Quick-SOFA score ≥ 2 predicts prolonged hospital stay in geriatric patients with influenza infection.

PURPOSE: The quick Sepsis-Related Organ Failure Assessment (qSOFA) score was designed to predict mortality among sepsis patients. However, it has never been used to identify prolonged length of hospital stay (pLOS) in geriatric patients with influenza infection. We conducted this study to clarify this issue. METHODS: We conducted a retrospective case-control study, including geriatric patients (aged ≥ 65 years) with influenza infection visiting the emergency department (ED) of a medical center between January 01, 2010 and December 31, 2015. The included patients were divided into two groups on the basis of their qSOFA score: qSOFA < 2, and qSOFA ≥ 2. Data regarding demographics, vital signs, qSOFA score, underlying diseases, subtypes of influenza, and outcomes were included in the analysis. We investigated the association between qSOFA score ≥ 2 and pLOS (>9 days) via logistic regression. RESULTS: Four hundred and nine geriatric patients were included in this study with a mean age of 79.5 (standard deviation [SD], 8.3) years. The median length of stay (LOS) was 7.0 (interquartile range [IQR], 4-12) days, while the rate of pLOS (> 9 days) was 32%. The median LOS in the qSOFA ≥ 2 group, 11.0 (7-15) days, was longer than the qSOFA < 2 group, 6.0 (4-10) days (p-value <0.01). Logistic regression showed that qSOFA ≥ 2 predicts pLOS with an odds ratio of 3.78 (95% confidence interval, 2.04-6.97). CONCLUSION: qSOFA score ≥ 2 is a prompt and simple tool to predict pLOS in geriatric patients with influenza infection.

MCT-1/miR-34a/IL-6/IL-6R signaling axis promotes EMT progression, cancer stemness and M2 macrophage polarization in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a poor prognostic breast cancer with the highest mutations and limited therapeutic choices. Cytokine networking between cancer cells and the tumor microenvironment (TME) maintains the self-renewing subpopulation of breast cancer stem cells (BCSCs) that mediate tumor heterogeneity, resistance and recurrence. Immunotherapy of those factors combined with targeted therapy or chemoagents may advantage TNBC treatment. RESULTS: We found that the oncogene Multiple Copies in T-cell Malignancy 1 (MCT-1/MCTS1) expression is a new poor-prognosis marker in patients with aggressive breast cancers. Overexpressing MCT-1 perturbed the oncogenic breast epithelial acini morphogenesis and stimulated epithelial-mesenchymal transition and matrix metalloproteinase activation in invasive TNBC cells, which were repressed after MCT-1 gene silencing. As mammary tumor progression was promoted by oncogenic MCT-1 activation, tumor-promoting M2 macrophages were enriched in TME, whereas M2 macrophages were decreased and tumor-suppressive M1 macrophages were increased as the tumor was repressed via MCT-1 knockdown. MCT-1 stimulated interleukin-6 (IL-6) secretion that promoted monocytic THP-1 polarization into M2-like macrophages to increase TNBC cell invasiveness. In addition, MCT-1 elevated the soluble IL-6 receptor levels, and thus, IL-6R antibodies antagonized the effect of MCT-1 on promoting M2-like polarization and cancer cell invasion. Notably, MCT-1 increased the features of BCSCs, which were further advanced by IL-6 but prevented by tocilizumab, a humanized IL-6R antibody, thus MCT-1 knockdown and tocilizumab synergistically inhibited TNBC stemness. Tumor suppressor miR-34a was induced upon MCT-1 knockdown that inhibited IL-6R expression and activated M1 polarization. CONCLUSIONS: The MCT-1 pathway is a novel and promising therapeutic target for TNBC.

Utilization of systemic inflammatory response syndrome criteria in predicting mortality among geriatric patients with influenza in the emergency department.

