Phosphocholine – an agonist of metabotropic but not of ionotropic functions of alpha9-containing nicotinic acetylcholine receptors

We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1beta from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1beta is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1beta release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing alpha9 and alpha10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of alpha9 subunits or heteromeric receptors containing alpha9 and alpha10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions

Manual for implementation or modification of child vision and hearing screening programmes:EUSCREEN

The euscreen study aimed to compare vision and hearing screening programmes for children in all EU states by using a cost-effectiveness model. The cost-effectiveness model predicts the most cost-effective and affordable way to screen children in each country, given the local circumstances. Representatives of countries in Europe were asked to provide detailed data on the following domains: demography, the general background of screening systems, existing screening systems, coverage/attendance, tests used, follow-up/diagnosis, treatment, benefits and adverse effects. Paediatric ophthalmologists, paediatric otolaryngologists, audiologists and professionals who organise and perform screening in each country were invited to participate in the study and report on the state of screening in their country. An extensive, detailed questionnaire was developed for that purpose. Screening programmes have been tested in the county of Cluj in Romania for vision, and in three counties in Albania for hearing screening. This manual for implementation or modification of child vision and hearing screening programmes was developed by detailed tracking, and from identified requisites, facilitators and barriers. The cost-effectiveness model and this manual for implementation will assist healthcare providers and policy makers worldwide in their decisions to introduce or modify vision and hearing screening programmes, and increase effectiveness, efficiency and equity of child healthcar

Manual for implementation or modification of child vision and hearing screening programmes:EUSCREEN

The euscreen study aimed to compare vision and hearing screening programmes for children in all EU states by using a cost-effectiveness model. The cost-effectiveness model predicts the most cost-effective and affordable way to screen children in each country, given the local circumstances. Representatives of countries in Europe were asked to provide detailed data on the following domains: demography, the general background of screening systems, existing screening systems, coverage/attendance, tests used, follow-up/diagnosis, treatment, benefits and adverse effects. Paediatric ophthalmologists, paediatric otolaryngologists, audiologists and professionals who organise and perform screening in each country were invited to participate in the study and report on the state of screening in their country. An extensive, detailed questionnaire was developed for that purpose. Screening programmes have been tested in the county of Cluj in Romania for vision, and in three counties in Albania for hearing screening. This manual for implementation or modification of child vision and hearing screening programmes was developed by detailed tracking, and from identified requisites, facilitators and barriers. The cost-effectiveness model and this manual for implementation will assist healthcare providers and policy makers worldwide in their decisions to introduce or modify vision and hearing screening programmes, and increase effectiveness, efficiency and equity of child healthcar

The cost-effectiveness of different visual acuity screening strategies in three European countries: a microsimulation study

Childhood vision screening programmes in Europe differ by age, frequency and location at which the child is screened, and by the professional who performs the test. The aim of this study is to compare the cost-effectiveness for three countries with different health care structures. We developed a microsimulation model of amblyopia. The natural history parameters were calibrated to a Dutch observational study. Sensitivity, specificity, attendance, lost to follow-up and costs in the three countries were based on the EUSCREEN Survey. Quality adjusted life-years (QALYs) were calculated using assumed utility loss for unilateral persistent amblyopia (1%) and bilateral visual impairment (8%). We calculated the cost-effectiveness of screening (with 3.5% annual discount) by visual acuity measurement at age 5 years or 4 and 5 years in the Netherlands by nurses in child healthcare centres, in England and Wales by orthoptists in schools and in Romania by urban kindergarten nurses. We compared screening at various ages and with various frequencies. Assuming an amblyopia prevalence of 36 per 1,000 children, the model predicted that 7.2 cases of persistent amblyopia were prevented in the Netherlands, 6.6 in England and Wales and 4.5 in Romania. The cost-effectiveness was €24,159, €19,981 and €23,589, per QALY gained respectively, compared with no screening. Costs/QALY was influenced most by assumed utility loss of unilateral persistent amblyopia. For all three countries, screening at age 5, or age 4 and 5 years were optimal. Despite differences in health care structure, vision screening by visual acuity measurement seemed cost-effective in all three countries

