210 results on '"T. Komatsu"'
Search Results
2. In-process monitoring of a tissue-engineered oral mucosa fabricated on a micropatterned collagen scaffold: use of optical coherence tomography for quality control
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O. Suebsamarn, Y. Kamimura, A. Suzuki, Y. Kodama, R. Mizuno, Y. Osawa, T. Komatsu, T. Sato, K. Haga, R. Kobayashi, E. Naito, M. Kida, K. Kishimoto, J. Mizuno, H. Hayasaki, and K. Izumi
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Picosecond laser machining ,Biomimetics ,Micropattern ,Optical coherence tomography ,Quality control ,Tissue-engineered oral mucosa ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Background: We previously reported a novel technique for fabricating dermo-epidermal junction (DEJ)-like micropatterned collagen scaffolds to manufacture an ex vivo produced oral mucosa equivalent (EVPOME) for clinical translation; however, more biomimetic micropatterns are required to promote oral keratinocyte-based tissue engineering/regenerative medicine. In addition, in-process monitoring for quality control of tissue-engineered products is key to successful clinical outcomes. However, evaluating three-dimensional tissue-engineered constructs such as EVPOME is challenging. This study aimed to update our technique to fabricate a more biomimetic DEJ structure of oral mucosa and to investigate the efficacy of optical coherence tomography (OCT) in combination with deep learning for non-invasive EVPOME monitoring. Methods: A picosecond laser-textured microstructure mimicking DEJ on stainless steel was used as a negative mould to fabricate the micropatterned collagen scaffold. During EVPOME manufacturing, OCT was applied twice to monitor the EVPOME and evaluate its epithelial thickness. Findings: Our moulding system resulted in successful micropattern replication on the curved collagen scaffold. OCT imaging visualised the epithelial layer and the underlying micropatterned scaffold in EVPOME, enabling to non-invasively detect specific defects not found before the histological examination. Additionally, a gradual increase in epithelial thickness was observed over time. Conclusion: These findings demonstrate the feasibility of using a stainless-steel negative mould to create a more biomimetic micropattern on collagen scaffolds and the potential of OCT imaging for quality control in oral keratinocyte-based tissue engineering/regenerative medicine.
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- 2022
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3. Three-dimensional strain evaluation of short-fiber-reinforced natural rubber using micro X-ray computed tomography
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M. Matsubara, S. Teramoto, T. Komatsu, S. Furuta, M. Kobayashi, S. Kawamura, A. Nagatani, N. Tsujiuchi, and A. Ito
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Damping material ,Loss factor ,Fiber orientation ,X-ray tomography ,3D strain mapping ,Polymers and polymer manufacture ,TP1080-1185 - Abstract
The vibration damping appears as a macroscopic material property due to the energy dissipation caused by the plastic deformation of the microstructure in the material, but the detailed mechanism is still unknown. This study prepared a damping material based on natural rubber (NR) and investigated its deformation behavior with/without fiber-shaped particles using synchrotron X-ray computed tomography (CT). High-resolution submicron X-ray CT was performed to evaluate the local strain in the microstructure from feature points scattered inside the NR. When the strain distribution changed under stepwise tensile loading, the NR-alone material deformed uniformly at the microscale, whereas the fiber composite rubber deformed nonuniformly. Furthermore, the number and volume of voids increased significantly with the compounding of fiber particles, and their values continued to increase depending on the strain amplitude and the loss factor. Controlling of non-uniform local strain and void formation will enable the design of damping characteristics.
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- 2022
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4. Multithreaded Algorithms for Lossless Intra Compression of Point Cloud Geometry Based on the Silhouette 3d Coder.
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Otho T. Komatsu, Edil Medeiros, Lucas M. Alves, and Eduardo Peixoto
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- 2023
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5. Macro- and microhabitat use patterns of holothurians in Buena Vista, Nggela, Solomon Islands: rock climber and bottom crawler species
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I Tanita, EB Hirohavi, BA Diau, K Masaki, T Komatsu, and C Ramofafia
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Ecology ,Aquatic Science ,Ecology, Evolution, Behavior and Systematics - Abstract
Densities and habitat use patterns of holothurians, including nocturnal species, were assessed in Buena Vista, Nggela, Solomon Islands, for community-based resource management. Nighttime snorkeling surveys were conducted along transects (maximum 1.6 km) with 3 to 5 searchers in nearshore, channel, and outer reef macrohabitats. Only the population in the seagrass macrohabitat was separately assessed in 30 m line transects during the daytime. Microhabitats were clearly separated between species living on 3-dimensional structures (e.g. surfaces of knolls and reef slopes; rock climber group) and those on flat bottoms (bottom crawler group), although they coexisted at macrohabitat scales. Potential shelters adjacent to each individual differed between the 2 groups. Among bottom crawler species, Bohadschia koellikeri, which was recently taxonomically divided from B. vitiensis, occupied macrohabitats intermediately ranging between those of B. argus in the channel and outer reef macrohabitats and those of B. vitiensis and B. marmorata in the nearshore and seagrass macrohabitats. The high-density population was observed in the seagrass macrohabitat, mainly composed of Holothuria scabra, B. marmorata, and H. fuscogilva, although most individuals of these species were smaller than the national legal size limits. Moreover, the body lengths of H. atra and H. fuscogilva increased from the seagrass macrohabitat to the outer reef macrohabitat, implying their migration during growth and the roles of seagrass areas as nurseries. These results revealed diversity of macro- and microhabitat use patterns among species and their growth stages and highlight the importance of considering these factors for conserving diverse species by areal-based protection measures.
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- 2022
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6. 1183 Expression of adhesion molecules and basic fibroblast growth factor 2 in non-segmental vitiligo-derived primary melanocytes
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T. Kawakami, Y. Dong, and T. Komatsu
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2023
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7. Investigation of a self-powered biosensor using a brush-based triboelectric nanogenerator and an enzymatic reaction.
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Komatsu T, Uejima R, and Sakamoto H
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In recent years, wearable devices have undergone remarkable developments. These can easily help us obtain useful information such as that related to our health. However, most devices require a power supply. This limits the utilization of portability and facilities. This can lead to dangerous situations for people who require immediate measurement of their condition. Therefore, novel wearable devices that do not need a power supply or generate power themselves are desirable. Therefore, triboelectric nanogenerators (TENG) have attracted considerable attention as renewable energy sources. In this study, we focused on using the TENG technique in wearable devices, particularly biosensors. An enzyme-modified TENG biosensor for glucose detection was constructed and evaluated. As a characteristic of our glucose biosensor, a fiber brush made nylon and fluorinated ethylene-propylene copolymer fibers was used to drive the TENG. Using chemical fibers, glucose can be detected from various contact directions. Glucose was detected sensitively by modifying the TENG with glucose oxidase (GOx) and polyaniline (PANI) that is an emeraldine base. The resulting biosensor showed better substrate specificity for glucose than for lactic acid. Overall, the proposed enzyme-modified B-TENG can be utilized as a wearable biosensor in the near future., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hiroaki Sakamoto reports financial support was provided by University of Fukui. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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8. Bathing-Related Ischemic Stroke: Association between Stroke Subtype and Cerebral Small Vessel Disease.
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Ishikawa T, Sato T, Okumura M, Kokubu T, Takahashi J, Kitagawa T, Tanabe M, Takatsu H, Onda A, Komatsu T, Sakuta K, Sakai K, Umehara T, Mitsumura H, and Iguchi Y
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- Humans, Male, Aged, Female, Retrospective Studies, Risk Factors, Middle Aged, Incidence, Magnetic Resonance Imaging methods, Follow-Up Studies, Prognosis, Cerebral Small Vessel Diseases epidemiology, Cerebral Small Vessel Diseases diagnosis, Cerebral Small Vessel Diseases complications, Ischemic Stroke etiology, Ischemic Stroke epidemiology, Ischemic Stroke diagnosis, Baths adverse effects
- Abstract
Aims: Bathing-related ischemic stroke (BIS) is sometimes fatal. However, its mechanisms and risk factors remain unclear. We aimed to identify the incidence of stroke subtypes in BIS, and clarify the impact of cerebral small vessel disease (CSVD) on BIS., Methods: Consecutive patients with ischemic stroke between October 2012 and February 2022 were retrospectively screened. The inclusion criteria were: 1) onset-to-door time within 7 days; and 2) availability of the results of MRI evaluation of CSVD markers during hospitalization. BIS was defined as an ischemic stroke that occurred while or shortly after bathing. We investigated the incidence of the stroke subtype and the correlation between CSVD markers and BIS., Results: 1,753 ischemic stroke patients (1,241 [71%] male, median age 69 years) were included. 57 patients (3%) were included in the BIS group. A higher frequency of large artery atherosclerosis (LAA) (prevalence ratio [PR] 2.069, 95% confidence interval [CI] 1.089 to 3.931, p=0.026) and lower frequency of cardio-embolism (CES) (PR 0.362, 95% CI 0.132 to 0.991, p=0.048) in BIS cases were identified. Moreover, lower periventricular hyperintensity (PVH) Fazekas grade (PR 0.671, 95% CI 0.472 to 0.956, p=0.027) and fewer cerebral microbleeds (CMBs) in deep brain region (PR 0.810, 95%CI 0.657 to 0.999, p=0.049) were associated with BIS cases., Conclusions: The BIS group was more likely to develop LAA and less likely to develop CES. Lower PVH grade and fewer CMBs in deep brain region were associated with the development of BIS.
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- 2024
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9. γ-Secretase Cleaves Bifunctional Fatty Acid-Conjugated Small Molecules with Amide Bonds in Mammalian Cells.
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Tahara K, Nakamura A, Wang X, Mitamura K, Ichihashi Y, Kano K, Mishiro-Sato E, Aoki K, Urano Y, Komatsu T, and Tsukiji S
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Connecting two small molecules, such as ligands, fluorophores, or lipids, together via a linker with amide bonds is a widely used strategy to generate synthetic bifunctional molecules for various biological and biomedical applications. Such bifunctional molecules have been used in live-cell experiments under the assumption that they should be stable in cells. However, we recently found that a membrane-targeting bifunctional molecule, composed of a lipopeptide and the small-molecule ligand trimethoprim, referred to as mgcTMP, underwent amide-bond cleavage in mammalian cells. In this work, we first identified γ-secretase as the major protease degrading mgcTMP in cells. We next investigated the intracellular degradation of several different types of amide-linked bifunctional compounds and found that N -terminally fatty acid-conjugated small molecules are susceptible to γ-secretase-mediated amide-bond cleavage. In contrast, amide-linked bifunctional molecules composed of two small molecules, such as ligands and hydrophobic groups, which lack lipid modification, did not undergo intracellular degradation. These findings highlight a previously overlooked consideration for the development and application of lipid-based bifunctional molecules in chemical biology research.
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- 2024
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10. Novel Rat Model of Embolic Cerebral Ischemia Using a Radiopaque Blood Clot and a Microcatheter Under Fluoroscopy.
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Komatsu T, Ohta H, Takeda M, Matsumura Y, Yokoyama M, Wang Z, Okano HJ, and Iguchi Y
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Conventional rat models of thromboembolic stroke do not allow control of infarct size or spontaneous recanalization. We aimed to develop a novel rat thromboembolic stroke model that ensures highly reproducible infarct sizes and locations within the MCA territory and does not require arterial ligation. Twenty male Sprague-Dawley rats and two sham-operated rats were included. A microcatheter was navigated from the caudal ventral artery to the internal carotid artery using digital subtraction angiography. A blood clot (diameter, 0.86 mm; length, 3 mm) containing zirconium dioxide was advanced in the catheter. Fluoroscopy was performed at 1, 3, 6, and 24 h after stroke model creation, and TTC staining was conducted at 24 h. Neurological deficit scores were measured. In all embolized rats, the ACA and MCA bifurcation were selective. Median operating time was 6 min. The position of the radiopaque blood clot remained unchanged for 24 h after model creation in 19/20 rats. Median infarct volume was 242 mm
3 (IQR, 239-262 mm3 ). We present a novel rat model of highly reproducible focal infarct in only the MCA territory. Fluoroscopy effectively identified any blood clot migration. This model could contribute to the development of new thrombolytic agents., Competing Interests: Declarations Animal Ethics Declaration The study received approval from the Institutional Animal Care and Use Committee of Jikei University School of Medicine (No. 2022–086). All procedures were conducted in compliance with the Fundamental Guidelines for Proper Conduct of Animal Experiments and Related Activities in Academic Research Institutions issued by the Japanese Ministry of Education, Culture, Sports, Science and Technology, and followed the ARRIVE guidelines. Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2024
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11. Self-Propelled Tubular Micromotors Powered by Hydrogen Bubbles under Mild Conditions: A Major Step toward Biological Applications with Live Cells.
