Search

Sequence-selective G-quadruplex ligands are valuable for controlling gene expression. Here, we established a new fluorescence displacement assay using a NRAS G-quadruplex selective fluorescent probe to identify sequence-selective DNA G-quadruplex ligands. These sequence-selective NRAS G-quadruplex ligands retained their binding affinity even in the presence of excessive human telomeric DNA G-quadruplex and regulated enzymatic activities in a sequence-selective manner.

A single session of aerobic or resistance training transiently enhances cognitive function, making it a valuable strategy for dementia prevention in the older people. Despite its acknowledged benefits, the precise mechanism behind exercise-induced cognitive improvement remains controversial. In the present study, we investigated the impact of altered cerebral blood flow (CBF) on brain neural activity originating from motor executive and inhibitory processing using electroencephalographic event-related potentials (EEG-ERPs). Sixteen healthy subjects participated in four sessions, with EEG-ERPs measured during somatosensory Go/No-go tasks. The sessions were conducted under four distinct respiratory conditions presented in random order: normal breathing (NB) and rapid breathing (RB) with room air, normal breathing with hypercapnic gas (5% CO 2 , 21% O 2 , and balanced N 2 ) (NB + Gas), and rapid breathing with the same gas (RB + Gas). Changes in CBF were evaluated based on the middle cerebral artery mean blood velocity (MCA V mean ) using transcranial Doppler. [Formula: see text] was decreased under the RB condition but increased under the NB + Gas condition, thereby decreasing and increasing MCA V mean , respectively. Under the NB + Gas condition, MCA V mean significantly increased, but it had no effect on either the executive or inhibitory function. In contrast, the reduction in MCA V mean induced by RB decreased the peak amplitudes of Go-P300 and No-go-P300. However, even under the RB + Gas condition while MCA V mean increased, the peak amplitudes of both also decreased. These findings suggest that neither increases nor decreases in CBF affected cognitive function. NEW & NOTEWORTHY A single session of aerobic or resistance training transiently enhances cognitive function, but the precise mechanism behind this exercise-induced cognitive improvement remains unknown. We investigated the effect of altered cerebral blood flow (CBF) on brain neural activity originating from motor executive and inhibitory processing using electroencephalographic event-related potentials. Exercise-induced improvement in cognitive function could not be explained by an increase in CBF, whereas a decrease in CBF did not affect cognitive function.

Artificial metalloenzymes, in which a metal complex and protein matrix are combined, have been synthesized to catalyze stereoselective reactions using the chiral environment provided by the protein cavity. Artificial metalloenzymes can be engineered by the chemical modification and mutagenesis of the protein matrix. We developed artificial non-heme metalloenzymes using a cupin superfamily protein (TM1459) with a 4-His tetrad-metal-binding motif. The Cu-bound H52A/C106D mutant with 3-His triad showed a S-enantioselective Michael addition of nitromethane to α,β-unsaturated ketone, 2-aza-chalcone 1. In this study, we demonstrated a chemical modification near the copper-binding site of this mutant to reverse its enantioselectivity. For chemical modification, the amino acid on the Si-face of the binding state of 1 to the copper center was replaced with Cys, followed by reaction with 4,4'-dithiopyridine (4-PDS) to form S-(pyridin-4-ylthio)cysteine (Cys-4py). Cu-bound I49C-4py/H52A/C106D showed reversal of the enantioselectivity from S-form to R-form (ee = 71%, (R)). The effect of steric hindrance of the amino acids at position 49 on enantioselectivity was investigated using I49X/H52A/C106D mutants (X = A, C, I, F, and W). Additionally, chemical modification with 2,2'-dithiopyridine (2-PDS) produced I49-2py/H52A/C106D, which showed lower R-enantioselectivity than I49-4py/H52A/C106D. Among the mutants, the 4py-modification on the Si-face was the most effective in reversing the enantioselectivity. By tuning the Re-face side, the H54A mutation introduced into the I49C-4py/H52A/C106D increased the R-enantioselectivity (ee = 88%, (R)). X-ray crystallography revealed a coordinated structure with ligation of thiopyridine in Cu-bound I49C-4py/H52A/H54A/C106D., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To determine whether calf circumference, hand grip strength, and physical performance are linked to the incidence of serious adverse events (SAEs) in patients with subacute stroke., Design: Retrospective cohort study., Setting: Single rehabilitation hospital., Participants: Patients with stroke admitted for rehabilitation hospital., Intervention: Not applicable., Main Outcome Measures: The incidence of SAEs, such as death, cardiovascular events including recurrent stroke, and conditions requiring transfer to another hospital for specialized care or immediate treatment for an acute illness during hospitalization., Results: A total of 341 patients (median age: 74y) participated in this study, with 232 patients (68%) exhibiting low-physical performance. In the adjusted model, low-physical performance was significantly associated with SAEs (hazard ratio [HR], 3.01; 95% confidence interval [CI], 1.04-8.68; P=.042). However, low calf circumference (HR, 1.60; 95% CI, 0.76-3.38; P=.219) and low hand grip strength (HR, 0.98; 95% CI, 0.39-2.42; P=.960) did not show an independent association., Conclusions: Low-physical performance was independently associated with the occurrence of SAEs during hospitalization for rehabilitation in patients with subacute stroke., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

An 88-year-old man was referred to our hospital for further examination of an asymptomatic liver tumor. MRI showed low-intensity regions on T1-weighted images, high-intensity regions on T2-weighted images, high-intensity regions on diffusion-weighted images, and low-intensity regions in the arterial, portal, and hepatocyte phases of Gd-EOB-DTPA. PET scan of the tumor was positive, while endoscopy exhibited no malignant findings. The CT and MRI findings showed that the tumor could be a metastatic liver tumor, cholangiocellular carcinoma, or hepatic inflammatory pseudotumor. Considering the possibility of a malignant tumor, laparoscopic partial hepatectomy was performed as a diagnostic treatment. The patient was discharged on the 8th postoperative day. The histopathological diagnosis was diffuse large B-cell lymphoma. Since the lesion was localized to the liver, a diagnosis of malignant lymphoma originating from the liver was made. Six courses of R-THP-COP therapy were administered. No indication of recurrence was noted 18 months after surgery. Although primary hepatic lymphoma is difficult to diagnose, laparoscopic hepatectomy allows for an accurate diagnosis and early postoperative recovery, enabling rapid administration of chemotherapy.

Background: This retrospective observational study aimed to examine whether clinical inflammatory parameters were associated with the requirement dosage of unfractionated heparin (UFH) to maintain the range of ACT in veno-arterial extracorporeal membrane oxygenation (V-A ECMO) during lung transplantation surgery., Methods: Among all patients who underwent lung transplantation using V-A ECMO from January 2021 to May 2022, 27 patients were included. These patients were divided into two groups based on whether the infusion rate of UFH was increased from the initial infusion rate (7-8 units/kg/h) (increased group, n = 10) or the infusion rate was maintained or decreased (non-increased group, n = 17). The infusion rate was adjusted with an activated clotting time (ACT) target of 160-200 s., Results: At 1-2 h after starting ECMO, ACT was significantly lower (179.0 (166.5-188.5) versus 224.0 (193.0-242.0) sec, p = 0.006) and white blood cell (WBC) counts were higher in the increased group (12.6 ± 3.3 versus 9.5 ± 4.0 × 10 3 /μL, p = 0.046). The UFH infusion rates were higher in the increased group during the surgery. The cutoff value of WBC count at 1-2 h after starting ECMO for discriminating the need for increasing the UFH dosage was determined as 10.2 × 10 3 /μL (sensitivity 90.0%, specificity 58.8%, area under the curve 0.712) and discrimination of this cut-off value was confirmed as statistically significant (p = 0.018)., Conclusion: These data suggested that WBC count was associated with the requirement of an increase in the UFH infusion rate of V-A ECMO during lung transplantation surgery. Further evaluation is necessary to clarify the role of WBC count in determining the optimal UFH dosage., (© The Author(s), published by EDP Sciences, 2024.)

Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that facilitates the observation of tissue metabolism. It holds potential not only in research but also in clinical settings for understanding pathophysiology. This report presents the case of a 73-year-old woman with cerebellar arteriovenous malformation (AVM) in which MRS contributed to understanding the condition. Preoperative magnetic resonance imaging revealed T2/fluid-attenuated inversion recovery hyperintensity in the right cerebellar hemisphere. MRS of the same site showed an increase in lactate (Lac) and a decrease in N-acetylaspartate (NAA) levels. Through examination, she was diagnosed with a micro-AVM. Although transarterial embolization was performed on another day, completely occluding the shunt and treating the AVM, MRS showed a persistent decrease in NAA and elevated Lac levels and suggested that irreversible brain tissue damage had occurred due to the progression of venous congestion. The use of MRS in patients with suspected cerebellar AVMs allows for evaluating the degree of brain damage due to venous congestion, providing valuable insights for treatment decisions, in addition to evaluating treatment outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This research was funded by Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Reseach Grant NFRCH 24-0012. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kubo et al.)

Main Conclusion: MpMYB02, a regulator of marchantin accumulation, also acts as a key regulator of oil body formation. MpMYB02 induces the expression of MpSYP12B and promotes oil body formation, subsequently leading to marchantin accumulation. The oil body observed in Marchantia polymorpha is a cellular organelle surrounded by a unit membrane, accumulating various secondary metabolites such as marchantins and terpenes. We observed that oil body formation is regulated by MpMYB02, a key regulator of marchantin accumulation. In the Mpmyb02 mutant, no oil bodies were observed, although idioblast-like cells were present in the gemma. We introduced MpMYB02-glucocorticoid receptor (GR), a steroid-inducible transcriptional activator, into Mpmyb02 and assessed the effect of dexamethasone (DEX) on oil body formation. Following DEX treatment, transformed liverworts began forming oil bodies within 12 h. During the initial stages of oil body development, we observed the aggregation of small globular structures. DEX treatment upregulated several genes implicated in oil body formation, including MpSYP12B. Our findings underscore that MpMYB02 plays a crucial role not only in marchantin accumulation but also in oil body formation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A series of isostructural reticular frameworks with systematic differences on chemical structures allows us to disclose correlations between specific structural factors and properties, providing insights for designing novel porous materials. However, even slight differences in the molecular structure often lead to non-isostructural polymorphic frameworks particularly in the case of hydrogen-bonded organic frameworks (HOFs) because the structures of HOFs are based on a subtle balance of reversible interactions. In this study, we found that three simple analogues of tetracarboxylic acids with naphthalene, quinoxaline, and pyrazinopyrazine cores (NT, QX, and PP, respectively) yielded isostructural solvated HOFs (NT-1, QX-1, and PP-1, respectively), where hydrogen-bonded sql-networked sheets were slip-stacked with closely similar manners. More importantly, these isostructural HOFs underwent structural transformations in different manners upon removal of the guest solvents. Comparison of the crystal structures of the HOFs before and after the transformation revealed that intermolecular interactions of the core significantly affected on rearrangements of hydrogen bonds in the transformation. The results suggest the potential to control the properties and functions of isostructural HOFs by elements in the core., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background: Little is known about the association between fatigue and physical activity in patients hospitalized with subacute stroke., Objectives: The aim of this study was to investigate the association between fatigue and physical activity in patients hospitalized with subacute stroke., Methods: This cross-sectional study enrolled 244 consecutive patients with stroke who were admitted to a subacute rehabilitation ward at our hospital. We assessed fatigue with the Fatigue Assessment Scale (FAS) and used an accelerometer (Active style Pro HJA750-C, OMRON) to record the mean duration of sedentary behavior, light-intensity physical activity (LIPA), and moderate-to-vigorous-intensity physical activity (MVPA). We assessed all factors at 1 month after stroke. Multivariate linear regression analysis revealed the associations between FASscore and objectively measured physical activity., Results: In total, we analyzed 85 patients. The duration of the sedentary behavior was significantly associated with the FAS score ( β  = 1.46, p  = 0.037) and the Functional Balance Scale score ( β  = -1.35, p  = 0.045). The LIPA time was significantly associated only with the FBS score ( β  = 1.38, p  = 0.045), whereas MVPA was not associated with any variable.

Objectives: The present multicenter prospective observational study investigated the effectiveness and safety of neoadjuvant chemotherapy (NAC) for patients with borderline resectable pancreatic cancer (BRPC) and those with RPC contacting major vessels, with respect to a historical control of upfront surgery., Materials and Methods: Patients with BRPC and RPC contacting major vessels were prospectively registered and administered NAC with durations and regimens determined by the corresponding treating physician. Our primary aim was to assess the R0 resection rate, and secondary aim was to evaluate safety, resection rate, time to treatment failure, overall survival, and response rate., Results: Fifty of 52 enrolled patients were analyzed; 2 with serious comorbidities died during treatment. Thirty-one patients underwent resection, with R0 resection being achieved in 26 (52% of total and 84% of all resected cases). Univariate and multivariate analyses indicated age (≥75 years) as the only independent predictor of nonresection. Median progression-free survival and median survival time were longer in the prospective cohort than in the historical cohort., Conclusions: Overall, NAC for BRPC in real-world setting might yield R0 resection rates similar to those reported in previous clinical studies. Development of safe regimens and management strategies that can maintain treatment intensity in geriatric patients is warranted., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The enhancement of insulin secretion and of the proliferation of pancreatic β cells are promising therapeutic options for diabetes. Signals from the vagal nerve regulate both processes, yet the effectiveness of stimulating the nerve is unclear, owing to a lack of techniques for doing it so selectively and prolongedly. Here we report two optogenetic methods for vagal-nerve stimulation that led to enhanced glucose-stimulated insulin secretion and to β cell proliferation in mice expressing choline acetyltransferase-channelrhodopsin 2. One method involves subdiaphragmatic implantation of an optical fibre for the photostimulation of cholinergic neurons expressing a blue-light-sensitive opsin. The other method, which suppressed streptozotocin-induced hyperglycaemia in the mice, involves the selective activation of vagal fibres by placing blue-light-emitting lanthanide microparticles in the pancreatic ducts of opsin-expressing mice, followed by near-infrared illumination. The two methods show that signals from the vagal nerve, especially from nerve fibres innervating the pancreas, are sufficient to regulate insulin secretion and β cell proliferation., (© 2023. The Author(s).)

