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Background: We developed a high-intensity parenting intervention (HIP) to help parents support the academic success of childhood cancer survivors (CCSs), who often face post-treatment challenges affecting their school-related functioning. This randomized controlled trial (NCT03178617) evaluated HIP's efficacy compared to lower-intensity, single-session, treatment-as-usual services (LIP) in Latino families. Primary outcomes were parenting efficacy and CCSs' school functioning; secondary outcomes included parenting knowledge and measures of CCSs' academic performance, attention, and functioning outside of school., Methods: 106 Latino survivors of childhood leukemia and lymphoblastic lymphoma (aged 6-12 years) and their parents were randomly assigned to HIP (n = 54) or LIP (n = 52). Linear mixed-effects models evaluated group differences across baseline, 6-month (T2), and 12-month (T3) assessments., Results: Parenting efficacy and knowledge improved significantly in the HIP arm, resulting in higher scores vs LIP at T2 and T3 (P ≤ .01). No significant between-group differences were found in child school functioning; however, HIP children showed significantly better social functioning and performance on one measure of attention (CPT-3 commissions) at T3 (P < .05). While HIP adherence challenges were observed, with only 33 (61%) completing the intervention, exploratory analyses suggest that benefits were most evident among those who fully engaged. Satisfaction and perceived benefit were greater for HIP vs LIP at both time points (P < .05)., Conclusions: Our results suggest the potential value of parent-directed behavioral interventions like HIP for CCSs and their families. Further studies are needed to address participation barriers and enhance engagement to maximize and sustain benefits., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The risk of inducing hypoglycaemia (low blood glucose) constitutes the main challenge associated with insulin therapy for diabetes 1,2 . Insulin doses must be adjusted to ensure that blood glucose values are within the normal range, but matching insulin doses to fluctuating glucose levels is difficult because even a slightly higher insulin dose than needed can lead to a hypoglycaemic incidence, which can be anything from uncomfortable to life-threatening. It has therefore been a long-standing goal to engineer a glucose-sensitive insulin that can auto-adjust its bioactivity in a reversible manner according to ambient glucose levels to ultimately achieve better glycaemic control while lowering the risk of hypoglycaemia 3 . Here we report the design and properties of NNC2215, an insulin conjugate with bioactivity that is reversibly responsive to a glucose range relevant for diabetes, as demonstrated in vitro and in vivo. NNC2215 was engineered by conjugating a glucose-binding macrocycle 4 and a glucoside to insulin, thereby introducing a switch that can open and close in response to glucose and thereby equilibrate insulin between active and less-active conformations. The insulin receptor affinity for NNC2215 increased 3.2-fold when the glucose concentration was increased from 3 to 20 mM. In animal studies, the glucose-sensitive bioactivity of NNC2215 was demonstrated to lead to protection against hypoglycaemia while partially covering glucose excursions., (© 2024. The Author(s).)