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Hashimoto M, Sakai Y, Yamada T, Kato R, and Komatsu T
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- Materials Testing, Particle Size, Biocompatible Materials chemistry, Biocompatible Materials pharmacology, Platinum chemistry, Metal Nanoparticles chemistry, Surface Properties, Escherichia coli drug effects, Hydrogen chemistry
- Abstract
Polymer-based tubular micromotors, featuring an inner layer of Pt nanoparticles (PtNPs), exhibit vigorous propulsion by emitting H
2 bubbles in an aqueous ammonia borane (NH3 BH3 ) solution. The hydrolysis of NH3 BH3 on the PtNPs facilitates the continuous release of H2 gas from the open-end terminus, driving its forward movement. Unlike conventional O2 bubbles' systems that rely on hydrogen peroxide (H2 O2 ) as fuel, these micromotors can operate in the presence of live cells within the NH3 BH3 medium. Consequently, micromotors functionalized with the lectin concanavalin A demonstrate the capability to capture and release Escherichia coli ( E. coli ) without inducing cell death. Remaining bacteria can be detected by using standard culture techniques. Conversely, micromotors coated with TiO2 nanoparticles enable photosterilization of E. coli without fuel-induced damage. The self-stirring motion of the tubes enhances both bacterial capture and sterilization efficiency. These advancements obviate the necessity for H2 O2 as a fuel source, and pave the way for the applications of micromotors in biological contexts.- Published
- 2024
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12. Intracranial atherosclerotic disease mechanism indicates poor outcomes of thrombectomy in acute cerebral infarction with large vessel occlusion: A matched cohort study.
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Nakada R, Sakuta K, Sato T, Okumura M, Kida H, Yamamoto S, Takahashi J, Kitagawa T, Takatsu H, Miyagawa S, Komatsu T, Sakai K, Mitsumura H, Yaguchi H, and Iguchi Y
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- Humans, Male, Female, Aged, Retrospective Studies, Middle Aged, Treatment Outcome, Cohort Studies, Aged, 80 and over, Ischemic Stroke surgery, Thrombectomy methods, Intracranial Arteriosclerosis surgery, Cerebral Infarction surgery
- Abstract
Background: Thrombectomy is a standard treatment for acute large vessel occlusion (LVO); however, its effectiveness in treating LVO related to intracranial atherosclerosis disease (ICAD) remains uncertain. This study aimed to compare thrombectomy outcomes in ICAD-related and embolic LVO, focusing on patients with similar symptom severities upon hospital admission., Methods: This retrospective study was conducted at Jikei University Hospital and Jikei University Kashiwa Hospital between October 2017 and March 2023. Ischemic stroke patients with LVO who underwent thrombectomy were categorized into ICAD and embolism groups based on the occlusion mechanism. Groups were matched using National Institutes of Health Stroke Scale scores at the time of admission. A modified Rankin Scale score of 5 or 6 at 90 days after symptom onset was defined as a devastating outcome. The procedural outcomes and frequency of devastating outcomes were compared between the ICAD and embolism groups., Results: The study included 33 matched pairs were included. The ICAD group showed lower rates of successful reperfusion (43 % vs. 82 %, p = 0.001), and longer procedural times (median 88 min vs. 50 min, p < 0.001) than the embolism group. The ICAD group had a significantly higher frequency of devastating outcomes than the non-ICAD group (39 % vs. 15 %, p = 0.027). Multivariate analysis identified ICAD as an independent factor associated with devastating outcomes (OR, 3.804; 95 % confidence interval (95 %CI), 1.148-12.603; p = 0.029)., Conclusion: In thrombectomy therapy, reperfusion rates and outcomes are significantly worse in patients with ICAD-LVO than in patients with embolic LVO., Competing Interests: Declaration of competing interest The authors declare that they have no financial conflicts of interest or personal relationships that may affect the work presented in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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13. Hydrosulphide-methaemoglobin-albumin cluster: a hydrogen sulphide donor.
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Suzuki Y, Yamada T, Enoki Y, Matsumoto K, Komatsu T, and Taguchi K
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- Animals, Mice, Male, Liver drug effects, Liver metabolism, Antioxidants chemistry, Antioxidants pharmacology, Albumins chemistry, Hydrogen Sulfide chemistry, Hydrogen Sulfide pharmacology, Reperfusion Injury drug therapy, Methemoglobin metabolism, Methemoglobin chemistry
- Abstract
Methaemoglobin (metHb) possesses inherent characteristics that facilitate reversible binding to hydrogen sulphide. Exogenous hydrogen sulphide supplementation imparts beneficial bioactive effects, including antioxidant and anti-inflammatory; hence, we hypothesized that the metHb-hydrogen sulphide complex could act as a hydrogen sulphide donor for medication. In this study, we prepared a hydrosulphide-metHb-albumin (H
2 S-metHb-albumin) cluster and examined its applicability as a hydrogen sulphide donor in the mice model of hepatic ischemia-reperfusion injury. Structural analysis revealed that the H2 S-metHb-albumin cluster exhibited a nanostructure wherein one metHb was wrapped by an average of three albumins, and hydrogen sulphide was bound to the haem. Additionally, the H2 S-metHb-albumin cluster exhibited low-pH responsiveness, leading to sustained release of hydrogen sulphide. Owing to these structural and pharmaceutical characteristics, the severity of hepatic ischemia-reperfusion injury was alleviated via antioxidant and anti-inflammatory effects of the H2 S-metHb-albumin cluster treatment. The protective effects were more potent in the H2 S-metHb-albumin cluster compared to that in a conventional hydrogen sulphide donor (sodium hydrogen sulphide). No abnormal signs of toxic and biological responses were observed after the H2 S-metHb-albumin cluster administration, confirming high biological compatibility. These results successfully establish the proof of concept that the H2 S-metHb-albumin cluster is a promising hydrogen sulphide donor. To the best of our knowledge, this is the first report demonstrating the remarkable potential of metHb as a biomaterial for hydrogen sulphide donors.- Published
- 2024
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14. Identification of a pancreatic juice-specific fluorescent probe through 411 probes activated by aminopeptidases/proteases or phosphatases/phosphodiesterases.
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Seki Y, Ishizawa T, Watanabe G, Komatsu T, Nanjo A, Ueno T, Urano Y, Kawaguchi M, Nakagawa H, and Hasegawa K
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Background: This study is a retrospective review aimed to identify pancreatic juice-specific fluorescent probes to visualize pancreatic juice using a library of 381 aminopeptidase/protease-activatable fluorescent probes and 30 phosphatase/phosphodiesterase probes. In 2013, we developed a fluorescence imaging technique using a chymotrypsin probe to visualize pancreatic juice, linked to postoperative pancreatic fistula (POPF). This probe required addition of trypsin to convert pancreatic chymotrypsinogen to chymotrypsin. Recently we accessed libraries of enzyme-activatable fluorescent probes to find probes that facilitated target-specific imaging., Methods: Pancreatic juice and ascitic fluid samples were collected in eight patients undergoing pancreaticoduodenectomy. Reaction rates of pancreatic juice to background ascitic fluids were calculated for these 411 fluorescent probes., Results: Forty-four fluorescent probes were screened in terms of high reactivity with pancreatic juice. Only one candidate probe targeting ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) 1 was selected for a pancreatic juice-specific fluorescent probe. Inhibitor experiments and Western blotting supported the presence of ENPP1 in the pancreatic juice., Conclusion: ENPP1-targeting fluorescent probe may have the potential to visualize pancreatic juice leakage during surgery. This finding may allow surgeons to suture leaking sites and decide the necessity of prophylactic abdominal drains; however, the role of ENPP1 in pancreatic juice remains to be clarified., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)
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- 2024
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15. Identification of Patients Who Require Two-Point Blood Sampling for the Peak and Trough Values Rather Than One-Point Blood Sampling for the Trough Value for the Evaluation of AUC of Vancomycin Using Bayesian Estimation.
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Suzuki A, Samura M, Ishigo T, Fujii S, Ibe Y, Yoshida H, Tanaka H, Ebihara F, Maruyama T, Hamada Y, Fujihara H, Yamaguchi F, Nagumo F, Komatsu T, Tomizawa A, Takuma A, Chiba H, Nishi Y, Enoki Y, Taguchi K, and Matsumoto K
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- Humans, Male, Female, Middle Aged, Aged, Adult, Creatinine blood, Aged, 80 and over, Blood Specimen Collection methods, Vancomycin pharmacokinetics, Vancomycin administration & dosage, Vancomycin blood, Drug Monitoring methods, Bayes Theorem, Area Under Curve, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents blood
- Abstract
Objectives: It is recommended to adjust the dose of vancomycin (VCM) with a target area under the concentration-time curve (AUC) of 400-600 μg·h/mL. Factors that affect the deviation between AUCs are estimated from the trough value alone and the trough and peak values using practical AUC-guided therapeutic drug monitoring (PAT) for vancomycin. In this study, factors that affect AUC were evaluated., Methods: AUCs were estimated from a single trough value and trough and peak values, and the patients were classified into those who showed a 10% or greater deviation (deviation group) and those in whom the deviation was less than 10% (no-deviation group). Risk factors related to ≥ 10% deviation of AUC were identified by univariate and multivariate analysis., Results: As a result of univariate and multivariate analysis of 30 patients in the deviation group and 344 patients in the no-deviation group, a creatinine clearance (CLcr) of ≥ 110 mL/min (odds ratio (OR) = 3.697, 95% confidence interval (CI) = 1.616-8.457, p = 0.002), heart failure with a brain natriuretic peptide (BNP) of ≥ 300 pg/mL (OR = 4.854, 95%CI = 1.199-19.656, p = 0.027), and the concomitant use of angiotensin converting enzyme inhibitor or angiotensin II receptor blocker (ACE-I/ARB) (OR = 2.544, 95%CI = 1.074-6.024, p = 0.034) were identified as risk factors of ≥ 10% deviation of AUC., Conclusions: Estimation of AUC by two-point blood sampling for the trough and peak values rather than one-point blood sampling for the trough value is suggested to improve the prediction accuracy in patients with enhanced renal function, severe heart failure, and patients using ACE-I/ARB., Competing Interests: Declarations. Conflict of Interest: KM received grant support funding from Meiji Seika Pharma Co., Ltd., Sumitomo Pharma Co., Ltd., and Shionogi & Co., Ltd., and speaker honoraria from Meiji Seika Pharma Co., Ltd. The other authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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16. A New Case of Abetalipoproteinemia Caused by Novel Compound Heterozygote Mutations in the MTTP Gene without Fat or Vitamin Malabsorption.
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Sasaki K, Tada H, Komatsu T, Terada H, Endo Y, Ikewaki K, and Uehara Y
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- Humans, Male, Dietary Fats, Malabsorption Syndromes genetics, Malabsorption Syndromes diagnosis, Malabsorption Syndromes metabolism, Vitamins, Adult, Abetalipoproteinemia genetics, Abetalipoproteinemia diagnosis, Mutation, Heterozygote, Carrier Proteins genetics, Carrier Proteins metabolism
- Abstract
Abetalipoproteinemia (ABL) is a rare disease characterized by extremely low apolipoprotein B (apoB)-containing lipoprotein levels, dietary fat, and fat-soluble vitamin malabsorption, leading to gastrointestinal, neuromuscular, and ophthalmological symptoms. We herein report a case of ABL with novel compound heterozygous mutations in the microsomal triglyceride transfer protein gene (c.1686_1687del [p.Ser563TyrfsTer10] and c.1862T>C [p.Ile621Thr]), identified via panel sequencing. Although the patient had extremely reduced low-density lipoprotein cholesterol levels and a fatty liver, he did not exhibit other typical complications. Furthermore, unlike typical ABL, this patient had a preserved apoB-48 secretion and increased concentrations of high-density lipoprotein cholesterol, which may account for the normal serum fat-soluble vitamin levels.
