Comparison of analgesic effectiveness between nefopam and propacetamol in living kidney donors following rectus sheath block after hand-assisted living donor nephrectomy: a prospective, randomized controlled trial.

BACKGROUND: Nefopam and propacetamol are the most commonly used analgesics in postoperative multimodal analgesic regimens. Distinct mechanisms are involved in each drug's anti-nociceptive effects. No studies have compared pain relief efficacy between the two drugs in patients undergoing transplantation surgery. Here, we investigated whether the administration of nefopam or propacetamol to healthy living kidney donors who underwent rectus sheath block (RSB) for parietal pain could reduce the subsequent opioid dose necessary to produce adequate analgesia. METHODS: This prospective, randomized controlled trial included 72 donors undergoing elective hand-assisted living donor nephrectomy into two groups: propacetamol (n = 36) and nefopam (n = 36). Intraoperative RSB was performed in all enrolled donors. The primary outcome was the total volume of intravenous opioid-based patient-controlled analgesia (PCA) used on postoperative day 1 (POD 1). Additionally, the Numeric Rating Scale scores for flank (visceral) and umbilicus (parietal) pain at rest and during coughing were compared, and the Korean adaptation of the Quality of Recovery-15 Questionnaire (QoR-15 K) was evaluated on POD 1. RESULTS: Both groups had similar preoperative and intraoperative characteristics. On POD 1, the total amount of PCA infusion was significantly lower in the nefopam group than in the propacetamol group (44.5 ± 19.3 mL vs. 70.2 ± 29.0 mL; p < 0.001). This group also reported lower pain scores at the flank and umbilical sites and required fewer rescue doses of fentanyl in the post-anesthesia care unit. However, pain scores and fentanyl consumption in the ward were comparable between groups. The QoR-15 K scores were similar between groups; there were substantial improvements in breathing, pain severity, and anxiety/depression levels in the nefopam group. The incidences of postoperative complications, including sweating and tachycardia, were similar between groups. CONCLUSION: Compared with propacetamol, nefopam provides a greater analgesic effect for visceral pain and enhances the effects of blocks that reduce the opioid requirement in living kidney donors with parietal pain managed by RSB. TRIAL REGISTRATION: The trial was registered prior to patient enrollment in the clinical trial database using the Clinical Research Information Service (registration no. KCT0007351 , Date of registration 03/06/2022).

Relationship Between High-Density Lipoprotein Cholesterol and Mortality in Elderly Hemodialysis Patients: Data From the Korean Society of Geriatric Nephrology Retrospective Cohort.

OBJECTIVES: The association between high-density lipoprotein (HDL) cholesterol levels and mortality in elderly patients undergoing hemodialysis is not well established. Thus, this study investigated HDL levels and mortality in elderly Korean patients undergoing hemodialysis. METHODS: We recruited 1860 incident hemodialysis patients aged greater than 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology. The primary outcome measure was all-cause mortality. RESULTS: The mean age of the cohort was 77.8 years, and 1049 (56.4%) were men. When we grouped the patients into HDL cholesterol tertiles, the T1 group (HDL level <30 mg/dL in men and <33 mg/dL in women) had a higher proportion of patients with end-stage kidney disease due to diabetic nephropathy. During the median follow-up period of 3.1 years, 1109 (59.7%) deaths occurred. In a multivariable Cox regression model, the T1 group had a significantly higher risk of mortality (hazard ratio [HR], 1.28; 95% confidence interval, 1.10-1.50; P = .002) compared to the T3 group. A nonlinear analysis using a restrictive spline curve showed that low HDL cholesterol levels were associated with increased HR when HDL cholesterol levels were <40 mg/dL; however, there was no association between HDL cholesterol and mortality when HDL cholesterol levels were >40 mg/dL. Triglyceride/HDL ratio was not significantly associated with the risk of mortality (HR per 1 log increase, 1.08; 95% confidence interval, 0.99-1.18; P = .069). CONCLUSIONS: Low HDL cholesterol levels are associated with an increased risk of mortality in elderly patients undergoing hemodialysis. However, there was no significant relationship between HDL cholesterol levels and mortality when levels were below 40 mg/dL. Therefore, low HDL cholesterol levels may be a useful risk factor for predicting mortality in elderly patients undergoing hemodialysis.

The impact of nurse's sense of calling, organizational commitment, job stress, and nursing work environment on patient safety management activities in comprehensive nursing care service units during the covid-19 pandemic.

