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Satoshi Ida, Ryutaro Kaneko, Kanako Imataka, Kaoru Okubo, Yoshitaka Shirakura, Kentaro Azuma, Ryoko Fujiwara, Hiroka Takahashi, Kazuya Murata Department of Diabetes and Metabolism, Ise Red Cross Hospital, Ise-shi, Mie 516-8512, JapanCorrespondence: Satoshi IdaDepartment of Diabetes and Metabolism, Ise Red Cross Hospital, 1-471-2, Funae, 1-Chome, Ise-shi, Mie 516-8512, JapanTel +81 596-28-2171Fax +81 596-28-2965Email bboy98762006@yahoo.co.jpPurpose: To determine the frequency of social isolation (hereinafter, isolation) and homeboundness in elderly diabetic patients and to investigate their relationships with high-level functional capacity.Patients and Methods: Subjects were diabetic outpatients aged 65 years and older who were visiting the Japanese Red Cross Ise Hospital. Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) was used to evaluate high-level functional capacity. Isolation was defined as having less than one interaction per week with someone other than co-habiting family members. Homeboundness was defined as leaving the house less than once a day. Multiple regression analysis was performed with the TMIG-IC score as the dependent variable and isolation and homeboundness as independent variables.Results: Four hundred fifty-one patients were included in the analysis. The frequency of isolation and homeboundness affected 37% and 13.3% of men and 28.9% and 20.6% of women, respectively. The adjusted partial regression coefficient of the TMIG-IC scores of isolated, homebound, and isolated+homebound men was − 0.94 [95% confidence interval (CI), − 1.68 to − 0.21; P = 0.012], − 0.27 (95% CI, − 1.93 to 1.39; P = 0.746), and − 4.03 (95% CI, − 5.37 to − 2.68; P < 0.001) in relation to that of the non-isolated and non-homebound group as reference. In women, the respective coefficients to the reference were − 1.33 (95% CI, − 2.93 to 0.25; P = 0.099), − 0.65 (95% CI, − 2.56 to 1.26; P = 0.501), and − 3.01 (95% CI, − 4.92 to − 1.1; P = 0.002), respectively.Conclusion: The frequency of isolation was high in both female and male elderly diabetic patients. In men, there was a significant relationship between isolation and decline in high-level functional capacity. In both men and women, there was a significant relationship between isolation+homeboundness and decline in high-level functional capacity.Keywords: community-dwelling elderly, Tokyo Metropolitan Institute of Gerontology Index of Competence, TMIG-IC, diabetes in the elderly, activities of daily living

The Weyl semimetal (WSM), which hosts pairs of Weyl points and accompanying Berry curvature in momentum space near Fermi level, is expected to exhibit novel electromagnetic phenomena. Although the large optical/electronic responses such as nonlinear optical effects and intrinsic anomalous Hall effect (AHE) have recently been demonstrated indeed, the conclusive evidence for their topological origins has remained elusive. Here, we report the gigantic magneto-optical (MO) response arising from the topological electronic structure with intense Berry curvature in magnetic WSM Co3Sn2S2. The low-energy MO spectroscopy and the first-principles calculation reveal that the interband transitions on the nodal rings connected to the Weyl points show the resonance of the optical Hall conductivity and give rise to the giant intrinsic AHE in dc limit. The terahertz Faraday and infrared Kerr rotations are found to be remarkably enhanced by these resonances with topological electronic structures, demonstrating the novel low-energy optical response inherent to the magnetic WSM. The evidence of topological origin for the recently observed anomalous Hall effect remains elusive. Here, the authors report that the resonance of the optical Hall conductivity resulted from topological electronic structure gives rise to the large intrinsic anomalous Hall effect in the magnetic Weyl semimetal Co3Sn2S2. [ABSTRACT FROM AUTHOR]

