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.

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.

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.

Advancing the debate on hotel employees' environmental psychology by promoting energy-saving behavior in a corporate social responsibility framework.

Considering the vulnerable climatic conditions in most parts of the planet, a successful transition toward a carbon-free future is a critical challenge worldwide. In this respect, around 35% of the world's total greenhouse gas emission (GHG) is associated with the power sector (especially electrical energy). To this end, a vast of electrical energy has been used by the people in buildings. Specifically, a significant amount of energy in buildings is used for heating, cooling, and ventilation. While the available literature highlights the importance of neat, clean, and green electrical energy for the decarbonization of society, a critical gap exists in such literature. That is, most of the literature under this stream deals with the supply side (production) of electrical energy, while the demand side (consumption at an individual level) was neglected. To bridge this critical knowledge gap, this study investigates how the CSR engagement of a hotel organization can promote the energy-related pro-environmental behavior (ERPEB) among the employees with the intervening effect of employees' environmental commitment (EMEC) and Green intrinsic motivation (GRIM). Further, the conditional indirect role of altruistic values was also tested in this study. The data were collected from different hotel employees in Pakistan with the help of a self-administered questionnaire. We tested the hypothesized relationship through structural equation modeling (SEM). The results confirmed that CSR can be a potential motivator to impact the ERPEB of employees, while EMEC and GRIM mediated this relationship significantly. The findings of this study also confirmed the conditional indirect role of altruistic values. These findings offer various theoretical and practical contributions which are conversed in detail.

Forward Bending in Supine Test: Diagnostic Accuracy for Acute Vertebral Fragility Fracture.

Despite its high incidence rate, vertebral fragility fracture (VFF) is frequently underdiagnosed due to the absence of marked symptoms. This study evaluated the diagnostic accuracy of our suggested physical examinations and compared them with that of plain radiographs. Patients over 65 years of age with sudden back pain within the preceding 3 weeks were enrolled. Physical examinations in three different positions and a closed-fist percussion test were performed, and the presence of VFF was evaluated through confirmatory radiographic tools. We assessed the diagnostic accuracy of each physical examination and compared them with the interpretation of plain radiographs and examined the patient-reported pain locations based on the VFF level. A total of 179 patients were enrolled. The forward bending in supine (FB-SU) test demonstrated superior diagnostic values (sensitivity: 90.6%, specificity: 71.2%), which outperformed those of plain radiographs (sensitivity: 68.9%, specificity: 71.9%). The location of patient-reported pain was generally close to or lower than the index fracture level. FB-SU showed the highest diagnostic accuracy and was more valuable than plain radiographs in diagnosing acute VFF. FB-SU is a simple and affordable screening test. If positive, physicians should highly suspect VFF even when based on vague evidence of acute fracture provided by plain radiographs.

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.

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.

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.

Biologic therapy for amyloid A amyloidosis secondary to rheumatoid arthritis treated with interleukin 6 therapy: Case report and review of literature.

INTRODUCTION: Secondary amyloidosis is a rare complication of rheumatoid arthritis (RA) that is histologically characterized by the deposition of amyloid fibrils in target organs, such as the kidneys and gastrointestinal tract. Controlling the inflammatory response is essential to prevent organ dysfunction in amyloid A (AA) amyloidosis secondary to RA, and no clear treatment strategy exists. PATIENT CONCERNS AND DIAGNOSIS: A 66-year-old woman with RA, who had been treated with disease-modifying anti-rheumatic drugs for 1 year, presented with recurrent abdominal pain and prolonged diarrhea. Endoscopy showed chronic inflammation, and colon tissue histology confirmed AA amyloidosis. INTERVENTIONS AND OUTCOMES: After tocilizumab therapy was begun, her diarrhea and abdominal pain subsided, and articular symptoms improved. Biologic drugs for RA have been used in patients with secondary AA amyloidosis, including tumor necrosis factor and Janus kinase inhibitors, interleukin 6 blockers, and a T cell modulator. Here, we systematically review existing case reports and compare the outcomes of RA-related AA amyloidosis after treatment with various drugs. CONCLUSION: The data indicate that biologic drugs like tocilizumab might be treatments of choice for AA amyloidosis secondary to RA.

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.

Nitrogen-rich graphitic-carbon@graphene as a metal-free electrocatalyst for oxygen reduction reaction.

The metal-free nitrogen-doped graphitic-carbon@graphene (Ng-C@G) is prepared from a composite of polyaniline and graphene by a facile polymerization following by pyrolysis for electrochemical oxygen reduction reaction (ORR). Pyrolysis creates a sponge-like with ant-cave-architecture in the polyaniline derived nitrogenous graphitic-carbon on graphene. The nitrogenous carbon is highly graphitized and most of the nitrogen atoms are in graphitic and pyridinic forms with less oxygenated is found when pyrolyzed at 800 °C. The electrocatalytic activity of Ng-C@G-800 is even better than the benchmarked Pt/C catalyst resulting in the higher half-wave potential (8 mV) and limiting current density (0.74 mA cm-2) for ORR in alkaline medium. Higher catalytic performance is originated from the special porous structure at microscale level and the abundant graphitic- and pyridinic-N active sites at the nanoscale level on carbon-graphene matrix which are beneficial to the high O2-mass transportation to those accessible sites. Also, it possesses a higher cycle stability resulting in the negligible potential shift and slight oxidation of pyridinic-N with better tolerance to the methanol.

Numerical and experimental analysis of thermal-flow characteristics in a pyrolysis reactor of a gas scrubber designed based on similitude theory.