BACKGROUND: As the number of COVID-19 patients rises, there has been a notable increase in the workload for nurses. However, medium-sized hospitals lacked standardized protocols or consistent approaches to address the specific working conditions of nurses. Furthermore, concerns about patient care have heightened as the issue of nursing shortages coincides with the expansion of the comprehensive nursing care services project. PURPOSE: This study aimed to investigate the factors that influence patient safety management activities, such as calling, organizational commitment, job stress, and nursing work environment, among comprehensive nursing care service unit nurses during the COVID-19 pandemic. METHODS: A conceptual framework based on the Job Demand-Resource model and literature review of patient safety management activities was used to develop structured questionnaires that were distributed to 206 participants working in 7 comprehensive nursing care service units of small and medium-sized hospitals with at least 300 beds in the S and K provinces. Data analysis was conducted using descriptive statistics, chi-squared tests, t-tests, ANOVA, and hierarchical regression with the SPSS/WIN 23.0 program. RESULTS: The results showed that calling (ß =.383, p<.001) and job stress (ß= -.187, p=.029) significantly influenced patient safety nursing activities in comprehensive care service ward nurses. The explanatory power of the model was 26.0% (F= 6.098, p<.001). CONCLUSIONS: Our findings suggest that comprehensive care service ward nurses' career, income, COVID-19 patient nursing anxiety, calling, and job stress were important factors that influence patient safety nursing activities. Therefore, it was essential to develop calling education programs and improve the nursing work system and establish a fair compensation system during the pandemic situation.

Effect of low-density lipoprotein level and mortality in older incident statin-naïve hemodialysis patients.

BACKGROUND: This study aimed to analyze low-density lipoprotein cholesterol (LDL-C) levels and their relationship with mortality in order to identify the appropriate lipid profile for older Korean hemodialysis patients. METHODS: We enrolled a total of 2,732 incident hemodialysis patients aged > 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology from 2010 Jan to 2017 Dec, which included 17 academic hospitals in South Korea. Of these patients, 1,709 were statin-naïve, and 1,014 were analyzed after excluding those with missing LDL-C level data. We used multivariate Cox regression analysis to select risk factors from 20 clinical variables among the LDL-C groups. RESULTS: The mean age of the entire patient population was 78 years, with no significant differences in age between quartiles Q1 to Q4. However, the proportion of males decreased as the quartiles progressed towards Q4 (p < 0.001). The multivariate Cox regression analysis, which included all participants, showed that low LDL-C levels were associated with all-cause mortality. In the final model, compared to Q1, the hazard ratios (95% confidence interval) were 0.77 (0.620-0.972; p = 0.027), 0.85 (0.676-1.069; p = 0.166), and 0.65 (0.519-0.824; p < 0.001) for Q2, Q3, and Q4, respectively, after adjusting for covariates, such as conventional and age-specific risk factors. The final model demonstrated that all-cause mortality increased as LDL-C levels decreased, as confirmed by a restrictive cubic spline plot. CONCLUSIONS: In older hemodialysis patients who had not previously received dyslipidemia treatment, elevated LDL-C levels were not associated with increased all-cause mortality. Intriguingly, lower LDL-C levels appear to be associated with an unfavorable effect on all-cause mortality among high-risk hemodialysis patients.

Giant Pilomatricoma Mistaken for a Malignant Tumor.

Pilomatricomas are tumors originating from the matrices of hair follicles. Giant pilomatricomas, defined as pilomatricomas that are 5 cm or larger, are benign but may appear malignant clinically. We present the case of a 69-year-old man with a rapidly growing mass on his scalp. When he visited our department, the tumor measured 10.0×6.0×4.0 cm and showed inflammation and ulceration. Magnetic resonance imaging and 18 F-fluorodeoxyglucose positron emission tomography-computed tomography showed findings resembling lymph node metastasis from a malignant tumor. However, upon an incisional biopsy, the tumor was diagnosed as a pilomatricoma. Therefore, we performed an excisional biopsy instead of radical surgery and lymph node dissection. The tumor was ultimately diagnosed as a giant pilomatricoma based on the excisional biopsy, and the patient received reconstruction only at the site of the defect. A giant pilomatricoma can be mistaken for a malignant tumor due to its characteristics. In such uncertain cases, it can be helpful to first perform an excisional biopsy.

