, 76 consecutive patients were selected and asked to fill in three questionnaires on quality of life related to oropharyngeal dysphagia (the SWAL-QOL, the MDADI, and the DHI) as well as a simple one-item visual analog Dysphagia Severity Scale. None of the quality-of-life questionnaires showed any floor or ceiling effect. The test-retest reliability of the MDADI and the Dysphagia Severity Scale proved to be good. The test-retest reliability of the DHI could not be determined because of insufficient data, but the intraclass correlation coefficients were rather high. The internal consistency proved to be good. However, confirmatory factor analysis could not distinguish the underlying constructs as defined by the subscales per questionnaire. When assessing criterion validity, both the MDADI and the DHI showed satisfactory associations with the SWAL-QOL (reference or gold standard) after having removed the less relevant subscales of the SWAL-QOL. In conclusion, when assessing the validity and reliability of the Dutch version of the DHI or the MDADI, not all psychometric properties have been adequately met. In general, because of difficulties in the interpretation of study results when using questionnaires lacking sufficient psychometric quality, it is recommended that researchers strive to use questionnaires with the most optimal psychometric properties

The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders

Mutation of pescadillo Disrupts Oligodendrocyte Formation in Zebrafish

Background: In vertebrates, the myelin sheath is essential for efficient propagation of action potentials along the axon shaft. Oligodendrocytes are the cells of the central nervous system that create myelin sheaths. During embryogenesis, ventral neural tube precursors give rise to oligodendrocyte progenitor cells, which divide and migrate throughout the central nervous system. This study aimed to investigate mechanisms that regulate oligodendrocyte progenitor cell formation. Methodology/Principal Findings: By conducting a mutagenesis screen in transgenic zebrafish, we identified a mutation, designated vu166, by an apparent reduction in the number of oligodendrocyte progenitor cells in the dorsal spinal cord. We subsequently determined that vu166 is an allele of pescadillo, a gene known to play a role in ribosome biogenesis and cell proliferation. We found that pescadillo function is required for both the proper number of oligodendrocyte progenitors to form, by regulating cell cycle progression, and for normal levels of myelin gene expression. Conclusions/Significance: Our data provide evidence that neural precursors require pes function to progress through th

Meta-analysis of prophylactic corticosteroid use in post-ERCP pancreatitis

<p>Abstract</p> <p>Background</p> <p>Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography and benefit of pharmacological treatment is unclear. Although prophylactic use of corticosteroid for reduction of pancreatic injury after ERCP has been evaluated, discrepancy about beneficial effect of corticosteroid on pancreatic injury still exists. The aim of current study is to evaluate effectiveness and safety of corticosteroid in prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP).</p> <p>Methods</p> <p>We employed the method recommended by the Cochrane Collaboration to perform a meta-analysis of seven randomized controlled trials (RCTs) of corticosteroid in prevention of post-ERCP pancreatitis (PEP) around the world.</p> <p>Results</p> <p>Most of the seven RCTs were of high quality. When the RCTs were analyzed, odds ratios (OR) for corticosteroid were 1.13 [95% CI (0.89~1.44), p = 0.32] for PEP, 1.61 [95% CI (0.74~3.52), p = 0.23] for severe PEP, 0.92 [95% CI (0.57~1.48), p = 0.73] for post-ERCP hyperamylasemia respectively. The results indicated that there were no beneficial effects of corticosteroid on acute pancreatitis and hyperamylasemia. No evidence of publication bias was found.</p> <p>Conclusion</p> <p>Corticosteroids cannot prevent pancreatic injury after ERCP. Therefore, their use in the prophylaxis of PEP is not recommended.</p

Physicists attempt to scale the ivory towers of finance

Physicists have recently begun doing research in finance, and even though this movement is less than five years old, interesting and useful contributions have already emerged. This article reviews these developments in four areas, including empirical statistical properties of prices, random-process models for price dynamics, agent-based modeling, and practical applications.Comment: 13 pages, 5 figure

Rates of influenza vaccination in older adults and factors associated with vaccine use: A secondary analysis of the Canadian Study of Health and Aging

BACKGROUND: Influenza vaccination has been shown to reduce morbidity and mortality in the older adult population. In Canada, vaccination rates remain suboptimal. We identified factors predictive of influenza vaccination, in order to determine which segments of the older adult population might be targeted to increase coverage in influenza vaccination programs. METHODS: The Canadian Study of Health and Aging (CSHA) is a population-based national cohort study of 10263 older adults (≥ 65) conducted in 1991. We used data from the 5007 community-dwelling participants in the CSHA without dementia for whom self-reported influenza vaccination status is known. RESULTS: Of 5007 respondents, 2763 (55.2%) reported having received an influenza vaccination within the previous 2 years. The largest predictive factors for flu vaccination included: being married (57.4 vs. 52.6%, p = 0.0007), having attained a higher education (11.0 vs. 10.3 years, p < 0.0001), smoking (57.1% vs. 52.9%, p = 0.0032), more alcohol use (57.9% of those who drank more vs. 53.2% of those who drank less, p = 0.001), poorer self-rated health (54.1% of those with good self-rated health vs. 60.6% of those with poor self-rated health, p = 0.0006), regular exercise (56.8% vs. 52.0%, p = 0.001), and urban living (55.8% vs. 51.0%, p = 0.03). While many other differences were statistically significant, most were small (e.g. mean age 75.1 vs. 74.6 years for immunized vs. unimmunized older adults, p = 0.006, higher Modified Mini Mental Status Examination score (89.9 vs. 89.1, p < 0.0001), higher comorbidity (2.7 vs. 2.3 comorbidities, p < 0.0001). Residents of Ontario were more likely (64.6%) to report vaccination (p < 0.0001), while those living in Quebec were less likely to do so (48.2%, p < 0.0001). Factors retaining significance in a multivariate analysis included older age, higher education, married status, drinking alcohol, smoking, engaging in regular exercise, and having higher comorbidity. CONCLUSIONS: The vaccination rate in this sample, in whom influenza vaccination is indicated, was low (55.2%). Even in a publicly administered health care setting, influenza vaccination did not reach an important proportion of the elderly population. Whether these differences reflect patient preference or access remains to be determined

