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The pebbles of Li2TiO3 with excess Li, which is in a developmental stage in JAEA (Japan Atomic Energy Agency) as an advanced tritium breeding material, were exposed to water vapor at elevated temperatures. In the temperature rising process from room temperature to 900°C, pore distribution and BET surface area were largely changed. The surface area decreased gradually by a sintering effect when maintained at 900°C for a long time. The release of water vapor was observed at about 450°C by the decomposition of LiOH in addition to the release of adsorbed water at the beginning of heating. A large release peak of CO2 was observed at 700°C. This is caused by the decomposition of Li2CO3. A remarkable melt layer was formed on the pebble surface over 700°C by melting of Li2CO3. The change of pebble structure and the influences of LiOH and Li2CO3 have to be taken into account, when the release behavior of bred tritium from Li2TiO3 pebbles is discussed.

Under tritium production method using a high-temperature gas-cooled reactor loaded Li compound, Li compound has to be coated by ceramic materials in order to suppress the spreading of tritium to the whole reactor. Pyrolytic carbon (PyC) is a candidate of the coating material because of its high resistance for gas permeation. In this study, hydrogen permeation experiments using a PyC-coated isotropic graphite tube were conducted and hydrogen diffusivity, solubility and permeability were evaluated. Tritium permeation behavior through PyC-coated Li compound particles was simulated by using obtained data. Hydrogen permeation flux through PyC in a steady state is proportional to the hydrogen pressure and is larger than that through Al2O3 which is also candidate coating material. However, total tritium leak within the supposed reactor operation period through the PyC-coated Li compound particles is lower than that through the Al2O3-coated ones because the hydrogen absorption capacity in PyC is considerably larger than that in Al2O3.

Introduction: Injury prevention is valuable for pediatric burns at home. To develop future target of prevention, we aimed to elucidate characteristics and chronological changes of pediatric burn injuries at home in urban areas., Patients and Methods: We conducted a retrospective observational study using the database of the Tokyo Burn Unit Association, which comprises 14 tertiary burn centers, the Tokyo Fire Department, Tokyo Medical Association, and the Tokyo city government. We included pediatric patients aged ≤ 15 years who had a burn injury at home in the last 30 years and divided them into five groups at 6-year intervals. We compared the mechanism, severity, and outcome of burn injuries between the groups., Results: We included 1092 pediatric patients, with no significant chronological changes in the incidence of burn injuries at home (approximately 200 patients in each 6-year period). The median age was 1 year in all the groups. Flame burns decreased from 7.7 % to 1.6 %, whereas scald burns remained at > 80 %. The burn area decreased from 10 (5-16) % total body surface area (%TBSA) to 7 (3-11) %TBSA. The length of hospital stay was reduced from 6 to 2 days, and in-hospital mortality was 0.4-0.5 % in the last decade., Conclusions: The incidence of flame burns and burn area decreased over time with improving clinical outcomes in pediatric burns. The number of scald burns remained the same over time; thus, further social intervention is needed to prevent scald burns., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Non-typhoid Salmonella (NTS) includes many serotypes that differ in host, geographic distribution, and virulence. We report the case of a 64-year-old man who developed enteritis caused by Salmonella Kedougou without bacteremia after returning from Thailand. The patient stayed in Chiang Mai, Thailand, for 10 days to play golf and was hospitalized with fever, chills, watery diarrhea, and vomiting on the day the patient returned to Japan. The patient was treated with intravenous azithromycin followed by ceftriaxone for 6 days. NTS was detected in the patient's stool culture, and additional strain analyses were performed. Polymerase chain reaction for the O-antigen and sequence analysis of fliC and fliB genes determined the serotype of the strain to be O13: i: l,w. The strain was assigned to sequence type 1543 using multilocus sequence typing. These results confirmed that the strain was S. Kedougou. Considering the incubation period of salmonellosis, the patient was most likely infected with S. Kedougou in Thailand, which is consistent with the epidemiological information that S. Kedougou is frequently detected in northern Thailand. The identification of NTS serovars may not affect clinical management; however, we believe that it is important to accumulate epidemiological information to understand the interactions between the environment, animals, and humans., Competing Interests: Declaration of competing interest None., (Copyright © 2025 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: A histologically involved surgical margin (R1) is often observed after resection for cholangiocarcinoma. Compared with a negative margin (R0), R1 with invasive carcinoma (R1inv) markedly worsens survival, whereas the prognostic effect of R1 with carcinoma in situ (R1cis) remains controversial., Methods: Patients who underwent resection for perihilar cholangiocarcinoma between 2002 and 2019 were retrospectively reviewed. According to the pathological assessment, the duct margin was classified as R0, R1cis, or R1inv; radial margin positivity was treated as R1inv. Recurrence and survival were compared., Results: Among the 681 patients, 457 had R0, 69 had R1cis, and 155 had R1inv. The overall five-year recurrence rate was 82.8 % with R1inv, 67.8 % with R1cis, and 47.6 % with R0 (P < 0.001); the local recurrence rate also significantly differed among these groups (P < 0.001). The five-year survival rate was significantly worse with R1cis than with R0 (37.3 % vs. 56.7 %, P < 0.001) and better than that with R1inv (20.9 %, P = 0.007). Multivariate analysis revealed that R1cis was an independent predictor of survival (hazard ratio, 1.65; P < 0.001)., Conclusion: Compared with R0, R1cis significantly deteriorated overall survival in the whole resection subset of patients with perihilar cholangiocarcinoma. However, the prognostic impact of R1cis was milder than that of R1inv., Competing Interests: Conflicts of interest None declared., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background &aims: Thiamine is an essential micronutrient for energy metabolism. Thiamine deficiency is frequently observed in critically ill patients. However, the effect of thiamine administration is unclear in critically ill patients., Methods: We conducted a systematic review and meta-analysis. To identify randomized controlled trials on the effect of thiamine administration in critically ill