Improved syntheses of D-ribo- and 2-deoxy-D-ribofuranose phospho sugars from methyl β-D-ribopyranoside

Methyl 4-deoxy-4-dimethoxyphosphinoyl-2,3-O-isopropylidene-beta-D-ribopyranoside (12a) and methyl 2,4-dideoxy-4-dimethoxyphosphinoyl-beta-D-erythro-pentopyranoside (20) were efficiently prepared respectively from methyl 2,3-O-isopropylidene-beta-D-ribopyranoside (7a) and its 3,4-O-isopropylidene isomer (7b) in appreciably improved total yields compared with those via previously reported routes. Compounds (12a, 20) were led to D-ribofuranose and 2-deoxy-D-ribofuranose phospho sugars (4, 5)

Distribution of diffuse plexiform neurofibroma on the body surface in patients with neurofibromatosis 1

Neurofibromatosis 1 (NF1) is a genetic disease characterized by cutaneous, neurological and osseous abnormalities. Approximately 20% of patients develop plexiform neurofibroma (PN), resulting in impaired quality of life. To evaluate distribution of diffuse PN on the body surface, a retrospective study was conducted for 354 patients with NF1 from 2007 to 2018 in Japan. We investigated a total of 40 patients with clinically apparent superficial diffuse PN. In the cases evaluated, 57.4% of the diffuse PN were located on the trunk, 19.2% the head and neck, 12.8% the lower limbs and 10.6% the upper limbs. Remarkably, 75.0% of the diffuse PN were located on the dorsal side. The frequency was significantly higher on the trunk than on the head and neck (P = 0.026). Our findings provide useful information for giving attention to the high possibility of diffuse PN on the dorsal side before progression in childhood and for future treatment in NF1

Epidemiological Analysis of Major Complications Requiring Medical Intervention in Patients with Neurofibromatosis 1

Neurofibromatosis 1 has various complications. To elucidate the frequency of neurofibromatosis 1-related major complications requiring medical intervention, a nationwide retrospective study was conducted of 3,530 patients with neurofibromatosis 1 registered from 2001 to 2014 in Japan. The ratio of certified patients requiring medical intervention (>stage 3) was 82%. Patients classified in the most severe grade experienced dermatological complications (71.8% of patients), neurological complications (38.1%) and bone complications (33.3%). In patients with dermatological manifestations, medical treatment was needed for cutaneous neurofibromas (58%), diffuse plexiform neurofibromas (31%) and malignant peripheral nerve sheath tumours (10%). Patients with neurological manifestations needed medical treatment mainly for brain tumours (53%) and intellectual disability (26%). Patients with bone manifestations needed medical treatment for pseudoarthrosis (9%), scoliosis (55%) and bone defects (16%). It is necessary for physicians to be aware of neurofibromatosis 1-related complications requiring medical intervention in order to provide appropriate care for patients with neurofibromatosis 1

Exophiala dermatitidis infection in non-cystic fibrosis bronchiectasis

SummaryA 54-year-old female presented with an exacerbation of right middle lobe bronchiectasis. A bronchoscopic bronchial washing and repeated trials of sputum culture consistently recovered no other infectious agent except Exophiala dermatitidis. Her illness was improved by administrations of intravenous miconazole and nebulized amphotericin B when sputum cultures yielded no fungi, demonstrating a pathogenic role of the fungi. The present case illustrates E. dermatitidis as a pathogenic agent in non-cystic fibrosis bronchiectasis

40歳未満の勤務助産師の職務満足度調査 : 病院・診療所・助産所の比較

【目的】40歳未満助産師の就業場所と職務満足度との関連を明らかにする． 【方法】研究デザインは職務満足度を従属変数とする相関関係型量的研究．東京，神奈川の病院・診療所・助産所勤務 の40歳未満の助産師423名に無記名自記質式質問紙調査を郵送法で実施．期間は平成23年9月6日～30日．職務満足 度調査の内容は労働条件・人間関係・業務内容・やりがいと自律の4つをカテゴリーとした．国際医療福祉大学の倫理 委員会で承認を得た． 【結果】病院142人診療所26人助産所31人計199人の有効回答を分析（回答率47％）．職務満足度は助産所，診療所，病 院勤務助産師の順に高かった．また，カテゴリー別でみると，人間関係（相関比η0.553），業務内容（相関比η0.735）， やりがい（相関比η0.605）で，関連性がみられ，平均点はすべてにおいて助産所が高かった． 【考察】施設毎で職務満足度に相違があり，その要因に自律した助産業務が関係することから，助産師が主体的に働 くための業務の見直しが必要であると考える． (Purpose) The principal aim of the present study was to clarify the relationship between the workplace and the degree of job satisfaction among working midwives younger than 40 years. (Methods) The study was designed as a correlational and quantitative study using the degree of job satisfaction as the dependent variable.　An anonymous self-administered questionnaire was mailed to 423 midwives younger than 40 years who were working in hospitals, clinics, or birthing centres in the Tokyo Metropolis or Kanagawa Prefecture.　The study period was from September 6 to 30, 2011.　The content of the degree of work satisfaction survey was categorized into four categories: working conditions, human relationships, work duties, and sense of fulfilment and autonomy.　The present study was approved by the institutional review board of the International University of Health and Welfare. (Results) A total of 199 valid responses (hospitals: 142 responses; clinics: 26; birthing centres: 31) were analysed (valid response rate: 47％).　The degree of job satisfaction among working midwives was highest in birthing centres, followed by clinics and then hospitals.　Furthermore, an examination by category revealed a relationship between human relationships (correlation ratio: η0.553), work duties (correlation ratio: η0.735), and sense of fulfilment (correlation ratio: η0.605); the mean score of all categories was highest for birthing centres. (Discussion) Because there were differences in the degree of job satisfaction for each facility and autonomous midwifery work was a related factor, it is the authors' opinion that it is necessary to review the work of midwives to allow them to work more autonomously

