Gene Delivery into the Central Nervous System (CNS) Using AAV Vectors

Application of gene therapies is a promising approach to the treatment of various neurological disorders, including Parkinson\u27s disease, amyotrophic lateral sclerosis (ALS), and lysosomal storage disorders, which are not treatable by any other means. However, the blood–brain barrier (BBB) is a key obstacle to gene delivery to the central nervous system (CNS). Adeno-associated virus (AAV) vectors have emerged as a promising tool for gene delivery to the CNS, thanks to their safety and ability to transduce non-dividing neuronal cells. In this chapter, we discuss strategies for delivering genes across the BBB, focusing especially on potential routes of administration of AAV vectors and promising applications of AAV vectors to the treatment of CNS disorders

Neonatal Gene Therapy for Inherited Disorders

In spite of developments of neonatal intensive care medicine, it is still difficult or impossible to treat several inherited genetic disorders using conventional pharmacological methods. Gene therapy is a promising alternate approach for treating a variety of genetic disorders. By the time the patient reaches adulthood, however, it is often too late for effective treatment. But in several of these cases, neonatal gene therapy appears potentially useful against inherited disorders that are not obviously treatable through any other methods. This chapter describes the strategy for neonatal gene therapy for inherited disorders and presents preclinical neonatal gene therapy data for two inherited disorders, metachromatic leukodystrophy and hypophosphatasia. We also discuss the utility, advantages, problems and potential of neonatal gene therapy for inherited disorders

Tryptophanase-Catalyzed l-Tryptophan Synthesis from d-Serine in the Presence of Diammonium Hydrogen Phosphate

Tryptophanase, an enzyme with extreme absolute stereospecificity for optically active stereoisomers, catalyzes the synthesis of l-tryptophan from l-serine and indole through a β-substitution mechanism of the ping-pong type, and has no activity on d-serine. We previously reported that tryptophanase changed its stereospecificity to degrade d-tryptophan in highly concentrated diammonium hydrogen phosphate, (NH4)2HPO4 solution. The present study provided the same stereospecific change seen in the d-tryptophan degradation reaction also occurs in tryptophan synthesis from d-serine. Tryptophanase became active to d-serine to synthesize l-tryptophan in the presence of diammonium hydrogen phosphate. This reaction has never been reported before. d-serine seems to undergo β-replacement via an enzyme-bonded α-aminoacylate intermediate to yield l-tryptophan

生後1年児の泣きと泣きに対する母親の困難感

This study was performed to determine the actual situation of maternal distress regarding 1-year-old infant s cries. 　A self-completed questionnaire survey was performed 1 year after birth among 305 mothers who gave birth to term infants at maternity hospitals in the Hokuriku region. The survey content included : state of infant cries (characteristics of the cry and frequency, occurrence of crying at night, and the period when cries at night were observed), mother s sleeping condition and health condition, status of night feeding, support, feelings of mothers, and period when mothers began to understand the reasons for the infant s cries. In this study, the frequency of maternal distress regarding infant s crying was converted to a score, with higher scores indicating higher levels of distress related to crying. The number of valid responses was 251 (rate of valid response, 82.3%). One hundred eighty-five mothers reported night crying (73.7%), and night crying occurred most often around 6 to 8 months. The period when mothers felt they understood the reasons for the infant s cries was at 7 to 8 months in the majority of cases, and 1 year at the latest. At 1 year after birth, only approximately 20% of mothers reported feelings of distress related to crying. The results indicated that maternal distress associated with child crying is related to nuclear family, presence of someone to talk to about childcare, characteristics of infant s cry, mother s health condition, and mother s feelings toward childcare.１年児の泣きとその母親の泣きに対する困難感の実態を明らかにすることを目的とし た。 　北陸地方の病産院にて正期産児を出産した母親３０５名を対象に、出生後１年時に、自己記 入式質問紙調査を実施した。調査内容は、児の泣きの状態（泣き方の特徴や頻度、夜泣き の有無と夜泣きの時期等）、母親の睡眠・健康状態、夜間の授乳状況、サポート状況、児が 泣いた時の母親の気持ちや泣きの理由がわかるようになった時期などである。本研究にお いては、児が泣くと戸惑う母親の頻度を得点化し、得点が高いほど、泣きに対する困難感 が高いと解釈した。有効回答は２５１名（有効回答率８２３. %）であった。乳児の夜泣きは、１８５ 名（７３７. ％）の母親にみられ、夜泣きの時期は６～８ヶ月頃が最も多かった。母親が児の泣 きの理由がわかるようになったと感じる時期は、大部分が７～８ヶ月頃から遅くとも１年 までであった。１年時においては、泣きに対して戸惑う母親は２割程度であった。泣きに 対する母親の困難感には、核家族、子育て相談者の存在、児の泣きの特性、母親の健康状態、 育児に対する母親の気持ちやなどが関連していることが明らかとなった。[原著:Originals

