Parental genome unification is highly error-prone in mammalian embryos.

Most human embryos are aneuploid. Aneuploidy frequently arises during the early mitotic divisions of the embryo, but its origin remains elusive. Human zygotes that cluster their nucleoli at the pronuclear interface are thought to be more likely to develop into healthy euploid embryos. Here, we show that the parental genomes cluster with nucleoli in each pronucleus within human and bovine zygotes, and clustering is required for the reliable unification of the parental genomes after fertilization. During migration of intact pronuclei, the parental genomes polarize toward each other in a process driven by centrosomes, dynein, microtubules, and nuclear pore complexes. The maternal and paternal chromosomes eventually cluster at the pronuclear interface, in direct proximity to each other, yet separated. Parental genome clustering ensures the rapid unification of the parental genomes on nuclear envelope breakdown. However, clustering often fails, leading to chromosome segregation errors and micronuclei, incompatible with healthy embryo development.

Feasibility and impact of haplogroup matching for mitochondrial replacement treatment.

Mitochondrial replacement technology (MRT) aims to reduce the risk of serious disease in children born to women who carry pathogenic mitochondrial DNA (mtDNA) variants. By transplanting nuclear genomes from eggs of an affected woman to enucleated eggs from an unaffected donor, MRT creates new combinations of nuclear and mtDNA. Based on sets of shared sequence variants, mtDNA is classified into ~30 haplogroups. Haplogroup matching between egg donors and women undergoing MRT has been proposed as a means of reducing mtDNA sequence divergence between them. Here we investigate the potential effect of mtDNA haplogroup matching on clinical delivery of MRT and on mtDNA sequence divergence between donor/recipient pairs. Our findings indicate that haplogroup matching would limit the availability of egg donors such that women belonging to rare haplogroups may have to wait > 4 years for treatment. Moreover, we find that intra-haplogroup sequence variation is frequently within the range observed between randomly matched mtDNA pairs. We conclude that haplogroup matching would restrict the availability of MRT, without necessarily reducing mtDNA sequence divergence between donor/recipient pairs.

Formation and Growth of Atomic Scale Seeds of Au Nanoparticle in the Nanospace of an Organic Cage Molecule.

Seed-mediated growth has been widely used to synthesize noble metal nanoparticles with controlled size and shape. Although it is becoming possible to directly observe the nucleation process of metal atoms at the single atom level by using transmission electron microscopy (TEM), it is challenging to control the formation and growth of seeds with only a few metal atoms in homogeneous solution systems. This work reports site-selective formation and growth of atomic scale seeds of the Au nanoparticle in a nanospace of an organic cage molecule. We synthesized a cage molecule with amines and phenols, which were found to both capture and reduce Au(III) ions to spontaneously form the atomic scale seeds containing Au(0) in the nanospace. The growth reaction of the atomic scale seeds afforded Au nanoparticles with an average diameter of 2.0±0.2 nm, which is in good agreement with the inner diameter of the cage molecule.

The degree of satisfaction and level of learning in male and female surgical residents: a nationwide questionnaire survey of graduating residents in Japan.

PURPOSE: Since 2002, the Japan Surgical Society has established a board certification system for surgeons to be certified for a specialty. Surgery remains a male-dominated field in Japan. This study aimed to clarify if the Japanese surgical residency training system is equally suitable for female and male residents. METHODS: The Japan Surgical Society conducted the first questionnaire survey regarding the system of surgical training for the residents in 2016. The questionnaire included the degree of satisfaction with 7 aspects of the training system, including the number and variety of cases experienced and duration and quality of instruction, and the learning level for 31 procedures. The degree of satisfaction and level of learning were compared between female and male residents. RESULTS: The degree of satisfaction was similar for all items between female and male residents. Female residents chose breast surgery as their subspecialty more frequently than male residents and were more confident in breast surgery procedures than male residents. Conversely, fewer female residents chose gastrointestinal surgery and were less confident in gastrointestinal surgery procedures than male residents. CONCLUSION: Female residents were as satisfied with the current surgical training system as male residents. However, there may be room for improvement in the surgical system, considering that fewer applications for gastrointestinal surgery come from female residents than from males.

Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease.

Mitochondrial DNA (mtDNA) mutations are maternally inherited and are associated with a broad range of debilitating and fatal diseases. Reproductive technologies designed to uncouple the inheritance of mtDNA from nuclear DNA may enable affected women to have a genetically related child with a greatly reduced risk of mtDNA disease. Here we report the first preclinical studies on pronuclear transplantation (PNT). Surprisingly, techniques used in proof-of-concept studies involving abnormally fertilized human zygotes were not well tolerated by normally fertilized zygotes. We have therefore developed an alternative approach based on transplanting pronuclei shortly after completion of meiosis rather than shortly before the first mitotic division. This promotes efficient development to the blastocyst stage with no detectable effect on aneuploidy or gene expression. After optimization, mtDNA carryover was reduced to <2% in the majority (79%) of PNT blastocysts. The importance of reducing carryover to the lowest possible levels is highlighted by a progressive increase in heteroplasmy in a stem cell line derived from a PNT blastocyst with 4% mtDNA carryover. We conclude that PNT has the potential to reduce the risk of mtDNA disease, but it may not guarantee prevention.

Improving the communication skills of medical students --A survey of simulated patient-based learning in Chinese medical universities.

BACKGROUND: It is useful to advance simulated patient (SP) participation in teaching to improve the communication skills of medical students, so this study aims to explore the current state of Chinese mainland SP education. METHODS: A cross sectional survey was designed utilizing well defined quantitative research methods and descriptive statistics. The questionnaire sought information which elucidated the current status of SP-based education, the origin of SP-based learning, SP training, challenges of this learning strategy and future developments. Questionnaires were distributed to 79 medical colleges in mainland China, and 68 were returned. Of these, 64 constituted valid responses (81%). RESULTS: The number of SP-based education activities in medical colleges offering 5-year、7-year and 8-year clinical medicine programs was significantly higher than that in medical colleges which offered only a single 5-year program (p < 0.01). Communication skills training accounted for 73% of the content of SP-based learning activities, and was expected to rise in the future to 90%, in response to a need to improve doctor-patient relationships. Persons recruited as 'simulated patients' included students (21% of the total), residents (49%), medical staff (15%) and teaching staff (14%). Colleges, planning a SP-based education program, preferred teachers (80%) and students (55%) to assume 'simulated patient' roles. In objective structured clinical education (OSCE) scenarios, co-scoring by both SPs and teachers featured more highly in the 'consultation' station and 'doctor-patient communication' station. A number of factors were identified as hindering future development and implementation of SP-based learning including budget restraints, SP selection and training. CONCLUSIONS: SP-based learning programs offer clear benefits for improving the clinical education of medical students and their communication skills. The main obstacles to achieving more widespread and higher quality SP-based education are insufficient funding and the lack of standardized training and performance evaluation processes for simulated patients. Medical colleges should consider reducing the proportion of students and teachers acting as SPs, and attract more citizens to participate in SP-based learning activities. Formalised training and evaluation of SPs performance are necessary to establish a 'standard simulated patient' for a particular medical discipline, thus improving SP-based activities and student learning.

Evaluation of postgraduate rural medical training programs and implications for rural workforce development: a systematic review.