育児中の助産師学生に関する研究

国際助産師連盟（以下ICM）では1年6ヶ月以上の教育を推奨している。これに対して日本では保健師助産師看護師法学校指定規則において1年以上の教育課程を必須としている。1年間でICM が提唱する教育内容を取得するには過密スケジュールが予測される。 　日本では1年制の助産師養成課程においてはほぼ30単位以上の単位履修をもって修了となり、指定規則の28単位より多くの単位取得にて卒業する1）。このように1年課程ではカリキュラムの過密状態が前提であるため、クリアできるのは学生の強い動機などが要因となっていると推測する。 　また助産学実習では看護学実習とは異なり、分娩介助等の実践が単位取得の必須要件であり、学生は時間を問わず厳しい実習状況下におかれる。このため身体的にも精神的にも強さが要求される。田中ら2）は、助産学実習は対象者との関わりが多い、学生に求められる能力が高い、学生としての責任が重い、実習体制などが看護学生の実習とは異なることを指摘している。従って学生はこれまで体験した実習よりも厳しい状況下におかれる。 　助産学実習はウェイトの大きいものであり、保健師助産師看護師学校養成所指定規則で助産学実習は11単位を必須とされている。助産学実習以外の講義においても、学生にとって学習内容が濃厚で課題が多く、1年課程であるために過密スケジュールとなることが前提となる。 　大学専攻科、別科又は専修学校など助産師養成の1年課程は、学費の負担が少ない、看護大学の卒業生のほか、看護師などの臨床経験者、社会人経験者などが入学できるメリットがあると考える。高野ら3）による社会人経験のある新人看護師を対象とした報告や、高橋4）の社会人経験者の実態などの報告、渡邉ら5）の社会人経験がある看護学生に対する教育側からの困難感などの報告があるものの、助産師学生を対象とした報告はみられないため、追究する意義があると考える。 　中島ら6）は、助産学教育の質的向上を図るためには、学生の特性を踏まえた教育法の開発や教育的支援を強化する必要性を指摘している。このため学生の特性として、育児経験者、臨床経験者、社会人経験者などを対象とし、その背景を踏まえた教育を検討することが期待される。 　そこで今回本研究では、育児中の助産師学生の1年間の学生生活の実態に焦点をあて、今後の教育側の対応への検討に資する目的で半構成的面接を行い、質的帰納的に分析したので報告する。 In order to contribute to midwifery education, semi-structured interviews for eight midwifery students who were also raising children were conducted, regarding the motivation for enrolling on the course, their challenges after enrolling, impact on their child/children, and relationship with other younger students. The results were analyzed inductively and qualitatively. As for the motivation and preparation for the enrollment, two categories:‘ long-held aspiration’‘, midwives seen in many situations’, and ‘desperate to pass the exam’ were identified. As for the challenges faced after enrollment, three categories:‘ hardship of studying that exceeded the expectation’,‘ thoughts about the child that are always in mind’, and‘ life as a student which cannot stand without support of others’ were identified. As for the feelings towards their child/children, three categories:‘ life changing that involves others’,‘ situations where, like it or not, study has to come first, not the child’, and‘ a parent who tries to convince herself that the child is understanding and appreciative’ were identified. In addition, as for the future image of themselves at the time of graduating, three categories:‘ re-acknowledgment of the work of a midwife’,‘ midwives who had become the occupational model either positively or negatively’, and‘ hopes and worries about using the obtained qualification’were identified. 　All the interviewees had childbearing experience, and their motivation of choosing the vocation came from their own childbirth experience, whether it was a positive one or a negative one. After enrolling on the course, they were worn out trying to balance the household and childcare chores and the study, involving their family members, trying to convince themselves that the child was understanding and appreciative, and trying their best to balance the child-rearing and studying while feeling guilty. 　Their priority in finding work is that it should be somewhere easily commutable, putting childcare arrangements first in their consideration. It is expected that they will re-acknowledge the serious responsibility and the breadth of the work through onsite practice and other experiences, find various midwifery role models that they had not known at the time of the enrollment, and form an occupational identity after graduation

Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone

BACKGROUND: Giant cell tumors (GCTs) of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells (MNCs). Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells, while monocyte-like cells and MNCs are reactive osteoclast precursor cells (OPCs) and osteoclasts (OCs), respectively. In this study, we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor (VEGF)-Flt-1 (type-1 VEGF receptor)-focal adhesion kinase (FAK) pathway. METHODS: The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry. RESULTS: In GCT samples, CD68, a marker of OPCs and OCs, co-localized with Flt-1. Conditioned media from GCT tissue (GCT-CM) enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover, there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK. CONCLUSIONS: Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs

Polycystic Kidney Disease in the Medaka (Oryzias latipes) pc Mutant Caused by a Mutation in the Gli-Similar3 (glis3) Gene

Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients