Disruption of transfer entropy and inter-hemispheric brain functional connectivity in patients with disorder of consciousness

Severe traumatic brain injury can lead to disorders of consciousness (DOC) characterized by deficit in conscious awareness and cognitive impairment including coma, vegetative state, minimally consciousness, and lock-in syndrome. Of crucial importance is to find objective markers that can account for the large-scale disturbances of brain function to help the diagnosis and prognosis of DOC patients and eventually the prediction of the coma outcome. Following recent studies suggesting that the functional organization of brain networks can be altered in comatose patients, this work analyzes brain functional connectivity (FC) networks obtained from resting-state functional magnetic resonance imaging (rs-fMRI). Two approaches are used to estimate the FC: the Partial Correlation (PC) and the Transfer Entropy (TE). Both the PC and the TE show significant statistical differences between the group of patients and control subjects; in brief, the inter-hemispheric PC and the intra-hemispheric TE account for such differences. Overall, these results suggest two possible rs-fMRI markers useful to design new strategies for the management and neuropsychological rehabilitation of DOC patients.Comment: 25 pages; 4 figures; 3 tables; 1 supplementary figure; 4 supplementary tables; accepted for publication in Frontiers in Neuroinformatic

Backward in Coming Forward.

As far back as the ancient Egyptians and Greeks, physicians have observed and interpreted the arterial pulse to help diagnose certain illnesses. However, until William Harvey’s discoveries in the 17th century, some of the basic concepts were misunderstood. Harvey described the circular blood flow in the body and discovered that the arterial pulse is generated by the contraction of the left ventricle. He also came up with the concept that the arterial pulse is a wave, thus paving the way for modern studies in pulse wave analysis. Another pivotal discovery was the introduction of pulse wave velocity (PWV) by Crighton Bramwell in the early 20th century. He recognised that PWV changes in proportion to the arterial wall tension and blood pressure, and thus, is an indirect measure of atrial wall elasticity1. Despite these important historic discoveries, it has only been in the last 20 years, with advances in modern engineering, that the pulse wave analysis has become more widely available, reliable, and reproducible technique to assess arterial pulse waves.Professor Wilkinson is funded by British Heart Foundation (Grant number: FS/12/8/29377)

Associations of tissue transglutaminase antibody seropositivity with coronary heart disease: Findings from a prospective cohort study.

Clinical experience and observational studies suggest that individuals with coeliac disease are at increased risk of coronary heart disease (CHD), but the precise mechanism for this is unclear. Laboratory studies suggest that it may relate to tissue transglutaminase antibodies (tTGAs). Our aim was to examine whether seropositivity for tTGA and endomysial antibodies (EMAs) are associated with incident CHD in humans. We used data from Mini-Finland Health Survey, a prospective cohort study of Finnish men and women aged 35-80 at study baseline 1978-80. TTGA and EMA seropositivities were ascertained from baseline blood samples and incident CHD events were identified from national hospitalisation and death registers. Cox regression was used to examine the associations between antibody seropositivity and incident CHD. Of 6887 men and women, 562 were seropositive for tTGAs and 72 for EMAs. During a median follow-up of 26 years, 2367 individuals experienced a CHD event. We found no clear evidence for an association between tTGA positivity (hazard ratio, HR: 1.04, 95% confidence interval, CI: 0.83, 1.30) or EMA positivity (HR: 1.16, 95% CI: 0.77, 1.74) and incident CHD, once pre-existing CVD and known CHD risk factors had been adjusted for. We found no clear evidence for an association of tTGA or EMA seropositivity with incident CHD outcomes, suggesting that tTG autoimmunity is unlikely to be the biological link between coeliac disease and CHD

Genetic variances, trends and mode of inheritance for hip and elbow dysplasia in Finnish dog populations

