超音波断層法を用いた嚥下運動評価法

The aim of this study is to develop an index to assess swallowing function by ultrasonography in order to evaluate the relationship between movements of the hyoid bone and the larynx while swallowing water. Forty-two younger participants (mean age, 20.3 ± 3.4 years) and 42 older participants (mean age, 75.1 ± 10.6 years) with normal swallowing function were included in the study. Movements of the hyoid bone and the larynx while swallowing 5 mL of water were observed using ultrasonography. Two-dimensional distances from the starting points of the hyoid bone and the larynx to their points of maximum movement were measured as displacements. The hyoid bone–laryngeal motion ratio was defined as the hyoid bone displacement divided by the laryngeal displacement. Parameters were compared among four groups: younger male, younger female, older male, and older female. The hyoid bone displacement differed significantly between the younger and older groups, and the laryngeal displacement differed significantly between age groups and sexes. The hyoid bone–laryngeal motion ratio was not significantly correlated with age, height, or body weight, and did not show a significant difference between the four groups. Thus, the hyoid bone–laryngeal motion ratio is an index that evaluates swallowing movement and is independent of physique and physiological changes associated with aging

Behavioral Profiles of Three C57BL/6 Substrains

C57BL/6 inbred strains of mice are widely used in knockout and transgenic research. To evaluate the loss-of-function and gain-of-function effects of the gene of interest, animal behaviors are often examined. However, an issue of C57BL/6 substrains that is not always appreciated is that behaviors are known to be strongly influenced by genetic background. To investigate the behavioral characteristics of C57BL/6 substrains, we subjected C57BL/6J, C57BL/6N, and C57BL/6C mice to a behavior test battery. We performed both a regular scale analysis, in which experimental conditions were tightly controlled, and large-scale analysis from large number of behavioral data that we have collected so far through the comprehensive behavioral test battery applied to 700–2,200 mice in total. Significant differences among the substrains were found in the results of various behavioral tests, including the open field, rotarod, elevated plus maze, prepulse inhibition, Porsolt forced swim, and spatial working memory version of the eight-arm radial maze. Our results show a divergence of behavioral performance in C57BL/6 substrains, which suggest that small genetic differences may have a great influence on behavioral phenotypes. Thus, the genetic background of different substrains should be carefully chosen, equated, and considered in the interpretation of mutant behavioral phenotypes

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

99m-Technetium galactosyl human serum albumin scanning to evaluate liver function after stereotactic body radiotherapy for hepatocellular carcinoma: A case report

The primary choice among treatment options for liver malignancies is surgery. However, if surgery cannot be performed, Stereotactic body radiotherapy (SBRT) may be effective. 99m-technetium galactosyl human serum albumin (GSA) single-photon emission computed tomography (SPECT) imaging is useful for the assessment of liver function before surgery. We report the case of a 77-year-old man who had undergone SBRT for hepatocellular carcinoma of the left lobe of the liver 2 years previously. Follow-up revealed a 15-mm hepatocellular carcinoma at the edge of the right lobe of the liver. 99m-technetium GSA SPECT was performed before SBRT to confirm that there was no accumulation in the left lobe and to ensure that there was good function of the right lobe. Three months after SBRT, the tumor had responded, and decreases in GSA accumulation were observed in line with the radiation beam. Because hepatocellular carcinoma often relapses, it is important to assess the anatomic site of liver dysfunction before and after radiation. This case demonstrates that 99m-technetium GSA SPECT is useful for this purpose

The Comparative Study of Dysphagia Screening Tests

【目的】本研究では，嚥下スクリーニングテストの包括的な評価方法の有用性を検討した． 【方法】嚥下障害者3例に対して，嚥下スクリーニングとして単一の項目で標準化されたテストであるRSST とMWST，および包括的評価を行うStandardized Swallowing Assessment（以下，SSA）とThe Toronto Bedside Swallowing Screening Test（以下，TOR-BSST）の4つのテストを用いた評価場面をビデオ撮影し，独自に教則ビデオを作成した．その後，言語聴覚士65名（平均臨床経験年数5.2±3.6年）を対象に，作成した教則ビデオを視聴させた後，アンケート調査を実施した．アンケートの質問は10項目で，嚥下障害のスクリーニングテストにおける ① 簡便性，② 嚥下障害における問題の所在の確認と推測，③安全性，④ 重症度の判定，⑤ 食事形態の決定への活用，⑥ 嚥下訓練につながるアセスメントの可否，⑦嚥下訓練の効果判定，⑧ 嚥下機能の経時的変化，⑨ 嚥下障害の検出力，⑩ 総合的な使い勝手，についての ① から ⑩ 項目で構成され，各質問を「思わない」から「そう思う」までの5 件法で尋ねた．解析方法はKruskal―Wallis 検定を用いて，有意水準5%未満として検討した． 【結果】単一項目で行う評価方法と包括的に行う評価方法との比較では，今回使用したアンケート調査の10項目中7項目（ ②，④，⑤，⑥，⑦，⑧，⑨）において，包括的評価方法の有用性が支持された． 【結論】術者の主観的な評価として，今回調査した4つすべての嚥下スクリーニングテストは総合的に使い勝手がよいと判断され，さらにSSAやTOR-BSSTで用いられる包括的な評価方法は，嚥下障害の問題の所在の確認および推測，嚥下障害の重症度の判定，食事形態の決定への活用，嚥下訓練につながるアセスメントの可否，嚥下訓練の効果判定，嚥下機能の経時的変化を捉えていくことへの活用，嚥下障害の検出力において，RSST やMWST を単一項目で評価する場合よりも有用であることが示唆された．Objective:　In this research, two types (comprehensive evaluation methods and single evaluation methods) of dysphagia screening test were compared effectiveness to confirm more appropriate as the screening test. Methods:　Video recordings were made of 3 patients with dysphagia who underwent single evaluation methods (RSST and MWST) or comprehensive evaluation methods (SSA and TOR-BSST) in dysphagia screening tests. These recordings were then used to create a teaching video movie, which was shown to 65 speech therapists with clinical experience (mean years of experience, 5.2±3.6 years); these therapists were then administered a questionnaire. This questionnaire consisted of 10 items, which covered the following aspects of the dysphagia screening tests: simplicity of the tests, confirmation or inference of the site of dysphagia, their safety, severity evaluation, determination of the food types, determination of their usefulness for assessment of swallowing training, evaluation of the effect of swallowing training, evaluation of the changes in swallowing functions over a period of time, ability to diagnose dysphagia, and usefulness of the tests. A 5-point scale was used to answer each question, and the subjective evaluations of the practitioners who used the 4 tests were analyzed. The Kruskal─Wallis test was used for analysis of the results and a value less than 5% was considered to be significant. Results:　As a result of questionnaire survey, it has become apparent that comprehensive evaluation methods were more appropriate than single evaluation methods as dysphagia screening tests. Conclusion:　The result of this study suggested that effectiveness of comprehensive evaluation methods in dysphagia screening test. It might be contribute for the dysphasic patients to introduce the comprehensive evaluation methods in Japan

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

Risk for the occupational infection by cytomegalovirus among health-care workers

Background Cytomegalovirus (CMV) are ubiquitously distributed worldwide, causing a wide range of clinical manifestations from congenital infection to a life-threatening disease in immunocompromised individuals. CMV can be transmitted via human-to-human contact through body fluids; however, the risk of CMV infection among healthcare workers (HCWs) has not been fully evaluated. Aim This study aimed to assess the risk of CMV infection among HCWs through daily medical practices. Methods Serum samples from HCWs at Osaka University Hospital (Japan) were analysed. Initially, we compared CMV IgG seropositivity among HCWs (medical doctors, nurses, and others) in 2017, which was examined after 1 year to evaluate seroconversion rates among those with seronegative results. Then, we examined CMV seroconversion rates in HCWs who were exposed to blood and body fluids. Findings We analysed 1153 samples of HCWs (386 medical doctors, 468 nurses, and 299 others), of which CMV seropositivity rates were not significantly different (68.9%, 70.3%, and 70.9%, respectively). Of these, 63.9% (221/346) of CMV seronegative HCWs were followed after 1 year, with CMV seroconversion rates of 3.2% (7/221). Among 72 HCWs who tested negative for CMV IgG when exposed to blood and body fluids, the CMV seroconversion rate was 2.8% (2/72). The CMV seroconversion rates between the two situations were not significantly different. Conclusion Our study indicated that CMV infection through daily patient care seems quite rare. Further well-designed studies with a large sample size are warranted to verify our finding

The role of Kupffer cells in complement activation in D-Galactosamine/lipopolysaccharide-induced hepatic injury of rats.

