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Daiji Nagayama,1,2 Haruki Imamura,2 Yuta Sato,2 Takashi Yamaguchi,2 Noriko Ban,2 Hidetoshi Kawana,2 Masahiro Ohira,2 Atsuhito Saiki,2 Kohji Shirai,3 Ichiro Tatsuno2 1Center of Endocrinology and Metabolism, Shin-Oyama City Hospital, Oyama-City, 2Center of Diabetes, Endocrinology and Metabolism, 3Department of Vascular Function, Sakura Medical Center, Toho University, Sakura-City, Japan Objective: The objective of this study is to investigate the association of body mass index (BMI) with arterial stiffness assessed by cardioankle vascular index (CAVI). Subjects and methods: A retrospective cross-sectional study was conducted in 23,257 healthy Japanese subjects (12,729 men and 10,528 women, aged 47.1 ± 12.5 years, BMI 22.9 ± 3.4 kg/m2) who underwent health screening between 2004 and 2006 in Japan. Exclusion criteria were current medication use and a past history of cardiovascular disease, hypertension, stroke, diabetes, and nephritis. Results: Male subjects showed significantly higher BMI, CAVI, and triglycerides and lower high-density lipoprotein (HDL)-cholesterol compared with female subjects. Next, the subjects were divided into tertiles of BMI: lower, middle, and upper, in a gender-specific manner. After adjusting for confounders including age, systolic blood pressure, and HDL-cholesterol identified by multiple regression analysis, the mean CAVI decreased progressively as BMI tertile increased in both genders. Furthermore, a negative inverse relationship between BMI and adjusted CAVI was observed throughout the BMI distribution. Multivariate logistic regression model for contributors of high CAVI (≥90th percentile) identified obesity (odds ratios (95% confidence interval): 0.804 (0.720–0.899)], older age [15.6 (14.0–17.4)], male gender [2.26 (2.03–2.51)], hypertension [2.28 (2.06–2.54)], impaired fasting glucose [1.17 (1.01–1.37)], and low HDL-cholesterol [0.843 (0.669–1.06)] as independent factors. Conclusion: We demonstrated an inverse relationship between CAVI and BMI in healthy Japanese subjects, suggesting that systemic accumulation of adipose tissue per se may lead to a linear decrease of arterial stiffness in nonobese and obese subjects without metabolic disorders. Keywords: BMI, cardioankle vascular index, arterial stiffness

Masahiro Ohira,1 Takashi Yamaguchi,1 Atsuhito Saiki,1 Noriko Ban,1 Hidetoshi Kawana,1 Ayako Nagumo,1 Takeyoshi Murano,2 Kohji Shirai,3 Ichiro Tatsuno1 1Center for Diabetes, Endocrinology and Metabolism, 2Department of Clinical Laboratory Medicine, 3Department of Vascular Function, Sakura Hospital, Toho University Medical Center, Chiba, Japan Background: Type 2 diabetes is known to be associated with elevated cardiovascular mortality. Pioglitazone improves blood pressure (BP) and pulse wave velocity (PWV), which is an arterial stiffness parameter. Arterial stiffness is closely associated with cardiovascular disease. However, PWV is correlated with BP. The cardio-ankle vascular index (CAVI) reflects arterial stiffness independent of BP. Pioglitazone improves PWV but reduces blood pressure. The aim of this study was to re-evaluate the effect of pioglitazone on arterial stiffness with CAVI. Methods: Sixty patients with type 2 diabetes mellitus and already on 500 mg/day of metformin received add-on therapy of pioglitazone 15 mg/day or glimepiride 1 mg/day for 6 months, during which time changes in their metabolic parameters and CAVI were observed. Results: After 6 months of treatment, both pioglitazone (n=30) and glimepiride (n=30) improved fasting blood glucose and glycated hemoglobin. The changes in fasting blood glucose and glycated hemoglobin between the two groups were greater in the pioglitazone group. Systolic and diastolic BP was decreased in both groups, with no significant between-group differences. Only pioglitazone increased serum adiponectin levels, and the change in adiponectin between the pioglitazone and glimepiride groups was significantly different. CAVI was decreased significantly by pioglitazone but remained unchanged after treatment with glimepiride. The change in CAVI between the two groups was significantly different. Conclusion: These results suggest that pioglitazone improves CAVI, a BP-independent arterial stiffness parameter, in patients with type 2 diabetes mellitus treated with metformin. Keywords: biguanide, thiazolidinediones, sulfonylurea, blood pressure, cardiovascular disease, arterial stiffness

