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Abstract Background Although copper oxide nanoparticles (CuONPs) offer certain benefits to humans, they can be toxic to organs and exacerbate underlying diseases upon exposure. Chronic obstructive pulmonary disease (COPD), induced by smoking, can worsen with exposure to various harmful particles. However, the specific impact of CuONPs on COPD and the underlying mechanisms remain unknown. In this study, we investigated the toxic effects of CuONPs on the respiratory tract, the pathophysiology of CuONPs exposure-induced COPD, and the mechanism of CuONPs toxicity, focusing on thioredoxin-interacting protein (TXNIP) signaling using a cigarette smoke condensate (CSC)-induced COPD model. Results In the toxicity study, CuONPs exposure induced an inflammatory response in the respiratory tract, including inflammatory cell infiltration, cytokine production, and mucus secretion, which were accompanied by increased TXNIP, NOD-like receptor protein 3 (NLRP3), caspase-1, and interleukin (IL)-1β. In the COPD model, CuONPs exposure induced the elevation of various indexes related to COPD, as well as increased TXNIP expression. Additionally, TNXIP-knockout (KO) mice showed a significantly decreased expression of NLRP3, caspase-1, and IL-1β and inflammatory responses in CuONPs-exposed COPD mice. These results were consistent with the results of an in vitro experiment using H292 cells. By contrast, TNXIP-overexpressed mice had a markedly increased expression of NLRP3, caspase-1, and IL-1β and inflammatory responses in CuONPs-exposed COPD mice. Conclusions We elucidated the exacerbating effect of CuONPs exposure on the respiratory tract with underlying COPD, as well as related signaling transduction via TXNIP regulation. CuONPs exposure significantly increased inflammatory responses in the respiratory tract, which was correlated with elevated TXNIP-NLRP3 signaling.

Abstract Background The mitochondria are essential organelles not only providing cellular energy in the form of ATP, but also regulating the inflammatory response and the cell death program. Mitochondrial dysfunction has been associated with various human diseases, including metabolic syndromes as well as inflammatory and neurodegenerative diseases. Acute respiratory distress syndrome (ARDS) is an acute pulmonary disorder characterized by uncontrolled alveolar inflammation, apoptotic lung epithelial/endothelial cells, and pulmonary edema. Despite the high mortality of ARDS, an effective pharmacotherapy to treat this disease has not been established yet. Therefore, identifying a novel targeted therapy for ARDS is important. Recently, exogenous mitochondrial transplantation was reported to be beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transplantation on ARDS in vitro and in vivo. Methods Mitochondria were isolated from human stem cells. For in vitro efficacy of mitochondrial transplantation on the inflammation and cell death, murine alveolar macrophages MH-S and human pulmonary microvascular endothelial cells HPMECs were exposed to LPS, respectively. The ARDS mice model established by a single intratracheal instillation of LPS was used for in vivo efficacy of intravenously treated mitochondria. Results Our results showed that the mitochondria isolated from human stem cells exhibited an anti-inflammatory effect against alveolar macrophages and an anti-apoptotic effect against the alveolar epithelial cells. Furthermore, intravenous mitochondrial treatment was associated with the attenuation of lung injury in the LPS-induced ARDS mice. Conclusion Dual effects of mitochondria on anti-inflammation and anti-apoptosis support the potential of mitochondrial transplantation as a novel therapeutic strategy for ARDS.

Abstract Background An idiopathic outflow tract premature ventricular complex (OT-PVC) is a common arrhythmia, and the accuracy of site of origin prediction using the 12-lead electrocardiogram (ECG) algorithm is not high. There are no studies about a systematic strategy that can provide practical help to electrophysiologists in OT-PVC mapping and ablation. This study aims to evaluate the efficacy and safety of the proposed ablation protocol and establish an optimal catheter ablation strategy by simultaneously investigating and synthesizing various indicators observed during the mapping procedure. Methods and design This study (ABOUT-PVC) was designed as a prospective multicenter study to enroll 210 patients from 11 tertiary university hospitals over an estimated 27 months. Patients with idiopathic OT-PVC requiring catheter ablation will receive the procedure through a proposed ablation strategy and will be followed up for at least 12 months. The primary outcome is the acute procedural success rate. The secondary outcomes are clinical success rate, procedure time, complication rate, symptom relief, and changes in echocardiographic parameters. Conclusions The ABOUT-PVC study was designed to investigate the efficacy and safety of the proposed ablation strategy and establish an optimal catheter ablation strategy. We expect this study to overcome the limitations of the ECG prediction algorithms and provide a practical guide to electrophysiologists, increasing the procedure’s success rate and reducing complications and procedure time.

Abstract Background The lead of left bundle branch area pacing (LBBAP) inserted into the muscular septum will make the transvenous lead extraction (TLE) of LBBAP more challenging and because in LBBAP ventricular lead (V lead) should be inserted into the part of the septum, damage to the vessel near the lead could occur. The case reports introduced the complications of LBBAP previously introduced, but not being considered in detail. Case presentation The two patients (76-year-old man, 90-year-old man) with a complete atrioventricular block (CAVB) undergoing the LBBAP procedure experienced complications related to the procedure. The complications were abrupt dysfunction of V lead and damage to the septal vein in the process of the procedure, respectively. Fortunately, they were discharged without any other complications. Conclusions A deliberate approach for the procedure would be needed as well as successful insertion appropriate for the protocol of LBBAP. And long-term follow-up of complications should be needed.

Abstract Malalignment in the lower limb structure occurs due to various causes. Accurately evaluating limb alignment in situations where malalignment needs correction is necessary. To create an automated support system to evaluate lower limb alignment by quantifying mechanical tibiofemoral angle (mTFA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA) on full-length weight-bearing radiographs of both lower extremities. In this retrospective study, we analysed 404 radiographs from one hospital for algorithm development and testing and 30 radiographs from another hospital for external validation. The performance of segmentation algorithm was compared to that of manual segmentation using the dice similarity coefficient (DSC). The agreement of alignment parameters was assessed using the intraclass correlation coefficient (ICC) for internal and external validation. The time taken to load the data and measure the four alignment parameters was recorded. The segmentation algorithm demonstrated excellent agreement with human-annotated segmentation for all anatomical regions (average similarity: 89–97%). Internal validation yielded good to very good agreement for all the alignment parameters (ICC ranges: 0.7213–0.9865). Interobserver correlations between manual and automatic measurements in external validation were good to very good (ICC scores: 0.7126–0.9695). The computer-aided measurement was 3.44 times faster than was the manual measurement. Our deep learning-based automated measurement algorithm accurately quantified lower limb alignment from radiographs and was faster than manual measurement.