元留学生外国人社員の日本企業における適応に関する研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学准教授 中原 淳, 東京大学教授 水越 伸, 東京大学教授 山内 祐平, 順天堂大学教授 石黒 武人, 横浜国立大学教授 服部 泰宏University of Tokyo(東京大学

Medium-term outcomes of a program to upgrade the nursing faculty in Cambodia: A qualitative study

Continuous professional development is important for improving professional competencies, such as cognitive knowledge, technical skills, behaviors, and attitudes. Trainees who complete training programs can have a positive influence on their workplaces. However, it is challenging to establish a process that can facilitate individual learning and help achieve training outcomes in educational and clinical workplaces. In Cambodia, a tumultuous history has played a part in the deficit of adequately prepared nursing faculty. Since the faculty development is vital to ensuring the quality of education, the application of upgraded nursing programs has started in 2011. After the completion of upgraded program, an immediate post-training study was conducted in 2014. Results showed that some faculty members did not accept trainees because they lacked an understanding about nursing concepts. The current study aimed to evaluate the medium-term outcomes of an established program that can improve nursing education and to identify relevant factors in light of the institutional development of educational and clinical facilities in Cambodia. A qualitative study incorporating focus group discussions, key-informant interviews, and teaching document reviews was performed with a thematic analysis using the four-level training evaluation model of Kirkpatrick. Finally, factors influencing outcomes were assessed based on the Bronfenbrenner's ecological system theory. Five themes for behavior and three themes for results were identified as medium-term outcomes from an institutional development aspect. The major enabling factors for the above-mentioned themes were the support of institutional managers, continuous networking among trainees, and supportive national policy. Compared with the immediate post-training study findings, the perceived medium-term outcomes became more strategically focused. Then, the impact of training at a considerably broader scale within the workplace was discussed. The findings highlighted the importance of medium-term program delivery and monitoring if one understands the role played in stimulating outcomes. Moreover, the importance of contextual factors including the influence of managers and policy environment were emphasized

Gross E esophageal atresia with unique course

The patient was a 15 months-old boy who had been diagnosed CHARGE syndrome, which is a multiple congenital anomaly syndrome caused by mutations in the CHD7 gene. Mechanical ventilation management was initiated 2 hours after birth for dysphagia and respiratory failure, and tracheotomy was performed 3 months after birth for dysphagia and failed extubation. He was repeatedly hospitalized due to pneuomoniae. Approximately 1 year after birth, the boy had two consecutive episodes of sudden ventilatory insufficiency while replacing the tracheotomy cannula. A bronchoscopic examination under general anesthesia revealed a tracheoesophageal fistula directly below the tracheostomy. The patient was diagnosed with Gross E esophageal atresia, and we speculated that the cannula migrated to the esophagus via the fistula during tracheostomy cannula replacement. Gross E esophageal atresia is a rare disease. Its diagnosis is often delayed, and it is discovered by recurrent pneumonia in many cases. A tracheoesophageal fistula may also be found in children with deformities of the respiratory system. Furthermore, tracheoesophageal fistulae are often found in the neck. Therefore, when sudden ventilatory insufficiency occurs in a child with a tracheostomy after replacing the tracheostomy cannula, caution must be exercised since the cannula may have migrated to the esophagus via a fistula