A 78-year-old man complained of subacute general fatigue and anorexia, following diplopia and gait disturbance. He demonstrated wide-based and small-stepped gait without objectively abnormal ocular movements. Brain ‍MRI showed enlargement of the pituitary stalk and gland with uniform contrast enhancement. PET-CT showed FDG ‍uptake in the pituitary gland, mediastinal lymph nodes, and left hilar lymph nodes. Blood investigations revealed panhypopituitarism and high serum IgG4 levels up to 265 ‍mg/dl. Histopathological examination revealed no IgG4-positive cell infiltration in the biopsied mediastinal lymph nodes. However, we suspected IgG4-associated hypophysitis based on the clinical symptoms and MRI findings, which were markedly resolved with steroid. Central masked diabetes insipidus was manifested, but was improved with oral desmopressin. We should pay close attention to the fact that IgG4-related hypophysitis may present with various symptoms regarded as indefinite complaints related to aging or underlying diseases, especially in elderly patients with multimorbidity.

Objective: To establish the Minimal Clinically Important Differences (MCIDs) for lower limb strength measured by the Motricity Index (LLMI) and trunk function assessed by the Trunk Control Test (TCT) in the acute phase of stroke in older patients. Further, the study sought to determine the cutoff values predicting functional prognosis at discharge for both the LLMI and TCT., Methods: This prospective cohort study was conducted for older patients (≥65 years) admitted for acute stroke, receiving guideline-based stroke care that includes early rehabilitation. The LLMI and TCT were measured within 7 days of admission and at discharge. The MCID was derived from receiving operating characteristic curves, based on a ≥ 1 point shift in the modified Rankin Scale (mRS) from admission to discharge. A good functional prognosis at discharge was defined as an mRS score of ≤ 3., Results: A total of 201 older patients with acute stroke were included. The TCT achieved an MCID of 13 (area under the curve [AUC] = 0.704, 95% confidence interval [CI]: 0.633-0.775), whereas the LLMI lacked the precision to produce a significant MCID. The optimal cutoff points for predicting a good outcome were found to be an LLMI score of 65 (AUC = 0.770, 95% CI: 0.705-0.835) and a TCT score of 25 (AUC = 0.827, 95% CI: 0.768-0.887) upon admission., Conclusions: This study identified a valid MCID for the TCT, failed to do so for the LLMI, and established cutoff values for both the LLMI and TCT that can predict good outcomes in older patients with acute stroke.

Objectives: This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA)., Methods: Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual for development clinical practice guidelines by Minds, a project promoting evidence-based medicine in Japan, for observational studies., Results: One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 (95% confidence interval [CI]: 0.94-1.79)/1.48 (95% CI: 0.95-2.29)/1.89 (95% CI: 0.81-4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection and malignancy caused by TNF inhibitors was 0%-4%., Conclusions: Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, particularly well-designed RCTs, are necessary to confirm the efficacy and safety of TNF inhibitors for systemic JIA., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA)., Methods: Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan., Results: Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6 and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9% and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases., Conclusions: Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL -6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background Aims: Tacrolimus (TAC) plus short-term methotrexate (stMTX) is used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). TAC blood concentrations are frequently adjusted to enhance the graft-versus-leukemia/lymphoma effect or attenuate severe GVHD. Limited information is available on the clinical impact of these adjustments and the optimal time to perform them in order to achieve good clinical outcomes., Methods: We retrospectively analyzed 211 patients who underwent allo-HSCT at our institutes., Results: Higher TAC concentrations in week 3 correlated with a significantly higher cumulative incidence of relapse (CIR) (P = 0.03) and lower nonrelapse mortality (P = 0.04). The clinical impact of high TAC concentrations in week 3 on CIR was detected in the refined disease risk index: low/intermediate (P = 0.04) and high (P < 0.01), and conditioning regimens other than cyclophosphamide/total body irradiation and busulfan/cyclophosphamide (P = 0.07). Higher TAC concentrations in week 1 correlated with a lower grade 2-4 acute GVHD rate (P = 0.01). Higher TAC concentrations in weeks 2 and 3 correlated with slightly lower (P = 0.05) and significantly lower (P = 0.02) grade 3-4 acute GVHD rates, respectively. Higher TAC concentrations in weeks 1 and 3 were beneficial for severe acute GVHD in patients with a human leukocyte antigen-matched donor (P = 0.03 and P < 0.01, respectively), not treated with anti-thymocyte globulin (P = 0.02 and P = 0.02, respectively), and receiving three stMTX doses (P = 0.03 and P = 0.02, respectively)., Conclusions: The clinical impact of TAC concentrations varied according to patient characteristics, including disease malignancy, conditioning regimens, donor sources, and GVHD prophylaxis. These results suggest that TAC management needs to be based on patient profiles., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: We investigated the reliability and validity of the 2-min step test (2MST) for assessing the exercise endurance of individuals with stroke and lower-limb musculoskeletal disorders., Participants and Methods: The participants were 39 individuals with stroke and 42 with lower-limb musculoskeletal disorders (mainly hip fractures) from the convalescent rehabilitation wards of four hospitals. The concurrent validity and congruence between the 2MST and the 6-min walk test (6MWT) and construct validity by hypotheses testing, including mobility and lower limb muscle strength, were also confirmed. A subset of participants (stroke-group, n  = 15; musculoskeletal-group, n  = 19) underwent a retest 2MST for our evaluation of relative and absolute reliability using the intraclass correlation coefficient (ICC 1,1 ) and Bland-Altman plot., Results: Both groups showed a moderate correlation between the 2MST and 6MWT ( ρ  = 0.55-0.60), but the congruence was not sufficient. The 6MWT was correlated with mobility in both groups and with muscle strength in the stroke group, whereas the 2MST did not show a significant correlation with mobility. The relative reliability was excellent in both groups (ICC 1,1  > 0.9). In terms of absolute reliability, the width of the limit of agreement was 18.8% for the stroke group and 15.4% for the musculoskeletal group, relative to their respective sample means of 2MST. A fixed bias was identified in the stroke group, in which step counts increased by 6.5 steps upon retesting., Discussion: Our analyses revealed that the 2MST is a valid and reliable tool for assessing the exercise endurance of individuals with stroke or lower-limb musculoskeletal disorders. However, it is necessary to validate the absolute reliability observed herein by using a larger sample size. In addition, when assessing the exercise endurance of individuals with stroke, it may be necessary to consider the potential bias of an increased step count during retesting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Ishigaki, Kubo, Yoshida, Shimizu and Ogawa.)

