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At the 7th Electropalatography Symposium in Japan, held online on the 24 January 2021, a few speakers were invited to talk about how the COVID-19 pandemic had impacted their research and/or speech therapy that involved the use of electropalatography (EPG) as well as the procedures adopted in order to continue their work in a safe manner. The information on protective measures when using instrumental techniques in speech research and therapy may be useful for colleagues in research and the clinic.The primary aims are: (1) to find out whether there are any published recommendations regarding protective measures for using EPG in research and clinic settings; (2) to discuss the impact of the pandemic and the corresponding restrictions and general protective measures directed (or advised) by local government and professional bodies at each stage of EPG work; and (3) to share experiences in using modified procedures for face-to-face EPG therapy sessions and combined EPG teletherapy. In addition, a brief overview of EPG and a summary of EPG research and clinical activities in Japan presented by one of the symposium organizers at the symposium are included.A review of the literature regarding protective measures recommended for using EPG for speech assessment and treatment or research, supplemented by a discussion of our own experiences.The literature review showed that there are no guidelines regarding protective measures for using EPG, but there is some advice regarding speech recording using microphones. Most published articles related to speech and language therapy (SLT) service during COVID-19 are about telepractice or general clinical guidelines for face-to-face speech therapy sessions. The protective measures for using EPG developed based on the general guidelines recommended by local government and professional bodies (e.g., using visors, transparent acrylic board) were described. Using EPG in telepractice was discussed as well.It has been challenging to continue EPG research and therapy during the pandemic. In order to deal with this crisis, available knowledge regarding infection control and recommendations from local government and professional bodies were applied to design methods and procedures that allowed EPG research and therapy to continue.What is already known on the subject There are general protective measures recommended by local government and professional bodies regarding speech therapy sessions (e.g., using personal protective equipment (PPE), social distancing), but little is known about the measures for using instrumental techniques in speech research and therapy, particularly EPG. The equipment of each instrumental technique is different, so measures that are appropriate for one may not be suitable for others. Hence, specific recommendations are needed for EPG. What this paper adds to existing knowledge This paper provides pointers to information about recommendations regarding protective measures for speech research and therapy, supplemented with suggestions specific to EPG provided by experienced users based on actual experience. What are the potential or actual clinical implications of this work? In evaluating the impact of the COVID-19 pandemic on EPG research and therapy, an analytical approach was taken to break down the steps involved in carrying out those activities, and the challenges we faced and the possible alternatives for completing the tasks were discussed. A similar approach can be applied to evaluate other aspects of speech therapy service.

The production of chemicals and fuels from renewable resources using engineered microbes is an attractive alternative for current fossil-dependent industries. Metabolic engineering has contributed to pathway engineering for the production of chemicals and fuels by various microorganisms. Recently, dynamic metabolic engineering harnessing synthetic biological tools has become a next-generation strategy in this field. The dynamic regulation of metabolic flux during fermentation optimizes metabolic states according to each fermentation stage such as cell growth phase and compound production phase. However, it is necessary to repeat the evaluation and redesign of the dynamic regulation system to achieve the practical use of engineered microbes. In this study, we performed quantitative metabolome analysis to investigate the effects of dynamic metabolic flux regulation on engineered Escherichia coli for γ-amino butyrate (GABA) fermentation. We prepared a stable isotope-labeled internal standard mixture (SILIS) for the stable isotope dilution method (SIDM), a mass spectrometry-based quantitative metabolome analysis method. We found multiple candidate bottlenecks for GABA production. Some metabolic reactions in the GABA production pathway should be engineered for further improvement in the direct GABA fermentation with dynamic metabolic engineering strategy.

Dynamic metabolic engineering that harnesses synthetic biological tools is a next-generation strategy for microbial chemical and fuel production. We previously reported a synthetic quorum sensing system combined with a metabolic toggle switch (QS-MTS) in E. coli. It autonomously redirected endogenous metabolic flux toward the synthetic metabolic pathway and improved biofuel production. However, its functions and effects on host metabolism were attenuated by induction timing delay. Here, we redesigned the QS-MTS to stabilize QS signaling efficiency and metabolic regulation. We performed a metabolome analysis to clarify the effects of QS-MTS redesign on host metabolism. We compared the contributions of conventional and redesigned QS-MTS to fed-batch fermentation. The redesigned QS-MTS was more conducive than the conventional QS-MTS to long-term processes such as fed-batch fermentation. Here, we present a circuit redesign for metabolic flux control based on dynamic characteristic evaluation and metabolome analysis.

Electropalatography (EPG) has been used in the past 50 years for studying the patterns of contact between the tongue and the palate during speech production in typical speakers and those with speech disorders due to different causes. At the 7th EPG Symposium in Japan that was held online on 24 January 2021 (see: https://epg- research.sakura.ne.jp/), a panel of invited experts discussed their views regarding further developments and application of the technique. This paper provides a summary of this discussion. EPG offers information on articulation which cannot be replaced by other instrumental measures of speech. Identified areas for further hardware development are thinner EPG plates, better dental and palatal coverage, wireless connectivity, and sensors that provide additional articulatory information (e.g. tongue pressure, tongue-palate distance). EPG can serve as a resource for teaching speech disorders and phonetics. Furthermore, EPG therapy can be combined with telepractice in the speech therapy of clients with speech disorders.

Glioblastoma (GBM) has high mortality rates because of extremely therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) is an emerging and promising approach combined with low-intensity ultrasonication (US) and PpIX as a sonosensitizer for cancer, whereas its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, a MDR1 inhibitor and augmented anti-tumor effects of SDT. MDR1 down-regulation via Akt/NF-kB pathway by celecoxib was confirmed, using a NF-kB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via Akt/NF-kB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.

γ-aminobutyric acid (GABA) is a drug and functional food additive and is used as a monomer for producing the biodegradable plastic, polyamide 4. Recently, direct GABA fermentation from glucose has been developed as an alternative to glutamate-based whole cell bioconversion. Although total productivity in fermentation is determined by the specific productivity and cell amount responsible for GABA production, the optimal metabolic state for GABA production conflicts with that for bacterial cell growth. Herein, we demonstrated metabolic state switching from the cell growth mode based on the metabolic pathways of the wild type strain to a GABA production mode based on a synthetic metabolic pathway in Escherichia coli through rewriting of the metabolic regulatory network and pathway engineering. The GABA production mode was achieved by multiple strategies such as conditional interruption of the TCA and glyoxylate cycles, engineering of GABA production pathway including a bypass for precursor metabolite supply, and upregulation of GABA transporter. As a result, we achieved 3-fold improvement in total GABA production titer and yield (4.8g/L, 49.2% (mol/mol glucose)) in batch fermentation compared to the case without metabolic state switching (1.6g/L, 16.4% (mol/mol glucose)). This study reports the highest GABA production performance among previous reports on GABA fermentation from glucose using engineered E. coli.

研究報告, Original Articles, CVC の無意味音節において先行母音・後続母音が/s//t//k/ に及ぼす影響について定量的に検証することを目的に調査を行った．成人被験者3 名を対象に30 個の無意味音節についてEPG を用いて測定した．無意味音節は/s//t//k/ における前後の母音の影響を検討できるような音節の組み合せになるように，CVC 音節の一方の先行母音，あるいは後続母音を/a/ に統一し，もう一方を日本語5 母音に変化させた．EPG から得られたデータは，各子音における最大接触フレームから累積パターンを作成し，舌の口蓋への接触の前後の程度を示すCoG を算出した．/s//t/ については，先行母音・後続母音に/i/ が来る場合に他の母音に比べてCoG の平均値が有意に低く，舌の接触範囲が後方に広がっていることが示唆された．また，/s/ においては硬口蓋中央部にかけて正中方向に接触が広がった．/k/ においては，先行母音・後続母音ともにCoG の平均値が［ika］，［ɯka］・［eka］，［aka］・［oka］の順に低くなり，各音節群間に有意差が認められた．つまり，/i/ → /e//u/ → /a//o/ の順に接触面が前方に広がることが示唆された．これらは，効率的に構音するために先行母音や後続母音の舌の位置が子音に影響を与えているものと考えられ，先行・後続母音のような音環境を考慮した構音訓練が必要と思われた．, The aim of this study was to analyze co-articulatory effect of vowel environments on VCV contexts. The study used electropalatography (EPG) to record three normally speaking adults’ tongue-palate contact patterns of /s//t//k/ in thirty VCV contexts. A cumulative template was generated from the maximum contact frame for each sound and the center of gravity (CoG) value was calculated, which represents the relative concentration of electrodes in the anterior-posterior dimension of the palate. The most fronted and most contact occurred in /i/ contexts during utterances with /s//t/. The tongue-to-plate contacts spread backward in the order / i/ → /e//u/ → /a//o/ during utterances with /k/. It is considered that different vowel contexts influence the tongue-palate contact of these consonants for efficient articulation.

