Significant discordance between point of care BNP values obtained by the i-STAT and the Beckman DXI 800, causing confusion in patient management when both methods are used interchangeably by clinicians.

B-type natriuretic peptide (BNP) is used as a biomarker of heart failure. In our hospital point of care (POCT) BNP test is performed in EDTA whole blood using i-STAT (Abbott Laboratories, Abbott Park, IL, USA) and in the clinical laboratory using EDTA plasma and the DXI 800 analyzer (Beckman, Brea, CA, USA). We compared BNP values in 88 patients obtained by using the i-STAT followed by using the DXI 800. The time difference between the two analyses varied from 32 min to less than 12 h. In addition, 11 specimens were simultaneously analyzed for BNP using both the i-STAT and the DXI 800 analyzer. Plotting BNP concentrations obtained by the DXI 800 in the x-axis (reference method) and the i-STAT values in the y-axis, we observed the following regression equation; y = 1.4758 x + 23.452 (n = 88, r = 0.96), indicating significant positive bias with the i-STAT. In addition, we also observed significant differences between BNP values obtained by the i-STAT and the DXI 800 in 11 specimens analyzed simultaneously. Therefore, clinicians should not use BNP concentrations obtained by the i-STAT interchangeably with BNP concentrations obtained by the DXI 800 analyzer for patient management.

Reference interval, longitudinal variability and reliability of activated clotting time in healthy dogs using a point-of-care analyser.

BACKGROUND: Activated clotting times (ACTs) are used to screen for coagulopathies and monitor heparin therapy. OBJECTIVES: To determine a reference interval (RI) for ACT in dogs using a point-of-care analyser, to quantify intra-subject within- and between-day variability, to quantify analyser reliability and inter-analyser agreement and to study the influence of a delay in measurement. METHODS: Forty-two healthy dogs were included. Measurements were performed on fresh venous blood using the i-STAT 1 analyser. The RI was determined using the Robust method. Intra-subject within-day variability and between-day variability were quantified between baseline and 2 h (n = 8) or 48 h (n = 10) later. Analyser reliability and inter-analyser agreement were studied by duplicate measurements (n = 8) on identical analysers. The influence of measurement delay was studied before and after a delay of one analytical run (n = 6). RESULTS: Mean, lower and upper reference limits for ACT were 92.9 ± 9.1, 74.4 and 111.2 s, respectively. Coefficients of variation of intra-subject within- and between-day variability were 8.1% and 10.4%, respectively, resulting in a significant between-day measurement difference. Analyser reliability assessed by the intraclass correlation coefficient and coefficient of variation were 0.87% and 3.3%, respectively. Significantly lower ACT values were observed after a measurement delay compared to direct analysis. CONCLUSIONS: Our study provides an RI for ACT in healthy dogs using the i-STAT 1 and suggests low intra-subject within- and between-day variability. Analyser reliability and inter-analyser agreement were good; however, analysis delay and between-day differences could significantly influence ACT results.

Analytical Performances of the Novel i-STAT Alinity Point-of-Care Analyzer.

Many Point-of-Care devices have been released over the past decade. However, data regarding their analytical performances in real-world situations remains scarce. Herein, we aimed to assess the analytical performances of the i-STAT Alinity system. We conducted an analytical performances study with the i-STAT Alinity device using cartridges CG4+ (pH, Pco2, Po2, lactate, bicarbonate and base excess); CHEM8+ (Na, K, Cl, ionized Ca, urea, creatinine, glucose, hematocrit and hemoglobin) and PT/INR (prothrombin time and international normalized ratio). We assessed the imprecision and compared the results to those obtained on existing instruments in the central laboratory. We found that the within-lab coefficients of variation (CV) were very low (<2%) or low (2−5%), except for creatinine and PT (CV = 5.2% and CV = 6.3%, respectively). For almost all the parameters, the results were strongly (R2 = 90−95%) or very strongly (R2 > 95%) correlated with those of the existing laboratory instruments, and the biases were very low (<2%) or low (2−5%). However, correlations of the PT and INR measurements with existing instruments were lower (R2 = 86.0% and 89.7%), and biases in the Po2 (7.9%), creatinine (5.4%) and PT (−6.6%) measurements were higher. The i-STAT Alinity appeared as a convenient device for measurements of numerous parameters. However, clinicians should interpret Po2, creatinine and PT results with caution.