Retrospective comparison between a regular and a split-dose protocol of 5-fluorouracil, cisplatin, and mitoxantrone for the treatment of far advanced hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>In patients with advanced hepatocellular carcinoma (HCC), combination chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone (FMP) could achieve a response rate > 20%, but the beneficial effect was compromised by formidable adverse events. Chemotherapy given in a split-dose manner was associated with reduced toxicities. In this retrospective study, we compared the efficacies and side effects between a regular and a split-dose FMP protocol approved in our medical center.</p> <p>Methods</p> <p>From 2005 to 2008, the clinical data of 84 patients with far advanced HCC, who had either main portal vein thrombosis and/or extrahepatic metastasis, were reviewed. Of them, 65 were treated by either regular (n = 27) or split-dose (n = 38) FMP and had completed at least one therapeutic course. The remaining 19 patients were untreated. Clinical parameters, therapeutic responses, survivals and adverse events were compared.</p> <p>Results</p> <p>The median overall survival was 6.0, 5.2, and 1.5 months, respectively, in patients receiving regular FMP, split-dose FMP, and no treatment (regular versus split-dose group, P = 0.447; regular or split-dose versus untreated group; P < 0.0001). Patients receiving split-dose treatment had a significantly lower risk of grade 3/4 neutropenia (51.9 versus 10.5%, P = 0.0005). When the two treated groups were combined, the median overall survival was 10.6 and 3.8 months respectively for patients achieving disease control and progressive disease (P < 0.001). Cox proportion hazard model identified Child-Pugh stage B (hazard ratio [HR], 2.216; P = 0.006), presence of extrahepatic metastasis (HR, 0.574; P = 0.048), and achievement of disease control (HR, 0.228; P < 0.001) as independent factors associated with overall survival. Logistic regression analysis revealed that anti-hepatitis C virus antibody (odds ratio [OR], 9.219; P = 0.002) tumor size (OR, 0.816; P = 0.036), and previous anti-cancer therapy (OR, 0.195; P = 0.017) were significantly associated with successful disease control.</p> <p>Conclusions</p> <p>Comparable overall survival was observed between patients receiving regular and split-dose FMP therapies. Patients receiving split-dose therapy had a significantly lower risk of grade 3/4 neutropenia. Positive anti-hepatitis C virus antibody, smaller tumor size, and absence of previous anti-cancer therapy were independent predictors for successful disease control.</p

Lung glutathione adaptive responses to cigarette smoke exposure

<p>Abstract</p> <p>Background</p> <p>Smoking tobacco is a leading cause of chronic obstructive pulmonary disease (COPD), but although the majority of COPD cases can be directly related to smoking, only a quarter of smokers actually develop the disease. A potential reason for the disparity between smoking and COPD may involve an individual's ability to mount a protective adaptive response to cigarette smoke (CS). Glutathione (GSH) is highly concentrated in the lung epithelial lining fluid (ELF) and protects against many inhaled oxidants. The changes in GSH that occur with CS are not well investigated; therefore the GSH adaptive response that occurs with a commonly utilized CS exposure was examined in mice.</p> <p>Methods</p> <p>Mice were exposed to CS for 5 h after which they were rested in filtered air for up to 16 h. GSH levels were measured in the ELF, bronchoalveolar lavage cells, plasma, and tissues. GSH synthesis was assessed by measuring γ-glutamylcysteine ligase (GCL) activity in lung and liver tissue.</p> <p>Results</p> <p>GSH levels in the ELF, plasma, and liver were decreased by as much as 50% during the 5 h CS exposure period whereas the lung GSH levels were unchanged. Next, the time course of rebound in GSH levels after the CS exposure was examined. CS exposure initially decreased ELF GSH levels by 50% but within 2 h GSH levels rebound to about 3 times basal levels and peaked at 16 h with a 6-fold increase and over repeat exposures were maintained at a 3-fold elevation for up to 2 months. Similar changes were observed in tissue GCL activity which is the rate limiting step in GSH synthesis. Furthermore, elevation in ELF GSH levels was not arbitrary since the CS induced GSH adaptive response after a 3d exposure period prevented GSH levels from dropping below basal levels.</p> <p>Conclusions</p> <p>CS exposures evoke a powerful GSH adaptive response in the lung and systemically. These data suggests there may be a sensor that sets the ELF GSH adaptive response to prevent GSH levels from dipping below basal levels. Factors that disrupt GSH adaptive responses may contribute to the pathophysiology of COPD.</p