Enhanced oxidation of parabens in an aqueous solution by air-assisted cold plasma.

Various contaminants of emerging concern (CECs) including pharmaceuticals and personal care products (PPCPs) have been known to threaten the aquatic ecosystem and human health even at low levels in surface water. Among them, the wide variety use of parabens as preservatives may pose potential threat to human because parabens may present estrogenic activity. Various advanced oxidation processes have been attempted to reduce parabens, but challenges using cold plasma (CP) are very rare. CP is worth paying attention to in reducing parabens because it has the advantage of generating radical ions, including reactive oxygen/nitrogen species and various ions. Accordingly, this study demonstrates how CP can be utilized and how CP competes with other advanced oxidation processes in energy requirements. Quantified ethyl-, propyl-, and butyl-paraben indicate that CP can effectively degrade them up to 99.1% within 3 h. Regression reveals that the kinetic coefficients of degradation can be increased to as high as 0.0328 min-1, comparable to other advanced oxidation processes. Many by-products generated from the oxidation of parabens provide evidence of the potential degradation pathway through CP treatment. In addition, we found that the electrical energy consumption per order of CP (39-95 kWh/m3/order) is superior to other advanced oxidation processes (69∼31,716 kWh/m3/order). Overall, these results suggest that CP may be a viable option to prevent adverse health-related consequences associated with parabens in receiving water.

Two cases of extraluminal migration of fishbones into the thyroid gland and submandibular gland.

Laryngopharyngeal or cervical pain following ingestion of foreign bodies is one of the most frequently encountered emergencies in otolaryngologic practice. Although most of these foreign bodies can be easily removed under laryngoscopic examination without any complications, surgical removal may be required when foreign bodies migrate extraluminally. This report describes two rare cases of ingested fishbones that had migrated, one each to the thyroid gland and submandibular gland. Extraluminal migration fishbones should always be considered in otolaryngologic clinics.

Comparison of clinical outcomes and second-look arthroscopic evaluations between anterior cruciate ligament anteromedial bundle augmentation and single-bundle anterior cruciate ligament reconstruction.

SUBJECT: This study compared clinical outcomes and second-look arthroscopic evaluations between anterior cruciate ligament (ACL) anteromedial (AM) bundle augmentation and single-bundle ACL reconstruction. PURPOSE: We compared the clinical results and the second-look arthroscopic findings between (1) single-bundle ACL reconstruction in complete rupture and (2) ACL AM bundle augmentation in isolated AM bundle rupture. MATERIALS AND METHODS: Two groups of patients underwent ACL surgery from January 2013 to December 2018. Group 1, who had 64 cases of single-bundle ACL reconstruction with second-look arthroscopy, and Group 2, who had 21 cases of AM bundle augmentation of ACL with second-look arthroscopy, were targeted. We evaluated and compared the clinical results (Lysholm score, Tegner activity score, Lachman test, and pivot-shift test) and synovialization at second-look arthroscopy before the operation and in the final follow-up period, between Group 1 and Group 2. RESULTS: The Lysholm score (p = 0.96) and Tegner activity score (p = 0.351) at final follow-up (mean 27.1 months) were 78.3 and 7.2 in Group 1 and 89.1 and 8.1 in Group 2, respectively. The Lachman test (p = 0.074) and pivot-shift test (p = 0.031) results at final follow-up were improved; however, there was no statistical significance. Second-look arthroscopy showed that percentages of synovialization area of grafted tendon at mean 15.6 months follow-up were 61.4% and 93.1% in Group 1 and Group 2, respectively (p = 0.008). The synovial coverage in Group 2 was higher than in Group 1. CONCLUSION: The AM bundle augmentation for ACL injury in which the posterolateral bundle was preserved showed better clinical scores and synovial coverage than single-bundle ACL reconstruction for complete ACL rupture. LEVEL OF EVIDENCE: The level of evidence is Level III, retrospective with case series.

Directly Printed Low-Cost Nanoparticle Sensor for Vibration Measurement during Milling Process.