Abstract Purpose This systematic review aimed to evaluate the effects of concurrent cartilage procedures on cartilage regeneration when performed alongside high tibial osteotomy (HTO). Materials and methods The systematic review followed the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A comprehensive search was conducted on databases including PubMed, Embase, Cochrane Library, and Google Scholar, covering articles published until August 31, 2023. Results Sixteen studies (1277 patients) revealed that HTO, with or without concurrent cartilage procedures, leads to cartilage regeneration based on the International Cartilage Repair Society (ICRS) grade during second-look arthroscopy. No concurrent procedure showed improvement in ICRS grade (mean difference: − 0.80 to − 0.49). Microfracture (mean difference: − 0.75 to − 0.22), bone marrow aspirate concentrate (BMAC) (mean difference: − 1.37 to − 0.67), and human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) (mean difference: − 2.46 to − 1.81) procedures also demonstrated positive outcomes. Clinical outcome assessments for each cartilage procedure were also improved during postoperative follow-up, and no specific complications were reported. Conclusions HTO with or without concurrent cartilage procedures promotes cartilage regeneration observed during second-look arthroscopy, with improved clinical outcomes. Future randomized controlled trials on the same topic, along with subsequent meta-analyses, are necessary for conclusive findings.

Abstract Background Posterior tibial slope (PTS) exhibits considerable variability among individuals and is anticipated to influence the accuracy of radiographic measurements related to the knee. Despite this potential impact, there is a lack of prior research investigating how PTS affects the accuracy of these measurements. Therefore, this study aimed to investigate the effect of PTS on the measurement reliability regarding the radiographic parameter of the knee. Methods The medical records of patients who took full-length anteroposterior radiographs of the lower limb between January 2020 and June 2022 were evaluated retrospectively. Radiographic parameters related to the knee joint characteristics such as osteoarthritis grade, hip-knee-ankle angle, weight-bearing line ratio, medial proximal tibial angle (MPTA), lateral distal femoral angle, joint-line convergence angle (JLCA), and PTS were measured. Subjects were classified into 3 groups according to PTS (group A, PTS

IntroductionVideo head-impulse tests (video-HITs) often fail to detect anterior inferior cerebellar artery (AICA) infarction due to peripheral and central vestibular system involvement. Anecdotal studies suggest that video-HITs may reveal bilateral impairment in AICA infarction. However, the diagnostic utility of video-HITs has not been established, particularly when compared to labyrinthitis, which accounts for the majority of acute audiovestibular syndrome (AAVS) cases.MethodsWe reviewed the medical records of consecutive patients presenting with new-onset acute hearing loss and spontaneous vertigo (i.e., AAVS) between March 2018 and July 2023 at a tertiary hospital in South Korea. Video-HIT patterns were categorized as follows: (1) ipsilaterally positive, (2) contralaterally positive, (3) bilaterally normal, and (4) bilaterally positive.ResultsTwenty-eight patients with AICA infarction (mean age±standard deviation = 67±15 years; 14 men) and 51 with labyrinthitis (63±17 years, 26 men) were included in the analyses. Among the 28 patients with AICA infarction, 15 presented with AAVS in isolation, without other co-morbid neurologic deficits (15/28, 54%). The vestibulo-ocular reflex (VOR) gains of ipsilesional horizontal canals (HCs) ranged from 0.21 to 1.22 (median = 0.81, interquartile range [IQR] = 0.50–0.89). However, those for contralateral HC gain ranged from 0.57 to 1.19 (median = 0.89 [IQR = 0.73–0.97]). Collectively, HITs were bilaterally positive in 13 patients (including 12 patients with bilaterally positive HITs for the horizontal canal), normal in eight, ipsilesionally positive in six, and contralesionally positive in one patient with AICA infarction. The VOR gains were typically decreased ipsilaterally in 28 (28/51, 55%), normal in 17 (17/51, 33%), and decreased bilaterally in six patients with labyrinthitis (6/51, 12%). Logistic regression analysis revealed that bilaterally positive HITs (p = 0.004) and multiple vascular risk factors (p = 0.043) were more frequently associated with AICA infarction than labyrinthitis.DiscussionAmong patients presenting with AAVS, bilaterally positive HITs can be indicative of AICA infarction in patients with multiple vascular risk factors.

Abstract This study compared cartilage regeneration outcomes in knee osteoarthritis (OA) using allogeneic human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation and microdrilling with high tibial osteotomy (HTO). Fifty-four patients (60 knees) were included: 24 (27 knees) in the hUCB-MSC group and 30 (33 knees) in the microdrilling group. Both groups showed significant improvements in pain and functional scores at 6, 12, and 24 months compared to baseline. At 24 months, the hUCB-MSC group had significantly improved scores. Arthroscopic assessment at 12 months revealed better cartilage healing in the hUCB-MSC group. In subgroup analysis according to the defect site, hUCB-MSC implantation showed superior cartilage healing for anterior lesions. In conclusion, both treatments demonstrated effectiveness for medial OA. However, hUCB-MSC implantation had better patient-reported outcomes and cartilage regeneration than microdrilling. The study suggests promising approaches for cartilage restoration in large knee defects due to OA.

Abstract Hair loss caused by malfunction of the hair follicle stem cells (HFSCs) and physical damage to the skin is difficult to recover from naturally. To overcome these obstacles to hair follicle (HF) regeneration, it is essential to understand the three-dimensional (3D) microenvironment and interactions of various cells within the HFs. Therefore, 3D cell culture technology has been used in HF regeneration research; specifically, multicellular spheroids have been generally adapted to mimic the 3D volumetric structure of the HF. In this study, we culture HF-derived cells, which are mainly composed of HFSCs, in the form of 3D spheroids using a microwell array and discuss the effects of the 3D cellular environment on HF morphogenesis by expression measurements of Sonic hedgehog signaling and stem cell markers in the HF spheroids. Additionally, the influences of microwell depth on HF spheroid formation and biological conditions were investigated. The biomolecular diffusion and convective flow in the microwell were predicted using computational fluid dynamics, which allows analysis of the physical stimulations occurring on the spheroid at the micro-scale. Although a simple experimental method using the microwell array was adopted in this study, the results provide fundamental insights into the physiological phenomena of HFs in the 3D microenvironment, and the numerical analysis is expected to shed light on the investigation of the geometric parameters of the microwell system.

IntroductionThe anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated.MethodsTo investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro, we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors. ResultsThe GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)‐13, IL-5, and IL‐4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase‐9 activity and protein levels. ConclusionGTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma.

Titanium dioxide nanoparticles (TiO2NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO2NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO2NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO2NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO2NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO2NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO2NP-induced pulmonary toxicity.

Among the graft options for anterior cruciate ligament reconstruction (ACLR), hamstring autografts are widely regarded as the preferred choice for primary ACLR among orthopedic surgeons worldwide. However, concerns persist regarding postoperative knee flexor weakness. We aimed to compare knee extensor and flexor strengths between hamstring autograft and tibialis anterior allograft groups in ACLR patients, who were propensity score-matched based on baseline characteristics. A retrospective analysis included 58 matched pairs who underwent isokinetic strength tests at 6 and 12 months post operation. Isokinetic muscle strength tests found no significant difference in knee extensor and flexor strength at 6 months post operation between the hamstring autograft and tibial anterior allograft groups. At 12 months, the hamstring autograft group exhibited significantly greater knee flexor deficit (total work and average power) compared to the allograft group, despite no differences in extensor strength or patient-reported outcomes. This study highlights the impact of hamstring autograft harvesting on muscle strength and recovery following ACLR in short-term period.

Abstract This study aimed to examine change in the graft bending angle (GBA) according to various knee flexion angles in creating femoral tunnel by the transportal technique in ACL reconstruction, and to reveal knee flexion angle minimizing GBA while maintaining stable femoral tunnel characteristics. Patients who underwent ACL reconstruction using the transportal technique between January 2017 and December 2018 were retrospectively reviewed. Patients were classified into three groups according to knee flexion angle when creating femoral tunnel (group 1:

Inhalation of polyhexamethylene guanidine phosphate (PHMG) can cause pulmonary fibrosis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are enzymes that produce reactive oxygen species, which may be involved in tissue damage in various lung diseases. To investigate whether the Nox2 isoform of Nox is involved in the progression of PHMG-induced lung damage, we studied the contribution of Nox2 in PHMG-induced lung injury in Nox2-deficient mice. We treated wild-type (WT) and Nox2 knockout mice with a single intratracheal instillation of 1.1 mg/kg PHMG and sacrificed them after 14 days. We analyzed lung histopathology and the number of total and differential cells in the bronchoalveolar lavage fluid. In addition, the expressions of cytokines, chemokines, and profibrogenic genes were analyzed in the lung tissues. Based on our results, Nox2-deficient mice showed less PHMG-induced pulmonary damage than WT mice, as indicated by parameters such as body weight, lung weight, total cell count, cytokine and chemokine levels, fibrogenic mediator expression, and histopathological findings. These findings suggest that Nox2 may have the potential to contribute to PHMG-induced lung injury and serves as an essential signaling molecule in the development of PHMG-induced pulmonary fibrosis by regulating the expression of profibrogenic genes.

Purpose: We investigated the efficacy and optimal dosage of recombinant Bacillus Calmette-Guérin-dltA (rBCG-dltA) in a high-throughput 3D bio-printed bladder cancer-on-a-chip (BCOC) and orthotopic bladder cancer mouse model. Materials and Methods: We fabricated high-throughput BCOC with microfluidic systems, enabling efficient drug screening. The efficacy of rBCG-dltA was evaluated using BCOC by the cell viability assay, monocyte migration assay, and measuring cytokine levels. The anti-tumor effect was compared using the orthotopic bladder cancer mouse model. Results: The cell proliferation rates of T24 and 253J bladder cancer cell lines (mean±standard error) were measured at three days after treatment. In T24 cell line, there was significantly decreased T24 cells compared to control at rBCG 1 multiplicity of infection (MOI) and 10 MOI (30 MOI: 63.1±6.4, 10 MOI: 47.4±5.2, 1 MOI: 50.5±7.5, control: 100.0±14.5, p

A ganglion cyst is a benign mass consisting of high-viscosity mucinous fluid. It can originate from the sheath of a tendon, peripheral nerve, or joint capsule. Compressive neuropathy caused by a ganglion cyst is rarely reported, with the majority of documented cases involving peroneal nerve palsy. To date, cases demonstrating both peroneal and tibial nerve palsies resulting from a ganglion cyst forming on a branch of the sciatic nerve have not been reported. In this paper, we present the case of a 74-year-old man visiting an outpatient clinic complaining of left-sided foot drop and sensory loss in the lower extremity, a lack of strength in his left leg, and a decrease in sensation in the leg for the past month without any history of trauma. Ankle dorsiflexion and great toe extension strength on the left side were Grade I. Ankle plantar flexion and great toe flexion were Grade II. We suspected peroneal and tibial nerve palsy and performed a screening ultrasound, which is inexpensive and rapid. In the operative field, several cysts were discovered, originating at the site where the sciatic nerve splits into peroneal and tibial nerves. After successful surgical decompression and a series of rehabilitation procedures, the patient’s neurological symptoms improved. There was no recurrence.

A method of preparing heated tobacco product aerosol condensate (HTPAC) was developed to expedite HTP toxicity evaluation, and the effectiveness was assessed. To prepare HTPAC, HTP aerosol was generated and collected using a Cambridge filter (particulate phase) and Dulbecco's phosphate buffered saline (DPBS; gaseous phase). The aerosol collected on the Cambridge filter was extracted using methanol, which was thereafter removed by nitrogen purging. The HTP aerosol residue was mixed with DPBS loaded with the collected HTP vapor, ultimately yielding HTPAC. Nicotine and formaldehyde, key harmful compounds in HTP aerosol, were detected in HTPAC (901 ± 224 and 22.2 ± 3.90 µg stick–1, respectively, comparable to those in HTP aerosol (990–1350 (nicotine) and 2.33–21.9 µg stick–1 (formaldehyde)). Propylene glycol and vegetable glycerin, which influence the amount of HTP aerosol, were detected at similar levels in HTPAC and HTP aerosol (propylene glycol = 616 ± 57.1 (HTPAC) and 320–630 µg stick–1 (aerosol) and vegetable glycerin = 2418 ± 224 (HTPAC) and 1667–4000 µg stick–1 (aerosol)). Known components of HTP aerosol (hydroxyacetone, acetic acid, triacetin, and 2-furanmethanol) were also detected in HTPAC. Consequently, HTPAC offers an effective method for concentrating harmful compounds found in HTP aerosols. This, in turn, facilitates comprehensive toxicity assessments, paving the way for guidelines ensuring the safe utilization of HTP.