BACKGROUND: Systemic Inflammatory Response Syndrome (SIRS) criteria are often used to evaluate the risk of sepsis and to identify in-hospital mortality among patients with suspected infection. However, utilization of the SIRS criteria in mortality prediction among geriatric patients with influenza in the emergency department (ED) remains unclear. Therefore, we conducted a research to delineate this issue. METHODS: This is a retrospective case-control study including geriatric patients (age ≥ 65 years) with influenza, who presented to the ED of a medical center between January 1, 2010 and December 31, 2015. Vital signs, past history, subtype of influenza, demographic data, and outcomes were collected from all patients and analyzed. We calculated the accuracy for predicting 30-days mortality using the SIRS criteria. We also performed covariate adjustment of the area under the receiver operating characteristic curve (AUROC) via regression modeling. RESULTS: We recruited a total of 409 geriatric patients in the ED, with mean age 79.5 years and an equal sex ratio. The mean SIRS criteria score was 1.9 ± 1.1. The result of a Hosmer-Lemeshow goodness-of-fit test was 0.34 for SIRS criteria. SIRS criteria score ≥ 3 showed better mortality prediction, with odds ratio (OR) 3.37 (95% confidence interval (CI), 1.05-10.73); SIRS score ≥ 2 showed no statistical significance, with p = 0.85 (OR, 1.15; 95% CI, 0.28-4.69). SIRS score ≥ 3 had acceptable 30-days mortality discrimination, with AUROC 0.77 (95% CI, 0.68-0.87) after adjustment. SIRS score ≥ 3 also had a notable negative predictive value of 0.97 (95% CI, 0.94-0.99). CONCLUSION: The presence of a higher number of SIRS criteria (≥ 3) showed greater accuracy for predicting mortality among geriatric patients with influenza.

Misalignment of a novel single-piece acrylic intraocular lens in the first three months after surgery.

PURPOSE: To evaluate the misalignment of a new single-piece microincisional hydrophobic acrylic intraocular lens (IOL) in emmetropic, myopic and hyperopic eyes within the first 3 months after surgery. SETTING: Vienna Institute for Research in Ocular Surgery, Karl Landsteiner Institute, Hanusch Hospital, Department of Ophthalmology, Vienna, Austria. METHODS: Patients with age-related cataract were included in this prospective study. Each patient received a single-piece microincisional hydrophobic acrylic IOL (AF-1 NY-60, Hoya) in the study eye. Subgroups of emmetropic, myopic and hyperopic eyes were defined according to IOL power calculation. Anterior chamber depth (ACD) measurements were performed with an AC-Master. Tilt and decentration of the IOL were measured with a Purkinje meter. Follow-up assessments were performed 1 h, 3 weeks and 3 months after surgery. RESULTS: Forty-two eyes of 42 patients (21 emmetropic, 10 myopic and 11 hyperopic eyes) were included. The mean ACD 1 h, 3 weeks and 3 months after surgery was 4.597 ± 0.533, 4.483 ± 0.347 and 4.438 ± 0.398 mm, respectively. Differences in ACD between follow-ups and between subgroups were not statistically significant (both p > 0.05). On average, 3 months after surgery IOLs were tilted 0.81 ± 2.86° nasally and 0.70 ± 3.13° inferiorly and decentered 0.06 ± 0.24 mm nasally and 0.15 ± 0.29 mm superiorly. Differences in tilt and decentration were not statistically significant (both p > 0.05). We observed 1 case of severe capsular fibrosis. CONCLUSIONS: The single-piece microincisional hydrophobic acrylic IOL showed good axial stability and only little, clinically not relevant tilt and decentration in the first 3 months after surgery.

Pharmacokinetics of fexofenadine in healthy Taiwanese volunteers.

The aim of presented study was to assess pharmacokinetic properties of fexofenadine in Taiwanese volunteers. Thirty-three healthy male subjects received 180mg fexofenadine. Blood samples were drawn at appropriate times. Drug concentrations of fexofenadine were measured by a LC/MS/MS method. Non-compartmental models were applied to describe the pharmacokinetic characters of fexofenadine. After oral administration of fexofenadine, the Tmax was 1.90 ± 0.81h. The Cmax was 703.76 ± 298.94ng/mL and AUC0-oo was 4582.52 ± 1812.59h´ng/mL. The elimination half-life of fexofenadine was 12.18 ± 3.61h. One of the most important determinants was to prove the similar results in the pharmacokinetics of fexofenadine in Taiwan subjects compared with the reported data of other ethnic origin.

Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer.

Rationale: Multiple copies in T-cell malignancy 1 (MCT-1) is a prognostic biomarker for aggressive breast cancers. Overexpressed MCT-1 stimulates the IL-6/IL-6R/gp130/STAT3 axis, which promotes epithelial-to-mesenchymal transition and cancer stemness. Because cancer stemness largely contributes to the tumor metastasis and recurrence, we aimed to identify whether the blockade of MCT-1 and IL-6R can render these effects and to understand the underlying mechanisms that govern the process. Methods: We assessed primary tumor invasion, postsurgical local recurrence and distant metastasis in orthotopic syngeneic mice given the indicated immunotherapy and MCT-1 silencing (shMCT-1). Results: We found that shMCT-1 suppresses the transcriptomes of the inflammatory response and metastatic signaling in TNBC cells and inhibits tumor recurrence, metastasis and mortality in xenograft mice. IL-6R immunotherapy and shMCT-1 combined further decreased intratumoral M2 macrophages and T regulatory cells (Tregs) and avoided postsurgical TNBC expansion. shMCT-1 also enhances IL-6R-based immunotherapy effectively in preventing postsurgical TNBC metastasis, recurrence and mortality. Anti-IL-6R improved helper T, cytotoxic T and natural killer (NK) cells in the lymphatic system and decreased Tregs in the recurrent and metastatic tumors. Combined IL-6R and PD-L1 immunotherapies abridged TNBC cell stemness and M2 macrophage activity to a greater extent than monotherapy. Sequential immunotherapy of PD-L1 and IL-6R demonstrated the best survival outcome and lowest postoperative recurrence and metastasis compared with synchronized therapy, particularly in the shMCT-1 context. Multiple positive feedforward loops of the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 axis were identified in TNBC cells, which boosted metastatic niches and immunosuppressive microenvironments. Clinically, MCT-1high/PD-L1high/CXCL7high and CXCL7high/IL-6high/IL-6Rhigh expression patterns predict worse prognosis and poorer survival of breast cancer patients. Conclusion: Systemic targeting the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 interconnections enhances immune surveillance that inhibits the aggressiveness of TNBC.

Influence of a modified Nd:YAG laser treatment outside the visual axis on the morphology of Elschnig pearls.

PURPOSE: To observe changes in posterior capsule opacification (PCO) after Nd:YAG treatment with and without opening the posterior lens capsule. METHOD: This prospective randomized study included patients with regeneratory PCO. In substudy 1, a small low-energy Nd:YAG capsulotomy was performed (MiniYAG). In substudy 2, a low-energy Nd:YAG laser treatment without opening the lens capsule was performed (GentleYAG). Concerning analysis, in both substudies, the posterior capsule was divided into 4 quadrants and the quadrant where the Nd:YAG laser treatment was performed was randomly allocated. Change in PCO was analyzed using retroillumination images objectively (AQUA score: 0-10). RESULTS: In total, 27 eyes of 25 patients were used for this study. In substudy 1, the mean amount of PCO (AQUA score) for the entire posterior capsule decreased significantly (p < 0.05, ANOVA) from 5.2 (SD: 1.6) before to 4.0 (SD: 1.9) immediately after the MiniYAG. In substudy 2, the mean amount of PCO (AQUA score) for the entire posterior capsule analyzed before and immediately after the GentleYAG was 5.1 (SD: 2.4) and 5.2 (SD: 2.3), respectively. CONCLUSION: Performing a MiniYAG led to a significant PCO reduction. Gentle polishing of the posterior capsule resulted in a relevant reduction of PCO in one third of the patients.

Palladium-Catalyzed Chemo- and Regiocontrolled Tandem Cyclization/Cross-Coupling of 2-Benzyl-3-alkynyl Chromones with Aryl Iodides for the Synthesis of 4H-Furo[3,2-c]chromenes and Xanthones.

