Development and validation of the COugh Assessment Test (COAT).

BACKGROUND AND OBJECTIVE: A cough-specific quality-of-life questionnaire is recommended to assess the impact of cough; however, a simple instrument to quantify cough is required for everyday clinical practice. This study was aimed to develop a short patient-completed questionnaire (COugh Assessment Test, COAT). METHODS: The COAT was developed and validated by comparison with the Korean version of Leicester Cough Questionnaire (K-LCQ) and cough numeric rating scale (NRS, 0-10, 11-point scale) for chronic cough patients. RESULTS: Item selection identified five items regarding cough frequency, daily activity, sleep disturbance, fatigue and cough hypersensitivity (0-4 scaling of items, 0-20 score range) through reliability test cohort (n = 78). Test-retest reliability was strong (intra-class correlation coefficient = 0.88). The final COAT was compared with K-LCQ and cough NRS in a validation cohort (n = 323). In Rasch analysis, COAT fitted well to a unidimensional model. Pearson correlations of COAT versus K-LCQ (i) before treatment, (ii) after treatment; COAT versus cough NRS (iii) before treatment, (iv) after treatment; (v) delta-COAT versus delta-cough NRS, (vi) delta-COAT versus delta-K-LCQ were (i) -0.71, (ii) -0.81, (iii) 0.69, (iv) 0.82, (v) -0.66 and (vi) 0.72, respectively. CONCLUSION: The COAT is a useful, simple questionnaire for assessing and monitoring cough.

Enrichment of plasma membrane proteins using nanoparticle pellicles: comparison between silica and higher density nanoparticles.

Proteomic and other characterization of plasma membrane proteins is made difficult by their low abundance, hydrophobicity, frequent carboxylation, and dynamic population. We and others have proposed that underrepresentation in LC-MS/MS analysis can be partially compensated by enriching the plasma membrane and its proteins using cationic nanoparticle pellicles. The nanoparticles increase the density of plasma membrane sheets and thus enhance separation by centrifugation from other lysed cellular components. Herein, we test the hypothesis that the use of nanoparticles with increased densities can provide enhanced enrichment of plasma membrane proteins for proteomic analysis. Multiple myeloma cells were grown and coated in suspension with three different pellicles of three different densities and both pellicle coated and uncoated suspensions analyzed by high-throughput LC-MS/MS. Enrichment was evaluated by the total number and the spectral counts of identified plasma membrane proteins.

Efficacy and safety profile of combining agents against epidermal growth factor receptor or vascular endothelium growth factor receptor with gemcitabine-based chemotherapy in patients with advanced pancreatic cancer: a meta-analysis.

OBJECTIVES: Several clinical trials have been published on gemcitabine-based chemotherapy with or without addition of agents against epidermal growth factor receptor (EGFR) or vascular endothelium growth factor receptor (VEGFR) in patients with advanced pancreatic cancer, however, with diverse results. The objective of this study was to perform a meta-analysis of the published trials. METHODS: The database of CENTRAL, MEDLINE and EMBASE were searched. Eligible studies were randomized clinical trials (RCTs) that evaluated the efficacy and safety profile of adding targeted agents against EGFR or VEGFR to gemcitabine-based chemotherapy in patients with advanced pancreatic cancer. The primary outcome was overall survival (OS) while secondary outcomes included progression free survival (PFS) and overall response rate (ORR). Toxicity profiles were also assessed. Review Manager 5.1 was used to perform the analysis. RESULTS: Results reported from 6 RCTs involving 2733 patients were included in the analysis. Compared to gemcitabine-based chemotherapy alone, addition of an agent against EGFR resulted in significant longer OS [Hazard ratios (HR) 0.89 (0.79-0.99), p = 0.04] and longer PFS [HR 0.87 (0.79-0.97), p = 0.01], but no significant difference in ORR [RR 1.18 (0.82-1.70), p = 0.36]. The addition of an agent against VEGFR resulted in higher ORR [RR 1.54 (1.03-2.30), p = 0.04], but no advantage in OS [HR 0.95 (0.83-1.09), p = 0.47] or PFS [HR 0.97 (0.77-1.23), p = 0.82]. CONCLUSIONS: Addition of an agent against EGFR to gemcitabine-based chemotherapy improved OS compared to gemcitabine-based chemotherapy alone in patients with advanced pancreatic cancer, while addition of an agent against VEGFR showed a modest improvement in ORR but not PFS and OS.