BackgroundEducation years, as a measure of cognitive reserve, have been shown to affect the progression of Alzheimer’s disease (AD), both pathologically and clinically. However, inconsistent results have been reported regarding the association between years of education and intermediate structural changes in AD-vulnerable brain regions, particularly when AD risk factors were not considered during the preclinical phase.ObjectiveThis study aimed to examine how Aβ deposition and APOE ε4 carrier status moderate the relationship between years of education and cortical volume in AD-vulnerable regions among cognitively normal older adults.MethodsA total of 121 participants underwent structural MRI, [18F] flutemetamol PET-CT imaging, and neuropsychological battery assessment. Multiple regression analysis was conducted to examine the interaction between years of education and the effects of potential modifiers on cortical volume. The associations between cortical volume and neuropsychological performance were further explored in subgroups categorized based on AD risk factors.ResultsThe cortical volume of the left lateral occipital cortex and bilateral fusiform gyrus demonstrated a significant differential association with years of education, depending on the presence of Aβ deposition and APOE ε4 carrier status. Furthermore, a significant relationship between the cortical volume of the bilateral fusiform gyrus and AD-nonspecific cognitive function was predominantly observed in individuals without AD risk factors.ConclusionAD risk factors exerted varying influences on the association between years of education and cortical volume during the preclinical phase. Further investigations into the long-term implications of these findings would enhance our understanding of cognitive reserves in the preclinical stages of AD.

Abstract Background Conflicting results have been reported regarding the factors that can predict the discrepancy in the coronal alignment of the lower limb between radiographs taken in the standing and supine positions. Therefore, this study aimed to investigate factors that can predict discrepancies in the coronal alignment of the lower limb between radiographs taken in the standing and supine positions. Methods We retrospectively evaluated the medical records of patients who underwent full-length anteroposterior radiographs of the lower limb in both standing and supine positions between January 2019 and September 2021. The discrepancy in the coronal alignment of the lower limb between the standing and supine radiographs was defined as the absolute value of the difference in the hip-knee-ankle (HKA) angle between the two radiographs, which is presented as the ΔHKA angle. Correlation and regression analyses were performed to analyse the relationship among ΔHKA angle, demographic data, and several radiographic parameters. Results In total, 147 limbs (94 patients) were included in this study. The mean ΔHKA angle was 1.3 ± 1.1° (range, 0–6.5°). The ΔHKA angle was significantly correlated with body mass index and several radiographic parameters, including the HKA angle, joint line convergence angle, and osteoarthritis grade. Subsequent multiple linear regression analysis was performed using the radiographic parameters measured on the supine radiographs with the two separate models from the two observers, which revealed that body mass index and advanced osteoarthritis (Kellgren–Lawrence grades 3 and 4) had a positive correlation with the ΔHKA angle. Conclusions Body mass index and advanced osteoarthritis affected the discrepancy in the coronal alignment of the lower limb between standing and supine radiographs. A discrepancy in the coronal alignment of the lower limb could be more prominent in patients with an increased body mass index and advanced osteoarthritis, corresponding to Kellgren-Lawrence grades 3 and 4.

Abstract In performing medial open-wedge high tibial osteotomy, it is recommended not to alter the posterior tibial slope. However, it remains unclear whether the osteotomy inclination angle affects the posterior tibial slope in the sagittal plane. This study aimed to verify how anterior or posterior osteotomy inclination angle affects the tendency of change in the posterior tibial slope and to conduct quantitative analysis of the extent to which the posterior tibial slope changes according to the degree of the osteotomy inclination angle change in MOWHTO. Computed tomography images of 30 patients who underwent MOWHTO were collected. Three-dimensional models of preoperative original tibia were reconstructed, and virtual osteotomies were performed. The sagittal osteotomy inclination angles formed by the osteotomy line and the medial tibial plateau line were classified as positive in case of anteriorly inclined osteotomy and negative in case of posteriorly inclined osteotomy. Thirteen osteotomies were performed for each tibial model at intervals of 5° from − 30° to 30°. The posterior tibial slope was assessed, and the proportional relationship between the sagittal osteotomy inclination angle and the posterior tibial slope change was analyzed. The posterior tibial slope changed significantly after osteotomy (p

Abstract Background Given its similar structure and immune response to the human skin, porcine is a good model for dermal studies. Here, we sensitized ovalbumin (Ova) on minipig back skin for 2–4 weeks to induce chronic atopic dermatitis (AD). Results Gross observation, serum cytokine level, epidermal thickness, and epidermal integrity did not change after 4 weeks of Ova induction compared with the control, indicating AD modeling failure. Only the neutrophils in the blood and macrophages in bronchoalveolar lavage fluid changed slightly until 3 or 2 weeks after Ova sensitization, respectively. The successful and failed Ova-induced AD minipig models only differ in age and body weight of the minipigs. The minipigs, 12 months old with a 30-kg median weight, had a two-fold thicker dermis than minipigs 8–10 months old, with an 18.97-kg median weight, resulting in impaired Ova permeability and immune response. Conclusion Age and body weight are key factors that should be considered when developing an Ova-induced AD minipig model.

Purpose: The recombinant Bacillus Calmette–Guérin (BCG) containing the streptococcal inhibitor of the complement gene (rBCG-sic) may be more resistant to antimicrobial peptides and improve internalization; therefore, it can enhance the immunotherapeutic effect of the BCG. Here we determined the optimal dose of rBCG-sic and compared its effectiveness with that of BCG. Materials and Methods: We fabricated a high-throughput 3D-bioprinted bladder cancer-on-a-chip (BCOC) and used it to evaluate the effectiveness of the rBCG-sic in terms of cell viability, cell migration, and cytokine concentrations. Using an orthotopic mouse model, we evaluated its anticancer effect and toxicity via bioluminescence imaging. Results: T24 cell viability was decreased after treatment with rBCG-sic 30 multiplicities of infection (MOI) versus the same dosage of mock BCG (42.8%±6.4% vs. 75.7%±6.6%, p

Aircraft are exposed to cosmic radiation depending on their flight altitude and latitude. Therefore, flight attendants are exposed to radiation for long periods. In this study, a 0.3 mm thick fabric was designed with which to manufacture crew clothes to shield them against external exposure to space radiation, and the shielding performance was analyzed based on empirical experiments in a real environment. Gadolinium oxide, which has a high neutron reaction cross-section, and tungsten, which is useful for gamma-ray shielding, were proposed as the main raw materials for the shielding fabric, and the shielding performance was evaluated using detectors on Arctic flight routes. Composite (KG-01) and single (KG-02) shielding materials were used. In the case of KG-01, the transmission dose rate was 90.7 ± 5.6% compared with the unshielded case, showing an average space-radiation dose reduction of 9.3%. With KG-02, the transmission dose rate was 103.1 ± 2.0% compared with the unshielded case, and the average dose rate increased by 3.1%; therefore, there was no shielding effect against space radiation. Considering the statistical error of the environmental radiation at aircraft flight altitudes, KG-01 had a shielding effect of at least 5%; however, KG-02 yielded no significant shielding effects.