Desmoid fibromatosis (DF) is defined as a borderline tumor of the soft tissues with a low malignant potential. The most common tumor sites are the extremity, trunk, abdominal cavity, and head and neck. Surgical resection has been the standard treatment for DF. However, there are concerns regarding long-term cosmetic outcomes or functional morbidity associated with surgery particularly in the head and neck. Recently, the use of the front-line wait-and-see strategy and pharmacologic treatment such as chemotherapy for progression has been proposed as tumors can spontaneously stabilize and regress. Herein, we report the efficacy of vinblastine (VBL) and methotrexate (MTX) in a childhood patients with DF. A 21-month-old female patient with a 4-cm tumor at the left lower jaw was diagnosed with DF. She did not initially receive any therapies (wait-and-see) according to the recent treatment guidelines. However, the tumor gradually progressed, and the patient was managed with COX2 inhibitor. Since the tumor was not controlled with such a treatment and tracheal exclusion caused by the mass was a cause of concern, the patient was managed with chemotherapy with VBL and MTX. VBL and MTX were administered weekly for 26 weeks, every other week, and further for 26 weeks. The tumor size gradually decreased with VBL and MTX. Magnetic resonance imaging revealed no evidence of the disease at the end of chemotherapy. Good cosmetic outcomes were achieved, and recurrence was not observed after 24 months of follow-up.

A woman in her forties visited an ophthalmologist for rapidly progressive foggy vision. Naked visual acuity had decreased to 0.15, and although her eyes showed no abnormalities, internal disease was suspected and albumin 2.6 g/dL was found. Protein leakage from the intestinal tract was suspected since there was no urinary protein excretion. 99m Technetium-labeled albumin D scintigraphy showed protein leakage from the intestinal tract. A stool α1-antitrypsin clearance test showed an increase to 56.3 mL/day, leading to a diagnosis of protein-losing gastroenteropathy. Blood biochemistry revealed abnormally high levels of anti-SS-A and anti-SS-B antibodies (≥ 1200 U/mL and ≥ 1000 U/mL, respectively). A lip salivary gland biopsy revealed lymphocytic infiltrate at least 1 focus per 2 mm × 2 mm > 50 lymphocytes per conduit). The Schirmer test result was 5 mm/5 min or less, which led to the diagnosis of Sjögren's syndrome. The serum albumin level increased with intravenous administration of methylprednisolone 50 mg (1 mg/kg), and the patient is currently on oral prednisolone at a gradually decreasing dose. After administration of prednisolone, visual acuity recovered to 1.2 with recovery of albumin., (© 2024. Japanese Society of Gastroenterology.)