patients, a literature search was conducted in MEDLINE, CENTRAL, and ICHUSHI databases from inception to April 2023. Pooled effect estimates were calculated about mortality as the primary outcome and shock duration, lactate level, Sequential Organ Failure Assessment (SOFA) score, delirium, length of mechanical ventilation, length of intensive care unit (ICU) stay, infection rate, all adverse events, and Short-Form Health Survey (SF-36) as the secondary outcomes. The certainty of evidence (CoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach., Results: Overall, 35 studies (3494 patients) were included. Evidence suggested that thiamine administration resulted in little to no difference in mortality (risk ratio [RR], 0.89; 95% confidence interval [CI], 0.75 to 1.06; Low CoE); however, thiamine administration may reduce shock duration (mean difference [MD], -11.43 h; 95% CI, -20.16 to -2.69 h; Low CoE), lactate level (MD, -0.34 mmol/L; 95% CI, -0.63 to -0.05 mmol/L; Low CoE), and SOFA score (MD, -1.29; 95% CI, -1.91 to -0.66; Low CoE). Conversely, thiamine administration resulted in a slight increase in the length of ICU stay (MD, 0.40 days; 95% CI, 0.01-0.79 days; High CoE)., Conclusions: Although thiamine administration may reduce shock state, it may not reduce mortality, and slightly increases the length of ICU stay., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: High-fat, low-carbohydrate enteral nutrition has gained attention, with expectations of an improved respiratory condition, fewer complications, and lower mortality. The present study performed a systematic review and meta-analysis of randomized controlled trials to examine the effects of high-fat, low-carbohydrate enteral nutrition in critically ill adult patients., Methods: We searched MEDLINE via Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), and ICHUSHI for randomized controlled trials comparing high-fat, low-carbohydrate enteral nutrition to standard enteral nutrition in critically ill adult patients who received enteral nutrition. The primary outcome was mortality. Secondary outcomes included intensive care unit (ICU) mortality, length of ICU stay, length of mechanical ventilation, and adverse events of diarrhea and gastric residual volume. We examined the risk of bias using the Cochrane risk-of-bias tool for randomized trials version 2. We assessed the overall certainty of evidence based on the Grading of Recommendations Assessment, Development, and Evaluation methodology. Synthesis results were calculated with risk ratios and 95% confidence intervals using a Mantel-Haenszel random-effects model., Results: Eight trials with 607 patients were included. The effects of high-fat, low-carbohydrate enteral nutrition on mortality did not significantly differ from those of standard enteral nutrition (62/280 [22.1%] vs. 39/207 [18.8%], risk ratios = 1.14, 95% confidence intervals 0.80 to 1.62, P = 0.47). No significant differences were observed in ICU mortality, ICU length of stay, diarrhea, or gastric residual volume between the two groups. However, high-fat, low-carbohydrate enteral nutrition was associated with a significantly shorter duration of mechanical ventilation (mean difference -1.72 days, 95% confidence intervals -2.93 to -0.50, P = 0.005)., Conclusion: High-fat, low-carbohydrate enteral nutrition may not affect mortality, but may decrease the duration of mechanical ventilation in critically ill adult patients. Limitations include the small number of studies and potential for bias. Further research is needed to confirm these results and investigate effects on other outcomes and in a subgroup of patients requiring mechanical ventilation., Competing Interests: Conflict of interest The authors report no personal conflicts of interest pertaining to this work., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Cytokine receptor-like factor 2 (CRLF2) and interleukin-7 receptor α (IL-7Rα) form a receptor for thymic stromal lymphopoietin (TSLP). A somatic mutation consisting of the substitution of five amino acids (SLLLL) in the transmembrane domain of CRLF2 with three amino acids, including glutamic acid, isoleucine, and methionine (insEIM), which has been identified in acute lymphocytic leukemia, causes the TSLP-independent dimerization with IL-7Rα and activation. However, the dimerization mechanism remains unclear. In this study, we examined the involvement of the amino acids in the transmembrane domains of EIM CRLF2 and IL-7Rα in TSLP-independent activation. HEK293 cells were transfected with vectors encoding CRLF2 and IL-7Rα, or their mutants, in which the amino acid of the transmembrane domain was replaced with alanine. STAT5 phosphorylation was detected using western blotting, and receptor dimerization was analyzed using the NanoBiT assay. The substitution of glutamic acid within the insEIM mutation for alanine failed to cause the STAT5 phosphorylation in the absence of TSLP. Moreover, the alanine substation of the specific leucine residues in the transmembrane domains of both CRLF2 and IL-7Rα abrogated the TSLP-independent signal transduction and dimerization. The mutation of IL-7Rα W264 partially reduced the phosphorylation of STAT5 without affecting receptor dimerization. These results suggest that the amino acids in the transmembrane domains of EIM CRLF2 and IL-7Rα play at least three possible functions: interaction through hydrogen bonds, hydrophobic interaction, and signal transduction. Our findings contribute to a better understanding of the function of the transmembrane domains of cytokine receptors in their dimerization and signal transduction., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to assess the association between posterior occlusal support (POS) and the risk of tooth loss in older adults aged ≥75 years., Methods: This longitudinal study analyzed 94,422 participants who participated in multiple dental check-ups provided as part of the public healthcare services in Osaka, Japan, from 2018 to 2022. The participants were categorized into nine groups (A1-3, B1-4, and C1 and C2) according to their POS status using the Eichner index at baseline. The dental charts were compared between the initial and final assessments to assess tooth loss. Logistic regression analysis was used to examine the association between POS status and tooth loss, adjusted for several covariates, including age, sex, body mass index, periodontal status, oral hygiene, history of diabetes, history of hypertension, attendance at the annual dental check-up, and observational period. Furthermore, stratified logistic regression analyses were conducted using anterior or posterior tooth loss., Results: After controlling for confounders, POS status was associated with tooth loss. The odds ratios (ORs) with A1 as the reference were 1.74 in A2, 2.55 in A3, 3.40 in B1, 4.74 in B2, 5.79 in B3, 6.00 in B4, 4.44 in C1, and 3.00 in C2, respectively. The ORs for anterior tooth loss were higher than those for posterior tooth loss, with the highest OR observed in B4 (21.4)., Conclusions: This large population-based cohort study showed that a decreased POS was a risk indicator for tooth loss; furthermore, the risk increased even further in the anterior teeth region., 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 Ltd.)