The Value of Residual Volume/Total Lung Capacity as an Indicator for Predicting Postoperative Lung Function in Non-Small Lung Cancer.

Chronic obstructive pulmonary disease (COPD) is one of the most frequently occurring concomitant diseases in patients with non-small cell lung cancer (NSCLC). It is characterized by small airways and the hyperinflation of the lung. Patients with hyperinflated lung tend to have more reserved lung function than conventionally predicted after lung cancer surgery. The aim of this study was to identify other indicators in predicting postoperative lung function after lung resection for lung cancer. Patients with NSCLC who underwent curative lobectomy with mediastinal lymph node dissection from 2017 to 2019 were included. Predicted postoperative FEV1 (ppoFEV1) was calculated using the formula: preoperative FEV1 × (19 segments-the number of segments to be removed) ÷ 19. The difference between the measured postoperative FEV1 and ppoFEV1 was defined as an outcome. Patients were categorized into two groups: preserved FEV1 if the difference was positive and non-preserved FEV1, if otherwise. In total, 238 patients were included: 74 (31.1%) in the FEV1 non-preserved group and 164 (68.9%) in the FEV1 preserved group. The proportion of preoperative residual volume (RV)/total lung capacity (TLC) ≥ 40% in the FEV1 non-preserved group (21.4%) was lower than in the preserved group (36.1%) (p = 0.03). In logistic regression analysis, preoperative RV/TLC ≥ 40% was related to postoperative FEV1 preservation. (adjusted OR, 2.02, p = 0.041). Linear regression analysis suggested that preoperative RV/TLC was positively correlated with a significant difference. (p = 0.004) Preoperative RV/TLC ≥ 40% was an independent predictor of preserved lung function in patients undergoing curative lobectomy with mediastinal lymph node dissection. Preoperative RV/TLC is positively correlated with postoperative lung function.

Fabrication of patterned single-walled carbon nanotube films using electrophoretic deposition.

Thin films of chemically functionalized single-walled carbon nanotubes (SWNTs) were fabricated by using a direct current (dc) electrophoretic deposition method. SWNTs were shortened and then functionalized with acid chloride group to combine with the amine group-terminated gold substrate. Silica nanospheres with a diameter of about 190 nm were arrayed on gold substrate to pattern a thin SWNT film. Periodically patterned SWNT film was eventually produced and would be used in potential applications like electron emitters and large surface area electrodes.

Electrical properties of polyaniline and multi-walled carbon nanotube hybrid fibers.

We have fabricated for the first time one-dimensional multiwalled carbon nanotube (MWNT) nanocomposite fibers with improved electrical properties using electrospinning. Polyaniline (PANi) and poly(ethylene oxide) (PEO) were used as a conducting and a nonconducting matrix, respectively, for hybrid nanofibers including MWNTs. The hybrid nanofibers fabricated by electrospinning had a length of several centimeters and a diameter ranging from approximately 100 nm to approximately 1 microm. Transmission electron microscopic analysis confirmed that the MWNTs were successfully oriented along the fiber axis without any severe aggregation during electrospinning. The hybrid nanofibers showed an enhanced electrical conductance with increasing MWNT content up to 0.5 wt%, and compared to PANi/PEO fibers, they also showed a stable linear ohmic behavior. These hybrid conducting nanofibers can be applied to chemical and biosensors that require a high sensitivity.

Characteristics of electrodeposited single-walled carbon nanotube films.

Thin films of chemically-functionalized single walled carbon nanotubes (SWNTs) were fabricated by using a direct current (DC) electrodeposition method. SWNTs were shortened and then functionalized with acid chloride group to combine with amine group-terminated gold substrate. The electrodeposited SWNT films were characterized by using Raman spectroscopy, attenuated total reflectance infrared (ATR/IR) spectrometry and atomic force microscopy. We demonstrated that the SWNT film was well distributed on an electrode with robust adhesion.

