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Takuma Yuri,1,2 Nariyuki Mura,1,3,4 Kyosuke Hoshikawa,4 Hugo Giambini,2 Hiromi Fujii,1 Yoshiro Kiyoshige1,4 1Graduate School of Health Sciences, Yamagata Prefectural University of Health Sciences, Yamagata, Japan; 2Department of Biomedical Engineering, The University of Texas at San Antonio, San Antonio, TX, USA; 3Department of Orthopaedic Surgery, Yoshioka Hospital, Tendo, Japan; 4Department of Physical Therapy, Yamagata Prefectural University of Health Sciences, Yamagata, JapanCorrespondence: Takuma YuriGraduate School of Health Sciences, Yamagata Prefectural University of Health Sciences, 260 Kamiyanagi, Yamagata, 990-2212, JapanTel +81-23-686-6741Email d2167013@yachts.ac.jpPurpose: Ultrasound elastography has been used to evaluate the skeletal muscle stiffness as a biomarker for sarcopenia assessment. However, there is no consensus with respect to the size and location of the region of interest in assessing such fat infiltrated muscle. The objective of this study was to determine which cross-sectional area should be measured in torn disuse muscle with fat infiltration to accurately measure muscle activity using real-time tissue elastography (RTE).Methods: Twenty-seven patients, whose rotator cuff muscle with torn tendon was successfully repaired, were followed by programmed rehabilitation. RTE measurements of the supraspinatus muscle were obtained during muscle contraction before and one-year after surgery so that the activity value was defined as the difference between elastography measurements at rest and elastography measurements during contraction. Given that the patients with successfully repaired and completed rehabilitation showed an increased activity value, the sensitivity for three regions of interest; posterior portion of the anterior-middle subregion (AM-p), anterior region (AR), and whole cross-sectional area of the supraspinatus (whole) were compared with the number of patients showing an increase in activity values as sensitivity analysis.Results: The sensitivity showing an increase in activity values was 74.1% for the AM-p area, 70.4% for the AR area, and 81.5% for the whole area. Intraclass correlation coefficient1,3 was 0.87– 0.97 for the AM-p area, 0.88– 0.98 for the AR area and 0.92– 0.99 for the whole area.Conclusion: The whole cross-sectional area is suitable to measure muscle activity in muscle with fat infiltration. The results in this study will provide some beneficial information when ultrasound elastography is used for the assessment of sarcopenia muscle with fat infiltration.Keywords: ultrasound elastography, region of interest, sarcopenia, fat infiltration, supraspinatus muscle

In the Vietnamese Mekong Delta (VMD), water levels at some stations have increased. However, the factors that cause this rise in the VMD have not been identified. We considered four factors that may have contributed to the water level rise: (1) increased runoff from upstream, (2) sea-level rise, (3) land subsidence, and (4) decrease in flood mitigation function because of construction of high dykes. We analysed daily maximum and minimum water levels, and mean daily water levels from 24 monitoring stations from 1987 to 2006. Using daily and annual water level differences, we classified the delta into two groups: one is dominated by flows from upstream, while the other is tide dominated. We then tested the trends of annual maximum and minimum water levels using the Mann-Kendall test, and identified the slope of the trend using the method of Sen. The areas of dyke construction were estimated using the Enhanced Vegetation Index (EVI) and Land Surface Water Index (LSWI) from the Moderate Resolution Imaging Spectroradiometer (MODIS) data. Results show (1) river inflow has little impact on rising water levels in the VMD, (2) the influence of high dykes on water level rise could not be quantified in this study, and (3) both maximum and minimum water levels significantly increased in the tide-dominated area. Trend of annual minimum water level can be considered as the sum sea-level rise and land subsidence. Therefore, we attribute 6.05 mm year−1 (80%) to land subsidence and 1.42 mm year−1 (20%) to sea level rise, indicating that inundations have been severe in the VMD, caused primarily by land subsidence. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Bulk single crystals of the perovskite Li x La (1− x )/3 NbO 3 , which is one of the materials used as the solid electrolyte in all-solid lithium-ion batteries, have been grown for the first time by the directional solidification method. The ionic conductivity measured in the growth direction of a single crystal wafer of Li x La (1− x )/3 NbO 3 with x =0.08 showed a maximum value of 1.9×10 −4 Scm −1 . [ABSTRACT FROM AUTHOR]

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.)

