Metabolomic analysis of amino acids and organic acids in aging mouse eyes using gas chromatography-tandem mass spectrometry.

This is a metabolomics study for monitoring altered amino acid (AA) and organic acid (OA) metabolism of in eyes from aging an mouse model at 8 and 18 weeks and 18 months. Simultaneous metabolic profiling analysis of OAs and AAs was performed as ethoxycarbonyl/methoxime/tert-butyldimethylsilyl derivatives by gas chromatography-tandem mass spectrometry. A total of 42 metabolites-24 AAs and 18 OAs-were determined and their composition values were normalized to the corresponding mean values of 8-week-old mice as the control group. Then their normalized values were plotted as star graphs, which were distorted and readily distinguishable for each age-related group. Among the 42 metabolites, 18 AAs and 11 OAs were age dependent and significantly different (p < 0.05). Principal component analysis and partial least squares discriminant analysis showed unclear separation between 8- and 18-week-old mice but clear separation between these and 18-month-old mice. In particular, the variable importance in projection scores of 4-hydroxyproline, cis-aconitic acid, glycine, isocitric acid, leucine, pipecolic acid and lysine from partial least-squares-discriminant analysis were higher than 1.3. A heatmap for the classification and visualization of 42 metabolites showed differences in metabolite changes with aging. Altered AA and OA profiles were monitored, which may explain the metabolic disturbance of AA and OA. These findings are related to mitochondrial dysfunctions related to energy metabolism and the impaired antioxidant system in the aging eye. Therefore, the present metabolomics results of the association between physiological states and altered metabolism of AA and OA will be useful for understanding the aging eye and related diseases.

Comprehensive Targeted Metabolomic Study in the Lung, Plasma, and Urine of PPE/LPS-Induced COPD Mice Model.

(1) Background: Progression of chronic obstructive pulmonary disease (COPD) leads to irreversible lung damage and inflammatory responses; however, biomarker discovery for monitoring of COPD progression remains challenging. (2) Methods: This study evaluated the metabolic mechanisms and potential biomarkers of COPD through the integrated analysis and receiver operating characteristic (ROC) analysis of metabolic changes in lung, plasma, and urine, and changes in morphological characteristics and pulmonary function in a model of PPE/LPS-induced COPD exacerbation. (3) Results: Metabolic changes in the lungs were evaluated as metabolic reprogramming to counteract the changes caused by the onset of COPD. In plasma, several combinations of phenylalanine, 3-methylhistidine, and polyunsaturated fatty acids have been proposed as potential biomarkers; the α-aminobutyric acid/histidine ratio has also been reported, which is a novel candidate biomarker for COPD. In urine, a combination of succinic acid, isocitric acid, and pyruvic acid has been proposed as a potential biomarker. (4) Conclusions: This study proposed potential biomarkers in plasma and urine that reflect altered lung metabolism in COPD, concurrently with the evaluation of the COPD exacerbation model induced by PPE plus LPS administration. Therefore, understanding these integrative mechanisms provides new insights into the diagnosis, treatment, and severity assessment of COPD.

Acremonamide, a Cyclic Pentadepsipeptide with Wound-Healing Properties Isolated from a Marine-Derived Fungus of the Genus Acremonium.

Acremonamide (1) was isolated from a marine-derived fungus belonging to the genus Acremonium. The chemical structure of 1 was established using MS, UV, and NMR spectroscopic data analyses. Acremonamide (1) was found to contain N-Me-Phe, N-Me-Ala, Val, Phe, and 2-hydroxyisovaleric acid. The absolute configurations of the four aforementioned amino acids were determined through acid hydrolysis followed by the advanced Marfey's method, whereas the absolute configuration of 2-hydroxyisovaleric acid was determined through GC-MS analysis after formation of the O-pentafluoropropionylated derivative of the (-)-menthyl ester of 2-hydroxyisovaleric acid. As an intrinsic biological activity, acremonamide (1) did not exert cytotoxicity to cancer and noncancer cells and increased the migration and invasion. Based on these activities, the wound healing properties of acremonamide (1) were confirmed in vitro and in vivo.

Metabolomic analysis of organic acids, amino acids, and fatty acids in plasma of Hanwoo beef on a high-protein diet.