Heliorhodopsin (HeR) is a new rhodopsin family discovered in 2018 through functional metagenomic analysis. Similar to microbial rhodopsins, HeR has an all-trans retinal chromophore, and its photoisomerization to the 13-cis form triggers a relatively slow photocycle with sequential intermediate states (K, M, and O intermediates). The O intermediate has a relatively long lifetime and is a putative active state for transferring signals or regulating enzymatic reactions. Although the first discovered HeR, 48C12, was found in bacteria and the second HeR (TaHeR) was found in archaea, their key amino acid residues and molecular architectures have been recognized to be well conserved. Nevertheless, the rise and decay kinetics of the O intermediate are faster in 48C12 than in TaHeR. Here, using a new infrared spectroscopic technique with quantum cascade lasers, we clarified that the hydrogen bond between transmembrane helices (TM) 3 and 4 is essential for the altered O kinetics (Ser112 and Asn138 in 48C12). Interconverting mutants of 48C12 and TaHeR clearly revealed that the hydrogen bond is important for regulating the dynamics of the O intermediate. Overall, our study sheds light on the importance of the hydrogen bond between TM3 and TM4 in heliorhodopsins, similar to the DC gate in channelrhodopsins., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The immune system is involved in hypertension development with different immune cells reported to have either pro or anti-hypertensive effects. In hypertension, immune cells have been thought to infiltrate blood pressure-regulating organs, resulting in either elevation or reduction of blood pressure. There is controversy over whether macrophages play a detrimental or beneficial role in the development of hypertension, and the few existing studies have yielded conflicting results. This study aimed to determine the effects of angiotensin II (Ang II) salt-induced hypertension on renal immune cells and to determine whether renal macrophages are involved in the induction of hypertension. Hypertension was induced by administration of Ang II and saline for two weeks. The effects of hypertension on kidney immune cells were assessed using flow cytometry. Macrophage infiltration in the kidney was assessed by immunohistochemistry and kidney fibrosis was assessed using trichrome stain and kidney real time-qPCR. Liposome encapsulated clodronate was used to deplete macrophages in C57BL/6J mice and investigate the direct role of macrophages in hypertension induction. Ang II saline mice group developed hypertension, had increased renal macrophages, and had increased expression of Acta2 and Col1a1 and kidney fibrotic areas. Macrophage depletion blunted hypertension development and reduced the expression of Acta2 and Col1a1 in the kidney and kidney fibrotic areas in Ang II saline group. The results of this study demonstrate that macrophages infiltrate the kidneys and increase kidney fibrosis in Ang II salt-induced hypertension, and depletion of macrophages suppresses the development of hypertension and decreases kidney fibrosis. This indicates that macrophages play a direct role in hypertension development. Hence macrophages have a potential to be considered as therapeutic target in hypertension management., Competing Interests: Declaration of competing interest The authors declare that no conflict of interest exists., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Early appropriate care (EAC) is widely accepted as a safe strategy to perform early definitive fracture fixation, and good clinical outcomes have been reported in selected, multiply injured patients, although the optimal candidate for early definitive fixation (EDF) has not been validated. The aim of this study was to identify simple clinical parameters to help select patients who could undergo EDF., Methods: Patients with extremity injuries who underwent open reduction and internal fixation were retrospectively identified, using data from the Japan Trauma Data Bank (JTDB). Age, vital signs on hospital presentation, and the injury severity score (ISS) were examined by transforming these variables to binary categories. Patients were divided into categories based on these variables, and in-hospital mortality was compared between patients treated with EDF (EDF group) and those treated without EDF (non-EDF group) in each category., Results: Of the 12,735 patients who were eligible for the analyses, 3706 (29.1 %) were managed with EDF. In-hospital mortality was significantly higher in the EDF group than in the non-EDF group among patients with a low Glasgow Coma Scale (GCS) score (<13), low systolic blood pressure (sBP) (<90 mmHg), and ISS≥15, whereas in-hospital mortality was comparable between the EDF and non-EDF groups among patients with GCS scores ≥13, sBP ≥90 mmHg, and ISS <15., Discussion: In this large nationwide database of trauma patients, EDF was performed without affecting mortality in patients with GCS scores ≥13 and sBP ≥90 mmHg on hospital presentation, as well as ISS <15. These parameters might be useful as screening tools to select the candidates who could be treated with EDF safely., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Traumatic brain injury (TBI)-associated coagulopathy significantly influences survival outcomes in patients with multiple injuries. Severe TBI can potentially affect systemic hemostasis due to coagulopathy; however, there is limited evidence regarding whether the risk of hemorrhage increases in patients with pelvic fractures complicated with TBI. Therefore, through multivariable analysis, we aimed to examine the association between severe TBI and increased blood transfusion requirements in patients with pelvic fractures., Materials and Methods: This retrospective observational study was conducted at a tertiary care facility in Japan. Patients aged 16 years or older with pelvic fractures who were admitted to our intensive care unit between April 2014 and December 2021 were included in the analysis. The patients were categorized into no to mild and severe TBI groups according to whether the Head Abbreviated Injury Scale (AIS) score was 3 or higher. The primary outcome was the number of red blood cell (RBC) units transfused within 24 h after arrival at the hospital. The primary outcome was analyzed using univariable and multivariable linear regression analyses. The covariates used for the multivariable linear regression analysis were age, sex, antithrombotic therapy, mechanism of injury, Pelvic AIS score, and extravasation on contrast-enhanced computed tomography on admission., Results: We identified 315 eligible patients (221 and 94 in the no to mild and severe TBI