Quantification of steal flow on Doppler ultrasound in patients with arteriovenous graft for hemodialysis.

PURPOSE: Arteriovenous fistula (AVF) is the preferred treatment for long-term hemodialysis patients to allow reliable vascular access. Arteriovenous graft (AVG) is monitored using Doppler sonography to check a vessel's condition and predict complications such as steal syndrome. In this study, we developed an analysis algorithm and method to quantify steal syndrome using Doppler sonography. METHODS: Doppler sonography was used to determine the pattern of anterograde and retrograde flow. The ratio of blood volumes was calculated with a vision analysis software. First, performance of the developed algorithm was validated by comparing it with commercial Doppler sonography data. Doppler sonography was performed for an artificial vessel to analyze the steal flow. RESULTS: A total of 58 patients with steal flow were enrolled in this study. Of these patients, 23 did not have a difference in fingertip temperature between both sides. The median difference in temperature of 35 patients was 0.8°C (range, 0.3-1.9°C). The ratio of retrograde flow volume/antegrade flow volume in patients with the presence of temperature difference was significantly higher compared to that in patients without the temperature difference (p < .001). The ROC curve for the difference in flow volume had an AUC of 0.770. The optimal cutoff of difference in the flow volume between the two groups was 0.24 (sensitivity of 91.4 % and specificity of 52.2%). The flow volume difference was significantly positively correlated to temperature difference (r = 0.487, p < .003). CONCLUSION: Our algorithm could measure steal flow volume of a bidirectional waveform by antegrade arterial flow and retrograde reversal flow.

A Comprehensive Review: Robot-Assisted Treatments for Gait Rehabilitation in Stroke Patients.

Robot-assisted gait training (RAGT) is at the cutting edge of stroke rehabilitation, offering a groundbreaking method to improve motor recovery and enhance the quality of life for stroke survivors. This review investigates the effectiveness and application of various RAGT systems, including both end-effector and exoskeleton robots, in facilitating gait enhancements. The selection process for this comprehensive analysis involved a meticulous review of the literature from databases such as PubMed, the Cochrane Library, and EMBASE, focusing on studies published between 2018 and 2023. Ultimately, 27 studies met the criteria and were included in the final analysis. The focus of these studies was on the various RAGT systems and their role in promoting gait and balance improvements. The results of these studies conclusively show that patients experience significant positive effects from RAGT, and when combined with other physiotherapy methods, the outcomes are notably superior in enhancing functional ambulation and motor skills. This review emphasizes RAGT's capability to deliver a more customized and effective rehabilitation experience, highlighting the importance of tailoring interventions to meet the specific needs of each patient.

Detecting T-cell receptor clonality in patients with severe atopic dermatitis refractory to dupilumab.

BACKGROUND: Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response. OBJECTIVE: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab. METHODS: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL. RESULTS: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements. CONCLUSION: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.

Association between Atherosclerosis and High-Risk Colorectal Adenomas based on Cardio-Ankle Vascular Index and Ankle-Brachial Index.

Background/Aims: Colorectal adenomas are precancerous lesions that may lead to colorectal cancer. Recent studies have shown that colorectal adenomas are associated with atherosclerosis. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) are noninvasive methods for evaluating atherosclerosis. This study examined the association between atherosclerosis and high-risk colorectal adenomas based on the CAVI and ABI. Methods: The data of patients aged ≥50 years who had a colonoscopy and CAVI and ABI measurements from August 2015 to December 2021 at the Kangwon National University Hospital were analyzed retrospectively. After the colonoscopy, subjects were divided into no, overall, and high-risk (size ≥1 cm, high-grade dysplasia or villous adenoma, three or more adenomas) adenoma groups based on the pathology findings. The data were subjected to univariate and multivariate logistic regression analyses. Results: Among the 1,164 subjects, adenomas and high-risk adenomas were found in 613 (52.6%) and 118 (10.1%) patients, respectively. The rate of positive ABI (<0.9) and positive CAVI (≥9.0) were significantly higher in the high-risk adenoma group (22.0% and 55.9%) than in the no adenoma (12.3% and 39.6%) and the overall adenoma group (15.7% and 44.0%) (p=0.008 and p=0.006, respectively). Multivariate analysis revealed a positive CAVI and smoking status to be significantly associated with high-risk adenoma with an odds ratio of 1.595 (95% confidence interval 1.055-2.410, p=0.027) and 1.579 (1.072-2.324, p=0.021), respectively. Conclusions: In this study, a significant correlation between positive CAVI and high-risk adenomas was observed. Therefore, CAVI may be a significant predictor for high-risk colorectal adenoma.