A review of temperature-related challenges and solutions for the Abbott i-STAT and Siemens Healthineers epoc devices.

The Abbott i-STAT and Siemens Healthineers epoc are commonly used in the provision of care during emergency medical services calls and other settings. Maintaining these systems within manufacturer's temperature claims in these settings poses challenges across the world. This review summarizes solutions that have been reported in the peer-reviewed literature and proposes additional strategies to further address these challenges. A literature search was performed with Clarivate's Web of Science from inception to August 3, 2022. Search terms included i-STAT, epoc, temperature, cold, hot, heat, freeze, frozen, prehospital, disaster, POCT, point of care, blood gas, helicopter, airplane, and ambulance. One author also reviewed manually every issue of the Journal of Paramedic Practice. The search identified 17 solutions for addressing temperature-related challenges with the i-STAT device, nine solutions for i-STAT cartridges, one solution for the epoc device, and one solution for the epoc test card. The majority of solutions were highly portable and consisted of widely available, inexpensive components. The solutions demonstrated only partial or entirely questionable effectiveness in achieving temperature control. The search also identified five reports on the impact of storage temperatures on cartridges and test cards. The reports suggested that these reagents may be able to withstand storage at temperatures outside of manufacturer's claims with only minimal deterioration in performance. The heterogeneity of solutions and the paucity of evidence on their effectiveness suggest that additional strategies are needed to better understand and further address temperature-related challenges with these systems. A collaborative approach and shared decision making are recommended.

Identifying sources of error and selecting quality indicators for point of care testing.

OBJECTIVES: Point of Care Testing (POCT) is a rapidly expanding area of clinical laboratory testing and quality assurance is an important area of focus. Quality indicators (QIs) are a quality management system tool that monitors aspects of the testing process to help meet the challenges associated with maintaining high quality patient safety given the growth in POCT. Alberta aims to formalize the development and use of QIs for POCT. DESIGN: and Methods: Potential QIs were identified by reviewing both the current standards and guidelines for QIs in POCT, and the research regarding quality and sources of error in POCT. Quality practices and potential sources of error in POCT were identified by: 1) a Canadian national survey on POCT, and 2) direct observation in two local POCT programs. RESULTS: A proposed selection of QIs in POCT were identified by incorporating the results from these investigations, while considering the unique characteristics of POCT. These QIs monitor the preanalytical, analytical, and post-analytical phases of testing, and support processes. CONCLUSIONS: As POCT volumes and test menu expands, QIs will be a vital tool in monitoring error and maintaining high quality of results. Adoption of formal QIs will support continuous quality improvement and improved patient care.

The interruption of atypical PKC signaling and Temozolomide combination therapy against glioblastoma.

Current treatment options of glioblastoma include chemotherapy and limited surgical resection. Temozolomide (TMZ) is the current therapeutic choice for chemotherapy. Still, it has severe limitations due to the development of resistance that occurs by genetic modification and constitutive activation of several cell signaling pathways. Therefore, it is essential to develop combination therapy of TMZ with other novel compounds to prevent the development of chemo-resistance. In this study, we used two inhibitors; ICA, an inhibitor of PKC-ι and ζ-Stat, an inhibitor of PKC-ζ. T98G and U87MG glioblastoma cells were treated with either ICA or ζ-stat or TMZ monotherapies, as well as TMZ were combined with either ICA or ζ-stat for five consecutive days. Our in vitro results exhibited that ICA when combined with TMZ, significantly decreased the viability of cancerous cells compared with untreated or TMZ or ICA monotherapies. Additionally, glioblastoma cells were remarkably undergoing apoptosis against the combination treatment of TMZ and ICA nucleotide compared with untreated control cells, as suggested by our Annexin-V/PI flow cytometric analysis. Moreover, the combination of TMZ and ICA also decreased the invasion of glioblastoma cell lines by acting on FAK/Paxillin pathway, as evidenced by scratch assay, transwell invasion assay, Western blot and immunoprecipitation analysis. Furthermore, our in vivo data presented that the combination of ICA and TMZ also reduced glioblastoma tumor growth and volume in mice. These data suggest that atypical PKCs, particularly PKC-ι might be an important therapeutic target as adjuvant therapy in the treatment of glioblastoma.

