Genetic engineering strategy for generating a stable dsRNA virus vector using a virus-like codon-modified transgene.

IMPORTANCE: The stabilities of transgenes in RNA virus vectors differ between the genes of interest, but the molecular mechanisms determining genetic stability remain unknown. This study demonstrated that the stability of a transgene was affected by the nucleotide composition, and altering the codon usage of transgenes to resemble that of the viral genome significantly increased transgene stability in double-stranded RNA virus vectors. The virus-like codon modification strategy enabled generation of stable rotavirus and mammalian orthoreovirus vectors, which could be developed as machinery for gene delivery to the intestines and/or respiratory organs. This technology has further potential to be expanded to other RNA viruses.

Current situation and clinical burden of pediatricians for children with eating disorders during the COVID-19 pandemic.

During the COVID-19 pandemic, the incidence of eating disorders (ED) has increased not only in Japan but also worldwide. This online survey for pediatricians showed that caregivers tend to visit specific pediatric institutions or child psychiatry departments when children under junior high school age develop eating disorders. There are few pediatric institutions regarding treatment acceptance for children with ED. Of the 34 respondents, 16 (47.1%) answered that the number of visits for children with eating disorders had "stayed the same", one answered it had "decreased" and 17 (50.0%) answered it had "increased" or "increased very much". In addition, 28 of the 34 respondents (82.3%) experienced difficulties with psychotherapy for children with ED. For treating children with ED, pediatricians usually conducted physical examination and have some clinical burden. ED are increasing in the COVID-19 pandemic. Because children with severe ED need to be hospitalized, child and adolescent psychiatric wards are overcrowded and some children with other mental disorders can't be admitted.

Evaluating the daily life of child and adolescent psychiatric outpatients during temporary school closure over COVID-19 pandemic: A single-center case-control study in Japan.

This study evaluated the clinical characteristics of mental health of child and adolescent psychiatric patients during temporary school closure throughout the coronavirus 2019 (COVID-19) pandemic in Japan using the Questionnaire - Children with Difficulties (QCD) and other useful psychological rating scales. The participants were those who visited the Department of Child and Adolescent Psychiatry, Kohnodai Hospital. From those 1,463 participants, case and control groups were selected: 92 patients who visited the hospital during the temporary school closure from March 2020 to May 2020 (case group) and randomly sampled sex- and age-matched 92 patients during the pre-COVID period from April 2017 to March 2020 (control group). QCD is a parent-assessed questionnaire designed to evaluate the difficulties of children along the course of a day, right from waking up in the morning to retiring to bed at night. Lower scores indicate stronger difficulties. QCD scores were compared between the two groups in each of the following age groups: elementary school (6-12 years of age) and junior high school (12-15 years of age). In elementary school students, scores "during school" of QCD indicating functioning or disabilities during school hours were 3.31 ± 2.52 and 4.52 ± 2.33 in case group and control group, respectively (p < 0.05). In junior high school students, scores "Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS)" indicating ADHD symptoms were 16.78 ± 12.69 and 11.80 ± 10.40 in case group and control group, respectively (p < 0.05). The findings suggest that the closure of schools due to the pandemic might worsen difficulties among elementary school patients, and hyperactivity and impulsivity might increase among junior high school patients. The long-term impact of stress caused by school closure on child and adolescent psychiatric patients needs to be investigated in the future.

Current use of attention-deficit hyperactivity disorder (ADHD) medications and clinical characteristics of child and adolescent psychiatric outpatients prescribed multiple ADHD medications in Japan.

BACKGROUND/AIM: Patients with attention-deficit hyperactivity disorder (ADHD) manifest symptoms of hyperactivity, impulsivity, and/or inattention. ADHD medications available in Japan are limited compared with those in Western countries. Prescribing status has not been sufficiently evaluated in clinical settings in Japan. This study investigated the current use of ADHD medications and characteristics of patients who received multiple ADHD medications in a clinical setting in Japan. METHODS: Study participants were those who visited the Department of Child and Adolescent Psychiatry, Kohnodai Hospital between April 2015 and March 2020. We investigated patients who received osmotic-controlled release oral delivery system methylphenidate, atomoxetine, or guanfacine. A retrospective case-control design was used to evaluate the characteristics of patients who received multiple ADHD medications. Patients who were given three ADHD medications were defined as the case group. Randomly sampled sex- and age-matched patients diagnosed with ADHD were defined as the control group. We compared data for child-to-parent violence, antisocial behavior, suicide attempt or self-harm, abuse history, refusal to attend school, and two psychological rating scales (the ADHD-Rating Scale and Tokyo Autistic Behavior Scale). RESULTS: Among the 878 patients who were prescribed any ADHD medications, 43 (4.9%) received three ADHD medications. Logistic regression revealed that children with severe ADHD symptoms, autistic characteristics, or tendency of child-to-parent violence were more likely to have been prescribed three medications during their treatment. CONCLUSIONS: Our findings suggest the approach to prevent the use of multiple ADHD medications. A prospective study to investigate the causality between prescribing status and clinical characteristics is warranted.

Care for children's mental health during the COVID-19 pandemic in Japan.

COVID-19 causes very serious issues all over the world. In Japan, the number of new infections in Tokyo exceeded 2,000 for the first time on 7 January 2021, and the situation is becoming increasingly serious. Japan is in the midst of its third big outbreak. Japanese society will face several challenges regarding children's mental health during the COVID-19 pandemic. In order to develop healthy minds in children, it is important to view the changes in children's minds in a positive light and promote their healthy emotional development while correctly fearing COVID-19. This sense of social stagnation and uncertainty is likely to increase feelings of insecurity and isolation among children. It is also important to prevent the repetition of child abuse in the home due to parental unemployment, alcohol problems, and reduced contact with non-family members in stay home and the recession as a result of COVID-19. During the pandemic, adults should be sensitive to the unusual behavior of children. We propose six suggestions of care for children during the COVID-19 pandemic.