Five-Year Technological Changes of Distant Medical Education in Asia

All physicians would benefit from more comprehensive distance learning. However, the technology is often difficult to use because technological infrastructure is limited in many hospitals in Asia. Since 2003, we have worked to advance international distant medical education implemented through the Internet in Asia. This paper presents an analysis of our activities over the past five years to evaluate the technical transition and its effects on modes of distant medical education. Methods: We analysed distant medical education programmes that we conducted from 2011 to 2015. We used a Digital Video Transport System (DVTS), H.323 and Vidyo, along with commercial and research and education networks (REN) installed in the subject hospitals. Questionnaires were randomly distributed to the audience to evaluate image resolution, image movement, sound quality, and programme content. Results: The number of programmes increased to over 90 per year in 2014–2015. The main system gradually changed from DVTS (58%, 30/52 in 2011) to Vidyo (64%, 67/104 in 2015). The number of new institutions increased to 149 in 2014–2015. Over 92% of the ratings for image resolution and movement were positive. Sound quality was somewhat lower at 83%. Ultimately, 98% of respondents rated the programmes “very good” or “good.” Conclusions: Continuous technical development was observed with increasing numbers of sites for each programme. This resulted in expansion of activity involving non-university hospitals. Practical distant medical education, satisfies physicians’ need for quality and inclusiveness could be expanded to normal hospitals in Asia and beyond

Oral environment and cancer

Cancer is now the leading cause of death in Japan. A rapid increase in cancer mortality is expected as Japan is facing a super-aged society. Many causes of cancer are known to be closely linked to life style factors, such as smoking, drinking, and diet. The oral environment is known to be involved in the pathogenesis and development of various diseases such as bronchitis, pneumonia, diabetes, heart disease, and dementia. Because the oral cavity acts as the bodily entrance for air and food, it is constantly exposed to foreign substances, including bacteria and viruses. A large number of bacteria are endemic to the oral cavity, and indigenous oral flora act to prevent the settlement of foreign bacteria. The oral environment is influenced by local factors, including dental plaque, tartar, teeth alignment, occlusion, an incompatible prosthesis, and bad lifestyle habits, and systemic factors, including smoking, consumption of alcohol, irregular lifestyle and eating habits, obesity, stress, hormones, and heredity. It has recently been revealed that the oral environment is associated with cancer. In particular, commensal bacteria in the oral cavity are involved in the development of cancer. Moreover, Candida, human papilloma virus and Epstein-Barr virus as well as commensal bacteria have been reported to be associated with the pathogenesis of cancer. In this review, we introduce recent findings of the correlation between the oral environment and cancer

転入高齢者に対する民生委員の関わりの実際と支援のあり方

転居高齢者の支援のあり方を検討するために、民生委員の転居高齢者への関わりと困ったこと、関わりの工夫、活動に対する思いを明らかにすることを目的とした。民生委員46人へのアンケートと7人のグループインタビューを行い、質的分析を行った。困ったこととして、情報把握が大変、訪問しにくいこと、転入者を阻む地域や組織があることが明らかとなった。転入高齢者に関わる際の工夫として、情報把握の仕方、連携する、関係をつくる、有事に備える、安否を確認する、地域の組織に誘い出し仲間に入れるための具体的な工夫が明らかとなった。活動に対する思いでは、行政から最低限の情報は欲しいこと、誇りを持って地域のために活動したいこと、活動の負担感と限界が明らかとなった

Molecular phylogeny of the higher and lower taxonomy of the Fusarium genus and differences in the evolutionary histories of multiple genes