Accurate assessment of the response to the antiarrhythmic drug (AAD) in atrial fibrillation (AF) is crucial to achieve adequate rhythm control. We evaluated the effectiveness of extended cardiac monitoring using an adhesive ECG patch in the detection of drug-refractory paroxysmal AF. Patients diagnosed with paroxysmal AF and receiving AAD therapy were enrolled. The subjects simultaneously underwent 11-day adhesive ECG patch monitoring and a 24-h Holter test. The primary study outcome was a detection rate of drug-refractory AF or atrial tachycardia (AT) lasting ≥30 s. A total of 59 patients were enrolled and completed the study examinations. AF or AT was detected in 28 (47.5%) patients by an 11-day ECG patch monitor and in 8 (13.6%) patients by a 24-h Holter test (p < 0.001). The 11-day ECG patch monitor identified an additional 20 patients (33.8%) with drug-refractory AF not detected by the 24-h Holter, and as a result, the treatment plan was changed in 11 patients (10 catheter ablations, one medication change). In conclusion, extended cardiac rhythm monitoring using an adhesive ECG patch in patients with paroxysmal AF under AAD therapy led to over a threefold higher detection of drug-refractory AF episodes, compared to the 24-h Holter test.

Probiotics, including Lacticaseibacillus rhamnosus (L. rhamnosus), have gained recognition for their potential health benefits, such as enhancing immune function, maintaining gut health, and improving nutrient absorption. This study investigated the effectiveness of L. rhamnosus LM1019 (LM1019) in enhancing immune function. In RAW 264.7 cells, LM1019 demonstrated dose-dependent immune stimulation by increasing nitric oxide production, gene expression of proinflammatory cytokines, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These effects were mediated through the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) translocation without inducing cytotoxicity. Furthermore, orally administered LM1019 was evaluated in immunosuppressed mice induced by cyclophosphamide (CTX). High-dose administration of LM1019 significantly increased the subpopulations of lymphocytes, specifically helper T cells (CD4+), as well as two subtypes of natural killer (NK) cells, namely, IFN-γ+ and granzyme B+ NK cells. Additionally, LM1019 at a high dose led to elevated levels of proinflammatory cytokines, including IFN-γ and IL-12, compared to CTX-treated mice. These findings highlight the potential of LM1019 in enhancing the immune system. The study contributes to the growing body of research on the beneficial effects of probiotics on immune function.

Abstract This study aimed to analyze the reproducibility and reliability of the alignment parameters measured using the EOS image system in both limbs while standing with an even weight-bearing posture. Overall, 104 lower extremities in 52 patients were analyzed retrospectively. The patients stood with an even load over both lower extremities then rotated 15° in both directions. Two EOS images were acquired and 104 pairs of lower extremities were compared according to the position of the indexed lower extremities. Then, the inter-observer reliability of the EOS system and the inter-modality reliability between EOS and computed tomography (CT) were evaluated. Femoro-tibial rotation (FTR) and tibial torsion demonstrated a significant difference between the anterior and posterior positions of the indexed lower extremity. In the inter-observer reliability analysis, all values except for FTR and tibial torsion demonstrated good or very good reliability. In the anterior position, FTR demonstrated moderate, and tibial torsion demonstrated poor reliability. In the posterior position, both FTR and tibial torsion demonstrated poor reliability. In the reliability analysis between the three-dimensional (3D) EOS model and 3D CT images, all measurements of the femur demonstrated very good reliability, but measurements of the tibia did not. For the coronal and sagittal alignment parameters measured by the EOS 3D system with rotated standing posture, except for the measurement including tibial torsion., there were no significant difference for either position of the indexed extremities with high agreement between the observers as well as with the CT 3D model.

Medial meniscus posterior root tears (MMRTs), defined as tears or avulsions that occur within 1 cm of the tibial attachment of the medial meniscus posterior root, lead to biomechanically detrimental knee conditions by creating a functionally meniscal-deficient status. Given their biomechanical significance, MMRTs have recently been gaining increasing interest. Accordingly, numerous studies have been conducted on the anatomy, biomechanics, clinical features, diagnosis, and treatment of MMRTs, and extensive knowledge has been accumulated. Although a consensus has not yet been reached on several issues, such as surgical indications, surgical techniques, and rehabilitation protocols, this article aimed to comprehensively review the current knowledge on MMRTs and to introduce the author’s treatment strategies.

In this study, a post-weld heat treatment (PWHT) was proposed at high temperatures of 600 °C, 750 °C, and 900 °C for 30 min to significantly improve the impact absorbed energy of high manganese steel weld metal. Electron backscatter diffraction (EBSD), electron probe microanalysis (EPMA), and high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) were employed to characterize the production and study the deformation mechanisms in the high manganese steel weld metal. The impact absorbed energy is divided into crack initiation energy and crack propagation energy, which are divided by the value of Pmax. The cryogenic impact absorbed energy was 81 J. After PWHT at 600 °C, 750 °C, and 900 °C, it was 75 J, 69 J, and 88 J, respectively. The impact absorbed energies did not follow a proportional relationship with the PWHT temperatures. The increase in impact absorbed energy can be attributed to the narrowing of the dendritic region, which blocks the crack propagation path and efficiently prevents crack propagation. Conversely, the decrease in impact absorbed energy can be attributed to the presence of 100-nm-sized (Cr, Mn)23C6-type carbides at the grain boundaries, which facilitate crack propagation.

Abstract Background Nonhuman primates (NHPs) are superior model for ocular research due to its morphological and physiological similarities with humans. Thus, the effect of four different anesthetic combinations [ketamine (10 mg/kg), ketamine + xylazine (7 + 0.6 mg/kg), zoletil (4 mg/kg), and zoletil + xylazine (4 + 0.2 mg/kg)] on intraocular pressure (IOP) was determined in cynomolgus monkeys. Results The administration of ketamine + xylazine or zoletil + xylazine resulted in lower IOP compared to ketamine or zoletil alone. Moreover, the IOP in male monkeys was higher than in females. The difference between the right and left eye was not found. Conclusions Anesthetics affected the IOP, and gender differences should be considered when measuring the IOP of nonhuman primates (NHPs).

