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Abstract Antiferromagnets have attracted significant attention in the field of magnonics, as promising candidates for ultralow-energy carriers for information transfer for future computing. The role of crystalline orientation distribution on magnon transport has received very little attention. In multiferroics such as BiFeO3 the coupling between antiferromagnetic and polar order imposes yet another boundary condition on spin transport. Thus, understanding the fundamentals of spin transport in such systems requires a single domain, a single crystal. We show that through Lanthanum (La) substitution, a single ferroelectric domain can be engineered with a stable, single-variant spin cycloid, controllable by an electric field. The spin transport in such a single domain displays a strong anisotropy, arising from the underlying spin cycloid lattice. Our work shows a pathway to understanding the fundamental origins of magnon transport in such a single domain multiferroic.

Neutrophils as first line defender initiate a cascade of healing process immediately after muscle injury. At muscle injury site, neutrophils remove damaged muscle fibers and recruit other immune cells and these functions show in mature neutrophils. In the previous study, physical exercise can mediate neutrophils’ functional changes such as phagocytosis and chemotaxis, though there is no research on how exercise-induced neutrophils contribute the muscle regeneration.In this present study, we investigated the maturation of neutrophils after 4 weeks of mouse treadmill exercise and assessed wound healing assay to evaluate whether treatment with exercise-activated neutrophils is effective for skeletal muscle repair in vitro. In the exercise group, significantly higher mRNA levels of maturation markers compared to the sedentary group and exercise-activated neutrophils improved wound healing of mouse muscle cells.To confirm at the human cell level, based on the well-known fact that exercise increases circulating cortisol levels, neutrophil-like cells were treated with dexamethasone (dHL60 + dex) as exercise mimetics. dHL60 + dex had significantly higher mRNA levels of neutrophil maturation marker and improved wound healing of human skeletal muscle cells compared to the control. These findings suggest that exercise affects neutrophil maturation and that exercise-induced neutrophils contribute to skeletal muscle repair in vitro.

Abstract Bismuth ferrite has garnered considerable attention as a promising candidate for magnetoelectric spin-orbit coupled logic-in-memory. As model systems, epitaxial BiFeO3 thin films have typically been deposited at relatively high temperatures (650–800 °C), higher than allowed for direct integration with silicon-CMOS platforms. Here, we circumvent this problem by growing lanthanum-substituted BiFeO3 at 450 °C (which is reasonably compatible with silicon-CMOS integration) on epitaxial BaPb0.75Bi0.25O3 electrodes. Notwithstanding the large lattice mismatch between the La-BiFeO3, BaPb0.75Bi0.25O3, and SrTiO3 (001) substrates, all the layers in the heterostructures are well ordered with a [001] texture. Polarization mapping using atomic resolution STEM imaging and vector mapping established the short-range polarization ordering in the low temperature grown La-BiFeO3. Current-voltage, pulsed-switching, fatigue, and retention measurements follow the characteristic behavior of high-temperature grown La-BiFeO3, where SrRuO3 typically serves as the metallic electrode. These results provide a possible route for realizing epitaxial multiferroics on complex-oxide buffer layers at low temperatures and opens the door for potential silicon-CMOS integration.

Abstract Background We examined the incidence and predictors of clinical outcomes in metabolic dysfunction‐associated fatty liver disease (MAFLD), focusing on anthropometric parameters. Methods Adult patients with MAFLD were identified in nationwide databases and a hospital cohort. Primary endpoints were atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis. Logistic and Cox regression analyses were used to analyse the association between anthropometric parameters and endpoints. Results In total, 4407 of 15 256 (28.9%) and 6274 of 25 784 subjects (24.3%) had MAFLD in the nationwide database; of these, 403 (9.2%) and 437 (7.0%) subjects were of lean/normal weight, respectively. Compared to the overweight/obese group, the lean/normal weight group had a significantly lower muscle mass (15.0 vs. 18.9 kg) and handgrip strength (31.9 vs. 35.1 kg) and had a higher ASCVD risk (9.0% vs. 6.3% and 15.9% vs. 8.5%; Ps

Abstract Dysphagia is a fatal condition after acute stroke. We established machine learning (ML) models for screening aspiration in patients with acute stroke. This retrospective study enrolled patients with acute stroke admitted to a cerebrovascular specialty hospital between January 2016 and June 2022. A videofluoroscopic swallowing study (VFSS) confirmed aspiration. We evaluated the Gugging Swallowing Screen (GUSS), an early assessment tool for dysphagia, in all patients and compared its predictive value with ML models. Following ML algorithms were applied: regularized logistic regressions (ridge, lasso, and elastic net), random forest, extreme gradient boosting, support vector machines, k-nearest neighbors, and naïve Bayes. We finally analyzed data from 3408 patients, and 448 of them had aspiration on VFSS. The GUSS showed an area under the receiver operating characteristics curve (AUROC) of 0.79 (0.77–0.81). The ridge regression model was the best model among all ML models, with an AUROC of 0.81 (0.76–0.86), an F1 measure of 0.45. Regularized logistic regression models exhibited higher sensitivity (0.66–0.72) than the GUSS (0.64). Feature importance analyses revealed that the modified Rankin scale was the most important feature of ML performance. The proposed ML prediction models are valid and practical for screening aspiration in patients with acute stroke.