INTRODUCTION: Ketoacidosis of metabolic disease showed in beef cattle although body weight was increased by high-grain diets (HGDs). However, few studies have examined for health status related with metabolic disease of ketoacidosis following high-protein diet (HPD). OBJECTIVES: Metabolomic analysis was performed for the monitoring of health status associated with metabolic disease of ketoacidosis in the plasma of Hanwoo heifers following a HPD. METHODS: Hanwoo heifers of 24 months with 459 ± 42 kg weight were used under a 2 × 2 crossover design. The plasma was collected from control (n = 5) and HPD group (n = 5) on day 21 following diet adaptation for 20 days. Metabolic profiling analysis of organic acids (OAs), amino acids (AAs) and fatty acids (FAs) by gas chromatography-tandem mass spectrometry combined with star pattern analysis was performed in plasma. Levels of OAs, AAs and FAs were evaluated by Mann-Whitney test, PCA and PLS-DA. RESULTS: In HPD group, ketoacidosis as metabolic disease was monitored by elevated acetoacetic acid and 3-hydroxybutyric acid. In addition, the elevation of ketogenic AAs, reduction of medium chain FAs and OAs with energy metabolism in TCA cycle were monitored in HPD group. Star graphic pattern was characteristic and readily distinguished between control and HPD groups. In PLS-DA, two groups were separated with VIP score of top-ranked 10 FAs as important metabolites for discrimination. CONCLUSION: Elevation of ketone body including ketogenic AAs and reduced energy metabolism of FAs and OAs may useful for evaluation of health states associated with ketoacidosis from metabolic event by HPD in beef cattle.

Functional loss of ARID1A is tightly associated with high PD-L1 expression in gastric cancer.

Notwithstanding remarkable treatment success with anti-PD-1 monoclonal antibody, oncogenic mechanism of PD-L1 regulation in gastric cancer (GC) remains poorly understood. We hypothesized that ARID1A might be related to tumor PD-L1 expression in GC. We found that tumor PD-L1 positivity was associated with loss of ARID1A and showed trend toward better survival of patients with various molecular subtypes of GC (experimental set, n = 273). Considering heterogeneous ARID1A expression, we validated this using whole tissue sections (n = 159) and found that loss of ARID1A was correlated with microsatellite instability-high (MSI-H), Epstein-Barr virus (EBV), and PD-L1 positivity. Furthermore, for patients with MSI-H tumors, the degree of PD-L1 expression was significantly higher in ARID1A-deficient tumors. After ARID1A knockdown in GC cell lines, total and membranous PD-L1 protein, and PD-L1 mRNA levels were increased based on Western blot, flow cytometry, and qRT-PCR, respectively. With IFN-γ treatment, PD-L1 expression was significantly increased both in ARID1A-deficient cancer cells and controls, but the increase was not more pronounced in the former. Loss of ARID1A increased PD-L1 via activating AKT signaling, while LY294002 (PI3K inhibitor) decreased PD-L1 levels. Furthermore, we found that 3 MSI-H tumors showing highest expression of PD-L1 had simultaneous KRAS mutation and loss of ARID1A, suggesting a possible synergistic role boosting PD-L1. Our results strongly indicate that loss of ARID1A is tightly associated with high PD-L1 expression in GC. These results would increase our understanding of the oncogenic mechanism of PD-L1 regulation in GC, and also help to find the optimal candidates for immunotherapy.

Metabolomic approaches to polyamines including acetylated derivatives in lung tissue of mice with asthma.

INTRODUCTION: Recently, the relationship between polyamine (PA) metabolism and asthma has been studied in severe asthmatic therapy, but systematic PA metabolism including their acetylated derivatives was not fully understood. OBJECTIVES: Profiling analysis of polyamines (PAs) was performed to understand the biochemical events and monitor altered PA metabolism in lung tissue of mice with asthma. METHODS: Polyamine profiling of lung tissue of mice with asthma was performed without derivatization by liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with star pattern recognition analysis. The PA levels between control and asthma groups were evaluated by multivariate analysis. RESULTS: In mouse lung tissue, seven PAs were determined by LC-MS/MS in multiple reaction monitoring (MRM) mode. Their levels were normalized to the corresponding mean levels of the control group for star pattern analysis, which showed distorted heptagonal shapes with characteristic and readily distinguishable patterns for each group. Levels of putrescine (p < 0.0034), N1-acetylputrescine (p < 0.0652), and N8-acetylspermidine (p < 0.0827) were significantly increased in asthmatic lung tissue. The separation of the two groups was evaluated using multivariate analysis. In unsupervised learning, acetylated PAs including N1-acetylspermine were the main metabolites for discrimination. In supervised learning, putrescine and N1-acetylputrescine were evaluated as important metabolites. CONCLUSIONS: The present results provide basic data for understanding polyamine metabolism in asthma and may help to improve the therapy for severe asthma patients.

Predictive formula of ideal lumbar lordosis and lower lumbar lordosis determined by individual pelvic incidence in asymptomatic elderly population.

PURPOSE: This study aimed to obtain reference values of lumbar lordosis (LL) and lower LL (LLL) from normal asymptomatic groups, determine the relationship between them and pelvic incidence (PI), and establish the predictive formula for ideal LLL in the elderly Korean population. METHODS: Standing plain lateral radiographs of the whole spine, including the pelvis, were analyzed in asymptomatic adult male volunteers without back pain or prior surgery involving the spine or lower extremity. Volunteers with scoliosis, spondylolisthesis, segmental disk space narrowing, and/or compression fractures in the radiographs were excluded. The following parameters were measured: LL, LLL, and pelvic parameters including PI. The values of PI-LL and PI-LLL were calculated, and the formula using stepwise multiple regression analysis was made. A P value of < 0.05 was considered statistically significant. RESULTS: The study participants included 150 volunteers. All were male participants with an average age of 64.1 ± 6.4. The average value of height, weight, and body mass index was 167.0 ± 5.5 cm, 67.3 ± 9.8 kg, and 24.1 ± 3.1 kg/m2, respectively. The average LL was - 57.5° ± 9.0°, LLL was - 41.7° ± 7.0°, and PI was 48.6° ± 8.6°. The formula was established as follows: PI-LL = 0.38 × PI - 27.61 (R2 = 0.172), PI-LLL = 0.77 × PI - 28.69 (R2 = 0.516), ideal LL = 0.62 × PI + 27.61 (R2 = 0.348), and ideal LLL = 0.225 × PI + 28.63 (R2 = 0.083). CONCLUSIONS: The ideal values of PI-LL and PI-LLL were inconsistent, and they have a positive correlation with PI in asymptomatic elderly population. Our data would be helpful as a normal reference value of ideal LL and LLL according to PI. These slides can be retrieved under Electronic Supplementary Material.

Neural Invasion is a Significant Contributor to Peritoneal Recurrence in Signet Ring Cell Gastric Carcinoma.

BACKGROUND: Gastric signet ring cell carcinoma (SRC) has shown a favorable outcome in early stages but has a worse prognosis than non-SRC in advanced stages. However, the cause for this stage-dependent prognostic impact has not been determined. This study aimed to compare clinicopathologic features and recurrence patterns between gastric SRC and non-SRC in a cohort of Eastern patients. METHODS: This study reviewed the prospectively collected data of 764 patients undergoing curative resection for gastric cancer from 2005 to 2008. The demographics, clinicopathologic characteristics, disease-specific survival (DSS) rate, and recurrence-free survival (RFS) rate of the patients were analyzed. RESULTS: The SRC patients (n = 176) had a worse prognosis than the non-SRC patients (n = 588), especially in stages T3 and T4. Peritoneal recurrence and the incidence of neural invasion (NI) were significantly increased in the SRC patients, albeit only in stages T3 and T4. In the T3 and T4 patients with NI, peritoneal recurrence occurred more frequently in SRC than in non-SRC (28.7% vs. 13.7%; p = 0.001), but not in the T3 and T4 patients without NI. Only in the patients with NI, SRC led to a significantly shorter DSS (67.6 vs. 90.7 months; p = 0.008) and RFS (67.1 vs. 80.3 months; p = 0.036) than non-SRC. CONCLUSIONS: This report is the first to present the relationship between NI and peritoneal recurrence as the cause of stage-dependent prognoses for SRC. A better understanding of NI may lend insight into cancer spread and recurrence, especially in gastric SRC.

Discoidin domain receptor 1 activity drives an aggressive phenotype in gastric carcinoma.

BACKGROUND: Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that utilizes collagen as a ligand, is a key molecule in the progression of solid tumors as it regulates the interaction of cancer cells with the tumor stroma. However, the clinical relevance of DDR1 expression in gastric carcinoma is yet to be investigated. Here, we assessed the role of DDR1 in mediating the aggressive phenotype of gastric carcinoma and its potential as a therapeutic target. METHODS: We conducted DDR1 immunohistochemistry using a tissue microarray of 202 gastric carcinoma specimens. We examined the effect of collagen-induced activation of DDR1 on cell signaling, tumorigenesis, and cell migration in gastric cancer cell lines, and tumor growth in a xenograft animal model of gastric cancer. RESULTS: Our results showed that 50.5% of gastric cancer tissues are positive for DDR1 expression, and positive DDR1 expression was significantly correlated with a poor prognosis (P = 0.015). In a subgroup analysis, DDR1 expression was prognostically meaningful only in patients receiving adjuvant treatment (P = 0.013). We also demonstrated that collagen was able to activate DDR1 and increase the clonogenicity and migration of gastric cancer cells. We observed that a DDR1 inhibitor, 7rh benzamide, suppressed tumor growth in gastric cancer xenografts. CONCLUSIONS: Our findings suggest a key role for DDR1 signaling in mediating the aggressive phenotype of gastric carcinoma. Importantly, inhibition of DDR1 is an attractive strategy for gastric carcinoma therapy.

Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas.

OBJECTIVE: The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas. BACKGROUND: Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis. METHODS: One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro. Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts. RESULTS: Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (P = 0.045), large tumor size (P = 0.007), higher T category (P < 0.001), and the presence of perineural invasion (P = 0.018). Patients with stroma-rich SRC carcinomas had a significantly shorter disease-free survival (P < 0.001) and overall survival (P < 0.001). However, in a subgroup analysis, the prognostic significance of the stromal proportion correlated only with patients with T3/4 disease. From multivariate analysis, the high stromal proportion is an independent prognostic factor to predict worse disease-free survival (hazard ratio 2.288; P = 0.001) and overall survival (hazard ratio 2.503; P = 0.001). We found that CAFs enhanced the migratory abilities of cancer cells through the epithelial-mesenchymal transition, and RNA sequencing results confirmed these findings. CONCLUSIONS: The intratumor stromal proportion could be a useful prognostic biomarker and a potential therapeutic target in gastric SRC carcinomas.

Hepatitis B virus X protein activates the ATM-Chk2 pathway and delays cell cycle progression.

Genetic instability is intimately associated with tumour development. In particular, liver cancers associated with hepatitis B virus (HBV) exhibit high genetic instability; however, our understanding of the underlying molecular mechanisms remains limited. In this study, we found that γ-H2AX, a marker of DNA double-strand breaks (DSBs), and the levels of phospho-Chk2 (p-Chk2, the activated form) were significantly elevated in HBV-associated hepatocellular carcinomas and neighbouring regenerating nodules. Likewise, introduction of the pHBV or pMyc-HBx plasmids into cells induced accumulation of γ-H2AX foci and increased the p-Chk2 level. In these cells, inhibitory phosphorylation of Cdc25C phosphatase (Ser(216)) and CDK1 (Tyr(15)) was elevated; consequently, cell-cycle progression was delayed at G2/M phase, suggesting that activation of the ATM-Chk2 pathway by the HBV X protein (HBx) induces cell-cycle delay. Accordingly, inhibition of ataxia telangiectasia mutated (ATM) by caffeine or siRNA abolished the increase in the p-Chk2 level and restored the delayed CDK1 kinase activity in ChangX cells. We also found that cytoplasmic HBx, but not nuclear HBx, induced reactive oxygen species (ROS) production and led to the accumulation of γ-H2AX foci and the increased p-Chk2 level. Together, these data indicate that HBx-induced ROS accumulation induces DNA damage that activates the ATM-Chk2 pathway. Our findings provide insight into the mechanisms of HBV pathogenesis.

Loss of ACSS2 expression predicts poor prognosis in patients with gastric cancer.