Objective: In this study, we investigated whether the COVID-19 pandemic affected achievement of guideline targets for HbA1c, blood pressure (BP), and low-density lipoprotein (LDL) cholesterol in people with diabetes mellitus (DM)., Materials and Methods: Data for 556 people with DM who were treated regularly for 4 years before and during the COVID-19 pandemic in Japan were analyzed in this retrospective study. Achieved targets were defined as HbA1c < 7.0%, BP < 130/80 mmHg, and LDL cholesterol < 100 or < 120 mg/dL depending on the presence or absence of coronary artery disease., Results: In 2019, before the start of the COVID-19 pandemic, achievement rates of guideline targets for HbA1c, BP and LDL cholesterol were 53.4%, 45.9% and 75.7%, respectively. In 2020, the achievement rates for HbA1c and BP targets were significantly decreased to 40.8% and 31.3%, respectively. The achievement rates for the HbA1c target gradually recovered to 49.3% in 2021 and to 51.1% in 2022. However, recovery in achieving the BP target was slow, remaining at 40.5% even in 2022. On the other hand, the achievement rate for the LDL cholesterol target was not affected and remained relatively high during the COVID-19 pandemic., Conclusions: The rates of achieving therapeutic targets for HbA1c and BP have not been high enough in people with DM, and the rates were further reduced by lifestyle changes due to the COVID-19 pandemic. Although there has been a trend toward improvement with the lifting of behavioral restrictions, more intensified treatment is necessary to achieve good control., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00715-8., Competing Interests: Conflict of interestTS received honoraria for educational lectures from Daiichi Sankyo Co., Ltd. TaM received honoraria for educational lectures from AstraZeneca K.K., Eli Lilly Japan K.K., Nippon Boehringer Ingerheim Co., Novartis Pharma K.K., Novo Nordisk Pharma, and Ono Pharmaceutical Co. All other authors declare that they have no conflict of interest., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Although surgical resection is generally suggested for nonfunctioning pancreatic neuroendocrine tumors, observation can be proposed for carefully selected patients with small tumors. However, the indications for observation remain unclear., Methods: This retrospective study included 77 patients with nonfunctioning pancreatic neuroendocrine tumors, including small tumors (≤2.0 cm, n = 41), who received pancreatectomy. The ratio of the mean computed tomography value of a tumor in the late arterial/equilibrium phase (computed tomography a/e ratio) was used to evaluate tumor vascularity. Pathologic examinations of small tumors were conducted. The associations among the computed tomography a/e ratio, pathologic findings, and survival outcomes were investigated., Results: Small tumors were pathologically categorized by the degree of fibrosis as follows: medullary (n = 20), intermediate (n = 11), and fibrotic (n = 10). The fibrotic type had significantly lower computed tomography a/e ratios than the medullary type (median, 1.42 vs 2.03, P < .001). The median number of vessels with microscopic venous invasion was significantly higher in the fibrotic type than in the medullary type (4.5 vs 0.0, P < .001). The cutoff value of the computed tomography a/e ratio for predicting microscopic venous invasion was determined to be 1.54 by the receiver operating characteristic curve (area under the curve, 0.832; sensitivity, 80.0%; specificity, 83.9%; accuracy, 82.9%). Microscopic venous invasion was an independent prognostic factor for relapse-free survival in overall patients (hazard ratio 5.18, P = .017)., Conclusion: The computed tomography a/e ratio may be a useful predictor of the metastatic potential of nonfunctioning pancreatic neuroendocrine tumors and may help decide the indications of observation for small nonfunctioning pancreatic neuroendocrine tumors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Amyloid-beta (Aβ) and tau accumulations impair long-term potentiation (LTP) induction in animal hippocampi. We investigated relationships between motor-cortical plasticity and biomarkers for Alzheimer's disease (AD) diagnosis in subjects with cognitive decline., Methods: Twenty-six consecutive subjects who complained of memory problems participated in this study. We applied transcranial quadripuse stimulation with an interstimulus interval of 5 ms (QPS5) to induce LTP-like plasticity. Motor-evoked potentials were recorded from the right first-dorsal interosseous muscle before and after QPS5. Cognitive functions, Aβ42 and tau levels in the cerebrospinal fluid (CSF) were measured. Amyloid positron-emission tomography (PET) with 11 C-Pittsburg compound-B was also conducted. We studied correlations of QPS5-induced plasticity with cognitive functions or AD-related biomarkers., Results: QPS5-induced LTP-like plasticity positively correlated with cognitive scores. The degree of LTP-like plasticity negatively correlated with levels of CSF-tau, and the amount of amyloid-PET accumulation at the precuneus, and correlated with the CSF-Aβ42 level positively. In the amyloid-PET positive subjects, non-responder rate of QPS5 was higher than the CSF-tau positive rate., Conclusions: Findings suggest that QPS5-induced LTP-like plasticity is a functional biomarker of AD. QPS5 could detect abnormality at earlier stages than CSF-tau in the amyloid-PET positive subjects., Significance: Assessing motor-cortical plasticity could be a useful neurophysiological biomarker for AD pathology., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Rationale: Follow-up of patients with emphysema treated with endobronchial valves is limited to 3-12 months after treatment in prior reports. To date, no comparative data exist between treatment and control subjects with a longer follow-up. Objectives: To assess the durability of the Spiration Valve System (SVS) in patients with severe heterogeneous emphysema over a 24-month period. Methods: EMPROVE, a multicenter randomized controlled trial, presents a rigorous comparison between treatment and control groups for up to 24 months. Lung function, respiratory symptoms, and quality-of-life (QOL) measures were assessed. Results: A significant improvement in forced expiratory volume in 1 second was maintained at 24 months in the SVS treatment group versus the control group. Similarly, significant improvements were maintained in several QOL measures, including the St. George's Respiratory Questionnaire and the COPD Assessment Test. Patients in the SVS treatment group experienced significantly less dyspnea than those in the control group, as indicated by the modified Medical Research Council dyspnea scale score. Adverse events at 24 months did not significantly differ between the SVS treatment and control groups. Acute chronic obstructive pulmonary disease exacerbation rates in the SVS treatment and control groups were 13.7% (14 of 102) and 15.6% (7 of 45), respectively. Pneumothorax rates in the SVS treatment and control groups were 1.0% (1 of 102) and 0.0% (0 of 45), respectively. Conclusions: SVS treatment resulted in statistically significant and clinically meaningful durable improvements in lung function, respiratory symptoms, and QOL, as well as a statistically significant reduction in dyspnea, for at least 24 months while maintaining an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Background: Stroke-related sarcopenia is an important prognosis factor and an intervention target for improving outcomes in patients with stroke., Aim: This study aimed to identify the association between sarcopenia, possible sarcopenia, muscle weakness, muscle mass and calf circumference, and the functional outcomes 3 months after stroke., Methods: In this single-centre prospective observational study, muscle strength, muscle mass, and calf circumference were measured in patients with acute stroke at hospital discharge. Diagnosis of sarcopenia, possible sarcopenia, muscle weakness, low muscle mass, and low calf circumference were defined according to the 2019 Asian Working Group for Sarcopenia criteria. The primary outcome measure was the modified Rankin Scale (mRS) score at 3 months, with an mRS score of 3 or higher indicating a poor outcome. Logistic regression analysis was conducted to examine independent associations between each assessment and functional outcomes., Results: A total of 247 patients (median age: 73 years) were included in this study. The prevalence of sarcopenia was 28% (n = 70), and in the adjusted model, sarcopenia (aOR = 2.60, 95% CI 1.07-6.31, p = 0.034), muscle weakness (aOR = 3.40, 95% CI 1.36-8.52, p = 0.009), and low muscle mass (aOR = 2.61, 95% CI 1.04-6.52) were significantly associated with poor functional outcome. Nevertheless, other evaluations did not demonstrate an independent association with the outcome., Conclusion: Sarcopenia, muscle weakness, and low muscle mass were found to be independently associated with functional outcomes 3 months after stroke, and muscle weakness exhibited the strongest association with outcomes among them., (© 2024. The Author(s).)

