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Abstract This study aimed to examine the impact of both the initial state of emergency (SOE) imposed from April to May 2020 in response to the COVID-19 pandemic and the COVID-19 outbreak itself on the utilization of mental health services among children and adolescents in Japan during the recent pandemic. We conducted an interrupted time series analysis of the number of mental health visits and average incurred medical expenses, stratified by sex and age group, using monthly medical claims data on 3,029,048 patients for the period from January 2016 to December 2020. It was demonstrated that the SOE resulted in a reduced number of visits for mental health services. After the second outbreak of COVID-19 in Japan, which occurred after the SOE, the number of initial visits and the average incurred medical expenses for mental health services increased notably among girls and adolescent females. The findings of this study suggest that: (1) the provision of mental health services for potential patients with mental disorders was insufficient during the pandemic, and (2) the mental health of girls and adolescent females deteriorated during the pandemic. Early screening and treatment of potentially vulnerable patients with mental disorders should be enhanced during a pandemic.

This entry reviews the health condition known as Roemheld syndrome, or gastrocardiac syndrome in modern medicine. A pathology of gastrointestinal origin, the syndrome relies on a gut–brain–heart triad, interconnected by the vagus nerve. Pressure from the intestines pushes the stomach into the diaphragm and activates the vagus nerve, which affects the heart rate and gives the perception of cardiac issues. This distressing sensation, which usually comes after meals or with other digestive problems, causes anxiety or panic. Although events not arising from anatomic abnormalities are relatively harmless, hypersensitivity to these uncomfortable sensations may precipitate psychiatric problems (anxiety or depression) that cause repeated gastrocardiac events through sympathetic activation and the disruption of peristalsis. Treatment is usually symptomatic and may include diet, lifestyle changes, probiotics, or prescriptions that increase gut motility, but this specific set of reproducible symptoms may also be caused by hiatal hernia or side effects from medication/surgery and treated with respect to those mechanical causes. This review highlights details from the most current knowledge of the condition and offers suggestions for clinical management based on the literature.

Background and Objectives: Vasopressin increases blood pressure through aquaporin-2-mediated water retention and is useful for managing hemodynamics after surgery. However, even after decades of study, clear clinical guidelines on doses and ideal use cases after cardiovascular surgery remain unclear. Here, the existing literature is synthesized on vasopressin use for cardiac surgeries and coupled with real-world clinical experience to outline a clearer clinical path for vasopressin use. Materials and Methods: Literature from 1966 to the present was searched, and information on surgical outcomes for cardiovascular surgery was extracted. Clinicians from the University of Tsukuba with extensive vasopressin experience in pediatric cardiovascular patients were consulted for general use guidelines. Results: Vasopressin response after cardiovascular surgery is multifaceted, and low-power trials, plus conflicting study reports, generally render it as a secondary choice behind norepinephrine. Clinical experience indicates that low doses of 0.2–0.3 mU/kg/min with constant blood pressure and oxygen monitoring for response are required. Although sole use is not recommended, vasopressin may aid in controlling hemodynamics when given with other volemic or osmolal drugs. Conclusions: Vasopressin may work in a select population of first-line non-responders, but relevant response factors remain unanalyzed and clear guidelines for use remain unestablished. Future, large-scale studies are needed to delineate temporal and demographic characteristics that affect response to vasopressin for the purpose of managing post-surgical capillary leakage and hemodynamics.

Abstract Natto, known for its high vitamin K content, has been demonstrated to suppress atherosclerosis in large-scale clinical trials through a yet-unknown mechanism. In this study, we used a previously reported mouse model, transplanting the bone marrow of mice expressing infra-red fluorescent protein (iRFP) into LDLR-deficient mice, allowing unique and non-invasive observation of foam cells expressing iRFP in atherosclerotic lesions. Using 3 natto strains, we meticulously examined the effects of varying vitamin K levels on atherosclerosis in these mice. Notably, high vitamin K natto significantly reduced aortic staining and iRFP fluorescence, indicative of decreased atherosclerosis. Furthermore, mice administered natto showed changes in gut microbiota, including an increase in natto bacteria within the cecum, and a significant reduction in serum CCL2 expression. In experiments with LPS-stimulated macrophages, adding natto decreased CCL2 expression and increased anti-inflammatory cytokine IL-10 expression. This suggests that natto inhibits atherosclerosis through suppression of intestinal inflammation and reduced CCL2 expression in macrophages.