groups, respectively). In the univariable analysis, the RBC transfusion volume within 24 h after arrival was significantly higher in the severe TBI group than in the no to mild TBI group (2.53-unit increase; 95 % confidence interval [CI]: 0.46-4.61). However, in the multivariable analysis, no statistically significant association was detected between severe TBI and the RBC transfusion volume within 24 h after arrival at the hospital (0.87-unit increase; 95 % CI: -1.11-2.85)., Conclusions: Concomitant severe TBI was not associated with increased RBC transfusion volumes in patients with pelvic fractures on multivariable analysis., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Nardilysin (NRDC) is a multifunctional protein required for maintaining homeostasis in various cellular and tissue contexts. However, its role in hematopoietic stem cells (HSCs) remains unclear. Here, through the conditional deletion of NRDC in hematopoietic cells, we demonstrate that NRDC is required for HSCs expansion in vitro and the reconstitution of hematopoiesis in vivo after transplantation. We found NRDC-deficient HSCs lose their self-renewal ability and display a preferential bias to myeloid differentiation in response to replication stress. Transcriptome data analysis revealed the upregulation of heat shock response-related genes in NRDC-deficient HSCs. Additionally, we observed increased protein synthesis in cultured NRDC-deficient HSCs. Thus, loss of NRDC may cause the inability to control protein synthesis in response to replication induced protein stress, leading to the impaired HSC self-renewal ability. This highlights a novel model of action of NRDC specifically in HSCs., Competing Interests: Declaration of competing interest We have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: Regulation of lineage biases in hematopoietic stem and progenitor cells (HSPCs) is pivotal for balanced hematopoietic output. However, little is known about the mechanism behind lineage choice in HSPCs. Here, we show that messenger RNA (mRNA) decay factors regnase-1 (Reg1; Zc3h12a) and regnase-3 (Reg3; Zc3h12c) are essential for determining lymphoid fate and restricting myeloid differentiation in HSPCs. Loss of Reg1 and Reg3 resulted in severe impairment of lymphopoiesis and a mild increase in myelopoiesis in the bone marrow. Single-cell RNA sequencing analysis revealed that Reg1 and Reg3 regulate lineage directions in HSPCs via the control of a set of myeloid-related genes. Reg1- and Reg3-mediated control of mRNA encoding Nfkbiz, a transcriptional and epigenetic regulator, was essential for balancing lymphoid/myeloid lineage output in HSPCs in vivo. Furthermore, single-cell assay for transposase-accessible chromatin sequencing analysis revealed that Reg1 and Reg3 control the epigenetic landscape on myeloid-related gene loci in early stage HSPCs via Nfkbiz. Consistently, an antisense oligonucleotide designed to inhibit Reg1- and Reg3-mediated Nfkbiz mRNA degradation primed hematopoietic stem cells toward myeloid lineages by enhancing Nfkbiz expression. Collectively, the collaboration between posttranscriptional control and chromatin remodeling by the Reg1/Reg3-Nfkbiz axis governs HSPC lineage biases, ultimately dictating the fate of lymphoid vs myeloid differentiation., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Several guidelines recommend the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) to diagnose heart failure (HF); however, no screening criteria for measuring NT-proBNP in asymptomatic patients exist. We develop/validate a clinical prediction model for elevated NT-proBNP to support clinical outpatient decision-making., Methods: In this multicenter cohort study, we used a derivation cohort (24 facilities) from 2017 to 2021 and a validation cohort at one facility from 2020 to 2021. Patients were aged ≥65 years with at least one risk factor of HF. The primary endpoint was NT-proBNP ≥125 pg/mL. The final model was selected using backward stepwise logistic regression analysis. Diagnostic performance was evaluated for sensitivity and specificity, the area under the curve (AUC), and calibration. In total, 1645 patients (derivation cohort, n = 837; validation cohort, n = 808) were included, of whom 378 (23.0 %) had NT-proBNP ≥125 pg/mL. Body mass index, age, systolic blood pressure, estimated glomerular filtration rate, cardiothoracic ratio, and heart disease were used as predictors and aggregated into a BASE-CH score of 0-11 points., Results: Internal validation resulted in an AUC of 0.74 and an external validation AUC of 0.70., Conclusions: Based on available clinical and laboratory variables, we developed and validated a new risk score to predict NT-proBNP ≥125 pg/mL in patients at risk for HF or with pre-HF., Competing Interests: Declaration of competing interest Saito Y. received research funds from Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Bristol-Myers Squibb Company, Actelion Pharmaceuticals Japan Ltd., Kyowa Kirin Co., Ltd., Kowa Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Teijin Pharma Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Nihon Medi-Physics Co., Ltd., Novartis Pharma K.K., Pfizer Japan Inc., and Fuji Yakuhin Co., Ltd.; research expenses from Novartis Pharma K.K., Roche Diagnostics K.K., Amgen Inc., Bayer Yakuhin, Ltd., Astellas Pharma Inc., and Actelion Pharmaceuticals Japan Ltd.; speakers' bureau/honorarium from Alnylam Japan K.K., AstraZeneca K.K., Otsuka Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Tsumura & Co., Teijin Pharma Ltd., Toa Eiyo Ltd., Nippon Shinyaku Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Bayer Yakuhin Ltd., Pfizer Japan Inc., Bristol-Myers Squibb Company, and Mochida Pharmaceutical Co., Ltd.; and consultation fees from Ono Pharmaceutical Co., Ltd. and Novartis Pharma K.K. Masuda I. received research funds from Astra Zeneca K.K., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Bayer Yakuhin, Ltd., Nippon Boehringer Ingelheim Co., Mitsubishi Tanabe Pharma Co., Ltd.,Daiichi Sankyo Co., Ltd., Kowa Company, Ltd., MSD K.K., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., Novartis Pharma K.K., Teijin Pharma Ltd., Otsuka Pharmaceutical Co., Ltd.; and manuscript fees from OMRON HEALTHCARE Co., Ltd. The other authors have no financial conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The clinical benefits of faster recanalization in acute large vessel occlusion are well recognized, but the optimal procedure time remains uncertain. The aim of this study was to identify patient characteristics that necessitate puncture-to-recanalization (P-R) time within 30 min to achieve favorable outcome., Methods: We evaluated the patients from a prospective, multicenter, observational registry of acute ischemic stroke patients. The study included patients who underwent endovascular therapy for ICA or MCA M1 occlusion and achieved successful recanalization. Patients were categorized into subgroups based on pre-treatment characteristics