Background: The 3-min walk test (3MWT) has been used in the clinical setting., Objective: To present the 3MWT value and investigate its association with motor and respiratory functions of healthy older adults., Methods: Two hundred six older adults and 27 younger adults were enrolled. The 3MWT was assessed by the walking distance within 3 min. Knee extension muscle strength (KEMS), 5-repetition sit-to-stand (5 R-STS), Timed Up and Go (TUG), forced vital capacity (FVC), forced expiratory volume 1.0 (FEV1.0), maximal expiratory pressure (MEP), and maximal inspiratory pressure (MIP) were measured. The 3MWT distance was examined by age group (18-39, 60-69, 70-79, and 80-89 years). A multivariate regression analysis investigated the association between 3MWT and motor function test., Results: The 3MWT values in each age group were 273-385, 233-414, 93-351, and 171-345 m for men and 215-375, 220-349, 198-325, and 174-332 m for women respectively. The 3MWT values were correlated with age, body mass index (BMI), KEMS, 5 R-STS, TUG, FVC, FEV1.0, MEP, and MIP. On the multivariate regression analysis, 3MWT was significantly associated with BMI (standard beta = -0.18; 95% confidence interval [CI], -3.20 to 0.83), KEMS (standard beta = 0.37; 95% CI, 0.06-0.13), 5 R-STS (standard beta = -0.13; 95% CI, -5.70 to -0.13), and TUG (standard beta = -0.36; 95% CI, -17.15 to -7.73) in older adults (adjusted R 2  = 0.47)., Conclusions: The 3MWT distance decreased with age and was associated with motor and respiratory functions. No range trends were observed among groups. Our findings suggest that 3MWT reflects functional capacity.

Phyllodes tumors are uncommon breast neoplasms that constitute 1-2% of breast malignancies. Invasive ductal carcinoma in the epithelial component of phyllodes tumor is very rare. When carcinoma is detected within the specimen, the management of treatment changes completely. We report a rare case of invasive ductal carcinoma arising in a giant borderline malignancy phyllodes tumor in a 51-year-old female patient. A painful 20 cm mass was found in her right breast, and a needle biopsy revealed fibroadenoma or benign phyllodes tumor, and a total mastectomy was performed. Pathological results showed that a borderline malignant phyllodes tumor coexisted with invasive ductal carcinoma. We explained that axillary surgery was necessary because invasive cancer was diagnosed after surgery, but the patient requested follow-up using images. Endocrine therapy was performed as postoperative adjuvant therapy, and the follow-up is underway without recurrence.

The Omni Legend 32 PET/CT system features silicon photomultiplier (SiPM)-based detectors with bismuth germanium oxide crystals and a 32-cm axial field of view (FOV). The present study aimed to determine the performance characteristics of the Omni Legend 32 PET/CT system according to National Electrical Manufacturers Association (NEMA) NU 2-2018 standards. Methods: The PET component of this system comprises 22 detector modules; each module contains 24 detector blocks with 72 bismuth germanium oxide crystals with a volume of 4.1 × 4.1 × 30 mm coupled to 18 SiPM devices with a 6 × 6 mm area, resulting in an axial FOV of 32 cm. The spatial resolution, sensitivity, count rate performance, and image quality delivered by PET were evaluated using the NEMA NU 2-2018 standard. PET images of 2 patients were evaluated to get a visual first impression of the Omni Legend 32 PET/CT system together with Precision DL. Results: The average spatial resolution at 1, 10, and 20 cm from the central axis was 4.3, 5.3, and 6.2 mm, respectively, for filtered backprojection and 3.7, 4.3, and 5.1 mm, respectively, for ordered-subset expectation maximization. The NEMA sensitivity was 47.30 and 47.05 cps/kBq at the axial center of the FOV and at a 10-cm radial offset, respectively. The scatter fraction, count rate accuracy, and peak noise-equivalent count rates were 35.4%, 1.7%, and 501.7 kcps, respectively, at 15.7 kBq/mL. Contrast recovery for the NEMA body phantom from the smallest to the largest sphere ranged from 61.3% to 93.0%, with a background variability of 5.4%-11.7% and a lung error of 5.1% for Q.Clear (β-value, 50). Good patient image quality was obtained with the Omni Legend 32. Conclusion: The Omni Legend 32 has class-leading sensitivity and count rates within the category of whole-body PET systems while maintaining spatial resolution broadly comparable to that of other current SiPM-based PET/CT systems. This combination of properties results in a very good image quality., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Few therapies have produced significant improvement in cardiac structure and function after ischemic cardiac injury (ICI). Our possible explanation is activation of local inflammatory responses negatively impact the cardiac repair process following ischemic injury. Factors that can alter immune response, including significantly altered cytokine levels in plasma and polarization of macrophages and T cells towards a pro-reparative phenotype in the myocardium post-MI is a valid strategy for reducing infarct size and damage after myocardial injury. Our previous studies showed that cortical bone stem cells (CBSCs) possess reparative effects after ICI. In our current study, we have identified that the beneficial effects of CBSCs appear to be mediated by miRNA in their extracellular vesicles (CBSC-EV). Our studies showed that CBSC-EV treated animals demonstrated reduced scar size, attenuated structural remodeling, and improved cardiac function versus saline treated animals. These effects were linked to the alteration of immune response, with significantly altered cytokine levels in plasma, and polarization of macrophages and T cells towards a pro-reparative phenotype in the myocardium post-MI. Our detailed in vitro studies demonstrated that CBSC-EV are enriched in miR-182/183 that mediates the pro-reparative polarization and metabolic reprogramming in macrophages, including enhanced OXPHOS rate and reduced ROS, via Ras p21 protein activator 1 (RASA1) axis under Lipopolysaccharides (LPS) stimulation. In summary, CBSC-EV deliver unique molecular cargoes, such as enriched miR-182/183, that modulate the immune response after ICI by regulating macrophage polarization and metabolic reprogramming to enhance repair., Competing Interests: Declaration of competing interest The authors declare that S. R. Houser is a named inventor on intellectual property filings that are related to the cortical bone stem cells used in this study. In addition, S. R. Houser is a cofounder and scientific advisor and holds equity in MyocardTherapeutics, LLC, a biotech startup which will license S. R. Houser’s cortical bone cell technology from Temple University for commercial development and clinical trials. MyocardTherapeutics, LLC, has not funded any aspect of this research. S. Mohsin is a named inventor on intellectual property filings that are related to the cortical bone stem cells used in this study., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The regional differences in cerebral oxygen extraction fraction (OEF) in brain were investigated using positron emission tomography (PET) in detail with consideration of systemic errors in PET measurement estimated by simulation studies. The cerebral blood flow (CBF), cerebral blood volume (CBV), OEF, and cerebral metabolic rate of oxygen (CMRO 2 ) were measured on healthy men by PET with 15 O-labeled gases. The OEF values in the pons and the parahippocampal gyrus were significantly smaller than in the other brain regions. The OEF value in the lateral side of the occipital cortex was largest among the cerebral cortical regions. Simulation studies have revealed that errors in OEF caused by regional differences in the distribution volume of 15 O-labeled water, as well as errors in OEF caused by a mixture of gray and white matter, must be negligible. The regional differences in OEF in brain must exist which might be related to physiological meanings.Article title: Kindly check and confirm the edit made in the article title.I have checked the article title and it is OK as is. Trial registration: The UMIN clinical trial number: UMIN000033382, https://www.umin.ac.jp/ctr/index.htm., (© 2023. The Physiological Society of Japan.)

