Prolonged low flow reduces reactive hyperemia and augments low flow mediated constriction in the brachial artery independent of the menstrual cycle

© 2013 Rakobowchuk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Non-invasive forearm ischemia-reperfusion injury and low flow induced vascular dysfunction models provide methods to evaluate vascular function. The role of oestrogen, an endogenous anti-oxidant on recovery from ischemia-reperfusion injury has not been evaluated nor has the impact of prolonged low flow on vascular function been established. Eight healthy women (33610 yr) attended the lab during the follicular, ovulatory and mid-luteal phases of their menstrual cycles. After 30 minutes of rest, brachial artery vascular function was assessed by ultrasound measurements of diameter changes during 5 minutes of forearm ischemia and 3 minutes after. Subsequently, a 20-minute forearm ischemia period was completed. Further, vascular function assessments were completed 15, 30 and 45 minutes into recovery. Flow-mediated dilation, lowflow-mediated constriction, and reactive hyperaemia proximal to the area of ischemia were determined. Flow-mediated dilation was reduced at 15 minutes of recovery but recovered at 30 and 45 minutes (PRE: 7.161.0%, POST15:4.560.6%, POST30:5. 560.7% POST45:5.960.4%, p,0.01). Conversely, low-flow mediated constriction increased (PRE: 21.360.4%, POST15: 23.360.6%, POST30: 22.560.5% POST45: 21.560.12%, p,0.01). Reactive hyperaemia was reduced throughout recovery (p,0.05). Data were unaffected by menstrual phase. Prolonged low flow altered vascular function and may relate as much to increased vasoconstriction as with decreased vasodilation. Reductions in anterograde shear and greater retrograde shear likely modulate the brachial artery response, but the reduced total shear also plays an important role. The data suggest substantial alterations in vascular function proximal to areas of ischemia with potential clinical implications following reperfusion.British Heart Foundation (PG/08/060/25340),a Physiological Society summer studentship to SG, and a Wellcome Trust Vacation Studentship to EP

Urbanization and traffic related exposures as risk factors for Schizophrenia

BACKGROUND: Urban birth or upbringing increase schizophrenia risk. Though unknown, the causes of these urban-rural differences have been hypothesized to include, e.g., infections, diet, toxic exposures, social class, or an artefact due to selective migration. METHODS: We investigated the hypothesis that traffic related exposures affect schizophrenia risk and that this potential effect is responsible for the urban-rural differences. The geographical distance from place of residence to nearest major road was used as a proxy variable for traffic related exposures. We used a large population-based sample of the Danish population (1.89 million people) including information on all permanent addresses linked with geographical information on all roads and house numbers in Denmark. Schizophrenia in cohort members (10,755 people) was identified by linkage with the Danish Psychiatric Central Register. RESULTS: The geographical distance from place of residence to nearest major road had a significant effect. The highest risk was found in children living 500–1000 metres from nearest major road (RR = 1.30 (95% Confidence Interval: 1.17–1.44). However, when we accounted for the degree of urbanization, the geographical distance to nearest major road had no significant effect. CONCLUSION: The cause(s) or exposure(s) responsible for the urban-rural differences in schizophrenia risk were closer related to the degree of urbanization than to the geographical distance to nearest major road. Traffic related exposures might thus be less likely explanations for the urban-rural differences in schizophrenia risk

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

Modeling the cost of influenza: the impact of missing costs of unreported complications and sick leave

Background Estimating the economic impact of influenza is complicated because the disease may have non-specific symptoms, and many patients with influenza are registered with other diagnoses. Furthermore, in some countries like Norway, employees can be on paid sick leave for a specified number of days without a doctor's certificate ("self-reported sick leave") and these sick leaves are not registered. Both problems result in gaps in the existing literature: costs associated with influenza-related illness and self-reported sick leave are rarely included. The aim of this study was to improve estimates of total influenza-related health-care costs and productivity losses by estimating these missing costs. Methods Using Norwegian data, the weekly numbers of influenza-attributable hospital admissions and certified sick leaves registered with other diagnoses were estimated from influenza-like illness surveillance data using quasi-Poisson regression. The number of self-reported sick leaves was estimated using a Monte-Carlo simulation model of illness recovery curves based on the number of certified sick leaves. A probabilistic sensitivity analysis was conducted on the economic outcomes. Results During the 1998/99 through 2005/06 influenza seasons, the models estimated an annual average of 2700 excess influenza-associated hospitalizations in Norway, of which 16% were registered as influenza, 51% as pneumonia and 33% were registered with other diagnoses. The direct cost of seasonal influenza totaled US$22 million annually, including costs of pharmaceuticals and outpatient services. The annual average number of working days lost was predicted at 793 000, resulting in an estimated productivity loss of US$231 million. Self-reported sick leave accounted for approximately one-third of the total indirect cost. During a pandemic, the total cost could rise to over US$800 million. Conclusions Influenza places a considerable burden on patients and society with indirect costs greatly exceeding direct costs. The cost of influenza-attributable complications and the cost of self-reported sick leave represent a considerable part of the economic burden of influenza