INTRODUCTION: Providing postgraduate rural training programs has been recognised as central for successful recruitment and retention of medical workforce. While there have been many documented cases of rural training program development, documented program outcome evaluations are few. This review investigated how postgraduate training and educational programs for rural and remote medicine are evaluated worldwide. Through the use of a systematic review, the study explored three questions: 'What are the outcomes of postgraduate rural and remote training programs worldwide?', 'How are the program evaluations conducted?' and 'What evaluation models and approaches are used in evaluating the effectiveness of these training programs?' METHODS: A qualitative synthesis was undertaken of evaluations of postgraduate rural training programs published in the English language in medical education journals. The study involved pooling quantitative and mixed-methods research data and findings from qualitative studies, which were aggregated, integrated and interpreted. PubMed, PsycINFO, ERIC and Web of Science databases were searched to identify studies that satisfy the search criteria. RESULTS: Of the 1297 articles identified through the database search, 26 studies were included in the analysis. Most of the evidence from the studies consists of descriptive studies with some longitudinal tracking programs and cohort studies. Nine themes were identified: practice location after training completion; training location and decentralised model; educational aspects; incentives, political contexts and regulations; personal, social and cultural issues; professional development; rural orientation and community engagement; support system; and gender and racial issues. Key outcomes were analysed and cross-validated against the 2020 WHO guideline on health workforce development, attraction, recruitment and retention in rural and remote areas. These studies' most frequent evaluation methods were surveys, followed by interviews, questionnaires and secondary data from existing databases. Methodological characteristics, the relationship between rural background and program outcomes, and implications for decentralised training, telehealth and tele-assessment during the COVID-19 pandemic are discussed. Analysis from the key outcomes suggests evaluation as a strategy to uncover outcomes in postgraduate rural and remote training and medical education. CONCLUSION: Regardless of the similar outcomes, the program evaluations implemented and the robustness of evidence vary across programs and medical schools. The absence of solid evaluation designs and their alignment to the program objectives will lessen the strengths of evidence. Better quality research and evaluation design, objective settings, qualitative inquiry to uncover the contexts, and developing appropriate indicators and benchmarks for monitoring and evaluating strategies must be considered during program development and implementation.

Sharing genetic test results of germline pathogenic variants of hereditary cancer with relatives: A single-center cross-sectional study.

OBJECTIVE: This study aimed to determine whether Japanese cancer patients share test results of germline pathogenic variants of hereditary cancer with their relatives. METHODS: This single-center cross-sectional study enrolled 21 Japanese patients who received results of germline pathogenic variants of hereditary cancer at least 6 months prior. RESULTS: All patients shared their test results with at least one relative, with the following sharing rates: 85.7% for first-degree relatives, 10% for second-degree relatives and 8.3% for third-degree relatives. Patients most commonly shared the information with their children aged >18 years (86.7%), followed by their siblings (73.6%), spouses (64.7%) and parents (54.5%). Three categories were extracted from qualitative analysis: 'characteristics of my cancer', 'knowledge and caution about inheritability' and 'utilization of medical care.' CONCLUSIONS: The rate of test result sharing with first-degree relatives was comparable with those in Europe and the USA. Patients with germline pathogenic variants also tended to share their test results more with their children and siblings than with their parents. Informing their relatives of the results was suggestive of the motivation to influence their relatives' health outcome and contribute to the well-being of their children and siblings.

Is there disparity between regions and facilities in surgical resident training in Japan? Insights from a national survey.

PURPOSE: This study sought to assess the disparity between regions and facilities in surgical resident training in Japan via a national level needs-assessment. METHODS: A survey was sent to all 909 graduating residents of 2016. Residents trained in the six prefectures with a population of 7 million or more were included in the large prefecture (LP) group. Residents trained in the other 41 prefectures were included in the small prefecture (SP) group. Each group was further divided into a university hospital (UH) group and a non-university hospital (NUH) group. RESULTS: The response rate was 56.3% (n = 512). Excluding nine residents who did not report their prefectures and facilities, surveys from 503 residents were analyzed. The UH group received significantly more years of training. In the SP and UH groups, there were significantly fewer residents who had performed 150 procedures or more under general anesthesia in comparison to the LP and NUH groups, respectively. Self-assessed competencies for several procedures were significantly lower in the SP and UH groups. CONCLUSION: Disparity in surgical resident training was found between regions and facilities in Japan. The surgical residency curriculum in Japan could be improved to address this problem.

Are graduating residents sufficiently competent? Results of a national gap analysis survey of program directors and graduating residents in Japan.

