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Background: Endotoxin (Et) adsorption therapy with a column of polymyxin B-immobilized fibers (PMX) is effective in improving the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (PaO2/FiO2 ratio) and increasing mean arterial blood pressure (MAP) in sepsis. S100A12 and soluble receptor for advanced glycation end product (sRAGE) are useful as early markers of acute lung injury. Purpose: To investigate the effect of improving the PaO2/FiO2 ratio by PMX-direct hemoperfusion (PMX-DHP) on production of S100A12 and sRAGE. Subjects and Methods: Sepsis patients after surgery for perforation of the lower gastrointestinal tract were adopted as the subjects. We retrospectively reviewed the cases of 20 patients on mechanical ventilation and continuous administration of norepinephrine. We recorded PaO2/FiO2 ratio, MAP, and norepinephrine doses. S100A12, sRAGE, and Et levels were measured before and after PMX-DHP. Results: The PaO2/FiO2 ratio and MAP improved significantly after PMX-DHP (p < 0.05). S100A12 and Et decreased significantly after PMX-DHP (p < 0.05). No differences were observed in sRAGE. Conclusion: S100A12 is useful as a marker that reflected improvement in the PaO2/FiO2 ratio after PMX-DHP. We consider PMX-DHP to be useful as adjunctive therapy for sepsis that reduces the Et and corrects the pathology in the early stage. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Spatially resolved electrical and spectroscopic behavior around isolated grown-in dislocation in p-type undoped GaAs crystals grown by liquid-encapsulated Czochralski technique is investigated. Surface spreading resistance is found to remarkably increase at about 100 μm in diameter around dislocations. In a corresponding area, photoluminescence intensity of the 1.49-eV and 1.44-eV acceptor level peaks decreases. However, that of 0.8-eV deep level peak does not vary. These results demonstrate that dislocations should give rise to carrier density variation due to the relative concentration change of levels around them. [ABSTRACT FROM AUTHOR]

Abstract: Defects related to oxygen and other impurities in piezoelectric langasite (La3Ga5SiO14; LGS) single crystals grown by the vertical Bridgman (VB) method was investigated. The resistivity of an LGS crystal grown in an Ar atmosphere was about one-order higher than that grown in air. However, after annealing in air it decreased to the same level as that of LGS crystal grown in air. The results of optical transmission spectra showed a broad adsorption peak around 500nm, corresponding to 2.5eV of energy level, in LGS crystals grown in air and grown in an Ar atmosphere. Since VB-grown LGS crystal was p-type, excess interstitial oxygen atoms, not oxygen vacancies, operate as an acceptor in the VB-LGS crystal. [Copyright &y& Elsevier]

Micro-Tom is a cultivar of tomato (Solanum lycopersicum), which is known as a major crop and model plant in Solanaceae. Micro-Tom has phenotypic traits such as dwarfism, and substantial EMS-mutagenized lines have been reported. After Micro-Tom was generated in Florida, USA, it was distributed to research institutes worldwide and used as a genetic resource. In Japan, the Micro-Tom lines have been genetically fixed; currently, three lines have been re-distributed from three institutes, but many phenotypes among the lines have been observed. We have determined the genome sequence de novo of the Micro-Tom KDRI line, one of the Micro-Tom lines distributed from Kazusa DNA Research Institute (KDRI) in Japan, and have built chromosome-scale pseudomolecules. Genotypes among six Micro-Tom lines, including three in Japan, one in the United States, one in France, and one in Brazil showed phenotypic alternation. Here, we unveiled the swift emergence of genetic diversity in both phenotypes and genotypes within the Micro-Tom genome sequence during its propagation. These findings offer valuable insights crucial for the management of bioresources., (© The Author(s) 2024. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

Background: Multiple factors are involved in the pathogenesis of primary biliary cholangitis (PBC), a chronic cholestatic liver disease, characterized by intrahepatic cholangiopathy. In particular, studies have suggested that environmental factors such as the presence of granulomas in the portal vein region are important for the development of PBC. This study aimed to comprehensively analyze and identify foreign-derived antigens in PBC liver tissue to confirm their involvement in PBC pathogenesis., Methods: Portal areas and hepatocyte regions were selectively dissected from formalin-fixed paraffin-embedded PBC liver tissue samples using the microlaser method, followed by total DNA extraction. We then validated whether the bacterial strains identified through 16S rRNA metagenomic analysis were detected in PBC liver tissues., Results: The most frequently detected bacterial genera in the PBC liver tissue samples were Sphingomonas panacis, Providencia, and Cutibacterium. These bacterial genera were also detected in the other PBC samples. Validation for the detection of S. panacis, the most abundant genus, revealed polymerase chain reaction bands extracted from the portal areas of all samples. They were also more highly expressed than bands detected in the hepatocyte region., Conclusion: S. panacis antigen was specifically detected in the portal areas of PBC liver tissues. The introduction of foreign-derived antigens into the liver as an environmental factor could be a possible mechanism for the development of PBC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Katsumi 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.)