Availability of data for cost-effectiveness comparison of child vision and hearing screening programmes

Objective For cost-effectiveness comparison of child vision and hearing screening programmes, methods and data should be available. We assessed the current state of data collection and its availability in Europe. Methods The EUSCREEN Questionnaire, conducted in 2017–2018, assessed paediatric vision and hearing screening programmes in 45 countries in Europe. For the current study, its items on data collection, monitoring and evaluation, and six of eleven items essential for cost-effectiveness analysis: prevalence, sensitivity, specificity, coverage, attendance and loss to follow-up, were reappraised with an additional questionnaire. Results The practice of data collection in vision screening was reported in 36% (N = 42) of countries and in hearing screening in 81% (N = 43); collected data were published in 12% and 35%, respectively. Procedures for quality assurance in vision screening were reported in 19% and in hearing screening in 26%, research of screening effectiveness in 43% and 47%, whereas cost-effectiveness analysis was performed in 12% for both. Data on prevalence of amblyopia were reported in 40% and of hearing loss in 77%, on sensitivity of screening tests in 17% and 14%, on their specificity in 19% and 21%, on coverage of screening in 40% and 84%, on attendance in 21% and 37%, and on loss to follow-up in 12% and 40%, respectively. Conclusions Data collection is insufficient in hearing screening and even more so in vision screening: data essential for cost-effectiveness comparison could not be reported from most countries. When collection takes place, this is mostly at a local level for quality assurance or accountability, and data are often not accessible. The resulting inability to compare cost-effectiveness among screening programmes perpetuates their diversity and inefficiency

Environmental Enrichment Promotes Plasticity and Visual Acuity Recovery in Adult Monocular Amblyopic Rats

Loss of visual acuity caused by abnormal visual experience during development (amblyopia) is an untreatable pathology in adults. In some occasions, amblyopic patients loose vision in their better eye owing to accidents or illnesses. While this condition is relevant both for its clinical importance and because it represents a case in which binocular interactions in the visual cortex are suppressed, it has scarcely been studied in animal models. We investigated whether exposure to environmental enrichment (EE) is effective in triggering recovery of vision in adult amblyopic rats rendered monocular by optic nerve dissection in their normal eye. By employing both electrophysiological and behavioral assessments, we found a full recovery of visual acuity in enriched rats compared to controls reared in standard conditions. Moreover, we report that EE modulates the expression of GAD67 and BDNF. The non invasive nature of EE renders this paradigm promising for amblyopia therapy in adult monocular people

The Effect of Sensory Uncertainty Due to Amblyopia (Lazy Eye) on the Planning and Execution of Visually-Guided 3D Reaching Movements

Background: Impairment of spatiotemporal visual processing in amblyopia has been studied extensively, but its effects on visuomotor tasks have rarely been examined. Here, we investigate how visual deficits in amblyopia affect motor planning and online control of visually-guided, unconstrained reaching movements. Methods: Thirteen patients with mild amblyopia, 13 with severe amblyopia and 13 visually-normal participants were recruited. Participants reached and touched a visual target during binocular and monocular viewing. Motor planning was assessed by examining spatial variability of the trajectory at 50–100 ms after movement onset. Online control was assessed by examining the endpoint variability and by calculating the coefficient of determination (R 2) which correlates the spatial position of the limb during the movement to endpoint position. Results: Patients with amblyopia had reduced precision of the motor plan in all viewing conditions as evidenced by increased variability of the reach early in the trajectory. Endpoint precision was comparable between patients with mild amblyopia and control participants. Patients with severe amblyopia had reduced endpoint precision along azimuth and elevation during amblyopic eye viewing only, and along the depth axis in all viewing conditions. In addition, they had significantly higher R 2 values at 70 % of movement time along the elevation and depth axes during amblyopic eye viewing. Conclusion: Sensory uncertainty due to amblyopia leads to reduced precision of the motor plan. The ability to implemen