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.)

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 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.

Presepsin (sCD14-ST) is used as a marker for sepsis diagnosis. The production mechanism of presepsin is unique in that it is produced through phagocytosis of microorganisms. However, some studies have demonstrated that non-infected patients had increased presepsin levels and that presepsin is related to the risk or severity of diseases. This study was designed to describe a sensitive sandwich enzyme-linked immunosorbent assay for mouse presepsin developed to investigate the association of presepsin with diseases. Polyclonal antibodies were generated from peptide-immunized rabbit antiserum. Mouse presepsin standard was prepared using the recombinant method as an Fc-fusion protein. The linear detection range of the method was 4.7-300 pg/mL with a detection limit of 1.4 pg/mL. The assay detected mouse presepsin where mouse soluble CD14 (sCD14) was digested by cathepsin D proteinase and the cross-reactivity of sCD14 was not observed. The normal levels of mouse presepsin and sCD14 were compared; 65.9 ± 21.4 pg/mL and 43.2 ± 7.2 ng/mL were determined, respectively. Moreover, the levels of presepsin and sCD14 were compared with a lipopolysaccharide (LPS)-injected sepsis mouse model. The newly developed analytical method had high specificity to presepsin and is an efficient tool for studying the association between presepsin and diseases., (© 2022. The Author(s).)

Purpose: The diuretic effect of tolvaptan is largely blood level-dependent although it does exhibit interindividual differences according to cytochrome P450 (CYP) 3A5 genotype. This study aimed to investigate the pharmacokinetic relationship between plasma tolvaptan and its monohydroxylate enantiomers and the factors affecting their metabolism in heart failure patients., Methods: Japanese heart failure patients (n = 88) receiving oral tolvaptan (median dosage 7.5 mg/day) were enrolled. Blood samples were collected prior to the dosing on day 6 or later after first administration to determine the plasma concentrations of tolvaptan and its monohydroxylate enantiomers. Gene polymorphisms of CYP3A5, carbonyl reductase (CBR) 1/3, and ATP-binding cassette subfamily B member (ABCB) 1 were analyzed for their impact on tolvaptan pharmacokinetics. Serum laboratory test values and concomitant use of amiodarone were evaluated as factors related to tolvaptan metabolism., Results: The median of the sum of the 5S- and 5R-tolvaptan plasma concentrations was 48.9 (range, 15.3-100) ng/mL. CYP3A5 genotypes significantly affected the concentration ratio of all enantiomeric metabolites to tolvaptan, while the other metabolic-related gene polymorphisms had no influence. A negative correlation was found between serum albumin and the enantiomeric ratio of tolvaptan and monohydroxylate DM-4111. Concomitant use of amiodarone increased the plasma levels of whole tolvaptan but significantly decreased the metabolic ratios of 5R-tolvaptan. 5S-tolvaptan was selectively synthesized from ketone MOP-21826 by CBR1 with a substantially smaller reaction velocity compared to tolvaptan monohydroxylation by CYP3A4/5., Conclusion: This study clarified the racemic impact of CYP3A5 genotypes on tolvaptan metabolism. Amiodarone may stereoselectively interact with R-forms rather than S-forms of tolvaptan., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The purpose of this study was to evaluate the effect of fat infiltration, tear size, and post-operative tendon integrity, on post-operative contractility., Methods: Thirty-five patients who underwent rotator cuff repair were included. The fat infiltration, tear size, and post-operative tendon integrity were evaluated by Goutallier stage, Cofield classification, and Sugaya classification, respectively. The muscle elasticity at rest and at contraction was assessed by real-time tissue elastography pre- and one-year post-operatively. We defined the difference in elasticity between at rest and at contraction as the activity value which reflects muscle contractility., Results: The activity value in patients with Sugaya Type I tended to increase regardless of Cofield classification, whereas those with Sugaya Type III and IV tended to decrease. While the activity value in the patients classified as stage 1 and Type I tended to increase, patients classified as stage 2 showed decreased or constant in contractility even in those subjects classified as Type I. Stepwise multiple regression analysis showed both pre- (p = 0.004, r = -0.47) and post-operative activity values (p = 0.022, r = -0.39) to be significantly correlated only with the Goutallier stage., Conclusion: Multiple regression analysis indicated only the Goutallier stage was a significant independent factor for contractility of the supraspinatus muscle. Supraspinatus muscle contractility in patients classified as Types III and IV based on the Sugaya classification tended to decrease post-operatively, while patients whose contractility increased post-operatively were characterized by having a Type I tendon integrity., (© 2021. The Author(s).)