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- 2024
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17. Trends and Changes in Endoscopic Management and Clinical Outcomes of Colonic Diverticular Bleeding during the Coronavirus Disease-2019 Pandemic.
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Komatsu T, Sato Y, Tanabe K, Ishida J, Nakamoto Y, Kato M, Kiyokawa H, Yoshida Y, Kuroki Y, Maehata T, Yasuda H, Matsumoto N, and Tateishi K
- Abstract
Objectives: This study evaluated the endoscopic management and clinical outcomes of patients with colonic diverticular bleeding (CDB) during the coronavirus disease 2019 (COVID-19) pandemic., Methods: A total of 388 hospitalized patients diagnosed with CDB at two hospitals during (April 2020-March 2023) and before (April 2017-March 2020) the pandemic were enrolled in the study. We performed one-to-one propensity score matching (PSM) on the participants. We analyzed endoscopic management and clinical outcomes before and during the pandemic using a total of 264 patients matched in a PSM analysis., Results: A total of 213 (1.3%) and 172 (1.2%) colonoscopies were performed before and during the pandemic, respectively in patients with CDB (P = 0.70). After PSM, the number of early colonoscopies (63.6% vs. 76.5%, P = 0.03) and colonoscopies performed outside regular working hours (23.8% vs. 47.7%, P < 0.01) was significantly lower during the pandemic than before it. A univariate logistic regression analysis revealed that the risks of rebleeding within 30 days (odds ratio [OR]: 0.81, P = 0.42) and composite outcome (OR: 0.90, P = 0.69) were not increased during the pandemic., Conclusions: During the pandemic, the number of early colonoscopies and colonoscopies performed outside regular working hours decreased; however, this decrease did not influence rebleeding and composite outcome in patients with CDB., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)
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- 2024
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18. Comparison of Cancer Worries for Gastric Cancer by Helicobacter Pylori Infection Status at Health Check-Up Setting in Japan.
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Fukuda S, Watanabe K, Fujimori S, Komatsu T, Yoshida T, Kuramitsu T, Shimodaira Y, Matsuhashi T, and Iijima K
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- 2024
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19. Antitumor Effect of Oleoyl-siRNA against Pancreatic Cancer Using a Portal Vein Infusion Liver-Metastatic Mouse Model.
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Kubo T, Yanagihara K, Nishimura Y, Iino Y, Komatsu T, Tansou R, Mihara K, and Seyama T
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- Animals, Mice, Humans, Cell Line, Tumor, Disease Models, Animal, beta Catenin genetics, beta Catenin metabolism, Mice, Nude, Oleic Acid, RNA Interference, Mice, Inbred BALB C, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Pancreatic Neoplasms therapy, Pancreatic Neoplasms drug therapy, RNA, Small Interfering genetics, RNA, Small Interfering administration & dosage, Liver Neoplasms secondary, Liver Neoplasms therapy, Liver Neoplasms genetics, Portal Vein
- Abstract
In this study, we developed an oleoyl-siRNA conjugate in which oleic acid was conjugated at the 5'-end of the sense strand of the siRNA. Furthermore, we examined the effects of RNAi in a mouse model of pancreatic cancer with liver metastasis. The mouse model of pancreatic cancer with liver metastasis was developed by implanting Sui67Luc human pancreatic cancer cells into the portal veins of mice. Sui67Luc cells have high expression of tumor-related genes such as β -catenin , vascular endothelial growth factor , and programmed cell death ligand-1 . All genes were knocked down using siRNA, among which siRNA targeting β -catenin exhibited the most suitable RNAi effect. Therefore, we investigated the in vitro RNAi effect of oleoyl-siRNA (Ole-siRNA) targeting the β -catenin gene in Sui67Luc cells and found that it was stronger than that of unmodified siRNA. For in vivo experiments, we investigated the biodistribution, antitumor effect, and change in life expectancy of mice upon systemic administration of Ole-siRNA complexed with Invivofectamine 3.0 (IVF). In terms of biodistribution, the Ole-siRNA/IVF complex likely accumulates in the liver of mice. The antitumor effect of Ole-siRNA in a portal vein infusion liver-metastatic Sui67Luc tumor mouse model was evaluated using an in vivo imaging system. Ole-siRNA had a significant antitumor effect compared with nonmodified siRNA. In addition, mice with metastatic liver Sui67Luc tumors treated with Ole-siRNA showed increased survival. These results suggest that Ole-siRNAs are useful novel RNAi molecules for treating pancreatic cancer and liver metastasis.
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- 2024
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20. Novel Eu 3+ -Doped Glasses in the MoO 3 -WO 3 -La 2 O 3 -B 2 O 3 System: Preparation, Structure and Photoluminescent Properties.
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Aleksandrov L, Milanova M, Yordanova A, Iordanova R, Shinozaki K, Honma T, and Komatsu T
- Abstract
Novel multicomponent glasses with nominal compositions of (50-x)MoO
3 :xWO3 :25La2 O3 :25B2 O3 , x = 0, 10, 20, 30, 40, 50 mol% doped with 3 mol % Eu2 O3 were prepared using a conventional melt-quenching method. Their structure, thermal behavior and luminescent properties were investigated by Raman spectroscopy, differential thermal analysis and photoluminescence spectroscopy. The optical properties of the glasses were investigated by UV-vis absorption spectroscopy and a determination of the refractive index. Physical parameters such as density, molar volume, oxygen molar volume and oxygen packing density were determined. The glasses are characterized by a high glass transition temperature. Raman analysis revealed that the glass structure is built up mainly from tetrahedral (MoO4 )2- and (WO4 )2- units providing Raman bands of around 317 cm-1 , 341-352 cm-1 , 832-820 cm-1 and 928-935 cm-1 . At the same time, with the replacement of MoO3 with WO3 some fraction of WO6 octahedra are produced, the number of which increases with the increasing WO3 content. A strong red emission from the5 D0 level of Eu3+ ions was registered under near-UV (397 nm) excitation using the7 F0 →5 L6 transition of Eu3+ . Photoluminescence (PL) emission gradually increases with increasing WO3 content, evidencing that WO3 is a more appropriate component than MoO3 . The integrated fluorescence intensity ratio R (5 D0 →7 F2 /5 D0 →7 F1 ) was calculated to estimate the degree of asymmetry around the active ion, suggesting a location of Eu3+ in non-centrosymmetric sites. All findings suggest that the investigated glasses are potential candidates for red light-emitting phosphors.- Published
- 2024
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21. A genome-wide association study identified PTPN2 as a population-specific susceptibility gene locus for primary biliary cholangitis.
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Hitomi Y, Ueno K, Aiba Y, Nishida N, Kono M, Sugihara M, Kawai Y, Kawashima M, Khor SS, Sugi K, Kouno H, Kohno H, Naganuma A, Iwamoto S, Katsushima S, Furuta K, Nikami T, Mannami T, Yamashita T, Ario K, Komatsu T, Makita F, Shimada M, Hirashima N, Yokohama S, Nishimura H, Sugimoto R, Komura T, Ota H, Kojima M, Nakamuta M, Fujimori N, Yoshizawa K, Mano Y, Takahashi H, Hirooka K, Tsuruta S, Sato T, Yamasaki K, Kugiyama Y, Motoyoshi Y, Suehiro T, Saeki A, Matsumoto K, Nagaoka S, Abiru S, Yatsuhashi H, Ito M, Kawata K, Takaki A, Arai K, Arinaga-Hino T, Abe M, Harada M, Taniai M, Zeniya M, Ohira H, Shimoda S, Komori A, Tanaka A, Ishigaki K, Nagasaki M, Tokunaga K, and Nakamura M
- Subjects
- Female, Humans, Male, Case-Control Studies, Japan, Polymorphism, Single Nucleotide, East Asian People genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Liver Cirrhosis, Biliary genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 2 genetics
- Abstract
Background and Aims: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-nonspecific) and nonshared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC., Approach and Results: Protein tyrosine phosphatase nonreceptor type 2 ( PTPN2) was identified as a novel PBC susceptibility gene locus through GWAS and subsequent genome-wide meta-analysis involving 2181 cases and 2699 controls from the Japanese population (GWAS-lead variant: rs8098858, p = 2.6 × 10 -8 ). In silico and in vitro functional analyses indicated that the risk allele of rs2292758, which is a primary functional variant, decreases PTPN2 expression by disrupting Sp1 binding to the PTPN2 promoter in T follicular helper cells and plasmacytoid dendritic cells. Infiltration of PTPN2-positive T-cells and plasmacytoid dendritic cells was confirmed in the portal area of the PBC liver by immunohistochemistry. Furthermore, transcriptomic analysis of PBC-liver samples indicated the presence of a compromised negative feedback loop in vivo between PTPN2 and IFNG in patients carrying the risk allele of rs2292758., Conclusions: PTPN2 , a novel susceptibility gene for PBC in the Japanese population, may be involved in the pathogenesis of PBC through an insufficient negative feedback loop caused by the risk allele of rs2292758 in IFN-γ signaling. This suggests that PTPN2 could be a potential molecular target for PBC treatment., (Copyright © 2024 American Association for the Study of Liver Diseases.)
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- 2024
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22. Outcome of transvenous lead extraction in nonagenarians: A single-center retrospective study.
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Komatsu T, Okada A, Shoda M, Tanaka K, Kobayashi H, Oguchi Y, Saigusa T, Ebisawa S, Motoki H, and Kuwahara K
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- Humans, Female, Male, Retrospective Studies, Aged, 80 and over, Treatment Outcome, Device Removal, Prosthesis-Related Infections etiology, Defibrillators, Implantable, Pacemaker, Artificial
- Abstract
Background: Transvenous lead extraction (TLE) for cardiovascular implantable electronic device (CIED)-related infections has increased. The incidence of TLE in nonagenarians is low, with limited reports outlining the outcomes of this procedure. Therefore, in this study, we aimed to clarify the outcomes of TLE in nonagenarians., Methods: Patients with TLE treated at our hospital between 2014 and 2023 were retrospectively examined; patient characteristics, device type, indications, procedures, complications, and clinical data of nonagenarians were analyzed., Results: Of 12 patients with 24 leads (active fixation lead, n = 11; passive fixation lead, n = 13) who underwent TLE, the indication for TLE was infection (pocket infection, n = 8; sepsis, n = 4). Methicillin-resistant Staphylococcus epidermidis was the most frequently identified causative agent (n = 4). The median patient age was 91 years; five patients were female. The median lead dwell time was 9 years. Excimer laser sheath (16 leads), mechanical sheath (five leads), Evolution RL (one lead), and manual traction (two leads) were employed in TLE. The procedure was successful in all patients, and only one had a minor complication. Six patients required CIED re-implantation, and leadless pacemakers were selected for five patients. The 30-day mortality after TLE was 0%., Conclusion: TLE can be safely performed in nonagenarians. The decision to perform TLE should not be based on old age alone; the suitability of removing infected CIEDs should be determined based on each patient's condition., (© 2024 The Author(s). Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)
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- 2024
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23. Development of a prediction score for Barrett's esophagus in Japanese health checkup settings.