<p>Abstract</p> <p>Background</p> <p>Species of the <it>Fusarium </it>genus are important fungi which is associated with health hazards in human and animals. The taxonomy of this genus has been a subject of controversy for many years. Although many researchers have applied molecular phylogenetic analysis to examine the taxonomy of <it>Fusarium </it>species, their phylogenetic relationships remain unclear only few comprehensive phylogenetic analyses of the <it>Fusarium </it>genus and a lack of suitable nucleotides and amino acid substitution rates. A previous stugy with whole genome comparison among <it>Fusairum </it>species revealed the possibility that each gene in <it>Fusarium </it>genomes has a unique evolutionary history, and such gene may bring difficulty to the reconstruction of phylogenetic tree of <it>Fusarium</it>. There is a need not only to check substitution rates of genes but also to perform the exact evaluation of each gene-evolution.</p> <p>Results</p> <p>We performed phylogenetic analyses based on the nucleotide sequences of the rDNA cluster region (rDNA cluster), and the β-tubulin gene (<it>β-tub</it>), the elongation factor 1α gene (<it>EF-1α</it>), and the aminoadipate reductase gene (<it>lys2</it>). Although incongruence of the tree topologies between <it>lys2 </it>and the other genes was detected, all genes supported the classification of <it>Fusarium </it>species into 7 major clades, I to VII. To obtain a reliable phylogeny for <it>Fusarium </it>species, we excluded the <it>lys2 </it>sequences from our dataset, and re-constructed a maximum likelihood (ML) tree based on the combined data of the rDNA cluster, <it>β-tub</it>, and <it>EF-1α</it>. Our ML tree indicated some interesting relationships in the higher and lower taxa of <it>Fusarium </it>species and related genera. Moreover, we observed a novel evolutionary history of <it>lys2</it>. We suggest that the unique tree topologies of <it>lys2 </it>are not due to an analytical artefact, but due to differences in the evolutionary history of genomes caused by positive selection of particular lineages.</p> <p>Conclusion</p> <p>This study showed the reliable species tree of the higher and lower taxonomy in the lineage of the <it>Fusarium </it>genus. Our ML tree clearly indicated 7 major clades within the <it>Fusarium </it>genus. Furthermore, this study reported differences in the evolutionary histories among multiple genes within this genus for the first time.</p

Functional Analysis of MeCP2 Mutations Associated with Rett Syndrome Using Transient Expression Systems

レット症候群は生後半年から1歳半ころに発症する重度の精神発達遅滞を伴う疾患で女児の1万人から1万5千人に1人に発症する頻度の高い遺伝子疾患である。この疾患の原因遺伝子が最近MeCP2遺伝子であることが判明した。レット症候群の患者でみられる変異がMeCP2の本来の機能にどのような影響を及ぼすかを理解することは、レット症候群の病態を解明する上での手がかりになる。MeCP2は2つの機能ドメインを持ち、一つはメチル化CpGに結合するメチル化結合ドメイン(MBD)で、もう一つはヒストン脱アセチル化酵素をリクルートするSin3Aと結合する転写抑制ドメイン(TRD)である。報告されている変異の中でミスセンス変異の多くは、この二つのドメイン内でみられ、特にMBD内での変異の割合は多い。MBD内のミスセンス変異のMeCP2機能への影響を把握するため、培養細胞を用いた遺伝子導入発現系を開発して解析を行った

就寝時マウスガードを使用することによる、再発性アフタ性口内炎に対する予防効果 : 予備的介入研究

Recurrent aphthous stomatitis (RAS) is the most common inflammatory ulceration in the oral mucosa of otherwise healthy individuals and is often accompanied by severe pain. However, the etiology of RAS is not completely understood, and currently, no therapy can completely prevent RAS recurrence. In our clinical experience, we noticed that patients using a night guard, which is often used for bruxism treatment, did not develop RAS. Therefore, the aim of this study was to determine whether mouthguard use can suppress RAS development. The cohort of this interventional, prospective, single‐center, and self‐controlled study included 20 subjects who developed RAS at least once a month. The oral health of all the subjects was recorded for 60 days before and after intervention with a mouthguard. The average number of RAS incidences decreased from 5.5 to 1.0, the average days until healing decreased from 7.3 to 5.6, and the period with RAS decreased from 31.5 to 5.0 with mouthguard use. Mouthguard use may be beneficial for preventing RAS development

Functional Characterisation of MeCP2 Mutatiions Found in Male Patients with X Linked Mental Retardation

MeCP2の遺伝子変異は、Rett症候群以外の疾患の患者でも見つかり、X染色体性の精神発達遅滞を伴う男性患者においても報告された。これらの患者ではMBD内の変異として137番目のGluからGlyと140番目AlaからValのアミノ酸変異が確認された。これらの変異に関して、開発した二つの機能解析系を用いて解析を行ったところ、140番目の変異では、メチル化DNAに対しての転写抑制活性は完全に維持されており、137番目の変異ではわずかに転写抑制活性の低下がみられる程度であった。また、マウス細胞のヘテロクロマチン親和性についても140番と137番目の変異は共に明らかな点状の像を示し、親和性は維持されていた。これらの遺伝性の精神発達遅滞を伴う男性患者でのMeCP2の変異は、その機能への影響がレット症候群の場合と比較して軽度であるため、Rett症候群とは異なる病態を呈する成因となっている可能性が示唆された

