The Optokinetic Reflex as a Tool for Quantitative Analyses of Nervous System Function in Mice: Application to Genetic and Drug-Induced Variation

The optokinetic reflex (OKR), which serves to stabilize a moving image on the retina, is a behavioral response that has many favorable attributes as a test of CNS function. The OKR requires no training, assesses the function of diverse CNS circuits, can be induced repeatedly with minimal fatigue or adaptation, and produces an electronic record that is readily and objectively quantifiable

Proton-coupled electron transfer reactivities of electronically divergent heme superoxide intermediates: a kinetic, thermodynamic, and theoretical study.

From Europe PMC via Jisc Publications RouterHistory: epub 2021-05-27, ppub 2021-07-01Publication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; Grant(s): BB/J014478/1Heme superoxides are one of the most versatile metallo-intermediates in biology, and they mediate a vast variety of oxidation and oxygenation reactions involving O2(g). Overall proton-coupled electron transfer (PCET) processes they facilitate may proceed via several different mechanistic pathways, attributes of which are not yet fully understood. Herein we present a detailed investigation into concerted PCET events of a series of geometrically similar, but electronically disparate synthetic heme superoxide mimics, where unprecedented, PCET feasibility-determining electronic effects of the heme center have been identified. These electronic factors firmly modulate both thermodynamic and kinetic parameters that are central to PCET, as supported by our experimental and theoretical observations. Consistently, the most electron-deficient superoxide adduct shows the strongest driving force for PCET, whereas the most electron-rich system remains unreactive. The pivotal role of these findings in understanding significant heme systems in biology, as well as in alternative energy applications is also discussed

Parameter estimate of signal transduction pathways

BACKGROUND: The "inverse" problem is related to the determination of unknown causes on the bases of the observation of their effects. This is the opposite of the corresponding "direct" problem, which relates to the prediction of the effects generated by a complete description of some agencies. The solution of an inverse problem entails the construction of a mathematical model and takes the moves from a number of experimental data. In this respect, inverse problems are often ill-conditioned as the amount of experimental conditions available are often insufficient to unambiguously solve the mathematical model. Several approaches to solving inverse problems are possible, both computational and experimental, some of which are mentioned in this article. In this work, we will describe in details the attempt to solve an inverse problem which arose in the study of an intracellular signaling pathway. RESULTS: Using the Genetic Algorithm to find the sub-optimal solution to the optimization problem, we have estimated a set of unknown parameters describing a kinetic model of a signaling pathway in the neuronal cell. The model is composed of mass action ordinary differential equations, where the kinetic parameters describe protein-protein interactions, protein synthesis and degradation. The algorithm has been implemented on a parallel platform. Several potential solutions of the problem have been computed, each solution being a set of model parameters. A sub-set of parameters has been selected on the basis on their small coefficient of variation across the ensemble of solutions. CONCLUSION: Despite the lack of sufficiently reliable and homogeneous experimental data, the genetic algorithm approach has allowed to estimate the approximate value of a number of model parameters in a kinetic model of a signaling pathway: these parameters have been assessed to be relevant for the reproduction of the available experimental data

Year in review in Intensive Care Medicine 2011: III. ARDS and ECMO, weaning, mechanical ventilation, noninvasive ventilation, pediatrics and miscellanea

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Burden of community-acquired and nosocomial rotavirus gastroenteritis in the pediatric population of Western Europe: a scoping review

<p>Abstract</p> <p>Background</p> <p>Rotavirus affects 95% of children worldwide by age 5 years and is the leading cause of severe dehydrating diarrhea. The objective of this review was to estimate the burden of rotavirus gastroenteritis (RVGE) in the Western European pediatric population.</p> <p>Methods</p> <p>A comprehensive literature search (1999-2010) was conducted in PubMed and other sources (CDC; WHO, others). Data on the epidemiology and burden of RVGE among children < 5 years-old in Western Europe --including hospital-acquired disease--were extracted.</p> <p>Results</p> <p>76 studies from 16 countries were identified. The mean percentage of acute gastroenteritis (AGE) cases caused by rotavirus ranged from 25.3%-63.5% in children < 5 years of age, peaking during winter. Incidence rates of RVGE ranged from 1.33-4.96 cases/100 person- years. Hospitalization rates for RVGE ranged from 7% to 81% among infected children, depending on the country. Nosocomial RVGE accounted for 47%-69% of all hospital-acquired AGE and prolonged hospital stays by 4-12 days. Each year, RVGE incurred $0.54-$53.6 million in direct medical costs and $1.7-$22.4 million in indirect costs in the 16 countries studied. Full serotyping data was available for 8 countries. G1P[8], G2P[4], G9P[8], and G3P[8] were the most prevalent serotypes (cumulative frequency: 57.2%- 98.7%). Serotype distribution in nosocomial RVGE was similar.</p> <p>Conclusions</p> <p>This review confirms that RVGE is a common disease associated with significant morbidity and costs across Western Europe. A vaccine protecting against multiple serotypes may decrease the epidemiological and cost burden of RVGE in Western Europe.</p

Fracture in the Elderly Multidisciplinary Rehabilitation (FEMuR): study protocol for a phase II randomised feasibility study of a multidisciplinary rehabilitation package following hip fracture

Objective: To conduct a rigorous feasibility study for a future definitive parallel-group randomised controlled trial (RCT) and economic evaluation of an enhanced rehabilitation package for hip fracture.Setting: Recruitment from 3 acute hospitals in North Wales. Intervention delivery in the community.Participants: Older adults (aged ≥65) who received surgical treatment for hip fracture, lived independently prior to fracture, had mental capacity (assessed by clinical team) and received rehabilitation in the North Wales area.Intervention: Remote randomisation to usual care (control) or usual care+enhanced rehabilitation package (intervention), including six additional home-based physiotherapy sessions delivered by a physiotherapist or technical instructor, novel information workbook and goal-setting diary.Primary and secondary outcome measures: Primary: Barthel Activities of Daily Living (BADL). Secondary measures included Nottingham Extended Activities of Daily Living scale (NEADL), EQ-5D, ICECAP capability, a suite of self-efficacy, psychosocial and service-use measures and costs. Outcome measures were assessed at baseline and 3-month follow-up by blinded researchers.Results: 62 participants were recruited, 61 randomised (control 32; intervention 29) and 49 (79%) completed 3-month follow-up. Minimal differences occurred between the 2 groups for most outcomes, including BADL (adjusted mean difference 0.5). The intervention group showed a medium-sized improvement in the NEADL relative to the control group, with an adjusted mean difference between groups of 3.0 (Cohen's d 0.63), and a trend for greater improvement in self-efficacy and mental health, but with small effect sizes. The mean cost of delivering the intervention was £231 per patient. There was a small relative improvement in quality-adjusted life year in the intervention group. No serious adverse events relating to the intervention were reported.Conclusions: The trial methods were feasible in terms of eligibility, recruitment and retention. The effectiveness and cost-effectiveness of the rehabilitation package should be tested in a phase III RCT