Outcome of lung cancer patients with acute respiratory failure requiring mechanical ventilation

AbstractTo assess the weaning outcome of lung cancer patients with acute respiratory failure (ARF) requiring mechanical ventilation, we retrospectively analyzed the database of the respiratory intensive care unit at a university-affiliated tertiary care hospital.Charts were reviewed for cancer status, biochemistries before respiratory failure, causes of respiratory failure, acute physiology and chronic health evaluation (APACHE) III score, ventilatory settings, data recorded during spontaneous breathing, duration of ventilator days, and weaning outcome. Ninety-five consecutive respiratory failure events in 81 patients were recorded from January 1, 1995 through June 30, 1999.Twenty-six episodes ended with successful weaning (27.4%). Age, gender, and cancer status did not affect the weaning outcome. Serum albumin level, APACHE III score, highest fractional inspired O2 (FiO2) and highest positive end-expiratory pressure, organ failure, ability to shift to partial ventilatory support, and duration of mechanical ventilation could significantly influence the weaning outcome statistically. The overall hospital mortality rate was 85.2%.Our results suggested that lung cancer patients with ARF will have a better chance to wean if the initial APACHE III score was less than 70, use of FiO2 never exceeded 0.6, or less than 2 additional organ systems failed during the treatment course

High-global warming potential F-gas emissions in California: comparison of ambient-based versus inventory-based emission estimates, and implications of refined estimates.

To provide information for greenhouse gas reduction policies, the California Air Resources Board (CARB) inventories annual emissions of high-global-warming potential (GWP) fluorinated gases, the fastest growing sector of greenhouse gas (GHG) emissions globally. Baseline 2008 F-gas emissions estimates for selected chlorofluorocarbons (CFC-12), hydrochlorofluorocarbons (HCFC-22), and hydrofluorocarbons (HFC-134a) made with an inventory-based methodology were compared to emissions estimates made by ambient-based measurements. Significant discrepancies were found, with the inventory-based emissions methodology resulting in a systematic 42% under-estimation of CFC-12 emissions from older refrigeration equipment and older vehicles, and a systematic 114% overestimation of emissions for HFC-134a, a refrigerant substitute for phased-out CFCs. Initial, inventory-based estimates for all F-gas emissions had assumed that equipment is no longer in service once it reaches its average lifetime of use. Revised emission estimates using improved models for equipment age at end-of-life, inventories, and leak rates specific to California resulted in F-gas emissions estimates in closer agreement to ambient-based measurements. The discrepancies between inventory-based estimates and ambient-based measurements were reduced from -42% to -6% for CFC-12, and from +114% to +9% for HFC-134a

High-yield antibody production using targeted integration and engineering CHO host

To identify the high expression sites in the CHO cells, we employed NGS to analyze the integration sites of a high producing cell line (titer \u3e 3g/L). The pair-end reads with one read mapped to the vector and the other read mapped to the CHO reference genome are extracted to identify the integration sites. To test the expression activity of the integration sites, we employed CRISPR/Cas9 to specifically integrate the antibody gene into CHO genome for expression. Our data showed 4 integration sites are in the high producing cell line. Among the 4 integration site, one integration site was tested by CRISPR/Cas9 for target integration of antibody gene for expression. The target integrated cell pool present higher expression level (130 mg/L/copy) and less copy number when compared other integration sites. Through single-copy integration method, we can also achieve 60-150 mg/L/copy in a batch culture. About 80% of the single-copy cell clones were stable at generation 60. We have also applied the CHO-specific microarray transcriptomics technology to identify genes that contribute to high productivity. Transfection of our proprietary dual promoter vector J 1.0 resulting in 1.65 to 2.4 fold increase in the expression in engineered CHO DXB11 host. Through fed-batch process development, 3 – 5 g/L mAb productivity can be achieved through targeted integration and engineered CHO host

Selection of DDX5 as a novel internal control for Q-RT-PCR from microarray data using a block bootstrap re-sampling scheme

<p>Abstract</p> <p>Background</p> <p>The development of microarrays permits us to monitor transcriptomes on a genome-wide scale. To validate microarray measurements, quantitative-real time-reverse transcription PCR (Q-RT-PCR) is one of the most robust and commonly used approaches. The new challenge in gene quantification analysis is how to explicitly incorporate statistical estimation in such studies. In the realm of statistical analysis, the various available methods of the probe level normalization for microarray analysis may result in distinctly different target selections and variation in the scores for the correlation between microarray and Q-RT-PCR. Moreover, it remains a major challenge to identify a proper internal control for Q-RT-PCR when confirming microarray measurements.</p> <p>Results</p> <p>Sixty-six Affymetrix microarray slides using lung adenocarcinoma tissue RNAs were analyzed by a statistical re-sampling method in order to detect genes with minimal variation in gene expression. By this approach, we identified <it>DDX5 </it>as a novel internal control for Q-RT-PCR. Twenty-three genes, which were differentially expressed between adjacent normal and tumor samples, were selected and analyzed using 24 paired lung adenocarcinoma samples by Q-RT-PCR using two internal controls, <it>DDX5 </it>and <it>GAPDH</it>. The percentage correlation between Q-RT-PCR and microarray were 70% and 48% by using <it>DDX5 </it>and <it>GAPDH </it>as internal controls, respectively.</p> <p>Conclusion</p> <p>Together, these quantification strategies for Q-RT-PCR data processing procedure, which focused on minimal variation, ought to significantly facilitate internal control evaluation and selection for Q-RT-PCR when corroborating microarray data.</p

Chronic Kidney Disease Stage Is a Modulator on the Association between High-Sensitivity C-Reactive Protein and Coronary Vasospastic Angina

The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1–3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD

Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells

CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133+) and CD133-negative cells (LC-CD133−) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133+ displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133+, unlike LC-CD133−, highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133+ to form spheres and can further facilitate LC-CD133+ to differentiate into LC-CD133−. In addition, knock-down of Oct-4 expression in LC-CD133+ can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133+ can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133+. Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133+ and malignant lung cancer

Demographic and Clinical Characteristics of Patients with Severe Asthma in the Asian Pacific Region : data from the International Severe Asthma Registry (ISAR)

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