Optimizing Rehabilitation Outcomes for Stroke Survivors: The Impact of Speed and Slope Adjustments in Anti-Gravity Treadmill Training.

Background and Objectives: This study explored the efficacy of customized anti-gravity treadmill (AGT) training, with adjustments in speed and incline, on rehabilitation outcomes for stroke patients, focusing on knee extensor muscle strength, joint angle, balance ability, and activities of daily living (ADLs). Materials and Methods: In this study, 30 individuals diagnosed with a stroke were divided into three groups. Experimental group 1 (EG1) underwent training without changes to speed and incline, experimental group 2 (EG2) received training with an increased incline, and experimental group 3 (EG3) underwent training with increased speed. Initially, all participants received AGT training under uniform conditions for two weeks. Subsequently, from the third to the sixth week, each group underwent their specified training intervention. Evaluations were conducted before the intervention and six weeks post-intervention using a manual muscle strength tester for knee strength, TETRAX for balance ability, Dartfish software for analyzing knee angle, and the Korean version of the Modified Barthel Index (K-MBI) for assessing activities of daily living. Results: Within-group comparisons revealed that AGT training led to enhancements in muscle strength, balance ability, joint angle, and ADLs across all participant groups. Between-group analyses indicated that EG2, which underwent increased incline training, demonstrated significant improvements in muscle strength and balance ability over EG1. EG3 not only showed significant enhancements in muscle strength, joint angle, and ADLs when compared to EG1 but also surpassed EG2 in terms of knee strength improvement. Conclusions: In conclusion, the application of customized AGT training positively impacts the rehabilitation of stroke patients, underscoring the importance of selecting a treatment method tailored to the specific needs of each patient.

Managing Vascular Pedicle Exposure in Free Tissue Transfer Using a Reprocessed Micronized Dermal Substitute in Lower Extremity Reconstructions.

Lower extremity reconstruction is challenging because of its intricate anatomy and dynamic biomechanics. Although microsurgical free tissue transfer offers pivotal solutions to limited local tissue availability, vascular pedicle exposure after free tissue transfer is common. We evaluated a novel method of managing pedicle exposure after free tissue transfer using a reprocessed micronized dermal substitute. Ten patients who underwent lower-extremity reconstruction using free tissue transfer and micronized dermal substitute between January and December 2023 were retrospectively reviewed. When native tissue could not be closed over the pedicle, reprocessed micronized artificial dermal matrix (rmADM) was cut and stacked to protect and stabilize it. Epithelialization was achieved by secondary skin grafting or healing by secondary intention. Flap dimensions, recipient artery and vein, ADM size, time required for granulation tissue maturation and complete epithelialization, and flap outcomes were analyzed. The mean age was 55.80 ± 20.70 years, and six patients (60%) were diabetic. The mean rmADM coverage area was 8.70 ± 8.41 cm2, and the average time required for complete epithelialization was 50.89 ± 14.21 days. Except for one total necrosis due to bypass graft failure, nine limbs were successfully salvaged. Application of rmADM offers numerous advantages, including vascular collapse prevention, moisture maintenance, granulation tissue growth promotion, and pedicle stabilization.

Evolutionary Spread of Distinct O-methyltransferases Guides the Discovery of Unique Isoaspartate-Containing Peptides, Pamtides.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a structurally diverse class of natural products with a distinct biosynthetic logic, the enzymatic modification of genetically encoded precursor peptides. Although their structural and biosynthetic diversity remains largely underexplored, the identification of novel subclasses with unique structural motifs and biosynthetic pathways is challenging. Here, it is reported that peptide/protein L-aspartyl O-methyltransferases (PAMTs) present in several RiPP subclasses are highly homologous. Importantly, it is discovered that the apparent evolutionary transmission of the PAMT gene to unrelated RiPP subclasses can serve as a basis to identify a novel RiPP subclass. Biochemical and structural analyses suggest that homologous PAMTs convert aspartate to isoaspartate via aspartyl-O-methyl ester and aspartimide intermediates, and often require cyclic or hairpin-like structures for modification. By conducting homology-based bioinformatic analysis of PAMTs, over 2,800 biosynthetic gene clusters (BGCs) are identified for known RiPP subclasses in which PAMTs install a secondary modification, and over 1,500 BGCs where PAMTs function as a primary modification enzyme, thereby defining a new RiPP subclass, named pamtides. The results suggest that the genome mining of proteins with secondary biosynthetic roles can be an effective strategy for discovering novel biosynthetic pathways of RiPPs through the principle of "guilt by association".