A real-time, accurate, and reliable process monitoring is a basic and crucial enabler of intelligent manufacturing operation and digital twin applications. In this study, we represent a novel vibration measurement method for workpiece during the milling process using a low-cost nanoparticle vibration sensor. We directly printed the vibration sensor based on silver nanoparticles positioned onto a polyimide substrate using an aerodynamically-focused nanomaterials printing system, which is a direct printing technique for inorganic nanomaterials positioned onto a flexible substrate. Since it does not require any post-process such as chemical etching and heat treatment, a highly sensitive vibration sensor composed of a microscale porous structure was fabricated at a cost of several cents each. Furthermore, accurate and reliable vibration data was obtained by simple and direct attachment to a workpiece. In this study, we discussed the performance of vibration measurement of a fabricated sensor in comparison to a commercial vibration sensor. Using frequency and power spectrum analysis of obtained data, we directly measured the vibration of workpiece during the milling process, according to a process parameter. Lastly, we applied a fabricated sensor for the digital twins of turbine blade manufacturing in which vibration greatly affects the quality of the product to predict the process defects in real-time.

A Sustainable Ambulance Operation Model in a Low-Resource Country (the Democratic Republic of Congo).

Due to an increase in traffic collisions, the demand for prehospital medical services is on the rise, even in low-resource countries where emergency ambulance services have not been previously provided. To build a sustainable and continuous prehospital ambulance operation model, it is necessary to consider the medical system and economic conditions of the corresponding country. In an attempt to construct a prehospital ambulance operation model that ensures continuous operation, a pilot "emergency patient transporting service from field to hospital" operation was established for approximately three months in Kinshasa, the capital of the DR Congo. To construct a continuously operating model even after the pilot operation, willingness to pay (WTP) by type of emergency medical and transport service was investigated by implementing the contingent valuation method (CVM). Using CVM, the WTP for prehospital emergency services targeting ambulance services personnel, patients, policemen, and hospital staff participating in the pilot operation was calculated. The results of the pilot operation revealed that there were a total of 212 patients with a mean patient number of 2.4 per day. A total of 155 patients used the services for hospital transport, while 121 patients used the services for traffic collisions. Traffic collisions were the category in which ambulance services were most frequently needed (66.2%). Pay services were most frequently utilized in the home-visit services category (40.9%). Based on these results, eight independently operated ambulance operation models and sixteen models that utilize hospital medical personnel and policemen already belonging to existing institutions were proposed. In an effort to implement emergency medical ambulance services in the DR Congo, medical staff receiving pay for performance (incentive pay) should be deployed in the field and on call. Accordingly, with respect to sustainable development goals, various pay-for-service models should be used.

Dominant high expression of wild-type HSP110 defines a poor prognostic subgroup of colorectal carcinomas with microsatellite instability: a whole-section immunohistochemical analysis.

The aim of this study is to establish heat shock protein 110 (HSP110) as a prognostic biomarker of colorectal carcinomas (CRCs) with microsatellite instability-high (MSI-H) by considering the intratumoral heterogeneity of HSP110 expression. We performed whole-section immunohistochemistry (IHC) for wild-type HSP110 (HSP110wt) in 164 MSI-H CRCs. The intensity of the HSP110wt expression in tumor cells was semiquantitatively scored (0/1/2/3), and the HSP110wt expression status of each tumor was classified as low or high using the following four scoring criteria: H-score, dominant intensity score, lowest intensity score, and highest intensity score. Among the four criteria, only the dominant intensity score-based dichotomous classification of HSP110wt expression was significantly associated with a difference in disease-free survival (log-rank p = 0.035) in 164 MSI-H CRCs. The HSP110wt-low MSI-H CRCs were significantly correlated with larger deletions in the HSP110 T17 mononucleotide repeat (≥4 bp; p < 0.001). In conclusion, the dominant intensity score-based assessment of HSP110wt IHC can be a simple and useful method for the prognostic stratification of MSI-H CRCs. It is expected that HSP110wt IHC may be used to identify a subgroup of MSI-H CRCs with poor prognosis and/or candidates for further treatment, such as immunotherapy using immune checkpoint inhibitors in MSI-H CRCs.

Inhibitory effect of obovatol from Magnolia obovata on the Salmonella type III secretion system.

