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    Peripheral venous dilation using flow-mediated dilation response : A randomized crossover study

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    Background: Venodilation is crucial in enhancing the success rate of peripheral intravenous cannulation. Flow-mediated dilation (FMD) is a vasodilatory response initiated by temporary ischemia followed by reperfusion. This crossover study aimed to test the hypothesis that FMD induces dilation of the peripheral veins of the forearm. Methods: Fifteen healthy volunteers underwent the FMD and control conditions in a randomized order. FMD involved a 5-minute occlusion of blood flow in the brachial artery, followed by reperfusion, achieved by inflating and deflating a cuff placed on the upper arm. The control condition involved participants remaining at rest. The primary outcome measure was a change in the cross-sectional area of the cephalic vein post-intervention. The secondary outcomes included changes in venous diameter and perfusion index (PI). Results: FMD significantly increased the cross-sectional area of the cephalic vein compared with the control condition (relative change to baseline: 37.7% [31.4] vs 2.2% [11.7]), with a mean difference of 35.4% (95% confidence interval [CI]: 16.4 to 54.5, P=.001). Both longitudinal and transverse diameters were significantly expanded with FMD compared to the control (relative change to baseline: 15.7% [15.4] vs 2.6% [3.6], P=.004; 18.9% [15.6] vs −0.0 [10.2], P=.003, respectively). Additionally, PI significantly increased with FMD compared with the control (relative change to baseline: 77.8% [56.9] vs 14.6% [36.0]), with a mean difference of 63.2% (95% CI: 31.2 to 95.2, P=.001). Conclusion: FMD application induced dilation of the cephalic vein of the forearm. The findings suggest that FMD is an effective technique for dilating the venous area and potentially improving the success rate of peripheral intravenous cannulation.journal articl

    Structural insight into sugar-binding modes of microbial ß-amylase

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    ß-Amylase, which catalyses the release of ß-anomeric maltose from the non-reducing end of starch, is widely used in the food industry. Increasing its enzyme activity through protein engineering might improve the efficiency of food processing. To obtain detailed structural information to assist rationale design, here the crystal structure of Bacillus cereus β-amylase (BCB) complexed with maltose was determined by molecular replacement and refined using anisotropic temperature factors to 1.26 Å resolution with Rwork/Rfree factors of 12.4/15.7 %. The structure contains six maltose and one glucose molecules, of which two maltose and one glucose are bound at sites not previously observed in BCB structures. These three new sugar-binding sites are located on the surface and likely to be important in enhancing the degradation of raw-starch granules. In the active site of BCB, two maltose molecules are bound in tandem at subsites −2 ∼ −1 and +1 ∼ +2. Notably, the conformation of the glucose moiety bound at subsite −1 is a mixture of α-anomeric distorted 1,4B boat and 4C1 chair forms, while those at subsites −2, +1 ∼ +2 are all in the 4C1 chair forms. The O1 of the distorted α-glucose residue at subsite −1 occupies the position of the putative catalytic water, forming a hydrogen bond with OE1 of Glu367 (base catalyst), suggesting that this distorted sugar is not involved in catalysis. Together, these findings pave the way for further improving the functionality of microbial ß-amylase enzymes.journal articl

    Critical Limb Threatening Ischemia Due to Severe Polyarteritis Nodosa : A Case Report

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    A delayed diagnosis of polyarteritis nodosa may lead to critical limb-threatening ischemia (CLTI). A 74-year-old woman presented with left-foot pain and was treated with oral vasodilators and antiplatelet agents. However, the distal ischemia progressed to CLTI, including gangrene of the fingers and toes, and bilateral foot dropping appeared because of peroneal nerve paralysis. Angiography of the extremities revealed obstruction and stenosis of medium-sized arteries. Based on the progressive distal gangrene, mononeuropathy multiplex, and pathological findings of necrotic vasculitis, polyarteritis nodosa was diagnosed, and the patient's condition improved. A biopsy and neurological examination are essential for the appropriate diagnosis of PAN and immediate treatment.journal articl

    孤独に対する捉え方尺度の信頼性・妥当性の検討

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    This study examined the reliability and validity of the attitude toward solitude scale. In terms of reliability, we were able to confirm its test–retest reliability and reproduced the same factor structure as in previous studies. In terms of validity, we were able to confirm that attitude toward solitude and loneliness are separate concepts, and that the attitude toward solitude scale has criterion-related validity. We hope that further research using this scale in the future will contribute to the recovery of mental health related to solitude.departmental bulletin pape

    Resveratrol and piceid enhance efferocytosis by increasing the secretion of MFG-E8 in human THP-1 macrophages

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    The process of apoptotic cell clearance by phagocytes, known as efferocytosis, plays an essential role in maintaining homeostasis. Defects in efferocytosis can lead to inflammatory diseases such as atherosclerosis and autoimmune disorders. Therefore, the maintenance and promotion of efferocytosis are considered crucial for preventing these diseases. In this study, we observed that resveratrol, a representative functional food ingredient, and its glycoside, piceid, promoted efferocytosis in both human THP-1 macrophages differentiated with phorbol 12-myristate 13-acetate and peritoneal macrophages from thioglycolate-elicited mice. Resveratrol and piceid significantly increased mRNA expression and protein secretion of MFG-E8 in THP-1 macrophages. Furthermore, the activation of efferocytosis and the increment in MFG-E8 protein secretion caused by resveratrol or piceid treatment were canceled by MFG-E8 knockdown in THP-1 macrophages. In conclusion, we have demonstrated for the first time that resveratrol and piceid promote efferocytosis through the upregulation of MFG-E8 excretion in human THP-1 macrophages.journal articl