Background: A standardized multi-day antiemetic regimen for multi-day chemotherapy remains elusive. This systematic review evaluated the efficacy and safety of multi-day antiemetic regimens in patients undergoing multi-day intravenous chemotherapy., Methods: We conducted a comprehensive search of PubMed, Cochrane Library, and Ichushi-Web databases for relevant studies published from January 1990 to December 2020. We included studies comparing multi-day and single-day antiemetic regimens for preventing chemotherapy-induced nausea and vomiting., Results: No studies directly comparing multi-day versus single-day antiemetic regimens were found. Despite expanding control group criteria beyond "single-day antiemetic therapy" limited high-quality studies and variations in cancer types, chemotherapy regimens, and antiemetic treatments precluded meta-analysis. Among the included studies, some randomized controlled trials (RCTs) focused on complete response and vomiting rates. Two studies comparing two- and three-drug combinations reported higher complete response and no-vomiting rates with the three-drug regimen. Limited RCTs explored "nausea control" and "cost," and assessing "adverse events" proved challenging due to inconsistent reporting., Conclusion: The research on multi-day antiemetic therapy is limited, necessitating further investigation. Nonetheless, our findings suggest that three-drug combination therapy, including aprepitant, may offer superior antiemetic efficacy compared to two-drug regimens. Multi-day antiemetic therapy is strongly recommended during multi-day intravenous administration of cytotoxic anticancer drugs., Competing Interests: Declarations Conflict of interest Kazuhisa Nakashima received honoraria from Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., and Eli Lilly Japan K.K. Eriko Satomi received honoraria from Shionogi & Co., Ltd. Masayuki Takeda received honoraria from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., and Bayer. Takako Eguchi Nakajima received research funding from KBBM, Inc. and Takeda Pharmaceutical Co., Ltd. Junichi Nishimura received honoraria from Taiho Pharmaceutical Co., Ltd. Narikazu Boku received honoraria from Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Eli Lilly Japan K.K. Koji Matsumoto received honoraria from MSD K.K., Kyowa Kirin Co., Ltd., and Chugai Pharmaceutical Co., Ltd. as well as research funding from Daiichi Sankyo Co., Ltd., MSD K.K., Gilead Sciences, Inc., and Eli Lilly Japan K.K. Nobuyuki Yamamoto received honoraria from MSD K.K., Accuray Japan K.K., AstraZeneca K.K., Abbvie Inc., Amgen Inc., Ono Pharmaceutical Co., Ltd., Guardant Health Japan Corp., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Chugai Foundation for Innovative Drug Discovery Science, Lao Tsumura Co., Ltd., Terumo Corporation, Eli Lilly Japan K.K., Nippon Kayaku Co., Ltd., Novartis AG, Pfzer Global Supply Japan Inc., Merck Biopharma Co., Ltd, Pfzer Global Supply Japan Inc., Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., and USACO Corporation, as well as legal fees in case of lawsuit from Taiho Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Nippon Kayaku Co., Ltd., Prime Research Institute for Medical RWD, Inc., AstraZeneca K.K., and A2 Healthcare Corporation. Other authors declare that they have no conflict of interest. Ethical approval Not applicable. Informed consent Formal consent was not required for this type of study. Consent to participate Not applicable. Consent for publication All authors consented to the publication of this study., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Effect of drugs on the intracellular activity of lactate dehydrogenase (LDH) has been measured by using water-soluble tetrazolium (WST). Because the assay is usually conducted in the presence of dead cells, net activity of live cells is not evaluated. Here, we reported the assay of the net intracellular LDH activity of live cells by counting the live cells using fluorescent staining of nucleus. By using a deep red fluorescent dye, dual measurements of fluorescence signal of nucleus and absorbance of WST could be conducted with transparent 96-well-plates. We found that conventional assay in the presence of dead cells overestimate the effect of drugs on the LDH activity., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Hematopoietic stem cell transplants for inherited metabolic disorders performed at Tokai University Hospital between June 5, 1986, and May 28, 2021, were analyzed and compared between the period before 2007 and the period from 2007 onward based on availability of medical resources. Transplants were performed for 38 patients with mucopolysaccharidosis, 33 with adrenoleukodystrophy, and 16 with another disorder. Before 2007, oral busulfan-based regimens were mainly used. From 2007 onward, intravenous busulfan-based regimens or 4 Gy of thoracoabdominal irradiation (TAI), fludarabine, and melphalan (Mel)/treosulfan were adopted. Between 2002 and 2010, adrenoleukodystrophy was treated with 12 Gy of TAI and Mel. HLA-identical sibling bone marrow was used in 43% of cases before 2007 and 15% from 2007 onward, while alternative donors were selected for other transplants. Overall survival and event-free survival (EFS) before 2007 and from 2007 onward were 76% and 62%, and 97% and 85%, respectively (P = 0.006 and 0.017). Transplant era predicted superior overall survival and EFS, while myeloablative conditioning also predicted EFS. The incidence of primary graft failure decreased from 2007 onward, especially in cord blood transplant when 4 Gy of TAI with 150 mg/m 2 fludarabine and 180 mg/m 2 Mel or 42 g/m 2 treosulfan were used as conditioning., (© 2024. Japanese Society of Hematology.)