IntroductionSARS-CoV-2 infection increases the risk of worse outcomes in cancer patients, including those with breast cancer. Our previous study reported that the SARS-CoV-2 membrane protein (M-protein) promotes the malignant transformation of triple-negative breast cancer cells (triple-negative BCC).MethodsIn the present study, the effects of M-protein on the ability of extracellular vesicles (EV) derived from triple-negative BCC to regulate the functions of tissue stem cells facilitating the tumor microenvironment were examined.ResultsOur results showed that EV derived from M-protein-induced triple-negative BCC (MpEV) significantly induced the paracrine effects of adipose tissue-derived mesenchymal stem cells (ATMSC) on non-aggressive BCC, promoting the migration, stemness phenotypes, and in vivo metastasis of BCC, which is related to PGE2/IL1 signaling pathways, in comparison to EV derived from normal triple-negative BCC (nEV). In addition to ATMSC, the effects of MpEV on endothelial progenitor cells (EPC), another type of tissue stem cells, were examined. Our data suggested that EPC uptaking MpEV acquired a tumor endothelial cell-like phenotype, with increasing angiogenesis and the ability to support the aggressiveness and metastasis of non-aggressive BCC.DiscussionTaken together, our findings suggest the role of SARS-CoV-2 M-protein in altering the cellular communication between cancer cells and other non-cancer cells inside the tumor microenvironment via EV. Specifically, M-proteins induced the ability of EV derived from triple-negative BCC to promote the functions of non-cancer cells, such as tissue stem cells, in tumorigenesis.

Abstract Background The prevalence of metabolic syndrome (MetS) in Japan, a super-aged society, is increasing and poses a major public health issue. Several studies have reported sex differences in the association between age and MetS prevalence. This study aimed to examine the association between age and the prevalence of MetS based on multiple screening criteria and MetS components by sex. Methods We used 6 years of individual-level longitudinal follow-up data (June 2012 to November 2018; checkup year: 2012–2017) of middle-aged and older adults aged 40–75 years in Japan (N = 161,735). The Joint Interim Statement criteria, International Diabetes Federation criteria, and another set of criteria excluding central obesity were used as the screening criteria for MetS. The prevalence of MetS and MetS components was cross-sectionally analyzed according to sex and age. A longitudinal association analysis of age, MetS, and MetS components by sex was performed using a multilevel logistic model, adjusted for lifestyle- and regional-related factors. Results Sex differences were observed in the prevalence and association of MetS and MetS components. In all age groups, the prevalence of central obesity was higher among women, and the prevalence of high blood pressure and fasting glucose was higher among men (P 60 years (P 55 years (P

With over one-third of East Asia’s 1.7 billion people overweight or obese, mounting demographic pressure and burgeoning healthcare costs are forcing public health officials to grapple with the rising morbidity and mortality associated with obesity. However, the presence of metabolically healthy obesity, in which the short-term disease risks of diabetes and heart disease are low, represents a possible buffer for healthcare planning in East Asia. This narrative review analyzes the health risks from obesity through representative Japan- and China-specific analyses that take into account unique cultural, genetic, and other factors that drive obesity; the potential impact of metabolically healthy obesity on public health; and suggested non-surgical/non-pharmacological interventions to relieve pressure on the nationalized healthcare systems prevalent in the region. Such an emphasis on interventions to both delay obesity as well as potentially reverse metabolic syndrome could save millions of lives and billions of USD equivalents in healthcare throughout East Asia.

Abstract Aims/Introduction In Japan, the increasing frequency of underweight among women of reproductive age and the accompanying increase in the rate of low birth weight (LBW) are social issues. The study aimed to establish a prospective registry system for gestational diabetes mellitus (GDM) in Japan and to clarify the actual status of GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Materials and Methods Pregnant women with gestational diabetes mellitus and those in the normal glucose tolerance (NGT) group were enrolled in the Diabetes and Pregnancy Outcome for Mother and Baby study from October 2015. Pregnant women with positive glucose screening in early and mid‐to‐late pregnancy underwent a 75 g oral glucose tolerance test by gestational week 32. Gestational diabetes mellitus was diagnosed according to IADPSG criteria. Women with a positive glucose screening test at mid‐to‐late pregnancy but NGT were enrolled as references (NGT group). Treatment for gestational diabetes mellitus and maternal and neonatal pregnancy data were prospectively collected on outcomes. Results In total 1,795 singleton pregnancies (878 women with GDM and 824 NGT women) were analyzed. The risk of LBW and small‐for‐gestational age in the GDM group was significantly higher than in the NGT group. A similar relationship was found for LBW risk in the non‐overweight/obese group but not in the overweight/obese group. Conclusions We established a prospective GDM registry system in Japan. In the management of GDM in Japan, suppression of maternal weight gain may be associated with reduced fetal growth, especially in non‐overweight/obese women with GDM; however, further investigation is required.