Factors that determine clinical responses to vonoprazan remain unknown. This study aimed to characterize plasma vonoprazan and CYP3A activity using its endogenous marker and genetic variants in patients with digestive system disorders. Fifty-three patients who were receiving vonoprazan for at least 3 days were enrolled. Blood samples for determination of plasma vonoprazan and its metabolite (ODA-VP) were obtained. Plasma 4β-hydroxycholesterol (4β-OHC), CYP3A5 and ABCB1 genotypes, and plasma gastrin were determined. CYP3A recognition for vonoprazan was evaluated using recombinant CYP3A proteins. Plasma vonoprazan levels exhibited a large interindividual variation. The absolute plasma concentration of vonoprazan was correlated with its dose-normalized value, and had a positive correlation with the inverse value of its metabolic ratio. A negative correlation was observed between plasma vonoprazan and 4β-OHC levels. The metabolic ratio of vonoprazan was positively correlated with the plasma 4β-OHC level. Genetic variants of CYP3A5 and ABCB1 were not associated with the plasma concentration of vonoprazan and its metabolic ratio. Possible saturated metabolism of vonoprazan to its major metabolite was observed at a therapeutic dose. Although the CYP3A5 genotype did not alter plasma vonoprazan, CYP3A activity based on plasma 4β-OHC partially explained the variation in plasma vonoprazan in patients with digestive system disorders., (Copyright © 2024 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Background: The rotator cable functions as a stress and/or load transfer structure. Some studies suggested that a disruption of the cable negatively affects shoulder function and tendon integrity in patients with rotator cuff tears, while others found no functional impairment regardless of rotator cable tear severity. Although anatomical studies have identified distinct regions within the rotator cuff muscles, the strain distribution within the articular sides of the rotator cuff tendons that results from the tension in each region remains unknown. We hypothesized that the posterior region of the supraspinatus (SSP) muscle and the middle region of the infraspinatus (ISP) muscle, with their firm capsular attachments to the cable, transmit 3D strains, and thus tension, to the whole cable, leading to differences in tension within the cable., Methods: The 3D strain distributions in the articular sides of the SSP and ISP tendons of 8 fresh-frozen cadaveric intact shoulders were determined when tension was applied to the various SSP and ISP muscle regions., Results: Loading the anterior SSP muscle region yielded significantly higher strains in the anterior third of the cable compared with the posterior third (p < 0.05). Loading the posterior SSP muscle region yielded no significant differences among the cable and crescent regions. Loading the middle ISP muscle region yielded higher strains in the anterior and posterior thirds of the cable compared with the middle third (p < 0.01). Loading the superior ISP muscle region yielded no significant differences among the cable and crescent regions (p > 0.05)., Conclusions: Tension generated from the posterior region of the SSP muscle and middle region of the ISP muscle was evenly distributed to the anterior and posterior attachments of the rotator cable, while the tension generated from other SSP and ISP muscle regions was locally transmitted to the respective attachment area., Clinical Relevance: The rotator cable and crescent serve pivotal roles in transmitting tension generated from the deep regions of the rotator cuff muscles, i.e., the posterior SSP and middle ISP. These findings indicate that both the rotator cable and the rotator crescent play crucial roles as tension transmitters for the deep regions of the rotator cuff muscles. This information could have important implications for developing anatomically relevant repair techniques and enhancing rehabilitation protocols., Competing Interests: Disclosure: This study was internally funded by The University of Texas at San Antonio. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H957 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background and Purpose: Concentrations of calcitonin gene-related peptide, a neuropeptide and potent endogenous vasodilator, are reportedly higher in patients with migraine than in healthy subjects, both during and between migraine attacks, reflecting ongoing activation of the trigeminal nervous system. In this prospective study, we measured CBF during the interictal period of patients with migraine after considering insomnia and depression and examined the effects of ongoing activation of the trigeminal nervous system, including during the interictal period, on CBF., Materials and Methods: In a total of 242 patient with migraine (age range, 18-75 years), CBF was measured by MR imaging arterial spin-labeling during the interictal period and was compared with results from 26 healthy volunteers younger than 45 years of age as control subjects (age range, 22-45 years). Cortical hyperperfusion was defined as identification of ≥2 cerebral cortical regions with regional CBF values at least 2 SDs above the mean regional CBF in control subjects., Results: The overall frequency of cortical hyperperfusion was significantly higher in patients with migraine (115 of 242, 48%) than in control subjects (1 of 26, 4%). Multivariable analysis revealed the 18- to 40-year age group and patients with migraine without insomnia as significant positive clinical factors associated with cortical hyperperfusion. Among patients with migraine without insomnia, the frequency of cortical hyperperfusion was >92% (89 of 97). One-way ANOVA showed that in all ROIs of the cortex, regional CBF was significantly higher in patients with migraine without insomnia than in patients with migraine with insomnia or control subjects. In patients with migraine without insomnia, cortical hyperperfusion findings showed a sensitivity of 0.918 and a specificity of 0.962 for migraine in the interictal period, representing excellent accuracy. In contrast, among patients with migraine with insomnia, sensitivity was only 0.179 but specificity was 0.962., Conclusions: Patients with migraine without insomnia may have cortical hyperperfusion during the interictal period; however, the findings of the present study need to be prospectively validated on a larger scale before clinical applicability can be considered., (© 2024 by American Journal of Neuroradiology.)