BACKGROUND: Recent studies have demonstrated that acetyl-CoA synthetase 2 (ACSS2) plays a critical role in cancer cell survival; however, the role of ACSS2 in gastric carcinogenesis has not been determined. METHODS: We investigated the expression of ACSS2 in human gastric cancer (GC) tissues using immunohistochemistry, and analyzed its clinicopathological correlation and prognostic relevance. RESULTS: Among 350 GCs, 219 cases (62.6%) were classified as ACSS2-low, whereas 131 cases (37.4%) were ACSS2-high. Loss of ACSS2 expression (ACSS2-low) was more frequently observed in undifferentiated histology (P = 0.002), in cases with MLH1-loss (P = 0.003), and in cases with SIRT3-low (P < 0.001). The ACSS2-low cases showed significantly lower mean disease-free survival (DFS, 68.5 vs. 81.8 months; P = 0.025) and overall survival (OS, 73.5 vs. 86.6 months; P = 0.029). In multivariate analysis, loss of ACSS2 expression was identified as one of the independent prognostic factors predicting worse DFS (HR: 1.547, P = 0.018) and OS (HR: 1.476, P = 0.036). CONCLUSIONS: We revealed that the loss of ACSS2 expression is a reliable independent poor prognostic factor in GC. Our results may expand our understanding of the involvement of glucose metabolism, including the role of ACSS2, in the pathogenesis of GC.

A comparative analysis of sagittal spinopelvic alignment between young and old men without localized disc degeneration.

INTRODUCTION: The purpose of this study was to compare the sagittal spinopelvic parameters between young normal asymptomatic adults and older normal asymptomatic adults without localized segmental disc degeneration. MATERIALS AND METHODS: Standing sagittal radiographs of the whole spine including the pelvis in 342 adult male volunteers (Group 1: n = 184, average age 21.2 years, range 19-28 vs. Group 2: n = 158, average age 63.8 years, range 53-79) were analyzed prospectively. Volunteers with history of spine operation, spinal disease, chronic pain in their back or legs, scoliosis, spondylolisthesis, 1-3 segmental disc space narrowing, and/or compression fractures in radiographs were excluded. The following parameters were included: thoracic kyphosis between T5 upper endplate (UEP) and T12 lower endplate (LEP), thoracolumbar kyphosis (T10 UEP - L2 LEP), T12 LEP-horizontal (H) angle (minus denotes EP above the H line), lumbar lordosis (T12 LEP - S1 UEP), lower lumbar lordosis (L4 UEP - S1 UEP), sacral slope, pelvic incidence and distances from C7 plumb/T12 plumb to the postero-superior endplate of S1. Group 2 (old men group) demonstrated larger thoracic kyphosis (30.1° ± 8.6° vs. 21.1° ± 7.8° in Group 1, P < 0.001), thoracolumbar kyphosis (10.0° ± 7.5° vs. 2.8° ± 7.1° in Group 1, P < 0.001), total lumbar lordosis at T12-S1 (57.3° ± 8.8° vs. 52.2° ± 9.2° in Group 1, P < 0.001), lower lumbar lordosis at L4-S1 (39.4° ± 6.7° vs. 32.4° ± 6.4° in Group 1, P < 0.001), a higher ratio of lower to total lumbar lordosis (69.5 ± 11.6 vs. 62.7 ± 10.6 % in Group 1, P < 0.001) and T12 LEP-H angle (-20.4° ± 5.7° vs. -15.7° ± 5.1° in Group 1, P < 0.001). There were no significant differences in sacral slope (36.5° ± 7.3° in Group 1 vs. 36.8° ± 6.7° in Group 2, P = 0.67) and pelvic incidence (46.5° ± 7.7° in Group 1 vs. 48.2° ± 8.5° in Group 2, P = 0.06). There was no significant difference in the measurement of distance from C7 plumb to the postero-superior endplate of S1 (-0.7 ± 2.4 cm in Group 1 vs. -0.3 ± 2.7 cm in Group 2, P = 0.197). However, the distance from T12 plumb to the postero-superior endplate of S1 (-0.7 ± 1.7 cm in Group 1 vs. -2.2 ± 1.7 cm in Group 2, P < 0.001) demonstrated a significant difference. CONCLUSION: The old men group demonstrated a significant increase in thoracic kyphosis, thoracolumbar kyphosis, total and lower lumbar lordosis, a higher ratio of lower to total lumbar lordosis, and a longer distance from T12 plumb to the postero-superior endplate of S1 without changes in sacral slope and global sagittal balance.

Progressive paraplegia after upper thoracic epidural block-related pneumorachis: A case report.