Elucidating the mechanism(s) modulating appropriate tissue size is a critical biological issue. Pancreatic β cells increase during pregnancy via cellular proliferation, but how β cells promptly decrease to the original amount after parturition remains unclear. Herein, we demonstrate the role and mechanism of macrophage accumulation in this process. In the final stage of pregnancy, HTR1D signaling upregulates murine β cell CXCL10, thereby promoting macrophage accumulation in pancreatic islets via the CXCL10-CXCR3 axis. Blocking this mechanism by administering an HTR1D antagonist or the CXCR3 antibody and depleting islet macrophages inhibited postpartum β cell mass reduction. β cells engulfed by macrophages increased in postpartum islets, but Annexin V administration suppressed this engulfment and the postpartum β cell mass reduction, indicating the accumulated macrophages to phagocytose β cells. This mechanism contributes to both maintenance of appropriate β cell mass and glucose homeostasis promptly adapting to reduced systemic insulin demand after parturition., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Maternal hypothyroidism (MH) could adversely affect the cardiac disease responses of the progeny. This study tested the hypothesis that MH reduces early postnatal cardiomyocyte (CM) proliferation so that the adult heart of MH progeny has a smaller number of larger cardiac myocytes, which imparts adverse cardiac disease responses following injury. Thyroidectomy (TX) was used to establish MH. The progeny from mice that underwent sham or TX surgery were termed Ctrl (control) or MH (maternal hypothyroidism) progeny, respectively. MH progeny had similar heart weight (HW) to body weight (BW) ratios and larger CM size consistent with fewer CMs at postnatal day 60 (P60) compared with Ctrl (control) progeny. MH progeny had lower numbers of EdU + , Ki67 + , and phosphorylated histone H 3 (PH 3 ) + CMs, which suggests they had a decreased CM proliferation in the postnatal timeframe. RNA-seq data showed that genes related to DNA replication were downregulated in P5 MH hearts, including bone morphogenetic protein 10 ( Bmp10 ). Both in vivo and in vitro studies showed Bmp10 treatment increased CM proliferation. After transverse aortic constriction (TAC), the MH progeny had more severe cardiac pathological remodeling compared with the Ctrl progeny. Thyroid hormone (T4) treatment for MH mothers preserved their progeny's postnatal CM proliferation capacity and prevented excessive pathological remodeling after TAC. Our results suggest that CM proliferation during early postnatal development was significantly reduced in MH progeny, resulting in fewer CMs with hypertrophy in adulthood. These changes were associated with more severe cardiac disease responses after pressure overload. NEW & NOTEWORTHY Our study shows that compared with Ctrl (control) progeny, the adult progeny of mothers who have MH (MH progeny) had fewer CMs. This reduction of CM numbers was associated with decreased postnatal CM proliferation. Gene expression studies showed a reduced expression of Bmp10 in MH progeny. Bmp10 has been linked to myocyte proliferation. In vivo and in vitro studies showed that Bmp10 treatment of MH progeny and their myocytes could increase CM proliferation. Differences in CM number and size in adult hearts of MH progeny were linked to more severe cardiac structural and functional remodeling after pressure overload. T4 (synthetic thyroxine) treatment of MH mothers during their pregnancy, prevented the reduction in CM number in their progeny and the adverse response to disease stress.

Objective: To investigate the relationship between nutritional status measured by the Global Leadership Initiative on Malnutrition (GLIM) criteria and the intensity of physical activity, and to determine the association between these factors and the activities of daily living (ADLs) in patients with subacute stroke during hospitalization., Design: A cross-sectional study., Setting: The study was conducted in the rehabilitation unit at a neurosurgical hospital., Participants: One hundred and twenty-eight patients with subacute stroke (N=128)., Interventions: Not applicable., Main Outcome Measures: Nutritional status was assessed using GLIM criteria. Sedentary behavior (SB), light-intensity physical activity (LIPA), and moderate-to-vigorous physical activity (MVPA) were measured using an accelerometer. Multiple regression analysis was used to investigate the relationship between nutritional status and intensity of physical activity. Moreover, the association of nutritional status and physical activity intensity with ADLs was determined using multiple regression analysis and mediation analysis., Results: Malnutrition was associated with SB time (B = 16.241, P=.009) and LIPA time (B = -17.656, P=.002), but not MVPA time (B = -0.472, P=.776). SB time (B = -0.063, P=.009) and LIPA time (B = 0.093, P<.001) were associated with functional independence measure for motor function, while MVPA time (B = -0.080, P=.379) was not. SB time (coefficient = -10.785, P<.001) and LIPA time (coefficient = -12.054, P<.001) were significant mediators between nutrition status and ADLs., Conclusions: Malnutrition was associated with a SB time and LIPA time, but not MVPA time, in patients with sub-acute stroke. SB and LIPA times were associated with ADLs and mediated between nutrition status and ADLs in these patients. The association of nutritional status on physical activity and ADLs should be considered in stroke rehabilitation., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to investigate the prevalence and associated factors of sarcopenia in patients following stroke during acute hospitalisation., Methods: This single-centre prospective observational cohort study assessed skeletal muscle mass using bioelectrical impedance analysis and muscle strength of patients with acute stroke at hospital discharge. Sarcopenia was diagnosed according to the AWGS-2019 criteria. Multiple logistic regression analyses were performed to identify associated factors of post stroke sarcopenia., Results: A total of 286 participants (32% female; median age, 72 years) were included in this study. The prevalence of post-stroke sarcopenia was 32.5% (n = 93). In multiple logistic regression analysis, age (adjusted odds ratio [aOR]: 1.10; 95% confidence interval [CI]: 1.05-1.05), National Institute of Health Stroke Scale (aOR: 1.15; 95% CI: 1.04-1.27), body mass index (BMI) (aOR: 0.73; 95% CI: 0.64-0.84) and Functional Oral Intake Scale (aOR: 0.67; 95% CI: 0.51-0.89) were independently associated with post-stroke sarcopenia during acute hospitalisation., Conclusion: Approximately one-third of acute stroke patients were diagnosed with sarcopenia at hospital discharge, and older age, severe stroke, low BMI, and poor swallowing function are associated with sarcopenia following stroke during acute hospitalisation., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The nuclear receptor subfamily 5, Group A, Member 1 (NR5A1) gene encodes steroidogenic factor 1 (SF1), which is necessary for development of steroid hormone-producing tissues including the gonad and adrenal gland. An induced pluripotent stem cell line (iPSC) LCHi002-B was generated from a participant with differences (disorders) of sex development (DSD) and multiple genetic variants including a large deletion in NR5A1, and three single nucleotide changes in DYNC2H1, PDE4D, and ZFPM2. The line presented typical morphology, expressed stem cell markers, differentiated into three germ layers, had normal karyotype, was mycoplasma-free, and carried mutations in NR5A1, DYNC2H1, PDE4D, and ZFPM2., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Monica M Laronda reports financial support was provided by Burroughs Wellcome Fund., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Ascites is sometimes detected after allogeneic hematopoietic stem cell transplantation (allo-HSCT); however, since limited information is currently available, its clinical meaning remains unclear. Therefore, we herein examined potential factors for and the impact of ascites on the prognosis of patients after allo-HSCT at our institutes. Fifty-eight patients developed ascites within 90 days of allo-HSCT (small in 34 (16%), moderate-large in 24 (11%)). A multivariate analysis identified veno-occlusive disease/sinusoidal obstruction syndrome (p = 0.01) and myeloablative conditioning (p = 0.01) as significant potential factors for the development of small ascites. Thrombotic microangiopathy (TMA) (p < 0.01) was a significant potential factor for moderate-large ascites. The incidence of both small and moderate-large ascites correlated with lower overall survival (p = 0.03 for small ascites and p < 0.01 for moderate-large ascites) and higher non-relapse mortality rates (p = 0.03 for small ascites and p < 0.01 for moderate-large ascites). Lower OS and higher NRM rates correlated with the incidence of both small and moderate-large ascites. Further investigation is warranted to establish whether the clinical sign of ascites improves the diagnostic quality of TMA in a large-scale study., (© 2023. Springer Nature Limited.)

