Enteric Neurospheres Are Not Specific to Neural Crest Cultures: Implications for Neural Stem Cell Therapies

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Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

Not all shellfish "allergy" is allergy!

The popularity of shellfish has been increasing worldwide, with a consequent increase in adverse reactions that can be allergic or toxic. The approximate prevalence of shellfish allergy is estimated at 0.5-2.5% of the general population, depending on degree of consumption by age and geographic regions. The manifestations of shellfish allergy vary widely, but it tends to be more severe than most other food allergens

Identifying differentially methylated genes using mixed effect and generalized least square models

<p>Abstract</p> <p>Background</p> <p>DNA methylation plays an important role in the process of tumorigenesis. Identifying differentially methylated genes or CpG islands (CGIs) associated with genes between two tumor subtypes is thus an important biological question. The methylation status of all CGIs in the whole genome can be assayed with differential methylation hybridization (DMH) microarrays. However, patient samples or cell lines are heterogeneous, so their methylation pattern may be very different. In addition, neighboring probes at each CGI are correlated. How these factors affect the analysis of DMH data is unknown.</p> <p>Results</p> <p>We propose a new method for identifying differentially methylated (DM) genes by identifying the associated DM CGI(s). At each CGI, we implement four different mixed effect and generalized least square models to identify DM genes between two groups. We compare four models with a simple least square regression model to study the impact of incorporating random effects and correlations.</p> <p>Conclusions</p> <p>We demonstrate that the inclusion (or exclusion) of random effects and the choice of correlation structures can significantly affect the results of the data analysis. We also assess the false discovery rate of different models using CGIs associated with housekeeping genes.</p

Does improved functional performance help to reduce urinary incontinence in institutionalized older women? a multicenter randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Urinary incontinence (UI) is a major problem in older women. Management is usually restricted to dealing with the consequences instead of treating underlying causes such as bladder dysfunction or reduced mobility.</p> <p>The aim of this multicenter randomized controlled trial was to compare a group-based behavioral exercise program to prevent or reduce UI, with usual care. The exercise program aimed to improve functional performance of pelvic floor muscle (PFM), bladder and physical performance of women living in homes for the elderly.</p> <p>Methods</p> <p>Twenty participating Dutch homes were matched and randomized into intervention or control homes using a random number generator. Homes recruited 6–10 older women, with or without UI, with sufficient cognitive and physical function to participate in the program comprising behavioral aspects of continence and physical exercises to improve PFM, bladder and physical performance. The program consisted of a weekly group training session and homework exercises and ran for 6 months during which time the control group participants received care as usual. Primary outcome measures after 6 months were presence or absence of UI, frequency of episodes (measured by participants and caregivers (not blinded) using a 3-day bladder diary) and the Physical Performance Test (blinded). Linear and logistic regression analysis based on the Intention to Treat (ITT) principle using an imputed data set and per protocol analysis including all participants who completed the study and intervention (minimal attendance of 14 sessions).</p> <p>Results</p> <p>102 participants were allocated to the program and 90 to care as usual. ITT analysis (n = 85 intervention, n = 70 control) showed improvement of physical performance (intervention +8%; control −7%) and no differences on other primary and secondary outcome measures. Per protocol analysis (n = 51 intervention, n = 60 control) showed a reduction of participants with UI (intervention −40%; control −28%) and in frequency of episodes (intervention −51%; control −42%) in both groups; improvement of physical performance (intervention + 13%; control −4%) was related to participation in the exercise program.</p> <p>Conclusions</p> <p>This study shows that improving physical performance is feasible in institutionalized older women by exercise. Observed reductions in UI were not related to the intervention. [Current Controlled Trials ISRCTN63368283]</p

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Are mild head injuries as mild as we think? Neurobehavioral concomitants of chronic post-concussion syndrome

BACKGROUND: Mild traumatic brain injury (MTBI) can sometimes lead to persistent postconcussion symptoms. One well accepted hypothesis claims that chronic PCS has a neural origin, and is related to neurobehavioral deficits. But the evidence is not conclusive. In the attempt to characterise chronic MTBI consequences, the present experiment used a group comparison design, which contrasted persons (a) with MTBI and PCS, (b) MTBI without PCS, and (c) matched controls. We predicted that participants who have experienced MTBI but show no signs of PCS would perform similar to controls. At the same time, a subgroup of MTBI participants would show PCS symptoms and only these volunteers would have poorer cognitive performance. Thereby, the performance deficits should be most noticeable in participants with highest PCS severity. METHOD: 38 patients with a single MTBI that had occurred at least 12 month prior to testing, and 38 matched controls, participated in the experiment. A combination of questionnaires and neuropsychological test batteries were used to assess the extent of PCS and related deficits in neurobehavioral performance. RESULTS: 11 out of 38 MTBI participants (29%) were found to suffer from PCS. This subgroup of MTBI patients performed poorly on neuropsychological test batteries. Thereby, a correlation was found between PCS symptom severity and test performance suggesting that participants with more pronounced PCS symptoms performed worse in cognitive tasks. In contrast, MTBI patients with no PCS showed performed similar to matched control. We further found that loss of consciousness, a key criterion for PCS diagnosis, was not predictive of sustained PCS. CONCLUSION: The results support the idea that MTBI can have sustained consequences, and that the subjectively experienced symptoms and difficulties in everyday situations are related to objectively measurable parameters in neurocognitive function

Effect of crosslinking on the microtribological behavior of model polymer brushes

Polymer brushes in good solvents are known to exhibit excellent tribological properties. We have modeled polymer brushes and their gels using a multibead-spring model and studied their tribological behavior via nonequilibrium molecular-dynamics (MD) simulations. Simulations of brush- against-wall systems were performed using an implicit solvent-based approach. Polymer chains were modeled as linear chains, randomly grafted on a planar surface. Quantities extracted from the simulations are the normal stress, shear stress and concentration profiles. We find that while an increase in the degree of crosslinking leads to an increase in the coefficient of friction, an increase of the length of crosslinker chains does the opposite. Effect of crosslinking can be understood in two ways: (i) there are fewer polymer chains in the outer layer as the degree of crosslinking increases to take part in brush-assisted lubrication, and (ii) crosslinked polymer chains are more resistant to shear than non-crosslinked ones

A Pluralist Account of Knowledge as a Natural Kind

In an attempt to address some long-standing issues of epistemology, Hilary Kornblith proposes that knowledge is a natural kind the identification of which is the unique responsibility of one particular science: cognitive ethology. As Kornblith sees it, the natural kind thus picked out is knowledge as construed by reliabilism. Yet the claim that cognitive ethology has this special role has not convinced all critics. The present article argues that knowledge plays a causal and explanatory role within many of our more fruitful current theories, diverging from the reliabilist conception even in disciplines that are closely related to cognitive ethology, and thus still dealing with knowledge as a natural as opposed to a social phenomenon, where special attention will be given to cognitive neuroscience. However, rather than discarding the natural kind approach altogether, it is argued that many of Kornblith’s insights can in fact be preserved within a framework that is both naturalist and pluralist