研究報告, Original Articles, 日本語における発達途上でみられる音韻プロセスを明らかにする目的で，2 歳から6 歳の健常児116 名を対象に調査を行った．発話サンプルは構音障害研究会（2010）から出版されている新版- 構音検査の単語検査にて採取した．発話をIPA 表記に従って音声記号で表記した上で，その誤りを川合（2011）の提唱している音韻プロセス分類に従って整理した．その結果，健常発達で認められる音韻プロセスは，語全体プロセスでは「子音の省略」「子音の調和・同化」，分節音変化プロセスでは「前方化」，「破裂音化」，「破擦音化」，「口蓋音化」であった．また，これらの音韻プロセスが消失する年齢群については，3 歳代までに「子音の省略」，「子音の調和・同化」，「前方化」，「摩擦音の破裂音化」，「破擦音化」，4 歳代までに「弾き音の破裂音化」，5 歳代までに「口蓋音化」が消失することが明らかとなった．, To ascertain the developmental phonological processes in Japanese-speaking children, we examined speech samples from 116 normally developing children, aged two to six years. Speechsamples were elicited using the latest version of the articulation test. The assessor transcribed each child’s responses in the International Phonetic Alphabet and classified them according toKawai’s phonological process categories. Results indicated that the common phonological processes were consonant deletion, consonantharmony, fronting, stopping, affrication, and palatalization. Those which disappeared by age three were consonant deletion, consonant harmony, fronting, stopping of fricative, and affrication. Stopping of the tap or the flap disappeared by age four. Palatalization disappeared by age five.

実践報告, Practical report, 言語聴覚学科は，学生に対する臨床教育を目的に，2009 年3 月に「きこえとことばの相談室」（以下:相談室）を開設した．2009 年3 月の開設から2014 年10 月末までの相談室の活動実績は，新規数：63名，継続数：53 名．総臨床件数612 件．臨床実数は，100 ～ 120 件で定着していた．開設当初の目的であった演習協力には至っていないが，教育活動，研究活動，臨床指導等に貢献している．今後は，言語聴覚療法の対象障害の拡大（失語症等），教育及び地域貢献の一環としての発展が望まれる．, In the Division of Speech-Language-Hearing Therapy, we established an outpatient counselingroom for hearing and language therapy in March of 2009 with the aim of providing clinical education for the students. From March 2009 to end of October 2014, the total numbers of counselings amounted 612 cases (63 new cases, 53 follow-up cases). The number of clinical cases was stable, between 100 and 120. Although it had little therapeutic impact, which was its original purpose, it has been contributing to education and research work. We expect it to expand to include disorders of speech-language-hearing therapy such as aphasia, etc., and as a part of the educational and regional contribution.