INTRODUCTION AND IMPORTANCE: While the typical symptom associated with pneumorachis after an epidural block is radiculopathy in one or several corresponding segments, there has been a rare case report of significant complications such as cardiac arrest leading to death, or paraplegia. CASE PRESENTATION: We present a case of an eighty-nine-year-old male patient who developed progressive paraplegia following an upper thoracic epidural block-associated pneumorachis. The procedure was performed at a different hospital using the loss of resistance (LOR) technique. Interestingly, the onset of paraplegia was delayed, occurring six hours after the procedure. Furthermore, there was a discrepancy between the clinical symptoms and the identified lesion in imaging studies. Despite the performance of an emergency laminectomy to remove the epidural gas, the paralysis continued to progress proximally. CLINICAL DISCUSSION: Healthcare professionals should observe patients for an appropriate duration after the procedure to detect and manage any delayed symptoms. And it is crucial to recognize the potential for lesion extension beyond the symptomatic segment and perform thorough imaging examinations. CONCLUSION: These findings emphasize the importance of exercising caution during the procedure, even when using a minimal amount of air with the LOR technique in the thoracic spine.

Nanoscale RRAM-based synaptic electronics: toward a neuromorphic computing device.

Efforts to develop scalable learning algorithms for implementation of networks of spiking neurons in silicon have been hindered by the considerable footprints of learning circuits, which grow as the number of synapses increases. Recent developments in nanotechnologies provide an extremely compact device with low-power consumption.In particular, nanoscale resistive switching devices (resistive random-access memory (RRAM)) are regarded as a promising solution for implementation of biological synapses due to their nanoscale dimensions, capacity to store multiple bits and the low energy required to operate distinct states. In this paper, we report the fabrication, modeling and implementation of nanoscale RRAM with multi-level storage capability for an electronic synapse device. In addition, we first experimentally demonstrate the learning capabilities and predictable performance by a neuromorphic circuit composed of a nanoscale 1 kbit RRAM cross-point array of synapses and complementary metal-oxide-semiconductor neuron circuits. These developments open up possibilities for the development of ubiquitous ultra-dense, ultra-low-power cognitive computers.

Postoperative Segmental Motion up to 1 Year Following Single-Level Anterior Cervical Discectomy and Fusion: Plate versus Non-plate.

STUDY DESIGN: Retrospective observational study. PURPOSE: This study aimed to investigate the impact of plating on postoperative serial segmental motion and its correlation with clinical outcomes in single-level anterior cervical discectomy and fusion (ACDF) for up to 1 year. OVERVIEW OF LITERATURE: The advantages and disadvantages of using cervical plating in ACDF have been well discussed; however, few studies compared the early serial segmental motions at the postoperative level between plating and non-plating. METHODS: In retrospectively collected data, 149 patients who underwent single-level ACDF for degenerative disease were enrolled and divided into non-plating (n=66) and plating (n=83). Interspinous motion (ISM) at the arthrodesis segment, Numeric Rating Scale (NRS) for neck pain, and Neck Disability Index (NDI) were serially evaluated at 3, 6, and 12 months postoperatively. Predictable factors for fusion, including age, sex, plating, diabetes, smoking, and type of grafts, were investigated, and fusion was defined as ISM <1 mm. RESULTS: In both groups, ISM was the highest at 3 months and gradually decreased thereafter, and the plating group showed significantly lower serial ISM than the non-plating group at 12 months. The plating group had lower NRS and NDI scores than the nonplating group at 12 months, and the difference in the NRS scores was statistically significant, particularly at 3 and 6 months, although that of the NDI scores was not. In a multivariate analysis, plating was the most powerful predictor for fusion. CONCLUSIONS: Plating significantly decreases the serial ISM compared with non-plating in single-level ACDF, and such decreased motion is correlated with decreased neck pain until 12 months postoperatively, particularly at 3 and 6 months. Given that plating was the most predictive factor for fusion, we recommend plating even in single-level ACDF for better early clinical outcomes.

Longer Operative Time and the Use of Anticoagulants Are Associated With Increased Blood Loss in Elderly Patients Undergoing Arthroscopic Rotator Cuff Repair.