Climate change causes environmental variation worldwide, which is one of the most serious threats to global food security. In addition, more than 2 billion people in the world are reported to suffer from serious malnutrition, referred to as 'hidden hunger.' Dependence on only a few crops could lead to the loss of genetic diversity and high fragility of crop breeding in systems adapting to global scale climate change. The exploitation of underutilized species and genetic resources, referred to as orphan crops, could be a useful approach for resolving the issue of adaptability to environmental alteration, biodiversity preservation, and improvement of nutrient quality and quantity to ensure food security. Moreover, the use of these alternative crops will help to increase the human health benefits and the income of farmers in developing countries. In this review, we highlight the potential of orphan crops, especially amaranths, for use as vegetables and health-promoting nutritional components. This review highlights promising diversified sources of amaranth germplasms, their tolerance to abiotic stresses, and their nutritional, phytochemical, and antioxidant values for vegetable purposes. Betalains (betacyanins and betaxanthins), unique antioxidant components in amaranth vegetables, are also highlighted regarding their chemodiversity across amaranth germplasms and their stability and degradation. In addition, we discuss the physiological functions, antioxidant, antilipidemic, anticancer, and antimicrobial activities, as well as the biosynthesis pathway, molecular, biochemical, genetics, and genomic mechanisms of betalains in detail., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Knowledge of the morphological and functional differences in the anatomic subregions of the supraspinatus (SSP) and infraspinatus (ISP) muscles during forward flexion will provide useful information in the management of shoulder joint disorders. The purpose of this study was to investigate whether the SSP and ISP muscle subregions exhibit independent roles during forward flexion of the shoulder joint., Methods: Eight healthy male volunteers without any restriction in their shoulder joints were recruited for this study. Participants were instructed to sit on a chair with their back against the backrest. Shear modulus (kPa) was measured as a surrogate for muscle stiffness using shear wave elastography on the SSP and ISP muscle subregions. Active measurements of the nondominant arm were obtained during isometric contraction at a neutral position and every 15° intervals from 30° to 150° during forward flexion. Friedman test and Dunn's post hoc test were used to evaluate differences in measurement outcomes among angles during forward flexion in each muscle subregion., Results: Active stiffness outcomes of the anterior-middle subregion of the SSP muscle during forward flexion increased from 30° up to 45°, reaching a value of 182.4 ± 32.1 kPa ( P  < .001). Stiffness of the anterior-superficial subregion of the SSP muscle was highest at 30° (125.0 ± 20.6 kPa; P  < .019) and linearly decreased up to 105° with increasing shoulder angle position. Stiffness of the superior, middle, and inferior subregions of ISP muscle presented a mountain-shaped trend, with peaks of 99.9 ± 23.5 kPa at 90° ( P  < .013), 144.2 ± 11.2 kPa at 90° ( P  < .013), and 122.9 ± 27.9 kPa at 105° ( P  < .007), respectively. Finally, the stiffness outcomes of the pectoralis major and anterior region of the deltoid muscles showed a mountain-shaped trend with peaks of 89.4 ± 23.5 kPa at 60° ( P  < .007) and 176.7 ± 22.9 kPa at 90° ( P  < .026), respectively., Conclusions: The SSP and ISP muscle subregions play a significant role during active forward flexion motion. While closely overlapped, the activity of the muscle subregions changed during the forward flexion motion range, starting with an active anterior-superficial subregion of the SSP muscle at the initial range of motion and an active inferior subregion of the ISP muscle toward midrange of motion. The SSP and ISP subregions did not demonstrate independent functional behavior during forward flexion., (© 2022 The Authors.)

