Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Feasibility and preliminary effectiveness of a psychosocial support program for adolescent and young adult cancer patients in clinical practice: a retrospective observational study.

PURPOSE: Adolescent and young adult cancer patients (AYAs) often experience profound psychological distress, with various unmet supportive care needs that can be alleviated with appropriate screening and attention by healthcare workers. The Distress Thermometer and Problem List-Japanese version (DTPL-J) is our previously developed screening tool to facilitate individual support of AYAs. This study evaluated the feasibility and preliminary effectiveness of a psychosocial support program based on the DTPL-J for AYAs in clinical practice. METHODS: This multicenter, retrospective, observational study included 19 of 126 wards and 9 of 75 outpatient clinics at 8 institutions in Japan. Over 200 patients were expected to participate during the eligibility period. Patients participated in a support program at least once, and approximately once a month based on the DTPL-J results. The program was evaluated using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) implementation framework. RESULTS: The screening rate of the 361 participants was 90.3%, suggesting high feasibility. Distress Thermometer scores, the number of supportive care needs, and the rates of AYAs with high distress were significantly reduced 1 month after screening (p < 0.05), suggesting the preliminary effectiveness of the program. The program was continued at the 8 institutions as part of routine care after the study. CONCLUSION: Analysis using the RE-AIM suggested the sufficient feasibility and preliminary effectiveness of a psychosocial support program based on the DTPL-J for AYAs. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN CTR) UMIN000042857. Registered 25 December 2020-Retrospectively registered.

Medical staff's sense of awareness of informed consent for adolescent cancer patients and the need for decision-making support practiced from the perspective of trauma-informed approach.

It has not been established how to assess children's and adolescents' decision-making capacity (DMC) and there has been little discussion on the way their decision-making (DM). The purpose of this study was to examine actual situation and factors related to difficulties in explaining their disease to adolescent cancer patients or obtaining informed consent (IC). The cross-sectional questionnaire survey was conducted. Physicians who have been treating adolescent cancer patients for at least five years answered a self-administered questionnaire uniquely developed about clinical difficulties in explaining, IC and factors related patient's refusal of medical treatment (RMT). Descriptive statistics for each item and a polychoric correlation analysis of the problems and factors related to the explanation were conducted. As a result, fifty-six physicians were participated (rate of return: 39%). Explaining the disease and treatment to patients (83.9%), IC to patients (80.4%), and explaining the disease and treatment to parents (78.6%) was particularly problematic. Difficulties to provide support related with patient's refusal of medical treatment and to explain disease and treatment for patient and parents were related to difficulties obtaining IC for the patient. Conclusion: There are clinically difficult to explain for the patient or parents and to obtain IC for the patient. It is necessary to establish a disease acceptance assessment tool for the adolescence generation so that it can be applied in the field.

Effect of biotin supplementation in infant formula: A multi-center study in Japan.

BACKGROUND: This non-randomized intervention study aimed to evaluate the effect of supplementing infant formula with biotin on biotin metabolism and on development. METHODS: We enrolled healthy Japanese infants (n = 84) and assigned them to groups offered Formula A (total biotin, 0.5 µg/100 kcal) or Formula B (total biotin, 2.4 µg/100 kcal) until they were 6 months of age, and completed an additional follow up to age 36 months. Urinary biotin concentrations were measured at 1 and 6 months, and were compared among breast-fed, Formula A-fed, and Formula B-fed infants at each age. In a follow-up subgroup analysis, we compared scores on the Ages and Stages Questionnaire, version 3 (ASQ-3), from 9 to 36 months among infants continuously fed Formula A, Formula B, or breastmilk. RESULTS: No adverse events occurred during the intervention period. At 1 month, urinary biotin concentrations were highest in Formula B-fed infants and lowest in Formula A-fed infants. At 6 months, Formula B-fed infants retained higher biotin levels than Formula A-fed and breast-fed infants. Both differences were statistically significant (P < 0.05). The breast-fed, Formula A-fed, and Formula B-fed groups had similar ASQ scores at 9-36 months. CONCLUSIONS: Biotin supplementation of infant formula contributed to improving biotin status in formula-fed infants. The results support the official approval of the use of biotin in infant formula by the government of Japan in 2014.

Medical, welfare, and educational challenges and psychological distress in parents caring for an individual with 22q11.2 deletion syndrome: A cross-sectional survey in Japan.