Abstract Despite global consensus on the importance of screening pediatric delirium, correlations between pediatric delirium during acute brain injury and adult delirium are unclear. Therefore, we hypothesized that similar pediatric biomarkers reflect acute brain injury as in adult delirium. We observed pediatric cardiac surgery patients from neonatal age to 18 years, who were admitted to our pediatric intensive care unit after cardiovascular operations between October 2019 to June 2020, up to post-operative day 3 (4 days total). We recorded age, sex, risk score (Risk Adjustment in Congenital Heart Surgery [RACHS-1]), midazolam/dexmedetomidine/fentanyl dosage, and pediatric Sequential Organ Failure Assessment (pSOFA). Richmond Agitation-Sedation Scale (RASS), Cornell Assessment of Pediatric Delirium (CAPD), Face, Leg, Activity, Consolability (FLACC) behavioral scale, and Withdrawal Assessment Tool (WAT-1) scales were used and serum sampling for neuron specific enolase (NSE) was conducted. Consciousness status was considered hierarchical (coma > delirium > normal) and associations between conscious status and NSE were conducted by hierarchical Bayesian modeling. We analyzed 134 data points from 40 patients (median age 12 months). In the multi-regression model, NSE was positively associated with coma [posterior odds ratio (OR) = 1.1, 95% credible interval (CrI) 1.01–1.19] while pSOFA [posterior OR = 1.63, 95% CrI 1.17–2.5], midazolam [posterior OR = 1.02, 95% CrI 1.01–1.04], and dexmedetomidine [posterior OR = 9.52, 95% CrI 1.02–108.85] were also associated. We also evaluated consciousness state probability at each NSE concentration and confirmed both that consciousness was hierarchically sorted and CAPD scores were also associated with NSE [posterior OR = 1.32, 95% CrI 1.09–1.58]. “Eye contact” (r = 0.55) was the most correlated component with NSE within the pain, withdrawal syndrome, and PD items. PD within the hierarchy of consciousness (coma, delirium, normal) and CAPD scores are associated with brain injury marker levels. Using pediatric delirium assessment tools for monitoring brain injury, especially eye contact, is a reliable method for observing PD.

Abstract Triple negative breast cancer (TNBC) is associated with worse outcomes and results in high mortality; therefore, great efforts are required to find effective treatment. In the present study, we suggested a novel strategy to treat TNBC using mesenchymal stem cell (MSC)-derived extracellular vesicles (EV) to transform the behaviors and cellular communication of TNBC cells (BCC) with other non-cancer cells related to tumorigenesis and metastasis. Our data showed that, BCC after being internalized with EV derived from Wharton’s Jelly MSC (WJ-EV) showed the impaired proliferation, stemness properties, tumorigenesis and metastasis under hypoxic conditions. Moreover, these inhibitory effects may be involved in the transfer of miRNA-125b from WJ-EV to BCC, which downregulated the expression of HIF1α and target genes related to proliferation, epithelial-mesenchymal transition, and angiogenesis. Of note, WJ-EV-internalized BCC (wBCC) showed transformed behaviors that attenuated the in vivo development and metastatic ability of TNBC, the angiogenic abilities of endothelial cells and endothelial progenitor cells and the generation of cancer-associated fibroblasts from MSC. Furthermore, wBCC generated a new EV with modified functions that contributed to the inhibitory effects on tumorigenesis and metastasis of TNBC. Taken together, our findings suggested that WJ-EV treatment is a promising therapy that results in the generation of wBCC to interrupt the cellular crosstalk in the tumor environment and inhibit the tumor progression in TNBC.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Objective: Pericardial effusion after cardiac surgery remains an important cause of morbidity and mortality. We describe the risk factors of pericardial effusion after congenital heart surgery through analyzing data from a nationwide, multi-institutional registry. Methods: The Japan Congenital Cardiovascular Surgery Database, which reflects routine clinical care in Japan, was used for this retrospective cohort study. Multivariable regression analysis was done after univariable comparison of patients with pericardial effusion and no pericardial effusion. Results: The study enrolled 64,777 patients registered with the Japan Congenital Cardiovascular Surgery Database between 2008 and 2016; 909 of these had postoperative pericardial effusion (1.4%) and were analyzed along with 63,868 patients without pericardial effusion. Univariable analysis found no difference between the groups in terms of gender, early delivery, or preoperative mechanical ventilatory support. In the pericardial effusion group, cardiopulmonary bypass use was lower (58.4% vs 62.1%), whereas the cardiopulmonary bypass time (176.9 vs 139.9 minutes) and aortic crossclamp time (75.1 vs 62.2 minutes) were longer, and 30-day mortality was higher (4.1% vs 2.2%). Multivariable analysis identified trisomy 21 (odds ratio, 1.54), 22q.11 deletion (odds ratio, 2.17), first-time cardiac surgery (odds ratio, 2.01), and blood transfusion (odds ratio, 1.43) as independent risk factors of postoperative pericardial effusion. In contrast, neonates, infants, ventricular septal defect, atrial septal defect, tetralogy of Fallot repair, and arterial switch operation were correlated with a low risk of pericardial effusion development. Conclusions: The incidence of postoperative pericardial effusion in congenital cardiac surgery was 1.4%. Trisomy 21, 22q.11 deletion, first-time cardiac surgery, and blood transfusion were identified as the principal factors predicting the need for pericardial effusion drainage.