Objective: To investigate the association between prolonged oligohydramnios and a composite outcome of death or severe neurodevelopmental impairment (NDI) at 3 years of age., Methods: This single-center retrospective cohort study enrolled infants born at 22-29 weeks of gestational age without major congenital anomalies. The patients were classified into three groups depending on the existence and duration of oligohydramnios: no/non-prolonged oligohydramnios (no or 0-7 days of oligohydramnios), prolonged oligohydramnios (8-14 days), and very prolonged oligohydramnios (> 14 days). The primary outcome was a composite of death or severe NDI, which was defined as severe cerebral palsy, developmental delay, severe visual impairment, or deafness at age 3., Results: Out of the 843 patients, 784 (93 %), 30 (3.6 %), and 29 (3.4 %) were classified into the no/non-prolonged, prolonged, and very prolonged oligohydramnios groups, respectively. After excluding patients lost to follow-up, the adverse composite outcome at 3 years of age was observed in 194/662 (29 %), 7/26 (27 %), and 8/23 (35 %) in the corresponding groups. The composite outcome showed no significant trend with the duration of oligohydramnios (P = 0.70). In a logistic regression model controlling the known predictors of gestational age, birth weight, small-for-gestational-age, male sex, multiple pregnancy, hypertensive disorders of pregnancy, antenatal corticosteroids, and the number of family-social risk factors, the duration of oligohydramnios was not independently associated with the composite outcome; odds ratio 1.3 (95 % confidence interval, 0.78-2.0)., Conclusion: Prolonged oligohydramnios was not associated with the composite outcome of death or severe NDI at 3 years of age., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Antimicrobial-resistant bacteria, selected by antimicrobial agent use in livestock, are emerging and their spread to crops from feces via composting represents a public health concern as they are ultimately transmitted to humans. In this study, we investigated Escherichia coli and other ampicillin (AMP)-resistant coliform spread conditions in field soil and dent corn, an agricultural crop, on a livestock-derived compost-applying farm. No AMP-resistant E. coli was detected in any samples of field soil and dent corn. In contrast, AMP-resistant and extended-spectrum β-lactam (ESBL) producing coliforms were consistently present in field soil and dent corn during the entire study period. In particular, extremely high AMP-resistant coliform levels were detected in dent corn stems and roots. AMP-resistant coliform detection in crops is pivotal and raises significant concerns regarding antimicrobial-resistant bacterial spread. Furthermore, AMP-resistant coliform isolate identification defined Enterobacter bugandensis and Enterobacter asburiae as the dominant species among AMP-resistant coliforms, both tested positive for ESBL production. This means that high concentrations of AMP-resistant coliforms are to be present on farms where crops are grown. However, we identified no common species among the AMP-resistant coliforms in the compost, field soil, and dent corn samples. Therefore, the initial hypothesis of the compost being the source of antimicrobial-resistant bacteria was not confirmed. Although their source remains unknown, a certain antimicrobial-resistant bacterial concentration could nonetheless be detected in the field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Demographic changes and a low birth rate have led to a workforce shortage in Japan. To address this issue, the government has promoted engagement of female employment. However, increased female employment can impact women's health. Using Internet of Things (IoT) and apps to manage women's health has gained attention, but few studies have focused on working women., Objective: This study aimed to clarify the current situation of working women and their use of IoT or apps to manage their health., Methods: A large-scale, nationwide internet survey was conducted among 10,000 female participants aged from 20 years to 64 years in Japan. Participants were recruited from a marketing research company's active survey panel of 5.24 million members. The survey included questions about health status, sociodemographic factors, psychological characteristics, and the use of IoT or apps for health management. We compared perceived health status and reasons for current IoT use using t tests and assessed participant characteristics that predicted IoT use using the C5.0 decision tree algorithm. Ethical approval was granted by St. Luke's International University., Results: Among participants, 14.6% (1455/10,000) currently used IoT or apps, 7% (695/10,000) used them previously, and 78.5% (7850/10,000) had never used them. Current users (42.7 years old) were older than past users (39.7 years old). Discrepancies were observed between participants' perceived health problems and the purpose for using IoT or apps, with 21.3% (2130/10,000) of all women reporting they experienced menstrual symptoms or disorders but only 3.5% (347/10,000) used IoT or apps to manage the same symptom. On the other hand, current users were more likely to use IoT or apps to manage nutrition-related problems such as underweight or obesity (405/1455, 27.8%). Device use was highest among current users, with 87.3% (1270/1455) using smartphones, 19.7% (287/1455) using smartwatches, and 13.3% (194/1455) using PCs. Decision tree analysis identified 6 clusters, the largest consisting of 81.6% (5323/6523) of non-IoT users who did not exercise regularly, while pregnant women were more likely to use IoT or apps., Conclusions: Our findings highlight the idea that woman with particular health problems (ie, menstrual symptoms or disorders and premenstrual syndrome) have lower use of IoT or apps, suggesting an unmet need for IoT and apps in specific areas., (©Kirio Sasayama, Etsuko Nishimura, Noyuri Yamaji, Erika Ota, Hisateru Tachimori, Ataru Igarashi, Naoko Arata, Daisuke Yoneoka, Eiko Saito. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 31.07.2024.)

Insulin icodec is a once-weekly insulin analogue that has a long half-life of approximately 7 days, making it suitable for once weekly dosing. The Insulin icodec molecule was developed based on the hypothesis that lowering insulin receptor affinity and introducing a strong albumin-binding moiety would result in a long insulin half-life, provided that non-receptor-mediated clearance is diminished. Here, we report an insulin clearance mechanism, resulting in the splitting of insulin molecules into its A-chain and B-chain by a thiol-disulphide exchange reaction. Even though the substitutions in insulin icodec significantly stabilise insulin against such degradation, some free B-chain is observed in plasma samples from minipigs and people with type 2 diabetes. In summary, we identify thiol-disulphide exchange reactions to be an important insulin clearance mechanism and find that stabilising insulin icodec towards this reaction significantly contributes to its long pharmacokinetic/pharmacodynamic profile., (© 2024. The Author(s).)

Aim: Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady-state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real-world clinical setting., Methods: A non-randomized, open-label, single-arm study examining drug-drug interactions was conducted. Fifteen dementia patients taking donepezil for at least 4 weeks and eight schizophrenia patients taking risperidone for at least 2 weeks were orally administered 2.5 g of yokukansan three times a day before or between meals, and blood samples were collected before and 8 weeks after starting co-treatment with yokukansan. Plasma concentrations of donepezil, risperidone, and each metabolite were measured using high-performance liquid chromatography-tandem mass spectrometry and compared before and after the 8-week administration of yokukansan., Results: The plasma concentrations of donepezil and its metabolites (6-O-desmethyl-donepezil, 5-O-desmethyl-donepezil, and donepezil-N-oxide), risperidone, and its metabolite paliperidone did not differ before and after the 8-week treatment with yokukansan., Conclusions: The findings of this study show that the concomitant use of yokukansan may have little clinical impact on the steady-state blood levels of donepezil and risperidone in patients with dementia or schizophrenia., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, is reported to promote fat metabolism. This study investigated whether PIC affects sirtuin 1 (SIRT1) expression and metabolic factors in C2C12 skeletal muscle cells. C2C12 myotubes were stimulated with PIC, and alterations in gene expression, protein levels, mitochondrial DNA content, and fatty acid levels were assessed using real-time PCR, Western blotting, and Nile red staining. Furthermore, we examined changes in SIRT1 expression following the consumption of a test food containing 100 mg PIC for 2 weeks among adults with varying age and body mass index ranges. Both PIC and passion fruit seed extract induced SIRT1 expression in C2C12 myotubes to a greater extent than resveratrol. PIC also increased the expression of genes associated with mitochondrial biogenesis and fatty acid utilization, increased mitochondrial DNA content, and suppressed oleic acid-induced fat accumulation. Moreover, participants who consumed PIC exhibited significantly higher SIRT1 mRNA expression in whole blood compared to those in the placebo group. These findings suggest that PIC induces SIRT1 expression both in vitro and in the human body, which may promote mitochondrial biosynthesis and fat metabolism.