PURPOSE: To evaluate the self-assessed competency of graduating residents (GRs) in Japan upon completion of their residency and to identify the gap between their competency and the competency expected by their program directors (PDs). METHOD: A list of 31 essential surgical procedures was compiled according to the consensus of surgical educators from around the country. A survey with this list was sent to all 909 GRs and their 611 PDs in 2016. The GRs rated their competency to perform these procedures and the PDs were asked to evaluate the expected competency of their GRs using the Zwisch Scale. RESULT: The response rate was 56.3% for the GRs and 76.8% for the PDs. Fewer than half of the GRs who responded felt confident performing ten (32%) of the surgical procedures evaluated. For most procedures, the GRs' self-reported competency was lower than the expectation reported by their PDs. This gap was more than 10% for 13 of the procedures. CONCLUSION: More than half of the GRs in Japan lacked the confidence in their skill to perform one-third of the surgical procedures selected for evaluation in this study. These findings should be used to update the surgical education curriculum in Japan.

A snapshot of surgical resident training in Japan: results of a national-level needs assessment survey.

PURPOSE: To evaluate the status of surgical training in Japan through a national-level needs assessment. METHODS: A survey was sent to all 909 graduating residents (GRs) and their 611 program directors (PDs) for the year 2016. A working group of surgical educators from around the country was formed under the education committee of the Japan Surgical Society. The survey items were developed by consensus of this working group. The survey investigated the knowledge and problems of the current curriculum, and the status of the current residency training. RESULTS: The response rates were 56.3% of the GRs and 76.8% of the PDs. Among the participants, 47.6% of the GRs and 29.4% of the PDs believed that the residency curriculum did not match the clinical experience. Over 80% of the GRs and PDs agreed on the importance of training outside of the OR, whereas only 13% of the GRs had received such training regularly. Trainees also reported a lower satisfaction rate about the opportunity to train outside of the OR. CONCLUSION: This national-level needs assessment of surgical training in Japan identified several gaps in the curriculum. These results provide valuable data to assist the ongoing efforts for surgical residency curriculum improvement.

Mindfulness-based cognitive therapy for Japanese breast cancer patients-a feasibility study.

OBJECTIVES: Mindfulness-based intervention has been receiving growing attention in cancer care. This study aimed to examine feasibility and to preliminary explore effectiveness of mindfulness-based cognitive therapy (MBCT) in Japanese breast cancer patients, and to explore possible modification of the program so that it fits better with this population. METHODS: Twelve participants with diagnosis of Stage I-III breast cancer received an eight session, weekly MBCT intervention in a group therapy format. The participants were followed up until 3 months after the completion of the program. RESULTS: All the participants completed the program with high attendance rate (mean number of attended sessions = 7.7). Significant improvement in anxiety (Hospital Anxiety and Depression Scale (HADS) - anxiety subscale; effect size Cohen's d = 0.88, P < 0.05), trauma-related psychological symptoms (Impact of Event Scale-revised; d = 0.64, P < 0.01) and quality of life (Functional Assessment of Cancer Therapy-Breast Cancer: FACT-B; d = 0.72, P < 0.01), and trend-level improvement in depression (HADS - depression subscale; d = 0.53, P = 0.054) were observed. Qualitative analyses suggested the program may be beneficial for alleviating fear of cancer recurrence and for increasing spiritual well-being. Some recommended modification of the program was indicated from the post-intervention interviews. CONCLUSIONS: Mindfulness-based cognitive therapy was well accepted by Japanese breast cancer patients and yielded favorable effect on their psychological status and quality of life. Further effectiveness study in a randomized-control design is warranted.

Extracorporeal life support after cardiac surgery in children: outcomes from a single institution.