In many pathogenic Gram-negative bacteria, such as Salmonella, Escherichia coli, Yersinia and Chlamydia spp., which cause diseases in humans, the type III secretion system (TTSS) is an important virulence factor that translocates effector proteins into the cytosol of host cells. Thus, the TTSS is a good target for antibacterial agents. Here we used a hemolysis assay to search for TTSS inhibitors and found that a compound from Magnolia obovata called obovatol blocks the TTSS of Salmonella. Obovatol showed potent inhibitory activity (IC50=19.8 µM) against the TTSS-related hemolysis of Salmonella, which was not due to a reduction of bacterial growth. Instead, the compound inhibited bacterial motility, TTSS-related mRNA expression and effector protein secretion. These data demonstrate the inhibitory effect of obovatol on the Salmonella TTSS and suggest that it could be useful for the prevention and supplementary treatment of bacterial infections.

Optimal Temperature and Light Intensity for Improved Mixotrophic Metabolism of Chlorella sorokiniana Treating Livestock Wastewater.

Mixotrophic microalgal growth gives a great premise for wastewater treatment based on photoautotrophic nutrient utilization and heterotrophic organic removal while producing renewable biomass. There remains a need for a control strategy to enrich them in a photobioreactor. This study performed a series of batch experiments using a mixotroph, Chlorella sorokiniana, to characterize optimal guidelines of mixotrophic growth based on a statistical design of the experiment. Using a central composite design, this study evaluated how temperature and light irradiance are associated with CO2 capture and organic carbon respiration through biomass production and ammonia removal kinetics. By conducting regressions on the experimental data, response surfaces were created to suggest proper ranges of temperature and light irradiance that mixotrophs can beneficially use as two types of energy sources. The results identified that efficient mixotrophic metabolism of Chlorella sorokiniana for organics and inorganics occurs at the temperature of 30-40°C and diurnal light condition of 150-200 µmol E·m2·s-1. The optimal specific growth rate and ammonia removal rate were recorded as 0.51/d and 0.56/h on average, respectively, and the confirmation test verified that the organic removal rate was 105 mg COD·l-1·d-1. These results support the development of a viable option for sustainable treatment and effluent quality management of problematic livestock wastewater.

Deletion in HSP110 T17: correlation with wild-type HSP110 expression and prognostic significance in microsatellite-unstable advanced gastric cancers.

Deletion of the HSP110 T17 mononucleotide repeat has recently been identified as a prognostic marker that is correlated with wild-type HSP110 (HSP110wt) expression in microsatellite instability-high (MSI-H) colorectal cancers. The aim of this study was to assess the correlation between deletion of the HSP110 T17 repeat and expression of HSP110wt using DNA testing and immunohistochemistry and to determine the prognostic implications of HSP110 T17 deletion in MSI-H advanced gastric cancers (GCs). The status of HSP110wt expression was evaluated by immunohistochemistry using an HSP110wt-specific antibody in 142 MSI-H advanced GCs. The size of the HSP110 T17 repeat deletion was analyzed in 96 MSI-H advanced GCs; deletions were divided into small (0-2base pairs) and large deletions (3-5base pairs). Low and high expressions of HSP110wt were detected in 38 (26.8%) and 104 (73.2%) of the 142 cases, respectively. The HSP110 T17 deletion was observed in 45 (46.9%) of the 96 MSI-H GC samples. Tumors with high expression of HSP110wt showed a tendency to have small or no deletion of HSP110 T17. In Kaplan-Meier survival analysis, tumors with a large HSP110 T17 deletion were associated with favorable overall survival and disease-free survival compared with those with small/no deletion of HSP110 T17. However, HSP110 T17 deletion size was not an independent prognostic factor in multivariate analysis. In summary, deletion of the HSP110 T17 repeat was frequently observed in MSI-H GCs, and HSP110 T17 deletion size was inversely correlated with HSP110wt expression status. Large HSP110 T17 was not a prognostic indicator in MSI-H GCs.

Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system.