Background: Intraocular lens (IOL) fixation is performed after intraoperative anterior or total vitrectomy. This study aimed to compare the intraoperative and postoperative complications of these two techniques., Methods: This retrospective study included 235 eyes that underwent intrascleral fixation surgery at our hospital between July 2014 and January 2021. The eyes were classified into the anterior vitrectomy group (A-vit group; 134 eyes) and the pars plana vitrectomy group (PPV group; 101 eyes). The age, preoperative and postoperative best-corrected visual acuity, observation period, preoperative and postoperative intraocular pressure, and the incidence of intraoperative and postoperative complications were assessed., Results: Intrascleral fixation was performed more frequently in the PPV group, and a significant difference was observed between the eyes with a history of vitrectomy and eyes with scleral buckles (p = 0.00041). In terms of the incidence of postoperative complications following intrascleral fixation, the incidence of low intraocular pressure postoperative was higher in the PPV group than that in the A-vit group, and a significant difference was observed between the two groups (p = 0.01)., Conclusions: The visual outcome and complications following intrascleral fixation did not differ according to the extent of vitreous excision., (© 2024. The Author(s).)

Horse obesity is a growing concern that can result in negative welfare. The role horse owners play in horse weight management is not well understood. This study aimed to: (1) explore the attitudes, beliefs, and perceptions of owners with overweight or obese horses regarding their horses' weight; and (2) understand the motivators and barriers for owners to implement, improve and maintain weight management-related strategies. A semi-structured interview guide based on the Theoretical Domains Framework was developed. Qualitative interviews were conducted with 24 owners in Prince Edward Island, Canada whose horse(s) were previously classified as overweight or obese by a veterinarian. Interviews were analysed using template analysis, organising patterns in the data into a codebook and overarching themes. Owners believed horse weight management was important, however, their perceived complexity of the issue made the implementation of the weight management practices difficult. Owners held conflicting perceptions, viewing overweight horses as well cared for, yet recognised these horses were at increased risk for negative health outcomes. Ultimately, participants felt emotionally torn about compromising their horse's mental well-being to address weight issues. Owners considered the practicality of weight-management strategies, the strategies' effectiveness, and whether recommended strategies aligned with their beliefs regarding good horse care practices. Knowledge was embedded into owners' understanding of horse weight, however, some highlighted that traditional knowledge dominates the equine industry hindering systemic industry change. Increased understanding of the effectiveness and impacts of weight management strategies on horses and fostering a society that recognises and accepts horses within a healthy weight range are warranted., Competing Interests: None., (© The Author(s) 2024.)

Esophageal cancer is common worldwide, including in Japan, and its major histological subtype is squamous cell carcinoma. However, there are some rare esophageal cancers, including neuroendocrine neoplasm, gastrointestinal stromal tumor, carcinosarcoma and malignant melanoma. The biological and clinical features of these cancers differ from those of esophageal squamous cell carcinoma. Therefore, different treatment strategies are needed for these cancers but are based on limited evidence. Neuroendocrine neoplasm is mainly divided into neuroendocrine tumor and neuroendocrine carcinoma by differentiation and the Ki-67 proliferation index or mitotic index. Epidemiologically, the majority of esophageal neuroendocrine neoplasms are neuroendocrine carcinoma. The treatment of neuroendocrine carcinoma is similar to that of small cell lung cancer, which has similar morphological and biological features. Gastrointestinal stromal tumor is known to be associated with alterations in the c-KIT and platelet-derived growth factor receptor genes and, if resectable, is treated in accordance with the modified Fletcher classification. Carcinosarcoma is generally resistant to both chemotherapy and radiotherapy and requires multimodal treatments such as surgery plus chemotherapy to achieve cure. Primary malignant melanoma is resistant to cytotoxic chemotherapy, but immune checkpoint inhibitors have recently demonstrated efficacy for malignant melanoma of the esophagus. This review focuses on the current status and future perspectives for rare cancer of the esophagus., (© The Author(s) 2023. Published by Oxford University Press.)

