Monitoring Cognitive and Emotional Processes Through Pupil and Cardiac Response During Dynamic Versus Logical Task

The paper deals with the links between physiological measurements and cognitive and emotional functioning. As long as the operator is a key agent in charge of complex systems, the definition of metrics able to predict his performance is a great challenge. The measurement of the physiological state is a very promising way but a very acute comprehension is required; in particular few studies compare autonomous nervous system reactivity according to specific cognitive processes during task performance and task related psychological stress is often ignored. We compared physiological parameters recorded on 24 healthy subjects facing two neuropsychological tasks: a dynamic task that require problem solving in a world that continually evolves over time and a logical task representative of cognitive processes performed by operators facing everyday problem solving. Results showed that the mean pupil diameter change was higher during the dynamic task; conversely, the heart rate was more elevated during the logical task. Finally, the systolic blood pressure seemed to be strongly sensitive to psychological stress. A better taking into account of the precise influence of a given cognitive activity and both workload and related task-induced psychological stress during task performance is a promising way to better monitor operators in complex working situations to detect mental overload or pejorative stress factor of error

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Something is Amiss in Denmark: A Comparison of Preventable Hospitalisations and Readmissions for Chronic Medical Conditions in the Danish Healthcare System and Kaiser Permanente

Background: As many other European healthcare systems the Danish healthcare system (DHS) has targeted chronic condition care in its reform efforts. Benchmarking is a valuable tool to identify areas for improvement. Prior work indicates that chronic care coordination is poor in the DHS, especially in comparison with care in Kaiser Permanente (KP), an integrated delivery system based in the United States. We investigated population rates of hospitalisation and readmission rates for ambulatory care sensitive, chronic medical conditions in the two systems. Methods: Using a historical cohort study design, age and gender adjusted population rates of hospitalisations for angina, heart failure, chronic obstructive pulmonary disease, and hypertension, plus rates of 30-day readmission and mortality were investigated for all individuals aged 65+ in the DHS and KP. Results: DHS had substantially higher rates of hospitalisations, readmissions, and mean lengths of stay per hospitalisation, than KP had. For example, the adjusted angina hospitalisation rates in 2007 for the DHS and KP respectively were 1.01/100 persons (95%CI: 0.98-1.03) vs. 0.11/100 persons (95%CI: 0.10-0.13/100 persons); 21.6% vs. 9.9% readmission within 30 days (OR = 2.53; 95% CI: 1.84-3.47); and mean length of stay was 2.52 vs. 1.80 hospital days. Mortality up through 30 days post-discharge was not consistently different in the two systems. Conclusions: There are substantial differences between the DHS and KP in the rates of preventable hospitalisations and subsequent readmissions associated with chronic conditions, which suggest much opportunity for improvement within the Danish healthcare system. Reductions in hospitalisations also could improve patient welfare and free considerable resources for use towards preventing disease exacerbations. These conclusions may also apply for similar public systems such as the US Medicare system, the NHS and other systems striving to improve the integration of care for persons with chronic conditions

ATP-Sensitive Potassium Channels Exhibit Variance in the Number of Open Channels below the Limit Predicted for Identical and Independent Gating

In small cells containing small numbers of ion channels, noise due to stochastic channel opening and closing can introduce a substantial level of variability into the cell's membrane potential. Negatively cooperative interactions that couple a channel's gating conformational change to the conformation of its neighbor(s) provide a potential mechanism for mitigating this variability, but such interactions have not previously been directly observed. Here we show that heterologously expressed ATP-sensitive potassium channels generate noise (i.e., variance in the number of open channels) below the level possible for identical and independent channels. Kinetic analysis with single-molecule resolution supports the interpretation that interchannel negative cooperativity (specifically, the presence of an open channel making a closed channel less likely to open) contributes to the decrease in noise. Functional coupling between channels may be important in modulating stochastic fluctuations in cellular signaling pathways

GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation

Glucagon-like peptide-1 (GLP-1) promotes insulin secretion from pancreatic ß-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. Since GLP-1-induced insulin secretion requires glucose metabolism, we aimed to address the hypothesis that GLP-1 receptor (GLP-1R) signalling can modulate glucose uptake and utilization in ß-cells. We have assessed various metabolic parameters after short and long exposure of clonal BRIN-BD11 ß-cells and rodent islets to the GLP-1R agonist Exendin-4 (50 nM). Here we report for the first time that prolonged stimulation of the GLP-1R for 18 hours promotes metabolic reprogramming of ß-cells. This is evidenced by up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux after removal of Exendin-4. In our model, depletion of Hypoxia-Inducible Factor 1 alpha (HIF-1a) impaired the effects of Exendin-4 on glucose metabolism, while pharmacological inhibition of Phosphoinositide 3-kinase (PI3K) or mTOR completely abolished such effects. Considering the central role of glucose catabolism for stimulus-secretion coupling in ß-cells, our findings suggest that chronic GLP-1 actions on insulin secretion include elevated ß-cell glucose metabolism. Moreover, our data reveal novel aspects of GLP-1 stimulated insulin secretion involving de novo gene expression