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Kodama S, Watanabe K, Shimodaira Y, Fukuda S, Yoshida T, Saruta Y, Okubo R, Matsuhashi T, Komatsu T, and Iijima K
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- Humans, Male, Japan epidemiology, Female, Middle Aged, Retrospective Studies, Aged, Risk Assessment methods, Adult, Sensitivity and Specificity, Esophagoscopy methods, Risk Factors, Adenocarcinoma epidemiology, Adenocarcinoma diagnosis, Adenocarcinoma pathology, Incidence, Predictive Value of Tests, Precancerous Conditions epidemiology, Precancerous Conditions diagnosis, Precancerous Conditions pathology, East Asian People, Barrett Esophagus epidemiology, Barrett Esophagus pathology, Barrett Esophagus diagnosis, Esophageal Neoplasms epidemiology, Esophageal Neoplasms diagnosis, Esophageal Neoplasms pathology
- Abstract
Background: The incidence of esophageal adenocarcinoma has recently increased in Asia, including Japan. A system to identify individuals at high risk for Barrett's esophagus (BE), a pre-cancerous condition of esophageal adenocarcinoma, among the general population is needed to perform endoscopic surveillance appropriately. We therefore developed risk prediction scores for BE at health checkups in Japan., Methods: 4128 consecutive health checkup examinees were retrospectively enrolled from October 2021 to March 2022. A prediction score for BE was developed based on the linear transformation of β-regression coefficients in a multivariable regression model incorporating BE predictors. Internal validation was performed by evaluating discrimination and calibration of the prediction model., Results: Three prediction scores corresponding to BE based on its length were developed: all lengths, ≥ 1 cm, ≥ 2 cm. All scores were internally validated, and the model calibration was excellent. The performance of the prediction models was better for longer BE, with a c-statistic of 0.70 for BE ≥ 2 cm, than for shorter values. The prediction score for BE ≥ 2 cm yielded sensitivity and specificity of 52.9% and 78.6% in high-risk subjects and 91.2% and 29.3% in intermediate- or high-risk subjects, respectively., Conclusions: This prediction score can potentially increase the endoscopic detection of BE by identifying potentially high-risk individuals from the general population. This is the first report on developing a prediction score for BE that may suit the Japanese population., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)
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- 2024
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24. Liver-specific Lxr inhibition represses reverse cholesterol transport in cholesterol-fed mice.
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Nishida T, Ayaori M, Arakawa J, Suenaga Y, Shiotani K, Uto-Kondo H, Komatsu T, Nakaya K, Endo Y, Sasaki M, and Ikewaki K
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- Animals, Biological Transport, Mice, ATP Binding Cassette Transporter, Subfamily G, Member 5 metabolism, ATP Binding Cassette Transporter, Subfamily G, Member 5 genetics, Cholesterol, Dietary, ATP Binding Cassette Transporter, Subfamily G, Member 8 metabolism, ATP Binding Cassette Transporter, Subfamily G, Member 8 genetics, Male, Cholesterol, HDL blood, Cholesterol, HDL metabolism, Lipoproteins, HDL metabolism, Lipoproteins, Liver X Receptors metabolism, Liver X Receptors genetics, Liver metabolism, Mice, Knockout, Cholesterol metabolism, Macrophages metabolism, Mice, Inbred C57BL, Sulfotransferases metabolism, Sulfotransferases genetics
- Abstract
Background and Aims: High density lipoprotein (HDL) exerts an anti-atherosclerotic effect via reverse cholesterol transport (RCT). Several phases of RCT are transcriptionally controlled by Liver X receptors (Lxrs). Although macrophage Lxrs reportedly promote RCT, it is still uncertain whether hepatic Lxrs affect RCT in vivo., Methods: To inhibit Lxr-dependent pathways in mouse livers, we performed hepatic overexpression of sulfotransferase family cytosolic 2B member 1 (Sult2b1) using adenoviral vector (Ad-Sult2b1). Ad-Sult2b1 or the control virus was intravenously injected into wild type mice and Lxrα/β double knockout mice, under a normal or high-cholesterol diet. A macrophage RCT assay and an HDL kinetic study were performed., Results: Hepatic Sult2b1 overexpression resulted in reduced expression of Lxr-target genes - ATP-binding cassette transporter G5/G8, cholesterol 7α hydroxylase and Lxrα itself - respectively reducing or increasing cholesterol levels in HDL and apolipoprotein B-containing lipoproteins (apoB-L). A macrophage RCT assay revealed that Sult2b1 overexpression inhibited fecal excretion of macrophage-derived
3 H-cholesterol only under a high-cholesterol diet. In an HDL kinetic study, Ad-Sult2b1 promoted catabolism/hepatic uptake of HDL-derived cholesterol, thereby reducing fecal excretion. Finally, in Lxrα/β double knockout mice, hepatic Sult2b1 overexpression increased apoB-L levels, but there were no differences in HDL levels or RCT compared to the control, indicating that Sult2b1-mediated effects on HDL/RCT and apoB-L were distinct: the former was Lxr-dependent, but not the latter., Conclusions: Hepatic Lxr inhibition negatively regulates circulating HDL levels and RCT by reducing Lxr-target gene expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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25. Evaluation of Difference in Emergency Care Quality by Years of Physician Experience at the Emergency Department.
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Tokunaga S, Ikeda AI, Usuda D, Kawai K, Sakurai R, Tsuge S, Matsubara S, Suzuki M, Tanaka R, Shimozawa S, Hotchi Y, Osugi I, Kondo A, Mishima K, Mizuno K, Komatsu T, Takami H, Oba J, Nomura T, and Sugita M
- Abstract
Objective: To evaluate the effect of emergency medicine training credentials and years of medical experience on various clinical parameters in emergency medicine practice., Methods: A cross-sectional study was conducted at Juntendo University Nerima Hospital between 1 April 2019 and 31 March 2020. All patients who were transported by ambulance, were examined by emergency physicians, and underwent computed tomography (CT) or magnetic resonance imaging (MRI) in the emergency department were included. For these cases, data on the attending physician's qualification status and experience (specialist, nonspecialist with 1-2 years of experience, or nonspecialist with 3-4 years of experience), clinical parameters, and imaging were collected. The primary outcome was the patient's total length of stay (LOS) in the emergency department., Results: A total of 3,784 patients were included in the study. Patients attended by nonspecialists with 1-2 years of experience had a significantly longer time from arrival to assessment and LOS, especially in mild and severe cases and cases requiring head and abdominal CT imaging., Conclusion: Our findings suggest that for physicians with minimal work experience, mentorship and effective training using triage flow and medical examination protocols may help to reduce LOS in the emergency department., Competing Interests: We 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 The Juntendo Medical Society.)
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- 2024
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26. Consensus Definitions of Cytomegalovirus (CMV) Infection and Disease in Transplant Patients Including Resistant and Refractory CMV for Use in Clinical Trials: 2024 Update From the Transplant Associated Virus Infections Forum.
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Ljungman P, Chemaly RF, Khawaya F, Alain S, Avery R, Badshah C, Boeckh M, Fournier M, Hodowanec A, Komatsu T, Limaye AP, Manuel O, Natori Y, Navarro D, Pikis A, Razonable RR, Westman G, Miller V, Griffiths PD, and Kotton CN
- Subjects
- Humans, Drug Resistance, Viral, Organ Transplantation adverse effects, Cytomegalovirus Infections drug therapy, Cytomegalovirus Infections virology, Cytomegalovirus Infections diagnosis, Antiviral Agents therapeutic use, Cytomegalovirus drug effects, Transplant Recipients, Clinical Trials as Topic, Consensus
- Abstract
Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2017. Since then, there have been major developments, including registration of new antiviral agents. Therefore, the Transplant Associated Virus Infections Forum, which consists of scientists, clinicians, regulators, and industry representatives, has produced an updated version of these definitions that incorporates recent knowledge with the aim of supporting clinical research and drug development. This also includes an update regarding the definition of resistant and refractory CMV infections previously published in 2019. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts among clinicians, scientists, regulators, and industry representatives can provide a platform for this work., Competing Interests: Potential conflicts of interest. P. L. has received research grants from AlloVir, MSD, Takeda, and Astellas; has received honoraria from MSD, Moderna, and Gilead; participates on Moderna and OctaPharma data and safety monitoring/advisory boards; and participates as a board member of the European Conference on Infections in Leukemia. R. F. C. has received research grants from Merck/MSD, Karius, AiCuris, Ansun Pharmaceuticals, Takeda, Genentech, Oxford Immunotec, and Eurofins-Viracor; reports consulting fees from ADMA Biologics, Janssen, Merck/MSD, Partner Therapeutics, Takeda, Shinogi, AiCuris, Roche/Genentech, Astellas, Adagio Therapeutics, Tether, Oxford Immunotec, Karius, Moderna, and Ansun Pharmaceuticals; participates on ADMA Biologics, Merck/MSD, Takeda, Shinogi, AiCuris, Roche/Genentech, Tether, Karius, Moderna, and Ansun Pharmaceuticals data and safety monitoring/advisory boards; and reports stock options from Xenex. F. K. has received research grants from Eurofins Viracor and has received honoraria from MEDSCAPE. S. A. has received research grants from Takeda, Merck, MSD, BioMerieux, Hologic, and Elitech; has received honoraria from MSD, Biotest, and Takeda; has received support for attending meetings/travel from MSD, Biotest, and Takeda; and participates on Biotest, Takeda, MSD, QCMD, and GSK data and safety monitoring/advisory boards. R. A. has received research grants from AiCuris, Astellas, AstraZeneca, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, and Takeda. C. B. is an employee of Merck & Co. M. B. has received research grants from Merck. M. F. has received support for attending meetings/travel from, is employed by, and is a shareholder of Takeda. A. H. is an employee of the Division of Antiviral Products, Center for Drug Evaluation and Research, US FDA. T. K. is an employee of the Division of Antiviral Products, Center for Drug Evaluation and Research, US FDA. A. P. L. has received research grants from Merck, Moderna, and Takeda; reports consulting fees from Merck, GSK, and Novartis; and participates on the Novartis data and safety monitoring/advisory board. O. M. has received honoraria from Takeda, MSD, Biotest, and AstraZeneca. Y. N. reports consulting fees from Nobel Pharma. D. N. has received research grants from Pfizer, MSD, Abbot Diagnostics, and Roche Diagnostics; reports consulting fees from Roche Diagnostics, Takeda, and AstraZeneca; has received honoraria from Pfizer, MSD, Roche Diagnostics, Abbot Diagnostics, GSK, and BioMerieux; and has received support for attending meetings/travel from Pfizer. A. P. participates on the Antiretroviral Pregnancy Registry and is an employee of the Division of Antiviral Products, Center for Drug Evaluation and Research, US FDA. R. R. R. has received research grants from Regeneron, Roche Diagnostics, and Gilead; reports consulting fees from AlloVir; participates on the Novartis data and safety monitoring/advisory board; and participates in a leadership role for the American Society of Transplantation. G. W. is an employee of the Swedish Medical Products Agency, Uppsala, Sweden. V. M. has received research grants from AiCuris, AlloVir, Evrys Bio, Merck, Takeda, Symbio Pharma, Qiagen, Vera Therapeutics, and Eurofins-Viracor. P. D. G. reports consulting fees from Biotest, Evrys Bio, GSK, Hookipa, Takeda, and Moderna and reports the United Kingdom patent application 2020135.6 “Human CMV Vaccine,” assigned to University College London. C. N. K. reports consulting fees from Biotest, ExeVir, Evrys Bio, Hookipa, Takeda, Merck, Qiagen, Roche Diagnostics, and Abbot Laboratories; has received honoraria from Takeda, Roche Diagnostics, Qiagen, and Biotest; participates on Takeda, Roche Diagnostics, Abbot Laboratories, Biotest, ExeVir, and Evrys Bio data and safety monitoring/advisory boards; and participates in a leadership role for the Transplantation Society. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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27. Native valve endocarditis caused by Corynebacterium striatum without underlying structural heart disease or indwelling cardiovascular medical devices: a case report.