Background: The objective of this study was to predict when Bangladesh would achieve Sustainable Development Goal Target 3.1, which is to reduce the maternal mortality ratio (MMR) to less than 70 per 100 000 live births., Methods: We used secondary data from the 1993 to 2017 Bangladesh Demographic and Health Surveys and other sources to project the MMR until 2060 under several scenario assumptions using an autoregressive moving average model with exogenous variables (ARMAX). Explanatory variables were selected based on the three delays model, and a reference forecast and four practical scenarios were simulated: Scenario 1 assumed a 4% annual increase in institutional deliveries, Scenario 2 followed the national goals, the reference forecast and Scenario 3 varied in terms of district-wise increase rates (Scenario 3 had a lower rate of increase), and Scenario 4 assumed minimal changes in institutional deliveries., Results: Scenario 1 was the earliest, with an MMR of <70 per 100 000 live births in 2026. Scenario 2 would meet the target of <70 per 100 000 live births in 2029. The reference forecast had the third lowest MMR, with 69.78 per 100 000 live births (95% prediction intervals (PI) = 32.44 to 107.11) in 2049. Although the MMR for Scenario 3 decreased slowly, it would not reduce below 70 per 100 000 live births by 2060. Scenario 4, which had the highest MMR, also resulted in the MMR not reducing below 70 per 100 000 live births by 2060., Conclusions: To increase the institutional delivery rate and reduce the MMR, as in Scenarios 1 and 2, it is necessary to improve the institutional delivery rate in regions with low institutional delivery rates. Additionally, health facilities need to provide appropriate quality medical care to increase the institutional delivery rate and contribute to a decrease in the MMR, as shown by the results of this study., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Objective: We aimed to present the active management and outcomes of infants born at 22 weeks of gestation., Study Design: This retrospective observational study presented the resuscitation methods, management during hospitalization, and outcomes of 29 infants born at 22 weeks of gestation who were actively resuscitated and admitted to our center during 2013-2020., Results: The survival rate was 82.8% (24/29). Tracheal intubation was performed in all patients, and surfactant was administered for 27 (93.1%). Conventional mechanical ventilation was introduced in 27 (93.1%), and this was changed to high-frequency oscillatory ventilation in more than half by day 4. Surgical treatments of patent ductus arteriosus, necrotizing enterocolitis, and retinopathy of prematurity were required in 4 (13.7%), 3 (10.3%), and 15 (51.7%) patients, respectively. No patient required a tracheostomy or ventriculoperitoneal shunt., Conclusions: The overall survival rate and survival rate without morbidities were high among infants born at 22 weeks of gestation., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: This study aimed to synthesise available evidence on the efficacy of antenatal corticosteroid (ACS) therapy among women at risk of imminent preterm birth with pregestational/gestational diabetes, chorioamnionitis or fetal growth restriction (FGR), or planned caesarean section (CS) in the late preterm period., Methods: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Library, Web of Science and Global Index Medicus was conducted for all comparative randomised or non-randomised interventional studies in the four subpopulations on 6 June 2021. Risk of Bias Assessment tool for Non-randomised Studies and the Cochrane Risk of Bias tool were used to assess the risk of bias. Grading of Recommendations Assessment, Development and Evaluations tool assessed the certainty of evidence., Results: Thirty-two studies involving 5018 pregnant women and 10 819 neonates were included. Data on women with diabetes were limited, and evidence on women undergoing planned CS was inconclusive. ACS use was associated with possibly reduced odds of neonatal death (pooled OR: 0.51; 95% CI: 0.31 to 0.85, low certainty), intraventricular haemorrhage (pooled OR: 0.41; 95% CI: 0.23 to 0.72, low certainty) and respiratory distress syndrome (pooled OR: 0.59; 95% CI: 0.45 to 0.77, low certainty) in women with chorioamnionitis. Among women with FGR, the rates of surfactant use (pooled OR: 0.38; 95% CI: 0.23 to 0.62, moderate certainty), mechanical ventilation (pooled OR: 0.42; 95% CI: 0.26 to 0.66, moderate certainty) and oxygen therapy (pooled OR: 0.48; 95% CI: 0.30 to 0.77, moderate certainty) were probably reduced; however, the rate of hypoglycaemia probably increased (pooled OR: 2.06; 95% CI: 1.27 to 3.32, moderate certainty)., Conclusions: There is a paucity of evidence on ACS for women who have diabetes. ACS therapy may have benefits in women with chorioamnionitis and is probably beneficial in FGR. There is limited direct trial evidence on ACS efficacy in women undergoing planned CS in the late preterm period, though the totality of evidence suggests it is probably beneficial., Prospero Registration Number: CRD42021267816., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We have reported the possible benefits of radical esophagectomy with thoracic duct (TD) resection in elective esophageal cancer surgery. However, the effect of TD resection on the long-term nutrition status remains unclear., Methods: Patients who underwent esophagectomy at Keio University between January 2006 and December 2018 were included, and those who had no recurrence for more than three years were evaluated. Changes in each body composition (muscle mass and body fat) were comparatively assessed between those who underwent TD resection or not, before and at, one, three and five years after surgery. Computed tomography images were analyzed on postoperative year 1, 3 and 5., Results: This study included 217 patients categorized in the TD-resected (TD-R) (156 patients) and TD-preserved (TD-P) (61 patients) groups. The loss of muscle mass was comparable between the groups. On the other hand, the loss of adipose tissues was significantly greater in the TD-R group than in the TD-P group at one and three years after surgery, while there was no statistical difference five years after surgery. Additionally, among patients with cT1N0M0 disease in whom survival advantage of TD resection has been reported previously, the loss of muscle mass did not differ between each group., Conclusions: The change of muscle mass between the two groups was comparable. Although body fat mass was reduced by TD resection, it eventually recovered in the long term. In patients with esophageal cancer, TD resection may be acceptable without significant impact on body composition in the long term., (© The Author(s) 2023. Published by Oxford University Press.)