Serum laminin-γ2 monomer (Lm-γ2m) is a potent predictive biomarker for hepatocellular carcinoma (HCC) onset in patients with hepatitis C infection who achieve a sustained virologic response with liver cirrhosis (LC) and for the onset of extrahepatic metastases in early-stage HCC. Although Lm-γ2m involvement in late-stage cancer progression has been well investigated, its precise roles in HCC onset remain to be systematically investigated. Therefore, we analyzed an HCC model, human hepatocytes and cholangiocytes, and surgically resected liver tissues from patients with HCC to understand the roles of Lm-γ2m in HCC onset. Ck-19- and EpCAM-positive hepatic progenitor cells (HPCs) in the liver of pdgf-c transgenic HCC mouse model with ductular reaction showed ectopic expression of Lm-γ2m. Forced expression of Lm-γ2m in hepatocytes adjacent to HPCs resulted in enhanced tumorigenicity, cell proliferation, and migration in immortalized hepatocytes, but not in cholangiocytes in vitro. Further, pharmacological inhibition of epidermal growth factor receptor (EGFR) and c-Jun activator JNK suppressed Lm-γ2m-induced hepatocyte transformation, suggesting the involvement of EGFR/c-Jun signaling in the transformation, leading to HCC development. Finally, immunohistochemical staining of HCC tissues revealed a high level of Lm-γ2 expression in the HPCs of the liver with ductular reaction in normal liver adjacent to HCC tissues. Overall, HPC-derived Lm-γ2m in normal liver with ductular reaction acts as a paracrine growth factor on surrounding hepatocytes and promotes their cellular transformation through the EGFR/c-Jun signaling pathway. Furthermore, this is the first report on Lm-γ2m expression detected in the normal liver with ductular reaction, a human precancerous lesion of HCC., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objectives: We retrospectively examined the initial experience and learning curve after the introduction of thrombectomy with the combined technique using an aspiration catheter and a stent retriever as first-line attempt for acute ischemic stroke., Methods: Consecutive patients undergoing thrombectomy for acute ischemic stroke at our institution between January 2020 and December 2022 were divided into 3 groups according to the year of thrombectomy. Patient characteristics and procedural, safety, and clinical outcomes were compared between the three year periods to determine predictors of favorable clinical outcome., Results: In 2020, 2021, and 2022, the numbers of patients were 74, 70, and 90, respectively, with similar patient characteristics across the three years; successful recanalization rates were 79.7%, 97.1%, and 93.3%, respectively (P < 0.01 for the first 2 years); median procedure times were 67, 43, and 32 minutes, respectively (P < 0.01 for the first 2 years and P = 0.018 for the last 2 years); first pass effect rates were 20.3%, 41.4%, and 44.4%, respectively (P < 0.01 for the first 2 years); symptomatic intracranial hemorrhage rates were 14.9%, 2.9%, and 1.1%, respectively (P = 0.018 for the first 2 years); and percentages of modified Rankin Scale score 0-2 at 90 days were 24.3%, 42.9%, and 41.1%, respectively (P = 0.022 for the first 2 years). Procedure time (P = 0.038) and successful recanalization (P = 0.041) were independent predictors of favorable clinical outcome., Conclusions: The learning curve effect of the combined technique may be associated with better clinical outcome due to increased successful recanalization rates, shortened procedure time, and reduced symptomatic intracranial hemorrhage., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study introduces the α-rhamnose (Rham)-conjugated prodrug of SN-38 (Rham-SN-38) as a promising alternative to irinotecan. α-rhamnosidase, responsible for SN-38 release from Rham-SN-38, does not express in human cells, minimizing individual variability and side effects. The injection of the α-rhamnosidase into the tumor tissues makes it possible, for the first time, to activate the Rham-SN-38. Furthermore, α-rhamnosidase demonstrates significantly higher activity than carboxylesterase, the specific enzyme activating irinotecan. SN-38 release mediated by α-rhamnosidase completes within 2 h, with a k cat /K m value approximately 5.0 × 10 4 -fold higher than that of irinotecan. The 50% inhibition concentration (IC 50 ) of Rham-SN-38 against three types of cancer cells and one normal cell exceeds 4.5 × 10 3  nM. The addition of α-rhamnosidase significantly increases cytotoxicity, with IC 50 comparable to free SN-38. The QIC 50 , an index reflecting the difference in cytotoxicity with and without α-rhamnosidase, exceeds approximately 1.0 × 10 2 -fold. Rham-SN-38, synthesized in this study, demonstrates significant potential as a prodrug for cancer therapy., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