and the frequency of favorable outcomes was compared between P-R time < 30 min and ≥ 30 min. Interaction terms were incorporated into the models to assess the correlation between each patient characteristic and P-R time., Results: A total of 1053 patients were included in the study. Univariate analysis within each subgroup revealed a significant association between P-R < 30 min and favorable outcomes in patients with DWI ASPECTS ≤6, age > 85 and NIHSS ≥16. In the multivariable analysis, NIHSS, age, time from symptom recognition to puncture, and DWI ASPECTS were significant independent predictors of favorable outcomes. Notably, only DWI ASPECTS exhibited interaction terms with P-R < 30 min. The multivariable analysis indicated that P-R < 30 min was an independent predictor for favorable outcome in DWI ASPECTS ≤6 group, whereas not in DWI ≥7., Conclusions: P-R time < 30 min is predictive of favorable outcomes; however, the effect depends on DWI ASPECTS. Target P-R time < 30 min is appropriate for patients with DWI ASPECTS ≤6., Competing Interests: Declaration of Competing Interest The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. T.U. reports consulting fees from Kaneka Medix. Dr. Y.H. reports consulting fees from Bayer Pharmaceutical and Nippon Boehringer Ingelheim. Dr. M.T. reports consulting and lecture fees from Johnson and Johnson and Stryker., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Cytokine receptor-like factor 2 (CRLF2) is a subunit of the receptor for thymic stromal lymphopoietin (TSLP). A somatic mutation (insEIM) in the transmembrane domains of CRLF2 has been identified in acute lymphocytic leukemia (ALL), and Glu-Ile-Met (EIM) CRLF2 induces constitutive activation of signals. However, the signaling mechanism remains unclear., Methods: HEK293 cells were transfected with expression vectors encoding wild-type (WT), insEIM CRLF2, or their mutants which N-glycosylation site was replaced with a glutamine. Cell surface expression of CRLF2 was assessed by flow cytometry. Total CRLF2 and phosphorylated signal transducer and activator of transcription 5 (STAT5) were detected by western blotting., Results: Three major species of CRLF2 (53-, 57- and 58-kDa) were identified. Deglycosylation analysis revealed that they were modified with complex-type and oligomannose-type glycans. The expression of both WT and EIM CRLF2 decreased in N-acetylglucosaminyltransferase (GnT)-I (MGAT1) knockout (KO) cells and slightly decreased in α1,6-fucosyltransferase (Fut8) KO cells compared to that in the control cells. In GnT-I or Fut8 KO cells, WT CRLF2 did not induce ligand-independent activation. Both WT and EIM CRLF2 contained four N-glycosylation sites. N55 of CRLF2 was required for the cell surface expression and activation by EIM CRLF2., Conclusions: We found that N-glycosylation of CRLF2 plays crucial roles for its cell surface expression and signaling. However, N-glycan processing in the Golgi apparatus does not seem to be essential for ligand-independent activation of EIM CRLF2., General Significance: Our studies provide a crucial role of glycosylation in the cell surface expression of receptors., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The long-term trends of COVID-19 mental sequelae remain unknown. Thus, this study aimed to survey the one-year temporal trends of PTSD and health-related quality of life of COVID-19 survivors., Methods: Patients hospitalized with COVID-19 were followed up at three, six, and 12 months after discharge. Patients with COVID-19 who were able to communicate and complete the questionnaires were included in the study. All participants were asked to complete the Medical Outcomes Study 36-Item Short-Form Health (SF-36) survey and the Impact of Event Scale-Revised (IES-R). The cutoff point of 24/25 of IES-R was defined as preliminary PTSD. Patients exhibiting PTSD symptoms at six months or later were regarded as "delayed patients," while those exhibiting PTSD symptoms at all the time points were "persistent patients.", Results: Of the 98 patients screened between June and November 2020, 72 participated in the study. A total of 11 (15.3%) had preliminary PTSD at three months, 10 (13.9%) at six months, and 10 (13.9%) at 12 months; delayed and persistent patients were four patients (7.54%) each. Patients with preliminary PTSD had lower mental summary scores in SF-36; 47 (IQR 45, 53) for patients with preliminary PTSD and 60 (49, 64) without preliminary PTSD at three months, 50 (45, 51) and 58 (52, 64) at six months, and 46 (38, 52) and 59 (52, 64) at 12 months., Conclusion: Healthcare providers should care about the courses of PTSD in COVID-19 survivors and be aware that patients with PTSD symptoms may have a lower health-related quality of life., Competing Interests: Conflict of interest The authors have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Little is known about the predictability of mass flows of veterinary drugs in Asian catchments, where effluent from livestock farms is a major source. We therefore conducted this study to understand the applicability and limitations of a population-based emission model, which assumed usage of veterinary and human drugs to be evenly distributed over the national livestock or human population throughout the year, and sources to be effluent discharges at livestock farms, households, and sewage treatment plants in Japanese catchments. We monitored five veterinary drugs (lincomycin, sulfamonomethoxine, tiamulin, tylosin, and tilmicosin), two human and livestock drugs (sulfamethoxazole and trimethoprim), two human drugs (carbamazepine and clarithromycin), and a metabolite (sulfapyridine) of a human drug once a month over 2 years in eight Japanese rivers which have active livestock farming in their catchments. Mass flows of carbamazepine and sulfapyridine were stable, while those of veterinary drugs fluctuated widely, especially sulfamonomethoxine and tilmicosin, whose 25 %-100 % ranges averaged 1.5 and 1.2 log units, respectively, attributable mainly to their usage patterns. The model accurately predicted mean mass flows of carbamazepine in the rivers with errors of <±0.3 log unit. Although it slightly to moderately overestimated those of the other four human-related compounds, the incorporation of an empirical correction factor, determined to minimize mean absolute error (MAE) among the rivers, substantially lowered their MAEs to <0.23 log units. However, the MAEs of the five veterinary drugs were as high as 0.42 (sulfamonomethoxine) to 0.60 (tiamulin) log units even with the coefficient, likely due mainly to the spatial distribution of their usage per capita. So as not to overlook spatiotemporal elevation of risks of veterinary drugs, a stochastic method should be applied in their management. This is the first study to assess the use of spatiotemporal homogeneity in usage per capita of veterinary drugs in Asian catchments., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: The effectiveness of