Abstract Background Japan is one of the Organization for Economic Co-operation and Development (OECD) countries where population aging and increasing health care expenditures (HCE) are urgent issues. Recent studies have identified factors other than age, such as proximity to death and morbidity, as contributing factors to the increase in medical costs. It is important to assess HCE by disease and analyze their factors to estimate and improve future HCE. Methods We extracted individual records spanning approximately 2 years prior to the death of persons aged 65 to 95 years from the National Health Insurance data in Japan, and used a Bayesian approach to decompose monthly HCE into five disease groups (circulatory, chronic kidney disease, neoplasms, respiratory, and others). The relationship between the proximity to death and the average HCE in each disease group was stratified by sex and age and analyzed using a descriptive statistical method similar to the two-part model. Results The average HCE increased rapidly as death approached in most disease groups, but the increase-pattern differed greatly among disease groups, sex, and age groups. The effect of proximity to death on average HCE was small for chronic diseases, but large for lethal diseases. When stratified by age and sex, younger and male decedents tended to have higher average HCE, but the extent of this varied by disease group. The two-year cumulative average HCE for neoplasms in the 65–75 years age group was about six times larger than those in the 85–95 years age group. Conclusions In Japan, it was suggested that disease, proximity to death, age, and sex may contribute to HCE. However, these factors interact in a complex manner, and it is important to analyze HCE by disease. In addition, preventing or delaying the severity of diseases with high medical burdens in younger people may be effective in reducing future terminal care costs. These findings have important implications for future projections and improvements of HCE.

COVID-19 has a wide range of clinical presentations, and the susceptibility to SARS-CoV-2 infection and the mortality rate also vary by region and ethnicity. Here, we found that rs12329760 in the TMPRSS2 gene, a missense variant common in East Asian populations, contributes to protection against SARS-CoV-2 infection. TMPRSS2 is a protease responsible for SARS-CoV-2 entry and syncytium formation. rs12329760 (c.478G>A, p. V160M) was associated with a reduced risk of moderate symptoms. The enzymatic activity of Met160-TMPRSS2 was lower than that of Val160-TMPRSS2, and thus the viral entry and the syncytium formation of SARS-CoV-2 were impaired. Collectively, these results indicate that the genetic variation in TMPRSS2, which is common in East Asians, is one of the molecular determinants of COVID-19 susceptibility.

Abstract Background Obese pregnant women are known to experience poorer pregnancy outcomes and are at higher risk of postnatal arteriosclerosis. Hence, weight control during and after pregnancy is important for reducing these risks. The objective of our planned randomized controlled trial is to evaluate whether the rate of change in body weight in obese women before pregnancy to 12 months postpartum would be lower with the use of an intervention consisting of Internet of Things (IoT) devices and mobile applications during pregnancy to 1 year postpartum compared to a non-intervention group. Methods Women will be recruited during outpatient maternity checkups at four perinatal care institutions in Japan. We will recruit women at less than 30 weeks of gestation with a pre-pregnancy body mass index ≥ 25 kg/m2. The women will be randomly assigned to an intervention or non-intervention group. The intervention will involve using data (weight, body composition, activity, sleep) measured with IoT devices (weight and body composition monitor, activity, and sleep tracker), meal records, and photographs acquired using a mobile application to automatically generate advice, alongside the use of a mobile application to provide articles and videos related to obesity and pregnancy. The primary outcome will be the ratio of change in body weight (%) from pre-pregnancy to 12 months postpartum compared to before pregnancy. Discussion This study will examine whether behavioral changes occurring during pregnancy, a period that provides a good opportunity to reexamine one's habits, lead to lifestyle improvements during the busy postpartum period. We aim to determine whether a lifestyle intervention that is initiated during pregnancy can suppress weight gain during pregnancy and encourage weight loss after delivery. Trial registration UMIN: UMIN (University hospital Medical Information Network) 000,041,460. Resisted on 18th August 2020. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047278

Introduction: The therapeutic effects of endothelial progenitor cells (EPC) in neovascularization have been suggested; however, to date, few studies have been conducted on the ability of EPC-derived extracellular vesicles (EV) to rescue the ischemic tissues. In order to examine the functional sources of EV for cell-free therapy of ischemic diseases, we compared the functions of EPC-EV and those of Wharton’s Jelly-derived mesenchymal stem cell (WJ-EV) in the flap mouse model.Results and conclusion: Our results demonstrated that in the intravenous injection, EPC-EV, but not WJ-EV, were uptaken by the ischemic tissues. However, EPC-EV showed poor abilities to induce neovascularization and the recovery of ischemic tissues. In addition, compared to EPC-EV, WJ-EV showed a higher ability to rescue the ischemic injury when being locally injected into the mice. In order to induce the secretion of high-functional EPC-EV, EPC were internalized with hypoxic pre-treated WJ-EV, which resulted in a transformed hwEPC. In comparison to EPC, hwEPC showed induced proliferation and upregulation of angiogenic genes and miRNAs and promoted angiogenic ability. Interestingly, hwEPC produced a modified EV (hwEPC-EV) that highly expressed miRNAs related to angiogenesis, such as miR-155, miR-183, and miR-296. Moreover, hwEPC-EV significantly induced the neovascularization of the ischemic tissues which were involved in promoting the proliferation, the expression of VEGF and miR-183, and the angiogenic functions of endothelial cells. Of note, hwEPC-EV were highly uptaken by the ischemic tissues and showed a greater effect with regard to inducing recovery from ischemic injury in the intravenous administration, compared to EPC-EV. Therefore, hwEPC-EV can be considered a functional candidate for cell-free therapy to treat the distal ischemic tissues.