Although granule cell dispersion (GCD) in the hippocampus is known to be an important feature associated with epileptic seizures in temporal lobe epilepsy (TLE), the endogenous molecules that regulate GCD are largely unknown. In the present study, we have examined whether there is any change in AEG-1 expression in the hippocampus of a kainic acid (KA)-induced mouse model of TLE. In addition, we have investigated whether the modulation of astrocyte elevated gene-1 (AEG-1) expression in the dentate gyrus (DG) by intracranial injection of adeno-associated virus 1 (AAV1) influences pathological phenotypes such as GCD formation and seizure susceptibility in a KA-treated mouse. We have identified that the protein expression of AEG-1 is upregulated in the DG of a KA-induced mouse model of TLE. We further demonstrated that AEG-1 upregulation by AAV1 delivery in the DG-induced anticonvulsant activities such as the delay of seizure onset and inhibition of spontaneous recurrent seizures (SRS) through GCD suppression in the mouse model of TLE, while the inhibition of AEG-1 expression increased susceptibility to seizures. The present observations suggest that AEG-1 is a potent regulator of GCD formation and seizure development associated with TLE, and the significant induction of AEG-1 in the DG may have therapeutic potential against epilepsy.

Glaucoma is an irreversible ocular disease that may lead to vision loss. Here the authors develop a theranostic smart contact lens with an intraocular pressure sensor, a flexible drug delivery system, wireless power and communication systems and an application specific integrated circuit chip for both monitoring and control of intraocular pressure in glaucoma induced rabbits.

Abstract Background Endothelial cells (ECs) in cerebral vessels are considered the primary targets in acute hemorrhagic brain injuries. EC dysfunction can aggravate neuronal injuries by causing secondary inflammatory responses and blood–brain barrier (BBB) disruption. Previous studies have reported that enhancement of mitochondrial function within ECs may reduce BBB disruption and decrease the severity of acute brain injuries. However, the molecular signaling pathways through which enhanced EC mitochondrial function is enhanced to exert this BBB protective effect have not been fully elucidated. Methods To identify signaling pathways involved in linking EC-specific mitochondrial dysfunction and BBB disruption, we first performed RNA sequencing using isolated cerebral vessels from TEKCRIF1 KO mice, a mouse strain that displays EC-specific mitochondrial dysfunction. After identification, we assessed the significance of candidate signaling pathways using an intracerebral hemorrhage (ICH) mouse model. BBB integrity was assessed using an IgG leakage assay, and symptomatic changes were evaluated using behavioral assays. Results Transcriptome analyses of the TEKCRIF1 KO mouse revealed significant changes in Notch1 signaling, a pathway intimately involved in BBB maintenance. We also observed a decrease in Notch1 signaling and expression of the mitochondrial oxidative phosphorylation (OxPhos) complex in the ICH mouse model, which also exhibits BBB disruption. To further assess the function of Notch1 signaling in relation to BBB disruption, we injected ICH model mice with adropin, a protein that interacts with the Notch1 ligand NB-3 and activates Notch1 signaling. We found that adropin prevented BBB disruption and reduced the extent (area) of the injury compared with that in vehicle controls, in association with alteration of mitochondrial function. Conclusion These results suggest that the Notch1 signaling pathway acts as an upstream regulator of DEGs and can be a target to regulate the changes involved with endothelial mitochondrial dysfunction-dependent BBB disruption. Thus, treatment methods that activate Notch1 may be beneficial in acute brain injuries by protecting BBB integrity.

Abstract Ferroelectric (FE) capacitors exhibiting ultrahigh power densities are widely utilized as electrostatic energy storage devices in pulsed electronic devices. One approach to maximize the discharge energy density (Ud) of capacitors is to increase the breakdown strength (Eb) accompanied with high maximum polarization (Pm) while suppressing the energy loss. However, the inverse relationship between Eb and Pm challenges the simultaneous enhancement of Eb and Ud. To overcome this limitation, FE/relaxor FE (RFE) heterostructure capacitors composed of Co‐doped BaTiO3 (BTCO) and Sn‐doped BaTiO3 (BTS) epitaxial thin film layers to decouple the Eb and Pm values are fabricated and the simultaneous enhancement of the Eb and Ud up to 7.9 MV cm−1 and 117 J cm−3, respectively is achieved. The high Eb and Ud values can be attributed to the suppression of the leakage current at the BTCO/BTS interface, a narrower hysteresis loop contributed by the BTS, and high Pm and Eb from the BTCO layer. Additionally, the BTCO/BTS heterostructure capacitors exhibit excellent fatigue endurance of up to 108 cycles and are thermal stable even at 160 °C. Through properly designing the FE and RFE layers, thermally stable and reliable FE/RFE heterostructure capacitors exhibiting high Ud and Eb can be realized.