The aims of this study were to assess genetic variances, trends and mode of inheritance for hip and elbow dysplasia in Finnish dog populations. The influence of time-dependent fixed effects in the model when estimating the genetic trends was also studied. Official hip and elbow dysplasia screening records of 42 421 dogs from seven breeds were analysed with REML. To investigate the mode of inheritance of hip and elbow dysplasia, trait distributions, genetic variances and regressions of offspring phenotypes on parental predicted breeding values were studied separately in males and in females. Genetic trends for hip dysplasia between the years 1983 and 1998 were favourable only in the Rottweiler. In elbow dysplasia, the trends were favourable after the year 1992 in all the four breeds studied but the overall changes were small. The reason for this seemed to be negligible selection pressure against these traits. Time-dependent fixed effects in the model had an influence on the estimated genetic trends, resulting either in a more negative or more positive genetic trend compared with the model from which the time-dependent effects were removed. Mitochondrial or sex-linked inheritance did not seem likely in the expression of hip and elbow dysplasia in the populations studied. Regression coefficients of offspring phenotypes on estimated parental breeding values were approximately equal to their expected value in a situation with equal parental contribution. Furthermore, the phenotypic frequency distributions of hip and elbow dysplasia grades were similar among males and females in each breed studied. No indication of major genes was found in the offspring frequency distributions within individual sires. According to these Finnish data, mode of inheritance for both hip and elbow dysplasia is polygenic (quantitative) with equal expression of the genes from both parents, although the estimates of heritability for hip dysplasia in the Rough Collie and for elbow dysplasia in the German Shepherd and the Golden Retriever were somewhat different in males compared with females

Functional effects of schizophrenia-linked genetic variants on intrinsic single-neuron excitability: A modeling study

Background: Recent genome-wide association studies (GWAS) have identified a large number of genetic risk factors for schizophrenia (SCZ) featuring ion channels and calcium transporters. For some of these risk factors, independent prior investigations have examined the effects of genetic alterations on the cellular electrical excitability and calcium homeostasis. In the present proof-of-concept study, we harnessed these experimental results for modeling of computational properties on layer V cortical pyramidal cell and identify possible common alterations in behavior across SCZ-related genes. Methods: We applied a biophysically detailed multi-compartmental model to study the excitability of a layer V pyramidal cell. We reviewed the literature on functional genomics for variants of genes associated with SCZ, and used changes in neuron model parameters to represent the effects of these variants. Results: We present and apply a framework for examining the effects of subtle single nucleotide polymorphisms in ion channel and Ca2+ transporter-encoding genes on neuron excitability. Our analysis indicates that most of the considered SCZ- related genetic variants affect the spiking behavior and intracellular calcium dynamics resulting from summation of inputs across the dendritic tree. Conclusions: Our results suggest that alteration in the ability of a single neuron to integrate the inputs and scale its excitability may constitute a fundamental mechanistic contributor to mental disease, alongside with the previously proposed deficits in synaptic communication and network behavior

Risk of donor-site lymphatic vessel dysfunction after microvascular lymph node transfer

BACKGROUND: Microvascular lymph node transfer has been used to improve lymphatic function in patients with lymphoedema. We previously reported changes in the lymphatic function of the donor limb after lymph node transfer. For this reason, we modified our surgical method to be more conservative. SUBJECTS AND METHODS: Microvascular lymph node transfer was performed in 13 patients using the previously reported original method. Sixteen patients were operated upon using the more conservative modified method. Lymphatic function in the donor limb was evaluated using volumetry, lymphoscintigraphy and tissue water percentage. RESULTS: In the original method group, the donor-limb volume was on average greater (199 ± 540 ml) than in the non-operated control limb. The volume difference between the limbs was smaller (151 ± 463 ml) in the modified method group. Two patients in the original method group had abnormal transport index (Ti) values in lymphoscintigraphy indicating decreased lymphatic function of the donor limb. In the modified method group, the Ti-values remained normal. The tissue water percentage of the donor limb was on average 40% ± 4% in the original method group and 40% ± 3% in the modified method group. Importantly, none of the patients in either group developed clinical lymphoedema in the donor limb during the 11-84-month follow-up. CONCLUSIONS: Even with the more conservative lymph node transfer method, we can observe slight, subclinical signs of lymphatic dysfunction in the donor limb. These results highlight the importance of minimizing the surgical exploration in the inguinal area and avoiding damage to the lymphatic vessels or sentinel nodes draining the lower limb.</p