The effects of the climate change including an increase in the average global temperatures, and abnormal weather events such as frequent and severe heatwaves are emerging as a worldwide ecological concern due to their impacts on plant vegetation and crop productivity. In this review, the molecular processes of plants in response to heat stress-from the sensing of heat stress, the subsequent molecular cascades associated with the activation of heat shock factors and their primary targets (heat shock proteins), to the cellular responses-have been summarized with an emphasis on the classification and functions of heat shock proteins. Vegetables contain many essential vitamins, minerals, antioxidants, and fibers that provide many critical health benefits to humans. The adverse effects of heat stress on vegetable growth can be alleviated by developing vegetable crops with enhanced thermotolerance with the aid of various genetic tools. To achieve this goal, a solid understanding of the molecular and/or cellular mechanisms underlying various responses of vegetables to high temperature is imperative. Therefore, efforts to identify heat stress-responsive genes including those that code for heat shock factors and heat shock proteins, their functional roles in vegetable crops, and also their application to developing vegetables tolerant to heat stress are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kang, Lee, Hoshikawa, Kang and Jang.)

Climate change is a major threat to global food security. Changes in climate can directly impact food systems by reducing the production and genetic diversity of crops and their wild relatives, thereby restricting future options for breeding improved varieties and reducing the ability to adapt crops to future challenges. The global surface temperature is predicted to rise by an average of 0.3°C during the next decade, and the Paris Agreement (Paris Climate Accords) aims to limit global warming to below an average of 2°C, preferably to 1.5°C compared to pre-industrial levels. Even if the goal of the Paris Agreement can be met, the predicted rise in temperatures will increase the likelihood of extreme weather events, including heatwaves, making heat stress (HS) a major global abiotic stress factor for many crops. HS can have adverse effects on plant morphology, physiology, and biochemistry during all stages of vegetative and reproductive development. In fruiting vegetables, even moderate HS reduces fruit set and yields, and high temperatures may result in poor fruit quality. In this review, we emphasize the effects of abiotic stress, especially at high temperatures, on crop plants, such as tomatoes, touching upon key processes determining plant growth and yield. Specifically, we investigated the molecular mechanisms involved in HS tolerance and the challenges of developing heat-tolerant tomato varieties. Finally, we discuss a strategy for effectively improving the heat tolerance of vegetable crops., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hoshikawa, Pham, Ezura, Schafleitner and Nakashima.)

Background: This study investigated hyperintense vessel signs (HVS) on fluid-attenuated inversion recovery imaging in the P1-2 portions of posterior cerebral arteries (PCAs) as a "hyperintense PCA sign" and HVS of cortical arteries. We retrospectively examined whether these signs would be useful in diagnosing reversible cerebral vasoconstriction syndrome (RCVS) in the acute phase., Methods: Eighty patients with RCVS who underwent initial magnetic resonance imaging (MRI) within 7 days of onset were included in this study. HVS and related clinical factors were examined., Results: On initial MRI of RCVS patients, hyperintense PCA sign and HVS of cortical arteries were seen in 21 cases (26%) and 38 cases (48%), respectively. In patients showing hyperintense PCA sign, vasoconstriction of the A2-3 portion was a significant clinical factor. Conversely, vasoconstriction of the M1 and P1 portions and the presence of white matter hyperintensity on initial and chronic-stage MRI were significantly associated with the presence of HVS in cortical arteries., Conclusion: Because rich collateral flow exists around PCAs, the frequency of hyperintense PCA sign is not high. However, hyperintense PCA sign findings in patients with suspected RCVS offer credible evidence of extreme flow decreases due to vasoconstriction in peripheral PCAs and other arteries associated with the collateral circulation of PCAs. Conversely, HVS in cortical arteries tend to reflect slow antegrade circulation due to vasoconstriction of peripheral vessel and major trunks. Both signs appear useful for auxiliary diagnosis of acute-phase RCVS., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

The production of recombinant proteins is important in academic research to identify protein functions. Moreover, recombinant enzymes are used in the food and chemical industries, and high-quality proteins are required for diagnostic, therapeutic, and pharmaceutical applications. Though many recombinant proteins are produced by microbial or mammalian cell-based expression systems, plants have been promoted as alternative, cost-effective, scalable, safe, and sustainable expression systems. The development and improvement of transient expression systems have significantly reduced the period of protein production and increased the yield of recombinant proteins in plants. In this review, we consider the importance of plant-based expression systems for recombinant protein production and as genetic engineering tools., (© 2021 Japanese Society for Plant Biotechnology.)