Is refraction with a hand-held autorefractometer useful in addition to visual acuity testing and questionnaires in preschool vision screening at 3.5 years in Japan?

The vision-screening program for 3.5-year-old children in Japan consists of 3 steps:questionnaires and home visual acuity testing, visual acuity testing by nurses and inspection by medical officers at regional Public Health Centers, and examinations by ophthalmologists. In this study, we tested refraction with a hand-held autorefractometer in addition to visual acuity testing and inspection to reveal whether or not autorefraction leads to better detection of eye problems. Autorefraction was performed in 6 consecutive sessions by a single examiner in 265 children at 3.5 years of age who all visited the same center. The children were sent to the third step of examinations by ophthalmologists based on refractive error criteria:3 diopters myopia or 1 diopter hyperopia, and/or 2 diopters astigmatism in either eye, in addition to the current criteria:1) failure in either eye for 0.5 visual acuity at the center, 2) eye-related symptoms revealed by the questionnaires, or 3) eye problems detected by medical officers. Notices to visit ophthalmologists were issued for 64 children (24%), and 37 of those (58%) made the visits, so that documents containing final diagnoses were sent back to the Public Health Office. Of the 64 children, 12 were sent to ophthalmologists based on the current criteria only, 10 based on both the current criteria and the refractive error criteria, and 42 based on the refractive error criteria only. Twelve of the 13 children visiting ophthalmologists by the current criteria had diagnoses such as amblyopia and strabismus. In contrast, 15 of 24 children visiting ophthalmologists by only the refractive error criteria had mainly diagnoses of refractive errors, with no serious problems. In conclusion, autorefraction in addition to visual acuity testing and inspection led to detection of only one additional case of an eye disease at 3.5 years, while tripling the number of children sending to the third-step examination by an ophthalmologist. Thus, from a cost-effectiveness standpoint, autorefraction is not recommended as an additional test when the current system is conducted as designed.</p

Detection of strabismus and amblyopia in 1.5- and 3-year-old children by a preschool vision-screening program in japan

All children at the age of 1.5 and 3 years in Japan undergo physical, mental, and developmental checkups including dental, eye, and hearing examinations. The vision-screening program consists of 3 steps : questionnaires and home visual acuity testing as the first step (only for 3-year-old children), visual acuity testing by nurses and inspection by medical officers at regional Health Centers as the second step, and detailed examinations by ophthalmologists as the third step. This study aims to reveal the prevalence of strabismus and amblyopia as obtained from data in the vision-screening program. The final diagnoses made by ophthalmologists and sent back to the Health Centers in Okayama City were reviewed to elucidate the prevalence of strabismus, amblyopia, refractive errors, and other diseases in 1.5- and 3-year-old children in Okayama City in 5 years from 2000 to 2004. Of approximately 6,500-6,900 total children, 83.7-86.8% at 1.5 years old and 77.8-81.9% at 3 years old were brought to the Health Centers. The rates of strabismus were 0.01-0.12% at 1.5 years old and 0.20-0.34% at 3 years old, while the rates of amblyopia were 0% at 1.5 years old and 0.13-0.18% at 3 years old. The higher rates of strabismus at 3 years old were attributed mainly to the increase of exotropia and intermittent exotropia. In conclusions, the prevalence of strabismus was different between 1.5- and 3-year-old children. The vision-screening program in Japan functions to detect strabismus and amblyopia

Step-by-Step Procedure to Test Photoelectric Dye-Coupled Polyethylene Film as Retinal Prosthesis to Induce Light-Evoked Spikes in Isolated Retinal Dystrophic Tissue of rd1 Mice

Purpose: Multielectrode array recording for electric activity in cardiac and neuronal cells has been developed as preclinical tests for drug screening. This study aims to establish an in vitro assay system, using the multielectrode array, to record light-evoked spikes in isolated degenerative retinal tissues of retinal dystrophic rd1 mouse, as a preclinical test to examine the efficacy of photoelectric dye-coupled thin film retinal prosthesis. Methods: Light-evoked spike response was tested for 1 min at first step in the isolated degenerative retinal tissue of retinal dystrophic rd1 mouse only on the multielectrode array, tested in the same retinal tissue overlain with a plain control film for light-off and light-on 10 min each at second step, and tested in the same tissue overlain with a dye-coupled film at third step. The retinal tissues which showed light-evoked response at first or second step were not used for evaluation at third step. Results: Residual light-evoked spikes were recorded at first or second step in 18 of 35 retinal tissues (51%) at 6 weeks of the age in rd1 mice, 16 of 44 tissues (36%) at 7 weeks, and 10 of 39 tissues (25%) at 8 weeks. At third step, light-evoked spikes were recorded with dye-coupled films in 8 of 17 retinal tissues (47%) at 6 weeks, 10 of 28 tissues (35%) at 7 weeks, and 8 of 29 tissues (27%) at 8 weeks. Conclusion: A step-by-step procedure with internal control was established to measure light-evoked spikes by the multielectrode array in the isolated degenerative retinal tissue to evaluate photoelectric dye-coupled thin films. This preclinical study would present one line of evidence for the efficacy of photoelectric dye-coupled thin film retinal prosthesis towards a first-in-human clinical trial

De novo triplication of 11q12.3 in a patient with developmental delay and distinctive facial features