A novel Pd-catalyzed chemo- and regiocontrolled tandem cyclization/cross-coupling reaction of 3-alkynyl chromone with aryl iodide was developed for the synthesis of 4H-furo[3,2-c]chromenes and xanthones. The difunctionalization of alkynes through O-attack/5-exo-dig and C-attack/6-endo-dig cyclization was reported by this rare approach, which was selectively controlled by the addition of KF or a bidentate phosphine ligand. A one-pot tandem process was demonstrated directly from γ-alkynyl-1,3-diketone for this method.

A novel donor-derived cell-free DNA assay for the detection of acute rejection in heart transplantation.

BACKGROUND: Endomyocardial biopsy (EMB), the reference surveillance test for acute rejection (AR) in heart transplant (HTx) recipients, is invasive, costly, and shows significant interobserver variability. Recent studies indicate that donor-derived cell-free DNA (dd-cfDNA), obtained non-invasively from blood, is associated with AR and could reduce the frequency of EMB surveillance. The aim of this study was to examine the performance characteristics of a novel test for detecting AR in adult HTx recipients. METHODS: Plasma samples with contemporaneous EMBs were obtained from HTx recipients. A clinically available SNP-based massively multiplexed-PCR dd-cfDNA assay was used to measure dd-cfDNA fraction. dd-cfDNA fractions were compared with EMB-defined rejection status and test performance was assessed by constructing ROC curves and calculating accuracy measures. RESULTS: A total of 811 samples from 223 patients with dd-cfDNA testing and contemporaneous EMB were eligible for the study. dd-cfDNA fraction was significantly higher in AR (median 0.58%, IQR, 0.13%-1.68%) compared to non-AR (median 0.04%, IQR, 0.01%-0.11%, pc < 0.001). ROC analysis produced an area under the curve (AUC-ROC) of 0.86 (95% CI, 0.77-0.96). Defining samples with dd-cfDNA fraction ≥0.15% as AR yielded 78.5% sensitivity (95% CI, 60.7%-96.3%) and 76.9% specificity (95% CI, 71.1%-82.7%). Positive and negative predictive values were 25.1% (95% CI, 18.8%-31.5%) and 97.3% (95% CI, 95.1%-99.5%) respectively, calculated using the cohort AR prevalence of 9.0% (95% CI, 5.3%-12.8%) with adjustment for repeat samples. CONCLUSIONS: This novel dd-cfDNA test detects AR in HTx recipients with good accuracy and holds promise as a noninvasive test for AR in HTx recipients.

Clinical Validation of a Plasma Donor-derived Cell-free DNA Assay to Detect Allograft Rejection and Injury in Lung Transplant.

Background: Lung transplant patients are vulnerable to various forms of allograft injury, whether from acute rejection (AR) (encompassing acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), chronic lung allograft dysfunction (CLAD), or infection (INFXN). Previous research indicates that donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker for the detection of AR and allograft injury. Our aim was to validate a clinical plasma dd-cfDNA assay for detection of AR and other allograft injury and to confirm and expand on dd-cfDNA and allograft injury associations observed in previous studies. Methods: We measured dd-cfDNA fraction using a novel single-nucleotide polymorphism-based assay in prospectively collected plasma samples paired with clinical-pathologic diagnoses. dd-cfDNA fraction was compared across clinical-pathologic cohorts: stable, ACR, AMR, isolated lymphocytic bronchiolitis, CLAD/neutrophilic-responsive allograft dysfunction (NRAD), and INFXN. Performance characteristics were calculated for AR and combined allograft injury (AR + CLAD/NRAD + INFXN) versus the stable cohort. Results: The study included 195 samples from 103 patients. Median dd-cfDNA fraction was significantly higher for ACR (1.43%, interquartile range [IQR]: 0.67%-2.32%, P = 5 × 10-6), AMR (2.50%, IQR: 2.06%-3.79%, P = 2 × 10-5), INFXN (0.74%, IQR: 0.46%-1.38%, P = 0.02), and CLAD/NRAD (1.60%, IQR: 0.57%-2.60%, P = 1.4 × 10-4) versus the stable cohort. Area under the receiver operator characteristic curve for AR versus stable was 0.91 (95% confidence interval [CI]: 0.83-0.98). Using a ≥1% dd-cfDNA fraction threshold, sensitivity for AR was 89.1% (95% CI: 76.2%-100.0%), specificity 82.9% (95% CI: 73.3%-92.4%), positive predictive value, 51.9% (95% CI: 37.5%-66.3%), and negative predictive value, 97.3% (95% CI: 94.3%-100%). For combined allograft injury area under the receiver operator characteristic curve was 0.76 (95% CI: 0.66-0.85), sensitivity 59.9% (95% CI: 46.0%-73.9%), specificity 83.9% (95% CI: 74.1%-93.7%), positive predictive value, 43.6% (95% CI: 27.6%-59.6%), and negative predictive value, 91.0% (95% CI: 87.9%-94.0%). Conclusions: These results indicate that our dd-cfDNA assay detects AR and other allograft injury. dd-cfDNA monitoring, accompanied by standard clinical assessments, represents a valuable precision tool to support lung transplant health and is appropriate for further assessment in a prospective randomized-controlled study.