In teleost fish, branchial ionocytes are important sites for osmoregulation and acid-base regulation by maintaining ionic balance in the body fluid. During the early developmental stages before the formation of the gills, teleost ionocytes are localized in the yolk-sac membrane and body skin. By comparing with teleost fish, much less is known about ionocytes in developing embryos of elasmobranch fish. The present study investigated the development of ionocytes in the embryo and larva of cloudy catshark, Scyliorhinus torazame. We first observed ionocyte distribution by immunohistochemical staining with anti-Na + /K + -ATPase (NKA) and anti-vacuolar-type H + -ATPase (V-ATPase) antibodies. The NKA- and V-ATPase-rich ionocytes appeared as single cells in the gill filaments from stage 31, the stage of pre-hatching, while the ionocytes on the body skin and yolk-sac membrane were also observed. From stage 32, in addition to single ionocytes on the gill filaments, some outstanding follicular structures of NKA-immunoreactive cells were developed to fill the inter-filament region of the gill septa. The follicular ionocytes possess NKA in the basolateral membrane and Na + /H + exchanger 3 in the apical membrane, indicating that they are involved in acid-base regulation like single NKA-rich ionocytes. Three-dimensional analysis and whole-mount immunohistochemistry revealed that the distribution of follicular ionocytes was limited to the rostral side of gill septum. The rostral sides of gill septum might be exposed to faster water flow than caudal side because the gills of sharks gently curved backward. This dissymmetric distribution of follicular ionocytes is considered to facilitate efficient body-fluid homeostasis of catshark embryo., (© 2024. The Author(s).)

The study of phonon dynamics and its interplay with magnetic ordering is crucial for understanding the unique quantum phases in the pyrochlore iridates. Here, through inelastic x-ray scattering on a single crystal sample of the pyrochlore iridate Eu 2 Ir 2 O 7 , we map out the phonon excitation spectra in Eu 2 Ir 2 O 7 and compare them with the theoretical phonon spectra calculated using the density functional theory. Possible phonon renormalization across the magnetic long-range order transition is observed in our experiments, which is consistent with the results of the previous Raman scattering experiments., (© 2024 IOP Publishing Ltd.)

Cyclic vomiting syndrome (CVS) is a chronic digestive disorder characterized by recurrent episodes of severe nausea and vomiting. The perioperative management of patients with CVS undergoing general anesthesia is challenging, especially when combined with obesity. This case report describes the successful management of a patient with CVS and obesity who underwent dental surgery under general anesthesia. A 21-year-old woman with CVS, obesity (body mass index, 35), and intellectual disability was scheduled for tooth extraction and composite resin restoration under general anesthesia. The patient was diagnosed with CVS at the age of 20 years with frequent vomiting attacks requiring hospitalization. Surgery was scheduled during the CVS remission to reduce the risk of perioperative vomiting. Preoperative laboratory test results were normal, including serum adrenocorticotropic hormone (ACTH), anti-diuretic hormone (ADH), and cortisol levels. General anesthesia was induced using remifentanil and propofol. Nasal endotracheal intubation was performed after rocuronium administration. Local anesthesia (2% lidocaine with 1:80,000 epinephrine) was used for all dental procedures. Postoperatively, midazolam was administered to control agitation. No postoperative vomiting occurred. Serum ACTH, ADH, and cortisol levels showed no significant changes before and after anesthesia, suggesting that hypothalamic-pituitary-adrenal (HPA) axis activation due to surgical stress did not occur. This case highlights the importance of careful perioperative planning and monitoring stress-related hormone levels in patients with CVS or obesity. An anesthetic approach using midazolam may effectively suppress HPA axis activation and prevent postoperative vomiting., 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: All authors have declared that no financial support was received from any organization for the submitted work. 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, Kuroda et al.)

Panniculitis is an inflammation that occurs in subcutaneous adipose tissue. Panniculitis includes physical panniculitis (e.g., traumatic) and infectious panniculitis (e.g., bacterial, fungal, subcutaneous panniculitis-like T cell lymphoma [SPCTL], etc.). Accurate diagnosis is crucial due to similar clinical presentation of all types of panniculitis. Here, we report a case of SPCTL which was initially diagnosed with traumatic panniculitis. A 15-year-old male patient was admitted to a previous hospital due to a progressively enlarged right flank and inguinal mass after an abdominal bruise. He was initially diagnosed with traumatic panniculitis, but the mass expanded throughout the chest and abdomen accompanied by a fever of over 11 months. Computed tomography (CT) revealed a subcutaneous mass in the anterior chest and abdominal wall. Fludeoxyglucose F18 (FDG) uptake was observed at those lesions using FDG-positron emission tomography (PET). A biopsy of the mass lesion was performed, during which SPCTL was diagnosed based on pathological examination. He was initially treated with prednisolone and cyclosporine A for two weeks. His fever went down, but subcutaneous mass in the chest and abdominal wall persisted. Therefore, he received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen. After 6 courses of CHOP, CT revealed no disease evidence. He remained in complete remission at 30 months of therapy.