Stand type affects fluxes of volatile organic compounds from the forest floor in hemiboreal and boreal climates

The forest floor is a significant contributor to the stand-scale fluxes of biogenic volatile organic compounds. In this study, the effect of tree species (Scots pine vs. Norway spruce) on forest floor fluxes of volatile organic compounds (VOC) was compared in boreal and hemiboreal climates.Peer reviewe

Explaining job satisfaction and job control: a survey among finnish psychiatrists

Background: Job satisfaction has a major impact on mental health and job performance. Additionally, expected work satisfaction may influence choice of specialization within medicine. Methods: A postal survey was conducted in 2009 among the members (N=1398) of Finnish Psychiatric Association. Out of the members 1132 were still working-aged. All in all 64.8% (N=738) of the working-aged members returned the survey. Only psychiatrists and residents were included in the final cohort of the study (N=665). Factors associated to work satisfaction were studied and a principal component analysis was conducted on factors reported to disturb working. The correlations of factors scores with job satisfaction and job-control were analyzed. Spearman correlation coefficients were calculated between factor scores and work satisfaction. Results: Most respondents (73.8%) were satisfied with their work. Job satisfaction showed a negative correlation with increase in pace of work (rho=-0.24, p&lt;0.001). Job control correlated positively with job satisfaction (rho=0.46, p&lt;0.001). &quot;Working conditions&quot; factor explained 28.6%, &quot;leadership&quot; 8.8%, &quot;failure without support&quot; 7.8%, fear at work 6.5% and &quot;patient records&quot; factors 5.9% of the variation of perceived harmful factors at work. &quot;Working conditions&quot; and &quot;leadership&quot; factors showed the strongest and most significant negative correlations with job satisfaction (rho= -0.45, p&lt;0.001, rho=-0.32, p&lt;0.001, respectively. &quot;Working conditions&quot; associated strongly and significantly with job control (rho=-0.57, p&lt;0.001). Conclusion: Job satisfaction may be better than expected among psychiatrists considering the findings of prevalence estimates of burnout in various other studies. However, employers should put emphasis on matching employers and type of work to promote well-being of their employees.</p

Gene expression in TGFbeta-induced epithelial cell differentiation in a three-dimensional intestinal epithelial cell differentiation model

BACKGROUND: The TGFβ1-induced signal transduction processes involved in growth and differentiation are only partly known. The three-dimensional epithelial differentiation model, in which T84 epithelial cells are induced to differentiate either with TGFβ1 or IMR-90 mesenchymal cell-secreted soluble factors, is previously shown to model epithelial cell differentiation seen in intestine. That model has not been used for large scale gene expression studies, such as microarray method. Therefore the gene expression changes were studied in undifferentiated and differentiated three-dimensional T84 cultures with cDNA microarray method in order to study the molecular changes and find new players in epithelial cell differentiation. RESULTS: The expression of 372 genes out of 5188 arrayed sequences was significantly altered, and 47 of them were altered by both mediators. The data were validated and the altered genes are presented in ontology classes. For the genes tested the expressions in protein level were in accordance with the mRNA results. We also found 194 genes with no known function to be potentially important in epithelial cell differentiation. The mRNA expression changes induced by TGFβ1 were bigger than changes induced by soluble factors secreted by IMR-90 mesenchymal cells. The gene expression data was depicted in already known signaling pathway routes. CONCLUSION: Our results reveal potential new signaling pathways and several new genes affected by TGFβ in epithelial cell differentiation. The differentiation induced by TGFβ1 appears to be more potent than the differentiation induced by mesenchymal cells. This study indicates that our cell culture model is a suitable tool in studying regulatory mechanisms during epithelial cell differentiation in intestine. Furthermore the present results indicate that our model is a good tool for finding new players acting in the differentiation of epithelial cells