Self-propelling micro- and nano-motors (MNMs) have been extensively investigated as an emerging oral drug delivery carrier for gastrointestinal (GI) tract diseases. However, the propulsion of current MNMs reported so far is mostly based on the redox reaction of metals (such as Zn and Mg) with severe propulsion gas generation, remaining non-degradable residue in the GI tract. Here, we develop a bioinspired enzyme-powered biopolymer micromotor mimicking the mucin penetrating behavior of Helicobacter pylori in the stomach. It converts urea to ammonia and the subsequent increase of pH induces local gel-sol transition of the mucin layer facilitating the penetration into the stomach tissue layer. The successful fabrication of micromotors is confirmed by high-resolution transmission electron microscopy, electron energy loss spectroscopy, dynamic light scattering analysis, zeta-potential analysis. In acidic condition, the immobilized urease can efficiently converted urea to ammonia, comparable with that of neutral condition because of the increase of surrounding pH during propulsion. After administration into the stomach, the micromotors show enhanced penetration and prolonged retention in the stomach for 24 h. Furthermore, histological analysis shows that the micromotors are cleared within 3 days without causing any toxicity in the GI tract. The enhanced penetration and retention of the micromotors as an active oral delivery carrier in the stomach would be successfully harnessed for the treatment of various GI tract diseases.

Background: The surgical strategy for single-stage resection of primary colorectal cancer (CRC) and synchronous pulmonary metastases remains a matter of debate. Methods: Perioperative data of patients who underwent single-stage resection of primary CRC and synchronous pulmonary metastases were compared to those of patients who underwent 2-stage resections. The demographic data, number of metastases, type of pulmonary and colorectal resections, operation time, blood loss, postoperative complications, morbidities, mortality, medical costs, and length of hospital stay were analyzed. Results: Twenty-two patients underwent single-stage resection of primary CRC and pulmonary metastases, while 27 patients underwent 2-stage resection. Tumor size and the number of pulmonary metastases were not significantly different between the 2 groups. The extent of pulmonary metastasectomy and abdominal procedures were similar in both groups, as was the thoracic surgical approach (video-assisted thoracic surgery vs. thoracotomy). However, open laparotomy was performed more frequently in the 2-stage group than in the single-stage group (p=0.045), which also had a longer total anesthetic time (p=0.013). The operation time, medical costs, estimated blood loss, complication rates, and severity were similar in both groups, but the length of hospital stay was shorter in the single- stage group (p

BackgroundCopeptin has been reported as a predictive biomarker for the prognosis after traumatic brain injury (TBI). However, most of them were in patients with severe TBI and limited value in predicting outcomes in patients with moderate TBI defined as Glasgow Coma Scale (GCS) score from 9 to 12. We aimed to investigate the predictive value of copeptin in assessing the neurologic outcome following moderate TBI.MethodsPatients were prospectively enrolled between May 2017 and November 2020. We consecutively measured plasma copeptin within 24 h after trauma, days 3, 5, and 7 using ELISA. The primary outcome was to correlate plasma copeptin levels with poor neurologic outcome at 6 months after moderate TBI. The secondary outcome was to compare the prognostic accuracy of copeptin and C-reactive protein (CRP) in assessing the outcome of patient.ResultsA total of 70 patients were included for the final analysis. The results showed that 29 patients (41.4%) experienced a poor neurologic outcome at 6 months. Multivariable logistic regression analysis revealed that increased copeptin (odds ration [OR] = 1.020, 95% CI: 1.005–1.036), GCS score of 9 or 10 (OR = 4.507, 95% CI: 1.266–16.047), and significant abnormal findings on CT (OR = 4.770; 95% CI: 1.133–20.076) were independent risk factors for poor outcomes. Consecutive plasma copeptin levels were significantly different according to outcomes (p < 0.001). Copeptin on day 7 exhibited better prognostic performance than CRP with an area under receiver operating characteristic curve (AUROC) difference of 0.179 (95% CI: 0.032–0.325) in predicting 6-month poor outcomes.ConclusionPlasma copeptin level can be a useful marker in predicting 6-month outcomes in patients with moderate TBI.

Abstract Dual-functional quantum-dots light emitting diodes (QLEDs) have been fabricated using solution processable vanadium oxide (V2O5) hole injection layer to control the carrier transport behavior. The device shows selectable functionalities of photo-detecting and light-emitting behaviors according to the different operating voltage conditions. The device emitted a bright green light at the wavelength of 536 nm, and with the maximum luminance of 31,668 cd/m2 in a forward bias of 8.6 V. Meanwhile, the device could operate as a photodetector in a reverse bias condition. The device was perfectly turned off in a reverse bias, while an increase of photocurrent was observed during the illumination of 520 nm wavelength light on the device. The interfacial electronic structure of the device prepared with different concentration V2O5 solution was measured in detail using x-ray and ultraviolet photoelectron spectroscopy. Both the highest occupied molecular orbital and the gap state levels were moved closer to the Fermi level, according to increase the concentration of V2O5 solution. The change of gap state position enables to fabricate a dual-functional QLEDs. Therefore, the device could operate both as a photodetector and as a light-emitting diode with different applied bias. The result suggests that QLEDs can be used as a photosensor and as a light-emitting diode for the future display industry.