The Korean Cough Guideline: Recommendation and Summary Statement.

Cough is one of the most common symptom of many respiratory diseases. The Korean Academy of Tuberculosis and Respiratory Diseases organized cough guideline committee and cough guideline was developed by this committee. The purpose of this guideline is to help clinicians to diagnose correctly and treat efficiently patients with cough. In this article, we have stated recommendation and summary of Korean cough guideline. We also provided algorithm for acute, subacute, and chronic cough. For chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered. If UACS is suspicious, first generation anti-histamine and nasal decongestant can be used empirically. In CVA, inhaled corticosteroid is recommended in order to improve cough. In GERD, proton pump inhibitor is recommended in order to improve cough. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, angiotensin converting enzyme inhibitor, habit, psychogenic cough, interstitial lung disease, environmental and occupational factor, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and idiopathic cough can be also considered as cause of chronic cough. Level of evidence for treatment is mostly low. Thus, in this guideline, many recommendations are based on expert opinion. Further study regarding treatment for cough is mandatory.

Prevalence of chronic cough and possible causes in the general population based on the Korean National Health and Nutrition Examination Survey.

Although chronic cough is very common, its prevalence and causes have been rarely reported in the large general population including smokers. This study aimed to identify the prevalence of possible causes of chronic cough and their clinical impact.From Korean National Health and Nutrition Examination Survey (KNHANES) data including 119,280 adults aged over 40 years, 302 individuals with chronic cough were recruited irrespective of smoking status. Data from questionnaire, laboratory tests including spirometry, chest radiographs, and otorhinolaryngologic examination were analyzed.The prevalence of chronic cough in adults was 2.5% ±â€Š0.2%. Current smokers occupied 47.7% ±â€Š3.8% of study population and 46.8% ±â€Š3.9% of the subjects showed upper airway cough syndrome (UACS). Based on spirometry, chronic obstructive pulmonary disease (COPD) was identified in 26.4% ±â€Š3.5%. Asthma explained for 14.5% ±â€Š2.8% of chronic cough. Only 4.1% ±â€Š1.6% showed chronic laryngitis suggesting gastro-esophageal reflux-related cough. Abnormalities on chest radiography were found in 4.0% ±â€Š1.2%. Interestingly, 50.3% ±â€Š4.5% of study subjects had coexisting causes. In multivariate analysis, only current smoking (odds ratio [OR] 3.16, P < 0.001), UACS (OR 2.50, P < 0.001), COPD (OR 2.41, P < 0.001), asthma (OR 8.89, P < 0.001), and chest radiographic abnormalities (OR 2.74, P = 0.003) were independent risk factor for chronic cough. This pattern was not different according to smoking status excepting the prevalence of COPD.Smoking, COPD, and chest radiographic abnormalities should be considered as causes of chronic cough, along with UACS and asthma. Gastro-esophageal reflux-related cough is not prevalent in study population.

Arsenic sulfide inhibits cell migration and invasion of gastric cancer in vitro and in vivo.

BACKGROUND: We previously showed that arsenic sulfide (As4S4) induced cell cycle arrest and apoptosis in several human solid tumor cell lines, including those of gastric cancer. In this study, we investigated the effect of As4S4 on the migration and invasion of gastric cancer cells both in vitro and in vivo. METHODS: The human gastric cancer cell lines AGS and MGC803 were selected as in vitro models. Wound-healing migration assay and Transwell invasion assay were carried out to determine the effects of As4S4 on cell migration and invasion. The expressions of E-cadherin, ß-catenin, Sp1, KLF4, and VEGF were measured by Western blotting analysis. The activities of matrix metalloproteinase (MMP)-2 and MMP-9 in MGC803 cells were demonstrated by zymography assay. A mouse xenograft model was established by inoculation with MGC803 cells, then intraperitoneal injected with As4S4 for 3 weeks and monitored for body weight and tumor changes. Finally, the inhibition rate of tumor growth was calculated, and the expression of proteins and genes associated with tumor invasion and metastasis in tumor tissues were measured by immunohistochemistry, Western blotting, and real-time polymerase chain reaction assay. RESULTS: As4S4 significantly inhibited the migration and invasion of gastric cancer cell lines. The expression of E-cadherin and KLF4 was upregulated, while the expressions of ß-catenin, VEGF, and Sp1 were downregulated following treatment with As4S4. Moreover, the protease activities of MMP-2 and MMP-9 were suppressed by As4S4 in MGC803 cells. Meanwhile, As4S4 effectively suppressed the abilities of tumor growth and invasion in the xenograft tumor model. We found that As4S4 upregulated the expression of E-cadherin and downregulated the expression of ß-catenin, Sp1, VEGF, and CD34 in mouse tumor tissues, consistent with the results in vitro. CONCLUSION: As4S4 inhibited the migration and invasion of gastric cancer cells by blocking tumor cell adhesion, decreasing the ability of tumor cells to destroy the basement membrane, and therefore suppressing their angiogenesis.

