Normative references of heart rate variability and salivary alpha-amylase in a healthy young male population

<p>Abstract</p> <p>Background</p> <p>This study aimed to present normative reference values of heart rate variability and salivary alpha-amylase in a healthy young male population with a particular focus on their distribution and reproducibility.</p> <p>Methods</p> <p>The short-term heart rate variability of 417 young healthy Japanese men was studied. Furthermore, salivary alpha-amylase was measured in 430 men. The average age of the subjects were 21.9 years with standard deviation of 1.6 years. Interindividual variations in heart rate variability indices and salivary alpha-amylase levels were plotted as histograms. Data are presented as the mean, median, standard deviation, coefficient of variation, skewness, kurtosis, and fifth and 95th percentiles of each physiological index.</p> <p>Results</p> <p>Mean recorded values were heart period 945.85 ms, log-transformed high frequency component 9.84 ln-ms², log-transformed low frequency component 10.42 ln-ms², log-transformed low frequency to high frequency ratio 0.58 ln-ratio, standard deviation of beat-to-beat interval 27.17 ms and root mean square of successive difference 37.49 ms. The mean value of raw salivary alpha-amylase was 17.48 U/mL, square root salivary alpha-amylase 3.96 sqrt[U/mL] and log-transformed salivary alpha-amylase 2.65 ln[U/mL]. Log-transformed heart rate variability indices exhibited almost symmetrical distributions; however, time-domain indices of heart rate variability (standard deviation of beat-to-beat interval and root mean square of successive difference) exhibited right-skewed (positive skewness) distributions. A considerable right-skewed distribution was observed for raw salivary alpha-amylase. Logarithmic transformation improved the distribution of salivary alpha-amylase, although square root transformation was insufficient. The day-to-day reproducibility of these indices was assessed using intraclass correlation coefficients. Intraclass correlation coefficients of most heart rate variability and salivary indices were approximately 0.5 to 0.6. Intraclass correlation coefficients of raw salivary markers were approximately 0.6, which was similar to those of heart rate variability; however, log transformation of the salivary markers did not considerably improve their reproducibility. Correlations between sympathetic indicators of heart rate variability and salivary alpha-amylase were not observed.</p> <p>Conclusion</p> <p>Because the sample population examined in this study involved limited age and gender variations, the present results were independent of these factors and were indicative of pure interindividual variation.</p

In patient stroke rehabilitation efficiency: Influence of organization of service delivery and staff numbers

<p>Abstract</p> <p>Background</p> <p>Outcomes of inpatient stroke rehabilitation need to be reviewed in terms of optimal resource utilization (staff time, service organization, and duration of stay). We compared FIM efficiency scores between three hospitals, and also variation in FIM scores over a ten year period in one hospital undergoing reduction in staff numbers, to examine the relationship between outcome and service characteristics.</p> <p>Method</p> <p>This is a retrospective study comparing the mean FIM efficiency for stroke patients (FIM score – FIM admission score) divided by duration of stay for 2005 among three rehabilitation hospitals adjusting for age and baseline FIM score, and a longitudinal study of changes in mean FIM efficiency during a ten year period in one hospital, to examine the effects of different service organization and staff numbers.</p> <p>Results</p> <p>FIM efficiency (FIMEG) was inversely associated with age, and positively associated with admission FIM score. FIMEG was higher in the hospital with a coordinated care plan involving medical, nursing, occupational, physiotherapy staff and other healthcare providers working as a team, with a seamless interface with community rehabilitation services. Over a ten year period, reduction in staff numbers was associated with reduction in FIMEG, which may be offset to some extent by service re-engineering.</p> <p>Conclusion</p> <p>Within hospital organization of stroke rehabilitation services may influence outcome. A critical number of staff may be identified for the provision of services, below which rehabilitation efficiency may be affected.</p

A quantitative model for estimating risk from multiple interacting natural hazards: an application to northeast Zhejiang, China