The present safety pharmacology core battery studies (neurobehavior, respiratory, cardiovascular system, and human ether a-go-go (hERG) channel current) investigated the potential harmful effects of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG). The SAMiRNA-AREG was administered by single intravenous injection at up to 300 mg/kg and 100 mg/kg in mice and monkeys, respectively. The hERG assay was performed in Chinese hamster ovary (CHO) cells at SAMiRNA-AREG concentrations of up to 200 μg/mL. In the evaluation on neurobehavior, a transient decrease in body temperature was found at 0.5 h (30 min) post-dose at both sexes in mice, with a single 300 mg/kg dose of SAMiRNA-AREG. However, these effects had returned to normal at 1 h post-dose. In the evaluation on hERG channel current, there were statistically significant differences in the inhibition of peak hERG potassium channel current between the 20, 100, and 200 μg/mL SAMiRNA-AREG treatment groups and the vehicle control group. However, these effects were less potent than that of E-4031, a positive control article. For the respiratory and cardiovascular systems, no treatment-related changes were observed in mice or monkeys. Thus, under these experimental conditions, these studies suggest that SAMiRNA-AREG showed no adverse effects on the neurobehavior, respiratory, and cardiovascular function.

Abstract Background and Objectives The efficacy of radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) is well established. The standard approach to RFCA in AF is pulmonary vein isolation (PVI). However, a large proportion of patients experiences recurrence of atrial tachyarrhythmia. The purpose of this study is to find out whether the AI model can assess AF recurrence in patients who underwent PVI. Materials and methods This study was a retrospective cohort study that enrolled consecutive patients who underwent catheter ablation for symptomatic, drug-refractory AF and PVI. We developed an AI algorithm to predict recurrence of AF after PVI using patient demographics and three-dimensional (3D) reconstructed left atrium (LA) images. Results We included 527 consecutive patients in the study. The overall mean LA diameter was 42.0 ± 6.8 mm, and the mean LA volume calculated using 3D reconstructed images was 151.1 ± 46.7 ml. During the follow-up period, atrial tachyarrhythmia recurred in 158 patients. The area under the curve (AUC) of the AI model based on a convolutional neural network (including 3D reconstruction images) was 0.61 (95% confidence interval [CI] 0.53–0.74) using the test dataset. The total test accuracy was 66.3% (57.0–75.6), and the sensitivity was 53.3% (34.8–71.9). The specificity was 73.2% (51.8–75.0), and the F1 score was 52.5% 34.5–66.7). Conclusion In this study, we developed an AI algorithm to predict recurrence of AF after catheter ablation of PVI using individual reconstructed LA images. This AI model was unable to predict recurrence of AF overwhelmingly; therefore, further large-scale study is needed.

Abstract Background Although the measurement of coronal alignment of the lower limb on conventional full-length weight-bearing anteroposterior (FLWAP) radiographs was reported to be influenced by the knee joint rotation, no comparative analysis was performed considering the effects of knee joint rotation on the sagittal and axial planes simultaneously using the three-dimensional images while taking into account the actual weight-bearing conditions. The aim of this study was to investigate the effect of knee joint rotation on the measurement accuracy of coronal alignment of the lower limb on the FLWAP radiograph. Methods Radiographic images of 90 consecutive patients (180 lower limbs) who took both the FLWAP radiograph and the EOS image were retrospectively reviewed. The relationship among delta values of mechanical tibiofemoral angle (mTFA) between the FLWAP radiographs and the EOS images (ΔmTFA), knee flexion/extension angle (sagittal plane rotation) on the EOS images, and patellar rotation (axial plane rotation) on the FLWAP radiographs were analyzed. Further, subgroup analysis according to each direction of knee joint rotation was performed. Results There was a significant correlation between ΔmTFA and sagittal plane rotation (r = 0.368, P

We report a case of excessive QT prolongation and subsequent torsades de pointes (TdP) following the administration of ticagrelor in a 58-year-old male patient. The patient had no suspected cause of QT prolongation. After cessation of ticagrelor, QT interval was normalized and no further TdP was observed.

Abstract Background Although it has been known that medial open wedge high tibial osteotomy (MOWHTO) would adversely affect the patellofemoral joint, no previous study examined the surgical outcome of MOWHTO according to the preexisting cartilage status of the patellofemoral joint. The aim of this study was to investigate the effect of MOWHTO on the patellofemoral joint with regard to objective and subjective aspects according to the preexisting cartilage status. Methods Ninety-two patients who underwent MOWHTO and a following second-look arthroscopic assessment were included in this study. The patients were divided into two groups according to the preexisting cartilage status of the patellofemoral joint: group 1 (International Cartilage Repair Society [ICRS] grade 2 or 3) and group 2 (ICRS grade 0 or 1). Comparative analysis was performed regarding clinical scores, radiographic parameters, and arthroscopic measurements between the two groups. Results Clinical outcomes showed overall improvement from baseline to the time of second-look operation, with no significant difference between the two groups at each time point. There were no significant differences in radiographic parameters between the two groups. Radiographic grade of patellofemoral osteoarthritis in both groups showed a tendency to progress, without statistical significance. In arthroscopic assessment, the size of the cartilage lesion on the patellofemoral joint increased with time in both groups (P = 0.003), but the degree of change over time between the two groups was not statistically significant. Consistently, there was no significant difference in the frequency of progression of cartilage lesion grade in the patellofemoral joint between the two groups. Conclusions MOWHTO would contribute to osteoarthritis progression of the patellofemoral joint regardless of the preexisting cartilage status, without an association with clinical outcomes in short-term follow-up.

Abstract Background and objectives The efficacy of dexmedetomidine for radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) has not been well established. We evaluated the efficacy and safety of sedation using dexmedetomidine with remifentanil compared to conventional sedative agents during RFCA for AF. Subjects and methods A total of 240 patients undergoing RFCA for AF were randomized to either the dexmedetomidine (DEX) group (continuous infusion of dexmedetomidine and remifentanil) or the midazolam (MID) group (intermittent injections of midazolam and fentanyl) according to sedative agents. Non-invasive positive pressure ventilation was applied to all patients during the procedure. The primary outcome was patient movement during the procedure resulting in a 3D mapping system discordance, and the secondary outcome was adverse events including respiratory or hemodynamic compromise. Results During AF ablation, the incidence of the primary outcome was significantly reduced for the DEX group (18.2% vs. 39.5% in the DEX and the MID groups, respectively, p

Abstract Fascicular premature ventricular contractions (PVCs) can arise from anywhere in the His Purkinje system, but PVCs originating from the left bundle branch (LBB) are rarely reported. We report the case of PVC arising from the LBB, and also describe the electrophysiological features that might indicate the bracketing of the fascicular PVC focus.

Few reports have described direct fixation of the Chaput tubercle; screw fixation is usually employed. Herein, we introduce a novel technique for Chaput tubercle fixation using tension-band wiring. This technique is applicable to fractured tubercles of various sizes and has the advantage that the fragment breakage that may occur during screw fixation is impossible. In addition, our technique increases fixation strength.

Traumatic and degenerative lesions of articular cartilage usually progress to osteoarthritis (OA), a leading cause of disability in humans. MicroRNAs (miRNAs) can regulate the differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) and play important roles in the expression of genes related to OA. However, their functional roles in OA remain poorly understood. Here, we have examined miR-449a, which targets sirtuin 1 (SIRT1) and lymphoid enhancer-binding factor-1 (LEF-1), and observed its effects on damaged cartilage. The levels of chondrogenic markers and miR-449a target genes increased during chondrogenesis in anti-miR-449a-transfected hBMSCs. A locked nucleic acid (LNA)-anti-miR-449a increased cartilage regeneration and expression of type II collagen and aggrecan on the regenerated cartilage surface in acute defect and OA models. Furthermore, intra-articular injection of LNA-anti-miR-449a prevented disease progression in the OA model. Our study indicates that miR-449a may be a novel potential therapeutic target for age-related joint diseases like OA. Keywords: human mesenchymal stem cell, osteoarthritis, microRNA, miR-449a, cartilage regeneration

A 48-year-old female patient underwent a heart transplantation for acute fulminant myocarditis, following heterologous vaccination with the ChAdOx1 nCoV-19 and Pfizer-BioNTech COVID-19. She had no history of severe acute respiratory syndrome coronavirus-2 infection. She did not exhibit clinical signs or have laboratory findings of concomitant infection before or after vaccination. Heart transplantation was performed because her heart failed to recover with venoarterial extracorporeal oxygenation support. Organ autopsy revealed giant cell myocarditis, possibly related to the vaccines. Clinicians may have to consider the possibility of the development of giant cell myocarditis, especially in patients with rapidly deteriorating cardiac function and myocarditis symptoms after COVID-19 vaccination.

IntroductionAt present, information about clinical efficacy and adverse events of controlled release (CR) form of pelubiprofen, a prodrug of 2-arylopropionic acid with relatively selective effects on cyclooxygenase-2 activity, remains scarce. In this study, we sought to determine non-inferiority of pelubiprofen CR 90 mg/day compared to aceclofenac 200 mg/day regarding clinical efficacy and adverse events after a 4-week course of medication in the patients with symptomatic knee osteoarthritis.Materials and methodsA total of 191 patients were randomly assigned to take either pelubiprofen CR 90 mg (n = 95) or aceclofenac 200 mg (n = 96). The primary outcome variable was non-inferiority of pain reduction between baseline and week 4 when assessed using a 100 mm pain visual analogue scale (VAS). Pelubiprofen was considered non-inferior to aceclofenac if the upper limit of the one-sided 97.5% confidence interval for the difference in terms of pain VAS was above 15 mm (the average change of pain VAS in the pelubiprofen group-pain VAS reduction in the aceclofenac group). Secondary outcome variables were the changes in 100 mm pain VAS at week 2 versus baseline, K-Western Ontario, and McMaster University Arthritis Index (K-WOMAC) changes at weeks 2 and 4 as compared to baseline, patient global assessment at weeks 2 and 4. The frequency and amount of rescue medicine usage at weeks 2 and 4 were also evaluated as the secondary outcome variable. For safety analysis, adverse events, clinical laboratory tests, vital signs, and physical examinations were assessed and conducted at each follow-up visit.ResultsAt week 4, the pain VAS values were significantly reduced in both groups receiving either pelubiprofen CR 90 mg or aceclofenac 200 mg as compared to the baseline. However, the pelubiprofen group and the aceclofenac group respectively showed the pain VAS changes of -22 and -21.9 in the pre-protocol set and -20.8 and -21.7 in the full analysis set, confirming non-inferiority. The pelubiprofen CR 90 mg showed a reduced incidence of adverse events compared to the aceclofenac 200 mg (p = 0.005).ConclusionsPelubiprofen CR 90 mg is as effective as aceclofenac 200 mg with reduced adverse events for the treatment of symptomatic knee osteoarthritis.

All persons in self-driving vehicle would like to receive each service. To do it, the system has to know the person’s state from emotion or stress, and to know the person’s state, it has to catch by analyzing the person’s bio-information. In this paper, we propose a system for inferring emotion using EEG, pulse, blood pressure (systolic and diastolic blood pressure) of user, and recommending color and music according to emotional state of user for a user service in self-driving vehicle. The proposed system is designed to classify the four emotional information (stability, relaxation, tension, and excitement) by using EEG data to infer and classify emotional state according to user’s stress. SVM algorithm was used to classify bio information according to stress index using brain wave data of the fuzzy control system, pulse, and blood pressure data. When 80% of data were learned according to the ratio of training data by using the SVM algorithm to classify the EEG, blood pressure, and pulse rate databased on the biometric emotion information, the highest performance of 86.1% was shown. The bio-information classification system based on the stress index proposed in this paper will help to study the interaction between human and computer (HCI) in the 4th Industrial Revolution by classifying emotional color and emotional sound according to the emotion of the user it is expected.

ObjectiveCatheter ablation of persistent atrial fibrillation (AF) is still challenging, no optimal extra-pulmonary vein lesion set is known. We previously reported the clinical feasibility of computational modeling-guided AF catheter ablation.MethodsWe randomly assigned 118 patients with persistent AF (77.8% men, age 60.8 ± 9.9 years) to the computational modeling-guided ablation group (53 patients) and the empirical ablation group (55 patients) based on the operators’ experience. For virtual ablation, four virtual linear and one electrogram-guided lesion sets were tested on patient heart computed tomogram-based models, and the lesion set with the fastest termination time was reported to the operator in the modeling-guided ablation group. The primary outcome was freedom from atrial tachyarrhythmias lasting longer than 30 s after a single procedure.ResultsDuring 31.5 ± 9.4 months, virtual ablation procedures were available in 95.2% of the patients (108/118). Clinical recurrence rate was significantly lower after a modeling-guided ablation than after an empirical ablation (20.8 vs. 40.0%, log-rank p = 0.042). Modeling-guided ablation was independently associated with a better long-term rhythm outcome of persistent AF ablation (HR = 0.29 [0.12–0.69], p = 0.005). The rhythm outcome of the modeling-guided ablation showed better trends in males, non-obese patients with a less remodeled atrium (left atrial dimension < 50 mm), ejection fraction ≥ 50%, and those without hypertension or diabetes (p < 0.01). There were no significant differences between the groups for the total procedure time (p = 0.403), ablation time (p = 0.510), and major complication rate (p = 0.900).ConclusionAmong patients with persistent AF, the computational modeling-guided ablation was superior to the empirical catheter ablation regarding the rhythm outcome.Clinical Trial RegistrationThis study was registered with the ClinicalTrials.gov, number NCT02171364.