Arsenic sulfide as a potential anti­cancer drug.

Arsenic sulfide (As4S4) is the main component of realgar, which is widely used in traditional Chinese medicine. Previous studies have shown the beneficial effects of As4S4 in the treatment of hematological malignant diseases, however, its effects on solid tumors have yet to be fully elucidated. The current study aimed to explore the anti­cancer effect and the mechanism of As4S4 on solid tumors in vitro and in vivo. Cells from four human solid tumor cell lines, including the MKN45 gastric cancer cell line, the A375 malignant melanoma cell line, the 8898 pancreatic carcinoma cell line and the HepG2 hepatocellular carcinoma cell line, were treated with As4S4 in vitro, using the L02 embryonic liver cells as a control. The efficacy of As4S4 was assessed in vivo using mice implanted with Lewis lung carcinoma cells. The results of the current study demonstrated that As4S4 significantly inhibited the proliferation of solid tumor cells in a dose­ and time­dependent manner, but produced a less pronounced effect on L02 cells. Additionally, As4S4 was observed to induce apoptosis (including morphological changes and an enhanced sub­G1 population), which was accompanied by the activation of caspase­3 and ­9. Furthermore, treatment with As4S4 significantly inhibited the growth of implanted tumors in mice. These results suggest that As4S4 possesses potent in vitro and in vivo antitumor activity via the induction of cell apoptosis.

Arsenic sulfide, the main component of realgar, a traditional Chinese medicine, induces apoptosis of gastric cancer cells in vitro and in vivo.

BACKGROUND: Arsenic sulfide (As4S4), the main component of realgar, a traditional Chinese medicine, has shown antitumor efficacy in several tumor types, especially for acute promyelocytic leukemia. In this study, we aimed to explore the efficacy and mechanism of As4S4 in gastric cancer. METHODS: The effect of As4S4 on cell proliferation and apoptosis of gastric cancer cells was investigated by MTT assay, 4',6-diamidino-2-phenylindole (DAPI) staining, and annexin V-fluorescein isothiocyanate/propidium iodide staining using gastric cancer cell lines AGS (harboring wild-type p53) and MGC803 (harboring mutant p53) in vitro. The expression of apoptosis-related proteins was measured by Western blotting, real-time polymerase chain reaction, and immunohistochemistry analysis. Mouse xenograft models were established by inoculation with MGC803 cells, and the morphology and the proportion of apoptotic cells in tumor tissues were detected by hematoxylin and eosin staining and TdT-mediated dUTP nick end labeling (TUNEL) assay, respectively. RESULTS: As4S4 inhibited the proliferation and induced apoptosis of AGS and MGC803 cells in a time- and dose-dependent manner. As4S4 upregulated the expression of Bax and MDM2 while downregulated the expression of Bcl-2. The expression of p53 increased significantly in the AGS cells but did not readily increase in the MGC803 cells, which harbored mutant p53. Pifithrin-α, a p53 inhibitor, blocked the modulation of As4S4 on AGS cells, but not on MGC803 cells. Using xenograft as a model, we showed that As4S4 suppressed tumor growth and induced apoptosis in vivo and that the expression of p53 increased accordingly. CONCLUSION: As4S4 is a potent cytotoxic agent for gastric cancer cells, as it induced apoptosis both in vitro and in vivo through a p53-dependent pathway. Our data indicate that As4S4 may have therapeutic potential in gastric cancer.