Entomopathogenic Potential of Bacillus velezensis CE 100 for the Biological Control of Termite Damage in Wooden Architectural Buildings of Korean Cultural Heritage.

Biocontrol strategies are gaining tremendous attention in insect pest management, such as controlling termite damage, due to the growing awareness of the irreparable harm caused by the continuous use of synthetic pesticides. This study examines the proteolytic and chitinolytic activities of Bacillus velezensis CE 100 and its termiticidal effect through cuticle degradation. The proteolytic and chitinolytic activities of B. velezensis CE 100 systematically increased with cell growth to the respective peaks of 68.3 and 128.3 units/mL after seven days of inoculation, corresponding with the highest cell growth of 16 × 107 colony-forming units (CFU)/mL. The in vitro termiticidal assay showed that B. velezensis CE 100 caused a rapid and high rate of termite mortality, with a median lethal time (LT50) of >1 h and the highest mortality rates of 91.1% and 92.2% recorded at 11 h and 12 h in the bacterial broth culture and crude enzyme fraction, respectively. In addition to broken setae and deformed sockets, termites treated with the bacterial broth culture exhibited degraded epicuticles, while the crude enzyme fraction caused severe disintegration of both the epicuticle and endocuticle. These results indicate the tremendously higher potential of B. velezensis CE 100 in the biological control of subterranean termites compared to the previously used entomopathogenic bacteria.

Ceria-Zirconia nanoparticles reduce intracellular globotriaosylceramide accumulation and attenuate kidney injury by enhancing the autophagy flux in cellular and animal models of Fabry disease.

BACKGROUND: Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid-polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We analyzed whether they suppress globotriaosylceramide (Gb3) accumulation by enhancing autophagy flux and thereby attenuate kidney injury in both cellular and animal models of FD. RESULTS: Gb3 was significantly increased in cultured human renal proximal tubular epithelial cells (HK-2) and human podocytes following the siRNA silencing of α galactosidase A (α-GLA). PEG-CZNPs effectively reduced the intracellular accumulation of Gb3 in both cell models of FD and improved both intracellular inflammation and apoptosis in the HK-2 cell model of FD. Moreover these particles attenuated pro fibrotic cytokines in the human podocyte model of FD. This effect was revealed through an improvement of the intracellular autophagy flux function and a reduction in reactive oxygen species (ROS). An FD animal model was generated in which 4-week-old male B6;129-Glatm1Kul/J mice were treated for 8 weeks with 10 mg/kg of PEG-CZNPs (twice weekly via intraperitoneal injection). Gb3 levels were reduced in the kidney tissues of these animals, and their podocyte characteristics and autophagy flux functions were preserved. CONCLUSIONS: PEG-CZNPs alleviate FD associated kidney injury by enhancing autophagy function and thus provide a foundation for the development of new drugs to treat of storage disease.

Association between physical activity and risk of renal function decline and mortality in community-dwelling older adults: a nationwide population-based cohort study.

BACKGROUND: Physical activity (PA) is an important risk factor associated with health outcomes. However, the relationship between PA and kidney function decline in older adults remains unclear. We examined the influence of PA on kidney function decline and mortality in community-dwelling older adults. METHODS: Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 who had available health checkup data from 2009 to 2010 were included. The cohort was followed annually through December 2015 for anthropometric, sociodemographic, and medical information including outcomes and biennially for laboratory information from the health checkup. We divided these patients into three groups according to self-reported PA (Inactive group: no leisure-time PA, Active group: vigorous activity for at least 80 min/week or a sum of moderate-intensity activity and walking for at least 300 min/week, Low-active group: level of PA between the definitions of the other two groups). Associations between the intensity of PA and death, cardiovascular death, and ≥ 50% eGFR decline were investigated. RESULTS: Among 102,353 subjects, 32,984 (32.23%), 54,267 (53.02%), and 15,102 (14.75%) were classified into the inactive, low-active, and active groups, respectively. The active group was younger, contained a higher proportion of men, and had higher frequencies of hypertension, diabetes mellitus, drinking, and smoking than the other groups. The active group had significantly lower incidence rates of mortality, cardiovascular mortality, and kidney function decline than the other groups (all p < 0.001). The active group also showed lower all-cause (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.70-0.82) and cardiovascular mortality (HR, 0.64; 95% CI, 0.53-0.78) and protection against ≥ 50% eGFR decline (HR, 0.81; 95% CI, 0.68-0.97) compared with the inactive group in the fully adjusted Cox proportional hazards regression model. CONCLUSIONS: High PA was an independent modifiable lifestyle factor for reducing mortality and protecting against declines in kidney function in older adults.