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease in terms of molecular carcinogenic pathways. Based on recent findings regarding the multiple serrated neoplasia pathway, we revised an eight-marker panel for a new CIMP classification system. METHODS: 1370 patients who received surgical resection for CRCs were classified into three CIMP subtypes (CIMP-N: 0-4 methylated markers, CIMP-P1: 5-6 methylated markers and CIMP-P2: 7-8 methylated markers). Our findings were validated in a separate set of high-risk stage II or stage III CRCs receiving adjuvant fluoropyrimidine plus oxaliplatin (n=950). RESULTS: A total of 1287/62/21 CRCs cases were classified as CIMP-N/CIMP-P1/CIMP-P2, respectively. CIMP-N showed male predominance, distal location, lower T, N category and devoid of BRAF mutation, microsatellite instability (MSI) and MLH1 methylation. CIMP-P1 showed female predominance, proximal location, advanced TNM stage, mild decrease of CK20 and CDX2 expression, mild increase of CK7 expression, BRAF mutation, MSI and MLH1 methylation. CIMP-P2 showed older age, female predominance, proximal location, advanced T category, markedly reduced CK20 and CDX2 expression, rare KRAS mutation, high frequency of CK7 expression, BRAF mutation, MSI and MLH1 methylation. CIMP-N showed better 5-year cancer-specific survival (CSS; HR=0.47; 95% CI: 0.28-0.78) in discovery set and better 5-year relapse-free survival (RFS; HR=0.50; 95% CI: 0.29-0.88) in validation set compared with CIMP-P1. CIMP-P2 showed marginally better 5-year CSS (HR=0.28, 95% CI: 0.07-1.22) in discovery set and marginally better 5-year RFS (HR=0.21, 95% CI: 0.05-0.92) in validation set compared with CIMP-P1. CONCLUSIONS: CIMP subtypes classified using our revised system showed different clinical outcomes, demonstrating the heterogeneity of multiple serrated precursors of CIMP-positive CRCs.

Downregulation of acetyl-CoA synthetase 2 is a metabolic hallmark of tumor progression and aggressiveness in colorectal carcinoma.

Acetyl-CoA synthetase-2 is an emerging key enzyme for cancer metabolism, which supplies acetyl-CoA for tumor cells by capturing acetate as a carbon source under stressed conditions. However, implications of acetyl-CoA synthetase-2 in colorectal carcinoma may differ from other malignancies, because normal colonocytes use short-chain fatty acids as an energy source, which are supplied by fermentation of the intestinal flora. Here we analyzed acetyl-CoA synthetase-2 mRNA expression by reverse-transcription quantitative PCR in paired normal mucosa and tumor tissues of 12 colorectal carcinomas, and subsequently evaluated acetyl-CoA synthetase-2 protein expression by immunohistochemistry in 157 premalignant colorectal lesions, including 60 conventional adenomas and 97 serrated polyps, 1,106 surgically resected primary colorectal carcinomas, and 23 metastatic colorectal carcinomas in the liver. In reverse-transcription quantitative PCR analysis, acetyl-CoA synthetase-2 mRNA expression was significantly decreased in tumor tissues compared with corresponding normal mucosa tissues. In acetyl-CoA synthetase-2 immunohistochemistry analysis, all 157 colorectal polyps showed moderate-to-strong expression of acetyl-CoA synthetase-2. However, cytoplasmic acetyl-CoA synthetase-2 expression was downregulated (acetyl-CoA synthetase-2 low expression) in 771 (69.7%) of 1,106 colorectal carcinomas and 21 (91.3%) of 23 metastatic lesions. The colorectal carcinomas with acetyl-CoA synthetase-2-low expression were significantly associated with advanced TNM stage, poor differentiation, and frequent tumor budding. Regarding the molecular aspect, acetyl-CoA synthetase-2-low expression exhibited a tendency of frequent KRT7 expression and decreased KRT20 and CDX2 expression. In survival analysis, acetyl-CoA synthetase-2-low expression was an independent prognostic factor for poor 5-year progression-free survival (hazard ratio, 1.39; 95% confidence interval, 1.08-1.79; P=0.01). In conclusion, these findings suggest that downregulation of acetyl-CoA synthetase-2 expression is a metabolic hallmark of tumor progression and aggressive behavior in colorectal carcinoma.