Robotic surgery is considered to be the optimal means of performing nerve-sparing radical hysterectomy (RH) because this procedure requires very precise surgery. Nerve-sparing RH has become increasingly popular in Japan. However, with open surgery the operating field is only visible to the surgeon performing this delicate procedure, which makes it difficult to educate trainee assistants. However, robotic surgery provides an expanded operation field that is visible to the surgeon and assistants, which makes it suitable for teaching purposes. To perform this procedure, it is necessary to become proficient in RH by laparotomy and then to become familiar with the characteristics of robotic surgery. In shifting from laparotomy to robotic surgery, we have found that experience with open surgery does not fully prepare surgeons for the new experiences and discoveries associated with robotic surgery, which may initially be problematic. We here provide clear instructions for the procedure with notes concerning particular potentially problematic aspects.

Hysterectomy for placenta percreta with bladder invasion is a difficult operation because of the high possibility of massive bleeding; therefore, surgery should be performed in a facility equipped with a sufficient number of trained staff. The degree of bladder invasion should be assessed correctly before the operation, and it is necessary to carefully consider how to address intraoperative complications and massive bleeding in the preoperative conference. The following should be prepared preoperatively: autologous blood and stored blood; ureteral catheter and insertion materials; materials to separate and tape the internal iliac artery and ureter; balloon for insertion into the common iliac artery or aorta and aortic clamps; and materials for compression suturing, such as B-Lynch suture. Sufficient informed patient consent is also required. During surgery, which may cause massive and sometimes life-threatening bleeding, the general rule is to begin at a safe site without adhesions and then treat the adhesion site. According to this rule, bladder dissection should be performed last in cases of placenta percreta with bladder invasion. As a surgical technique using this principle, we introduce retrograde hysterectomy approaching from the posterior vaginal wall.

Abstract Aims/Introduction To compare pregnancy outcomes between women with gestational diabetes mellitus (GDM) diagnosed early and late in pregnancy in Japan. Materials and Methods We examined women diagnosed with GDM in this multi‐institutional retrospective study. Women were divided into two groups by gestational age at diagnosis:

Abstract Aims/Introduction To evaluate the differences in the results of 75‐g oral glucose tolerance tests (OGTTs) according to gestational age in Japan. Materials and Methods In this prospective cohort study, 2,578 pregnant women were divided into three categories based on their gestational age during the 75‐g OGTT:

Abstract Background Previous studies have shown a relationship between delirium and depressive symptoms after cardiac surgery with distress personalities linking to negative surgical outcomes. The aim of the present study is to further investigate the association between patients with Type D (distressed) personality with regards to delirium after cardiac surgery. Methods We conducted a consecutive-sample observational cohort pilot study with an estimated 142 patients needed. Enrollment criteria included patients aged ≥18 years who were undergoing planned cardiovascular, thoracic and abdominal artery surgery between October 2015 to August 2016 at the University of Tsukuba Hospital, Japan. All patients were screened by Type-D Personality Scale-14 (DS14) as well as the Hospital Anxiety and Depression Scale (HADS) the day before surgery. Following surgery, daily data was collected during recovery and included severity of organ dysfunction, sedative/analgesic exposure and other relevant information. We then evaluated the association between Type D personality and delirium/coma days (DCDs) during the 7-day study period. We applied regression and mediation modeling for this study. Results A total of 142 patients were enrolled in the present study and the total prevalence of delirium was found to be 34% and 26% of the patients were Type D. Non-Type D personality patients experienced an average of 1.3 DCDs during the week after surgery while Type D patients experienced 2.1 days over the week after surgery. Multivariate analysis showed that Type D personality was significantly associated with increased DCDs (OR:2.8, 95%CI:1.3–6.1) after adjustment for depressive symptoms and clinical variables. Additionally, there was a significant Type D x depression interaction effect (OR:1.7, 95% CI:1.2–2.2), and depressive symptoms were associated with DCDs in Type D patients, but not in non-Type D patients. Mediation modeling showed that depressive symptoms partially mediated the association of Type D personality with DCDs (Aroian test =0.04). Conclusions Type D personality is a prognostic predictor for prolonged acute brain dysfunction (delirium/coma) in cardiovascular patients independent from depressive symptoms and Type D personality-associated depressive symptoms increase the magnitude of acute brain dysfunction.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the endogenous antioxidant response to reactive oxygen species as well as a controller of Phase II detoxification in response to xenobiotics. This amenity to specific external manipulation exploits the binding affinity of Nrf2 for its constitutive repressor and degradation facilitator Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1). Derived from both natural and synthesized origins, these compounds have been extensively tested without definitive beneficial results. Unfortunately, multiple terminated trials have shown a negative side to Nrf2 with regard to cardiac pathologies while animal-based studies have demonstrated cardiomyocyte hypertrophy and heart failure after chronic Nrf2 upregulation. Putatively based on autophagic control of Nrf2 activity-modulating upstream factors, new evidence of miRNA involvement has added complexity to this mechanism. What follows is an extensive survey of Nrf2-regulating exogenous compounds that may promote cardiomyopathy, clinical trial evidence, and a comparison to exercise-induced factors that also upregulate Nrf2 while preventing cardiac pathologies.