Long-term language levels and reading skills in mandarin-speaking prelingually deaf children with cochlear implants.

The aim of this study was to document receptive and expressive language levels and reading skills achieved by Mandarin-speaking children who had received cochlear implants (CIs) and used them for 4.75-7.42 years. The effects of possible associated factors were also analyzed. Standardized Mandarin language and reading tests were administered to 39 prelingually deaf children with Nucleus 24 devices. The Mandarin Chinese version of the Peabody Picture Vocabulary Test was used to assess their receptive vocabulary knowledge and the Revised Primary School Language Assessment Test for their receptive and expressive language skills. The Graded Chinese Character Recognition Test was used to test their written word recognition ability and the Reading Comprehension Test for their reading comprehension ability. Raw scores from both language and reading measurements were compared to normative data of nor- mal-hearing children to obtain standard scores. The results showed that the mean standard score for receptive vocabulary measurement and the mean T scores for the receptive language, expressive language and total language measurement were all in the low-average range in comparison to the normative sample. In contrast, the mean T scores for word and text reading comprehension were almost the same as for their age-matched hearing counterparts. Among all children with CIs, 75.7% scored within or above the normal range of their age-matched hearing peers on receptive vocabulary measurement. For total language, Chinese word recognition and reading scores, 71.8, 77 and 82% of children with CIs were age appropriate, respectively. A strong correlation was found between language and reading skills. Age at implantation and sentence perception scores account for 37% of variance for total language outcome. Sentence perception scores and preimplantation residual hearing were revealed to be associated with the outcome of reading comprehension. We concluded that by using standard tests, the language development and reading skill of Mandarin-speaking children who use CIs from a young age appear to fall within the normal range of their hearing age mates, at least after 4.8-7.4 years of experience. However, to fully evaluate the fine linguistic skills of these subjects, a more detailed study and longer follow-up period are needed.

The functional characterization of phosphorylation of tristetraprolin at C-terminal NOT1-binding domain.

BACKGROUND: Tristetraprolin (TTP) family proteins contain conserved tandem CCCH zinc-finger binding to AU-rich elements and C-terminal NOT1-binding domain. TTP is phosphorylated extensively in cells, and its mRNA destabilization activity is regulated by protein phosphorylation. METHODS: We generated an antibody against phospho-Serine316 located at the C-terminal NOT1-binding site and examined TTP phosphorylation in LPS-stimulated RAW264.7 cells. Knockout of TTP was created in RAW264.7 cells using CRISPR/Cas9 gene editing to explore TTP functions. RESULTS: We demonstrated that Ser316 was phosphorylated by p90 ribosomal S6 kinase 1 (RSK1) and p38-activated protein kinase (MK2) and dephosphorylated by Protein Phosphatase 2A (PP2A). A phosphorylation-mimic mutant of S316D resulted in dissociation with the CCR4-NOT deadenylase complex through weakening interaction with CNOT1. Furthermore, Ser316 and serines 52 and 178 were independently contributed to the CCR4-NOT complex recruitment in the immunoprecipitation assay using phosphor-mimic mutants. In RAW264.7 macrophages, TTP was induced, and Ser316 was phosphorylated through RSK1 and MK2 by LPS stimulation. Knockout of TTP resulted in TNFα mRNA increased due to mRNA stabilization. Overexpression of non-phosphorylated S316A TTP mutant can restore TTP activity and lead to TNFα mRNA decreased. GST pull-down and RNA pull-down analyses demonstrated that endogenous TTP with Ser316 phosphorylation decreased the interaction with CNOT1. CONCLUSIONS: Our results suggest that the TTP-mediated mRNA stability is modulated by Ser316 phosphorylation via regulating the TTP interaction with the CCR4-NOT deadenylase complex.