BackgroundTo assess the association of haptoglobin (Hp) phenotype with neurological and cognitive outcomes in a large cohort of patients with subarachnoid hemorrhage (SAH).MethodsThis prospective multicenter study enrolled patients with aneurysmal SAH between May 2015 and September 2020. The Hp phenotype was confirmed via Western blots. The relative intensities of α1 in individuals carrying Hp2-1 were compared with those of albumin. Multivariable logistic and Cox proportional-hazard regression analyses were used to identify the risk factors for 6-month and long-term outcomes, respectively.ResultsA total of 336 patients including the phenotypes Hp1-1 (n = 31, 9.2%), Hp2-1 (n = 126, 37.5%), and Hp2-2 (n = 179, 53.3%) were analyzed. The Hp phenotype was closely associated with 6-month outcome (p = 0.001) and cognitive function (p = 0.013), and long-term outcome (p = 0.002) and cognitive function (p < 0.001). Compared with Hp1-1 as the reference value, Hp2-2 significantly increased the risk of 6-month poor outcome (OR: 7.868, 95% CI: 1.764–35.093) and cognitive impairment (OR: 8.056, 95% CI: 1.020–63.616), and long-term poor outcome (HR: 5.802, 95% CI: 1.795–18.754) and cognitive impairment (HR: 7.434, 95% CI: 2.264–24.409). Long-term cognitive impairment based on the Hp phenotype was significantly higher in patients under 65 years of age (p < 0.001) and female gender (p < 0.001). A lower relative α1/albumin intensity (OR: 0.010, 95% CI: 0.000–0.522) was associated with poor outcome at 6 months but not cognitive impairment in patients with SAH expressing Hp2-1.ConclusionHp2-2 increased the risk of poor neurological outcomes and cognitive impairment compared with Hp1-1. For Hp2-1, higher relative α1 intensities were related to 6-month favorable outcomes.

Abstract Background Renal tubulointerstitial fibrosis (TIF) plays an important role in the progression of chronic kidney disease (CKD) and its pathogenesis involves epithelial-to-mesenchymal transition (EMT) upon renal injury. Recombinant human erythropoietin (rhEPO) has been shown to display novel cytoprotective effects, in part by inhibiting transforming growth factor (TGF)-β1-induced EMT. Here, we evaluated the inhibitory effects of microparticles (MPs) derived from human EPO gene-transfected kidney mesenchymal stem cells (hEPO-KMSCs) against TGF-β1-induced EMT in Madin-Darby canine kidney (MDCK) cells and against TIF in mouse kidneys with unilateral ureteral obstruction (UUO). Methods EMT was induced in MDCK cells by treatment with TGF-β1 (5 ng/mL) for 48 h and then inhibited by co-treatment with rhEPO (100 IU/mL), mock gene-transfected KMSC-derived MPs (MOCK-MPs), or hEPO-KMSC-derived MPs (hEPO-MPs) for a further 48 h. UUO was induced in FVB/N mice, which were then treated with rhEPO (1000 IU/kg, intraperitoneally, every other day for 1 week), MOCK-MPs, or hEPO-MPs (80 μg, intravenously). Alpha-smooth muscle actin (α-SMA), fibronectin, and E-cadherin expression were evaluated in MDCK cells and kidney tissues, and the extent of TIF in UUO kidneys was assessed by immunohistochemical staining. Results TGF-β1 treatment significantly increased α-SMA and fibronectin expression in MDCK cells and decreased that of E-cadherin, while co-treatment with rhEPO, MOCK-MPs, or hEPO-MPs markedly attenuated these changes. In addition, rhEPO and hEPO-MP treatment effectively decreased phosphorylated Smad2 and Smad3, as well as phosphorylated p38 mitogen-activated protein kinase (MAPK) expression, suggesting that rhEPO and rhEPO-MPs can inhibit TGF-β1-induced EMT via both Smad and non-Smad pathways. rhEPO and hEPO-MP treatment also significantly attenuated the extent of renal TIF after 1 week of UUO compared to MOCK-MPs, with hEPO-MPs significantly reducing myofibroblast and F4/80+ macrophage infiltration as well as EMT marker expression in UUO renal tissues in a similar manner to rhEPO. Conclusions Our results demonstrate that hEPO-MPs modulate TGF-β1-induced EMT in MDCK cells via the Smad2, Smad3, and p38 MAPK pathways and significantly attenuated renal TIF in UUO kidneys.