Variation in CHI3LI in Relation to Type 2 Diabetes and Related Quantitative Traits

CHI3LI encoding the inflammatory glycoprotein YKL-40 is located on chromosome 1q32.1. YKL-40 is involved in inflammatory processes and patients with Type 2 Diabetes (T2D) have elevated circulating YKL-40 levels which correlate with their level of insulin resistance. Interestingly, it has been reported that rs10399931 (-329 G/A) of CHI3LI contributes to the inter-individual plasma YKL-40 levels in patients with sarcoidosis, and that rs4950928 (-131 C/G) is a susceptibility polymorphism for asthma and a decline in lung function. We hypothesized that single nucleotide polymorphisms (SNPs) or haplotypes thereof the CHI3LI locus might influence risk of T2D. The aim of the present study was to investigate the putative association between SNPs and haplotype blocks of CHI3LI and T2D and T2D related quantitative traits.Eleven SNPs of CHI3LI were genotyped in 6514 individuals from the Inter99 cohort and 2924 individuals from the outpatient clinic at Steno Diabetes Center. In cas-control studies a total of 2345 T2D patients and 5302 individuals with a normal glucose tolerance test were examined. We found no association between rs10399931 (OR, 0.98 (CI, 0.88-1.10), p = 0.76), rs4950928 (0.98 (0.87-1.10), p = 0.68) or any of the other SNPs with T2D. Similarly, we found no significant association between any of the 11 tgSNPs and T2D related quantitative traits, all p>0.14. None of the identified haplotype blocks of CHI3LI showed any association with T2D, all p>0.16.None of the examined SNPs or haplotype blocks of CHI3LI showed any association with T2D or T2D related quantitative traits. Estimates of insulin resistance and dysregulated glucose homeostasis in T2D do not seem to be accounted for by the examined variations of CHI3LI

A cost minimisation analysis of a telepaediatric otolaryngology service

Background: Paediatric ENT services in regional areas can be provided through telemedicine (tele-ENT) using videoconferencing or with a conventional outpatient department ENT service (OPD-ENT) in which patients travel to see the specialist. The objective of this study was to identify the least-cost approach to providing ENT services for paediatric outpatients

The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells.

INTRODUCTION: High cell density is known to enhance adipogenic differentiation of mesenchymal stem cells, suggesting secretion of signaling factors or cell-contact-mediated signaling. By employing microfluidic biochip technology, we have been able to separate these two processes and study the secretion pathways. METHODS AND RESULTS: Adipogenic differentiation of human adipose-derived stem cells (ASCs) cultured in a microfluidic system was investigated under perfusion conditions with an adipogenic medium or an adipogenic medium supplemented with supernatant from differentiating ASCs (conditioned medium). Conditioned medium increased adipogenic differentiation compared to adipogenic medium with respect to accumulation of lipid-filled vacuoles and gene expression of key adipogenic markers (C/EBPα, C/EBPβ, C/EBPδ, PPARγ, LPL and adiponectin). The positive effects of conditioned medium were observed early in the differentiation process. CONCLUSIONS: Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment phase of the differentiation process

Effects of cranberry powder on serum lipid profiles and biomarkers of oxidative stress in rats fed an atherogenic diet

This study investigated that the antioxidative effect of freeze-dried cranberry powder against protein and lipid oxidation and ameliorative effect of serum lipid profile in rat fed atherogenic diet. Six weeks old male Sprague-Dawley rats were divided into the following four groups: normal diet group with 5% corn oil (control), atherogenic diet group with 5% corn oil, 10% lard, 1% cholesterol, and 0.5% sodium cholate (HFC), atherogenic plus 2% cranberry powder diet group (HFC + C2), and atherogenic plus 5% cranberry powder diet group (HFC + C5), and respective diet and water were fed daily for 6 weeks. After the experimental period, the serum lipid profile, such as total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride, ferric reducing ability of plasma (FRAP), plasma phenolics content, superoxide dismutase (SOD) activity, serum protein carbonyl and thiobarbituric acid reactive substances (TBARS) levels were examined. Total phenolic compound and total flavonoid levels in freeze-dried cranberry powder were 9.94 mg/g and 8.12 mg/g, respectively. Serum total cholesterol and LDL-cholesterol levels were not significantly different for cranberry powder treatment, but serum HDL-cholesterol level was significantly increased in HFC + C5 group compared with HFC group. Plasma FRAP value tended to be increased by cranberry powder treatment though there was no significant difference. Plasma total phenol concentrations and SOD activities were not significantly different among all groups. Serum protein carbonyl and TBARS levels were significantly decreased in HFC + C5 group compared with HFC group. Overall results suggested that freeze-dried cranberry powder might have the serum lipid improving effect, as well as antioxidative effect demonstrated by its protective effect against protein and lipid oxidation

Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases

Mice lacking both PTEN and SHIP phosphatases develop spontaneous B cell lymphoma