The East Asian region (China, Japan, and South Korea) is comprised of almost 1.5 billion people and recent industrialization has brought with it a pandemic of rising obesity, even in children. As these countries are rapidly aging and functioning at sub-replacement birthrates, the burgeoning costs of obesity-related care may threaten socialized healthcare systems and quality of life. However, a condition called metabolically healthy obesity (MHO) has been found to be without immediate cardiopulmonary or diabetic risk. Thus, maintenance of the MHO condition for the obese in East Asia could buffer the burden of long-term obesity care on medical systems and knowledge of the biochemical, genetic, and physiological milieu associated with it could also provide new targets for intervention. Diverse physiological, psychological, environmental, and social factors play a role in obesogenesis and the transition of MHO to a metabolically unhealthy obesity. This review will give a broad survey of the various causes of obesity and MHO, with special emphasis on the East Asian population and studies from that region.

In patients with uterine myomas undergoing cesarean section, the site of the uterine incision differs depending on the location, size, and number of myomas and the location of the placenta. The difficulty is particularly high when the myomas are located on the anterior wall of the cervix. In all patients, safe fetal birth is the top priority. The incision is usually made to avoid uterine myomas, and enucleation of the myomas is performed after fetal birth. However, in some patients, the fetus must be delivered after enucleating the myomas, so practice is necessary to be prepared for such cases. In this report, I explain the critical points to be noted at the time of cesarean section, especially in patients with myomas located on the anterior wall of the cervix.

Cesarean section is the ultimate method of successful delivery of infants under various circumstances and is an indispensable operation in obstetrics. However, the degree of difficulty varies greatly depending on the gestational weeks, number of fetuses, number of previous cesarean sections, degree of placental adhesion, presence of uterine myomas, maternal obesity, and other factors. In addition, emergency cesarean section is a battle against time, and prompt surgery is required. During training in cesarean section, surgeons must master the basic techniques in cases of term head presentation first. They must then master the techniques in cases involving complications such as malpresentation, preterm birth, placenta previa, abruptio placentae, uterine myomas, and other conditions. Cesarean section itself is a simple operation. However, there are many difficult cases, and many complications such as placenta accreta and defects of the incision scar may occur after cesarean section. The present report describes the basic procedures and cautionary points to perform the cesarean section without complications.

Myomectomy for diffuse leiomyomatosis and giant fibroid exceeding 30 cm in length is a particularly difficult operation. For diffuse leiomyomatosis, what kind of incision is put in and nucleated, how to suture the wound is a problem. In the case of giant fibroids, the degree of difficulty varies greatly depending on the site, size, and number of fibroid. The points should be taken into account at the time of surgery are as follows: (1) how to incision because incision becomes long, (2) how to remove multiple fibroids together, reduce incisional wounds, and reconstruct the uterus, (3) how to reduce the bleeding, how to suture not to leave a dead space. From the preoperative magnetic resonance imaging findings for each case, we will conduct surgery as far as possible to simulate, but, in fact, it is necessary to judge instantaneously at the time of laparotomy. It is necessary to see many difficult operations and acquire the judgment ability.

Hysterectomy for cervical and intraligamental fibroids is particularly likely to cause massive bleeding, ureteral/bladder injury, and intestinal damage. In such cases, preoperative evaluation is very important, and the way in which surgery proceeds should be based on the preoperative evaluation findings. In other words, before starting surgery, it is important to discuss what second and third methods to use if the first surgical method is unsuccessful. The main points to consider during surgery are expanding the operative field, approaching the operation from a site with weak adhesions, and performing applied techniques such as myomectomy and retrograde hysterectomy.

Asthma is a life-altering, chronic disease of heterogenous origin that features a complex interplay of immune and environmental signaling. Although very little progress has been made in prevention, diverse types of medications and delivery systems, including nanoscale systems, have been or are currently being developed to control airway inflammation and prevent exacerbations and fibrosis. These medications are delivered through mechanical methods, with various inhalers (with benefits and drawbacks) existing, and new types offering some variety in delivery. Of particular interest is the progress being made in nanosized materials for efficient penetration into the epithelial mucus layer and delivery into the deepest parts of the lungs. Liposomes, nanoparticles, and extracellular vesicles, both natural and synthetic, have been explored in animal models of asthma and have produced promising results. This review will summarize and synthesize the latest developments in both macro-(inhaler) and micro-sized delivery systems for the purpose of treating asthma patients.