Comparison of Two Commercially Available Immunoassays for the Measurement of Bovine Cardiac Troponin I in Cattle With Induced Myocardial Injury.

Background: Multiple cardiac troponin I (cTnI) immunoassays are commercially available. Overall, assays have not been standardized, and inter-assay differences in the detection of the analyte cardiac troponin I can be clinically relevant. Objective: To compare the diagnostic accuracy of the commercially available Abbott i-STAT®1 cTnI immunoassay (i-STAT) and the previously validated ADVIA Centaur TnI-Ultra immunoassay (Centaur) in cattle. Hypothesis: There will be significant differences in bovine serum cTnI results measured by the Centaur and i-STAT methods. Animals: Ten dairy cows with experimentally induced myocardial injury due to monensin administration. Thirty apparently healthy dairy cows with no history of monensin exposure served as controls. Methods: Blood was collected at various time points after administration of a single dose of monensin (20 to 50 mg/kg) via orogastric tube. A total of 112 blood samples were collected. Cardiac TnI concentration was analyzed with the two methods and the association between methods analyzed via linear regression. Bland-Altman analysis to evaluate agreement between methods was performed on samples divided into groups (cTnI < 1.0 ng/mL and cTnI ≥ 1.0 ng/mL). Results: Analyzer results were linearly correlated with each other (R 2 = 0.931). Samples with cTnI concentrations <1.0 ng/mL had a bias of -0.13 ± 0.20 ng/mL and samples with cTnI concentrations >1.0 ng/mL had a bias of -9.81 ± 13.26 ng/mL. Conclusions and clinical importance: The results of this study reveal that cTnI concentrations determined with the i-STAT are systematically lower compared to the concentrations determined by the Centaur.

Point-of-care blood gas analyzers have an impact on the acceptance of donor lungs for transplantation.

An organ donor PaO2 above 40 kPa is generally required for lung transplantation. Point-of-care (POC) blood gas analyzers are commonly used by organ procurement organizations (OPO) but may underestimate the PaO2 at high levels. We hypothesized that changing to a more accurate blood gas analyzer would result in additional lungs transplanted. All PaO2 measurements on organ donors managed at one OPO's recovery center were performed on an i-STAT POC analyzer prior to October 2015, and on a GEM 4000 subsequently. For 24 weeks, all blood gases were tested simultaneously on both analyzers. We compared lung outcomes of 147 donors in the year prior to this change (using the i-STAT) with 56 donors in the 24-week study period (using the GEM 4000 for lung allocation). When the PaO2 was above 40 kPa, the i-STAT PaO2 was 7.2 kPa lower on average than the GEM 4000. When the GEM PaO2 measured between 40 and 50 kPa, the corresponding i-STAT PaO2 value registered less than 40 kPa 25 out of 48 times (52%), with an average difference of 7.3 kPa (SD = 2.9). The rate of lungs transplanted using the GEM 4000 was 48% compared with 35% in the year prior using the i-STAT (p = .11), with equivalent recipient outcomes. The i-STAT analyzer underestimated the PaO2 above 40 kPa and changing to a more accurate PaO2 analyzer may increase lungs transplanted.

A Comparative Assessment of the Nova Stat Profile Prime Plus® Critical Care Analyzer.