mRNA COVID-19 vaccines and the optimal timing of vaccine administration in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) recipients remains inadequately investigated. We examine the effectiveness and safety of mRNA COVID-19 vaccines in allo-HSCT recipients., Method: This prospective observational study included 44 allo-HSCT recipients and 38 healthy volunteers. The proportion of subjects acquiring anti-S1 IgG antibodies were considered as the primary endpoint. The occurrence of adverse events after vaccination and objective deterioration of chronic graft-versus-host disease (GVHD) were defined as secondary endpoints. In addition, we compared the geometric mean titers (GMT) of anti-S1 antibody titers in subgroups based on time interval between transplantation and vaccination., Results: A humoral response to the vaccine was evident in 40 (91%) patients and all 38 healthy controls. The GMT of anti-S1 titers in patients and healthy controls were 277 (95% confidence interval [CI]: 120-643) BAU/mL and 532 (95% CI 400-708) BAU/mL, respectively. (p = 0.603). A short time interval between transplantation and vaccination (≤6 months) was associated with low anti-S1 IgG antibody titers. No serious adverse events and deterioration of chronic GVHD were observed. Only one case of new development of mild chronic GVHD was recorded., Conclusion: Messenger RNA COVID-19 vaccines induce humoral responses in allo-HSCT recipients and can be administered safely., 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 © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for ischemic stroke prevention in patients with carotid artery stenosis. However, the beneficial effects of CEA/CAS for cerebral hypoperfusion due to carotid artery stenosis have yet to be fully established. As dizziness is a common symptom in patients with carotid artery stenosis, we aimed to evaluate the effects of CEA/CAS on cerebral function in patients with carotid artery stenosis, using equilibrium function tests., Methods: This prospective observational cohort study included 50 patients who had carotid artery stenosis and were scheduled to undergo CEA or CAS. Before CEA/CAS, we quantitatively evaluated the vestibulo-ocular reflex (VOR) and vestibular evoked myogenic potential (VEMP), as indicators of brainstem/inner ear functions related to balance, and visual suppression of VOR, as an indicator of cerebral control over the brainstem reflex related to balance. These were then compared with supratentorial cerebral blood flow (CBF). Changes in VOR, VEMP, visual suppression of VOR, CBF, and dizziness after CEA/CAS were also evaluated., Results: The visual suppression rates of VOR correlated with supratentorial CBFs before CEA/CAS (correlation coefficient = 0.47, p = 0.003). The visual suppression rates of VOR (p < 0.001) and supratentorial CBFs (p = 0.003) were improved by CEA/CAS, while VOR and VEMP did not change. Symptoms of dizziness improved after CEA/CAS., Conclusions: Our results suggest that visual suppression of the VOR may be a novel and practical marker for the beneficial effects of CEA/CAS on supratentorial cerebral function., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: While various strategies of fracture fixation for trauma patients have been discussed, optimal candidates remain unclear for early definitive fixation. The aim of this study was to integrate several clinical parameters into a scoring system and determine a cut-off value for safe early definitive surgery for extremity fractures., Methods: We retrospectively identified patients with fracture in an extremity in Japanese Trauma Data Bank from 2004 to 2019. We included adult patients who underwent open reduction and internal fixation for extremity injury before any other surgical intervention and excluded those who arrived with cardiac arrest. Several clinical parameters, such as age, vital signs, abbreviated injury scale (AIS) in the chest, and injury severity score (ISS), were examined with multivariate logistic regression models to predict in-hospital mortality, and then integrated into a scoring system based on each odds ratio. To determine a cut-off value of the scoring system for safe early definitive surgery, in-hospital mortality and/or postoperative complications were compared between patients who underwent definitive fixation within 24 h of injury and patients who did not in subgroups based on the scores., Results: Of 50,631 patients eligible for this study, 16,119 (31.8%) underwent early definitive fixation. A 0-15 scoring system with parameters including age >70 years, GCS <8, systolic blood pressure <90 mmHg, AIS in the chest ≥3, ISS ≥20, and transfusion requirement within 24 h of arrival was developed. At scores ≥10, early definitive fixation was found to be significantly associated with high in-hospital mortality, and at scores <10, in-hospital mortality was comparable between the two groups., Conclusions: We integrated clinical parameters into the scoring system with a scale of 0-15 and determined that a score of 10 is the cut-off score. We determined that patients with a score <10 can safely undergo early definitive fixation., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: Under clinical development for patients with growth hormone deficiency, JR-142 is a long-acting growth hormone with a half-life extended by fusion with modified serum albumin. We conducted a Phase 1 study to investigate the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles of once-weekly subcutaneous administrations of JR-142. The study consisted of two parts: an open-label single ascending dosing study (Part 1), and a randomized, placebo-controlled, assessor-blinded multiple ascending dosing study (Part 2)., Design: A total of 31 healthy Japanese male participants were enrolled. In Part 1, seven of them received a single subcutaneous injection of JR-142 each at dosages of 0.15 mg/kg (n = 1), 0.25 mg/kg (n = 2), 0.5 mg/kg (n = 2), or 1.0 mg/kg (n = 2). In Part 2, one weekly subcutaneous injection of JR-142 at 0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg or a placebo were given for four weeks to each of the other 24 participants (six in each group). Plasma JR-142 and serum insulin-like growth factor-1 (IGF-1) concentrations were measured for PK and PD assessments. Safety was evaluated on the basis of adverse events (AEs), laboratory tests, and other measures., Results: JR-142 induced dose-dependent increases in the maximum plasma JR-142 concentration (C max ) and the area under the plasma concentration-time curve from time 0 to τ (AUC 0-τ ). A similar dose-response relationship was observed in serum IGF-1 concentrations. All trough IGF-1 levels were well sustained one week after the final administrations of JR-142 at the three dosages, while the peak concentrations of IGF-1 remained mildly elevated. No serious AEs were observed, and laboratory tests, including assessment of anti-drug antibodies, uncovered no significant safety issues., Conclusions: Once-weekly subcutaneous injections of JR-142 produced positive dose-dependent PK and PD profiles over the dosage range. Drug accumulation was observed after the four-week administration period but did not raise safety concerns, indicating that JR-142 is well-tolerated in healthy participants. The PD profiles observed in terms of IGF-1 concentrations were also positive, and we believe the encouraging results of this study warrant substantiation in further clinical trials in patients with GHD., Ethics: This clinical study was conducted at one investigational site in Osaka, Japan, where the clinical study and the non-clinical data of JR-142 were reviewed and approved by its Institutional Review Board on 9th May 2019. The study was conducted in compliance with the approved study protocol, the Declaration of Helsinki, 1964, as revised in 2013, and Good Clinical Practice., Competing Interests: Declaration of Competing Interest This clinical study was fully sponsored by JCR Pharmaceuticals, Co., Ltd. Yasuko Owada was an investigator for the studies sponsored by JCR Pharmaceuticals, Co., Ltd. (formerly Japan Chemical Research, Co., Ltd. ) in 2012, 2018, and 2019. Mika Okazaki, Toshiaki Ikeda, Ryuji Yamamoto, Kohtaro Minami, Kenichi Takahashi, Tohru Hirato, Yoko Mita, Tatsuyoshi Yamamo, Kazunori Tanizawa, Hiroyuki Sonoda and Yuji Sato are employed by JCR Pharmaceuticals, Co., Ltd., of which Hiroyuki Sonoda is a board member., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cervical polyps removed during pregnancy have been reported to be associated with preterm birth; however, the association between unremoved cervical polyps and preterm birth has not been elucidated., Objective: This study aimed to clarify the relationship between cervical polyps detected before 12 weeks of gestation managed expectantly and spontaneous preterm birth., Study Design: This retrospective cohort study included pregnant women who visited a tertiary perinatal center before 12 weeks of gestation between January 2015 and December 2019. The exclusion criteria were as follows: multiple gestations, loss or termination of pregnancy before 12 weeks of gestation, major fetal anomalies, fetal chromosomal abnormalities, fetal demise, having undergone removal of cervical polyps before the first visit to our hospital, and moving to other hospitals before delivery. A vaginal speculum examination was routinely performed during a prenatal visit before 12 weeks of gestation. When a cervical polyp was detected on speculum examination, it was managed expectantly, unless gynecologic malignancy was suspected. Relationships between cervical polyps and spontaneous preterm birth before 34 weeks of gestation were evaluated using logistic regression analysis and Cox proportional-hazards analysis adjusted for known confounders for spontaneous preterm birth., Results: A total of 4172 pregnant women were included, of whom 92 (2.2%) had a cervical polyp detected before 12 weeks of gestation. None of the women underwent polypectomy during pregnancy. The incidence of spontaneous preterm birth before 34 weeks of gestation was higher in pregnant women with cervical polyps than in those without them (5.4% vs 0.7%; P<.01). Logistic regression analysis revealed that cervical polyps were an independent risk factor for spontaneous preterm birth before 34 weeks of gestation (adjusted odds ratio, 4.09; 95% confidence interval, 1.70-9.81; P<.01). The adjusted hazard ratio for spontaneous preterm birth before 34 weeks of gestation among women with vs without cervical polyps was 2.95 (95% confidence interval, 1.32-6.62; P<.01)., Conclusion: Cervical polyps detected before 12 weeks of gestation managed expectantly are a significant risk factor for spontaneous preterm birth before 34 weeks of gestation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Accumulating evidence suggests that the serotonergic (5-HT) system in the amygdala has significant effects on affective states. Dysregulation of the 5-HT system in the basolateral amygdaloid complex causes affective disorders. To search for therapeutic targets, subtype specification of 5-HT receptors is crucial. The present study was undertaken to identify the 5-HT receptor subtype responsible for the 5-HT-mediated suppression of excitatory transmission to principal neurons (PNs) in the lateral amygdala (LA). Whole-cell recordings were performed to record excitatory post synaptic currents (EPSCs) in acute rat brain slices. We confirmed that 5-HT and α-m-5-HT, a broad 5-HT 2 receptor agonist, attenuated EPSCs in LA PNs. The extent of suppressions by 5-HT and α-m-5-HT remained unchanged in the presence of ritanserin, a broad 5-HT 2 receptor antagonist. In the presence of NAS-181, a selective 5-HT 1B receptor antagonist, the extent of EPSC suppressions by 5-HT and α-m-5-HT was diminished. CP93129, a selective 5-HT 1B receptor agonist, attenuated EPSCs in LA PNs, and this effect was abolished in the presence of NAS-181. Additionally, the paired-pulse ratio of EPSCs was increased by CP93129. Thus, our results indicate that 5-HT and α-m-5-HT attenuate excitatory transmissions to LA PNs via presynaptic 5-HT 1B receptors., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Strategies to reduce sodium concentrations in packaged foods are effective and cost-effective approaches to reducing the burden of disease attributable to high sodium intakes. This review aimed to comprehensively describe, and explore characteristics of, national strategies to reduce sodium concentrations in packaged foods, and assess progress toward achieving national goals. A secondary aim was to understand the number, type, and variation of food category sodium targets set by countries compared with WHO global sodium benchmarks. National sodium reduction reformulation strategies were identified from a search of peer-reviewed and gray literature up to December 2019 supplemented by verified information from key contacts and experts up to December 2020. Key characteristics of countries' strategies were extracted, synthesized, and descriptively analyzed, including details of reformulation strategies and evaluation data. Country targets were mapped to the WHO global sodium benchmarks, and the number and variation of country sodium targets by WHO food categories were determined. Sixty-two countries had reformulation strategies to reduce sodium in packaged foods, and 19 countries had evaluated their reformulation strategies. Forty-three countries had sodium targets, which varied in type of targets (maximum sodium concentration: n = 26; maximum concentration plus relative reduction/average/sales-weighted average: n = 8; relative reduction: n = 7; average: n = 2), number of food category targets (range: n = 1 to 150), and regulatory approach (voluntary: n = 28; mandatory: n = 9; both: n = 6). Eight of 34 countries mapped to the WHO benchmarks had targets for just 1 specified food category (bread products). One-third of all countries were implementing