The COVID-19 pandemic has forced lifestyles changes and affected the relationships between fathers and their infants. However, the factors associated with paternal-infant bonding have not been clarified. This study aimed to explore the factors associated with father-infant bonding during the COVID-19 pandemic in Japan. This cross-sectional study used data from a nationwide survey and the Japanese version of the Mother-to-Infant Bonding Scale (MIBS) to measure father-infant bonding. The participants were divided into two groups depending on their partners' parity. A linear regression model (Gauss-Markov-type) was used for both groups. A total of 1055 men were included in the analysis. Of these men, 521 (49.4%) had a primipara partner, and 534 (50.6%) had a multipara partner. No significant differences were found between the two groups' MIBS-J scores. Fathers' mental health, relationship with the partner and family members, abusive behavior towards children, wanted pregnancy, and the youngest child's Neonatal Intensive Care Unit admission history were associated with father-infant bonding. Regarding factors related to COVID-19, caring for the child while the partner is at home has a negative impact on bonding, while fear related to infection with COVID-19 has no negative impact on bonding., (© 2023. Springer Nature Limited.)

Purpose: Systematic inflammation has been reported to contribute to cancer progression through various mechanisms; however, the exact mechanism is still the subject of research. In this study, we evaluated the influence of systematic inflammation on lung metastasis, using a murine abdominal sepsis model, and assessed its relationship with pneumonia after curative esophagectomy in patients with esophageal cancer., Methods: We used a murine abdominal sepsis model given highly metastatic osteosarcoma, to reveal the mechanism of systematic inflammation and its potential for lung metastasis. The therapeutic effect of aspirin (ASA) in preventing distant metastasis was also investigated. Subsequently, we analyzed, retrospectively, the relationship between pneumonia and lung metastasis after esophagectomy in patients who underwent esophagectomy at Keio University between January, 2007 and October, 2020., Results: Abdominal sepsis provoked lung injury in the acute phase. ASA inhibited the recruitment of neutrophils triggered by the lung injury, and it also suppressed lung metastasis. Our retrospective study revealed that lung metastasis was more frequent in patients with postoperative pneumonia., Conclusions: Postoperative acute lung injury is associated with a higher risk of lung metastasis. ASA may be a potential preoperative treatment for inhibiting lung metastasis by preventing the recruitment of neutrophils., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

The environmental disturbances in a critical neurodevelopmental period exert organizational effects on brain intrinsic plasticity including excitatory and inhibitory (E/I) neurotransmission those can cause the onset of psychiatric illness. We previously reported that treatment of neural precursor cells with N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 induced reduction of GABAergic interneuron differentiation, and these changes recovered by atypical antipsychotic blonanserin treatment in vitro. However, it remains unclear how this treatment affects neural circuit changes in hippocampus and amygdala, which might contribute to the prevention of onset process of schizophrenia. To elucidate the pathogenic/preventive mechanisms underlying prenatal environmental adversity-induced schizophrenia in more detail, we administered poly (I:C) followed by antipsychotics and examined alterations in social/cognitive behaviors, GABA/glutamate-related gene expressions with cell density and E/I ratio, and brain-derived neurotrophic factor (Bdnf) transcript levels, particularly in limbic areas. Treatment with antipsychotic blonanserin ameliorated impaired social/cognitive behaviors and increased parvalbumin (PV)-positive (+) cell density and its mRNA levels as well as Bdnf with long 3'UTR mRNA levels, particularly in the dorsal hippocampus, in rats exposed to maternal immune activation (MIA). Low dose of blonanserin and haloperidol altered GABA and glutamate-related mRNA levels, the E/I ratio, and Bdnf long 3'UTR mRNA levels in the ventral hippocampus and amygdala, but did not attenuate behavioral impairments. These results strongly implicate changes in PV expression, PV(+) GABAergic interneuron density, and Bdnf long 3'UTR expression levels, particularly in the dorsal hippocampus, in the pathophysiology and treatment responses of MIA-induced schizophrenia and highlight the therapeutic potential of blonanserin for developmental stress-related schizophrenia., Competing Interests: Declaration of competing interest None, (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We previously reported that endoscopic response evaluation can preoperatively predict the prognosis and distribution of residual tumors after neoadjuvant chemotherapy (NAC). In this study, we developed artificial intelligence (AI)-guided endoscopic response evaluation using a deep neural network to discriminate endoscopic responders (ERs) in patients with esophageal squamous cell carcinoma (ESCC) after NAC., Method: Surgically resectable ESCC patients who underwent esophagectomy following NAC were retrospectively analyzed in this study. Endoscopic images of the tumors were analyzed using a deep neural network. The model was validated with a test data set using 10 newly collected ERs and 10 newly collected non-ER images. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the endoscopic response evaluation by AI and endoscopists were calculated and compared., Results: Of 193 patients, 40 (21%) were diagnosed as ERs. The median sensitivity, specificity, PPV, and NPV values for ER detection in 10 models were 60%, 100%, 100%, and 71%, respectively. Similarly, the median values by the endoscopist were 80%, 80%, 81%, and 81%, respectively., Conclusion: This proof-of-concept study using a deep learning algorithm demonstrated that the constructed AI-guided endoscopic response evaluation after NAC could identify ER with high specificity and PPV. It would appropriately guide an individualized treatment strategy that includes an organ preservation approach in ESCC patients., (© 2023. Society of Surgical Oncology.)