A Case of Severe Pseudomembranous Tracheobronchitis Complicated by Co-infection of Influenza A (H1N1) and Staphylococcus aureus in an Immunocompetent Patient.

Although influenza A (H1N1) virus leads to self-limiting illness, co-infection with bacteria may result in cases of severe respiratory failure due to inflammation and necrosis of intra-airway, as pseudomembranous tracheobronchitis. Pseudomembranous tracheobronchitis is usually developed in immunocompromised patients, but it can also occur in immunocompetent patients on a very rare basis. We report a case of pseudomembranous tracheobronchitis complicated by co-infection of inflenaza A and Staphylococcus aureus, causing acute respiratory failure in immunocompetent patients.

Clinical response to sunitinib as a multitargeted tyrosine-kinase inhibitor (TKI) in solid cancers: a review of clinical trials.

Angiogenesis is an integral process in carcinogenesis, and molecular inhibitors of angiogenic factors are currently being tested as treatments for cancer. Sunitinib is an oral multitargeted tyrosine-kinase inhibitor that blocks activation through the stem cell-factor receptor (Kit) and platelet-derived growth-factor receptor. Sunitinib has shown potent antitumor activity against several solid tumors, including renal cell carcinoma, gastrointestinal stromal tumors, and neuroendocrine tumors in several Phase II/III trials. Recently, sunitinib has been used to treat other solid cancers, such as lung cancer, pancreatic cancer, chondrosarcoma, esophageal cancer, bladder cancer, glioma, and aggressive fibromatosis, and also showed potential efficacy in progression-free survival and overall survival. In this review, we examine the efficacy of sunitinib as a molecular-targeted therapy in patients with different types of solid cancers.

Nanowire pellicles for eukaryotic cells: nanowire coating and interaction with cells.

AIM: To construct a new robust nanowire-based pellicle for eukaryotic cells, to investigate the interactions between nanowires (NWs) and cell surfaces and the internalization of nanowires, and to demonstrate for isolation of the plasma membrane with improved enrichment of transmembrane proteins. MATERIALS & METHODS: Silica NWs were coated with alumina to give positive charges on their surface. Multiple myeloma cells were coated with the positively charged NWs by dropping the cells into a buffered suspension of NWs. After the NW-coated cells were lysed, plasma membrane fragments were enriched by differential centrifugation for proteomic studies. RESULTS: Here we demonstrate complete cell coating with positively charged, alumina-coated silica NWs via nonspecific electrostatic interactions, and characterize a robust pellicle and little/no uptake of NWs. CONCLUSION: Robust pellicles provide a new platform for therapeutic, diagnostic and biochemical interactions of nanostructures with eukaryotic cells.

Factors predictive of the failure of medical treatment in patients with pleural infection.

BACKGROUND/AIMS: The clinical outcomes of some patients with pleural infection may be favorable with medical treatment alone, but in others, the disease progresses and requires additional surgical treatment. However, little is known about the factors affecting this difference. The aim of this study was to investigate the factors predictive of failure of medical treatment in patients with pleural infection. METHODS: A cohort of 127 consecutive patients who were admitted to the hospital with pleural infection was studied. Clinical manifestations and laboratory findings in patients in whom medical treatment succeeded or failed were reviewed. RESULTS: In univariate analysis, the significant factors associated with medical treatment outcome were age, smoking history, duration of chief complaint, serum albumin level, and pleural fluid glucose and lactate dehydrogenase levels (p < 0.05). Multivariate logistic regression analysis identified age and duration of chief complaint as independent predictive factors for failure of medical treatment, with odds ratios of 0.871 (p = 0.013) and 0.797 (p = 0.026), respectively. Receiver operating characteristic curve analysis determined cutoff values of 50.5 years for age and 4.5 days for duration of chief complaint. CONCLUSIONS: We demonstrated that a younger age < 50.5 years and shorter duration of chief complaint < 4.5 days were independent predictive factors for the failure of medical treatment in patients with pleural infection. This suggests their role as evaluative criteria in setting indications for the optimal treatment in patients with pleural infection. A larger, prospective study is required to confirm these findings.

