Assessing seizure liability in vitro with voltage-sensitive dye imaging in mouse hippocampal slices

Non-clinical toxicology is a major cause of drug candidate attrition during development. In particular, drug-induced seizures are the most common finding in central nervous system (CNS) toxicity. Current safety pharmacology tests for assessing CNS functions are often inadequate in detecting seizure-inducing compounds early in drug development, leading to significant delays. This paper presents an in vitro seizure liability assay using voltage-sensitive dye (VSD) imaging techniques in hippocampal brain slices, offering a powerful alternative to traditional electrophysiological methods. Hippocampal slices were isolated from mice, and VSD optical responses evoked by stimulating the Schaffer collateral pathway were recorded and analyzed in the stratum radiatum (SR) and stratum pyramidale (SP). VSDs allow for the comprehensive visualization of neuronal action potentials and postsynaptic potentials on a millisecond timescale. By employing this approach, we investigated the in vitro drug-induced seizure liability of representative pro-convulsant compounds. Picrotoxin (PiTX; 1–100 μM), gabazine (GZ; 0.1–10 μM), and 4-aminopyridine (4AP; 10–100 μM) exhibited seizure-like responses in the hippocampus, but pilocarpine hydrochloride (Pilo; 10–100 μM) did not. Our findings demonstrate the potential of VSD-based assays in identifying seizurogenic compounds during early drug discovery, thereby reducing delays in drug development and providing insights into the mechanisms underlying seizure induction and the associated risks of pro-convulsant compounds

The Relationship between Individual Difference in Repressive Stles and Grief Reaction Coping Behaviors, and Onset of Pathological Grief, Anxiety and Mood Disorders after Child Loss

We examined the relationship between parental repressive styles, grief reaction/post-bereavement coping behavior and psychiatric symptoms in parents who had lost young children, In Study I, we administered a set of questionnaires to a sample of 177 parents who had experienced bereavement of children within the past several years in order to inquire about grief response, coping behavior, repressive styles, and social support .After controlling for sex, age, income, and self esteem, 1) subjects who had high anxiety (sensitizer and repressive-anxiety) showed stronger grief response whereas those with low anxiety (repressor and low-anxiety) showed weak response; 2) repressors were more likely to accept death and resolute grief after the loss than others; 3) those who had higher anxiety were more likely to ruminate after death; and 4) sensitizers were less likely to satisfy perceived social support. In Study II we interviewed 60 bereaved parents using a semi-structured diagnostic interview schedule to yield diagnoses of the parents based on the Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV). Parents with repressive-anxiety were more likely to manifest pathological grief and those parents recognized as sensitizers were more likely to have an onset of DSM-IV Major Depression or Social Phobia after the child\u27s death.抑圧様式と悲嘆反応、死別後の対処行動、精神症状との関連性について検討した。研究Iでは幼い子どもと死別した親177名を対象に悲嘆反応、対処行動、抑圧様式、ソーシャルサポートを測定した。性別、年齢、収入などを統制し分析した結果、①不安水準の高い sensitizer, repressive Anxiety 各群では悲嘆反応が強心不安水準の低い repressor, low-anxiety各群では悲嘆反応が弱い、②repressor群では悲嘆がすでに解決したことと認知し、死別体験を肯定的に捉える傾向が強い、③不安水準が高いと死別後に内的に考え込む対処を多く行う、④sensitizer群では知覚されたソーシャルサポートに対する満足度が低い傾向にあった。研究IIでは60名に半構造化面接を行い、死別後に罹患した精神疾患の診断を行った。その結果，⑤病的悲嘆はrepressive- anxiety傾向と，⑥大うつ病性障害や社会恐怖はsensitization傾向とそれぞれ関連することが示された

The Measurement of Grief and Coping after Loss of a Child

We administered Grief Response Scale (GRS), Japanese translation of "Core Bereavement Items," and a set of newly developed coping　behavior items (Scale for Coping with　Bereavement; SCB) to 48 fathers and 127　mothers who experienced the loss of a child within several years. Although a confirmatory factor analysis of GRS did not support the original seven-factor model byBurnett et al., an exploratory factor analysis yielded four factors: lmage and sorrow, Sense of presence， Non-resolution and conflict, and Resolution of grief. Grief reaction was significantly greater in mothers than in fathers. An exploratory factor analysis of SCB produced five factors: Distraction, Ruminative response, A cceptance and overcome, Support-seeking behavior, and Religious activity and existential meaning. As compared to fathers, mothers ruminated, sought support from others, and had religious activity more frequently. These results suggest that different aspects of grief were related with coping with bereavement after controlling for age, sex, income, and level of manifest anxiety

パネル トーク タブンカ シャカイ ニ モトメ ラレル ジンザイ トワ パネル トーク タブンカ シャカイ ニ モトメ ラレル ジンザイ トワ タブンカ シャカイ コーディネーター ヨウセイ プログラム ソノ センモンセイ ト リキリョウ ケイセイ ノ トリクミ

Membrane-based liquid desiccant dehumidification has attracted increasing interests with elimination of solution droplets carryover problem. In this study, a membrane-based hybrid liquid desiccant dehumidification cooling system is developed, which is mainly composed of a dehumidifier, a regenerator and an evaporative cooler. The system is capable to remove latent load by the liquid desiccant dehumidification unit and simultaneously to handle sensible load with an evaporative cooling unit. This paper presents a performance evaluation study of the hybrid system with calcium chloride as liquid desiccant based on experimental data. Series of tests are conducted to identify influences of operating variables and conditions (i.e. desiccant solution concentration ratio, regeneration temperature, inlet air condition, etc.) on the system performance. The experimental results indicate that the system is viable for dehumidification cooling purpose. Furthermore, it is noteworthy that mass balance between the dehumidifier and regenerator should be achieved for system steady operation. Thermal COPth of 0.70 and 24 electrical COPel of 2.62 are achieved respectively under steady operating condition at CaCl2 concentration ratio of 36%

Beam and SKS spectrometers at the K1.8 beam line

High-resolution spectrometers for both incident beams and scattered particles have been constructed at the K1.8 beam line of the Hadron Experimental Facility at J-PARC. A point-to-point optics is realized between the entrance and exit of QQDQQ magnets for the beam spectrometer. Fine-pitch wire chamber trackers and hodoscope counters are installed in the beam spectrometer to accept a high rate beam up to 107 Hz. The superconducting kaon spectrometer for scattered particles was transferred from KEK with modifications to the cryogenic system and detectors. A missing-mass resolution of 1.9 ± 0.1 MeV/c2 (FWHM) was achieved for the ∑ peaks of (π±, K+) reactions on a proton target in the first physics run of E19 in 2010

Preterm toddlers have low nighttime sleep quality and high daytime activity.

A number of studies have been made on the sleep characteristics of children born preterm in an attempt to develop methods to address the sleep problems commonly observed among such children. However, the reported sleep characteristics from these studies vary depending on the observation methods used, i.e., actigraphy, polysomnography and questionnaire. In the current study, to obtain reliable data on the sleep characteristics of preterm-born children, we investigated the difference in sleep properties between 97 preterm and 97 term toddlers of approximately 1.5 years of age using actigraphy. Actigraphy units were attached to the toddlers’ waists with an adjustable elastic belt for 7 consecutive days, and a child sleep diary was completed by their parents. In the study, we found that preterm toddlers had more nocturnal awakenings and more daytime activity, suggesting that preterm-born children may have a different process of sleep development in their early development