Out-of-hospital cardiac arrest patients treated with cardiopulmonary resuscitation using extracorporeal membrane oxygenation: focus on survival rate and neurologic outcome.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a useful treatment for refractory out-of-hospital cardiac arrest (OHCA). However, little is known about the predictors of survival and neurologic outcome after ECMO. We analyzed our institution's experience with ECMO for refractory OHCA and evaluated the predictors of survival and neurologic outcome after ECMO. METHODS: This was a retrospective review of the medical records of 23 patients who were treated with ECMO due to OHCA that was unresponsive to conventional cardiopulmonary resuscitation, between January 2009 and January 2014. RESULTS: Our ECMO team was activated within 10 min for refractory OHCA, and the 30-day survival rate was 43.5 %. In a multivariate analysis that evaluated independent factors contributing to mortality, urine output ≤ 0.5 mL · kg(-1) · h(-1) (defined as oliguria) during the 24 h after ECMO was statistically significant (OR, 32.271; 95 % CI, 1.379-755.282; p = 0.031). Just after ECMO implantation, 6 of the 9 patients (66.7 %) who had normal findings on brain computed tomography (CT) survived with a cerebral performance category (CPC) of grade 1. However, only 3 of the 11 patients (27 %) who had evidence of hypoxic brain damage on initial brain CT survived (their CPC grade was 4). CONCLUSIONS: Based on our findings, the survival rate can be improved by rapid implantation of ECMO, and oliguria seen during the first 24 h after ECMO may be an independent predictor of mortality. Furthermore, findings on brain CT just after ECMO and subsequent images may represent an important predictor for neurologic outcome after ECMO.

Associations and prognostic implications of Eastern Cooperative Oncology Group performance status and tumoral LINE-1 methylation status in stage III colon cancer patients.

BACKGROUND: Low methylation status of LINE-1 in tumors is associated with poor survival in patients with colon cancer. Eastern Cooperative Oncology Group performance status (ECOG-PS) is a method to assess the functional status of a patient. We retrospectively evaluated the relationship between ECOG-PS and LINE-1 methylation in colorectal cancers (CRCs) and their prognostic impact in CRC or colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX). RESULTS: LINE-1 methylation and microsatellite instability were analyzed in stage III or high-risk stage II CRCs (n = 336). LINE-1 methylation levels were correlated with clinicopathological features, including PS and recurrence-free survival (RFS). The association between the tumoral LINE-1 methylation level and PS was observed (OR = 2.56, P < 0.001). Differences in LINE-1 methylation levels in cancer tissue between the PS 0 and 1 groups were significant in patients older than 60 years (P = 0.001), the overweight body mass index group (P = 0.005), and the stage III disease group (P = 0.008). Prognostic significances of LINE-1 methylation status or combined PS and LINE-1 methylation statuses were identified in stage III colon cancers, not in stage III and high-risk stage II CRCs. Low LINE-1 methylation status was closely associated with a shorter RFS time. The difference between PS(0)/LINE-1(high) and PS(≥1)/LINE-1(low) was significant, which suggests that colon cancer patients with concurrent PS(≥1)/LINE-1 (low) have a higher recurrence rate. CONCLUSIONS: PS was associated with LINE-1 methylation in CRC tissue. LINE-1 methylation was associated with RFS in stage III colon cancer patients who were treated with adjuvant FOLFOX chemotherapy. Combined PS and LINE-1 methylation status might serve as a useful predictor of cancer recurrence.

The prognostic value of the grey-to-white matter ratio in cardiac arrest patients treated with extracorporeal membrane oxygenation.

AIM: The grey-to-white matter ratio (GWR) is a reliable predictor of the neurological outcome of out-of-hospital cardiac arrest (OHCA). However, the reliability in patients receiving extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation (ECPR) remains unknown. We evaluated the utility of the GWR in predicting neurological outcomes in ECPR-treated patients. METHODS: This single-centre retrospective study was conducted from July 2009 to January 2014. Patients who received ECPR for OHCA were classified into two groups: Cerebral performance category(CPC) 1-2 was defined as good, CPC 3-5 as poor outcome. Four GWR (GWR-AV[average], GWR-CO[cortex], GWR-BG[basal ganglia], and GWR-SI [simplified])were evaluated and compared between the groups. RESULTS: Of 38 patients who received ECPR for OHCA, 30 patients were enrolled. Five (16.7%) had a good outcome and 25(83.3%) a poor outcome. All GWR were significantly higher in the good outcome group than in the poor outcome group. ROC curve analysis produced the following areas under the curve: GWR-AV=0.920 (95% CI 0.761 to 0.987), GWR-BG=0.872 (95%CI 0.699 to 0.965), GWR-CO=0.952 (95% CI 0.806 to 0.997), and GWR-SI=0.848(95% CI 0.670 to 0.962). The cut-off value with 100% specificity for the prediction of the poor outcome was 1.23 for GWR-AV (sensitivity: 76%), 1.24 for GWR-BG (sensitivity: 88.0%), 1.22 for GWR-CO (sensitivity: 64%), and 1.21 for GWR-SI (sensitivity: 76%). CONCLUSIONS: In ECPR, GWR of patients with poor outcome was significantly lower than that of patients with good outcome.