BACKGROUND: Point-of-care testing (POCT) plays an integral role in the management of acutely ill patients presenting to the emergency department (ED). Due to its rapid turnaround time, POCT has been shown to improve ED workflow, reduce unnecessary admissions and lessen the burden on ED staff. The aim of the study was to compare the accuracy, precision and linearity of the Nova Stat Profile Prime Plus® (Nova Biomedical, Waltham, MA, USA) to the Radiometer ABL800 FLEX® (Radiometer South Africa Pty Ltd, Gauteng) and the Abbott i-stat Chem8+® (Abbott, Princeton, NJ, USA) POCT analyzers. METHODS: A convenience sample of 150 discarded whole blood specimens was obtained and analyzed. Paired test measurements were conducted for method comparison. Accuracy was measured by pairing individual results from the Nova Stat Profile Prime Plus® with either the Radiometer ABL800 FLEX® or the Abbot i-stat Chem8+® analyzers by calculating the differences. RESULTS: The with-in run percentage coefficient of variation (%CV) was below 2.4% for pH, carboxyhemoglobin (COHb), deoxyhemoglobin (HHb), total hemoglobin (tHb), total bilirubin (tBil), sodium (Na), potassium (K), chloride (Cl), ionized calcium (iCa), urea, glucose and lactate, and was below 5.1% for all other analytes. The day-to-day %CV was below 1.6% for pH, COHb, HHb, tHb, tBil, Na, K, Cl, iCa, urea, glucose and lactate, and below 6.10% for all other analytes. The correlation coefficient (r) was 0.351 and ranged from 0.897 to 0.998 for all analytes. The mean bias was minimal for all analytes. CONCLUSION: There was a good correlation between the Nova Stat Profile Prime Plus® and the Radiometer ABL800 FLEX®/Abbott i-STAT Chem8+® POCT analyzers. The Stat Profile Prime Plus® exhibited good precision both within-run and day-to-day.

Evaluation of the impact of delayed centrifugation on the diagnostic performance of serum creatinine as a baseline measure of renal function before antiretroviral treatment.

BACKGROUND: The measurement of serum creatinine is a standard requirement of the medical management of people living with HIV. Renal dysfunction is common, both as a complication of HIV-infection and as a result of its treatment. The detection of abnormal renal function before the start of antiretroviral therapy will impact patient management and the outcome of treatment. OBJECTIVES: This study aimed to determine if a time delay in the centrifugation of serum samples affected the creatinine level and the estimated glomerular filtration rate as recorded on the analytical platforms used in the laboratory. METHODS: Twenty-two (n = 22) HIV-positive, newly diagnosed and treatment-naïve patients were randomly recruited from Alexandra Health Clinic, Johannesburg, South Africa. Serum samples were centrifuged at six time intervals following receipt of the sample viz. < 4 h (baseline), 6 h, 24 h, 48 h, 72 h and 96 h. Creatinine concentrations were measured on the Roche platform utilising the enzymatic and kinetic Jaffe methods. Whole blood samples were also analysed with the Abbott i-STAT point-of-care instrument. The estimated glomerular filtration rate was calculated using the Cockcroft Gault, CKD-Epidemiology Collaboration and Modified Diet and Renal Disease v3/4 equations. RESULTS: At baseline (< 4 h) there was good agreement between the enzymatic and kinetic Jaffe methods: bias 1.7 µmol/l. The enzymatic and i-STAT creatinine concentrations were stable over 96 h viz. changes of 1.8% and 5.7%. However, from 24 h onwards agreement between the enzymatic and kinetic Jaffe methods was poor with the latter measuring 43.7 µmol/l higher than the enzymatic method at 96 h. Creatinine concentrations measured with the kinetic Jaffe method increased significantly in samples centrifuged after 6 h (p < 0.001, 61.7% change), and resulted in a 95% decline in eGFR at 96 h as determined with the CKD-Epidemiology Collaboration equation. CONCLUSION: The analysis of serum creatinine using the isotope dilution mass spectrometry traceable kinetic Jaffe method is unreliable if performed on samples centrifuged ≥ 6 h after collection. The raised creatinine concentration can affect clinical decisions such as renal functional assessment, choice of antiretroviral drug or regimen, and the dose and frequency of medication.

Research Note: Comparison of chicken blood chemistry and electrolyte parameters between the portable i-STAT1 clinical analyzer and VetScan VS2 serum biochemistry panel using Hy-Line commercial white-egg laying hens.