Extracorporeal life support (ECLS) is used after congenital heart surgery for several indications, including failure to separate from cardiopulmonary bypass, postoperative low cardiac output syndrome, and extracorporeal cardiopulmonary resuscitation. Here, we assessed the outcomes of ECLS in children after cardiac surgery at our institution. Medical records of all children who required postoperative ECLS at our institution were reviewed. Between 2003 and 2011, 36 (1.4%) of 2541 pediatric cardiac surgical cases required postoperative ECLS. Median age of patients was 64 days (range: 0 days-4.1 years). ECLS was in the form of either extracorporeal membrane oxygenation (ECMO; n = 24) or ventricular assist system (VAS; n = 12). Mean duration of ECLS was 4.9 ± 4.2 days. Overall, 21 patients (58%) were weaned off ECLS, and 17 patients (47%) were successfully discharged from the hospital. Patients with biventricular heart (BVH) had higher survival-to-hospital discharge rates compared with those with univentricular heart (UVH) (P = 0.019). Regarding ECLS type, UVH patients who received VAS showed higher rates of device discontinuation than UVH patients who received ECMO (P = 0.012). However, rates of hospital discharge were not significantly different between UVH patients who received VAS or ECMO. Surgical interventions, such as banding of Blalock-Taussig shunt to reduce pulmonary blood flow or placing bidirectional cavopulmonary shunt to minimize ventricular volume overload, were effective for weaning off ECLS in patients with UVH. ECLS is beneficial to children with low cardiac output after cardiac surgery. Rates of survival-to-hospital discharge were higher in BVH patients than UVH patients. Additional interventions to reduce ventricular volume load may be effective for discontinuing ECLS in patients with UVH.

[Improvement of outcomes in the surgical treatment of hypoplastic left heart syndrome (HLHS) with staged Norwood operation].

On behalf of rapid progress of diagnostic technologies and new development of surgical technique or strategy, outcomes of surgical treatment of hypoplastic left heart syndrome (HLHS) has remarkably improved in the current practice. One of such approaches is the staged Norwood operation. We have reviewed our patients (n=54) between 2003 and 2013. A half of the patients with the staged group accomplished Norwood procedure and concomitant bidirectional cavopulmonary shunt at the mean age of 4 months old. An another half of the patients underwent secondary Norwood operation with Blalock-Taussig( BT) shunt or right-ventricle to pulmonary artery( RV-PA) conduit, because of ductal closure in spite of prostaglandin, or progressive reversed coarctation. Cardiac catheterization showed good results in both the primary (n=17) and the staged approach (n=37), partly because even in the primary Norwood group we used a smaller calibered graft for BT shunt or RV-PA conduit to unload the ventricle as much as possible. In conclusion, since the surgical mortality of staged group was superior to that of the primary group and the mid-term survival in the staged seemed to be better than that of primary, we would pursue our strategy of the staged approach in the surgical treatment of hypoplastic left heart syndrome.

Identifying Unmet Social Needs in a Patient Living in Isolation: A Case Report.

Loneliness and social isolation are common among older adults. To deliver high-quality care to older patients, healthcare professionals should know the social conditions of their patients. Addressing social determinants of health (SDH) in daily practice is beneficial to both patients and healthcare professionals. We illustrate a patient with congestive heart failure and cognitive decline whose social conditions improved through an SDH assessment. An SDH assessment has some potential advantages, which include facilitating a comprehensive understanding of patients' social conditions, visualizing how patients' social conditions have changed, deepening interprofessional collaboration, and ameliorating unnecessary negative emotions toward patients. This case report conveys two key messages. Firstly, healthcare professionals have the capability to evaluate patients' social backgrounds and enhance their health and social conditions through routine care. Secondly, the utilization of an SDH screening toolkit can support and enhance this initiative.

Characteristic profiles among students and junior doctors with specific career preferences.