The pre-ECMO simplified acute physiology score II as a predictor for mortality in patients with initiation ECMO support at the emergency department for acute circulatory and/or respiratory failure: a retrospective study.

BACKGROUND: In the emergency department (ED), extracorporeal membrane oxygenation (ECMO) can be used as a rescue treatment modality for patients with refractory circulatory and/or respiratory failure. Serious consideration must be given to the indication, and the PRESERVE and RESP scores for mortality have been investigated. However these scores were validated to predict survival in patients who received mainly veno-venous (VV) ECMO in the intensive care unit. The aim of the present study was to investigate the factors that predicted the outcomes for patients who received mixed mode (veno-arterial [VA] and VV) ECMO support in the ED. METHODS: This single center retrospective study included 65 patients who received ECMO support at the ED for circulatory or respiratory failure between January 2009 and December 2013. Pre-ECMO SAPS II and other variables were evaluated and compared for predicting mortality. RESULTS: Fifty-four percent of patients received ECMO-cardiopulmonary resuscitation (E-CPR), 31 % received VA and V-AV ECMO, and 15 % received VV ECMO. The 28-day and 60-month mortality rates were 52 % and 63 %. In the multivariate analysis, only the pre-ECMO Simplified Acute Physiology Score II (SAPS II) (odd ratio: 1.189, 95 % confidence interval: 1.032-1.370, p = 0.016) could predict the 28-day mortality. The area under the receiver operating characteristic curve and the optimal cutoff value for pre-ECMO SAPS II in predicting 28-day mortality was 0.852 (95 % CI: 0.753-0.951, p < 0.001) and 80 (sensitivity of 97.1 % and specificity of 71.0 %), respectively. Validation of the 80 cutoff value revealed a statistically significant difference for the 28-day and 60-month mortality rates in the overall, E-CPR, and VA groups (28-day: p < 0.001, p = 0.004, p = 0.005; 60-month: p < 0.001, p = 0.004, p = 0.020). In the Kaplan-Meier analysis, the 28-day and 60-month survival rates were lower among the patients with a pre-ECMO SAPS II of ≤ 80, compared to those with a score of > 80 (both, p < 0.001). CONCLUSION: The pre-ECMO SAPS II could be helpful for identifying patients with refractory acute circulatory and/or respiratory failure who will respond to ECMO support in the ED.

Prognostic significance of promoter CpG island hypermethylation and repetitive DNA hypomethylation in stage I lung adenocarcinoma.

In carcinogenesis of peripheral pulmonary carcinomas, multiple genetic and epigenetic alterations are involved. In this study, we quantified methylation levels of repetitive DNA elements (L1 and Alu) and six CpG island methylator phenotype (CIMP)-panel markers in various lesions representing steps in the development of lung adenocarcinoma (ADC), including atypical adenomatous hyperplasia, adenocarcinoma in situ, and invasive ADC. We then assessed methylation levels in an independent set of stage I ADCs (n = 100) and correlated methylation status with clinicopathological findings and clinical outcome. The pattern of changes in the methylation levels of L1 and Alu was different during progression of the lesion along the process of multistep carcinogenesis. A methylation level of >52.4 % of L1 and of >19.7 % of Alu in stage I ADC was associated with shorter cancer-specific survival in univariate but not in multivariate analysis. A tumor to normal lung tissue methylation ratio of >0.693 of L1 was an independent parameter heralding poor prognosis for stage I ADC patients. Methylation of CIMP-related genes was found in ADC. Stage I ADC cases without methylation of any of the six markers had a significantly shorter cancer-specific survival than ADC with methylation of one or more markers. The combination of tumor to normal L1 methylation ratio > 0.693 and absence of methylation of CIMP markers correlated independently with shorter cancer-specific survival. In conclusion, our findings suggest that Alu hypomethylation is an early and L1 hypomethylation a later event during multistep pulmonary carcinogenesis. The prognostic significance of the combination of methylation status of L1 and CIMP markers must be validated in large-scale studies of pulmonary ADC.

Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients.

AIM: To investigate the clinicopathologic characteristics and prognostic implications associated with loss of CDX2 expression in colorectal cancers (CRCs). METHODS: We immunohistochemically evaluated CDX2 expression in 713 CRCs and paired our findings to clinicopathologic and molecular characteristics of each individual. Endpoints included cytokeratin 7 and CK20 expression, microsatellite instability, CpG island methylator phenotype, and KRAS and BRAF mutation statuses. Univariate and multivariate survival analysis was performed to reveal the prognostic value of CDX2 downregulation. RESULTS: CDX2 expression was lost in 42 (5.9%) patients. Moreover, loss of CDX2 expression was associated with proximal location, infiltrative growth, advanced T, N, M and overall stage. On microscopic examination, loss of CDX2 expression was associated with poor differentiation, increased number of tumor-infiltrating lymphocytes, luminal serration and mucin production. Loss of CDX2 expression was also associated with increased CK7 expression, decreased CK20 expression, CpG island methylator phenotype, microsatellite instability and BRAF mutation. In a univariate survival analysis, patients with loss of CDX2 expression showed worse overall survival (P < 0.001) and progression-free survival (P < 0.001). In a multivariate survival analysis, loss of CDX2 expression was an independent poor prognostic factor of overall survival [hazard ratio (HR) = 1.72, 95%CI: 1.04-2.85, P = 0.034] and progression-free survival (HR = 1.94, 95%CI: 1.22-3.07, P = 0.005). CONCLUSION: Loss of CDX2 expression is associated with aggressive clinical behavior and can be used as a prognostic marker in CRCs.

Efficacy of veno-venous extracorporeal membrane oxygenation in severe acute respiratory failure.

PURPOSE: The objective of this study was to evaluate our institutional experience with veno-venous (VV) extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory failure (ARF). MATERIALS AND METHODS: From January 2007 to August 2013, 31 patients with severe ARF that was due to various causes and refractory to mechanical ventilation with conventional therapy were supported with VV ECMO. A partial pressure of arterial oxygen (PaO2)/inspired fraction of oxygen (FiO2) <100 mm Hg at an FiO2 of 1.0 or a pH <7.25 due to CO2 retention were set as criteria for VV ECMO. RESULTS: Overall, 68% of patients survived among those who had received VV ECMO with a mean PaO2/FiO2 of 56.8 mm Hg. Furthermore, in trauma patients, early use of ECMO had the best outcome with a 94% survival rate. CONCLUSION: VV ECMO is an excellent, life-saving treatment option in patients suffering from acute and life-threatening respiratory failure due to various causes, especially trauma, and early use of VV ECMO therapy improved outcomes in these patients.

Increased immunoreactivity of c­Fos in the spinal cord of the aged mouse and dog.

Expression of c­Fos in the spinal cord following nociceptive stimulation is considered to be a neurotoxic biomarker. In the present study, the immunoreactivity of c­Fos in the spinal cord was compared between young adult (2­3 years in dogs and 6 months in mice) and aged (10­12 years in dogs and 24 months in mice) Beagle dogs and C57BL/6J mice. In addition, changes to neuronal distribution and damage to the spinal cord were also investigated. There were no significant differences in neuronal loss or degeneration of the spinal neurons observed in either the aged dogs or mice. Weak c­Fos immunoreactivity was observed in the spinal neurons of the young adult animals; however, c­Fos immunoreactivity was markedly increased in the nuclei of spinal neurons in the aged dogs and mice, as compared with that of the young adults. In conclusion, c­Fos immunoreactivity was significantly increased without any accompanying neuronal loss in the aged spinal cord of mice and dogs, as compared with the spinal cords of the young adult animals.