Parents of children with 22q11.2 deletion syndrome (22q11DS) experience distress not only due to multimorbidity in the patients, but also due to professionals' lack of understanding about 22q11DS and insufficient support systems. This study investigated relationships between medical, welfare, and educational challenges and parental psychological distress. A cross-sectional survey was conducted on primary caregivers of children with 22q11DS. Participants included 125 parents (114 mothers, 91.2%; average age = 44.3 years) who reported their challenges, psychological distress, and child's comorbidities of 22q11DS. Results showed that the difficulty in going to multiple medical institutions (ß = 0.181, p < 0.05) and lack of understanding by welfare staff and insufficient welfare support systems for 22q11DS (ß = 0.220-0.316, all p < 0.05) were associated with parental psychological distress, even after adjusting for child's comorbidities. In the subsample of parents whose child attended an educational institution, inadequate management in classroom and mismatch between service and users in educational settings were associated with psychological distress (ß = 0.222-0.296, all p < 0.05). This study reveals the importance of assessing not only severity of comorbidities in 22q11DS, but also the medical, welfare, and educational challenges for parental mental health.

The pilot study of group robot intervention on pediatric inpatients and their caregivers, using 'new aibo'.

The study on robot-assisted therapy in a pediatric field has not been applied sufficiently in clinical settings. The purpose of this pilot study is to explore the potential therapeutic effects of a group robot intervention (GRI), using dog-like social robot (SR) 'aibo' in pediatric ward. GRI by aibo was conducted for those children with chronic illness (127 in total) who are hospitalized in National Centre for Child Health and Development (NCCHD), and their caregivers (116 in total), from March to April 2018. The observer made structured behavioural observation records, based on which qualitative research on the features of their words and conducts, were carried out. As a result, first, during the GRI, about 2/3 of total expression by children were positive, while about 1/4 were negative or inappropriate. On the other hand, as seen in the 'change' group, those children who had originally responded with negative expression eventually came to express positive expression, while getting involved in a ternary relationship or participating in a session more than once. Secondly, as for the expression from the caregivers during the GRI, active expressions such as 'participation' and 'exploration' accounted for the 2/3, while 1/3 turned out to be rather placid expressions such as 'watch over' or 'encourage.'Conclusion: There has not been any precedent study on the features of words and conducts expressed by patients and their caregivers during the GRI by aibo. The outcome suggests that aibo could possibly be used as a tool for group robot-assisted therapy in the pediatric treatment setting. What is Known: • The study on robot-assisted therapy in a pediatric field has only just begun. • Though many kinds of social robot have been reportedly used so far, none has yet to be applied in clinical settings What is New: • Our study revealed the features of words and behaviour expressed by the patients and their caregivers, when dog-like social robot 'aibo' was used for a group robot intervention in the pediatric ward. • The outcome suggests that aibo could possibly be used as a tool for group robot-assisted therapy in the pediatric treatment setting.

The coronavirus disease 2019 pandemic and the rights of the child in Japan.

BACKGROUND: Few studies have used direct reports by children to assess how the rights documented in the United Nations Convention on the Rights of the Child (CRC) have been affected during the pandemic of coronavirus disease 2019 (COVID-19). METHODS: Data were obtained from the CORONA-CODOMO Survey, a web-based survey conducted from April to May 2020 in Japan, targeting children aged 7-17 and parents/guardians of children aged 0-17. We focused on self-reports from children, including two open-ended questions asking their needs and opinions. The results were analyzed according to the five categories of rights defined by the CRC: education, health, safety, play, and participation. RESULTS: Among the 2,591 children who participated in the survey, 1,292 children (49.9%) answered at least one of the two open-ended questions. The most frequent concern was COVID-19 infecting members of their families (78.2%), followed by the inability to see their friends (74.3%). There were 1,523 direct comments from children. The comments covered a wide range of the rights in the CRC, including reopening of schools, disparities in education, access to health information, alternatives for playing and seeing friends, and needs for participation and being heard. Few comments were related to safety whereas a certain proportion of children were victimized within households. CONCLUSIONS: Our results suggest that the rights outlined in the CRC have been restricted during the COVID-19 pandemic. Health and educational professionals working with children and policymakers should introduce the rights-based approach to protect the best interests of children during and after the pandemic.