Purpose: Following resection of malignant tumors from the mandible, immediate reconstruction of the discontinuous jaw is commonly performed. The present study aims to define the risks associated with dynamic loading of the reconstructed mandible. Materials and Methods: Computer-aided design simulations of eight mandibles were produced and termed normal models. The normal models were then modified by removing part of the right body and restoring the defects with bone from the rib or fibula. These modified models were termed reconstructed models. Thereafter, an implant was embedded in the first molar region of the left side for all models. Using finite element analysis, the stresses occurring at the implant-bone interface with simulated mastication were calculated. The Wilcoxon signed rank test was applied to compare the magnitudes of stresses in both models. Results: In terms of the stress exerted at the implant-bone interface during mastication, the normal models and the reconstructed models showed no significant differences (P > .05). Conclusion: Placement of an implant on the nonreconstructed side following partial resection and mandibular reconstruction presents no significant risk. [ABSTRACT FROM AUTHOR]

Human dental pulp stem/progenitor cells (hDPSCs) are attractive candidates for regenerative therapy because they can be easily expanded to generate colony-forming unit-fibroblasts (CFU-Fs) on plastic and the large cell numbers required for transplantation. However, isolation based on adherence to plastic inevitably changes the surface marker expression and biological properties of the cells. Consequently, little is currently known about the original phenotypes of tissue precursor cells that give rise to plastic-adherent CFU-Fs. To better understand the in vivo functions and translational therapeutic potential of hDPSCs and other stem cells, selective cell markers must be identified in the progenitor cells. Here, we identified a dental pulp tissue-specific cell population based on the expression profiles of 2 cell-surface markers LNGFR (CD271) and THY-1 (CD90). Prospectively isolated, dental pulp-derived LNGFR(Low+)THY-1(High+) cells represent a highly enriched population of clonogenic cells--notably, the isolated cells exhibited long-term proliferation and multilineage differentiation potential in vitro. The cells also expressed known mesenchymal cell markers and promoted new bone formation to heal critical-size calvarial defects in vivo. These findings suggest that LNGFR(Low+)THY-1(High+) dental pulp-derived cells provide an excellent source of material for bone regenerative strategies. [ABSTRACT FROM AUTHOR]

Myxoid liposarcoma (MLPS) is a rare sarcoma, typically arising in deep soft tissues during the fourth to fifth decades of life. Histologically, MLPS is composed of uniform oval cells within a background of myxoid stroma and chicken-wire capillaries. Genetically, MLPS is characterized by the FUS/EWSR1::DDIT3 fusion gene, which generally results from balanced interchromosomal translocation and is detectable via DDIT3 break-apart fluorescence in situ hybridization (FISH). Here, we report an unusual intra-articular MLPS case, negative for DDIT3 break-apart FISH but positive for EWSR1::DDIT3. An 18-year-old female was referred to our hospital complaining of an intra-articular mass in the right knee joint. Histologically, the tumor was mainly composed of mature adipocytes, brown fat-like cells, and lipoblasts. Nanopore sequencing detected DNA rearrangements between EWSR1 and DDIT3 and clustered complex rearrangements involving multiple chromosomes, suggesting chromoplexy. Methylation classification using random forest, t-distributed stochastic neighbor embedding, and unsupervised hierarchical clustering correctly classified the tumor as MLPS. The copy number was almost flat. The TERT promoter C-124T was also detected. This report highlights, for the first time, the potential value of a fast and low-cost nanopore sequencer for diagnosing sarcomas., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Functional mass spectrometry imaging (fMSI) is a potent tool for elucidating the spatial distribution of enzyme activities in tissues at high resolution. In this study, we applied fMSI to probe the intricate biosynthesis of phospholipids, which exist as thousands of molecular species in tissues and exhibit a unique distribution specific to cell type. By using deuterium- and 13 C-labeled substrates, we visualized the activities of key enzymes involved in phospholipid synthesis, including glycerol 3-phosphate acyltransferase (GPAT), lysophosphatidic acid acyltransferases (LPAAT), lysophospholipid acyltransferases (LPLAT), and long-chain acyl-CoA synthetase (ACSL). Additionally, we were able to visualize a two-step sequential enzyme reaction involving ACSL and LPLAT. This novel approach unveiled significant variations in enzyme activity distribution depending on the type of fatty acids used as substrates. It will also help to reveal the mechanisms underlying the formation of numerous phospholipid species.