A Mobility Aware Binary Tree Algorithm to Resolve RFID Jam and Bottleneck Problems in a Next Generation Specimen Management System.

Hospitals are continuously working to reduce delayed analysis and specimen errors during transfers from testing stations to clinical laboratories. Radio-frequency identification (RFID) tags, which provide automated specimen labeling and tracking, have been proposed as a solution to specimen management that reduces human resource costs and analytic delays. Conventional RFID solutions, however, confront the problem of traffic jams and bottlenecks on the conveyor belts that connect testing stations with clinical laboratories. This mainly results from methods which assume that the arrival rate of specimens to laboratory RFID readers is fixed/stable, which is unsuitable and impractical in the real world. Previous RFID algorithms have attempted to minimize the time required for tag identification without taking the dynamic arrival rates of specimens into account. Therefore, we propose a novel RFID anti-collision algorithm called the Mobility Aware Binary Tree Algorithm (MABT), which can be used to improve the identification of dynamic tags within the reader's coverage area and limited dwell time.

Effect of Small Cage Guests on Dissociation Properties of Tetrahydrofuran Hydrates.

It is well understood that tetrahydrofuran (THF) molecules are able to stabilize the large cages (51264) of structure II to form the THF hydrate with empty small cages even at atmospheric pressure. This leaves the small cages to store gas molecules at relatively lower pressures and higher temperatures. The dissociation enthalpy and temperature strongly depend on the size of gas molecules enclathrated in the small cages of structure II THF hydrate. A high-pressure microdifferential scanning calorimeter was applied to measure the dissociation enthalpies and temperatures of THF hydrates pressurized by helium and methane under a constant pressure ranging from 0.10 to 35.00 MPa and a wide THF concentration ranging from 0.25 to 8.11 mol %. The dissociation temperature of binary He + THF and methane + THF hydrates increases along with an increase in the THF concentration in the liquid phase at a fixed pressure (e.g., 30 MPa), reaching a maximum value of 280.8 and 312.8 K, respectively, at stoichiometric concentration (5.56 mol % THF), and then remains nearly constant for even higher THF concentrations (>5.56 mol %). The effect of gas occupancy in the small cages on the dissociation enthalpy of He + THF and methane + THF mixed hydrates was further examined by using molecular dynamics (MD) simulations. The dissociation enthalpy of the He-THF mixed hydrates is independent of pressure with an average of 5.68 kJ/mol H2O over the pressure ranging from 0.10 to 30.0 MPa, consistent with the MD results of the He-THF mixed hydrates with low single occupancy (<23%) of helium molecules in the small cages. Consequently, the heat of adsorption of helium molecules in the small cages of the He-THF mixed hydrates is rather too weak to be identified. On the other hand, the dissociation enthalpy of the methane-THF hydrates increases from 9.11 to 10.01 kJ/mol H2O along with an increase in methane pressure over the pressure ranging from 5.0 to 30.0 MPa, consistent with the MD results of the methane-THF mixed hydrates with full occupancy of methane molecules in the small cages. These findings provide important information for the design of a potential medium of gas storage and transportation.

Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression.