Children's daily lives and well-being: Findings from the CORONA-CODOMO survey 1st wave.

BACKGROUND: The coronavirus disease 2019 pandemic has changed people's lives dramatically. Few data on the acute effects of the pandemic on children's daily lives and well-being have been published to date. This study aimed to capture its effects on Japanese children during the first peak of the outbreak. METHODS: We conducted a web-based, anonymous cross-sectional survey targeting Japanese children aged 7-17 years and parents/guardians of children aged 0-17 years. Eligible individuals were invited to participate in the survey from April 30 to May 31, 2020. This self-report questionnaire examined daily life and behaviors, psychological symptoms, well-being, quality of life, and positive parenting or abusive behaviors at the very beginning of the outbreak. RESULTS: A total of 2,591 children and 6,116 parents/guardians participated in our survey. Sixty-two percent of children reported screen time exceeding 2 h. Twenty percent of children reported abusive behaviors by family members. Nine in ten parents/guardians of school-aged children reported that their child had at least one acute stress symptom in the past month. Average mental health subscale scores from KINDLR questionnaire on quality of life were lower than the national average for all grades. Nearly half of parents/guardians refrained from seeking medical care for the child's symptoms. CONCLUSIONS: The COVID-19 pandemic had serious acute impacts on Japanese children's daily lives, well-being, family relationships, and health-care utilization, including some impacts that are potentially long-lasting; thus, proactive interventions and services are needed, as well as longitudinal surveys.

Guideline for Gynecological Practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2020 edition.

Nine years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 4th Revised Edition was published in 2020. The 2020 Guidelines includes 4 additional clinical questions (CQ), which brings the total to 99 CQ (12 on infectious disease, 29 on oncology and benign tumors, 29 on endocrinology and infertility and 29 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Fertility-sparing trachelectomy for early-stage cervical cancer: A proposal of an ideal candidate.

OBJECTIVE: To propose an ideal patient candidate with early-stage cervical cancer for undergoing fertility-sparing trachelectomy. METHODS: This nationwide, multicenter, retrospective study was conducted by the Japan Society of Obstetrics and Gynecology involving women aged <45 years with clinical stage I-II cervical cancer who had planned fertility-sparing trachelectomy and pelvic lymphadenectomy between 2009 and 2013 (n = 393). Ideal candidates were defined to have a tumor size of ≤2 cm, no lymph node metastasis, no deep stromal invasion, and no high-risk histology (n = 284, 69.6%). Less-ideal candidates were defined to have any one of these four characteristics (n = 109, 30.4%). Propensity score inverse probability of treatment weighting was used to assess survival outcomes. RESULTS: Less-ideal candidates were more likely to undergo hysterectomy conversion (22.9% versus 3.2%), receive postoperative radiotherapy (11.9% versus 0.4%), or chemotherapy (32.1% versus 3.2%) compared with ideal candidates (all, P < 0.05). The weighted model revealed that among those who underwent trachelectomy (ideal candidates, n = 275 and less-ideal candidates, n = 84), less-ideal candidates had significantly decreased disease-free survival (5-year rates: 85.5% versus 95.5%; HR 3.93, 95% CI 1.99-7.74; P < 0.001) and cause-specific survival (92.5% versus 98.6%; HR 5.47, 95% CI 1.68-17.8, P = 0.001) compared with ideal candidates. Similarly, less-ideal candidates were significantly associated with decreased disease-free survival compared with ideal candidates among those who were young age, had small tumors or squamous histology, and underwent surgery alone (all, P < 0.05). CONCLUSION: Less-ideal candidates had approximately four-fold higher recurrence risk and cancer mortality compared with ideal candidates. Ideal candidates for fertility-sparing trachelectomy for early-stage cervical cancer proposed in our study may be useful as the future framework for developing guidelines for fertility-sparing trachelectomy in Japan.

Characterization of a novel glycolipid with a difucosylated H-antigen in human blood group O erythrocytes with monoclonal antibody HMMC-1 and its detection in human uterine cervical carcinoma tissues.