Humans have approximately 400 different olfactory receptors (hORs) and recognize odorants through the repertoire of hOR responses. Although the cell surface expression of hORs is critical to evaluate their response, hORs are poorly expressed on the surface of heterologous cells. To address this problem, previous studies have focused on hOR transportation to the membrane. Nevertheless, the response pattern of hORs to odorants has yet to be successfully linked, and the response sensitivity still remains to be improved. In this study, we demonstrate that increasing the transcriptional level can result in a significant increase in cell surface and functional expression of hORs. We used the TAR-Tat system, which increases the transcription efficiency through positive feedback, and found that OR1A1, OR6N2, and OR51M1 exhibited robust expression. Moreover, this system induces enhanced hOR responses to odorants, thus defining four hORs as novel n-hexanal receptors and n-hexanal is an inverse agonist to one of them. Our results suggested that using the TAR-Tat system and increasing the transcriptional level of hORs can help understanding the relationship between hORs and odorants that were previously undetectable. This finding could facilitate the understanding of the sense of smell by decoding the repertoire of hOR responses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ojiro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Acute lung injury (ALI) is characterized by respiratory failure resulting from the disruption of the epithelial and endothelial barriers as well as immune system. In this study, we evaluated the therapeutic potential of airway epithelial cell-derived extracellular vesicles (EVs) in maintaining lung homeostasis. We isolated human bronchial epithelial cell-derived EVs (HBEC-EVs), which endogenously express various immune-related surface markers and investigated their immunomodulatory potential in ALI. In ALI cellular models, HBEC-EVs demonstrated immunosuppressive effects by reducing the secretion of proinflammatory cytokines in both THP-1 macrophages and HBECs. Mechanistically, these effects were partially ascribed to nine of the top 10 miRNAs enriched in HBEC-EVs, governing toll-like receptor-NF-κB signaling pathways. Proteomic analysis revealed the presence of proteins in HBEC-EVs involved in WNT and NF-κB signaling pathways, pivotal in inflammation regulation. ANXA1, a constituent of HBEC-EVs, interacts with formyl peptide receptor (FPR)2, eliciting anti-inflammatory responses by suppressing NF-κB signaling in inflamed epithelium, including type II alveolar epithelial cells. In a mouse model of ALI, intratracheal administration of HBEC-EVs reduced lung injury, inflammatory cell infiltration, and cytokine levels. Collectively, these findings suggest the therapeutic potential of HBEC-EVs, through their miRNAs and ANXA1 cargo, in mitigating lung injury and inflammation in ALI patients., (© 2024. The Author(s).)

Objective: This study aimed to evaluate the incidence of early (up to 2 h) and late (2-24 h) postoperative nausea and vomiting (PONV) and hypotension in patients who underwent general anesthesia for orthognathic surgery using propofol or remimazolam along with remifentanil., Methods: This retrospective chart review included healthy adult patients under the age of 60 who underwent orthognathic surgery using propofol (P group) or remimazolam (R group) from January 2021 to March 2022. Records were reviewed to gather PONV and intraoperative hypotension data as well as patient characteristics and other variables., Results: Early PONV was significantly lower in the P group vs the R group (9.5% vs 34.1%, respectively; P = .002), although the difference in late PONV was insignificant (36.9% vs 51.2%, respectively; P = .13). A higher incidence of intraoperative hypotension was noted in the P group (22.6%) vs the R group (2.4%; P = .004); however, there were no differences in average intraoperative systolic blood pressure or vasopressor administration., Conclusion: These results suggest that propofol is associated with a lower incidence of early PONV as compared to remimazolam; however, antiemetics are still recommended given the frequency of late PONV in both groups. Propofol also caused more episodes of intraoperative hypotension vs remimazolam, but the increase in transient hypotension is likely to be irrelevant during orthognathic surgery in healthy adults under the age of 60.