Abstract Background For chronic kidney disease (CKD) patients, management of nutritional status is critical for delaying progression to end-stage renal disease. The purpose of this study is to provide the basis for personalized nutritional intervention in pre-dialysis patients by comparing the foods contributing to nutrients intake, nutritional status and potential dietary inflammation of CKD patients according to the diabetes mellitus (DM) comorbidity and CKD stage. Methods Two hundred fifty-six outpatients referred to the Department of Nephrology at SNUH from Feb 2016 to Jan 2017 were included. Subjects on dialysis and those who had undergone kidney transplantation were excluded. Bioelectrical impedance analysis (BIA), subjective global assessment (SGA), dietary intake, and biochemical parameters were collected. Subjects were classified into 4 groups according to DM comorbidity (DM or Non-DM) and CKD stage (Early or Late) by kidney function. Two-way analysis of variance and multinomial logistic regression analysis were performed for statistical analysis. Results Total number of malnourished patients was 31 (12.1%), and all of them were moderately malnourished according to SGA. The body mass index (BMI) of the DM-CKD group was significantly higher than the Non-DM-CKD group. The contribution of whole grains and legumes to protein intake in the DM-CKD group was greater than that in the Non-DM-CKD group. The DM- Early-CKD group consumed more whole grains and legumes compared with the Non-DM-Early-CKD group. The subjects in the lowest tertile for protein intake had lower phase angle, SGA score and serum albumin levels than those in the highest tertile. The potential for diet-induced inflammation did not differ among the groups. Conclusions Significant differences in intakes of whole grains and legumes between CKD patients with or without DM were observed. Since contribution of whole grains and legumes to phosphorus and potassium intake were significant, advice regarding whole grains and legumes may be needed in DM-CKD patients if phosphorus and potassium intake levels should be controlled. The nutritional status determined by BIA, SGA and serum albumin was found to be different depending on the protein intake. Understanding the characteristics of food sources can provide a basis for individualized nutritional intervention for CKD patients depending on the presence of diabetes.

Abstract Background Online haemodiafiltration (OL-HDF) may improve middle molecular clearance in contrast to conventional haemodialysis (HD). However, OL-HDF requires higher convective flows and cannot sufficiently remove large middle molecules. This study evaluated the efficacy of a medium cut-off (MCO) dialyser in removing large middle molecular uraemic toxins and compared it with that of conventional high-flux (HF) dialysers in HD and predilution OL-HDF. Methods Six clinically stable HD patients without residual renal function were investigated. Dialyser and treatment efficacies were examined during a single midweek treatment in three consecutive periods: 1) conventional HD using an HF dialyser, 2) OL-HDF using the same HF dialyser, and 3) conventional HD using an MCO dialyser. Treatment efficacy was assessed by calculating the reduction ratio (RR) for β2-microglobulin (β2M), myoglobin, κ and λ free light chains (FLCs), and fibroblast growth factor (FGF)-23 and measuring clearance for FLCs. Results All three treatments showed comparable RRs for urea, phosphate, creatinine, and uric acid. MCO HD showed greater RRs for myoglobin and λFLC than did HF HD and predilution OL-HDF (myoglobin: 63.1 ± 5.3% vs. 43.5 ± 8.9% and 49.8 ± 7.3%; λFLC: 43.2 ± 5.6% vs. 26.8 ± 4.4% and 33.0 ± 9.2%, respectively; P

Object. We aimed to investigate the association of Haptoglobin (Hp) phenotypes with perihematomal edema (PHE) and neurological outcomes after intracerebral hemorrhage (ICH). Methods. This prospective multicenter study enrolled patients that suffered ICH from March 2017 to February 2020. Hp phenotypes were determined using Western blotting; relative α1 intensity was calculated in patients with Hp2-1. A multivariable logistic regression analysis was then conducted to identify risk factors for increased relative PHE at 96 h and 3-month poor outcomes. Results. In total, 120 patients were ultimately enrolled: Hp1-1 (n = 15, 12.5%); Hp2-1 (n = 51, 42.5%); and Hp2-2 (n = 54, 45.0%). Hp phenotype was significantly associated with PHE (p = 0.028). With Hp1-1 as a reference value, Hp2-2 significantly increased the likelihood of increased rPHE (OR = 6.294, 95% CI: 1.283–30.881), while Hp2-1 did not (OR = 2.843, 95% CI: 0.566–14.284). Poor outcomes were found to be closely associated with hematoma volume at admission (OR = 1.057, 95% CI: 1.015–1.101) and surgical treatment (OR = 5.340, 95% CI: 1.665–17.122) but not Hp phenotypes (p = 0.190). Further, a high level of relative α1 intensity was identified to be significantly associated with decreased rPHE (OR = 0.020, 95% CI: 0.001–0.358). However, the relative α1 intensity was not associated with poor outcomes (OR = 0.057, 95% CI: 0.001–11.790). Conclusions: ICH patients with Hp2-2 exhibited a higher likelihood of increased rPHE than those with Hp1-1. Higher relative α1 intensities were identified to be closely associated with rPHE in patients with Hp2-1.