Abstract Background The purposes of this study were to identify 1) the feasibility of a novel exercise protocol (elderly Japanese male version of high-intensity interval aerobic training: EJ-HIAT) and 2) its preliminary data (%V̇O2peak, rating of perceived exertion) in comparison with traditional moderate-intensity continuous aerobic training (MICT). Results Twenty-one sedentary elderly men, aged 60–69 years, performed two exercise protocols: EJ-HIAT, consisting of 3 sets of 2−3-min cycling at 75−85%V̇O2peak with 1− 2-min active rests at 50%V̇O2peak between sets, and MICT, consisting of 40-min cycling at 65%V̇O2peak. The completion rate, defined as the rate of participants who 1) did not demand withdrawal, 2) were not interrupted by the tester, and 3) did not change the workload during either exercise protocol, of EJ-HIAT was similar to that of MICT (EJ-HIAT: 100%, MICT: 95.2%). Maximal perceived exertion ratings assessed by Borg scale were also similar between EJ-HIAT and MICT. However, objectively measured maximal intensity assessed by %V̇O2peak was higher for EJ-HIAT than for MICT (EJ-HIAT: 86.0 ± 5.6%, MICT: 67.1 ± 6.4%). Conclusion These results suggested that EJ-HIAT has good feasibility and perceived exertion similar to MICT despite having higher objectively measured intensity than MICT. An intervention aimed as identifying the effects of EJ-HIAT on exercise tolerance should be performed in the future. Trial registration UMIN000021185 (February 26, 2016).

The basic procedure of abdominal hysterectomy is extrafascial hysterectomy, and intrafascial hysterectomy (Aldridge operation) and retrograde hysterectomy are performed as applied surgical procedures. The Aldridge operation and retrograde hysterectomy are performed when strong adhesion is present around the uterus. Retrograde hysterectomy is also useful when the cervicovaginal junction is not clearly felt by palpation, such as when uterine rupture immediately occurs after vaginal delivery or when a large tumor mass is present in the vagina.

Abstract Total abdominal hysterectomy (TAH) is commonly referred to as extrafascial hysterectomy. This article explains the basic surgical procedure of TAH as taught to residents. TAH is an operation to remove the uterus with the outer wall of the uterus, and is a fundamental operation that gynecologists must master. Possible complications during TAH include ureteral injury, intestinal damage, and bladder injury. To avoid operative complications, it is important to follow the correct release layer procedure and ensure that “the uterus has been naturally removed.” The two most important points of the authors' method to avoid complications are as follows: (1) cut sequentially from the ligament away from the ureter which moves the ureter further away from the cervix with each transection stage; (2) cut the parametrial tissue along the circumference of the cervix in the next three steps: First step: clamping and cutting the uterine artery and upper part of the cardinal ligament; second step: clamping and cutting the sacrouterine ligament and the posterior half of the cardinal ligament; third step: clamping and cutting the vesicouterine ligament and anterior half of the cardinal ligament.

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy. Because CSP carries a high risk of uterine rupture and life-threatening bleeding, the pregnancy should be terminated upon confirmation of diagnosis. There have been few reports of CSP with successful delivery. We present a case of CSP under expectant management, with delivery via planned cesarean section at 35 weeks of gestation. This report suggests that successful pregnancy outcome can be achieved in some women with uterine cesarean scar, but further analysis and additional studies are required in order to describe the optimal protocol of expectant management in CSP.

The molecular characterization of endometrial cancer (EC) can facilitate identification of various tumor subtypes. Although EC patients with POLE mutations reproducibly demonstrate better prognosis, the outcome of patients with microsatellite instability (MSI) remains controversial. This study attempted to interrogate whether genetic stratification of EC can identify distinct subsets with prognostic significance.A cohort of 138 EC patients who underwent surgical resection with curative intent was enrolled. Sanger sequencing was used to evaluate mutations in the POLE and KRAS genes. MSI analysis was performed using four mononucleotide repeat markers and methylation status of the MLH1 promoter was measured by a fluorescent bisulfite polymerase chain reaction (PCR). Protein expression for mismatch repair (MMR) proteins was evaluated by immunohistochemistry (IHC).Extensive hypermethylation of the MLH1 promoter was observed in 69.6% ECs with MLH1 deficiency and 3.5% with MMR proficiency, but in none of the ECs with loss of other MMR genes (P < .0001). MSI-positive and POLE mutations were found in 29.0% and 8.7% EC patients, respectively. Our MSI analysis showed a sensitivity of 92.7% for EC patients with MMR deficiency, and a specificity of 97.9% for EC patients with MMR proficiency. In univariate and multivariate analyses, POLE mutations and MSI status was significantly associated with progression-free survival (P = 0.0129 and 0.0064, respectively) but not with endometrial cancer-specific survival.This study provides significant evidence that analyses of proofreading POLE mutations and MSI status based on mononucleotide repeat markers are potentially useful biomarkers to identify EC patients with better prognosis.