Cholestatic liver diseases causes inflammation and fibrosis around bile ducts. However, the pathological mechanism has not been elucidated. Extracellular vesicles (EVs) are released from both the basolateral and apical sides of polarized biliary epithelial cells. We aimed to investigate the possibility that EVs released from the basolateral sides of biliary epithelial cells by bile acid stimulation induce inflammatory cells and fibrosis around bile ducts, and they may be involved in the pathogenesis of cholestatic liver disease. Human biliary epithelial cells (H69) were grown on cell culture inserts and stimulated with chenodeoxycholic acid + IFN-γ. Human THP-1-derived M1-macrophages, LX-2 cells, and KMST-6 cells were treated with the extracted basolateral EVs, and inflammatory cytokines and fibrosis markers were detected by RT-PCR. Highly expressed proteins from stimulated EVs were identified, and M1-macrophages, LX-2, KMST-6 were treated with these recombinant proteins. Stimulated EVs increased the expression of TNF, IL-1β, and IL-6 in M1-macrophages, TGF-β in LX-2 and KMST-6 compared with the corresponding expression levels in unstimulated EVs. Nucleophosmin, nucleolin, and midkine levels were increased in EVs from stimulated cells compared with protein expression in EVs from unstimulated cells. Leukocyte cell-derived chemotaxin-2 (LECT2) is highly expressed only in EVs from stimulated cells. Stimulation of M1-macrophages with recombinant nucleophosmin, nucleolin, and midkine significantly increased the expression of inflammatory cytokines. Stimulation of LX-2 and KMST-6 with recombinant LECT2 significantly increased the expression of fibrotic markers. These results suggest that basolateral EVs are related to the development of pericholangitis and periductal fibrosis in cholestatic liver diseases. NEW & NOTEWORTHY Our research elucidated that the composition of basolateral EVs from the biliary epithelial cells changed under bile acid exposure and the basolateral EVs contained the novel inflammation-inducing proteins NPM, NCL, and MK and the fibrosis-inducing protein LECT2. We report that these new results are possible to lead to the potential therapeutic target of cholestatic liver diseases in the future.