Comparison of nanowire pellicles for plasma membrane enrichment: coating nanowires on cell.

A study is reported on the effect of nanowire density on the ease of pellicle formation and the enrichment of plasma membrane proteins for analysis by mass spectrometry. An optimized synthesis is reported for iron silicate nanowires with a narrow size range of 900 ±400 nm in length and 200 nm diameter. The nanowires were coated with Al2O3 and used to form pellicles around suspended multiple myeloma cells, which acted as a model for cells recovered from tissue samples. Lighter alumina-coated silica nanowires were also synthesized (Kim et al. 2013), which allowed a comparison of the construction of the two pellicles and of the effect of nanowire density on plasma membrane enrichment. Evidence is offered that the dense nanowire pellicle does not crush or distort these mammalian cells. Finally, the pellicles were incorporated into a mass-spectrometry-based proteomic workflow to analyze transmembrane proteins in the plasma membrane. In contrast to a prior comparison of the effect of density with nanoparticles pellicles (Choksawangkarn et al. 2013), nanowire density was not found to significantly affect the enrichment of the plasma membrane. However, nanowires with a favorable aspect for pellicle formation are more easily and reliably produced with iron silicate than with silica. Additionally, the method for pellicle formation was optimized through the use of iron silicate nanowires (ISNW), which is crucial to the improvement of PM protein enrichment and analysis.

Efficacy and safety profile of combining vandetanib with chemotherapy in patients with advanced non-small cell lung cancer: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety profile of combining vandetanib with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ASCO Abstracts, ESMO Abstracts, Wanfang Database, CNKI were searched. Eligible studies were the randomized clinical trials (RCTs) that compared the efficacy and safety profile of adding vandetanib to chemotherapy with single chemotherapy in patients with advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities. All meta-analysis were performed using Review Manager 5.1. The fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p<0.1, or I(2)>50%), further analysis (subgroup analysis, sensitivity analysis or random-effect model) was performed to identify potential cause. RESULTS: Results reported from 5 RCTs involving 2284 patients were included in the analysis. Compared to chemotherapy alone, the addition of vandetanib resulted in a significant longer PFS (HR 0.79 [0.72-0.87], p<0.00001) and a higher ORR (RR 1.75 [1.43-2.15], p<0.00001), but failed to show advantage on OS (HR 0.96 [0.87-1.06], p = 0.44). CONCLUSION: Vandetanib has activity in NSCLC. Identification of predictive biomarkers is warranted in future trials to select a subset of patients with advanced NSCLC who may benefit from vandetanib.

Pulmonary cryptococcosis mimicking primary lung cancer with multiple lung metastases.

Cryptococcosis is an invasive fungal infection, which is more common in immunocompromised patients. However, pulmonary cryptococcosis can occur in immunocompetent patients and should be considered on a differential diagnosis for nodular or mass-like lesions in chest radiograph. Recently, we experienced a patient with pulmonary cryptococcosis, successfully treated with oral fluconazole therapy. A 74-year-old female patient was referred for an evaluation of abnormal images, a large consolidative mass with multiple nodular consolidations and small nodules that mimics primary lung cancer with multiple lung to lung metastases. Computed tomography-guided lung biopsy confirmed the diagnosis of pulmonary cryptococcosis. The follow-up image taken after 4 months with oral fluconazole treatment showed marked improvement.

Field-induced cathodic oxidation of low-energy Ar-ion-bombarded silicon by AFM.

Local oxidation by atomic force microscopy (AFM) was studied on a 3keV Argon (Ar)-ion-bombarded silicon (Si) (100) substrate. Giant oxide features higher than 100nm were patterned by applying positive voltages to the tip with respect to the substrate. To analyze the growth rate of oxide features, we used the power-of-time law model. The growth rate of oxide features on an Ar-ion beam-bombarded silicon surface was increased approximately 1.8-fold compared to a common silicon surface. Furthermore, we obtained that the heights of oxide features increased as the exposure time to the tip decreased and the scan area increased.