    An Exploratory Study of the Potential of Online Counseling for University Students by a Human-Operated Avatar Counselor

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    Recently, the use of digital technologies, such as avatars and virtual reality, has been increasingly explored to address university students’ mental health issues. However, there is limited research on the advantages and disadvantages of counselors using avatars in online video counseling. Herein, 25 university students were enrolled in a pilot online counseling session with a human counselor-controlled avatar, and asked about their emotional experiences and impressions of the avatar and to provide qualitative feedback on their communication experience. Positive emotions during the session were associated with impressions of the avatar’s intelligence and likeability. The anthropomorphism, animacy, likeability, and intelligent impressions of the avatar were interrelated, indicating that the avatar’s smile and the counselor’s expertise in empathy and approval may have contributed to these impressions. However, no associations were observed between participant experiences and their prior communication with avatars, or between participant experiences and their gender or the perceived gender of the avatar. Accordingly, recommendations for future practice and research are provided. Accumulating practical and empirical findings on the effectiveness of human-operated avatar counselors is crucial for addressing university students’ mental health issues.journal articl

    Fine structural human phantom in dentistry and instance tooth segmentation

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    In this study, we present the development of a fine structural human phantom designed specifically for applications in dentistry. This research focused on assessing the viability of applying medical computer vision techniques to the task of segmenting individual teeth within a phantom. Using a virtual cone-beam computed tomography (CBCT) system, we generated over 170,000 training datasets. These datasets were produced by varying the elemental densities and tooth sizes within the human phantom, as well as varying the X-ray spectrum, noise intensity, and projection cutoff intensity in the virtual CBCT system. The deep-learning (DL) based tooth segmentation model was trained using the generated datasets. The results demonstrate an agreement with manual contouring when applied to clinical CBCT data. Specifically, the Dice similarity coefficient exceeded 0.87, indicating the robust performance of the developed segmentation model even when virtual imaging was used. The present results show the practical utility of virtual imaging techniques in dentistry and highlight the potential of medical computer vision for enhancing precision and efficiency in dental imaging processes.journal articl

    Eicosapentaenoic Acid Rescues Cav1.2-L-Type Ca2+ Channel Decline Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes

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    Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here, we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes in the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with an oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction in cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction in Cav1.2 L-type Ca2+ current, mRNA, and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3′,5′-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2 and CREB mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2 and CREB mRNA expressions, which was reversed by an ROS scavenger. Our data suggest that EPA rescues cellular Cav1.2-Ca2+ channel decline caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.journal articl

    Conformational Distribution of a Multidomain Protein Measured by Single-Pair Small-Angle X-ray Scattering

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    The difficulty in evaluating the conformational distribution of proteins in solution often hinders mechanistic insights. One possible strategy for visualizing conformational distribution is distance distribution measurement by single-pair small-angle X-ray scattering (SAXS), in which the scattering interference from only a specific pair of atoms in the target molecule is extracted. Despite this promising concept, with few applications in synthetic small molecules and DNA, technical difficulties have prevented its application in protein conformational studies. This study used a synthetic tag to fix the lanthanide ion at desired sites on the protein and used single-pair SAXS with contrast matching to evaluate the conformational distribution of the multidomain protein enzyme MurD. These data highlighted the broad conformational and ligand-driven distribution shifts of MurD in solution. This study proposes an important strategy in solution structural biology that targets dynamic proteins, including multidomain and intrinsically disordered proteins.journal articl

    Decoding the molecular mechanism of selective autophagy of glycogen mediated by autophagy receptor STBD1

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    Autophagy of glycogen (glycophagy) is crucial for the maintenance of cellular glucose homeostasis and physiology in mammals. STBD1 can serve as an autophagy receptor to mediate glycophagy by specifically recognizing glycogen and relevant key autophagic factors, but with poorly understood mechanisms. Here, we systematically characterize the interactions of STBD1 with glycogen and related saccharides, and determine the crystal structure of the STBD1 CBM20 domain with maltotetraose, uncovering a unique binding mode involving two different oligosaccharide-binding sites adopted by STBD1 CBM20 for recognizing glycogen. In addition, we demonstrate that the LC3-interacting region (LIR) motif of STBD1 can selectively bind to six mammalian ATG8 family members. We elucidate the detailed molecular mechanism underlying the selective interactions of STBD1 with ATG8 family proteins by solving the STBD1 LIR/GABARAPL1 complex structure. Importantly, our cell-based assays reveal that both the STBD1 LIR/GABARAPL1 interaction and the intact two oligosaccharide binding sites of STBD1 CBM20 are essential for the effective association of STBD1, GABARAPL1, and glycogen in cells. Finally, through mass spectrometry, biochemical, and structural modeling analyses, we unveil that STBD1 can directly bind to the Claw domain of RB1CC1 through its LIR, thereby recruiting the key autophagy initiation factor RB1CC1. In all, our findings provide mechanistic insights into the recognitions of glycogen, ATG8 family proteins, and RB1CC1 by STBD1 and shed light on the potential working mechanism of STBD1-mediated glycophagy.journal articl

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