OBJECTIVE:Although sacrocolpopexy (SCP) can provide durable apical support, the use of mesh may give rise to various complications, including vaginal mesh erosion. The aim of this study was to identify the risk factors for vaginal mesh erosion after SCP in Korean women. METHODS:This retrospective cohort study included 363 women who underwent SCP with type 1 polypropylene mesh. They were evaluated at 1, 4, and 12 months after surgery and then annually thereafter with respect to anatomy and complications. Univariate and multivariate analyses using the Cox proportional hazard model were performed to identify the risk factors for mesh erosion. RESULTS:During the median 2-year follow-up period, vaginal mesh erosion was found in 29 women (8.0%). Among them, 19 (65.5%) required surgical correction. Estrogenic status was the only independent risk factor for mesh erosion. The risk for mesh erosion was 4.5 times higher in premenopausal women than in menopausal women not on estrogen replacement therapy (ERT) (95% confidence intervals [CI] 1.9-10.9, p

Abstract Background To measure the absorbed dose rate to water and penumbra of a Gamma Knife® (GK) using a polymethyl metacrylate (PMMA) phantom. Methods A multi-purpose PMMA phantom was developed to measure the absorbed dose rate to water and the dose distribution of a GK. The phantom consists of a hemispherical outer phantom, one exchangeable cylindrical chamber-hosting inner phantom, and two film-hosting inner phantoms. The radius of the phantom was determined considering the electron density of the PMMA such that it corresponds to 8 g/cm2 water depth, which is the reference depth of the absorbed dose measurement of GK. The absorbed dose rate to water was measured with a PTW TN31010 chamber, and the dose distributions were measured with radiochromic films at the calibration center of a patient positioning system of a GK Perfexion. A spherical water-filled phantom with the same water equivalent depth was constructed as a reference phantom. The dose rate to water and dose distributions at the center of a circular field delimited by a 16-mm collimator were measured with the PMMA phantom at six GK Perfexion sites. Results The radius of the PMMA phantom was determined to be 6.93 cm, corresponding to equivalent water depth of 8 g/cm2. The absorbed dose rate to water was measured with the PMMA phantom, the spherical water-filled phantom and a commercial solid water phantom. The measured dose rate with the PMMA phantom was 1.2% and 1.8% higher than those measured with the spherical water-filled phantom and the solid water phantom, respectively. These differences can be explained by the scattered photon contribution of PMMA off incoming 60Co gamma-rays to the dose rate. The average full width half maximum and penumbra values measured with the PMMA phantom showed reasonable agreement with two calculated values, one at the center of the PMMA phantom (LGP6.93) and other at the center of a water sphere with a radius of 8 cm (LGP8.0) given by Leksell Gamma Plan using the TMR10 algorithm. Conclusions A PMMA phantom constructed in this study to measure the absorbed dose rates to water and dose distributions of a GK represents an acceptable and practical alternative for GK dosimetry considering its cost-effectiveness and ease of handling.

BackgroundA growing body of evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of mast cells and glial cells, and production of inflammatory mediators in the peripheral and central nervous systems, plays an important role in the induction and maintenance of chronic pain. Palmitoylethanolamide (PEA), which is a type of N-acylethanolamide and a lipid, has an anti-inflammatory effect. Relative to the anti-inflammatory effect, little is known about its analgesic effect in chronic pain. This study aimed to determine whether PEA relieves chronic inflammatory and neuropathic pain.MethodsMale Sprague-Dawley rats were injured by transection of the left L5 and L6 spinal nerves to induce neuropathic pain or were injected with monoiodoacetic acid into the synovial cavity of knee joints to induce inflammatory pain. To assess the degree of pain, two kinds of stimuli - pressing von Frey filaments and wetting with acetone - were applied to the plantar surface of the rat to measure mechanical and cold sensitivity, respectively. Pain was measured by assessing behavioral responses, including paw withdrawal response threshold and paw withdrawal frequency upon stimulation.ResultsNeuropathic pain caused by spinal nerve transection (SNT) decreased the mechanical threshold and increased the frequency of response to acetone application. But, cold allodynia caused by SNT did not decrease the withdrawal frequency. Mechanical hyperalgesia caused by chronic inflammation was significantly reduced by both intraperitoneal and intra-articular injections of PEA.ConclusionsThese outcomes revealed that PEA might be effective in relieving inflammatory and neuropathic pain, especially pain induced by mechanical hyperalgesia, but not cold allodynia.