Reactive oxygen species (ROS) produced during intracellular metabolism or triggered by extrinsic factors can promote neoplastic transformation and malignant microenvironment that mediate tumor development. Oligo-Fucoidan is a sulfated polysaccharide isolated from the brown seaweed. Using human THP-1 monocytes and murine Raw264.7 macrophages as well as human HCT116 colorectal cancer cells, primary C6P2-L1 colorectal cancer cells and human MDA-MB231 breast cancer cells, we investigated the effect of Oligo-Fucoidan on inhibiting M2 macrophage differentiation and its therapeutic potential as a supplement in chemotherapy and tumor prevention. We now demonstrate that Oligo-Fucoidan is an antioxidant that suppresses intracellular ROS and mitochondrial superoxide levels in monocytes/macrophages and in aggressive cancer cells. Comparable to ROS inhibitors (DPI and NAC), Oligo-Fucoidan directly induced monocyte polarization toward M1-like macrophages and repolarized M2 macrophages into M1 phenotypes. DPI and Oligo-Fucoidan also cooperatively prevented M2 macrophage invasiveness. Indirectly, M1 polarity was advanced particularly when DPI suppressed ROS generation and supplemented with Oligo-Fucoidan in the cancer cells. Moreover, cisplatin chemoagent polarized monocytes and M0 macrophages toward M2-like phenotypes and Oligo-Fucoidan supplementation reduced these side effects. Furthermore, Oligo-Fucoidan promoted cytotoxicity of cisplatin and antagonized cisplatin effect on cancer cells to prevent M2 macrophage differentiation. More importantly, Oligo-Fucoidan inhibited tumor progression and M2 macrophage infiltration in tumor microenvironment, thus increasing of anti-tumor immunity.

Pharmacokinetics of (-)-epicatechin in rabbits.

The aim of this study was to investigate the pharmacokinetics of (-)-epicatechin (EC) in rabbits after intravenous, intraperitoneal, and oral administration. A two-compartment model was used to describe the pharmacokinetics of EC after intravenous administration. EC showed dose-independent pharmacokinetics after intravenous administration. In addition, the area under the concentration-time curve was proportional to the dose over the range 5-25 mg/kg. After intraperitoneal administration of 25 mg/kg, a high percentage of EC escaped from first-pass hepatic elimination. After oral administration of 50 mg/kg, there was a great variation in the pharmacokinetics, and the mean oral bioavailability of EC was 4%. There was no significant difference in the elimination rate constants in all treatments (p>0.05). In conclusion, after intravenous, intraperitoneal, and oral administration of EC, the EC exhibits dose-independent pharmacokinetics in rabbits. The first-pass effect did not participate in the low oral bioavailability. Base on the results of the present study, the other factors may contribute the low oral bioavailability.

Synthesis of Methane Hydrate from Ice Powder Accelerated by Doping Ethanol into Methane Gas.

Clathrate hydrate is considered to be a potential medium for gas storage and transportation. Slow kinetics of hydrate formation is a hindrance to the commercialized process development of such applications. The kinetics of methane hydrate formation from the reaction of ice powder and methane gas doped with/without saturated ethanol vapor at constant pressure of 16.55 ± 0.20 MPa and constant temperature ranging from -15 to -1.0 °C were investigated. The methane hydrate formation can be dramatically accelerated by simply doping ethanol into methane gas with ultralow ethanol concentration (<94 ppm by mole fraction) in the gas phase. For ethanol-doped system 80.1% of ice powder were converted into methane hydrate after a reaction time of 4 h, while only 26.6% of ice powder was converted into methane hydrate after a reaction time of 24 h when pure methane gas was used. Furthermore, this trace amount of ethanol could also substantially suppress the self-preservation effect to enhance the dissociation rate of methane hydrate (operated at 1 atm and temperatures below the ice melting point). In other words, a trace amount of ethanol doped in methane gas can act as a kinetic promoter for both the methane hydrate formation and dissociation.

Quick-SOFA score to predict mortality among geriatric patients with influenza in the emergency department.