The i-STAT1 clinical analyzer has become an increasingly popular tool in clinical production animal medicine as it can provide pen-side results in a cost effective and timely manner when compared to standard benchtop serum biochemistry blood gas and chemistry analyses. This study compares the results of the portable Abbott i-STAT1 analyzer and the Abaxis VetScan VS2 for glucose (Glu, mg/dL), ionized Ca (mmol/L), Na (mmol/L), and K (mmol/L) values. Three genetically distinct commercial varieties (CV) of Hy-Line white-egg laying hens are used in this study (Hy-Line W-36, Hy-Line W-80, and Hy-Line W-80+). Thirty blood samples (n = 10 per CV) were obtained in the production house from the brachial vein and concurrently analyzed by the i-STAT1 portable device. Serum from 22 of these same samples was analyzed via VetScan VS2, a benchtop serum clinical biochemistry analyzer, using VetScan Avian/Reptilian Profile Plus reagent rotors. A paired T-test was used to test for statistical differences in means between the 2 instruments for each of the parameters. Parameters with significant mean differences were then subject to correlation and regression analysis to further evaluate relationships between the results from the 2 methods. Significant differences between means were found for Glu, Na, and K levels. Ca levels were found to be not directly comparable by the 2 analysis instruments. This comparison elucidates the importance of clinical analyzer validations when applying different strategies of diagnostic medicine in poultry.

Simultaneous inhibition of atypical protein kinase­C and mTOR impedes bladder cancer cell progression.

Despite enormous scientific advancements in cancer treatment, there is a need for research to combat cancer, particularly bladder cancer. Drugs once proved to be effective in treating bladder cancer have shown reduced efficacy; hence, the cancer recurrence rate is increasing. To overcome this situation, several strategies have been considered, including the development of novel active drugs or modification of existing therapeutic regimens by combining two or more existing drugs. In recent years, atypical protein kinase Cs (PKCs), phospholipid­dependent serine/threonine kinases, have been considered as a central regulator of various cancer­associated signaling pathways, and they control cell cycle progression, tumorigenesis and metastasis. Additionally, the biologically crucial mTOR signaling pathway is altered in numerous types of cancer, including bladder cancer. Furthermore, despite independent activation, atypical PKC signaling can be triggered by mTOR. The present study examined whether the concurrent inhibition of atypical PKCs and mTOR using a combination of novel atypical PKC inhibitors (ICA­I, an inhibitor of PKC­Î¹; or ζ­Stat, an inhibitor of PKC­Î¶) and rapamycin blocks bladder cancer progression. In the present study, healthy bladder MC­SV­HUCT2 and bladder cancer TCCSUP cells were tested and subjected to a WST1 assay, western blot analysis, immunoprecipitation, a scratch wound healing assay, flow cytometry and immunofluorescence analyses. The results revealed that the combination therapy induced a reduction in human bladder cancer cell viability compared with control and individual atypical PKC inhibitor and rapamycin treatment. Additionally, the concurrent inhibition of atypical PKCs and mTOR retards the migration of bladder cancer cells. These findings indicated that the administration of atypical PKC inhibitors together with rapamycin could be a useful therapeutic option in treating bladder cancer.

The Atypical Protein Kinase C Small Molecule Inhibitor ζ-Stat, and Its Effects on Invasion Through Decreases in PKC-ζ Protein Expression.

Ovarian cancer is estimated to reach 22,530 diagnoses and cause 13,980 cancer deaths per year. The most common histology diagnosed of ovarian cancer is epithelial ovarian carcinomas (EOC). An aggressive epithelial subtype is clear cell ovarian carcinoma (CCOC) and is characterized as a non-serous ovarian cancer. Protein kinase C (PKC) is an enzymatic family of proteins that have been found to be a component in cancer progression, tissue invasion, and metastasis. The atypical PKC (aPKC) isoforms, PKC-ι and PKC-ζ, have been suggested to participate in the increased proliferation of ovarian cancers. Previous studies have indicated that novel aPKC inhibitors ICA-1S and ζ-Stat decreased the migratory behaviors of colorectal cancer cells and were selective for PKC-ι/λ and PKC-ζ, respectively. The aims of this investigation were to further determine the binding mechanisms of ζ-Stat, expand on the tissue range of these compounds, investigate the therapeutic potential of ζ-Stat in CCOC, and to illustrate the disruption of invasion via the PKC-ζ signaling cascade. The methods utilized were molecular docking and virtual target screening, Western blot analysis, end-point PCR, GST pull down, cell viability and invasion and migration assays. We discovered that the small molecule inhibitor, ζ-Stat, is a prospective drug candidate to investigate as a novel potential treatment for CCOC. We also found that the PKC-ζ/Ect2/Rac1 activation pathway was decreased by ζ-Stat, which in turn decreased invasive behavior of CCOC.