BACKGROUND: Triplication is a rare chromosomal anomaly. We identified a de novo triplication of 11q12.3 in a patient with developmental delay, distinctive facial features, and others. In the present study, we discuss the mechanism of triplications that are not embedded within duplications and potential genes which may contribute to the phenotype. RESULTS: The identified triplication of 11q12.3 was 557 kb long and not embedded within the duplicated regions. The aberrant region was overlapped with the segment reported to be duplicated in 2 other patients. The common phenotypic features in the present patient and the previously reported patient were brain developmental delay, finger abnormalities (including arachnodactuly, camptodactyly, brachydactyly, clinodactyly, and broad thumbs), and preauricular pits. CONCLUSIONS: Triplications that are not embedded within duplicated regions are rare and sometimes observed as the consequence of non-allelic homologous recombination. The de novo triplication identified in the present study is novel and not embedded within the duplicated region. In the 11q12.3 region, many copy number variations were observed in the database. This may be the trigger of this rare triplication. Because the shortest region of overlap contained 2 candidate genes, STX5 and CHRM1, which show some relevance to neuronal functions, we believe that the genomic copy number gains of these genes may be responsible for the neurological features seen in these patients

Neural Activity Changes Underlying the Working Memory Deficit in Alpha-CaMKII Heterozygous Knockout Mice

The alpha-isoform of calcium/calmodulin-dependent protein kinase II (α-CaMKII) is expressed abundantly in the forebrain and is considered to have an essential role in synaptic plasticity and cognitive function. Previously, we reported that mice heterozygous for a null mutation of α-CaMKII (α-CaMKII+/−) have profoundly dysregulated behaviors including a severe working memory deficit, which is an endophenotype of schizophrenia and other psychiatric disorders. In addition, we found that almost all the neurons in the dentate gyrus (DG) of the mutant mice failed to mature at molecular, morphological and electrophysiological levels. In the present study, to identify the brain substrates of the working memory deficit in the mutant mice, we examined the expression of the immediate early genes (IEGs), c-Fos and Arc, in the brain after a working memory version of the eight-arm radial maze test. c-Fos expression was abolished almost completely in the DG and was reduced significantly in neurons in the CA1 and CA3 areas of the hippocampus, central amygdala, and medial prefrontal cortex (mPFC). However, c-Fos expression was intact in the entorhinal and visual cortices. Immunohistochemical studies using arc promoter driven dVenus transgenic mice demonstrated that arc gene activation after the working memory task occurred in mature, but not immature neurons in the DG of wild-type mice. These results suggest crucial insights for the neural circuits underlying spatial mnemonic processing during a working memory task and suggest the involvement of α-CaMKII in the proper maturation and integration of DG neurons into these circuits

Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice

<p>Abstract</p> <p>Background</p> <p>Neuronal nitric oxide synthase (nNOS) is involved in the regulation of a diverse population of intracellular messenger systems in the brain. In humans, abnormal NOS/nitric oxide metabolism is suggested to contribute to the pathogenesis and pathophysiology of some neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Mice with targeted disruption of the nNOS gene exhibit abnormal behaviors. Here, we subjected nNOS knockout (KO) mice to a battery of behavioral tests to further investigate the role of nNOS in neuropsychiatric functions. We also examined the role of nNOS in dopamine/DARPP-32 signaling in striatal slices from nNOS KO mice and the effects of the administration of a dopamine D1 receptor agonist on behavior in nNOS KO mice.</p> <p>Results</p> <p>nNOS KO mice showed hyperlocomotor activity in a novel environment, increased social interaction in their home cage, decreased depression-related behavior, and impaired spatial memory retention. In striatal slices from nNOS KO mice, the effects of a dopamine D1 receptor agonist, SKF81297, on the phosphorylation of DARPP-32 and AMPA receptor subunit GluR1 at protein kinase A sites were enhanced. Consistent with the biochemical results, intraperitoneal injection of a low dose of SKF81297 significantly decreased prepulse inhibition in nNOS KO mice, but not in wild-type mice.</p> <p>Conclusion</p> <p>These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders.</p

Effects of Activity Participation of the Elderly on Quality of Life

Quality of life (QOL) and personality were examined in 2 groups of elderly subjects with and without activity participation (AP). A survey was conducted with 321 elderly subjects over 65 years of age using a 24-item questionnaire regarding personality and depressive inclination and the visual analogue scale-happiness to measure QOL. The AP group was involved in 5 types of activity: community center activity course, learning and lecture participation, club activity, elderly manpower service activity and other activities. The QOL of the AP group was significantly higher than the non-AP group as expected. The perceptual difference between the 2 groups obtained by the correspondence and cluster analyses was that although the elderly of the AP group were satisfied and not bored with their current life, this trend was not clear for the non-AP group. Among the 5 activity types, other activities, characterized as activities adhered to by participants over a long period, showed the highest QOL compared with the 4 other types. In conclusion, the AP of the elderly should be encouraged, and continuing AP might be an important factor in improving QOL of the elderly

Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis

Shimada, M., Goshima, T., Matsuo, H. et al. Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis. Nat Commun 7, 12059 (2016). https://doi.org/10.1038/ncomms1205

Self-Organized Formation of Polarized Cortical Tissues from ESCs and Its Active Manipulation by Extrinsic Signals

SummaryHere, we demonstrate self-organized formation of apico-basally polarized cortical tissues from ESCs using an efficient three-dimensional aggregation culture (SFEBq culture). The generated cortical neurons are functional, transplantable, and capable of forming proper long-range connections in vivo and in vitro. The regional identity of the generated pallial tissues can be selectively controlled (into olfactory bulb, rostral and caudal cortices, hem, and choroid plexus) by secreted patterning factors such as Fgf, Wnt, and BMP. In addition, the in vivo-mimicking birth order of distinct cortical neurons permits the selective generation of particular layer-specific neurons by timed induction of cell-cycle exit. Importantly, cortical tissues generated from mouse and human ESCs form a self-organized structure that includes four distinct zones (ventricular, early and late cortical-plate, and Cajal-Retzius cell zones) along the apico-basal direction. Thus, spatial and temporal aspects of early corticogenesis are recapitulated and can be manipulated in this ESC culture