Ameloblastin regulates osteogenic differentiation

Ameloblastin, the most abundant non-amelogenin enamel matrix protein, plays a role in ameloblast differentiation. Here we found that ameloblastin was expressed in osteosarcoma cells; to explore the potential functions of ameloblastin in osteoblasts, we investigated whether this protein is involved in osteogenic differentiation and bone formation on the premise that CD63, a member of the transmembrane-4 glycoprotein superfamily, interacts with integrins in the presence of ameloblastin. Ameloblastin bound to CD63 and promoted CD63 binding to integrin β1. The interaction between CD63 and integrin β1 induced Src kinase inactivation via the binding of CD63 to Src. The reduction of Src activity and osteogenic differentiation mediated by ameloblastin was abrogated by treatment with anti-CD63 antibody and overexpression of constitutive active Src, respectively. Moreover, amelobastin upregulated the formation of stress-fibre and focal adhesions and downregulated cell migration in association with RhoA regulation via Src activity. Therefore, our results suggest that ameloblastin is expressed in osteoblasts and functions as a promoting factor for osteogenic differentiation via a novel pathway through the interaction between CD63 and integrin β1

Quantification of Cell Migration and Invasion, and Their Association with Periostin in Anaplastic Thyroid Cancer, Using a Real-time Cell Analyzer

Anaplastic thyroid cancer (ATC) is known to be a highly malignant cancer of the thyroid with a high mortality rate. In a previous study, we used real-time cell analysis (RTCA) to analyze cell migration and invasion of oral squamous cell carcinomas (OSCCs) of the tongue and floor of the mouth. In the present study, we investigated cell migration and invasion of ATC using RTCA, as well as their association with periostin, matrix metalloproteinases (MMPs), and integrins. Experiments were performed on TCO-1 and HTC/C3 cells, which are human ATC cell lines. OSCC cell lines were used for comparison. Using the cell analysis system, cell migration was assessed on fibronectin-coated CIM-Plates, whereas invasion was assessed on fibronectin- and matrigel-coated CIM-Plates. SCC-4 cells exhibited high cell migration and invasion activity compared with other OSCC cell lines. TCO-1 cells exhibited equivalent cell invasion but stronger migration than SCC-4 cells. Although TCO-1 cells had strong invasive activity, they did not express MMP-9, unlike SCC-4 cells. Conversely, periostin expression was high in TCO-1 cells. Therefore, periostin expression appears to be associated with the cell migration and invasion activity of ATC. The RTCA system will be useful for the analysis of the metastatic characteristics of ATC in head and neck cancer

Construction of an All-in-one Double-conditional shRNA Expression Vector

Gene silencing by RNA interference （RNAi） is widely used for assessing gene function. An important advance in the RNAi field was the discovery that plasmid-based RNAi can substitute for synthetic small interfering RNA in vitro and in vivo. However, constitutive and ubiquitous knockdown of gene expression by RNAi in mice can limit the scope of experiments because this process can lead to embryonic lethality, or result in compensatory overexpression of other genes such that no phenotypic abnormalities occur. Either way, analyses of the physiological roles of the gene of interest in adult mice are not possible. To overcome these limitations, we previously constructed a double-conditional short-hairpin RNA （shRNA） expression vector that can regulate shRNA expression in a spatio-temporal manner with a tetracycline-inducible floxed stuffer sequence selectively excised by application of Cre recombinase. In this study, we aimed to modify this vector to create an all-in-one vector that produces double-conditional transgenic mice through a single round of gene transfer to fertilized eggs. We added a coding region for nuclear localizing Cre （NCre） recombinase with a multi-cloning site for a cell-specific promoter into the double-conditional short-hairpin RNA （shRNA） expression vector that we previously constructed. Using Escherichia coli, we confirmed successful construction of the vector. First, we confirmed isopropyl-β-D-thiogalactopyranoside-induced expression of NCre recombinase through the lac operon as a specific promoter by western blotting. Second, we confirmed functional recombination of the floxed sequence of loxP-like TATA-lox by analysing restriction enzyme-digested fragments. This all-in-one double-conditional shRNA expression vector will be useful for reversible in vitro and in vivo knockdown of target gene expression, in target cells via promoter-specific expression of NCre, and at specific times by tetracycline application