With the continuous development of the semiconductor industry, interest in the technology for treating various pollutant gases in the semiconductor fabrication process has increased recently. Various gas scrubbers are being used to remove the pollutant gas from the processes. An efficient design of the pyrolysis reactor is crucial in a scrubber system due to the effective removal of pollutant sources and the overall operation stability. In this study, the thermal and flow characteristics in the reactor were examined through experiments and numerical analysis using a small-scale model of simplified pyrolysis reactor. Furthermore, a prototype model of pyrolysis reactor was designed through analysis result of small-scale model based on the similitude theory. The results of this study can be used as basic data for analyzing thermal and flow characteristics in a variety of scrubber systems.Implications: This study investigated and suggested a methodology for designing a pyrolysis reactor of the gas scrubber to overcome the design failure by using the concept of similarity, which can use the results from one system to explain phenomena in another system. We believe that our study makes a significant contribution to the literature because it provides a way to improve the performance of the gas scrubbers and test this performance with a smaller scalable model. And, we expect this study to be used as basic data when applying innovative and new design proposals in various industries.

Changes in Thoracic Kyphosis and Thoracolumbar Kyphosis in Asymptomatic Korean Male Subjects Aged >50 Years: Do They Progress Above T5, T10, T12, or L2?

STUDY DESIGN: Retrospective analysis of prospectively collected data. PURPOSE: To evaluate the natural progression of segmental kyphosis in thoracic and thoracolumbar spine with advancing age. OVERVIEW OF LITERATURE: To our knowledge, the evolution of segmental thoracic kyphosis (TK) in individuals aged >50 years has not been reported. METHODS: Total 179 normal, asymptomatic Korean men were divided in to three groups (6th, 7th, and 8th decade) according to their age. Standard sagittal spinopelvic parameters, including TK and thoracolumbar kyphosis, were measured and subdivided into the following four segments: A (C7 upper end plate [UEP]-T5 UEP), B (T5 UEP-T10 UEP), C (T10 UEP-T12 lower end plate [LEP]), and D (T12 LEP-L2 LEP). These segments of the three study groups were analyzed. RESULTS: In segment B, the segmental kyphosis of group 3 (20.2°±8.0°) showed a statistically larger value than that of group 1 (15.6°±6.8°) and group 2 (16.7°±8.8°) (p=0.017). In segment C, the segmental kyphosis of group 2 (12.9°±6.5°) and group 3 (12.2°±7.1°) showed statistically larger values than that of group 1 (9.5°±6.2°) (p=0.016). The A and D segments of the three groups were not significantly different. CONCLUSIONS: Increased TK was observed in the middle (segment B) and lower (segment C) thoracic segments in normal asymptomatic male subjects with age. The results from the natural progression of segmental kyphosis with age would provide baseline reference data to help surgeons choose the optimal point of the upper instrumented vertebra level for preventing proximal junctional kyphosis.

Carbon nanotubes-based PdM bimetallic catalysts through N4-system for efficient ethanol oxidation and hydrogen evolution reaction.

Transitional metal-nitrogen-carbon system is a promising candidate to replace the Pt-based electrocatalyst due to its superior activity, durability and cost effectiveness. In this study, we have designed a simple strategy to fabricate carbon nanotubes-supported binary-nitrogen-carbon catalyst via wet-chemical method. Palladium and transitional metals (M, i.e. manganese cobalt and copper) nanoparticles are anchored through four-nitrogen system onto carbon nanotubes (denoted as PdM-N4/CNTs). This material has been used as bifunctional electrocatalyst for electrochemical ethanol oxidation reaction and hydrogen evolution reaction for the first time. The N4-linked nanoparticles onto carbon nanotubes plays a crucial role in intrinsic catalytic activity for both reactions in 1 M KOH electrolyte. Among three PdM-N4/CNTs catalysts, the PdMn-N4/CNTs catalyst exhibits higher catalytic activity in terms of current density, mass activity and stability compared to the benchmark Pt/C. The robust electrocatalysis are inherited from the better attachment of PdMn through N4-system onto carbon nanotubes, comparatively smaller particles formation with better dispersion and higher electrical conductivity.

Molecular classification of hepatocellular adenoma: A single-center experience.

BACKGROUNDS/AIMS: Hepatocellular adenoma (HCA) is a rare benign tumor that has a risk of malignant transformation into hepatocellular carcinoma (HCC) and bleeding. The aim of this study was to analyze the characteristics of HCA by performing molecular classification. METHODS: We retrospectively collected data from nine patients who were diagnosed with HCA from 1995 to 2016. The patients underwent liver surgery due to the existence of clinical symptoms. Immunohistochemical (IHC) staining was performed to classify the subgroups of HCA. RESULTS: Four patients with both ß-catenin and inflammation were classified as ß-IHCA. Two patients were defined as ß-HCA. Two patients were classified as HHCA. Only one patient was defined as IHCA. None of the patients had unclassified HCA. Seven of nine patients had a malignant transformation. By comparing the characteristics of HCA between two groups, we found the mean tumor size in the malignant transformation group was greater than the non-malignant transformation group. CONCLUSIONS: Taken together, the mean tumor size and activation of catenin ß1 mutation status might be the risk factors for the malignant transformation of HCA into HCC. Moreover, IHCA without the catenin ß1 mutation could also have a possibility of malignant transformation into HCC.

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.

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.

Retraction Note to: Analysis of loxoprofen in tablets, patches, and equine urine as tert-butyldimethylsilyl derivative by gas chromatography-mass spectrometry.

The authors have retracted this article [1] because after publication they became aware that the equine urine samples analysed for loxoprofen in this study were in fact equine plasma samples. Therefore the results and conclusions of this article cannot be relied upon. All authors agree to this retraction.

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.