Determination of progressive stages of type 2 diabetes in a 45% high-fat diet-fed C57BL/6J mouse model is achieved by utilizing both fasting blood glucose levels and a 2-hour oral glucose tolerance test.

Type 2 diabetes is considered one of the top ten life-threatening diseases worldwide. Following economic growth, obesity and metabolic syndrome became the most common risk factor for type 2 diabetes. In this regard, high-fat diet-fed C57BL/6J mouse model is widely used for type 2 diabetes pathogenesis and novel therapeutics development. However, criteria for classifying type 2 diabetes progressive stages in this mouse model are yet to be determined, led to the difficulty in experimental end-point decision. In this study, we fed C57BL/6J male mice with 45% high-fat diet, which is physiologically close to human high-fat consumption, and evaluated the progression of type 2 diabetes. After consuming high-fat diet for 4 weeks, mice developed metabolic syndrome, including obesity, significant increase of fasting plasma cholesterol level, elevation of both C-peptide and fasting blood glucose levels. By combining both fasting blood glucose test and 2-hour-oral glucose tolerance test, our results illustrated clear progressive stages from metabolic syndrome into pre-diabetes before onset of type 2 diabetes in C57BL/6J mice given a 45% high-fat diet. Besides, among metabolic measurements, accumulating body weight gain > 16.23 g for 12 weeks could be utilized as a potential parameter to predict type 2 diabetes development in C57BL/6J mice. Thus, these results might support future investigations in term of selecting appropriate disease stage in high-fat diet-fed C57BL/6J mouse model for studying early prevention and treatment of type 2 diabetes.

Spatiotemporal estimation of nutrient data from the northwest pacific and east asian seas.

Nutrient data obtained from field observations have the potential to enhance our understanding of oceanic biogeochemical cycling and productivity changes. In particular, long-term nutrient data can provide valuable information on the links between climate change and biogeochemical changes. However, unlike other observational variables such as sea surface temperature, nutrient data are limited in terms of their broad-scale observations and automated sensor-based measurements. In this study, we analyzed nitrate and phosphate data obtained from coastal regions in Northeast Asia and the northwest Pacific from 1980 to 2019 using the spatiotemporal kriging technique and provide results in a spatiotemporal grid format. The data are available at monthly intervals and may be attractive to researchers in the fields of oceanography, marine ecology, and marine biogeochemistry at the climate change scale. Furthermore, sharing the source code of the data production process can contribute to better long-term data reproduction in the future.

A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage.

This study was conducted to investigate the effects of anti-gravity treadmill (AGT) training, which provides visual feedback and Biorescue training on proprioception, muscle strength, balance, and gait, in stroke patients. A total of 45 people diagnosed with post-stroke were included as study subjects; they were randomized to an AGT training group provided with visual feedback (Group A), a Biorescue training group provided with visual feedback (Group B), and an AGT/Biorescue group that subsequently received AGT training and Biorescue training (Group C). A muscle strength-measuring device was used to evaluate muscle strength. Timed Up and Go and Bug Balance Scale assessment sheets were used to evaluate balance ability. Dartfish software was used to evaluate gait ability. The results of the study showed that Groups A and C had a significant increase in muscle strength compared with Group B; in terms of balance and gait abilities, Group C showed a significant increase in balance ability and gait speed and a significant change in knee joint angle compared with Groups A and B. In conclusion, this study suggests that including a method that applies multiple therapeutic interventions is desirable in the rehabilitation of stroke patients to improve their independence.

Scaling-Up Insights for Zinc-Air Battery Technologies Realizing Reversible Zinc Anodes.