Aim NAFLD is the most abdominal ultrasonography examination cases in our clinic. Among these cases, complicated fibrosis is important in relation to Metabolic Syndrome (MS). Among 327 NAFLD examples (2017), in cases with High (> 0.676) NAFLD Fibrosis Score (NFS): MS merger is 41.1%, Intermediate: 25.4, Low ( Material and Method We examined 255 NAFLD cases (51.5y.o.; M 148: F 107, BMI: 24.0. ALT 25IU/L, TG 130 mg/dL; FBG 110, HbA1c 6.1%, MS Merger Ratio 26.4%) out of 449 patients who performed abdominal ultrasound in March - May 2018. Focusing on Strain Imaging (Real-time Tissue Elastography: Liver Fibrosis Index: LFI) and Share Wave Measurement (Vs), at the time of ultrasonic examination and NFS, Fib4index (F4i) which is a fibrosis index in serum, were used to predict MS merger. The apparatus used was Coni-Elasto of Hitachi Arietta 850. Correlation between each Fibrosis Index LFI and Vs (r = 0.178) LFI 286: 1.24. LFI and NFS (r = 0.265) NFS; High: LFI 2.64, Intermediate: 2.38, Low: 2.17. LFI and F4i (r = 0.195) F4i; High (> 2.67): LFI 2.48, Intermediate (2.67-1.30): 2.10, Low ( Study of MS Merger rate LFI; 3.00 (13): 84.6. MS cut off is considered as LFI > 2.4 (sensitivity 0.72, specificity 0.73). Vs; > 1.2 (69): 18.5%, 1.2-1.4 (149): 37.8, > 1.4 (15): 10.9. NFS; High (12): MS 50.0%, Intermediate (100): 27.5, Low (134): 23.1. F4i; High (11): MS 27.3%, Intermediate (96): 25.0, Low (147): 26.5. There is no difference between High and Low in Vs and F4i. Conclusion LFI can numerically estimate the MS merger of NAFLD and MS should be considered above 2.4. For serum markers NFS can be used as a reference, however due to the small number of cases? Vs and F4i were not useful. In patients with NAFLD complicated with fibrosis, we should look for MS based on LFS with NFS.

EPGを用いた構音訓練の目標として示す日本語音韻のEPGパターンを得ることを目的に, 正常例の構音動態を分析した.顎口腔機能に異常がない成人5例を対象とし, 日本語5母音と歯茎音・硬口蓋音・軟口蓋音をWinEPGシステム (Articulate Instruments Ltd.) を用いて記録した.各音について最も舌と口蓋の接触が多いフレームを選択し, 5名の被験者の累積頻度パターンを作成した.また, 舌と口蓋の接触が前後方向いずれに偏っているかを示すCenter of Gravity (COG) 値の平均値を算出した.結果, 累積頻度パターンは個人間の共通部分が明らかとなり, 変動の許容範囲も示せるので, 視覚的フィードバック訓練の有用な目標パターンとなった.COG値は構音点の前後方向の違いを具現しており, 構音場所の誤りを定量的に評価する指標となりうることがわかった.

The primary objective of this study was to determine the effectiveness of electropalatography (EPG) home training using a portable training unit (PTU) for clients with residual articulation disorders. The participants were five Japanese children with cleft lip and palate ranging in age from 8 to 13 years when they began EPG home training. These children had residual articulation disorders caused by abnormal tongue-palate contact, although four of them had received conventional speech therapy for 3 to 8 years before starting EPG training. The WinEPG system (Articulate Instruments, Edinburgh) was used to make recordings during the initial assessment and the monthly follow-up. The participants received EPG training sessions when they attended for their monthly recordings. A training programme was developed for each participant, and they were instructed to carry out their homework assignments using the PTU. After 7 to 9 months of home training, marked changes in the EPG patterns and “centre of gravity” values...

A very rare case of hepatoid carcinoma with serous component arising in the fallopian tube of a 79-year-old woman is presented. The lesion was a 5.0-cm unencapsulated, yellowish-white soft mass. The tumor was composed of hepatoid carcinoma (90%) and serous carcinoma (10%) components. The hepatoid carcinoma was histologically characterized by a proliferation of round to polygonal cells arranged in a trabecular, tubular, sinusoidal, papillary, or solid pattern. The serous component in the fallopian tube also showed in situ lesions. Both components showed an infiltration into the surface of the left ovary, omentum, peritoneum including the pouch of the Douglas, and serosa of the colon. Immunohistochemically, the hepatoid carcinoma was positive for alpha-fetoprotein, polyclonal carcinoembryonic antigen (CEA), hepatocyte paraffin 1, albumin, epithelial membrane antigen, and cytokeratin (CAM5.2). Ultrastructurally, the cytoplasm contained abundant ribosomes, moderate amounts of mitochondria, and rough endoplasmic reticulum that developed into a meshwork and contained mitochondria within it. Microbile channel-like structures and desmosomes were occasionally observed. The association with serous carcinoma indicates mullerian origin rather than germ cell origin. The patient received chemotherapy and was alive without disease at 10 months after surgery.