Humanized monoclonal antibody HMMC-1 established by immunizing transchromosomal mice with a human uterine endometrial cancer cell line has been found to react with the H-antigen carried on core l O-glycans through cotransfection of glycosyltransferases for O-glycans and inhibition of antibody-binding with synthetic oligosaccharides. However, direct binding analysis of an antibody against glycosphingolipids from human erythrocytes with different ABO blood groups revealed that it was able to bind selectively with polar glycolipids in blood group O, but not blood group A, B and AB erythrocytes. Unexpectedly, typical monofucosylated H-glycolipids, IV2Fucα-nLc4Cer and VI2Fucα-nLc6Cer, which are the precursors for A and B-glycolipids, and were present not only in blood group O, but also A, B and AB-erythrocytes, were not the antigens for the HMMC-1 antibody. The antigen comprised less than 0.001% of the total glycolipids in blood group O-erythrocytes, and was purified by conventional silica gel column chromatography. Structural determination by permethylation, GC-MS, and ESI-TOFMS demonstrated that the structure was a novel glycolipid with a difucosylated H-antigen, Fucα1-2Galß1-4GlcNAcß1-3Gal(2-1αFuc)ß1-4GlcNAcß1-3Galß1-4GlcNAcß1-3Galß1-4Glcß1-1'Cer, VI2,VIII2(Fucα)2-nLc8Cer, whose terminal difucosylated structure was the epitope of the HMMC-1 antibody. The HMMC-1 glycolipid was detected in five out of 29 tissues from patients suffering from uterine cervical carcinomas, irrespective of their ABO-blood groups.

Theoretical analysis of crystallization by homogeneous nucleation of water droplets.

We propose a novel method for analyzing the crystallization process from supercooled water droplets. The method, which is based on nucleation theory, simultaneously evolves homogeneous ice nucleation and crystal growth in the cooling process and obtains the crystallization temperature and the number of crystal nuclei in the droplets. The model can reproduce not only the crystallization of water but also the vitrification process. The model well replicated the results of previous laboratory experiments, especially, the different responses of the crystallization temperatures of the micrometer- and nanometer-sized particles as a function of cooling rates. For particle sizes ranging from 1 to 1000 µm and cooling rates below 104 K s-1, the crystallization temperature was 230-240 K. At cooling rates above 104 K s-1, the crystallization temperature decreased rapidly. On the other hand, the crystallization temperature of 10 nm particles was 200-230 K at cooling rates below 104 K s-1. When describing the interfacial tension by σ = 29.1 + 0.1(T - 273.15) erg cm-2 (where T is the water droplet temperature in K), the analyses explained well the previously reported crystallization temperatures of droplets sized from a few nm to 100 µm under various cooling conditions. Our model also predicts the critical cooling rate for vitrification of the liquid water droplets. The critical cooling rate of vitrification is predicted to be 107-108 K s-1, consistent with the experimental rates. These analyses are useful not only for comprehensively understanding the ice nucleation process but also for predicting the crystallization processes in various environments such as cirrus clouds, which are difficult to reproduce in experiments.

Water nucleation at extreme supersaturation.

We report water cluster formation in the uniform postnozzle flow of a Laval nozzle at low temperatures of 87.0 and 47.5 K and high supersaturations of lnS ∼ 41 and 104, respectively. Cluster size distributions were measured after soft single-photon ionization at 13.8 eV with mass spectrometry. Critical cluster sizes were determined from cluster size distributions recorded as a function of increasing supersaturation, resulting in critical sizes of 6-15 and 1, respectively. Comparison with previous data for propane and toluene reveals a systematic trend in the nucleation behavior, i.e., a change from a steplike increase to a gradual increase of the maximum cluster size with increasing supersaturation. Experimental nucleation rates of 5 · 1015 cm-3 s-1 and 2 · 1015 cm-3 s-1 for lnS ∼ 41 and 104, respectively, were retrieved from cluster size distributions recorded as a function of nucleation time. These lie 2-3 orders of magnitude below the gas kinetic collision limit assuming unit sticking probability, but they agree very well with a recent prediction by a master equation model based on ab initio transition state theory. The experimental observations are consistent with barrierless growth at 47.5 K, but they hint at a more complex nucleation behavior for the measurement at 87.0 K.

Enhanced fucosylation of GA1 in the digestive tracts of X-ray-irradiated mice.