Aim: There are few reports on the prognosis of liver-related events in Japanese patients with nonalcoholic fatty liver disease (NAFLD). We undertook an observational study to compare the prognosis between fibrotic and nonfibrotic groups in Japanese NAFLD patients., Methods: Prognosis in 393 NAFLD patients who underwent liver biopsy between April 2013 and April 2015 at multiple centers were investigated. The time to onset of liver-related events, cardiovascular events, development of extrahepatic cancers, and death were compared between the pathologically fibrotic nonalcoholic steatohepatitis (NASH) group and nonalcoholic fatty liver (NAFL) + nonfibrotic NASH group. A similar analysis was carried out based on the fibrotic classification diagnosed using four noninvasive fibrosis prediction models., Results: The mean age and body mass index at the time of liver biopsy was 55.7 years old and 28.04 kg/m 2 , respectively The cumulative incidence of liver-related events at 1080 days after liver biopsy was 5.79% in the pathologically fibrotic NASH group and 0% in the NAFL + nonfibrotic NASH group, with a significant difference (p = 0.0334). The cumulative incidence of liver-related events was significantly higher in the positive group for the prediction model than in the negative group in all four models (all p values were <0.0001). There was no significant difference between the pathologically fibrotic NASH group and NAFL + nonfibrotic NASH group in terms of cumulative incidence of cardiovascular events, development of extrahepatic cancers, and death., Conclusions: The incidence of liver-related events was significantly higher in the fibrotic NASH group than that of the NAFL + nonfibrotic NASH group in Japanese NAFLD patients., (© 2023 Japan Society of Hepatology.)

Background: A torn rotator cuff muscle deteriorates over time leading with an increase in muscle atrophy and fatty infiltration. There are several clinical assessments for evaluating the atrophy of the torn supraspinatus muscle. However, it is unclear which approach can more accurately estimate the activity of the torn supraspinatus muscle. The purpose of this study was to determine which magnetic resonance imaging-based muscle atrophy imaging assessment currently implemented in the clinical setting accurately estimates the activity of the torn supraspinatus muscle., Methods: Forty patients who were diagnosed with a rotator cuff tear and were candidates for repairs were selected for this study. Cross-sectional area, occupation ratio, and tangent sign were analyzed on T1-weighted oblique sagittal plane magnetic resonance images in which the scapular spine leads to the Y-section. Muscle belly ratio of the supraspinatus muscle was analyzed by calculating the ratio of the width of the muscle belly to the distance from the greater tubercle to the proximal end of the muscle on T1-weighted coronal plane magnetic resonance imaging images. Fatty infiltration was evaluated using the Goutallier classification system. Tear size was obtained intraoperatively by measuring the width and length of the tear and classified based on the Cofield's classification. To assess activity of the torn supraspinatus muscle, participants were first instructed to sit on a chair with the affected arm resting on a table and the shoulder abducted to 60° in the scapular plane with neutral rotation. Elasticity of the supraspinatus muscle belly was then obtained at rest and during isometric contraction using with real-time tissue elastography. Muscle activity, a surrogate for contractility, was defined as the difference between the elasticities measured at rest and during isometric contraction. A stepwise multiple regression analysis was used to investigate independent factors, such as sex, tear width, cross-sectional area, occupation ratio, tangent sign, and muscle belly ratio, related to muscle activity., Results: Stepwise multiple regression analysis ( R 2  = 0.522, P  < .001) revealed that supraspinatus muscle activity was significantly correlated with muscle belly ratio ( β  = 0.306, P  = .044) and Goutallier stage ( β  = -0.490, P  = .002)., Conclusion: Estimations of muscle belly ratio are most suitable for assessing the activity of a torn supraspinatus muscle compared to other clinical measurements., (© 2023 The Authors.)