Multi-hazard risk assessment is a major concern in risk analysis, but most approaches do not consider all hazard interactions when calculating possible losses. We address this problem by developing an improved quantitative model - Model for multi-hazard Risk assessment with a consideration of Hazard Interaction (MmhRisk-HI). This model calculates the possible loss caused by multiple hazards, with an explicit consideration of interaction between those hazards. There are two main components to the model. In the first, based on the hazard-forming environment, relationships among hazards are classified into four types for calculation of the exceedance probability of multiple hazards occurrence. In the second, a Bayesian network is used to calculate possible loss caused by multiple hazards with different exceedance probabilities. A multi-hazard risk map can then be drawn addressing the probability of multi-hazard occurrence and corresponding loss. This model was applied in northeast Zhejiang, China and validated by comparison against an observed multi-hazard sequence. The validation results show that the model can more effectively represent the real world, and that the modelled outputs, possible loss caused by multiple hazards, are reliable. The outputs can additionally help to identify areas at greatest risk, and allows a determination of the factors that contribute to that risk, and hence the model can provide useful further information for planners and decision-makers concerned with risk mitigation

A graphical vector autoregressive modelling approach to the analysis of electronic diary data

<p>Abstract</p> <p>Background</p> <p>In recent years, electronic diaries are increasingly used in medical research and practice to investigate patients' processes and fluctuations in symptoms over time. To model dynamic dependence structures and feedback mechanisms between symptom-relevant variables, a multivariate time series method has to be applied.</p> <p>Methods</p> <p>We propose to analyse the temporal interrelationships among the variables by a structural modelling approach based on graphical vector autoregressive (VAR) models. We give a comprehensive description of the underlying concepts and explain how the dependence structure can be recovered from electronic diary data by a search over suitable constrained (graphical) VAR models.</p> <p>Results</p> <p>The graphical VAR approach is applied to the electronic diary data of 35 obese patients with and without binge eating disorder (BED). The dynamic relationships for the two subgroups between eating behaviour, depression, anxiety and eating control are visualized in two path diagrams. Results show that the two subgroups of obese patients with and without BED are distinguishable by the temporal patterns which influence their respective eating behaviours.</p> <p>Conclusion</p> <p>The use of the graphical VAR approach for the analysis of electronic diary data leads to a deeper insight into patient's dynamics and dependence structures. An increasing use of this modelling approach could lead to a better understanding of complex psychological and physiological mechanisms in different areas of medical care and research.</p

Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2.5g/L, PDTC group, N = 6). Static pulmonary compliance (SPC), peak airway pressure (PAWP), pulmonary vascular resistance (PVR), and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema), and the concentration of LDH (cell damage), proteins (permeability edema) and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL), and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation

C. elegans SWAN-1 Binds to EGL-9 and Regulates HIF-1-Mediated Resistance to the Bacterial Pathogen Pseudomonas aeruginosa PAO1

Pseudomonas aeruginosa is a nearly ubiquitous human pathogen, and infections can be lethal to patients with impaired respiratory and immune systems. Prior studies have established that strong loss-of-function mutations in the egl-9 gene protect the nematode C. elegans from P. aeruginosa PAO1 fast killing. EGL-9 inhibits the HIF-1 transcription factor via two pathways. First, EGL-9 is the enzyme that targets HIF-1 for oxygen-dependent degradation via the VHL-1 E3 ligase. Second, EGL-9 inhibits HIF-1-mediated gene expression through a VHL-1-independent mechanism. Here, we show that a loss-of-function mutation in hif-1 suppresses P. aeruginosa PAO1 resistance in egl-9 mutants. Importantly, we find stabilization of HIF-1 protein is not sufficient to protect C. elegans from P. aeruginosa PAO1 fast killing. However, mutations that inhibit both EGL-9 pathways result in higher levels of HIF-1 activity and confer resistance to the pathogen. Using forward genetic screens, we identify additional mutations that confer resistance to P. aeruginosa. In genetic backgrounds that stabilize C. elegans HIF-1 protein, loss-of-function mutations in swan-1 increase the expression of hypoxia response genes and protect C. elegans from P. aeruginosa fast killing. SWAN-1 is an evolutionarily conserved WD-repeat protein belonging to the AN11 family. Yeast two-hybrid and co-immunoprecipitation assays show that EGL-9 forms a complex with SWAN-1. Additionally, we present genetic evidence that the DYRK kinase MBK-1 acts downstream of SWAN-1 to promote HIF-1-mediated transcription and to increase resistance to P. aeruginosa. These data support a model in which SWAN-1, MBK-1 and EGL-9 regulate HIF-1 transcriptional activity and modulate resistance to P. aeruginosa PAO1 fast killing

Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5

Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas)