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This study aimed to investigate the linguistic factors involved in stuttering among Japanese-speaking preschool children. The participants included 10 Japanese children who stutter, with a mean age of 5 years and 9 months. Speech samples comprised spontaneous conversations of the participants with their parents for about 20 minutes. We compared the percentages of the occurrence of stuttering-like disfluencies (SLDs) at the word and sentence levels, using the Wilcoxon signed-rank test. The results showed no significant differences in SLDs based on syllable structure when comparing light and heavy syllables and comparing consonants and vowels in the initial position of each content word. SLDs occurred more frequently in the initial than non-initial position of words and in longer rather than shorter words. Additionally, SLDs occurred more frequently in sentences that contained more 'bunsetsu' (a kind of linguistic unit in Japanese). Our study is the first to show that both word and sentence-level factors could contribute to SLDs in preschool children who stutter in agglutinating languages, such as Japanese. This aspect is rarely reported in psycholinguistic studies based on stuttering occurrence in inflecting languages, such as English.

Purpose In this study, we investigated the classification of cluttering by assessing speech based on the ratio of disfluencies (RDF) and attempted to identify cluttering and cluttering–stuttering by classifying disfluencies according to previous studies and the Japanese Standardized Test for Stuttering. We further investigated the factors that contribute to the occurrence of disfluency by comparing the disfluencies of three tasks (spontaneous speech, oral reading, and retelling a memorized story) and examining the relationship between RDF and speech rate. Method The participants comprised 20 Japanese adults who stutter. Participants were required to perform an oral reading task, retelling a memorized story task, and a spontaneous speech task. We subsequently classified their disfluencies and calculated the RDF (normal disfluencies that are often observed in cluttering/stuttering-like disfluencies). Results About half of the participants met the cluttering criteria, that is, an RDF of above 3. Analyzing speech disfluencies revealed that a high RDF is associated with fewer stuttering-like disfluencies that increase the denominator of the RDF formula or many “interjections” that make its numerator smaller. Conclusions These tendencies of speech disfluencies could influence cluttering identification. We should further utilize the RDF considering the findings of this study.

Purpose Children who stutter (CWS) face communication difficulties in school activities and at home. Although the importance of receiving support from their surroundings has been documented, few studies have investigated potential requests of CWS from their surroundings. This study aimed to elucidate such requests. Method A total of 43 school-age children and 25 adolescents who stutter completed a free-description questionnaire, including questions such as “what you want your classmates/your classroom teacher/your family to do about your stuttering?” Their descriptions were summarized and categorized based on similarity. Results The results indicate that 90.6% of the participants had more than one request for their classmates, classroom teacher, or family. A total of 197 items were extracted and categorized into seven themes. In particular, the responses included “listen attentively,” “treat us naturally,” and “make arrangements.” While participants tended to hope for classmates or family to “listen attentively” and “treat us naturally,” the request to “make arrangements” was higher for their teacher. Their potential requests varied by age: While school-age CWS wanted people around them to “listen carefully,” the hope of adolescents who stutter was “treat us naturally.” Conclusions The various potential requests of CWS were categorized, and the responses shed light on the importance of increasing knowledge of stuttering. The difference between the requests could reflect psychosocial differences between school-age children and adolescents who stutter. In addition, social interaction among peers is more developed in adolescents, and they could harbor fear of being excluded within their community.

Previous studies have indicated that stuttering is often accompanied by co-occurring disorders, including social anxiety disorder, attention deficit/hyperactivity disorder (ADHD), and autism spectr...

Combination treatment using fingolimod (FTY720), an immunomodulator, and a pathogenic antigen prevents the progression of glucose-6-phosphate isomerase (GPI)

Purpose: This systematic review identified and synthesized published research articles, written in Japanese, on the clinical effectiveness of a broad range of nonpharmacological interventions for school-age children who stutter. Method: A systematic review of Japanese literature published between January 1, 1980, and July 7, 2020, reporting interventions for school-age children who stutter, was carried out through a search of two databases (CiNii Article database and Japan Medical Abstract Society database) using the key words “stuttering” and “school-age” or “child” or “primary school students” or “children” or “school child” in Japanese. To be included in the review, the articles must report studies where data were subjectively reported by clinicians, where school-age participants were treated for developmental stuttering, where participants received interventions conducted by clinicians, and where quantitative outcomes (pre- and/or posttreatment) were measured; and they must be published in Japanese. Results: Forty articles met all the inclusion criteria. Most articles adopted a case series or single-case study design. A total of 179 intervention programs were identified from all the articles and broadly classified into speech therapy, psychological therapy, interventions for modifying the child's environment, and others. Conclusions: Our systematic review provided a broad overview of the treatments used for school-age children who stutter in Japan. Future research should focus on gathering more reliable, systematic, and rigorous evidence to establish the effectiveness of stuttering treatments for school-age children and thereby develop evidence-based practices.

We aimed to compare the efficacy of insulin degludec/insulin aspart (IDegAsp) and insulin degludec/liraglutide (IDegLira) in controlling glucose fluctuation and suppressing postprandial glucose levels using intermittently scanned continuous glucose monitoring.Twenty-four patients with type 2 diabetes mellitus were randomly allocated to receive either IDegLira or IDegAsp followed by IDegAsp or IDegLira, respectively. A crossover study was conducted with intermittently scanned continuous glucose monitoring. We compared the postprandial blood glucose level, time in range, and time below range from a 3-day intermittently scanned continuous glucose monitoring period for each treatment group.The time in range was significantly higher in IDegLira than in IDegAsp. Postprandial glucose levels 90 and 120 min after breakfast and 60, 90, and 120 min after lunch were significantly lower for IDegLira than for IDegAsp. However, postprandial glucose levels 90 and 120 min after supper were significantly lower for IDegAsp than for IDegLira. There was no significant difference in the time below range between IDegLira and IDegAsp.IDegLira was more effective in treating type 2 diabetes mellitus than IDegAsp, as indicated by a higher time in range and lower postprandial glucose level at breakfast and lunch. This study was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000039221).

2022, この博士論文は内容の要約のみの公開（または一部非公開）になっています

The number of case reports of children with autism spectrum disorder (ASD) who stutter is increasing. The duration of intervention for stuttering in children with attention-deficit hyperactivity disorder (ADHD) is often greater than for children who only stutter. Whether there is a similar pattern in children with ASD who stutter should also be examined. In this study, the factors influencing the prognoses of two children with stuttering and ASD were investigated. One child's stuttering had improved and had almost been eliminated, and the other's stuttering continued. The results of the investigation showed that a significant increase in language ability and the absence of physiological problems assisted in eliminating stuttering. The child who continued to stutter originally showed a higher than average language level and high anxiety. Preventing and eliminating anxiety that accompanies ASD, in addition to intervention for stuttering, may be indispensable to reduce stuttering and improve fluency.

Purpose This article presents a collaborative initiative of members of the Committee of the International Representatives of the International Cluttering Association (ICA) upon celebrating the 10th anniversary of the ICA. Such collaborative efforts are designed to improve communication skills, enlighten lives of people with cluttering, and serve as models for speech therapists and other health care professionals in countries around the globe. Method This initiative began with a seminar at the Inaugural Joint World Congress in Japan in 2018 and continues with an article for this special issue on cluttering based on the contents of the papers presented at the Congress. Sixteen researchers and speech therapists from 15 countries in Africa, Asia, Europe (East and West), America (North and South), and the Middle East have explored the following themes related to cluttering: cluttering awareness, research, professional preparation, intervention, and self-help groups. Results This article adds to the body of international literature on cluttering and illustrates that, for the past 10 years, hypothesis-testing research in cluttering continues to be conducted across language barriers and national boundaries, and interventions that are implemented in some locales are being tested and taught in other parts of the world; furthermore, new cluttering treatments are being disseminated for professional preparation and clinical practices. Conclusions This article demonstrates how global engagement of the ICA's international representatives has led to the exchange of ideas about awareness of cluttering and professional preparation and the best strategies for the treatment of this communication disorder in countries around the world.

Purpose Negative attitudes toward stuttering by people in their work roles have been previously reported. These attitudes could differ depending on whether or not someone knows a person or has been in contact with a person who stutters. This study aimed to elucidate public attitudes toward people who stutter at work. Methods A web-based questionnaire survey of 730 adults drawn from the general public throughout Japan was conducted. It gathered information on respondents’ demographics, contact experience with people who stutter, knowledge of stuttering, and attitudes and experiences toward stuttering at work, using a Likert-type scale. To investigate the factors associated with their attitudes and experiences toward stuttering at work, respondents’ demographic information and contact experience were entered into a multivariable model using ordinal logistic regression analysis. Results We analyzed the data of 671 respondents, of whom 77.2 % were company employees; 41.3 % knew a person who stutters at their workplace, among their friends, and/or in their family, and 34.7 % had been in the position of hiring any individual. Respondents perceived the employment of people who stutter to be somewhat positive overall. Regression analysis revealed that only the factor of workplace contact experience to be significantly positively associated with the respondents’ attitudes toward stuttering. That is, knowing a person who stutters in one’s workplace was significantly associated with more positive attitudes. Conclusion Previous studies have reported widespread negative public attitudes toward stuttering. Our results can supplement this literature, especially regarding attitudes in the workplace. Our findings suggest that the main factor that is associated with people’s positive attitudes is their contact experience with people who stutter in their workplace.

[Purpose] To examine the ability of young and elderly individuals to control the timing and force of periodic sequential foot tapping. [Subjects and Methods] Participants were 10 young (age, 22.1 ± 4.3 years) and 10 elderly individuals (74.8 ± 6.7 years) who were healthy and active. The foot tapping task consisted of practice (stimulus-synchronized tapping with visual feedback) and recall trials (self-paced tapping without visual feedback), periodically performed in this order, at 500-, 1,000-, and 2,000-ms target interstimulus-onset intervals, with a target force of 20% maximum voluntary contraction of the ankle plantar-flexor muscle. [Results] The coefficients of variation of force and intertap interval, used for quantifying the steadiness of the trials, were significantly greater in the elderly than in the young individuals. At the 500-ms interstimulus-onset interval, age-related effects were observed on the normalized mean absolute error of force, which was used to quantify the accuracy of the trials. The coefficients of variation of intertap interval for elderly individuals were significantly greater in the practice than in the recall trials at the 500- and 1,000-ms interstimulus-onset intervals. [Conclusion] The elderly individuals exhibited greater force and timing variability than the young individuals and showed impaired visuomotor processing during foot tapping sequences.

This article features contributions of 15 young and experienced researchers and clinicians from 12 countries from Africa, Asia, Eastern Europe, the Middle East, South America, and North America. The growing fascination with cluttering continues to spread around the world, in a spirit of being open-minded to the ideas of colleagues from different cultures, languages, and streams of thought. The following topics discussed are believed to be of interest to consumers, practitioners, and researchers: conceptual and theoretical aspects of cluttering, awareness, and understanding of cluttering across countries and continents, professional preparation in cluttering, assessment, treatment, and support groups.

The calcium-binding proteins S100A8 and S100A9 can dimerize to form calprotectin, the release of which during tissue damage has been implicated in inflammation and metastasis. However, receptor(s) mediating the physiologic and pathophysiologic effects of this damage-associated “danger signal” are uncertain. In this study, searching for candidate calprotectin receptors by affinity isolation-mass spectrometry, we identified the cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG). EMMPRIN specifically bound to S100A9 but not S100A8. Induction of cytokines and matrix metalloproteases (MMP) by S100A9 was markedly downregulated in melanoma cells by attenuation of EMMPRIN. We found that EMMPRIN signaling used the TNF receptor–associated factor TRAF2 distinct from the known S100-binding signaling pathway mediated by RAGE (AGER). S100A9 strongly promoted migration when EMMPRIN was highly expressed, independent of RAGE, whereas EMMPRIN blockade suppressed migration by S100A9. Immunohistologic analysis of melanomas revealed that EMMPRIN was expressed at both the invasive edge of lesions and the adjacent epidermis, where S100A9 was also strongly expressed. In epidermal-specific transgenic mice, tail vein–injected melanoma accumulated in skin expressing S100A9 but not S100A8. Together, our results establish EMMPRIN as a receptor for S100A9 and suggest the therapeutic use in targeting S100A9–EMMPRIN interactions. Cancer Res; 73(1); 172–83. ©2012 AACR.

Skeletal muscle differentiation entails organized sequential events, including cell cycle arrest of proliferating myoblast cells and cell fusion, which lead to the formation of multinucleated myotubes. This process involves both transcriptional and post-transcriptional regulation of the gene expression of myogenic proteins, as well as cell-cycle related proteins. RNA-binding proteins bind to specific sequences of target RNA and regulate gene expression in a post-transcriptional manner. However, few tissue-specific RNA binding proteins have been identified. Herein, we report that the RNA binding proteins Rbm24 and Rbm38 were found to be preferentially expressed in muscle during differentiation in vitro. Further, knockdown of either by RNA interference suppressed cell-cycle arrest and delayed myogenic differentiation in C2C12 cells. In contrast, over-expression of Rbm24 or Rbm38 induced cell cycle arrest, and then had a positive effect on myogenic differentiation. Immunoprecipitation-RT-PCR analysis using tagged Rbm proteins indicated that Rbm38 binds to the p21 transcript in vivo. Consistent with this, differentiation of Rbm38 knockdown cells was rescued by over-expression of p21. Together, our results suggest that Rbm38 plays a crucial role in cell cycle arrest and myogenic differentiation via its binding to p21.

［目的］地域の職能を有した人材資源を有効に活用した介護予防事業において，過去4年間に我々が介入してきた運動教室の効果検証を行った。［対象］過去4年間の運動教室参加者95名（平均年齢77.8±6.1歳，男性20名，女性75名）である。［方法］体力の総合的効果を検証できるよう，運動教室実施前後の体力測定値を得点化し，総合得点により比較した。得点化には，同市の高齢者健診の結果から作成した体力標準値を利用した。また，運動教室による効果の要因を検討するために，運動教室による効果あり群と効果なし群に分類し，運動教室開始時の体力を比較した。［結果］運動教室の前後で総合得点の有意な向上を認めた。また，効果あり群の教室開始時の総合得点が有意に低く，運動教室開始時の体力水準が低い者に運動効果があったと推察された。［結語］地域に根ざした高齢者運動教室の効果が認められたが，体力水準が低く且つ類似した体力の対象者を選定することによって，より有効な運動教室の運営が可能になることが考えられた。

[Purpose] Agility includes three factors: rapidity of reaction, rapidity of directional change, and velocity of muscle contraction. We proposed the Ten-Step Test (TST) as a new performance test for agility. In our previous study, the criterion-related validity of TST was evaluated by comparing TST with a timed supine-to-stand test which reflects motion speed. However, timed supine-to-stand doesn't include rapidity of reaction. The purpose of this study was to evaluate the criterion-related validity of TST using motor reaction time (MRT). [Subjects] One hundred fifty-two community-dwelling adults were recruited. [Methods] TST requires the subjects to place one foot at a time, ten times on a block 10 cm in height while standing. TST was conducted twice, and the quickest time of the two trials was used for analysis. MRT was measured as the time between a touch on the malleous and the response of the ankle dorsi-flexion in a sitting position. For evaluating the relationship between TST and MRT, the conformity of the regression formulae of aging changes and correlation coefficients were analyzed. TST was also compared with the Functional Reach Test (FRT) and muscle strength of the knee. [Results] Both TST and MRT showed a quadratic rather than a linear relationship with age. The single correlation coefficient between TST and MRT was 0.59. [Conclusion] Age-related changes of TST and MRT showed a similar curve. These curves showed a significant increase after the age of 50, and the correlation coefficient between TST and MRT was high. The findings suggest that TST includes a factor related to motor reaction.

日本におけるcluttering症状を呈する児童の存在を仮説的に提唱し, 彼らの発話の特徴を明らかにするために, 聴覚的な印象で「発話速度が速く聞き取りづらい」と判断された児童18名を対象とし, 発話速度と非流暢性頻度 (3項目) , MLUの測定を行った.その結果, 発話特徴の結果が類似した傾向をもつ6群が浮かび上がった.6群中, 3群は「挿入・言い直し・filler」という非流暢性タイプの頻度が高い点が, 他の3群と顕著に異なっていた.また, その3群の医療的な診断歴, 知能検査, PRS検査結果の結果から, 6名全員にLD, ADHDなどの傾向が見られた.これらの特徴は欧米で研究されているclutteringの特徴と一致した.この結果から, 本研究において, (1) 聴覚的な印象で発話速度が速く, 聞き取りづらい, (2) 非流暢性タイプが特徴的である, (3) LDやADHDなどの合併が認められる群をcluttering群であると仮定した.

吃音児の母親と非吃音児の母親の言語的行動の特徴, また母親の言語行動と子供の非流暢性の関連性を知ることを目的として母子の自由な遊びの場面の観察を試みた.対象は4～6歳の吃音 (男) 児10名, 吃音児の母親10名, 非吃音 (男) 児10名, 非吃音児の母親10名である.1) 発話速度 (speaking rate)2) 反応時間 (responsetime latency)3) 阻止行為 (interrupting behavior) の3尺度について4群間で比較し, またそれぞれの尺度と子供のdiscontinuityの相関を調べた.その結果, 対象群間での比較において, 有意差がみられたのは, 吃音児の母親群の発話速度が非吃音児の母親群より発話速度が速かったことであった.また, 吃音児の母親群の発話速度と吃音児群の吃音症状 (discontinuity) に正の相関性がみられた結果などが得られた.この結果から, 母親の発話速度は子供の吃音症状に何らかの影響を与えているのではないかと考えられる.

Skin pigmentation is a complex process including melanogenesis within melanocytes and melanin transfer to the keratinocytes. To develop a comprehensive screening method for novel pigmentation regulators, we used immortalized melanocytes and keratinocytes in co-culture to screen large numbers of compounds. High-throughput screening plates were subjected to digital automated microscopy to quantify the pigmentation via brightfield microscopy. Compounds with pigment suppression were secondarily tested for their effects on expression of microphthalmia transcription factor (MITF) and several pigment regulatory genes, and further validated in terms of non-toxicity to keratinocytes/melanocytes and dose-dependent activity. The results demonstrate a high-throughput, high-content screening approach, which is applicable to the analysis of large chemical libraries using a co-culture system. We identified candidate pigmentation inhibitors from 4000 screened compounds including zoxazolamine, 3-methoxycatechol and alpha-mangostin, which were also shown to modulate expression of MITF and several key pigmentation factors and are worthy of further evaluation for potential translation to clinical use.

The first purpose of this study was to examine whether decreases in muscle force similar to the bilateral deficit occur during simultaneous use of arm and leg. The second purpose was to examine the effect on the muscle force of one leg by a division of attention through the regulation of the muscle force in the arm. Six participants completed each of the following three tasks in a random order: (1) maximal unilateral flexion of the right or left elbow, (2) maximal unilateral extension of the left knee, and (3) multilimb effort (a maximal contraction of the muscles in the leg while maintaining a constant submaximal isometric elbow flexion force at 25%, 50%, 75%, or 100% MVC). The results showed that muscle force was lower during simultaneous exertion of arm and leg than during exertion of one limb alone. The maximal knee extension force was significantly (p < .05) lower, by as much as 40% or so, during regulation at 25% MVC. The division of attention is also thought to be involved in task execution and may thus explain the test results. A decrease in the muscle force of the leg due to the level of regulation of the muscle force of the arm indicates that the regulation of the muscle force affects the division of attention, and the finer level of muscle force regulation is a task that requires greater attention. When the muscle force is precisely controlled, a more accurate and more appropriate adjustment is required to focus attention.

Background: Not only the reduction of muscle strength or balance, but also the reduction of the agility are regarded as important factors of falls in elderly people. If an agility test for elderly people is established, the precision of the fall prediction rises and can be used for individual training. Objectives: To develop a new performance test focused on agility for elderly people and to evaluate the usefulness of this test. Design: Cross-sectional study. Setting: The Welfare Center of Kagami Town, Kagami Town Office, etc., Kochi, Japan. Participants: 828 community-dwelling, independent adults aged 20–99 years with no obvious cognitive or functional disability, were randomly recruited from Kagami town and the surrounding areas. Measurements: The Ten Step Test (TST, a new performance test), motor reaction time (MRT), knee extensor isometric strength, single leg standing time (SLST), and some other tests were used to evaluate the criterion-related validity and the content validity. TST was developed as a modified version of other step tests which require the subjects to place the whole foot on a block, then return it to the floor. In addition, female participants over 70 were asked whether or not they had fallen in the past year. Results: Excellent reliability for TST was found for interrelation (intra-class correlation coefficients, ICC = 0.96), and re-test reliability was sufficient (ICC = 0.86). Evidence for criterion-related validity was found through high single correlation with the timed supine-to-stand (r = 0.68) and high single correlation with MRT (r = 0.59). In addition, content validity was found through low correlation with knee extensor strength (–0.35) and SLST (–0.36) in 112 women over 70 years of age. The error rate by TST to predict falls (35.2%) was lower than the error rate by muscle strength (44.4%) and the balance (38.7%). TST confirmed decline after 50 years of age, and it conformed to a cubic curve. Conclusion: The findings indicate that TST is a reliable measure of agility, and it can help to predict the risk of falls. The decline of agility accelerates after 50 years of age. It shows that the decline of agility differs from the decline of leg muscle strength and balance.