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Usuda D, Kojima Y, Ono R, Kaneoka Y, Kato M, Sugawara Y, Shimizu R, Inami T, Nakajima E, Tsuge S, Sakurai R, Kawai K, Matsubara S, Tanaka R, Suzuki M, Shimozawa S, Hotchi Y, Osugi I, Katou R, Ito S, Mishima K, Kondo A, Mizuno K, Takami H, Komatsu T, Nomura T, and Sugita M
- Subjects
- Humans, Female, Adult, Mitral Valve surgery, Mitral Valve microbiology, Corynebacterium Infections microbiology, Corynebacterium Infections drug therapy, Corynebacterium isolation & purification, Endocarditis, Bacterial microbiology, Endocarditis, Bacterial drug therapy, Anti-Bacterial Agents therapeutic use
- Abstract
Background: Corynebacterium striatum (C. striatum) is a gram-positive, anaerobic bacillus found both environmentally and in human skin and nasal mucosa flora. It is reportedly the etiologic agent of community-acquired and nosocomial diseases and is significantly associated with bacteremia and medical endovascular devices. This is the rare case of mitral valve native valve endocarditis (NVE) caused by C. striatum occurring in a young adult without underlying structural heart disease or indwelling cardiovascular medical devices successfully treated with multidisciplinary therapy., Case Presentation: The patient was a 28-year-old female with no medical history. She was transferred our hospital due to sudden onset of vertigo and vomit. A computed tomography on day 2 revealed the hydrocephalus due to the cerebellar infarction, and she underwent posterior fossa decompression for cerebellar infarction. An angiography on day 8 revealed a left vertebral artery dissection, which was suspected be the etiology. Afterwards, a sudden fever of 39 degrees developed on day 38. She was diagnosed with aspiration pneumonia and treated with ampicillin/sulbactam but was still febrile at the time of transfer for rehabilitation. Treatment continued with levofloxacin, the patient had no fever decline, and she was readmitted to our hospital. Readmission blood cultures (3/3 sets) revealed C. striatum, and an echocardiogram revealed an 11 mm long mitral valve vegetation, leading to NVE diagnosis. On the sixth illness day, cardiac failure symptoms manifested. Echocardiography revealed mitral valve rupture. She was transferred again on the 11th day of illness, during which time her mitral valve was replaced. C. striatum was detected in the vegetation. Following surgery, she returned to our hospital, and vancomycin administration continued. The patient was discharged after 31 total days of postoperative antimicrobial therapy. The patient experienced no exacerbations thereafter., Conclusions: We report the rare case of C. striatum mitral valve NVE in a young adult without structural heart disease or indwelling cardiovascular devices., Clinical Trial Number: Not applicable., (© 2024. The Author(s).)
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- 2024
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28. Cerebral Small Vessel Disease is Associated with Prehospital Delay in Acute Ischemic Stroke.
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Masui M, Sato T, Okumura M, Ishikawa T, Sakuta K, Kokubu T, Takahashi J, Kitagawa T, Tanabe M, Onda A, Komatsu T, Sakai K, Umehara T, Mitsumura H, and Iguchi Y
- Abstract
Aim: To determine whether the severity of cerebral small vessel disease (SVD) is associated with prehospital delay in acute ischemic stroke., Methods: Consecutive patients with ischemic stroke were included in this study. We evaluated the SVD burden using the total SVD score. Patients were divided into 2 groups: onset-to-door time within 4.5 hours (early arrival group) and onset-to-door time over 4.5 hours (delayed arrival group). First, we assessed whether the total SVD score was related to prehospital delay using a logistic regression analysis. Second, we assessed which item of the score was independently associated with delays. Finally, we determined whether the item had a linear association with the delay., Results: Of the 2,112 screened patients, 1,754 were enrolled in the study (1,253 males [71%]; median age, 69 years). There were 1,105 patients (63%) in the delayed arrival group. The total SVD score was independently associated with delay (OR 1.11, 95% CI 1.01-1.21, p=0.025). Among the 4 items of the score, only enlarged perivascular spaces (EPVS) in the basal ganglia was independently associated with delay (OR 1.37, 95% CI 1.05-1.80, p=0.022). A linear trend was observed between EPVS grade and delay with reference to EPVS grade 0-1 (EPVS grade 2: OR 1.22, 95% CI 0.92-1.62, p=0.170, EPVS grade 3: OR 1.69, 95% CI 1.20-2.38, p=0.002, EPVS grade 4: OR 2.17, 95% CI 1.37-3.44, p=0.001)., Conclusions: Prehospital delay in acute ischemic stroke could be associated with the severity of SVD, particularly EPVS in the basal ganglia.
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- 2024
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29. Transport of Zinc-Phthalocyanine to Cancer Cells Using Myoglobin-Albumin Fusion Protein for Photodynamic Therapy.
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Yamada T, Funamoto M, Takada R, Morita Y, and Komatsu T
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- Humans, Cell Line, Tumor, Serum Albumin, Human chemistry, Serum Albumin, Human metabolism, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins pharmacology, Recombinant Fusion Proteins metabolism, Apoptosis drug effects, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Neoplasms drug therapy, Neoplasms pathology, Photochemotherapy, Indoles chemistry, Indoles pharmacology, Myoglobin chemistry, Myoglobin metabolism, Photosensitizing Agents chemistry, Photosensitizing Agents pharmacology, Photosensitizing Agents chemical synthesis, Organometallic Compounds chemistry, Organometallic Compounds pharmacology, Organometallic Compounds chemical synthesis, Isoindoles, Zinc Compounds chemistry
- Abstract
Photodynamic therapy (PDT) is a noninvasive approach to cancer treatment, wherein cell death is initiated by singlet oxygen (
1 O2 ) production via energy transfer from excited photosensitizers to ground-state O2 . Effective clinical photosensitizers necessitate water solubility for in vivo administration. Hydrophobic dyes, such as phthalocyanines, cannot be used directly as photosensitizers. Herein, we synthesized a myoglobin-(human serum albumin) fusion protein reconstituted with zinc-phthalocyanine (ZnPc), termed ZnPcMb-HSA. The photophysical properties of ZnPcMb-HSA closely resemble those of ZnPc-substituted Mb. Notably, ZnPc dissociates from ZnPcMb-HSA and selectively accumulates within cancer cells, while the protein components remain extracellular. Treatment of four distinct cell lines with ZnPcMb-HSA, followed by red-light irradiation, effectively induced apoptosis. The half-maximal inhibitory concentrations (IC50 ) against these cancer cell lines ranged between 0.1-0.5 μM. Reconstituted Mb-HSA emerges as a promising carrier for transporting various water-insoluble porphyrinoid photosensitizer to target cancer cells in PDT applications., (© 2024 Wiley-VCH GmbH.)- Published
- 2024
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30. Spatiotemporal variations of zooplankton community structure in the oyster (Crassostrea gigas)-macroalgae reef dual ecosystems adjacent to Luanhe River Estuary.
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Xu M, Zhao Q, Wang S, Wang Y, Shen J, Zhang Y, Yang L, Xu K, Hou X, Zhang Y, Zhang H, Otaki T, Komatsu T, and Xu Y
- Subjects
- Animals, China, Rivers, Biodiversity, Coral Reefs, Zooplankton, Ecosystem, Estuaries, Crassostrea growth & development, Crassostrea physiology
- Abstract
Majority of macrozooplankton have a wider dietary niche breadth and utilize small invertebrates, microzooplankton and mesozooplankton, so effect on primary production might be through trophic cascading effect. To better understand the ecosystem structure of benthic oyster-macroalgae reefs, we analyzed zooplankton community structure before (July 2016) and after (from September 2016 to October 2017) the construction of benthic reefs in the 2 km2 sea ranch area in Xiangyun Cove, Tangshan, China. We identified 57 zooplankton species, including the 12 cnidarian (e.g., Clytia hemisphaerica Linnaeus and Eirene ceylonensis Browne), 1 ctenopharyngodon (Pleurobrachia globosa Moser), 24 crustacean (e.g., Calanus sinicus Brodsky, Paracalanus parvus Claus, Labibocera euchaeta Glesbrecht, Labibocera bipinnata Tanaka, Calanopia thompsoni Scott, and Centropages dorsispinatus Thompson), 1 chaetognath (Sagitta crassa Tokioka), 1 urochordate species (Oikopleura dioica Fol), and 18 species of planktonic polychaete and gastropod larvae. The zooplankton density and biomass values before reef construction were 266.14 ind/m3 and 2.72 mg/m3, respectively, and those after reef construction were 138.06 ind/m3 and 32.91 mg/m3, respectively. The biomass trend was as follow: October 2017 (89.08 mg/m3) > August 2017 (70.97) > September 2016 (3.17) > July 2016 (2.72) > June 2017 (0.86) > May 2017 (0.44). The common dominant organisms were crustaceans and chaetognaths. According to the RDA ranking results, water temperature was positively correlated with the Shannon-Wiener diversity index and Margalef's richness indexes. With the increasement of Margalef's richness index, the value of dissolved oxygen content showed a significant negative correlation with zooplankton abundance. The results of this study are applicable to sustainable development and management strategies of coastal reef ecosystems and provide a basis for further surveys of secondary productivity in the sea ranch area., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Xu 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.)
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- 2024
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31. Effects and safety of high-frequency rTMS in subacute ischemic stroke patients.
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Komatsu T, Hada T, Sasaki N, Kida H, Maku T, Nakada R, Kitagawa T, Sato T, Takatsu H, Sakuta K, Sakai K, Umehara T, Mitsumura H, Abo M, and Iguchi Y
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Treatment Outcome, Prospective Studies, Stroke Rehabilitation methods, Transcranial Magnetic Stimulation methods, Transcranial Magnetic Stimulation adverse effects, Ischemic Stroke therapy
- Abstract
Objective: Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has shown benefits in chronic stroke, its application in subacute ischemic stroke remains underexplored. This study aims to investigate the effects and safety of lesion-side HF-rTMS in subacute ischemic stroke., Methods: Prospective lesion-side HF-rTMS was conducted on consecutive ischemic stroke patients within 3 days of onset from February 2019 to June 2022. Inclusion criteria required persistent paralysis (NIHSS score ≥ 1 for at least 7 days). Exclusion criteria comprised cortical infarction, disturbance of consciousness, and age over 80 years. A conventional rehabilitation group meeting the same criteria from June 2015 to January 2019 served as a comparison. We compared the two groups regarding clinical background and outcome. We also evaluated incidence of epilepsy and exacerbation of the NIHSS score in the rTMS group., Results: Seventy-eight patients participated, with 50% in the HF-rTMS group. Median time from onset to HF-rTMS initiation was 9 (IQR 7-12) days. A favorable outcome (modified Rankin Scale score 0-2) at 3 months was more frequent in the rTMS group (80% vs. 44%, p = 0.002). HF-rTMS was independently associated with a favorable outcome at 3 months (OR = 5.60, 95% CI = 1.53-20.50, p = 0.009). No cases of epilepsy or exacerbation of NIHSS score were observed., Conclusions: HF-rTMS demonstrates potential effectiveness and safety in subacute ischemic stroke patients., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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32. Population pharmacokinetics and pharmacodynamic target attainment analysis of cefazolin using total and unbound serum concentration in patients with prostatectomy or nephrectomy.
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Komatsu T, Kawai Y, Takayama Y, Akamada Y, Kusume E, Ikeda M, Tsumura H, Ishii D, Iwamura M, Okamoto H, Hanaki H, and Otori K
- Subjects
- Humans, Male, Middle Aged, Aged, Female, Staphylococcus aureus drug effects, Adult, Protein Binding, Aged, 80 and over, Cefazolin pharmacokinetics, Cefazolin blood, Cefazolin therapeutic use, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents blood, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Nephrectomy, Microbial Sensitivity Tests, Prostatectomy, Escherichia coli drug effects
- Abstract
The aim of this study was to analyze the population pharmacokinetics of total and unbound concentrations of prophylactic cefazolin (CFZ) in patients with prostatectomy or nephrectomy. We also aimed to calculate a pharmacodynamics target unbound concentration that exceeded the minimum inhibitory concentration (MIC), to design an effective dosing regimen. Briefly, 614 total concentration and 610 unbound concentration samples from 152 individuals were evaluated, using a nonlinear mixed-effects model. The obtained pharmacodynamics index target value reflected the probability of maintaining CFZ unbound trough concentrations exceeding MIC
90 , 0.5 mg/L, and MIC50 , and 1.0 mg/L, to account for methicillin-susceptible Staphylococcus aureus (MSSA) or Escherichia coli . Population pharmacokinetics were estimated using a two-compartment model with nonlinear protein binding. Unbound systemic clearance (CL) was significantly associated with creatinine clearance, while the maximum protein-binding constant was significantly associated with albumin levels. The probability of achieving an unbound concentration exceeding the MIC50 for E. coli or MIC90 for MSSA in a patient with normal renal function following a 1 g CFZ infusion over 15 min was above 90% at 3 h after the initial dose. Our findings indicated that population pharmacokinetic parameters are useful for determining unbound CFZ pharmacokinetics and evaluating intraoperative CFZ redosing intervals., Competing Interests: The authors declare no conflict of interest.- Published
- 2024
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33. Relationship between nephrotoxicity and area under the concentration-time curve of vancomycin in critically ill patients: a multicenter retrospective study.