Cardiac arrhythmias are a common problem in the neurological intensive care unit and represent a major cause of ischemic stroke. Significant arrhythmias are most likely to occur in elderly patients. In this review, we focus on three arrhythmias: premature beats, atrial fibrillation, and QT prolongation. The goal of this review is to provide a current concept of diagnosis and acute management of arrhythmias in the neurological intensive care unit.

In a previous study, we found that Lactobacillus curvatus HY7602-fermented antler (FA) improved exercise endurance by increasement of muscle mass and strength in a young mouse model. In this study, we investigated the effect of FA on recovery of muscle mass and strength in aging-induced muscle loss. We have used a middle-aged model in which muscle decline begins in many mammalian species. All mice performed treadmill exercise and forced swimming, and measured muscle grip strength. Then, calf muscle weight and histological analysis, blood biomarker and gene expression in soleus muscle tissue were measured. Muscle strength and forced swimming time were significantly increased in the FA-intake groups compared to controls. The levels of muscle and liver damage-related indicators (ATL, ALP, LDH and CK) and muscle endurance, fatigue and exercise performance-related indicators (lactate and creatinine) were significantly improved by FA supplementation. In addition, FA regulates genes related to muscle protein degradation (Atrogin-1 and MuRF1) and muscle fiber synthesis (MyoD and Myf5), resulting in increased muscle mass, and fiber diameter and area values. The Bax/Bcl-2 ratio, related to apoptosis in skeletal muscle was significantly decreased. These results demonstrate that FA improves exercise performance with ameliorating blood biomarkers and also increases muscle mass and muscle strength by inhibiting muscle proteolysis and promoting muscle synthesis in a middle-aged mouse.

In this study, we investigated whether antler fermented with lactic acid bacteria (LAB) increases mitochondrial biogenesis and muscle strength in vitro and in vivo. LAB from a strain library were grown in antler extract agar at the Yakult Central Research Institute of Korea. Isolated LAB, named Lactobacillus curvatus HY7602, were used to ferment antlers. Analysis of the effects of fermented antler (FA) revealed that it enhanced the insulin-like growth factor 1 (IGF-I), signaling pathway and mitochondrial metabolic activity in mouse skeletal myotube (C2C12) cells. Next, we evaluated the effect of non-fermented antler (NFA) and FA on exercise performance in C57BL/6J mice. The results showed that HY7602-FA increased treadmill exercise capacity and forced swimming endurance. Furthermore, blood markers associated with muscle fatigue, endurance, and energy supply (e.g., alanine aminotransferase, lactate dehydrogenase, creatinine, creatine kinase, and lactate) in the FA-intake group were lower than in the NFA-intake group. In addition, the expression index of genes associated with muscle protein synthesis, and with mitochondrial energy production and supply, in muscle tissue was remarkably higher in the FA group than in the control and NFA groups. Taken together, these results suggested that HY7602-FA may be an effective functional food and health supplement.

Abstract This study investigated the protective effects of diallyl disulfide (DADS) against acetaminophen (AAP)-induced acute renal injury in male rats. We also investigated the effects of DADS on kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NCAL), which are novel biomarkers of nephrotoxicity in renal tissues, in response to AAP treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) AAP (1,000 mg/kg), (3) AAP&DADS, and (4) DADS (50 mg/kg/day). AAP treatment caused acute kidney injury evidenced by increased serum blood urea nitrogen (BUN) levels and histopathological alterations. Additionally, Western blot and immunohistochemistry analysis showed increased expression of KIM-1 and NCAL proteins in renal tissues of AAP-treated rats. In contrast, DADS pretreatment significantly attenuated the AAP-induced nephrotoxic effects, including serum BUN level and expression of KIM-1 and NCAL proteins. Histopathological studies confirmed the renoprotective effect of DADS. The results suggest that DADS prevents AAP-induced acute nephrotoxicity, and that KIM-1 and NCAL may be useful biomarkers for the detection and monitoring of acute kidney injury associated with AAP exposure.

Posterolateral corner (PLC) structures of the knee joint comprise complex anatomical soft tissues that support static and dynamic functional movements of the knee. Most previous studies analyzed posterolateral stability in vitro under static loading conditions. This study aimed to evaluate the contributions of the lateral (fibular) collateral ligament (LCL), popliteofibular ligament (PFL), and popliteus tendon (PT) to cruciate ligament forces under simulated dynamic loading conditions by using selective individual resection. We combined medical imaging and motion capture of healthy subjects (four males and one female) to develop subject-specific knee models that simulated the 12 degrees of freedom of tibiofemoral and patellofemoral joint behaviors. These computational models were validated by comparing electromyographic (EMG) data with muscle activation data and were based on previous experimental studies. A rigid multi-body dynamics simulation using a lower extremity musculoskeletal model was performed to incorporate intact and selective resection of ligaments, based on a novel force-dependent kinematics method, during gait (walking) and squatting. Deficiency of the PLC structures resulted in increased loading on the posterior cruciate ligament and anterior cruciate ligament. Among PLC structures, the PT is the most influential on cruciate ligament forces under dynamic loading conditions.

Emotion information represents a user’s current emotional state and can be used in a variety of applications, such as cultural content services that recommend music according to user emotional states and user emotion monitoring. To increase user satisfaction, recommendation methods must understand and reflect user characteristics and circumstances, such as individual preferences and emotions. However, most recommendation methods do not reflect such characteristics accurately and are unable to increase user satisfaction. In this paper, six human emotions (neutral, happy, sad, angry, surprised, and bored) are broadly defined to consider user speech emotion information and recommend matching content. The “genetic algorithms as a feature selection method” (GAFS) algorithm was used to classify normalized speech according to speech emotion information. We used a support vector machine (SVM) algorithm and selected an optimal kernel function for recognizing the six target emotions. Performance evaluation results for each kernel function revealed that the radial basis function (RBF) kernel function yielded the highest emotion recognition accuracy of 86.98%. Additionally, content data (images and music) were classified based on emotion information using factor analysis, correspondence analysis, and Euclidean distance. Finally, speech information that was classified based on emotions and emotion information that was recognized through a collaborative filtering technique were used to predict user emotional preferences and recommend content that matched user emotions in a mobile application.