Maternal immunoglobulin (Ig)G is present in breast milk and has been shown to contribute to the development of the immune system in infants. In contrast, maternal IgG has no known effect on early childhood brain development. We found maternal IgG immunoreactivity in microglia, which are resident macrophages of the central nervous system of the pup brain, peaking at postnatal one week. Strong IgG immunoreactivity was observed in microglia in the corpus callosum and cerebellar white matter. IgG stimulation of primary cultured microglia activated the type I interferon feedback loop by Syk. Analysis of neonatal Fc receptor knockout (FcRn KO) mice that could not take up IgG from their mothers revealed abnormalities in the proliferation and/or survival of microglia, oligodendrocytes, and some types of interneurons. Moreover, FcRn KO mice also exhibited abnormalities in social behavior and lower locomotor activity in their home cages. Thus, changes in the mother-derived IgG levels affect brain development in offsprings., (© 2024. The Author(s).)

Protein kinase C γ (PKCγ), a neuronal isoform present exclusively in the central nervous system, is most abundantly expressed in cerebellar Purkinje cells (PCs). Targeted deletion of PKCγ causes a climbing fiber synapse elimination in developing PCs and motor deficit. However, physiological roles of PKCγ in adult mouse PCs are little understood. In this study, we aimed to unravel the roles of PKCγ in mature mouse PCs by deleting PKCγ from adult mouse PCs of PKCγ fl/fl mice via cerebellar injection of adeno-associated virus (AAV) vectors expressing Cre recombinase under the control of the PC-specific L7-6 promoter. Whole cell patch-clamp recording of PCs showed higher intrinsic excitability in PCs virally lacking PKCγ [PKCγ-conditional knockout (PKCγ-cKO) PCs] than in wild-type (WT) mouse PCs in the zebrin-negative module, but not in the zebrin-positive module. AAV-mediated PKCγ re-expression in PKCγ-deficient mouse PCs in the zebrin-negative module restored the enhanced intrinsic excitability to a level comparable to that of wild-type mouse PCs. In parallel with higher intrinsic excitability, we found larger hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents in PKCγ-cKO PCs located in the zebrin-negative module, compared with those in WT mouse PCs in the same region. However, pharmacological inhibition of the HCN currents did not restore the enhanced intrinsic excitability in PKCγ-cKO PCs in the zebrin-negative module. These results suggested that PKCγ suppresses the intrinsic excitability in zebrin-negative PCs, which is likely independent of the HCN current inhibition., 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., (Copyright © 2024 Watanave, Kawachi, Konno, Aoki, Fukai, Matsuzaki, Kaneko and Hirai.)