Introduction: The treatment of ultrasound unstable hips with the Tübingen splint is currently under discussion. However, there is a lack of long-term follow-up data. This study presents to the best of our knowledge first radiological mid-term to long-term data of the successful initial treatment with the Tübingen splint of ultrasound unstable hips., Materials and Methods: From 2002 to 2022 the treatment of ultrasound unstable hips type D, III and IV (age ≤ 6 weeks, no severe limitation of abduction) with the Tübingen splint worn as a plaster is evaluated. Based on data derived from routine X-rays during the follow-up period, a radiological follow-up (FU) analysis until the age of 12 years was performed. The acetabular index (ACI) and center-edge angle (CEA) were measured and classified according to Tönnis as normal findings (NF), slightly (sliD) or severely dysplastic (sevD)., Results: 193 of 201 (95.5%) unstable hips could be successfully treated showing normal findings with an alpha angle > 65°. The few patients showing treatment failures were successfully treated applying a Fettweis plaster (human position) under anesthesia. The radiological FU of 38 hips showed a favorable trend with increase of normal findings from 52.8% to 81.1% and decrease of 38.9% to 19.9% of sliD respectively 8.3% to 0% of sevD hips. The analysis of avascular necrosis of the femoral head showed 2 cases (5.3%) of grade 1 according to Kalamchi and McEwen, which were improving over time in the further course., Conclusions: The Tübingen splint as alternative to replace a plaster has proven a successful therapeutic option for ultrasound unstable hips type D, III and IV with favorable and over time improving radiological parameter up to the age of 12 years., (© 2023. The Author(s).)

Purpose: The aim of this study was to determine the success rate for treatment of ultrasound unstable hips (type D, III and IV) with Fettweis plaster in terms of a midterm follow-up from the very beginning in the neonatal period until the age of 4 to 8 years., Methods: In total, 69 unstable hips, which were successfully treated with Fettweis plaster and after with a flexion-abduction splint, were included into the study. Hip delvelopment was followed by determining the acetabular index (ACI) on routine pelvic radiographs at the age of 12 to ≤24, 24 to ≤48 and 48 to ≤96 months and the center edge angle on the latter, and classifying both angles according to Tönnis., Results: After initially successful treatment, the first radiograph at the age of 12 to ≤24 months showed 39.1% (n=27) hips with normal findings, 33.2% (n=23) hips with slightly dysplastic findings, and 27.5% (n=19) hips with severe dysplastic findings. Comparison between first and second radiograph showed improvement of the ACI in 9/69 hips and between the second and third time point in 20/69 hips. Overall, 20 hip joints showed deteriorations. Hereby, 16 deteriorations took place after the first radiograph and 4 after the second radiograph. Deteriorations were observed independently of the initial hip type (D, III, and IV)., Conclusions: Midterm results indicate that radiologic controls should be provided to detect deteriorations after finishing treatment. ACI and center edge angle are helpful parameters in the assessment of hip joint development in the age range of 4 to 8 years., Level of Evidence: Level III., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aurones constitute one of the major classes of flavonoids, with a characteristic furanone structure that acts as the C-ring of flavonoids. Members of various enzyme families are involved in aurone biosynthesis in different higher plants, suggesting that during evolution plants acquired the ability to biosynthesize aurones independently and convergently. Bryophytes also produce aurones, but the biosynthetic pathways and enzymes involved have not been determined. The present study describes the identification and characterization of a polyphenol oxidase (PPO) that acts as an aureusidin synthase (MpAS1) in the model liverwort, Marchantia polymorpha. Crude enzyme assays using an M. polymorpha line overexpressing MpMYB14 with high accumulation of aureusidin showed that aureusidin was biosynthesized from naringenin chalcone and converted to riccionidin A. This activity was inhibited by N-phenylthiourea, an inhibitor specific to enzymes of the PPO family. Of the six PPOs highly induced in the line overexpressing MpMyb14, one, MpAS1, was found to biosynthesize aureusidin from naringenin chalcone when expressed in Saccharomyces cerevisiae. MpAS1 also recognized eriodictyol chalcone, isoliquiritigenin and butein, showing the highest activity for eriodictyol chalcone. Members of the PPO family in M. polymorpha evolved independently from PPOs in higher plants, indicating that aureusidin synthases evolved in parallel in land plants., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cell proliferation processes play pivotal roles in timely adaptation to many biological situations. Herein, we establish a highly sensitive and simple strategy by which time-series showing the proliferation of a targeted cell type can be quantitatively monitored in vivo in the same individuals. We generate mice expressing a secreted type of luciferase only in cells producing Cre under the control of the Ki67 promoter. Crossing these with tissue-specific Cre-expressing mice allows us to monitor the proliferation time course of pancreatic β-cells, which are few in number and weakly proliferative, by measuring plasma luciferase activity. Physiological time courses, during obesity development, pregnancy and juvenile growth, as well as diurnal variation, of β-cell proliferation, are clearly detected. Moreover, this strategy can be utilized for highly sensitive ex vivo screening for proliferative factors for targeted cells. Thus, these technologies may contribute to advancements in broad areas of biological and medical research., (© 2023. The Author(s).)

We report a case of foreign body in chest wall with traumatic pneumothorax caused by fang of wild boar performed video-assisted thoracic surgery. The patient was a 69-year-old woman. She was attacked from behind by a wild boar during farm work. She was transferred to the emergency and critical care center of our hospital. She was in a state of hemorrhagic shock when arrived with multiple bite wounds on her back. Computed tomography( CT) scan revealed left pneumothorax and a foreign body in chest wall suspected to be a wild boar fang. Thoracoscopic surgery was performed to remove the foreign body.