In mice at 4 days after X-ray-irradiation at 0.5 Gy/min for 16 min, the tissue weights of immune organs, i.e., thymus and spleen, were decreased due to injury to lymphocytes by the X-rays. The resulting immunosuppressive condition allowed the growth of lactobacilli, i.e., L. murinus, which contained LacßTH-DG and possessed the ability to induce transcription of the fucosyltransferase gene for synthesis of FGA1. LacßTH-DG was detected in the jejunal and ileal contents of X-ray-irradiated mice, but not in those of control mice, whereas LacTetH-DG of L. johnsonii was present in the stomach and caecal contents of both mice. The amounts of FGA1 in the duodenal and jejunal tissues of X-ray-irradiated mice increased to 4- and 9-fold of those in controls, respectively. Reflecting the enhanced fucosylation of GA1, the total amounts of FGA1 excreted into the contents of X-ray-irradiated mice were 1.4-times higher than those in controls. Also, when the extent of enhanced fucosylation of GA1 in several regions of the digestive tracts of X-ray-irradiated mice was compared with that in immune deficient nude, scid and pIgR(-/-) mice, the more than 4-fold increases of FGA1 observed in duodenal and jejunal tissues corresponded to those in pIgR(-/-) mice without secretory IgA. Since an increased amount of FGA1 in the small intestine was observed only 4 days after X-ray-irradiation, and diminished synthesis of FGA1 occurred on administration of penicillin and streptomycin, fucosylation of GA1 in the small intestine was revealed to occur quickly in response to a change in the intestinal bacterial population.

Effective Selection of a Well-Differentiated Type of Human Uterine Endometrial Carcinoma Cells by Transfection of the Sulfotransferase Gene and Possible Association of Sulfoglycolipids With Well-Differentiated Phenotypes.

OBJECTIVES: Sulfatide has been shown to be characteristically increased on the apical surface of the normal endometrium at the secretory phase, and to be related with the formation of the glandular structure and the secretion of mucin from glands for the implantation of a fertilized egg. Additionally, sulfatides are expressed in the well-differentiated type, but not in the poorly differentiated type, of endometrial carcinomas. This suggests that sulfatides are a molecular marker of differentiated phenotypes. To further elucidate the biological significance of sulfoglycolipids, we transfected the sulfotransferase gene into endometrial carcinoma-derived cells without sulfoglycolipids and compared their glycolipid compositions and phenotypes with those of the original cells. MATERIALS AND METHODS: The glycolipid sulfotransferase gene was transfected into endometrial carcinoma-derived SNG-II cells, the resultant transfected cells being found to frequently form a domelike structure, and some of them were selected as SNG-II-GST cells. We compared the glycolipid compositions and phenotypes of SNG-II and SNG-II-GST cells. RESULTS: Although the original SNG-II cells grew in a paving stone pattern, SNG-II-GST cells formed a domelike structure. SNG-II-GST cells exhibited high GST activity and contained sulfoglycolipids, IISO3-LacCer and IISO3-Gg3Cer, which were not found in SNG-II cells. The amounts of sulfoglycolipids in SNG-II-GST cells were 1.5 times higher than those of gangliosides, and the proportions of LacCer and GM3 in SNG-II-GST cells were greatly different from those in SNG-II cells. SNG-II and SNG-II GST cells exhibited poorly differentiated and well-differentiated phenotypes on histochemical examination of cancerous nodules in nude mice. However, by means of an oxygen electrode, SNG-II-GST cells were found to be more resistant to anticancer drugs than SNG-II cells. CONCLUSION: Enhanced expression of sulfoglycolipids in poorly differentiated cells is a feasible means of selecting well-differentiated ones, and sulfoglycolipids are involved in the well-differentiated phenotype like those in the normal endometrium at the secretory phase.

[Amyloidoma Adjacent to the Thoracic Vertebral Body Developed into Systemic Amyloid Light-chain amyloidosis].

Amyloidoma is very rare case of amyloidosis, and seldom develop into systemic disease. We report a case of an 82-year-old man who was referred to our hospital because of an oppressive feeling in the upper chest. Chest computed tomography showed a tumor on thoracic vertebral body. Percutaneous needle biopsy showed pathological findings of AL amyloidosis. No obvious systemic finding was confirmed, and the tumor was diagnosed as amyloidoma. After a 1-year observation, heart amyloidosis was appeared, then 6 months later he died. The autopsy revealed amyloid deposit on thoracic vertebral body, heart, arterial walls, esophagus, kidney, thyroid gland, stomach and lung. Careful observation is suggested to be necessary for amyloidoma considering the possibility of the development into systemic amyloidosis.