Weakly coupled ferroelectric/dielectric superlattice thin-film heterostructures exhibit complex nanoscale polarization configurations that arise from a balance of competing electrostatic, elastic, and domain-wall contributions to the free energy. A key feature of these configurations is that the polarization can locally have a significant component that is along the thin-film surface normal direction with an overall configuration maintaining zero net in-plane polarization. PbTiO_{3}/SrTiO_{3} thin-film superlattice heterostructures on a conducting SrRuO_{3} bottom electrode on SrTiO_{3} have a room-temperature stripe nanodomain pattern with a nanometer-scale lateral period. Ultrafast time-resolved x-ray free electron laser diffraction and scattering experiments reveal that above-bandgap optical pulses induce propagating acoustic pulses and a perturbation of the domain diffuse scattering intensity arising from the nanoscale stripe domain configuration. With 400-nm optical excitation, two separate acoustic pulses are observed: a high-amplitude pulse resulting from strong optical absorption in the bottom electrode and a weaker pulse arising from the depolarization-field-screening effect due to absorption directly within the superlattice. The picosecond scale variation of the nanodomain diffuse scattering intensity is consistent with a larger polarization change than would be expected due to the polarization-tetragonality coupling of uniformly polarized ferroelectrics. The polarization change is consistent, instead, with polarization rotation facilitated by the reorientation of the in-plane component of the polarization at the domain boundaries of the striped polarization structure. The complex steady-state configuration within these ferroelectric heterostructures leads to ultrafast polarization rotation phenomena that have previously been available only through the selection of bulk crystal composition.

BackgroundThe primary outcome of sugammadex reversal for rocuronium-induced neuromuscular block (NMB) is a train-of-four ratio (TOFR) of 0.9, not first twitch (T1) height. We investigated whether the recovery of TOFR or T1 differs based on the reversal of NMB with neostigmine or sugammadex.MethodsThe acceleromyographic responses from 0.6 mg/kg of rocuronium were monitored supramaximally in 80 patients after induction of anesthesia. The TOFR and T1 height were recorded, and saved in a personal computer using TOF-Watch SX Monitor software in all patients. Patients were randomly assigned to 2 groups to receive either neostigmine 50 µg/kg with glycopyrrolate 10 µg/kg (neostigmine group, n = 40) or sugammadex 2.0 mg/kg (sugammadex group, n = 40). The primary objective was to determine the difference of recovery time between TOFR to 0.9 and T1 to 0.9 after sugammadex or neostigmine administration during moderate rocuronium-induced NMB.ResultsThe recovery pattern of the TOFR 2 min after sugammadex administration was 1.0 or more, but that of T1 was less than 90% (T1 / control value) up to 6 min after drug was injected. The recovery pattern of TOFR and T1 was similar during the 20 min after reversal with neostigmine.ConclusionsIf you have not performed the T1 monitoring, both TOFR and T1 should be considered to confirm suitable recovery during the 6 min after reversal with sugammadex during rocuronium-induced moderate NMB.

Oxidative stress reflects an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense systems, and it can be associated with the pathogenesis and progression of neurodegenerative diseases such as multiple sclerosis, stroke, and Parkinson’s disease (PD). The application of antioxidants, which can defend against oxidative stress, is able to detoxify the reactive intermediates and prevent neurodegeneration resulting from excessive ROS production. There are many reports showing that numerous flavonoids, a large group of natural phenolic compounds, can act as antioxidants and the application of flavonoids has beneficial effects in the adult brain. For instance, it is well known that the long-term consumption of the green tea-derived flavonoids catechin and epigallocatechin gallate (EGCG) can attenuate the onset of PD. Also, flavonoids such as ampelopsin and pinocembrin can inhibit mitochondrial dysfunction and neuronal death through the regulation of gene expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Additionally, it is well established that many flavonoids exhibit anti-apoptosis and anti-inflammatory effects through cellular signaling pathways, such as those involving (ERK), glycogen synthase kinase-3β (GSK-3β), and (Akt), resulting in neuroprotection. In this review article, we have described the oxidative stress involved in PD and explained the therapeutic potential of flavonoids to protect the nigrostriatal DA system, which may be useful to prevent PD.

Vitamin D status has been implicated in obesity and adipose tissue inflammation. In the present study, we explored the effects of dietary vitamin D supplementation on adipose tissue inflammation and immune cell population, and the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) treatment on pro-inflammatory cytokine production by stromal vascular cells (SVCs) and adipocytes in lean and high-fat diet-induced obese mice. The results show that epididymal fat Mcp-1 and Rantes mRNA levels, which were higher in obese mice compared with lean mice, were significantly down-regulated by vitamin D supplementation. While obese mice had higher numbers of macrophages and natural killer (NK) cells within adipose tissue, these remained unaltered by vitamin D supplementation. In accordance with these in vivo findings, the in vitro 1,25(OH)2D3 treatment decreased IL-6, MCP-1, and IL-1β production by SVCs from obese mice, but not by adipocytes. In addition, 1,25(OH)2D3 treatment significantly decreased Tlr2 expression and increased mRNA levels of Iκba and Dusp1 in SVCs. These findings suggest that vitamin D supplementation attenuates inflammatory response in adipose tissue, especially in SVCs, possibly through inhibiting NF-κB and MAPK signaling pathways in SVCs but not by the inhibition of macrophage infiltration.