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Ishigo T, Matsumoto K, Yoshida H, Tanaka H, Ibe Y, Fujii S, Fukudo M, Fujihara H, Yamaguchi F, Ebihara F, Maruyama T, Hamada Y, Samura M, Nagumoi F, Komatsu T, Tomizawa A, Takuma A, Chiba H, Nishi Y, Enoki Y, Taguchi K, and Suzuki A
- Subjects
- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Vancomycin adverse effects, Vancomycin pharmacokinetics, Critical Illness, Acute Kidney Injury chemically induced, Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents administration & dosage, Area Under Curve, Intensive Care Units, Drug Monitoring methods
- Abstract
We aimed to assess the frequency of acute kidney injury (AKI) in different areas under the concentration-time curve (AUC) values of vancomycin (VAN) using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. This multicenter retrospective observational study was conducted in eight hospitals. We retrospectively analyzed the data of patients who had received VAN in an intensive care unit (ICU) between January 2020 and December 2022. The primary outcome was the incidence of AKI. Patients were classified into three groups according to the AUC
24-48h at the initial therapeutic drug monitoring (TDM) as follows: <500, 500-600, and ≥600 µg·h/mL. The AUC24-48h values were calculated using the Bayesian estimation software Practical AUC-guided TDM. Among 146 patients [median age (interquartile range), 67 (56-78) years; 39% women], the AUC24-48h <500 µg·h/mL had an AKI rate of 6.5% (7/107), the AUC24-48h 500-600 µg·h/mL had an AKI rate of 28.0% (7/25), and the AUC24-48h ≥600 µg·h/mL had an AKI rate of 42.9% (6/14). In multivariate Cox proportional hazard analysis, the AUC24-48h 500-600 µg·h/mL [hazard ratio 5.4, 95% confidence interval (CI) 1.64-17.63] and the AUC24-48h ≥600 μg·h/mL (hazard ratio 7.0, 95% CI 2.31-21.18) significantly correlated with a higher incidence of AKI compared with the AUC24-48h <500 μg·h/mL. In conclusion, we identified an association between AUC on day 2 and the risk of AKI in ICU patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI., Importance: Vancomycin (VAN) is a glycopeptide antibiotic and one of the most commonly used antibiotics for severe infections caused by methicillin-resistant Staphylococcus aureus . However, higher VAN concentrations have been associated with an increased risk of acute kidney injury (AKI). Herein, we aimed to assess the frequency of AKI in different areas under the concentration-time curve (AUC) values of VAN using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. We identified an association between AUC on day 2 and the risk of AKI in intensive care unit patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI. Therefore, individualized dosing is feasible, with pharmacists being able to optimize VAN doses to attain appropriate targets., Competing Interests: K.M. received grant support funding from Meiji Seika Pharma Co., Ltd., Sumitomo Pharma Co., Ltd. and Shionogi & Co., Ltd., and speaker honoraria from Meiji Seika Pharma Co., Ltd. The other authors declare no conflicts of interest.- Published
- 2024
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34. Dual delivery of carbon monoxide and doxorubicin using haemoglobin-albumin cluster: proof of concept for well-tolerated cancer therapy.
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Ito C, Taguchi K, Yamada T, Hanaya K, Enoki Y, Sugai T, Komatsu T, and Matsumoto K
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- Animals, Mice, Humans, Drug Carriers chemistry, Mice, Inbred BALB C, Antibiotics, Antineoplastic pharmacology, Antibiotics, Antineoplastic chemistry, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Cell Line, Tumor, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Drug Delivery Systems, Neoplasms, Experimental drug therapy, Neoplasms, Experimental pathology, Neoplasms, Experimental metabolism, Cell Survival drug effects, Doxorubicin pharmacology, Doxorubicin chemistry, Carbon Monoxide chemistry, Carbon Monoxide pharmacology, Hemoglobins chemistry
- Abstract
A serious concern of doxorubicin (DOX) therapy is that it causes severe adverse effects, particularly cardiotoxicity. Carbon monoxide (CO) possesses powerful cytoprotective effects against drug-induced organ injury and is expected to ameliorate DOX-induced cardiotoxicity. In this study, a dual carrier of DOX and CO (CO-HemoAct-DOX) was fabricated based on a haemoglobin-albumin cluster (HemoAct), which is a protein cluster with a haemoglobin core structure wrapped by serum albumin. CO-HemoAct-DOX was synthesised by binding CO to a haemoglobin core and covalently conjugating (6-maleimidocaproyl)hydrazone derivative of DOX to an albumin shell. The average DOX/cluster ratio was about 2.6. In the in vitro cytotoxicity assay against cancer cells, the anti-tumour activity of CO-HemoAct-DOX was 10-fold lower than that of DOX in a 2D-cultured model, whereas CO-HemoAct-DOX suppressed the growth of tumour spheroids to the same extent as DOX in the 3D-cultured model. In colon-26 tumour-bearing mice, CO-HemoAct-DOX achieved DOX delivery to the tumour site and alleviated tumour growth more effectively than DOX. Furthermore, CO-HemoAct attenuated DOX-induced cardiomyocyte atrophy in H9c2 cells and elevated the levels of cardiac biomarkers in mice exposed to DOX. These results suggest that the dual delivery of CO and DOX using HemoAct is a promising strategy as an anti-tumour agent to realise well-tolerated cancer therapy with minimal cardiotoxicity.
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- 2024
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35. Synthesis of Macrolactone Core of ent -Formosalide A via Regioselective Ether Cyclization.
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Mozumi R, Fukaya K, Ito H, Komatsu T, and Urabe D
- Abstract
Formosalide A is a cytotoxic macrolide isolated from the dinoflagellate Prorocentrum sp, whose structure is characterized by functionalized 5- and 6-membered ether rings embedded in the macrolactone and an all cis -tetraene side chain. Here, we report the synthesis of the macrolactone core of ent -formosalide A. Our approach is highlighted by the Au-mediated 6- exo - dig cyclization for the synthesis of the 6-membered ether ring, which proceeded in a highly regioselective manner. Control experiments demonstrated that the acyclic protecting group of the C9,C10-diol was crucial for the desired 6- exo - dig cyclization. Theoretical studies were performed focusing on structural component analysis, which suggested that the C8-C9-C10-C11 dihedral angle induced by the protecting group controlled the regioselectivity. An additional 6 steps including Shiina macrolactone formation from the 6-membered ether ring completed the synthesis of the macrolactone core of ent -formosalide A.
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- 2024
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36. How did COVID-19 pandemic affect the older adults' needs for robot technologies in Japan?: comparison of participatory design workshops during versus after the COVID-19 pandemic.
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Komatsu T, Fraune MR, Tsui KM, Suda S, and Kobayashi M
- Abstract
Social technology can improve the quality of social lives of older adults (OAs) and mitigate negative mental and physical health outcomes. When people engage with technology, they can do so to stimulate social interaction (stimulation hypothesis) or disengage from their real world (disengagement hypothesis), according to Nowland et al.'s model of the relationship between social Internet use and loneliness. External events, such as large periods of social isolation like during the COVID-19 pandemic, can also affect whether people use technology in line with the stimulation or disengagement hypothesis. We examined how the COVID-19 pandemic affected the social challenges OAs faced and their expectations for robot technology to solve their challenges. We conducted two participatory design (PD) workshops with OAs during and after the COVID-19 pandemic. During the pandemic, OAs' primary concern was distanced communication with family members, with a prevalent desire to assist them through technology. They also wanted to share experiences socially, as such OA's attitude toward technology could be explained mostly by the stimulation hypothesis. However, after COVID-19 the pandemic, their focus shifted towards their own wellbeing. Social isolation and loneliness were already significant issues for OAs, and these were exacerbated by the COVID-19 pandemic. Therefore, such OAs' attitudes toward technology after the pandemic could be explained mostly by the disengagement hypothesis. This clearly reflect the OA's current situation that they have been getting further digitally excluded due to rapid technological development during the pandemic. Both during and after the pandemic, OAs found it important to have technologies that were easy to use, which would reduce their digital exclusion. After the pandemic, we found this especially in relation to newly developed technologies meant to help people keep at a distance. To effectively integrate these technologies and avoid excluding large parts of the population, society must address the social challenges faced by OAs., Competing Interests: Author KT was employed by the company Toyota Research Insitute. Author KT receives a nominal financial award for publishing academic papers. The remaining 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 Komatsu, Fraune, Tsui, Suda and Kobayashi.)
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- 2024
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37. Zinc-Substituted Hemoglobin-Albumin Cluster as a Porphyrin-Carrier for Enhanced Photodynamic Therapy.
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Yamada T, Katsumi M, Ishii K, and Komatsu T
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- Humans, Cell Survival drug effects, Porphyrins chemistry, Porphyrins pharmacology, Cell Line, Tumor, Drug Carriers chemistry, Drug Carriers chemical synthesis, Protoporphyrins chemistry, Protoporphyrins pharmacology, Photochemotherapy, Zinc chemistry, Photosensitizing Agents chemistry, Photosensitizing Agents pharmacology, Photosensitizing Agents chemical synthesis, Hemoglobins chemistry, Hemoglobins metabolism, Serum Albumin, Human chemistry
- Abstract
Apohemoprotein is focused on the field of theranostics, serving as a porphyrin carrier. Hemoglobin (Hb) consists of α
2 β2 tetramer with iron(II)-protoporphyrin IX (heme) bound to each globin. However, heme-removed Hb (apoHb) causes dissociation at αβ interfaces and aggregation under physiological conditions. We synthesized a stable apoHb derivative comprising intramolecular-crosslinked apoHb (apoXHb) and human serum albumin (HSA), apoXHb-HSA3 . ApoXHb-HSA3 engendered no aggregates in the physiological solutions. Moreover, apoXHb-HSA3 was reconstituted with zinc(II)-protoporphyrin IX (ZnP), generating ZnXHb-HSA3 , a potent photosensitizer for photodynamic therapy (PDT). The photophysical properties of ZnXHb-HSA3 were identical to those of zinc-substituted XHb (ZnXHb). Cellular uptake behavior was evaluated using various cancer cell lines. ZnXHb-HSA3 released ZnP around the cells, and the free ZnP penetrated cell membranes. In contrast, protein units were not observed within the cells. ZnXHb-HSA3 showed no cytotoxicity under dark conditions and demonstrated superior PDT activity in comparison to naked ZnXHb. ZnXHb-HSA3 acts as an innovative porphyrin carrier for enhanced PDT., (© 2024 Wiley-VCH GmbH.)- Published
- 2024
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38. Epidemiology, microbiology, and diagnosis of infection in diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: A multicenter retrospective observational study.
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Takahashi K, Uenishi N, Sanui M, Uchino S, Yonezawa N, Takei T, Nishioka N, Kobayashi H, Otaka S, Yamamoto K, Yasuda H, Kosaka S, Tokunaga H, Fujiwara N, Kondo T, Ishida T, Komatsu T, Endo K, Moriyama T, Oyasu T, Hayakawa M, Hoshino A, Matsuyama T, Miyamoto Y, Yanagisawa A, Wakabayashi T, Ueda T, Komuro T, Sugimoto T, and Sasabuchi Y
- Subjects
- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Adult, Japan epidemiology, Risk Factors, Procalcitonin blood, Biomarkers blood, Diabetic Ketoacidosis diagnosis, Diabetic Ketoacidosis blood, Diabetic Ketoacidosis epidemiology, Hyperglycemic Hyperosmolar Nonketotic Coma diagnosis, Hyperglycemic Hyperosmolar Nonketotic Coma blood, Hyperglycemic Hyperosmolar Nonketotic Coma complications, Bacteremia diagnosis, Bacteremia mortality, Bacteremia epidemiology, C-Reactive Protein analysis, C-Reactive Protein metabolism
- Abstract
Aims: We investigated the characteristics of infection and the utility of inflammatory markers in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS)., Methods: A multicenter, retrospective observational study in 21 acute-care hospitals was conducted in Japan. This study included adult hospitalized patients with DKA and HHS. We analyzed the diagnostic accuracy of markers including C-reactive protein (CRP) and procalcitonin (PCT) for bacteremia. Multiple regression models were created for estimating bacteremia risk factors., Results: A total of 771 patients, including 545 patients with DKA and 226 patients with HHS, were analyzed. The mean age was 58.2 (SD, 19.3) years. Of these, 70 tested positive for blood culture. The mortality rates of those with and without bacteremia were 14 % and 3.3 % (P-value < 0.001). The area under the curve (AUC) of CRP and PCT for diagnosis of bacteremia was 0.85 (95 %CI, 0.81-0.89) and 0.76 (95 %CI, 0.60-0.92), respectively. Logistic regression models identified older age, altered level of consciousness, hypotension, and higher CRP as risk factors for bacteremia., Conclusions: The mortality rate was higher in patients with bacteremia than patients without it. CRP, rather than PCT, may be valid for diagnosing bacteremia in hyperglycemic emergencies., Trial Registration: This study is registered in the UMIN clinical trial registration system (UMIN000025393, Registered December 23, 2016)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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39. A Novel Rat Model of Embolic Cerebral Ischemia Using a Cell-Implantable Radiopaque Hydrogel Microfiber.