Purpose: To study the effects of rotator cuff tear size, operation time, and the use of anticoagulant on blood loss in elderly patients undergoing arthroscopic rotator cuff surgery. Methods: Patients aged older than 65 years who underwent arthroscopic rotator cuff repair with subacromial decompression at our hospital from January 2015 to December 2021 were identified. We measured hemoglobin levels preoperatively, postoperatively, and 7 days after surgery. First, subjects were divided according to the operation time (group I, <90 minutes; group II, <120 minutes; group III <150 minutes; and group IV, >150 minutes). Second, we classified the subjects by the size of the rotator cuff tear (group A, <3 cm; group B, <5 cm; and group C, >5 cm). Lastly, we categorized the subjects into 2 groups according to the use of anticoagulant medication. Results: A total of 566 patients were included. The mean hemoglobin (Hgb) levels were 13.8 ± 1.4 g/dL preoperatively, 13.2 ± 1.4 g/dL postoperatively, and 12.8 ± 1.3 g/dL 7 days after surgery, and the differences among them were statistically significant (P < .001). The Hgb level changes 7 days after surgery showed a significant decrease in the group with a longer operation time, and the Hgb loss increased from group 1 to group 4 (P < .001). They did not show any difference in the Hgb levels among the groups according to the size of a cuff tear preoperatively, postoperatively, and 7 days after surgery. The subjects with anticoagulant use showed more decrease in Hgb levels between immediately after the surgery and 7 days after the surgery (P = .031). Still, both groups did not show a statistical difference in the Hgb level 7 days after surgery (P = .115). Conclusions: In this study, blood loss after arthroscopic rotator cuff repair in elderly patients was greater than expected. Bleeding increased in elderly patients who had longer surgical times or were taking anticoagulant medications after surgery. Tear size was not associated with a decrease in Hgb levels. Level of Evidence: Level III, retrospective comparative study.

Therapeutic Potential of Peucedanum japonicum Thunb. and Its Active Components in a Delayed Corneal Wound Healing Model Following Blue Light Irradiation-Induced Oxidative Stress.

Blue light is reported to be harmful to eyes by inducing reactive oxygen species (ROS). Herein, the roles of Peucedanum japonicum Thunb. leaf extract (PJE) in corneal wound healing under blue light irradiation are investigated. Blue-light-irradiated human corneal epithelial cells (HCECs) show increased intracellular ROS levels and delayed wound healing without a change in survival, and these effects are reversed by PJE treatment. In acute toxicity tests, a single oral administration of PJE (5000 mg/kg) does not induce any signs of clinical toxicity or body weight changes for 15 days post-administration. Rats with OD (oculus dexter, right eye) corneal wounds are divided into seven treatment groups: NL (nonwounded OS (oculus sinister, left eye)), NR (wounded OD), BL (wounded OD + blue light (BL)), and PJE (BL + 25, 50, 100, 200 mg/kg). Blue-light-induced delayed wound healing is dose-dependently recovered by orally administering PJE once daily starting 5 days before wound generation. The reduced tear volume in both eyes in the BL group is also restored by PJE. Forty-eight hours after wound generation, the numbers of inflammatory and apoptotic cells and the expression levels of interleukin-6 (IL-6) largely increase in the BL group, but these values return to almost normal after PJE treatment. The key components of PJE, identified by high-performance liquid chromatography (HPLC) fractionation, are CA, neochlorogenic acid (NCA), and cryptochlorogenic acid (CCA). Each CA isomer effectively reverses the delayed wound healing and excessive ROS production, and their mixture synergistically enhances these effects. The expression of messenger RNAs (mRNAs) related to ROS, such as SOD1, CAT, GPX1, GSTM1, GSTP1, HO-1, and TRXR1, is significantly upregulated by PJE, its components, and the component mixture. Therefore, PJE protects against blue-light-induced delayed corneal wound healing via its antioxidative, anti-inflammatory, and antiapoptotic effects mechanistically related to ROS production.

A fast, high-endurance and scalable non-volatile memory device made from asymmetric Ta2O(5-x)/TaO(2-x) bilayer structures.

Numerous candidates attempting to replace Si-based flash memory have failed for a variety of reasons over the years. Oxide-based resistance memory and the related memristor have succeeded in surpassing the specifications for a number of device requirements. However, a material or device structure that satisfies high-density, switching-speed, endurance, retention and most importantly power-consumption criteria has yet to be announced. In this work we demonstrate a TaO(x)-based asymmetric passive switching device with which we were able to localize resistance switching and satisfy all aforementioned requirements. In particular, the reduction of switching current drastically reduces power consumption and results in extreme cycling endurances of over 10(12). Along with the 10 ns switching times, this allows for possible applications to the working-memory space as well. Furthermore, by combining two such devices each with an intrinsic Schottky barrier we eliminate any need for a discrete transistor or diode in solving issues of stray leakage current paths in high-density crossbar arrays.