To investigate the role of Kupffer cells in complement activation, we used a rat model of acute hepatic injury induced by D-Galactosamine (GalN) and lipopolysaccharide (LPS). In in vivo study, minimal histological changes were observed after i.p. GalN (200 mg/kg) single administration. Complement hemolytic activity (CH 50) decreased to 70% of its initial value 2-3 h after i.p. LPS (1.5 mg/kg) single administration. Massive hepatic necrosis was induced by simultaneous administration of GalN and LPS. After 2-3 h, CH 50 decreased to 70% of its initial value, and deposition of C3 fluorescence (C3) was observed in Kupffer cells. After 4 h, GPT was greatly increased (1286 +/- 240 IU/l), CH 50 was further reduced, and C3 was observed on hepatocyte membranes and in the cytosol. In in vitro study, we used hepatocyte cultures and co-cultures of hepatocytes and Kupffer cells to investigate the participation of GalN, LPS, complement, and Kupffer cells in hepatic cell necrosis. We found no increase of LDH (% leakage) when LPS and complement were added to the medium (22.7 +/- 5.7%). A moderate increase was observed with the addition of GalN (33.2 +/- 2.6%). A remarkable increase was observed only with the addition of GalN, LPS, and complement to the co-culture (50.0 +/- 8.8%). These results suggest that Kupffer cells activated by LPS are very important in promoting acute hepatic injury by complement.</p

Scores of Child–Pugh Classification Impact Overall Survival After Stereotactic Body Radiation Therapy for Primary and Metastatic Liver Tumors

BackgroundStereotactic body radiotherapy (SBRT) delivers high-dose radiation to tumor tissues in few fractions, thereby reducing radiation damage to at-risk organs. There are more potential effects of SBRT owing to the higher biological equivalent dose delivered. Herein, we retrospectively analyzed its effectiveness and toxicity at our institution.MethodsData from patients with hepatocellular carcinoma (HCC; n = 10) and liver metastases (n = 10) who underwent SBRT (total dose of 30–50 Gy in 5–10 fractions) between 2013 and 2016 were analyzed. Adverse events were recorded at the end of RT, 6 months after treatment, or upon death. Overall survival (OS) was calculated according to the biological effective dose (BED α/β = 10) and liver function (Child–Pugh [CP] classification 5 or 6 vs. 7 or 8) after SBRT, using Kaplan–Meier analyses.ResultsOf the 20 patients, 6 declined the CP classification score after SBRT; grade 3 adverse events were not seen in any patient. A higher OS rate was seen in patients receiving a higher BED and in those with better CP classification after SBRT. Kaplan–Meier survival analysis yielded a median OS of 401 days and 1- and 2-year OS of 45% and 15%, respectively.ConclusionThe higher BED was significantly associated with tumor control, and there were no differences in the tumor control rate between HCC and metastatic tumors. Changes in CP scores after SBRT also affected the survival rate. Good liver function may permit multiple rounds of SBRT

Successful treatment of unresectable advanced rectal cancer with liver metastases by hemostasis re-irradiation of the rectal cancer and palliative low-dose whole-liver radiation therapy: a case report.

A 72-year-old man was admitted to the hospital with fatigue. Colonoscopy revealed a 50 × 50 mm rectal tumor with bleeding. Based on close inspection, he was diagnosed with unresectable advanced rectal cancer with multiple liver metastases. Chemotherapy was administered as 10 cycles of bevacizumab + mFOLFOX6 and 7 cycles of bevacizumab + FOLFIRI. Nine months later, he presented with hematochezia and progression of anemia. It was difficult to stop the bleeding via endoscopy. He underwent radiation therapy (39 Gy in 13 fractions), and hemostasis was confirmed. Then, further chemotherapy was performed with 3 cycles of bevacizumab + FOLFIRI and 2 cycles of TAS102. However 14 months after the initial visit, he presented with right hypochondralgia and abdominal fullness due to the progression of multiple liver metastases. Palliative low-dose whole-liver radiation therapy (WLRT) (30 Gy in 10 fractions) was performed. He developed Grade 2 nausea, but his right hypochondralgia reduced, liver dysfunction improved, and he successfully completed radiotherapy. At approximately the same time his anemia progressed, and colonoscopy revealed recurrent bleeding from the tumor. Re-irradiation (15 Gy in 5 fractions) of the rectal tumor was carried out and a blood transfusion was performed for the bleeding. He was discharged after confirmation the anemia had not progressed. Few reports have been published on the use of both palliative re-irradiation to stop bleeding from rectal cancer and palliative low-dose WLRT. Based on our experience with this case, we believe that palliative radiotherapy can be useful in treating patients with a poor prognosis