Background: Hypoglycemia in type 1 diabetes (T1D) is associated with mortality and morbidity, especially when awareness of hypoglycemia is impaired. This study aimed to investigate the protective and risk factors for impaired awareness of hypoglycemia (IAH) in adults with T1D., Methods: This cross-sectional study enrolled 288 adults with T1D (mean age, 50.4 ± 14.6 years; male, 36.5%; diabetes duration, 17.6 ± 11.2 years; mean HbA1c level, 7.7 ± 0.9%), who were divided into IAH and non-IAH (control) groups. A survey was conducted to assess hypoglycemia awareness using the Clarke questionnaire. Diabetes histories, complications, fear of hypoglycemia, diabetes distress, hypoglycemia problem-solving abilities, and treatment data were collected., Results: The prevalence of IAH was 19.1%. Diabetic peripheral neuropathy was associated with an increased risk of IAH (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.13-5.91; P = 0.014), while treatment with continuous subcutaneous insulin infusion and hypoglycemia problem-solving perception scores were associated with a decreased risk of IAH (OR, 0.48; 95% CI, 0.22-0.96; P = 0.030; and OR, 0.54; 95% CI, 0.37-0.78; P = 0.001, respectively). There was no difference in continuous glucose monitoring use between the groups., Conclusion: We identified protective factors in addition to risk factors for IAH in adults with T1D. This information may help manage problematic hypoglycemia., Trial Registration: University hospital Medical Information Network (UMIN) Center: UMIN000039475). Approval date 13 February 2020., (© 2023. The Author(s).)

Soluble epoxide hydrolase (EC 3.3.2.10) is a key enzyme in the regulation of inflammation and metabolism, whereas, the role of its N-terminal phosphatase activity (N-phos) has been poorly understood because of a lack of selective inhibitors. Here we report 4-aminobenzoic (Ki 15.3 µm) and 3-amino-4-hydroxy benzoic acid (Ki 11.7 µm) as selective competitive inhibitors of N-phos., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: Women often experience many unique health issues and conditions throughout their working lives. The Internet of Things (IoT) is a system of interrelated digital devices that can enable data exchanges over a network without human-to-human or human-to-computer interaction. The usage of applications and IoT in improving women's health has recently increased worldwide. However, there has been no consensus on the effectiveness of IoT in improving women's health outcomes., Objective: This systematic review and network meta-analysis (NMA) aims to assess and synthesize the role of apps and the IoT in improving women's health and to identify the ranking of interventions for ensuring better results for each stated outcome., Methods: Our systematic review and NMA will be conducted in accordance with the guidelines of the Cochrane Handbook. We will comprehensively search the following electronic databases: PubMed (including MEDLINE), Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature (ie, CINAHL), PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry, along with other resources to identify relevant randomized controlled trials that have assessed the effects of various apps and the IoT with regard to improving working-aged women's health in high-income countries. We will segment and analyze the results of the included studies based on age categories (women undergoing a preconception period, those undergoing gestational and postpartum periods, and menopausal and pre- and postmenopausal women) and the medical history (women who have a specific medical condition-eg, cancer or diabetes-and women who do not have them) separately. Two independent reviewers will perform the study selection, data extraction, and quality assessment. Our primary outcomes include health status, well-being, and quality of life. We will perform pairwise meta-analysis and NMA to estimate the direct, indirect, and relative effects of apps and the IoT on women's health outcomes. We will also assess the hierarchy of interventions, statistical inconsistencies, and certainties of evidence for each outcome., Results: We plan to conduct the search in January 2023 and are currently discussing search strategies with the literature search specialists. The final report is planned for submission to a peer-reviewed journal in September 2023., Conclusions: To the best of our knowledge, this review will be the first to identify the ranking of IoT intervention for ensuring working-aged women's health outcomes. These findings may be of great use to researchers, policy makers, and others with an interest in the field., Trial Registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42022384620; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=384620., International Registered Report Identifier (irrid): PRR1-10.2196/45178., (©Noyuri Yamaji, Aya Nitamizu, Etsuko Nishimura, Daichi Suzuki, Kiriko Sasayama, Md. Obaidur Rahman, Eiko Saito, Daisuke Yoneoka, Erika Ota. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 04.04.2023.)