Intraoperative Monitoring of Heparin: Comparison of Activated Coagulation Time and Whole Blood Heparin Measurements by Different Point-of-Care Devices with Heparin Concentration by Laboratory-Performed Plasma Anti-Xa Assay.

BACKGROUND: Cardiac surgical interventions, extracorporeal membrane oxygenation, transcutaneous coronary-artery angioplasty, and stenting are carried out while patients are being treated with the anticoagulation drug heparin. Monitoring the level and reversal of heparinization during and at the conclusion of medical and surgical procedures is a critical issue in patient care. METHODS: We performed parallel testing of the ACCRIVA Hemochron Signature Elite ACT+ and Hemochron Response analyzer, iSTAT platform, and 2 Hepcon Hemostasis Management System (HMS) Plus analyzers for monitoring intraoperative heparin treatment. Laboratory anti-Xa assay was used as the criterion standard for heparin measurement. RESULTS: Poor correlation between the 2 Hemochron analyzers was identified at 0.78. Correlation between the analyzers on the i-STAT platform was 0.97. Regression analysis revealed that i-STAT values were generally lower, by 43 seconds, than Hemochron values. The correlation between Hepcon and i-STAT activated clotting time (ACT) results was 0.94. The i-STAT ACT results were generally 23 seconds lower than the Hepcon ACT values. Correlation coefficients on comparing Hepcon ACT and i-STAT ACT using laboratory anti-Xa assay were 0.83 and 0.87, respectively. The correlation between Hepcon heparin concentration and anti-Xa results was 0.85. CONCLUSIONS: ACT monitoring with iSTAT offers good correlation between instruments and with the Hepcon ACT. Hepcon occupies a specific niche in cardiac operating departments because of its ability to provide additional information regarding heparin concentration; however, lack of suitable proficiency testing may impair its use. The iSTAT is a more reliable platform for broader, hospital-wide application.

Venous blood gas and chemistry components are moderately heritable in commercial white egg-laying hens under acute or chronic heat exposure.

Heat stress has a large negative impact on poultry around the world in both intensive and small-scale production systems. Better understanding of genetic factors contributing to response to high ambient temperatures would provide a basis to develop strategies for alleviating negative impacts of heat on poultry production. The objective of this work was to characterize the genetic control (heritability estimate and quantitative trait loci (QTL)) of blood chemistry components before and after exposure to acute and chronic high ambient temperature in a commercial egg laying line Hy-Line W-36 female parent line mature hens were exposed to 4 wk of daily cyclic heat exposure. Blood was collected pre-heat, on the first day of heat, and 2 and 4 wk post heat initiation and analyzed immediately using an i-STAT® hand-held blood analyzer. Thirteen blood components were quantified at the 4 time points: pH, pCO2, pO2, HCO3, TCO2, sO2, iCa, Na, K, base excess, glucose, "hematocrit" (estimated from blood electrical conductivity, BEC), and "hemoglobin" (calculated from BEC). Heritabilities were estimated using genomic relationship information obtained from 600k SNP chip data. All 13 parameters exhibited a significant change after 5 h of heat exposure and most did not return to pre-heat levels throughout the duration of the study. Eight parameters (base excess, glucose, hemoglobin, HCO3, hematocrit, K, pCO2, TCO2) had heritability estimates differing from zero at one or more time points (0.21 to 0.45). The traits with significant heritability would be good candidates for use as biomarkers in a selection program if they are correlated with traits of economic importance that are more difficult to measure. QTL were identified for nine of the traits at one or more time point. These nine traits, however, did not have significant heritability estimates suggesting that while some QTL have been identified their effects are generally small.