Violacein-embedded nanofiber filters with antiviral and antibacterial activities.

Most respiratory masks are made of fabrics, which only capture the infectious virus carriers into the matrix. However, these contagious viruses stay active for a long duration (∼7 days) within the fabric matrix possibly inducing post-contact transmissions. Moreover, conventional masks are vulnerable to bacterial growth with prolonged exposure to exhaled breaths. Herein, we combined violacein, a naturally-occurring antimicrobial agent, with porous nanofiber membranes to develop a series of functional filters that autonomously sterilizes viruses and bacteria. The violacein-embedded membrane inactivates viruses within 4 h (99.532 % reduction for influenza and 99.999 % for human coronavirus) and bacteria within 2 h (75.5 % reduction). Besides, its nanofiber structure physically filters out the nanoscale (<0.8 µm) and micron-scale (0.8 µm - 3 µm) particulates, providing high filtration efficiencies (99.7 % and 100 % for PM 1.0 and PM 10, respectively) with long-term stability (for 25 days). In addition, violacein provides additional UV-resistant property, which protects the skin from sunlight. The violacein-embedded membrane not only proved the sterile efficacy of microbe extracted pigments for biomedical products but also provided insights to advance the personal protective equipment (PPE) to fight against contagious pathogens.

Developing a structural equation model from Grandey's emotional regulation model to measure nurses' emotional labor, job satisfaction, and job performance.

AIMS: This study constructed and tested a structural equation model on clinical nurses' emotional labor, job satisfaction, and job performance based on Grandey's emotion regulation model. DESIGN: We performed a correlational study to predict the relationship between the following variables: emotional labor (surface and deep acting), job satisfaction, job performance, self-efficacy, emotional intelligence, display rules, job autonomy, social support, and job stress. METHODS: Our hypothetical model was based on Grandey's emotional regulation model and on a literature review of emotional labor, job satisfaction, and job performance. Structured questionnaires were distributed to participants who worked in seven general hospitals with no less than 300 beds in a province, South Korea. We analyzed 424 questionnaires and used AMOS 23 to explore the relationships between the constructs. RESULTS: Our model fit the data well (χ2 = 96.420, GFI = 0.966, CFI = 0.956, RMSEA = 0.084). Display rules, self-efficacy, job autonomy, and job stress accounted for 20.5% of variance in surface acting. Self-efficacy, emotional intelligence, job autonomy, and job stress accounted for 23.3% of variance in deep acting. Job stress, self-efficacy, job autonomy, surface acting, and deep acting accounted for 45.0% of variance in job satisfaction. Self-efficacy, job autonomy, emotional intelligence, and deep acting accounted for 43.3% of variance in job performance. CONCLUSION: We confirmed that display rules, emotional intelligence, job stress, self-efficacy, and job autonomy are important factors that could decrease nurses' emotional labor and increase their job satisfaction and performance. These findings support the development and application of various interventions to decrease emotional labor and increase job satisfaction and job performance among nurses. IMPLEMENTATION: This study filled the need for an integrated structural equation model of emotional labor. With this model, we found that emotional labor operates differently in nursing practice than in other service fields. As such, this model can help hospital management to adjust their customer service guidelines to improve nurses' job satisfaction and performance.

Assessment of doses in contaminated urban areas: modelling exercise based on Fukushima data.

State-of-the-art dose assessment models were applied to estimate doses to the population in urban areas contaminated by the Fukushima Daiichi Nuclear Power Plant accident. Assessment results were compared among five models, and comparisons of model predictions with actual measurements were also made. Assessments were performed using both probabilistic and deterministic approaches. Predicted dose distributions for indoor and outdoor workers from a probabilistic approach were in good agreement with the actual measurements. In addition, when the models were applied to assess the doses to the representative person, based on a concept recommended by the International Commission on Radiological Protection and in the International Atomic Energy Agency Safety Standards, it was evident that doses to the representative person obtained with a deterministic approach were always higher than those obtained with a probabilistic approach using the same model.

Urban working groups in the IAEA's model testing programmes: overview from the MODARIA I and MODARIA II programmes.