The number of chronic kidney disease (CKD) patients is increasing worldwide, and it is necessary to diagnose CKD patients in earlier stages to improve their prognosis. Previously, in a study using human samples, we reported that DNA methylation and DNA damage in podocytes are potential markers for kidney function decline in IgA nephropathy; however, these candidate markers have not been adequately investigated in other glomerular diseases. Here, we report that the association of podocyte DNA damage and DNA methylation with eGFR decline and proteinuria differs depending on the type of glomerular disease. Patients diagnosed with minor glomerular abnormality (MGA, n = 33), membranous nephropathy (MN, n = 9) or diabetic nephropathy (DN, n = 10) following kidney biopsy at Keio University Hospital from 2015 to 2017 were included. In MGA patients, both podocyte DNA damage and glomerular DNA methylation were associated with the severity of proteinuria. In DN patients, podocyte DNA double-strand breaks (DSBs) and glomerular DNA methylation were associated with an eGFR decline. When patients with urinary protein levels of more than 1 g/gCr were examined, fewer podocyte DNA DSBs were detected in MN patients than in MGA patients, and the level of glomerular DNA methylation was lower in MN patients than in MGA or DN patients. These results indicate that investigating podocyte DNA DSBs and DNA methylation changes may be useful for understanding the pathogenesis of CKD with proteinuria in humans. This study suggested the association of podocyte DNA damage and subsequent DNA methylation with proteinuria in minor glomerular abnormalities (MGA) patients and those with eGFR declines in diabetic nephropathy (DN) patients, respectively., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Objectives: The objective of this study was to elucidate whether the survival and long-term neurodevelopmental outcomes of extremely preterm infants have improved in a Japanese tertiary center with an active treatment policy for infants born at 22-23 weeks of gestation., Study Design: This single-centered retrospective cohort study enrolled extremely preterm infants treated at Saitama Medical Center, Saitama Medical University, from 2003 to 2014. Patients with major congenital abnormalities were excluded. Primary outcomes were in-hospital survival and severe neurodevelopmental impairment (NDI) at 6 years of age, which was defined as having severe cerebral palsy, severe cognitive impairment, severe visual impairment, or deafness. We assessed the changes in primary outcomes between the first (period 1; 2003-2008) and the second half (period 2; 2009-2014) of the study period and evaluated the association between birth-year and primary outcomes using multivariate logistic regression models., Results: Of the 403 eligible patients, 340 (84%) survived to discharge. Among 248 patients available at 6 years of age, 43 (14%) were classified as having severe NDI. Between the 2 periods, in-hospital survival improved from 155 of 198 (78%) to 185 of 205 (90%), but severe NDI increased from 11 of 108 (10%) to 32 of 140 (23%). In multivariate logistic regression models adjusted for gestational age, birthweight, sex, singleton birth, and antenatal corticosteroids, the aOR (95% CI) of birth-year for in-hospital survival and severe NDI was 1.2 (1.1-1.3) and 1.1 (1.0-1.3), respectively., Conclusion: Mortality among extremely preterm infants has improved over the past 12 years; nevertheless, no significant improvement was observed in the long-term neurodevelopmental outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Changes in muscle mass may be an objective approach toward measuring the quality of life after surgery, but long-term changes due to surgery without the effect of cachexia remain unclear. Patients with esophageal cancer who underwent esophagectomy and did not experience cancer recurrence for 3 years were analyzed. The psoas muscle mass index (PMI) was assessed before surgery and 7 days, 1 year, and 3 years after surgery. Patients with no change or increased PMI within 7 days after surgery were categorized into the Nondecreasing-PMI group, whereas those with decreased PMI were categorized into the Decreasing-PMI group. Eighty-four and 51 patients were categorized into the Nondecreasing- and Decreasing-PMI groups, respectively. The Decreasing-PMI group had a higher incidence rate of anastomotic leakage than the Nondecreasing-PMI group (25% vs. 12%, respectively; P = 0.042). Moreover, the Decreasing-PMI group showed a significantly greater decrease in the PMI 1 year after surgery than the Nondecreasing-PMI group (-9.2% vs. -4.0%, respectively; P = 0.048). However, although the Decreasing-PMI group had a greater decrease in the PMI than the Nondecreasing-PMI group, no significant difference was observed 3 years after surgery (-9.8% vs. -5.3%, respectively; P = 0.115). A decrease in PMI in the acute phase after esophagectomy may contribute to a long-term decrease in the PMI. Intensive interventions may be beneficial for these patients to improve their long-term quality of life., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Esophagectomy is a highly invasive surgical procedure; however, anastomotic leakage is one of the major surgical complications that should be prevented. Institutions have their own inherited or specialized anastomosis methods. The superior anastomosis procedure remains unknown despite the many studies to determine the optimal method. The present study enrolled 341 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between January 2009 and January 2019. The anastomosis method was changed from circular stapled anastomosis to hand-sewn anastomosis in February 2014 to reduce the risk of anastomotic leakage. We retrospectively compared short-term results (anastomotic leakage and stricture) between hand-sewn and circular stapled anastomoses. Analysis of heterogeneity after propensity score matching between the 107 patients in the hand-sewn anastomosis group and 107 patients in the circular stapled anastomosis group revealed almost equal distributions. The incidence rate of anastomotic leakage was significantly lower in the hand-sewn anastomosis group than in the circular stapled anastomosis group (9 vs. 20%, hazard ratio: 2.521; 95% confidence interval: 1.112-5.716; P = 0.027). No significant difference was found in the incidence of anastomotic stricture (16 vs. 18%, P = 0.844). Furthermore, no significant difference was found in the incidence of anastomotic leakage in any of the tumor locations between the two anastomosis procedures. For esophagogastric anastomosis in the neck after esophagectomy, hand-sewn anastomosis is superior to circular stapled anastomosis with regard to reducing the risk of anastomotic leakage., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The objective of this review is to assess and synthesize the role of the maternal and child health (MCH) handbook on improving healthcare service utilization, behavior change, and health outcomes for women and children. A systematic search of all relevant existing reports was conducted on 14 January 2021, using the following online bibliographic databases: PubMed, EMBASE, MEDLINE, The Cochrane Library, Academic Search Premier, Emcare, APA PsycINFO, and Web of Science. Two reviewers independently performed study selection, data extraction, and quality assessment. We included 7 trials from 1430 articles, and a total of 2643 women. As overall risk of bias assessment, most domains of the Cochrane risk-of-bias assessment tool showed a high or unclear risk of bias. The risk of ≥6 antenatal care (ANC) visits was 19% higher (RR 1.19, 95% CI 1.09 to 1.30, I2 = 47%, 2 studies, 955 women, moderate certainty of evidence) and skilled birth attendants during delivery was 13% higher (RR 1.13, 95% CI 1.04 to 1.24, I2 = 0%, 2 studies, 1094 women, low certainty of the evidence) in the intervention group than in the control group. The MCH handbook can increase maternal health service utilization and early breastfeeding practice. It also leads to a sense of autonomy during ANC, better communication with healthcare providers, and support from family members.