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Komatsu T, Ohta H, Takakura N, Hata J, Kitagawa T, Kurashina Y, Onoe H, Okano HJ, and Iguchi Y
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- Animals, Male, Rats, Brain Ischemia diagnostic imaging, Brain Ischemia therapy, Hydrogels administration & dosage, Magnetic Resonance Imaging, Rats, Sprague-Dawley, Disease Models, Animal
- Abstract
The failure of neuroprotective treatment-related clinical trials, including stem cell therapies, may be partially due to a lack of suitable animal models. We have developed a stem cell-implantable radiopaque hydrogel microfiber that can survive for a long time in vivo. The microfiber is made of barium alginate hydrogel containing zirconium dioxide, fabricated in a dual coaxial laminar flow microfluidic device. We aimed to develop a novel focal stroke model using this microfiber. Using male Sprague-Dawley rats (n=14), a catheter (inner diameter, 0.42 mm; outer diameter, 0.55 mm) was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography. A radiopaque hydrogel microfiber (diameter, 0.4 mm; length, 1 mm) was advanced through the catheter by slow injection of heparinized physiological saline to establish local occlusion. Both 9.4-T magnetic resonance imaging at 3 and 6 h and 2% 2,3,5-triphenyl tetrazolium chloride staining at 24 h after stroke model creation were performed. Neurological deficit score and body temperature were measured. The anterior cerebral artery-middle cerebral artery bifurcation was selectively embolized in all rats. Median operating time was 4 min (interquartile range [IQR], 3-8 min). Mean infarct volume was 388 mm
3 (IQR, 354-420 mm3 ) at 24 h after occlusion. No infarction of the thalamus or hypothalamus was seen. Body temperature did not change significantly over time (P = 0.204). However, neurological deficit scores before and at 3, 6, and 24 h after model creation differed significantly (P < 0.001). We present a novel rat model of focal infarct restricted to the middle cerebral artery territory using a radiopaque hydrogel microfiber positioned under fluoroscopic guidance. By comparing the use of stem cell-containing versus non-containing fibers in this stroke model, it would be possible to determine the efficacy of "pure" cell transplantation in treating stroke., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2024
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40. High versus low chloride load in adult hyperglycemic emergencies with acute kidney injury: a multicenter retrospective cohort study.
- Author
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Takahashi K, Uenishi N, Sanui M, Uchino S, Yonezawa N, Takei T, Nishioka N, Kobayashi H, Otaka S, Yamamoto K, Yasuda H, Kosaka S, Tokunaga H, Fujiwara N, Kondo T, Ishida T, Komatsu T, Endo K, Moriyama T, Oyasu T, Hayakawa M, Hoshino A, Matsuyama T, Miyamoto Y, Yanagisawa A, Wakabayashi T, Ueda T, Komuro T, Sugimoto T, and Sasabuchi Y
- Subjects
- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Japan epidemiology, Chlorides blood, Chlorides analysis, Cohort Studies, Adult, Hyperglycemia complications, Hyperglycemic Hyperosmolar Nonketotic Coma complications, Fluid Therapy methods, Emergencies, Acute Kidney Injury etiology, Acute Kidney Injury therapy, Acute Kidney Injury physiopathology, Diabetic Ketoacidosis complications
- Abstract
Hyperglycemic emergencies frequently lead to acute kidney injury (AKI) and require treatment with large amount of intravenous fluids. However, the effects of chloride loading on this population have not yet been investigated. We conducted a multicenter, retrospective, cohort study in 21 acute-care hospitals in Japan. The study included hospitalized adult patients with diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) who had AKI upon arrival. The patients were classified into high and low chloride groups based on the amount of chloride administered within the first 48 h of their arrival. The primary outcome was recovery from AKI; secondary outcome was major adverse kidney events within 30 days (MAKE30), including mortality and prolonged renal failure. A total of 390 patients with AKI, including 268 (69%) with DKA and 122 (31%) with HHS, were included in the study. Using the criteria of Kidney Disease Improving Global Outcomes, the severity of AKI in the patients was Stage 1 (n = 159, 41%), Stage 2 (n = 121, 31%), and Stage 3 (n = 110, 28%). The analysis showed no significant difference between the two groups in recovery from AKI (adjusted hazard ratio, 0.96; 95% CI 0.72-1.28; P = 0.78) and in MAKE30 (adjusted odds ratio, 0.91; 95% CI 0.45-1.76; P = 0.80). Chloride loading with fluid administration had no significant impact on recovery from AKI in patients with hyperglycemic emergencies.Trial Registration This study was registered in the UMIN clinical trial registration system (UMIN000025393, registered December 23, 2016)., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)
- Published
- 2024
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41. Relationship between ω3 and ω6 polyunsaturated fatty acids and atrial fibrillation in acute ischemic stroke.
- Author
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Sato T, Okumura M, Ishikawa T, Sakuta K, Takahashi J, Tanabe M, Onda A, Komatsu T, Sakai K, Umehara T, Mitsumura H, and Iguchi Y
- Subjects
- Humans, Male, Female, Aged, Retrospective Studies, Middle Aged, Aged, 80 and over, Natriuretic Peptide, Brain blood, Brain Ischemia blood, Brain Ischemia epidemiology, Brain Ischemia etiology, Risk Factors, Atrial Fibrillation blood, Atrial Fibrillation complications, Fatty Acids, Omega-3 blood, Ischemic Stroke blood, Ischemic Stroke epidemiology, Ischemic Stroke etiology, Fatty Acids, Omega-6 blood
- Abstract
Background & Aims: Some ω3 polyunsaturated fatty acids (PUFAs) are said to demonstrate a dose-related risk of atrial fibrillation (AF), conversely, some ω6 PUFAs might have AF protective potential. However, few investigated the relation among ischemic strokes. Primarily, we aimed to examine a relation between ω3 and ω6 PUFAs and the presence of AF in ischemic strokes. Further, since, some PUFAs are said to affect the cardiac load, we secondarily aimed to investigate the association between ω3 and ω6 PUFAs and brain natriuretic peptide (BNP) and the occurrence of cerebral large vessel occlusion (LVO) in ischemic strokes with AF., Methods: Consecutive patients with ischemic stroke admitted between 2012 and 2022 were retrospectively screened. Plasma levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid, dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), were assayed. Data were analyzed using a Poisson regression analysis with a robust variance estimator and a multiple linear regression analysis., Results: We screened 2112 consecutive ischemic strokes, including 1574 (1119 [71%] males, median age 69 years). Lower DGLA (prevalence ratio (PR) 0.885, 95% CI 0.811-0.966, p = 0.006), lower AA (PR 0.797, 95% CI 0.649-0.978, p = 0.030), and higher EPA/AA ratio (PR 1.353, 95% CI 1.036-1.767, p = 0.026) were associated with AF. Checking the linearity between AF and PUFAs, negative linear trends were observed between DGLA quartiles (Q1: PR 1.901, Q2: PR 1.550, Q3: PR 1.423, Q4: 1.000, p < 0.001 for trend) and AA quartiles (Q1: PR 1.499, Q2: PR 1.204, Q3: PR 1.125, Q4: 1.000, p = 0.004 for trend), with positive linear trends between EPA/AA ratio quartiles (Q1: 1.000, Q2: PR 1.555, Q3: PR 1.612, Q4: PR 1.797, p = 0.001 for trend). Among patients with AF, a negative association between AA and BNP (unstandardized coefficient -1.316, 95% CI -2.290∼-0.342, p = 0.008) was observed, and lower AA was associated with LVO (PR 0.707, 95% CI 0.527-0.950, p = 0.021)., Conclusion: Lower DGLA and AA and a higher EPA/AA ratio might be related to the development of AF in ischemic strokes. Further, AA might have a cardio-cerebrovascular protective role in ischemic strokes with AF., Competing Interests: Conflict of interest Hidetaka Mitsumura received grants/research funding from JSPS KAKENHI. Yasuyuki Iguchi reports personal fees from Bayer Healthcare Co. Ltd., grants and personal fees from Pfizer Japan Inc., grants and personal fees from Nippon Boehringer Ingelheim Co. Ltd., grants and personal fees from Takeda Pharmaceutical Co. Ltd., grants and personal fees from Otsuka Pharmaceutical Co. Ltd., and grants and personal fees from Daiichi Sankyo Co. Ltd. outside the submitted work., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)
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- 2024
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42. Current perspectives of viral hepatitis.
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Usuda D, Kaneoka Y, Ono R, Kato M, Sugawara Y, Shimizu R, Inami T, Nakajima E, Tsuge S, Sakurai R, Kawai K, Matsubara S, Tanaka R, Suzuki M, Shimozawa S, Hotchi Y, Osugi I, Katou R, Ito S, Mishima K, Kondo A, Mizuno K, Takami H, Komatsu T, Nomura T, and Sugita M
- Subjects
- Humans, Hepatitis Viruses pathogenicity, Hepatitis Viruses drug effects, Hepatitis Viruses genetics, Prevalence, Liver virology, Liver pathology, Antiviral Agents therapeutic use, Hepatitis, Viral, Human epidemiology, Hepatitis, Viral, Human virology, Hepatitis, Viral, Human therapy, Hepatitis, Viral, Human diagnosis
- Abstract
Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2024
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43. Influence of ankle invertor muscle fatigue on workload of the lower extremity joints during single-leg landing in the sagittal and frontal planes.
- Author
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Komatsu T, Tateuchi H, Hirono T, Yamagata M, and Ichihashi N
- Subjects
- Humans, Male, Female, Young Adult, Biomechanical Phenomena, Hip Joint physiology, Adult, Knee Joint physiology, Weight-Bearing physiology, Lower Extremity physiology, Torque, Ankle Joint physiology, Muscle Fatigue physiology, Muscle, Skeletal physiology
- Abstract
Background: Insufficient rigidity of the foot owing to its ligaments and muscles can decrease the attenuation of the ground reaction force during landing. Therefore, dysfunction of the ankle invertors may increase the proximal joint load during landing., Research Question: What are the effects of the fatigued ankle invertors on workload in the lower extremity joints during single-leg landing?, Methods: Twenty-seven young adults (13 men and 14 women) performed landing trials in the forward and medial directions before and after exercise-induced fatigue of the ankle invertors. The exercise consisted of repeated concentric and eccentric ankle inversions until the maximum torque was below 80% of the baseline value. Negative joint workload during the landing tasks was calculated for the hip, knee, and ankle in the sagittal and frontal planes. Additionally, lower extremity work (the sum of the work of the hip, knee, and ankle) was calculated., Results: Invertor fatiguing exercise resulted in a significant increase in negative joint work in the frontal and sagittal plane hip and the frontal plane knee during medial landing, whereas no significant change in negative joint work was observed during forward landing., Significance: These findings suggested that ankle invertor dysfunction may induce a high load on the proximal joints and have direction-specific effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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44. Small ischemic lesions accompanying intracerebral hemorrhage: The underlying influence of old lacunes and polyunsaturated fatty acids.