Background: Rotator cuff muscles are responsible for humeral rotation. Moment arms of different regions of these muscles during humeral rotation were analyzed in neutral and abducted positions., Methods: In eight cadaveric shoulders, subregions of the rotator cuff muscles were identified and their excursion during humeral rotation was measured in neutral and abducted positions from an internal rotation of 30° to an external rotation of 45°, with 15° increments, using a 3-D digitizing system. Statistical tests were used to assess differences between subregions within a single muscle., Findings: The posterior-deep subregion of the supraspinatus muscle had greater moment arms compared to the anterior-superficial and anterior-middle subregions in both positions (p < 0.001). The middle and inferior subregions of the infraspinatus muscle and the teres minor muscle showed differences in moment arms compared to the superior region in an abducted position (p < 0.042). The superior subregion of the subscapularis muscle showed differences in moment arms compared to the middle and inferior subregions in an abducted position (p < 0.001)., Interpretation: The posterior-deep subregion of the supraspinatus muscle behaved similar to the infraspinatus muscle, as an external rotator. The anterior-superficial and anterior-middle subregions of the supraspinatus muscle showed a biphasic behavior during rotation at a neutral position, but acted as pure external rotators during rotation at an abducted position. Inferior subregions of the infraspinatus and subscapularis muscles showed the largest moment arms compared to superior subregions. These findings support distinct functional roles of the rotator cuff muscle subregions., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Crosstalk among organs/tissues is important for regulating systemic metabolism. Here, we demonstrate inter-organ crosstalk between hepatic insulin and hypothalamic leptin actions, which maintains survival during food shortages. In inducible liver insulin receptor knockout mice, body weight is increased with hyperphagia and decreased energy expenditure, accompanied by increased circulating leptin receptor (LepR) and decreased hypothalamic leptin actions. Additional hepatic LepR deficiency reverses these metabolic phenotypes. Thus, decreased hepatic insulin action suppresses hypothalamic leptin action with increased liver-derived soluble LepR. Human hepatic and circulating LepR levels also correlate negatively with hepatic insulin action indices. In mice, food restriction decreases hepatic insulin action and energy expenditure with increased circulating LepR. Hepatic LepR deficiency increases mortality with enhanced energy expenditure during food restriction. The liver translates metabolic cues regarding energy-deficient status, which is reflected by decreased hepatic insulin action, into soluble LepR, thereby suppressing energy dissipation and assuring survival during food shortages., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although liver regeneration has been extensively studied, the effects of bile-derived extracellular vesicles (bile EVs) on hepatocytes has not been elucidated. We examined the influence of bile EVs, collected from a rat model of 70% partial hepatectomy (PH), on hepatocytes. We produced bile-duct-cannulated rats. Bile was collected over time through an extracorporeal bile duct cannulation tube. Bile EVs were extracted via size exclusion chromatography. The number of EVs released into the bile per liver weight 12 h after PH significantly increased. Bile EVs collected 12 and 24 h post-PH, and after sham surgery (PH12-EVs, PH24-EVs, sham-EVs) were added to the rat hepatocyte cell line, and 24 h later, RNA was extracted and transcriptome analysis performed. The analysis revealed that more upregulated/downregulated genes were observed in the group with PH24-EVs. Moreover, the gene ontology (GO) analysis focusing on the cell cycle revealed an upregulation of 28 types of genes in the PH-24 group, including genes that promote cell cycle progression, compared to the sham group. PH24-EVs induced hepatocyte proliferation in a dose-dependent manner in vitro, whereas sham-Evs showed no significant difference compared to the controls. This study revealed that post-PH bile Evs promote the proliferation of the hepatocytes, and genes promoting cell cycles are upregulated in hepatocytes.

A newly developed semi-automatic synthetic luminescence substrate (SALS) method for measuring endotoxin was compared with the existing turbidimetric kinetic assay (TKA) using leukocyte-rich plasma to verify its usefulness. As a result, the endotoxin levels by this method were higher than that by the existing assay in most specimens, and the time required for measurement was much shorter. In addition, the leukocyte-rich plasma endotoxin level minus the plasma endotoxin levels were named leukocyte-associated endotoxin, and these levels per one leukocyte were compared. As a result, those levels were highly correlated with the endotoxin measurement levels of leukocyte-rich plasma. The correlation coefficient of SALS method was superior to the existing TKA method, the endotoxin level by this method may be close to true endotoxin levels., (© 2023. The Author(s).)

Objective We investigated the clinical characteristics of patients with reversible cerebral vasoconstrictor syndrome who had a history of migraine before the onset and considered the relationship between these two pathologies. Methods We investigated 98 patients who underwent magnetic resonance angiography within 14 days of the onset of reversible cerebral vasoconstriction syndrome at our hospital. Of these, 11 cases involved recurrences, so data from 87 patients were analyzed. Materials All consecutive patients diagnosed with reversible cerebral vasoconstrictor syndrome at our institution between October 2010 and July 2021. Results Fifty of the 87 patients (57%) had a history of migraine. A multivariate analysis revealed that the following clinical factors were significantly more frequent in patients with a history of migraine than in those without such a history: female sex; emotional situations as a trigger of the onset; presence of deep and subcortical white matter hyperintensity, absence of vasoconstriction in the M1 portion of the middle cerebral artery, and absence of other cerebral lesions on initial magnetic resonance imaging; absence of vasoconstriction of the basilar artery on follow-up magnetic resonance imaging; and progression of deep and subcortical white matter hyperintensity in the chronic stage. Conclusion Reversible cerebral vasoconstrictor syndrome patients with a history of migraine showed clinical features of migraine, including one aspect of cerebral small-vessel disease due to endothelial dysfunction, as a common causative condition.