Hypertrophic obstructive cardiomyopathy (HOCM) is cardiac hypertrophy of ventricular myocardium with left ventricular outflow tract obstruction. We report a pregnancy with HOCM after defibrillator implantation surgery. The patient was a 33-year-old nulligravida and was categorized as New York Heart Association class II. Her brain natriuretic peptide (BNP) level was 724.6 pg/dL at preconception. She received careful pregnancy management. However, because frequent uterine contractions were observed at 25 weeks and 6 days of pregnancy, she was hospitalized, and magnesium sulfate was started as a tocolytic agent. At 27 weeks and 5 days of pregnancy, she had respiratory discomfort and orthopnea with a sudden decrease in peripheral oxygen saturation. Cardiac ultrasonography showed a worsened condition of HOCM and her BNP level was 1418.0 pg/mL. We performed an emergent cesarean section and she delivered a boy weighing 999 g. The Apgar score was 8 and 9 points at 1 and 5 minutes, respectively. The mother’s heart failure quickly improved after birth and she was discharged at 10 days postoperatively. Fluctuations in circulatory dynamics during pregnancy may sometimes exacerbate heart disease. Therefore, the risks should be fully explained and careful assessment of cardiac function should be performed during pregnancy in patients with severe HOCM.

Cases of cardiac metastasis from uterine cervical carcinoma are rare. While they are occasionally found on autopsy, antemortem recognition is extremely rare. We confirmed a case of cardiac metastasis from cervical carcinoma antemortem, because we observed a decrease in platelet count during the course of treatment. The patient was a 27-year-old woman diagnosed with stage Ib1 uterine cervical carcinoma. Radical hysterectomy with pelvic lymphadenectomy was performed. Para-aortic lymph node metastasis was detected on positron emission tomography/computed tomography (PET-CT). Adjuvant chemotherapy was started, and most of the metastatic lesions disappeared. Pelvic lymph node recurrence was suspected on PET-CT during continued chemotherapy; therefore, treatment was shifted to radiation therapy. Tumor shrinkage was recognized, and the initial therapy was completed. A noticeable decrease in platelet count was recognized seven months after treatment. Multidetector CT was performed, and an intracardiac tumor was detected. The patient did not desire any further treatment. She died three weeks after the intracardiac tumor was confirmed. Few previous autopsy studies have reported cardiac metastasis from cervical carcinoma. Thus, it is necessary to consider the possibility of cardiac metastasis for patients diagnosed with terminal cervical carcinoma.

Myocardial perforation by a pacing lead occurred 12 days after implantation. The lead was propelled into the myocardium of the anterior wall of ventricles without passing through the left ventricular cavity, and finally protruded into the pericardial cavity. Computed tomography of the chest was helpful for confirming the perforation by the pacing lead.

Recent reports indicated that nutrition in early infancy might influence later child health outcomes such as obesity and metabolic syndrome. Therefore, we examined the effects of maternal high fat diet (HFD) during lactation on the onset of a metabolic syndrome in their offspring. All offspring were cross-fostered by dams on the same or opposite diet to yield 4 groups: offspring from HFD-fed dams suckled by HFD-fed dams (OHH) and by control diet (CD)-fed dams (OHC) and CD-fed dams suckled by HFD-fed dams (OCH) and by CD-fed dams (OCC) mice. We examined several metabolic syndrome-related factors including body weight, blood pressure, glucose tolerance and adipocytokines. Mean body weights of OHH and OCH mice were significantly higher than those of OHC and OCC mice, respectively, with elevated systolic blood pressure. Moreover, OHH and OCH mice revealed significantly worse glucose tolerance compared with the OHC and OCC mice, respectively. Triglyceride and leptin levels were significantly increased and adiponectin levels were significantly reduced by the maternal HFD during lactation, with similar changes in leptin and adiponectin mRNA expression but without histone modifications in adipose tissues. In addition, maternal obesity induced by HFD during lactation increased and prolonged the leptin surge in the offspring and the gender differences of leptin surge were observed. Our data suggested that maternal HFD during lactation might have an additive effect on the onset of the metabolic syndrome in the offspring, irrespective of the nutritional status in utero through the modified leptin surge.

Introduction. The objective is to report a case of Cornelia de Lange syndrome (CdLS) diagnosed by detailed observations using three-dimensional sonography. Case Report. A 33-year-old healthy multipara was referred to our hospital at 34-week gestation after severe fetal growth restriction, congenital heart anomaly, and antebrachium abnormality were diagnosed during the third trimester. Further sonography diagnosis on cardiac abnormalities diagnosed the existence of ventricular septal defect in the outflow tract, atrioventricularis communis, and truncus arteriosus communis where the pulmonary artery branched from the common arterial trunk. As for abnormalities of the forearms, ectrodactylia and monodactylism were suspected and the abnormalities were observed sterically by using three-dimensional sonography. A 1986 g (1.07 percentile) male newborn was delivered by assisted breech extraction at 37-week gestation. After birth, from characteristic facies including bushy eyebrow, broad nasal bridge, micrognathia, and abnormalities of the forearms (ectrodactylia and monodactylism), the case was diagnosed with CdLS. Conclusion. Through detailed observation including abnormalities of fingers, we could exemplify this very rare disease as an antenatal diagnoses for fetal growth retardation.