Zinc-air battery (ZAB) technology is considered one of the promising candidates to complement the existing lithium-ion batteries for future large-scale high-energy-storage demands. The scientific literature reveals many efforts for the ZAB chemistries, materials design, and limited accounts for cell design principles with apparently superior performances for liquid and solid-state electrolytes. However, along with the difficulty of forming robust solid-electrolyte interphases, the discrepancy in testing methods and assessment metrics severely challenges the realistic evaluation/comparison and commercialization of ZABs. Here, strategies to formulate reversible zinc anodes are proposed and specific cell-level energy metrics (100-500 Wh kg-1 ) and realistic long-cycling operations are realized. Stabilizing anode/electrolyte interfaces results in a cumulative capacity of 25 Ah cm-2 and Coulomb efficiency of >99.9% for 5000 plating/stripping cycles. Using 1-10 Ah scale (≈500 Wh kg-1 at cell level) solid-state zinc-air pouch cells, scale-up insights for Ah-level ZABs that can progress from lab-scale research to practical production are also offered.

Li, Na, K, Mg, Zn, Al, and Ca Anode Interface Chemistries Developed by Solid-State Electrolytes.

Solid-state batteries (SSBs) have received significant attention due to their high energy density, reversible cycle life, and safe operations relative to commercial Li-ion batteries using flammable liquid electrolytes. This review presents the fundamentals, structures, thermodynamics, chemistries, and electrochemical kinetics of desirable solid electrolyte interphase (SEI) required to meet the practical requirements of reversible anodes. Theoretical and experimental insights for metal nucleation, deposition, and stripping for the reversible cycling of metal anodes are provided. Ion transport mechanisms and state-of-the-art solid-state electrolytes (SEs) are discussed for realizing high-performance cells. The interface challenges and strategies are also concerned with the integration of SEs, anodes, and cathodes for large-scale SSBs in terms of physical/chemical contacts, space-charge layer, interdiffusion, lattice-mismatch, dendritic growth, chemical reactivity of SEI, current collectors, and thermal instability. The recent innovations for anode interface chemistries developed by SEs are highlighted with monovalent (lithium (Li+ ), sodium (Na+ ), potassium (K+ )) and multivalent (magnesium (Mg2+ ), zinc (Zn2+ ), aluminum (Al3+ ), calcium (Ca2+ )) cation carriers (i.e., lithium-metal, lithium-sulfur, sodium-metal, potassium-ion, magnesium-ion, zinc-metal, aluminum-ion, and calcium-ion batteries) compared to those of liquid counterparts.

Single-cell RNA sequencing identifies distinct transcriptomic signatures between PMA/ionomycin- and αCD3/αCD28-activated primary human T cells.

Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell-derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55+) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.

Interaction effects between insomnia and depression on risk of out-of-hospital cardiac arrest: Multi-center study.

BACKGROUND: Insomnia and depression have been known to be risk factors of several diseases, including coronary heart disease. We hypothesized that insomnia affects the out-of-hospital cardiac arrest (OHCA) incidence, and these effects may vary depending on whether it is accompanied by depression. This study aimed to determine the association between insomnia and OHCA incidence and whether the effect of insomnia is influenced by depression. METHODS: This prospective multicenter case-control study was performed using Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiology Surveillance (CAPTURES-II) project database for OHCA cases and community-based controls in Korea. The main exposure was history of insomnia. We conducted conditional logistic regression analysis to estimate the effect of insomnia on the risk of OHCA incidence and performed interaction analysis between insomnia and depression. Finally, subgroup analysis was conducted in the patients with insomnia. RESULTS: Insomnia was not associated with increased OHCA risk (0.95 [0.64-1.40]). In the interaction analysis, insomnia interacted with depression on OHCA incidence in the young population. Insomnia was associated with significantly higher odds of OHCA incidence (3.65 [1.29-10.33]) in patients with depression than in those without depression (0.84 [0.59-1.17]). In the subgroup analysis, depression increased OHCA incidence only in patients who were not taking insomnia medication (3.66 [1.15-11.66]). CONCLUSION: Insomnia with depression is a risk factor for OHCA in the young population. This trend was maintained only in the population not consuming insomnia medication. Early and active medical intervention for patients with insomnia may contribute to lowering the risk of OHCA.

Establishment of a humanized mouse model of keloid diseases following the migration of patient immune cells to the lesion: Patient-derived keloid xenograft (PDKX) model.