Background Pincer nail deformity is a transverse overcurvature of the nail. This study aimed to define the anatomical characteristics of pincer nail deformity and to evaluate the surgical outcomes. Methods A retrospective review was conducted on 20 cases of pincer nail deformity of the great toe. Thirty subjects without pincer nail deformity or history of trauma of the feet were selected as the control group. Width and height indices were calculated, and interphalangeal angles and base widths of the distal phalanx were measured with radiography. We chose the surgical treatment methods considering perfusion-related factors such as age, diabetes mellitus, kidney disease, and peripheral vascular disease. The zigzag nail bed flap method (n=9) and the inverted T incision method (n=11) were used to repair deformities. The outcomes were evaluated 6 months after surgery. Results The interphalangeal angle was significantly greater in the preoperative patient group (14.0°±3.6°) than in the control group (7.9°±3.0°) (P

Post-tonsillectomy hemorrhage (PTH) is the most frequent complication of tonsillectomy, and occasionally results in a lethal outcome. A 21-year-old man (height 180 cm, weight 95 kg) was scheduled for a bilateral tonsillectomy and uvulopalatopharyngoplasty for treatment of obstructive sleep apnea. He required 5 rounds of general anesthesia due to recurrent PTH. The anesthesiologist used sugammadex a total of 3 times to achieve the successful reversal of the deep neuromuscular blockade (NMB) induced by rocuronium. After sugammadex 2 mg/kg was administered, the NMB was reversed in 2 minutes each time. Re-administration of rocuronium within a short time interval after sugammadex may result in unpredictable effects of neuromuscular blocking agents. Sugammadex made it possible to perform a rapid, complete reverse when the residual block was maintained by an incomplete reversal of anticholinesterase.

Background The septal cartilage is the most useful donor site for autologous cartilage graft material in rhinoplasty. For successful nasal surgery, it is necessary to understand the developmental process of the nasal septum and to predict the amount of harvestable septal cartilage before surgery. Methods One hundred twenty-three Korean patients who underwent three-dimensional (3D) facial bone computed tomography (CT) were selected for evaluation of the midsagittal view of the nasal septum. Multiple parameters such as the area of each component of the nasal septum and the amount of harvestable septal cartilage were measured using Digimizer software. Results The area of the total nasal septum showed rapid growth until the teenage years, but thereafter no significant change throughout the lifetime. However, the development of the septal cartilage showed a gradual decline due to ossification changes with aging after puberty in spite of a lack of change in the total septal area. The area of harvestable septal cartilage in young adults was 549.84±151.26 mm2 and decreased thereafter with age. Conclusions A 3D facial bone CT scan can provide valuable information on the septal cartilage graft before rhinoplasty. Considering the developmental process of the septal cartilage identified in this study, septal surgery should not be performed until puberty due to the risk of nasal growth impairment. Furthermore, in elderly patients who show a decreased cartilage area due to ossification changes, septal cartilage harvesting should be performed carefully due to the risk of saddle nose deformity.

BackgroundAmong all facial fractures, nasal bone fractures are the most common, and they have been reduced by closed reduction (CR) for a long time. But several authors have reported suboptimal results when using CR, and the best method of nasal bone reduction is still being debated. We have found that indirect open reduction (IOR) through an endonasal incisional approach is a useful method for more accurate reduction of the nasal bone.MethodsA retrospective chart review was performed of 356 patients who underwent reduction of a nasal bone fracture in our department from January, 2006, to July, 2011. We treated 263 patients with IOR. We assessed patients' and doctors' satisfaction with surgical outcomes after IOR or CR. We evaluated the frequency of nasal bleeding owing to mucosal injury, and followed the surgical outcomes of patients who had simultaneous dorsal augmentation rhinoplasty.ResultsAccording to the analysis of the satisfaction scores, both patients and doctors were significantly more satisfied in the IOR group than the CR group (P

Voltage-gated Ca(2+) (Ca(v)) channels control neuronal functions including neurotransmitter release and gene expression. The Cacna1a gene encodes the α1 subunit of the pore-forming Ca(v)2.1 channel. Mice with mutations in this gene form useful tools for defining channel functions. The recessive ataxic tottering-6j strain that was generated in the Neuroscience Mutagenesis Facility at The Jackson Laboratory has a mutation in the Cacna1a gene. However, the effect of this mutation has not been investigated in detail. In this study, mutation analysis shows a base substitution (C-to-A) in the consensus splice acceptor sequence linked to exon 5, which results in the skipping of exon 5 and the splicing of exon 4 directly to exon 6. The effect of this mutation is expected to be severe as the expressed α1 subunit protein lacks a significant part of the S4-S5 linker, S5, and part of S5-S6 linker in domain I. Tottering-6j mice display motor dysfunctions in the footprint, rotating rod, and hind-limb extension tests. Although cytoarchitecture of the mutant brains appears normal, tyrosine hydroxylase was persistently expressed in cerebellar Purkinje cells in the adult mutant mice. These results indicate that tottering-6j is a useful model for functional studies of the Ca(v)2.1 channel.