The IAEA's model testing programmes have included a series of Working Groups concerned with modelling radioactive contamination in urban environments. These have included the Urban Working Group of Validation of Environmental Model Predictions (1988-1994), the Urban Remediation Working Group of Environmental Modelling for Radiation Safety (EMRAS) (2003-2007), the Urban Areas Working Group of EMRAS II (2009-2011), the Urban Environments Working Group of (Modelling and Data for Radiological Impact Assessments) MODARIA I (2013-2015), and most recently, the Urban Exposures Working Group of MODARIA II (2016-2019). The overarching objective of these Working Groups has been to test and improve the capabilities of computer models used to assess radioactive contamination in urban environments, including dispersion and deposition processes, short-term and long-term redistribution of contaminants following deposition events, and the effectiveness of various countermeasures and other protective actions, including remedial actions, in reducing contamination levels, human exposures, and doses to humans. This paper describes the exercises conducted during the MODARIA I and MODARIA II programmes. These exercises have included short-range and mid-range atmospheric dispersion exercises based on data from field tests or tracer studies, hypothetical urban dispersion exercises, and an exercise based on data collected after the Fukushima Daiichi accident. Improvement of model capabilities will lead to improvements in assessing various contamination scenarios (real or hypothetical), and in turn, to improved decision-making and communication with the public following a nuclear or radiological emergency.

Does the adoption of emerging technologies improve technical efficiency? Evidence from Korean manufacturing SMEs.

Despite the proliferation of innovative technologies during the Fourth Industrial Revolution (4IR), there is a severe lack of quantitative and empirical studies that deal with the effectiveness of recently emerging technologies. This study examines the impact of employing core technologies of the 4IR on small and medium enterprises (SMEs). We used the firm-level cross-sectional data on Korean manufacturing SMEs, including the information on technology utilization. The stochastic production frontier estimation with selectivity correction is employed, besides matching technique to obtain unbiased estimates on technology efficiency. The empirical analysis finds that adopting emerging technologies enhances the productivity of SMEs. After observed and unobserved factors are controlled, the technical efficiency of adopters is higher by more than 26% on average, compared to non-adopters. Moreover, if the gap among production frontiers is considered, the difference in productivity would rise further. Additionally, a strategic alliance is a crucial route for SMEs to accept new technologies.

PLD1 and PLD2 differentially regulate the balance of macrophage polarization in inflammation and tissue injury.

Phospholipase D (PLD) isoforms PLD1 and PLD2 serve as the primary nodes where diverse signaling pathways converge. However, their isoform-specific functions remain unclear. We showed that PLD1 and PLD2 selectively couple to toll-like receptor 4 (TLR4) and interleukin 4 receptor (IL-4R) and differentially regulate macrophage polarization of M1 and M2 via the LPS-MyD88 axis and the IL-4-JAK3 signaling, respectively. Lipopolysaccharide (LPS) enhanced TLR4 or MyD88 interaction with PLD1; IL-4 induced IL-4R or JAK3 association with PLD2, indicating isozyme-specific signaling events. PLD1 and PLD2 are indispensable for M1 polarization and M2 polarization, respectively. Genetic and pharmacological targeting of PLD1 conferred protection against LPS-induced sepsis, cardiotoxin-induced muscle injury, and skin injury by promoting the shift toward M2; PLD2 ablation intensified disease severity by promoting the shift toward M1. Enhanced Foxp3+ regulatory T cell recruitment also influenced the anti-inflammatory phenotype of Pld1LyzCre macrophages. We reveal a previously uncharacterized role of PLD isoforms in macrophage polarization, signifying potential pharmacological interventions for macrophage modulation.

Phospholipase D1 is upregulated by vorinostat and confers resistance to vorinostat in glioblastoma.

Glioblastoma (GBM) is an aggressive brain tumor and drug resistance remains a major barrier for therapeutics. Epigenetic alterations are implicated in GBM pathogenesis, and epigenetic modulators including histone deacetylase (HDAC) inhibitors are exploited as promising anticancer therapies. Here, we demonstrate that phospholipase D1 (PLD1) is a transcriptional target of HDAC inhibitors and confers resistance to HDAC inhibitor in GBM. Treatment of vorinostat upregulates PLD1 through PKCζ-Sp1 axis. Vorinostat induces dynamic changes in the chromatin structure and transcriptional machinery associated with PLD1 promoter region. Cotreatment of vorinostat with PLD1 inhibitor further attenuates invasion, angiogenesis, colony-forming capacity, and self-renewal capacity, compared with those of either treatment. PLD1 inhibitor overcomes resistance to vorinostat in GBM cells intracranial GBM tumors. Our finding provides new insight into the role of PLD1 as a target of resistance to vorinostat, and PLD1 inhibitor might provide the basis for therapeutic combinations with improved efficacy of HDAC inhibitor.