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global pandemic. Although several vaccines targeting SARS-CoV-2 spike proteins protect against COVID-19 infection, mutations affecting virus transmissibility and immune evasion potential have reduced their efficacy, leading to the need for a more efficient strategy. Available clinical evidence regarding COVID-19 suggests that endothelial dysfunction with thrombosis is a central pathogenesis of progression to systemic disease, in which overexpression of plasminogen activator inhibitor-1 (PAI-1) may be important. Here we developed a novel peptide vaccine against PAI-1 and evaluated its effect on lipopolysaccharide (LPS)-induced sepsis and SARS-CoV-2 infection in mice. Administration of LPS and mouse-adapted SARS-CoV-2 increased serum PAI-1 levels, although the latter showed smaller levels. In an LPS-induced sepsis model, mice immunized with PAI-1 vaccine showed reduced organ damage and microvascular thrombosis and improved survival compared with vehicle-treated mice. In plasma clot lysis assays, vaccination-induced serum IgG antibodies were fibrinolytic. However, in a SARS-CoV-2 infection model, survival and symptom severity (i.e., body weight reduction) did not differ between vaccine- and vehicle-treated groups. These results indicate that although PAI-1 may promote the severity of sepsis by increasing thrombus formation, it might not be a major contributor to COVID-19 exacerbation., (© 2023. The Author(s).)

Background: Although proximal gastrectomy (PG) is a function-preserving surgical option, it remains unclear as to which reconstruction method can prevent reflux and maintain body composition., Methods: Patients who underwent PG at Keio University between April 2011 and November 2018 were analyzed. Changes in the subcutaneous and visceral adipose tissues were comparatively assessed before and after a year of surgery for three common reconstruction methods. We also compared the endoscopic findings of reflux esophagitis and the number of patients prescribed with proton-pump inhibitor after a year of surgery., Results: This study included 76 patients, of which 33 patients underwent esophagogastrostomy with a circular stapler (CS), 35 under double flap (DF) reconstruction, and 8 underwent double tract (DT) reconstruction. Comparing esophagogastrostomy (CS and DF) and DT showed that esophagogastrostomy could significantly preserve both subcutaneous and visceral adipose tissues (P < 0.001 and P = 0.04, respectively). However, the change in the subcutaneous and visceral adipose tissues was comparable between CS and DF. As for reflux esophagitis, DF showed the lowest incidence rate for esophagitis and the least number of patients who were prescribed a proton-pump inhibitor., Conclusion: DF is a relatively better reconstruction method for preserving fat mass and preventing reflux among the three common reconstruction methods., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)