national strategies to reduce sodium concentrations in packaged foods including establishing targets and/or processes for industry engagement. This review determined that there is scope to improve most countries' strategies. There has been limited progress in implementing and evaluating strategies between 2014 and 2019, and regional and income-level disparities persist. The WHO global sodium benchmarks present an important opportunity to accelerate reformulation action globally., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Cellular xenogeneic rejection by the innate immune system is a major immunological obstruction that needs to be overcome for the successful clinical use of xenografts. Our focus has been on macrophage-mediated xenogeneic rejection, since suppressing macrophage function has considerable potential for practical applications in the area of xenotransplantation. We report herein on an investigation of the suppressive effect of human CD177 (hCD177) against macrophage-mediated xenogeneic rejection. Wild type swine aortic endothelial cell (SEC) and an SEC transfectant with hCD177 (SEC/hCD177) were co-cultured with macrophages, and the degree of cytotoxicity was evaluated by WST-8 assays, and phagocytosis was examined using Calcein-AM labeling methods. The expression of anti/pro-inflammatory cytokines was evaluated by RT-qPCR and the phosphorylation of SHP-1 on macrophages in co-culture was evaluated by Western blotting. The result of cytotoxicity assays indicated that hCD177 suppressed M1 macrophage-mediated xenogeneic rejection (vs. SEC, p < 0.0001). Similarly, the result of phagocytosis assays indicated that hCD177 suppressed it (vs. SEC, p < 0.05). In addition, hCD177 significantly suppressed the expression of IL-1β, a pro-inflammatory cytokine, in M1 macrophages (vs. SEC, p < 0.01). Luciferase assays using THP1-Lucia NF-kB also showed a significant difference in NF-kB activation (vs. SEC, p < 0.001). In addition, hCD177 was found to induce the phosphorylation of SHP-1 in M1 macrophages (vs. SEC, p < 0.05). These findings indicate that hCD177 suppresses M1 macrophage-mediated xenogeneic rejection, at least in part via in the phosphorylation of SHP-1., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To investigate the incidence of umbilical cord prolapse (UCP) and its influence on infant prognosis in pregnant women with preterm premature rupture of membranes (PPROM)., Materials and Methods: We conducted a retrospective cohort study in a single tertiary perinatal center between 2009 and 2017. Singleton pregnancies with PPROM that occurred between 22 and 33 weeks of gestation were included. Infantile composite adverse outcome consisted of death, severe intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis, and sepsis before discharge. Infantile outcomes were compared between pregnancies that were complicated by UCP and those that were not., Results: Out of 208 singleton pregnancies included in the analysis, UCP occurred in 12 (5.8%) cases. The gestational age of pregnancies with UCP was significantly lesser than that of those without UCP. The incidence of infantile composite adverse outcome in patients with UCP was 16.7%, and this was not significantly higher than the incidence in patients without UCP (6.6%, P = 0.21). UCP was not shown to be associated with infantile composite adverse outcome in a multivariate regression model. Gestational age <25 weeks at delivery was significantly associated with infantile composite adverse outcome., Conclusions: The incidence of UCP was 5.8% among singleton pregnancies, with PPROM being managed expectantly between 22 and 33 weeks' gestation. Preterm UCP may not be associated with infantile adverse outcomes provided emergency cesarean delivery is available at all time., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Oropharyngeal swallowing is centrally mediated by a swallowing central pattern generator (Sw-CPG) in the medulla oblongata. The activity of the Sw-CPG depends on the sensory inputs determined by physical and chemical bolus properties. Here we investigate the sensory-motor integration during swallowing arising from different sensory sources. To do so we electrically stimulated the superior laryngeal nerve and we triggered swallowing with oral injections of distilled water or capsaicin solution and extracellularly recorded from swallowing interneurons in arterially perfused brainstem preparations of rats. We recorded the activities of 40 neurons, while monitoring the motor activities of the phrenic, vagal and hypoglossal nerves. Eighteen neurons responded to electrical stimulation of the ipsilateral superior laryngeal nerve, and 6 neurons were excited by oral fluid injection, while 16 non-respiratory neurons did not receive afferent inputs to either electrical or physiological stimuli. The cellular activities displayed by swallowing interneurons during electrical and physiological stimulation of pharyngeal and laryngeal afferent input reveal complex adaptations of the timing of firing patterns and frequencies. The modulation of neuronal activity is likely to contribute to the coordination of efficient bolus transfer during the pharyngeal stage of swallowing., (Copyright © 2021 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Objective: To elucidate the impact of the intended delivery mode on long-term outcomes among extremely preterm infants., Materials and Methods: Women who delivered singletons between 23 0/7 and 25 6/7 weeks of gestation from January 2010 to March 2014 and their infants were included in this study. The cases of fetal growth restriction and those with a chromosomal or major structural abnormality were excluded. The cases of fetal death that was diagnosed before labor onset and cases of non-reassuring fetal status, placental abruptions or umbilical cord prolapse that was diagnosed at labor onset were also excluded. The primary outcome was the incidence of composite adverse events, including death, cerebral palsy, or neurodevelopmental delay, at the age of three years. The composite adverse events, including death, grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis, focal intestinal perforation, and sepsis of neonatal period, were assessed as short-term outcomes. The association between the intended delivery mode and primary outcome, short-term outcome, and each component was analyzed using a multivariate logistic regression model., Results: Eighty cases were included in the analyses. Primary outcomes could be assessed in 72 cases. Infantile composite adverse events before discharge were observed in 19 cases (24%). The prevalence of primary outcomes was 40% (29 cases). The intended delivery mode was not associated with primary and short-term outcomes and each component complication., Conclusion: An advantage of intended cesarean delivery in terms of prognosis at three years of age in extremely preterm infants was not observed., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier B.V.)