Mechanical perturbation triggers activation of resident myogenic stem cells to enter the cell cycle through a cascade of events including hepatocyte growth factor (HGF) release from its extracellular tethering and the subsequent presentation to signaling-receptor c-met. Here, we show that with aging, extracellular HGF undergoes tyrosine-residue (Y) nitration and loses c-met binding, thereby disturbing muscle homeostasis. Biochemical studies demonstrated that nitration/dysfunction is specific to HGF among other major growth factors and is characterized by its locations at Y198 and Y250 in c-met-binding domains. Direct-immunofluorescence microscopy of lower hind limb muscles from three age groups of rat, provided direct in vivo evidence for age-related increases in nitration of ECM-bound HGF, preferentially stained for anti-nitrated Y198 and Y250-HGF mAbs (raised in-house) in fast IIa and IIx myofibers. Overall, findings highlight inhibitory impacts of HGF nitration on myogenic stem cell dynamics, pioneering a cogent discussion for better understanding age-related muscle atrophy and impaired regeneration with fibrosis (including sarcopenia and frailty)., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Introduction: Ankle fractures are one of the most common lower extremity fractures. After surgery, the ankle joint is often immobilized in a plantar flexion position, and there have been many reported cases of limited ankle joint range of motion. Therefore, the purpose of the present study was to investigate the effect of regular massage interventions on ankle joint range of motion after removal of fixation., Methods: The massage group comprised 30 patients who had sustained an ankle fracture and had undergone surgical fixation, physical therapy, and massage between November 2020 and March 2022. These subjects received a 3-min massage twice daily, five times a week. The control group consisted of 38 patients who had sustained an ankle fracture between January 2015 and September 2020 and had undergone surgical fixation as well as regular physical therapy., Results: The respective ankle dorsiflexion and plantarflexion ranges of motion after cast removal were 2.50 ± 7.2° and 42.3 ± 7.2° in the massage group and -8.62 ± 2.9° and 34.8 ± 8.3° in the control group. An unpaired t-test showed that the ankle dorsiflexion and plantarflexion ranges of motion in the massage group were significantly greater than those in the control group (p = 0.036 and p < 0.01)., Conclusions: Our results indicate that regular 3-min massage interventions of the plantar flexors could prevent the progression of a range of motion limitations in postoperative patients with an ankle fracture more effectively than regular physical therapy alone., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Temcell is a mesenchymal stem cell (MSC) product approved for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in Japan. However, reports regarding Temcell's efficacy in pediatric patients have been scarce, and the appropriate use of MSC therapy against pediatric SR-aGVHD also remains to be determined., Patients and Methods: We retrospectively assessed a cohort of pediatric patients treated with Temcell for SR-aGVHD following allogeneic hematopoietic transplantation. MSCs were infused intravenously at a dose of 2 × 10 6 cells/kg according to the manufacturer's instructions., Results: Twelve patients received eighteen cycles of MSC therapy (median age, 10.3 [1.7-17.8] years), with four receiving additional cycles (one cycle: n = 3, three cycles: n = 1). The severity of aGVHD before MSC therapy was grade I-II in three patients and grade III-IV in nine patients (gut stage 3-4, n= 7; liver stage 3-4; n =2). The median number of immunosuppressive therapy regimens received prior to MSC administration was two (range: 1-5). The first MSC cycle displayed the best overall response rate of 83%, including six patients with a complete response (CR) and with a 49% reduction in the mean daily dose of prednisone after eight weeks. The median time to first response was 3.5 days (range: 2-15 days). Two of the four patients who were re-administered MSCs for recurrent or persistent GVHD achieved a CR. The three-year overall survival rate was 69.4%, while the three-year failure free survival (FFS) rate was 22.2%, with a median FFS of 4.9 months. There were no observable side effects of MSC therapy., Conclusions: MSC therapy appears to be an effective and safe treatment for pediatric SR-aGVHD, with a steroid-sparing effect and satisfactory efficacy upon re-administration. Further studies are needed to determine its appropriate combination with additional treatments and the optimal use of re-administration of MSCs., Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website., (Copyright Ⓒ2024 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)

Objective: Pseudoaneurysms are a serious complication of neuroendovascular therapy with femoral artery puncture, for which ultrasound-guided compression repair (UGCR) is often the first choice of radical therapy. We sought to retrospectively investigate the factors for failure of UGCR for pseudoaneurysm at the femoral artery puncture site., Methods: Among patients undergoing neuroendovascular therapy with femoral artery puncture at our hospital between January 2018 and April 2021, those who received a diagnosis of pseudoaneurysm and underwent UGCR were enrolled. They were classified into two groups according to whether UGCR was successful (UGCR group) or was converted to surgical repair (SR group). Patient and procedural characteristics were compared between the two groups., Results: During the study period, 577 patients underwent neuroendovascular therapy with femoral artery puncture, 10 of whom (1.7%) received a diagnosis of pseudoaneurysm and underwent UGCR. There were seven patients in the UGCR group and three patients in the SR group. The sheath diameter tended to be larger in the SR group than in the UGCR group ( p = 0.16). The modified Rankin scale score when a diagnosis of pseudoaneurysm was made was significantly lower in the SR group than in the UGCR group (1 [0-2] vs. 3 [2-5], p = 0.037)., Conclusions: Physical activity may be associated with failure of UGCR. In patients with high physical activity, the use of sedatives and analgesics to keep them at rest during puncture site compression after UGCR may lead to successful UGCR., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.