BACKGROUND: Factors influencing specialty choice have been studied in an attempt to find incentives to enhance the workforce in certain specialties. The notion of "controllable lifestyle (CL) specialties," defined by work hours and income, is gaining in popularity. As a result, many reports advocate providing a 'lifestyle-friendly' work environment to attract medical graduates. However, little has been documented about the priority in choosing specialties across the diverse career opportunities.This nationwide study was conducted in Japan with the aim of identifying factors that influence specialty choice. It looked for characteristic profiles among senior students and junior doctors who were choosing between different specialties. METHODS: We conducted a survey of 4th and 6th (final)-year medical students and foundation year doctors, using a questionnaire enquiring about their specialty preference and to what extent their decision was influenced by a set of given criteria. The results were subjected to a factor analysis. After identifying factors, we analysed a subset of responses from 6th year students and junior doctors who identified a single specialty as their future career, to calculate a z-score (standard score) of each factor and then we plotted the scores on a cobweb chart to visualise characteristic profiles. RESULTS: Factor analysis yielded 5 factors that influence career preference. Fifteen specialties were sorted into 4 groups based on the factor with the highest z-score: "fulfilling life with job security" (radiology, ophthalmology, anaesthesiology, dermatology and psychiatry), "bioscientific orientation" (internal medicine subspecialties, surgery, obstetrics and gynaecology, emergency medicine, urology, and neurosurgery), and "personal reasons" (paediatrics and orthopaedics). Two other factors were "advice from others" and "educational experience". General medicine / family medicine and otolaryngology were categorized as "intermediate" group because of similar degree of influence from 5 factors. CONCLUSION: What is valued in deciding a career varies between specialties. Emphasis on lifestyle issues, albeit important, might dissuade students and junior doctors who are more interested in bioscientific aspects of the specialty or have strong personal reasons to pursue the career choice. In order to secure balanced workforce across the specialties, enrolling students with varied background and beliefs should be considered in the student selection process.

Barriers encountered by nurses in the care of walk-in international patients in an emergency department in Japan.

BACKGROUND: An increasing number of international patients continue to visit emergency departments (EDs) in Japanese hospitals. However, nurses in Japan perceive challenges when caring for patients from other countries. This study explored ED nurses' perceptions of barriers when caring for walk-in international patients. METHODS: Five semi-structured online focus group interviews involving 15 registered nurses with experience in caring for patients in an ED at a university referral hospital located in the center of Tokyo were conducted. Thematic analysis was used to identify patterns from the interviews. RESULTS: The themes that emerged were as follows: (1) hesitation to engage with patients due to ambiguity, (2) loss of harmony in the ED, (3) difficulty with mutual goal settings, and (4) decreased professional self-efficacy. CONCLUSION: The findings provide an understanding of the challenges faced when caring for walk-in international patients. Educational interventions for ED nurses and other strategies, such as the use of interpreters, can enhance nurses' abilities to improve patient safety and maintain equality.

Impact of medical students' socioeconomic backgrounds on medical school application, admission and migration in Japan: a web-based survey.

OBJECTIVES: The aim of this study was to clarify and compare the socioeconomic backgrounds of medical students with those of other health professions and non-health faculty students in an era of increasing inequity in Japanese society. DESIGN: This was a quantitative nationwide study. Data were collected by a cross-sectional web-based anonymous questionnaire. SETTING: Data from years 3 and 4 medical, health professions and non-health faculty students across Japan were collected in 2021. PARTICIPANTS: Participants were 1991 students from medical schools, 224 from dental, 419 from pharmacy, 326 from nursing, 144 from other health professions and 207 from non-health faculties. RESULTS: The proportion of high-income families (>18 million yen: ca. US$140 000) among medical students was 25.6%, higher than that of pharmacy (8.7%) and nursing students (4.1%) (p<0.01). One-third of medical students had a physician parent, more common than in non-medical students (p<0.01). Students who only applied to public medical schools and a regional quota 'Chiiki-waku' students with scholarship had lower family income and physician parents compared with those who applied to private medical schools (p<0.01), but they still had higher physician parents compared with non-medical students (p<0.01). Logistic regression revealed that having a physician parent (p<0.01), aspiring to the present profession during elementary school (p<0.01) and private upper secondary school graduation (p<0.01) predicted the likelihood of studying medicine. There were regional differences of backgrounds among medical students, and 80% of medical students with urban backgrounds intended to work in urban localities after graduation. CONCLUSIONS: This study provides evidence that medical students in Japan hail from urban and higher income classes and physicians' families. This finding has implications for the health workforce maldistribution in Japan. Widening the diversity of medical students is essential for solving physician workforce issues and meeting broad healthcare needs.