Ketamine-Induced Oscillations in the Motor Circuit of the Rat Basal Ganglia

Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion

Improved homology-driven computational validation of protein-protein interactions motivated by the evolutionary gene duplication and divergence hypothesis

<p>Abstract</p> <p>Background</p> <p>Protein-protein interaction (PPI) data sets generated by high-throughput experiments are contaminated by large numbers of erroneous PPIs. Therefore, computational methods for PPI validation are necessary to improve the quality of such data sets. Against the background of the theory that most extant PPIs arose as a consequence of gene duplication, the sensitive search for homologous PPIs, i.e. for PPIs descending from a common ancestral PPI, should be a successful strategy for PPI validation.</p> <p>Results</p> <p>To validate an experimentally observed PPI, we combine FASTA and PSI-BLAST to perform a sensitive sequence-based search for pairs of interacting homologous proteins within a large, integrated PPI database. A novel scoring scheme that incorporates both quality and quantity of all observed matches allows us (1) to consider also tentative paralogs and orthologs in this analysis and (2) to combine search results from more than one homology detection method. ROC curves illustrate the high efficacy of this approach and its improvement over other homology-based validation methods.</p> <p>Conclusion</p> <p>New PPIs are primarily derived from preexisting PPIs and not invented <it>de novo</it>. Thus, the hallmark of true PPIs is the existence of homologous PPIs. The sensitive search for homologous PPIs within a large body of known PPIs is an efficient strategy to separate biologically relevant PPIs from the many spurious PPIs reported by high-throughput experiments.</p

Modified constraint-induced movement therapy or bimanual occupational therapy following injection of Botulinum toxin-A to improve bimanual performance in young children with hemiplegic cerebral palsy: a randomised controlled trial methods paper

<p>Abstract</p> <p>Background</p> <p>Use of Botulinum toxin-A (BoNT-A) for treatment of upper limb spasticity in children with cerebral palsy has become routine clinical practice in many paediatric treatment centres worldwide. There is now high-level evidence that upper limb BoNT-A injection, in combination with occupational therapy, improves outcomes in children with cerebral palsy at both the body function/structure and activity level domains of the International Classification of Functioning, Disability and Health. Investigation is now required to establish what amount and specific type of occupational therapy will further enhance functional outcomes and prolong the beneficial effects of BoNT-A.</p> <p>Methods/Design</p> <p>A randomised, controlled, evaluator blinded, prospective parallel-group trial. Eligible participants were children aged 18 months to 6 years, diagnosed with spastic hemiplegic cerebral palsy and who were able to demonstrate selective motor control of the affected upper limb. Both groups received upper limb injections of BoNT-A. Children were randomised to either the modified constraint-induced movement therapy group (experimental) or bimanual occupational therapy group (control). Outcome assessments were undertaken at pre-injection and 1, 3 and 6 months following injection of BoNT-A. The primary outcome measure was the Assisting Hand Assessment. Secondary outcomes included: the Quality of Upper Extremity Skills Test; Pediatric Evaluation of Disability Inventory; Canadian Occupational Performance Measure; Goal Attainment Scaling; Pediatric Motor Activity Log; modified Ashworth Scale and; the modified Tardieu Scale.</p> <p>Discussion</p> <p>The aim of this paper is to describe the methodology of a randomised controlled trial comparing the effects of modified constraint-induced movement therapy (a uni-manual therapy) versus bimanual occupational therapy (a bimanual therapy) on improving bimanual upper limb performance of children with hemiplegic cerebral palsy following upper limb injection of BoNT-A. The paper outlines the background to the study, the study hypotheses, outcome measures and trial methodology. It also provides a comprehensive description of the interventions provided.</p> <p>Trial Registration</p> <p>ACTRN12605000002684</p

ATP release via anion channels

ATP serves not only as an energy source for all cell types but as an ‘extracellular messenger-for autocrine and paracrine signalling. It is released from the cell via several different purinergic signal efflux pathways. ATP and its Mg2+ and/or H+ salts exist in anionic forms at physiological pH and may exit cells via some anion channel if the pore physically permits this. In this review we survey experimental data providing evidence for and against the release of ATP through anion channels. CFTR has long been considered a probable pathway for ATP release in airway epithelium and other types of cells expressing this protein, although non-CFTR ATP currents have also been observed. Volume-sensitive outwardly rectifying (VSOR) chloride channels are found in virtually all cell types and can physically accommodate or even permeate ATP4- in certain experimental conditions. However, pharmacological studies are controversial and argue against the actual involvement of the VSOR channel in significant release of ATP. A large-conductance anion channel whose open probability exhibits a bell-shaped voltage dependence is also ubiquitously expressed and represents a putative pathway for ATP release. This channel, called a maxi-anion channel, has a wide nanoscopic pore suitable for nucleotide transport and possesses an ATP-binding site in the middle of the pore lumen to facilitate the passage of the nucleotide. The maxi-anion channel conducts ATP and displays a pharmacological profile similar to that of ATP release in response to osmotic, ischemic, hypoxic and salt stresses. The relation of some other channels and transporters to the regulated release of ATP is also discussed