The quick sequential organ failure assessment (qSOFA) score is widely used to assess the risk of sepsis and predict in-hospital mortality in patients with suspected infection. However, its ability to predict mortality among geriatric patients with influenza in the emergency department (ED) remains unclear. Therefore, this study was conducted to delineate this issue.A retrospective case-control study was conducted on geriatric patients (age ≥65 years) with influenza who visited the ED of a medical center between January 01, 2010, and December 31, 2015. Demographic data, vital signs, past histories, influenza subtypes, and treatment outcomes were included in the analysis. We assessed the accuracy of the qSOFA score in predicting 30-day mortality via logistic regression. Covariate adjustment of the area under the receiver operating characteristic curve (AUROC) via regression modeling was performed too.In total, 409 geriatric ED patients with mean age of 79.5 years and nearly equal sex ratio were recruited. The mean qSOFA score was 0.55 ±â€Š0.7. The Hosmer-Lemeshow goodness-of-fit test was 0.79 for qSOFA score. Patients with qSOFA score of ≥2 (odds ratio, 4.21; 95% confidence interval [CI], 1.56-11.40) had increased in-hospital mortality. qSOFA score of ≥2 also had excellent in-hospital mortality discrimination with an adjusted AUROC of 0.81 (95% CI, 0.71-0.90). A qSOFA of ≥2 had prominent specificity of 0.89 (95% CI, 0.86-0.92).An increase in qSOFA score of 2 greatly predicts mortality in geriatric patients with influenza.

Warfarin Overdose Associated Inferior Mesentery Artery Aneurysm Rupture Mimicking Spontaneous Bowel Hematoma.

Inferior mesentery artery (IMA) aneurysm rupture is easily overlooked in patients with abdominal pain due to its uncommon occurrence. It may result in catastrophic consequence once misdiagnosed as spontaneous bowel hematoma in patients with anticoagulant overdose and intra-abdominal hematoma, as treatment strategy for both diseases varies differently. We present a case of a 70-year-old male who came to our emergency department with the chief complaint of abdominal pain over periumbilical area, eventually diagnosed as anticoagulant overdose associated IMA aneurysm rupture without occlusion of superior mesentery artery (SMA) and celiac artery (CA). This case report alerts us to consider the rare other source of bleeding, for instance ruptured inferior mesentery aneurysm, while encountering such an extraordinary large intra-abdominal hematoma in patients on anticoagulant.

Oligo-Fucoidan prevents IL-6 and CCL2 production and cooperates with p53 to suppress ATM signaling and tumor progression.

Low-molecular-weight Fucoidan (Oligo-Fucoidan) is a sulfated polysaccharide that has a variety of biological effects and has also been shown to have beneficial health effects. However, the molecular mechanisms underlying the therapeutic effects of Oligo-Fucoidan in patients with cancer remain unclear. Using human colorectal cancer HCT116 cells with (p53+/+) or without (p53-/-) normal p53 expression, we found that Oligo-Fucoidan treatment reduces the occurrence of spontaneous DNA lesions. Etoposide induces double strand DNA breaks. Subsequent administration of Oligo-Fucoidan to etoposide-treated cells promotes p53 accumulation, p21 expression and significant decreases in ataxia-telangiectasia-mutated (ATM), checkpoint kinase 1 (Chk1) and γ-H2AX phosphorylation in p53+/+ cells compared with p53-/- cells. Similarly, co-administration of Oligo-Fucoidan with etoposide inhibits ATM, Chk1 and γ-H2AX phosphorylation, particularly in the presence of p53. Furthermore, Oligo-Fucoidan supplementation increases cancer cell death and attenuates the adverse effects induced by etoposide that decreases production of the pro-inflammatory cytokine IL-6 and chemokine CCL2/MCP-1. Importantly, Oligo-Fucoidan decreases the tumor-promoting M2 macrophages in microenvironment as well as collaborates with p53 and works in combination with etoposide to prevent HCT116 tumorigenicity. Our results first demonstrate that p53 enables Oligo-Fucoidan to effectively inhibit tumor progression, and Oligo-Fucoidan minimizes the side effects of chemotherapy and alters tumor microenvironment.