Purpose: To perform content analysis of perceptual speech assessment methods appearing in articles in Japanese journals.Data extraction and analysis: We extracted 59 articles from four major journals on cleft palate published between 1988 and 2004, and analyzed their content with respect to numbers and ages of subjects, variables of speech samples, types of speech sounds, judgment method, variables of judges, and reliability measurement.Results and conclusion: The subjects' numbers and ages showed a wide range. Two major variables of the samples were resonance and articulation, and the types of speech sounds were diverse. The most prominent judging method for articulation was transcription. The numbers and professions of the judges were missing in almost half, and a description of reliability measurement was absent in most articles. We concluded that these diversities and lacks of information constitute potential hindrances to effective comparison and sharing of information not only at the domestic level but also in global terms.

軟口蓋の易疲労性が初発症状で重症筋無力症と診断された23歳の女性について報告する.重症筋無力症の初発症状として一般的な眼症状や四肢筋易疲労性は認められなかったため診断は難渋したが, 音声・言語症状の評価および鼻咽腔ファイバースコピー, X線造影ビデオ検査, 空気力学的検査により軟口蓋のwaning現象が明らかとなり, Antirex test, 抗Ach-R抗体陽性で重症筋無力症と診断された.音声の聴覚的判定に加えて, 画像的あるいは空気力学的検査を行ってより客観的に軟口蓋の易疲労性を裏付け, 確実な診断がなされた.

視野に入った文字を自動的に音読してしまう特異な現象を呈した症例を報告した。症例は80歳の右利き女性。発語不能と右不全片麻痺で発症。発症後約１ヵ月の転院時の言語所見では, 発動性の低下を前景に, きわめて乏しい自発語に対し復唱は良好で反響言語と理解力障害を認め, 混合型超皮質性失語と診断した。回復に伴い理解力が改善, 反響言語は減少し自発的語彙が増え超皮質性運動失語により近い病像に移行した。その回復過程で, 言語訓練中や検査時に, カレンダーや物品上の印刷文字などを前後の文脈と無関連に音読する現象がたびたび観察された。この音読現象は, 「強迫的音読現象」 (田丸ら1986)や「視覚性反響言語」 (波多野ら1987 a, 1987 b, 1988)に類似の現象と考えられた。本症例はMRIで確認された補足運動野を含む左前頭葉内側部に限局病変を有し, 同部位が本現象の発現に関与した可能性が示唆された。

Lumican is a member of a small leucine-rich proteoglycan family and its overexpression has been reported in carcinoid tumor, breast, colorectal, neuroendocrine cell, uterine cervical and pancreatic cancers. The expression of lumican in stromal tissues in breast cancer is associated with a high tumor grade, a low estrogen receptor expression level and young age. Lumican expression in the cytoplasm in advanced colorectal cancer is correlated with a poor prognosis. Lumican expression was previously reported in pancreatic cancer, but the role of lumican in pancreatic cancer is still not well understood. In this study, we aimed to clarify the role of lumican in pancreatic cancer. Reverse-transcription polymerase chain reaction and Western blot analyses revealed lumican mRNA and protein expression in six pancreatic ductal adenocarcinoma cell lines (i.e. PANC-1, MIA PaCa-2, KLM-1, Capan-1, PK-1 and PK-8). On the basis of its immunoreactivity, lumican was found to be localized in islet cells of normal pancreatic tissues, but not in exocrine cells. In pancreatic cancer tissues, lumican was predominantly localized in the cytoplasm of cancer cells in 30 out of 53 (56.6%) cancer patients, whereas lumican was detected in stromal tissues in 36 out of 53 (67.9%) cancer patients. Lumican expression in pancreatic cancer cells did not correlate with clinicopathological factors, whereas lumican expression in stromal tissues correlated with the female gender, advanced stage, retroperitoneal and duodenal invasion and residual tumor (p=0.030, 0.038, 0.049, 0.049 and 0.048, respectively). Patients with lumican-positive cancer cells tended to survive longer than those with lumican-negative cancer cells (p=0.286), but patients with lumican-positive stromal tissues had shorter survival than those with lumican-negative stromal tissues (p=0.062). These results suggest that lumican in stromal tissues plays an important role in the growth and invasion of pancreatic cancer.