- Author
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Okumura M, Sato T, Takahashi J, Kokubu T, Nakada R, Kitagawa T, Tanabe M, Takatsu H, Onda A, Komatsu T, Sakuta K, Sakai K, Umehara T, Mitsumura H, and Iguchi Y
- Subjects
- Male, Humans, Middle Aged, Cerebral Hemorrhage diagnostic imaging, Magnetic Resonance Imaging methods, Fatty Acids, Unsaturated, Cerebral Small Vessel Diseases
- Abstract
Background and Aims: Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs., Methods and Results: We screened consecutive ICH patients (October 2012-December 2021) meeting two inclusion criteria: (1) the patients were hospitalized for acute ICH and were undergoing magnetic resonance imaging and (2) the patients' PUFA measurements were available. After excluding patients with isolated intraventricular hemorrhage, we evaluated whether three SVD markers (white matter hyperintensities, old lacunes, cerebral microbleeds) and PUFAs might be associated with the development of SILs. We selected 319 participants from 377 screened consecutive ICH patients (median age = 64, males = 207 [65 %]). Of the 319 patients, 45 patients (14 %) developed SILs. In a multivariable logistic regression analysis, the factors associated with SILs were old lacunes (OR 3.255, 95 % CI 1.101-9.622, p = 0.033) and DHA/AA ratio (OR 0.180, 95 % CI 0.046-0.704, p = 0.013). Furthermore, in our multivariable analysis using DHA/AA ratio tertiles with and without SILs, we observed a linear trend between SILs and the Higher Tertile of the DHA/AA ratio (DHA/AA ratio Mid-Tertile: OR 1.330, 95%CI 0.557-3.177, p = 0.521, and DHA/AA ratio Lower Tertile: OR 2.632, 95%CI 1.124-6.162, p = 0.026)., Conclusion: The presence of old lacunes and lower DHA/AA ratios might be associated with SILs accompanying ICH., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)
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- 2024
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45. Retropharyngeal abscess due to Fusobacterium necrophorum complicated by progressive internal carotid artery stenosis and multiple cranial nerve palsies.
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Matsumura S, Sato T, Matsushima S, Kokubu T, Umehara T, Komatsu T, Sakai K, Mitsumura H, and Iguchi Y
- Subjects
- Female, Humans, Adult, Fusobacterium necrophorum, Inflammation, Carotid Artery, Internal, Retropharyngeal Abscess diagnosis, Retropharyngeal Abscess diagnostic imaging, Carotid Stenosis complications, Carotid Stenosis diagnostic imaging, Cranial Nerve Diseases etiology
- Abstract
Background: A case of retropharyngeal abscess complicated by both artery and nerve injury has rarely been reported., Methods: A 36-year-old woman suddenly presented with right eye visual loss, dilated pupil, reduced direct light reflex, ptosis and ocular motility disorder on the side of inflammation progression, and was diagnosed with retropharyngeal abscess due to Fusobacterium necrophorum. The patient was treated only with antibiotics and, no further surgery was necessary but tracheotomy. Four months later, MRA showed right ICA occlusion and left ICA stenosis. MRI revealed continuous spread of inflammation due to the abscess from the retropharyngeal to the intracranial space., Results: These severe complications would be attributed to an endothelial damage to the arterial wall and an ischemic neuropathy caused by inflammation and thrombogenesis due to Fusobacterium necrophorum., Conclusions: This case should provide a better understanding of the mechanism of vascular and cranial nerve injury due to retropharyngeal infections, and highlights the need for early antibiotic therapy and repeated vascular evaluation., (© 2024 Wiley Periodicals LLC.)
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- 2024
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46. Graphical user interface-based convolutional neural network models for detecting nasopalatine duct cysts using panoramic radiography.
- Author
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Ito K, Hirahara N, Muraoka H, Sawada E, Tokunaga S, Komatsu T, and Kaneda T
- Subjects
- Humans, Radiography, Panoramic, Neural Networks, Computer, Databases, Factual, Deep Learning, Cysts diagnostic imaging
- Abstract
Nasopalatine duct cysts are difficult to detect on panoramic radiographs due to obstructive shadows and are often overlooked. Therefore, sensitive detection using panoramic radiography is clinically important. This study aimed to create a trained model to detect nasopalatine duct cysts from panoramic radiographs in a graphical user interface-based environment. This study was conducted on panoramic radiographs and CT images of 115 patients with nasopalatine duct cysts. As controls, 230 age- and sex-matched patients without cysts were selected from the same database. The 345 pre-processed panoramic radiographs were divided into 216 training data sets, 54 validation data sets, and 75 test data sets. Deep learning was performed for 400 epochs using pretrained-LeNet and pretrained-VGG16 as the convolutional neural networks to classify the cysts. The deep learning system's accuracy, sensitivity, and specificity using LeNet and VGG16 were calculated. LeNet and VGG16 showed an accuracy rate of 85.3% and 88.0%, respectively. A simple deep learning method using a graphical user interface-based Windows machine was able to create a trained model to detect nasopalatine duct cysts from panoramic radiographs, and may be used to prevent such cysts being overlooked during imaging., (© 2024. The Author(s).)
- Published
- 2024
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47. Beat-to-beat alterations of acoustic intensity and frequency at the maximum power of heart sounds are associated with NT-proBNP levels.
- Author
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Fujiyoshi K, Yamaoka-Tojo M, Fujiyoshi K, Komatsu T, Oikawa J, Kashino K, Tomoike H, and Ako J
- Abstract
Background: Auscultatory features of heart sounds (HS) in patients with heart failure (HF) have been studied intensively. Recent developments in digital and electrical devices for auscultation provided easy listening chances to recognize peculiar sounds related to diastolic HS such as S
3 or S4 . This study aimed to quantitatively assess HS by acoustic measures of intensity (dB) and audio frequency (Hz)., Methods: Forty consecutive patients aged between 46 and 87 years (mean age, 74 years) with chronic cardiovascular disease (CVD) were enrolled in the present study after providing written informed consent during their visits to the Kitasato University Outpatient Clinic. HS were recorded at the fourth intercostal space along the left sternal border using a highly sensitive digital device. Two consecutive heartbeats were quantified on sound intensity (dB) and audio frequency (Hz) at the peak power of each spectrogram of S1 -S4 using audio editing and recording application software. The participants were classified into three groups, namely, the absence of HF ( n = 27), HF ( n = 8), and high-risk HF ( n = 5), based on the levels of NT-proBNP < 300, ≥300, and ≥900 pg/ml, respectively, and also the levels of ejection fraction (EF), such as preserved EF ( n = 22), mildly reduced EF ( n = 12), and reduced EF ( n = 6)., Results: The intensities of four components of HS (S1 -S4 ) decreased linearly ( p < 0.02-0.001) with levels of body mass index (BMI) (range, 16.2-33.0 kg/m2 ). Differences in S1 intensity (ΔS1 ) and its frequency (Δ fS1 ) between two consecutive beats were non-audible level and were larger in patients with HF than those in patients without HF (ΔS1 , r = 0.356, p = 0.024; Δ fS1 , r = 0.356, p = 0.024). The cutoff values of ΔS1 and Δ fS1 for discriminating the presence of high-risk HF were 4.0 dB and 5.0 Hz, respectively., Conclusions: Despite significant attenuations of all four components of HS by BMI, beat-to-beat alterations of both intensity and frequency of S1 were associated with the severity of HF. Acoustic quantification of HS enabled analyses of sounds below the audible level, suggesting that sound analysis might provide an early sign of HF., 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 Fujiyoshi, Yamaoka-Tojo, Fujiyoshi, Komatsu, Oikawa, Kashino, Tomoike and Ako.)- Published
- 2024
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48. Flowchart for predicting achieving the target area under the concentration-time curve of vancomycin in critically ill Japanese patients: A multicenter retrospective study.
- Author
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Ishigo T, Fujii S, Ibe Y, Aigami T, Nakano K, Fukudo M, Yoshida H, Tanaka H, Ebihara F, Maruyama T, Hamada Y, Suzuki A, Fujihara H, Yamaguchi F, Samura M, Nagumo F, Komatsu T, Tomizawa A, Takuma A, Chiba H, Nishi Y, Enoki Y, Taguchi K, and Matsumoto K
- Subjects
- Humans, Female, Aged, Male, Bayes Theorem, Japan, Retrospective Studies, Software Design, Critical Illness, Vancomycin therapeutic use
- Abstract
Introduction: In therapeutic drug monitoring (TDM) of vancomycin (VCM), the area under the concentration-time curve (AUC) is related to the clinical efficacy and toxicity. Therefore, herein, we examined the factors associated with achieving the target AUC at follow-up and developed a decision flowchart for achieving the target AUC in critically ill patients., Methods: This multicenter retrospective observational study was conducted at eight hospitals. We retrospectively analyzed data from patients who had received VCM in the intensive care unit from January 2020 to December 2022. Decision-tree (DT) analysis was performed using factors with p < 0.1 in univariate analysis as the independent variables. Case data were split up to two times, and four subgroups were included. The primary endpoint was achieving the target AUC at the follow-up TDM (AUC
follow-up ) and target AUCfollow-up achievement was defined as an AUC of 400-600 μg‧h/mL. The initial AUC values were calculated with the 2-point concentrations (peak and trough) using the Bayesian estimation software Practical AUC-guided TDM (PAT)., Results: Among 70 patients (median age [interquartile range], 66 [56, 79] years; 50 % women), the AUCfollow-up was achieved in 70 % (49/70). Three factors were selected for the decision flow chart: predicted AUCfollow-up of 400-600 μg‧h/mL, dosing at 12-h intervals, and CCr of 130 mL/min/1.73 m2 or higher; the accuracy was adequate (92 %, R2 0.52)., Conclusion: We successfully identified the factors associated with achieving the target AUC of VCM at follow-up TDM and developed a simple-to-use DT model. However, the validity of the findings needs to be evaluated., Competing Interests: Declaration of competing interest KM received grant support funding from Meiji Seika Pharma Co., Ltd., Sumitomo Pharma Co., Ltd., and Shionogi & Co., Ltd., and speaker honoraria from Meiji Seika Pharma Co., Ltd. The other authors have no conflicts of interest to declare., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)- Published
- 2024
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49. Thin aortic arch plaque is associated with the development of atrial fibrillation for embolic stroke of undetermined source in patients with an insertable cardiac monitor.
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Komatsu T, Okumura M, Kida H, Takahashi J, Maku T, Kitagawa T, Sato T, Takatsu H, Sakuta K, Sakai K, Umehara T, Mitsumura H, Oseto H, and Iguchi Y
- Subjects
- Humans, Aorta, Thoracic diagnostic imaging, Cross-Sectional Studies, Risk Factors, Atrial Fibrillation diagnosis, Atrial Fibrillation diagnostic imaging, Embolic Stroke complications, Plaque, Atherosclerotic diagnosis, Plaque, Atherosclerotic diagnostic imaging, Stroke diagnostic imaging, Stroke epidemiology, Intracranial Embolism diagnostic imaging, Intracranial Embolism etiology
- Abstract
Background and Objective: This study's objective is to investigate whether mild aortic arch plaque is associated with the development of atrial fibrillation (AF) in stroke patients with embolic stroke of undetermined source (ESUS) during the first year following the implantation of an insertable cardiac monitor (ICM)., Methods: The participants in this cross-sectional observational study were consecutive patients with ESUS, even after transesophageal echocardiography. We assessed the relationship between the thickness of the participants' aortic arch plaque and AF detected after ICM implantation., Results: Of the 50 consecutive patients with ESUS enrolled in this study, 12 (24%) developed AF. We observed that thicker aortic arch plaque was associated with undetected AF (2.3 mm vs. 1.2 mm, p < 0.001). Aortic arch plaque thickness was independent associated with undetected AF (OR 54.00, 95% CI 2.706-1077.544, p = 0.009). When the cut-off value for aortic arch plaque thickness was 1.8 mm, the sensitivity and specificity were 71.1% and 91.7%, respectively (95% CI = 0.75-0.98, p < 0.001). Also, patients having both aortic arch plaque with a thickness < 1.8 mm and a CHADS
2 score ≥ 4 were more likely to have detectable AF than no AF (88% vs. 12%, p < 0.001)., Conclusion: A thinner aortic arch plaque was associated with the development of AF. Patients with mild aortic plaques below 4 mm but ≥1.8 mm in thickness and without other high-risk features are less likely to have paroxysmal AF on ICM, and these plaques may be a possible source of embolism for their strokes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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50. Two different right ventricular pacing waveforms.
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Komatsu T, Okada A, and Kuwahara K
- Abstract
Competing Interests: Conflict of interest: None declared.
- Published
- 2024
- Full Text
- View/download PDF
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