Cellular and subcellular localization of endogenous phospholipase D6 in seminiferous tubules of mouse testes.

Phospholipase D6 (PLD6) plays pivotal roles in mitochondrial dynamics and spermatogenesis, but the cellular and subcellular localization of endogenous PLD6 in testis germ cells is poorly defined. We examined the distribution and subcellular localization of PLD6 in mouse testes using validated specific anti-PLD6 antibodies. Ectopically expressed PLD6 protein was detected in the mitochondria of PLD6-transfected cells, but endogenous PLD6 expression in mouse testes was localized to the perinuclear region of pachytene spermatocytes, and more prominently, to the round (Golgi and cap phases) and elongating spermatids (acrosomal phase); these results suggest that PLD6 is localized to the Golgi apparatus. The distribution of PLD6 in the round spermatids partially overlapped with that of the cis-Golgi marker GM130, indicating that the PLD6 expression corresponded to the GM130-positive subdomains of the Golgi apparatus. Correlative light and electron microscopy revealed that PLD6 expression in developing spermatids was localized almost exclusively to several flattened cisternae, and these structures might correspond to the medial Golgi subcompartment; neither the trans-Golgi networks nor the developing acrosomal system expressed PLD6. Further, we observed that PLD6 interacted with tesmin, a testis-specific transcript necessary for successful spermatogenesis in mouse testes. To our knowledge, these results provide the first evidence of PLD6 as a Golgi-localized protein of pachytene spermatocytes and developing spermatids and suggest that its subcompartment-specific distribution within the Golgi apparatus may be related to the specific functions of this organelle during spermatogenesis.

Phospholipase D1 inhibition sensitizes glioblastoma to temozolomide and suppresses its tumorigenicity.

Resistance of glioblastoma to the chemotherapeutic compound temozolomide is associated with the presence of glioblastoma stem cells in glioblastoma and is a key obstacle for the poor prognosis of glioblastoma. Here, we show that phospholipase D1 is elevated in CD44High glioblastoma stem cells and in glioblastoma, especially recurring glioblastoma. Phospholipase D1 elevation positively correlated with the level of CD44 and poor prognosis in glioblastoma patients. Temozolomide significantly upregulated the expression of phospholipase D1 in the low and moderate CD44 populations of glioblastoma stem cells, but not in the CD44High population in which phospholipase D1 is highly expressed. Phospholipase D1 conferred resistance to temozolomide in CD44High glioblastoma stem cells and increased their self-renewal capacity and maintenance. Phospholipase D1 expression significantly correlated with levels of temozolomide resistance factors, which were suppressed by microRNA-320a and -4496 induced by phospholipase D1 inhibition. Genetic and pharmacological targeting of phospholipase D1 attenuated glioblastoma stem cell-derived intracranial tumors of glioblastoma using the microRNAs, and improved survival. Treatment solely with temozolomide produced no benefits on the glioblastoma, whereas in combination, phospholipase D1 inhibition sensitized glioblastoma stem cells to temozolomide and reduced glioblastoma tumorigenesis. Together, these findings indicate that phospholipase D1 inhibition might overcome resistance to temozolomide and represents a potential treatment strategy for glioblastoma. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Radial Plus Ipsilateral Femoral Approach is Feasible in Percutaneous Interventions for Iliac Artery Chronic Total Occlusion.