Extracellular vesicles (EVs) are crucial for transferring bioactive materials between cells and play vital roles in both health and diseases. Cellular protrusions, including filopodia and microvilli, are generated by the bending of the plasma membrane and are considered to be rigid structures facilitating various cellular functions, such as cell migration, adhesion, and environment sensing. Compelling evidence suggests that these protrusions are dynamic and flexible structures that can serve as sources of a new class of EVs, highlighting the unique role they play in intercellular material transfer. Cytonemes are specialized filopodia protrusions that make direct contact with neighboring cells, mediating the transfer of bioactive materials between cells through their tips. In some cases, these tips fuse with the plasma membrane of neighboring cells, creating tunneling nanotubes that directly connect the cytosols of the adjacent cells. Additionally, virus particles can be released from infected cells through small bud-like of plasma membrane protrusions. These different types of protrusions, which can transfer bioactive materials, share common protein components, including I-BAR domain-containing proteins, actin cytoskeleton, and their regulatory proteins. The dynamic and flexible nature of these protrusions highlights their importance in cellular communication and material transfer within the body, including development, cancer progression, and other diseases., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hu, Nishimura, Kawana, Dante, D’Angelo and Suetsugu.)

An aneurysmal bone cyst (ABC) is a benign bone neoplasm that typically occurs during the first and second decades of life. ABC usually presents as a rapidly growing intramedullary expansile mass with multiple blood-filled cysts in the metaphysis of the long tubular bones. Here, we report a case of a periosteal solid ABC that was initially diagnosed as a high-grade surface osteosarcoma. A 10-year-old male was referred to our hospital for swelling and tenderness of the left upper arm. Radiography revealed periosteal mass without fluid-fluid levels. On performing open biopsy, the tumor showed hypercellular proliferation of uniform spindle to epithelioid cells with brisk mitotic activity (up to 12/2 mm 2 ) and lace-like osteoid formation, which was diagnosed as a high-grade surface osteosarcoma. After one course of chemotherapy using adriamycin and cisplatin, peripheral sclerosis was conspicuous, which led to pathological review and revision of diagnosis as "possibly osteoblastoma." The patient was disease-free for 4 years after marginal resection and curettage. Retrospective nanopore DNA sequencing unexpectedly detected a PAFAH1B1::USP6 rearrangement. The fusion gene was further validated using reverse transcription-polymerase chain reaction and the diagnosis was revised to ABC. Chromothripsis involving chromosome 17 has also been identified. Methylation analysis classified the present tumor as an ABC or non-ossifying fibroma using t-distributed stochastic neighbor embedding and unsupervised hierarchical clustering. This case report highlights the utility of nanopore DNA sequencing for soft tissue and bone tumor diagnosis., (© 2024 Wiley Periodicals LLC.)

Background: Dynamic navigation for implant placement is becoming popular under the concept of top-down treatment. The purpose of this study is to verify the accuracy of a dynamic navigation system for implant placement., Methods: Implant placement was performed on 38 patients using 50 implant fixtures. Patients in group C were treated using a conventional method, in which thermoplastic clips were fixed to the teeth, and patients in group M were treated using thermoplastic clips fixed to a mouthpiece attached to the teeth. The groups were compared to verify whether an accuracy difference existed. A treatment planning support program for dental implants was used to superimpose the postoperative computed tomography data on the preoperative implant design data to measure the entry point, apex point, and angular deviation., Results: The accuracy of group C was 1.36 ± 0.51 mm for entry point, 1.30 ± 0.59 mm for apex point, and 3.20 ± 0.74° for angular deviation. The accuracy of group M was 1.06 ± 0.31 mm for the entry point, 1.02 ± 0.30 mm for the apex point, and 2.91 ± 0.97° for angular deviation. Significant differences were observed in the entry and apex points between the two groups., Conclusions: The results indicate that group M exhibited better accuracy than group C, indicating that the stability of the thermoplastic clip is important for ensuring the accuracy of the dynamic navigation system. No previous studies have verified the accuracy of this system using the mouthpiece method, and additional data is required to confirm its accuracy for dental implant placement. The mouthpiece method improves the accuracy of implant placement and provides a safer implant treatment than the conventional method., Trial Registration: University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), Registration Number: UMIN000051949, URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view_his.cgi on August 21, 2023., (© 2024. The Author(s).)