Comparison of point-of-care and central laboratory analyzers for blood gas and lactate measurements.

BACKGROUND: Blood gas analysis and blood lactate measurement have important roles in patient management. Point-of-care (POC) testing simplifies and provides rapid blood gas and lactate measurements. This study aimed to compare pH, pCO2 , pO2 , and lactate measurements between a POC device and a benchtop blood gas analyzer typically used in a hospital central laboratory, and to evaluate the inter-device variability of the POC device. METHODS: A cross-sectional study was conducted with a sample size of 100. Each sample was measured for pH, pCO2 , pO2 , and lactate using a Nova pHOx plus L® benchtop blood gas analyzer in the central laboratory and an i-STAT® handheld POC device. The results of both devices were compared using Pearson or Spearman correlation coefficients and Bland-Altman tests. Testing of the inter-device variability was done by using three different i-STAT® devices, and the results were compared statistically. RESULTS: Strong correlations were observed for all test results. In Bland-Altman analysis, ≥95% of the results were within the limits of agreement, with the exception of lactate, which had only 93%. The results that were beyond the limits were primarily lactate levels >8 mmol/L. Biases between the benchtop analyzer and the i-STAT® were not clinically significant, except pH. No significant inter-device variability was observed between the i-STAT® analyzers. CONCLUSION: This comparison study of pH, pCO2 , pO2 , and lactate measurements between Nova pHOx plus L® and i-STAT® analyzers showed good agreement. However, lactate measurement results >8 mmol/L on the i-STAT® analyzer should be interpreted with caution.

Establishment of Hy-Line commercial laying hen whole blood gas and biochemistry reference intervals utilizing portable i-STAT1 clinical analyzer.

Blood gas and biochemistry reference intervals were established for 3 genetically distinct commercial varieties (CVs) of Hy-Line laying hens: 2 brown-egg layers (Hy-Line Brown, Hy-Line Silver Brown) and a tint-egg layer (Hy-Line Sonia) utilizing the i-STAT1 analyzer. Each respective variety of laying hen was sampled on a replicate cycle of 2 wk for a total of 6 replicates (35 to 46 wk of age). Blood samples were obtained in the production house from the brachial vein, and subsequently analyzed by the i-STAT1 portable device. i-STAT1 clinical analyzer reports blood gas and biochemistry values for the following parameters: pH, partial pressure of carbon dioxide (pvCO2, mm Hg), partial pressure of oxygen (pvO2, mm Hg), bicarbonate (HCO3, mmol/L), base excess (BE, mmol/L), saturation of oxygen on hemoglobin (sO2%), glucose (Glu, mg/dL), sodium (Na, mmol/L), potassium (K, mmol/L), total concentration of carbon dioxide (TCO2, mmol/L), ionized calcium (iCa, mmol/L), hematocrit (Hct % packed cell volume [PCV]), hemoglobin (Hb, g/dL). A total of 1,800 individual hen i-STAT1 records were utilized in the establishment of reference interval values for the 13 parameters between the 3 CVs. Statistical analysis via ANOVA and Tukey's test revealed significant line differences for all 13 blood gas and chemistry parameters measured, with particularly interesting results in iCa. The blood gas and chemistry parameters collected in this study will serve as reference intervals to set the framework for potential future correlations to genetic markers, physiological abnormalities, and production performance.

Discovery of a polysaccharide from the fruiting bodies of Lepista sordida as potent inhibitors of indoleamine 2, 3-dioxygenase (IDO) in HepG2 cells via blocking of STAT1-mediated JAK-PKC-δ signaling pathways.