BACKGROUND: Compared with conventional bilateral femoral (BF) approach, radial plus ipsilateral femoral (RF) approach may be feasible in the percutaneous intervention for iliac artery chronic total occlusion (CTO). METHODS: We included patients who underwent iliac CTO intervention between August 2009 and July 2018 in a tertiary referral center in Korea. RESULTS: A total of 83 patients were enrolled in this study. Of them, 51 and 32 patients were categorized into RF and BF initial access groups, respectively. The overall success rates were 98.0% and 96.7% in RF and BF group, respectively, and the techniques were also similar including use of bilateral wiring, stent type and profile, and post balloon but longer procedure time in the BF group. Additional contralateral femoral access was needed in 6 patients for the treatment of contralateral lesions, distal embolization, and due to tortuous right subclavian artery. Periprocedural complications including vascular injury, iliac perforation, and distal embolization occurred similarly in both groups with numerically lower rate of periprocedural bleeding in the RF group (9.8%) than in the BF group (21.9%). Clinical follow-up at 6 months showed there were no difference in the rates of death, cardiovascular death, target-limb reintervention, and unplanned target limb amputation in both groups. CONCLUSIONS: RF approach for iliac CTO intervention was related to similar technical success rate with acceptable periprocedural safety outcomes compared with conventional BF approach.

Analysis of pain markers and epidural fibrosis caused by repeated spinal surgery in Sprague-Dawley rats.

BACKGROUND: Epidural fibrosis is one of the aetiologies of pain following a spinal revision surgery. It is reported that the specific members of the mitogen - activated protein kinases (MAPK) family might mediate neuropathic pain. However, roles of epidural fibrosis caused by repeated spinal surgeries and pain-related proteins in causing the post spinal surgery syndrome remain unknown. Using a rat spinal surgery epidural fibrosis and adhesion model, in this study, we evaluated and investigated the relationship between pain markers and epidural fibrosis. METHODS: Sprague-Dawley rats that underwent the spinal surgery were divided into three groups: group A (single laminectomy), group B (two repeated surgeries) and group C (three repeated surgeries). Dural thickness was measured in each experimental group, and immunohistochemical analysis and western blotting of mitogen-activated protein kinases were performed (ERK, p38 and JNK) using the spine cord. RESULTS: Dural thickness was 6.363 ± 1.911 µm in group A, 13.238 ± 2.123 µm in group B and 19.4 ± 2.115 µm in group C, respectively. In the western blotting, phosphorylated ERK expression gradually increased with the number of repeated surgeries, and expression in groups B (1.77-fold) and C (2.42-fold) increased as compared to expression in group A. Phosphorylated p38 showed an increasing trend with the number of repeated surgeries, and groups B (1.17-fold) and C (1.33-fold) expression increased compared with group A. However, phosphorylated JNK expression did not gradually increase with the number of repeated surgeries, and groups B (1.62-fold) and C (1.43-fold) expression increased compared with group A. Excluding phosphorylated JNK, immunohistochemical analysis revealed that phosphorylated ERK and p38 expression gradually increased with the number of repeated surgeries in the spine dorsal horn, as evidenced by western blotting. CONCLUSIONS: Repeated spinal surgeries may increase dural thickness and expression of phosphorylated ERK and p38 in the spinal dorsal horn, and it suggests that the neuropathic pain is likely induced by epidural fibrosis and that the pain increases with the number of repeated surgeries.

Locus-Specific Reversible DNA Methylation Regulates Transient IL-10 Expression in Th1 Cells.

IL-10 is a pleiotropic cytokine with multifaceted functions in establishing immune homeostasis. Although expressed by Th1 and Th2 cells, conventional Th1 cells produce marginal levels of IL-10 compared with their Th2 counterparts. In this study, we investigated the epigenetic mechanisms of Il-10 gene expression in Th1 cells. Bioinformatics EMBOSS CpG plot analysis and bisulfite pyrosequencing revealed three CpG DNA methylation sites in the Il-10 gene locus. Progressive DNA methylation at all of the CpG regions of interest (ROIs) established a repressive program of Il-10 gene expression in Th1 cells. Interestingly, Th1 cells treated with IL-12 and IL-27 cytokines, thereby mimicking a chronic inflammatory condition in vivo, displayed a significant increase in IL-10 production that was accompanied by selective DNA demethylation at ROI 3 located in intron 3. IL-10-producing T cells isolated from lymphocytic choriomeningitis virus-infected mice also showed enhanced DNA demethylation at ROI 3. Binding of STAT1 and STAT3 to demethylated ROI 3 enhanced IL-10 expression in an IL-12/IL-27-dependent manner. Accordingly, CD4+ T cells isolated from STAT1- or STAT3-knockout mice were significantly defective in IL-10 production. Our data suggest that, although stably maintained DNA methylation at the promoter may repress IL-10 expression in Th1 cells, locus-specific reversible DNA demethylation may serve as a threshold platform to control transient Il-10 gene expression.