Background: Acquired hemophilia A (AHA) is a rare disease characterized by a prolonged activated partial thromboplastin time (aPTT) and the production of coagulation factor VIII inhibitors. We encountered two cases of AHA in the perioperative period of pancreatoduodenectomy (PD)., Case Presentation: Case 1: A 76-year-old woman with intraductal papillary mucinous carcinoma developed acute cholecystitis 5 days before PD. Despite immediate improvement in her acute cholecystitis with biliary drainage and antibiotics, her aPTT level was prolonged (55.9 s). PD was performed as scheduled. On postoperative day (POD) 2, she developed intra-abdominal hemorrhaging that required reoperation. However, intra-abdominal bleeding and concomitant anemia persisted after reoperation. On POD 13, she was diagnosed with AHA based on the detection of an inhibitor of coagulation factor VIII. Despite hemostatic and immunosuppressive treatment, including massive blood transfusion, her general condition gradually worsened due to continuous bleeding and secondary infections. She ultimately died of multiple organ failure on POD 71. Case 2: An 82-year-old man received PD for distal cholangiocarcinoma. On POD 3, a small amount of blood via abdominal drainage was observed. On POD 4, his aPTT level was prolonged (61.5 s). On POD 8, subcutaneous hemorrhaging of the median wound was observed, and corticosteroids were administered under suspicion of AHA on POD 9. On POD 15, an inhibitor of FVIII was detected, and he was diagnosed with AHA. On POD 17, the aPTT level had normalized, and an inhibitor of FVIII was undetectable. On POD 41, he was discharged without any serious hemorrhagic events., Conclusions: AHA may be more frequent than previously reported. When unexplained prolonged aPTT or bleeding symptoms are observed, it is important to keep AHA in mind during the perioperative period of invasive surgery., (© 2023. The Author(s).)

The present study investigated the effects of hypocapnia and hypercapnia on human somatosensory processing by utilizing somatosensory evoked magnetic fields (SEFs) with magnetoencephalography (MEG). Thirteen volunteers participated in two experiments separately to measure respiratory and cardiovascular data and SEFs. Both experiments consisted of a combination of normal and rapid respiratory rhythms and two inspiratory gas conditions (air and a hypercapnic gas); normal breathing with air (NB), rapid breathing with air (RB), normal breathing with the hypercapnic gas (NB+Gas), and rapid breathing with gas (RB+Gas). Partial pressures of end-tidal CO 2 (P ETCO2 ) increased during inhaling the hypercapnic gas and decreased during RB, but the RB+Gas condition continued to cause elevated PETCO 2 compared with the baseline. Subsequently, middle cerebral artery blood (MCA) velocity using transcranial Doppler changed as well, while mean MCA velocity increased under the RB+Gas condition. The peak amplitude of the M60 component in SEFs was also significantly larger under with-gas than without-gas conditions, irrespective of the respiratory frequency. These results suggest that there is a close relationship between cerebral blood flow and neural activity of the M60 component in SEFs. This study provides evidence to further understanding on one of the neural mechanisms of hypercapnia., Competing Interests: Declaration of Competing Interest No conflicts of interest, financial or otherwise, are declared by the author(s)., (Copyright © 2022 Japan Neuroscience Society and Elsevier Ltd. All rights reserved.)

Background Aims: The L-index, designed as a quantitative parameter to simultaneously assess the duration and severity of lymphopenia, and absolute lymphocyte count (ALC) have a prognostic impact after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, discrepancies have been reported in the impact of ALC, and limited information is currently available on the L-index., Methods: To search for a better clinical tool, the authors retrospectively compared the simple L-index at 30 days (sL-index(30)), which aims to make the original L-index more compact, and ALC at 30 days (ALC(30)) after allo-HSCT in 217 patients who underwent allo-HSCT at the authors' institutions., Results: Median sL-index(30) was 11 712 (range, 4419-18 511) and median ALC(30) was 404 (range, 0-3754). In a multivariate analysis, higher sL-index(30) was associated with a significantly higher cumulative incidence of relapse (CIR) (hazard ratio [HR], 1.01, 95% confidence interval [CI], 1.00-1.02, P = 0.02 for every increase of 100 in sL-index(30)) as well as non-relapse mortality (NRM) (HR, 1.02, 95% CI, 1.00-1.03, P = 0.01 for every increase of 100 in sL-index(30)). Although higher ALC(30) was associated with significantly lower CIR (HR, 0.94, 95% CI, 0.89-1.00, P = 0.04 for every increase of 100/μL in ALC(30)), it was not extracted as an independent risk factor for NRM (HR, 0.96, 95% CI, 0.88-1.05, P = 0.39). Higher sL-index(30) was associated with a slightly higher rate of grade 3-4 acute graft-versus-host disease (GVHD) (HR, 1.02, 95% CI, 1.00-1.04, P = 0.12 for every increase of 100 in sL-index(30)) but not chronic GVHD (HR, 1.00, 95% CI, 0.99-1.01, P = 0.63). ALC(30) was not associated with rates of grade 3-4 acute GVHD (HR, 1.02, 95% CI, 0.88-1.17, P = 0.81) or chronic GVHD (HR, 1.02, 95% CI, 0.98-1.06, P = 0.34). In a receiver operating characteristic curve, the cutoff values of sL-index(30) and ALC(30) for CIR were 9000 and 500, respectively, and the cutoff value of sL-index(30) for NRM was 12 000., Conclusions: sL-index(30) is a promising tool that may be applied to various survival outcomes. A large-scale prospective study is needed to clarify whether medical interventions based on sL-index(30) values will improve the clinical prognosis of patients., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Heart failure (HF) with preserved ejection fraction (HFpEF) is defined as HF with an ejection fraction (EF) ≥ 50% and elevated cardiac diastolic filling pressures. The underlying causes of HFpEF are multifactorial and not well-defined. A transgenic mouse with low levels of cardiomyocyte (CM)-specific inducible Cavβ2a expression (β2a-Tg mice) showed increased cytosolic CM Ca 2+ , and modest levels of CM hypertrophy, and fibrosis. This study aimed to determine if β2a-Tg mice develop an HFpEF phenotype when challenged with two additional stressors, high-fat diet (HFD) and N ω -nitro-l-arginine methyl ester (l-NAME, LN). Four-month-old wild-type (WT) and β2a-Tg mice were given either normal chow (WT-N, β2a-N) or HFD and/or l-NAME (WT-HFD, WT-LN, WT-HFD-LN, β2a-HFD, β2a-LN, and β2a-HFD-LN). Some animals were treated with the histone deacetylase (HDAC) (hypertrophy regulators) inhibitor suberoylanilide hydroxamic acid (SAHA) (β2a-HFD-LN-SAHA). Echocardiography was performed monthly. After 4 mo of treatment, terminal studies were performed including invasive hemodynamics and organs weight measurements. Cardiac tissue was collected. Four months of HFD plus l-NAME treatment did not induce a profound HFpEF phenotype in FVB WT mice. β2a-HFD-LN (3-Hit) mice developed features of HFpEF, including increased atrial natriuretic peptide (ANP) levels, preserved EF, diastolic dysfunction, robust CM hypertrophy, increased M 2 -macrophage population, and myocardial fibrosis. SAHA reduced the HFpEF phenotype in the 3-Hit mouse model, by attenuating these effects. The 3-Hit mouse model induced a reliable HFpEF phenotype with CM hypertrophy, cardiac fibrosis, and increased M 2 -macrophage population. This model could be used for identifying and preclinical testing of novel therapeutic strategies. NEW & NOTEWORTHY Our study shows that three independent pathological stressors (increased Ca 2+ influx, high-fat diet, and l-NAME) together produce a profound HFpEF phenotype. The primary mechanisms include HDAC-dependent-CM hypertrophy, necrosis, increased M 2 -macrophage population, fibroblast activation, and myocardial fibrosis. A role for HDAC activation in the HFpEF phenotype was shown in studies with SAHA treatment, which prevented the severe HFpEF phenotype. This "3-Hit" mouse model could be helpful in identifying novel therapeutic strategies to treat HFpEF.