The present study examined the role of a polysaccharide (LSP, 25 and 100 µg/ml) from the fruiting bodies of Lepista sordid on the immunosuppressive enzyme indoleamine 2, 3-dioxygenase (IDO) in HepG2 cells, and the possible mechanism of action. IDO expression and kynurenine production from LSP-treated HepG2 cells following IFN-γ stimulation were dramatically inhibited by LSP treatment. In line with this, the medium of HepG2 cells pretreated with LSP improved the survival rate of primary CD4+ and CD8+ T cells as compared with IFN-γ-treated control cells. Moreover, tyrosine 701 and serine 727 phosphorylation of STAT1 were dramatically reduced by LSP pretreatment in IFN-γ-stimulated HepG2 cells. Furthermore phosphorylation of JAK-1 and JAK-2 was also inhibited by LSP. Additionally, two IDO promoters (GAS and ISRE) were inhibited in cells pretreated with LSP prior to IFN-γ exposure. These findings suggest that LSP exerts antitumor effects on HepG2 cells by inhibiting IDO via JAK-PKC-δ-STAT1 signaling pathway.

Assessment of Heparin Anticoagulation Measured Using i-STAT and Hemochron Activated Clotting Time.

OBJECTIVE: Adequate anticoagulation, measured using activated clotting time (ACT), is important during vascular and cardiac surgeries. Unfractionated heparin is the most common anticoagulant used. The purpose of this analysis was to compare the i-STAT ACT (iACT) to the Hemochron ACT (hACT), both of which were then compared to anti-factor Xa (anti-Xa) assay, a representation of heparin level and activity. DESIGN: Prospective study. SETTING: Tertiary care cardiovascular center. PARTICIPANTS: Eleven consecutive elective adult cardiac surgical patients. INTERVENTIONS: Prior to cardiopulmonary bypass, ACTs were measured using i-STAT and Hemochron technologies and compared to each other and to anti-Xa assay prior to and during a cumulative administration of heparin. Data were compared using bias analyses. MEASUREMENTS AND MAIN RESULTS: Heparin (300 U/kg) was administered in quarterly doses. Coagulation labs were collected prior to and 3 minutes after each quarterly dose of heparin. The baseline ACTs for i-STAT and Hemochron were 147 and 142 seconds, respectively. A significant association was found between iACT and hACT (p = 0.002). The iACT measurements underestimated hACT at ACT levels >180 seconds or anti-Xa levels >0.75 U/mL. No significant difference was found between ACT data at anti-Xa levels <0.5 U/mL. CONCLUSION: There was a good association between the iACT and hACT; however, the 2 tests are not equivalent. Overall, the iACT underestimated the hACT. Agreement between the ACT technologies was good at lower ACTs and anti-Xa levels, but declined with an anti-Xa >0.75 U/mL.

Protein Kinase C-ζ stimulates colorectal cancer cell carcinogenesis via PKC-ζ/Rac1/Pak1/ß-Catenin signaling cascade.

Colorectal cancer (CRC) is the second most common cancer in the world and death from CRC accounts for 8% of all cancer deaths both in men and women in the United States. CRC is life-threatening disease due to therapy resistant cancerous cells. The exact mechanisms of cell growth, survival, metastasis and inter & intracellular signaling pathways involved in CRC is still a significant challenge. Hence, investigating the signaling pathways that lead to colon carcinogenesis may give insight into the therapeutic target. In this study, the role of atypical Protein Kinase C (aPKC) on CRC was investigated by using two inhibitors of that protein class: 1) ζ-Stat (8-hydroxynaphthalene-1,3,6-trisulfonic acid) is a specific inhibitor of PKC-ζ and 2) ICA-I 5-amino-1-(2,3-dihydroxy-4-hydroxymethyl)cyclopentyl)-1H-imidazole-4-carboxamide) is a specific inhibitor of PKC-ι. The cell lines tested were CCD18CO normal colon epithelial and LOVO metastatic CRC cells. The inhibition of aPKCs did not bring any significant toxicity on CCD18CO normal colon cell line. Although PKC-ι is an oncogene in many cancers, we found the overexpression of PKC-ζ and its direct association with Rac1. Our findings suggest that the PKC-ζ may be responsible for the abnormal growth, proliferation, and migration of metastatic LOVO colon cancer cells via PKC-ζ/Rac1/Pak1/ß-Catenin pathway. These results suggest the possibility of utilizing PKC-ζ inhibitor to block CRC cells growth, proliferation, and metastasis.