Keloid disorder is an abnormal fibroproliferative reaction that can occur on any area of skin, and it can impair the quality of life of affected individuals. To investigate the pathogenesis and develop a treatment strategy, a preclinical animal model of keloid disorder is needed. However, keloid disorder is unique to humans, and the development of an animal model of keloid disorder is highly problematic. We developed the patient-derived keloid xenograft (PDKX), which is a humanized mouse model, and compared it to the traditional mouse xenograft model (transplantation of only keloid lesions). To establish the PDKX model, peripheral mononuclear cells (PBMCs) from ten keloid patients or five healthy control subjects were injected into NOD/SCID/IL-2Rγnull mice, and their keloid lesions were grafted onto the back after the engraftment of immune cells (transplantation of keloid lesions and KP PBMCs or HC PBMCs). Four weeks after surgery, the grafted keloid lesion was subjected to histologic evaluation. Compared to the traditional model, neotissue formed along the margin of the grafted skin, and lymphocyte infiltration and collagen synthesis were significantly elevated in the PDKX model. The neotissue sites resembled the margin areas of keloids in several respects. In detail, the levels of human Th17 cells, IL-17, HIF-1a, and chemokines were significantly elevated in the neotissue of the PDKX model. Furthermore, the weight of the keloid lesion was increased significantly in the PDKX model, which was due to the proinflammatory microenvironment of the keloid lesion. We confirmed that our patient-derived keloid xenograft (PDKX) model mimicked keloid disorder by recapitulating the in vivo microenvironment. This model will contribute to the investigation of cellular mechanisms and therapeutic treatments for keloid disorders.

Treatment of Sagittal Fracture of the Zygomatic Arch Root.

A sagittal fracture at the temporal root of the zygomatic arch (ZAR) often occurs as a component of zygomaticomaxillary complex (ZMC) fractures. However, this area is difficult to access, and anchorage is limited due to the unstable structure around it. Therefore, a preauricular approach using single-screw fixation is proposed, and this study reports its results and usefulness. Forty-four patients with sagittal fractures of ZAR occurring with ZMC fractures were evaluated from 2012 to 2021. Open reduction and internal fixation were performed on all patients with ZMC fractures. Closed reduction using Dingman incision and external finger pressure in group A (indirect approach; 30 patients) and single-screw fixation using a preauricular approach in group B (direct approach; 14 patients) were performed to address sagittal fractures in ZAR. For single-screw fixation, the additional mean operation time was 11.34±3.25 minutes. On postoperative 3-dimensional computed tomography and plain radiographs, group B showed more accurate reduction and less deformity and trismus ( P <0.05). Moreover, a normal diet was initiated more quickly in group B than in group A ( P <0.05). Some cases in group A showed nonunion or malunion. This study revealed that a direct approach (group B) toward sagittal fractures of ZAR is recommended due to more accurate results and fewer complications than those observed with the indirect approach (group A). Moreover, the total operation time and complications may be lesser than those with the bicoronal approach.

Discovery of a New Antibiotic Demethoxytetronasin Using a Dual-Sided Agar Plate Assay (DAPA).

For over a century, researchers have cultured microorganisms together on solid support─typically agar─in order to observe growth inhibition via antibiotic production. These simple bioassays have been critical to both academic researchers that study antibiotic production in microorganisms and to the pharmaceutical industry's global effort to discover drugs. Despite the utility of agar assays to researchers around the globe, several limitations have prevented their widespread adoption in advanced high-throughput compound discovery and dereplication campaigns. To address a list of specific shortcomings, we developed the dual-sided agar plate assay (DAPA), which exists in a 96-well plate format, allows microorganisms to compete through opposing sides of a solid support in individual wells, is amenable to high-throughput screening and automation, is reusable, and is low-cost. Herein, we validate the use of DAPA as a tool for drug discovery and show its utility to discover new antibiotic natural products. From the screening of 217 bacterial isolates on multiple nutrient media against 3 pathogens, 55 hits were observed, 9 known antibiotics were dereplicated directly from agar plugs, and a new antibiotic, demethoxytetronasin (1), was isolated from a Streptomyces sp. These results demonstrate that DAPA is an effective, accessible, and low-cost tool to screen, dereplicate, and prioritize bacteria directly from solid support in the front end of antibiotic discovery pipelines.