The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer.

The advances in targeted therapies for lung cancer are based on the evaluation of specific gene mutations especially the epidermal growth factor receptor (EGFR). The assays largely depend on the acquisition of tumor tissue via biopsy before the initiation of therapy or after the onset of acquired resistance. However, the limitations of tissue biopsy including tumor heterogeneity and insufficient tissues for molecular testing are impotent clinical obstacles for mutation analysis and lung cancer treatment. Due to the invasive procedure of tissue biopsy and the progressive development of drug-resistant EGFR mutations, the effective initial detection and continuous monitoring of EGFR mutations are still unmet requirements. Circulating tumor DNA (ctDNA) detection is a promising biomarker for noninvasive assessment of cancer burden. Recent advancement of sensitive techniques in detecting EGFR mutations using ctDNA enables a broad range of clinical applications, including early detection of disease, prediction of treatment responses, and disease progression. This review not only introduces the biology and clinical implementations of ctDNA but also includes the updating information of recent advancement of techniques for detecting EGFR mutation using ctDNA in lung cancer

The Effect of Lavender Aromatherapy on Autonomic Nervous System in Midlife Women with Insomnia

The objective of this study is to determine the effects of 12 weeks of lavender aromatherapy on self-reported sleep and heart rate variability (HRV) in the midlife women with insomnia. Sixty-seven women aged 45–55 years, with a CPSQI (Chinese version of Pittsburgh Sleep Quality Index) greater than 5, were recruited from communities in Taiwan. The experimental group (n = 34) received lavender inhalation, 20 min each time, twice per week, for 12 weeks, with a total of 24 times. The control group (n = 33) received health education program for sleep hygiene with no intervention. The study of HRV was analyzed by time- and frequency-domain methods. Significant decrease in mean heart rate (HR) and increases in SDNN (standard deviation of the normal-to-normal (NN) intervals), RMSDD (square root of the mean squared differences of successive NN intervals), and HF (high frequency) of spectral powers analysis after lavender inhalation were observed in the 4th and 12th weeks of aromatherapy. The total CPSQI score of study subjects was significantly decreased in the experimental group (P < 0.001), while no significant difference was observed across the same time period (P = 0.776) in the control group. Resting HR and HRV measurements at baseline 1 month and 3 months after allocation showed no significant difference between the experimental and control groups. The study demonstrated that lavender inhalation may have a persistent short-term effect on HRV with an increase in parasympathetic modulation. Women receiving aromatherapy experienced a significant improvement in sleep quality after intervention. However, lavender aromatherapy does not appear to confer benefit on HRV in the long-term followup

Foreign body in the urinary bladder causing persistent cystitis

SummaryAn unusual cause of a urinary tract infection (UTI) that presented in a woman who had previously undergone anti-incontinence sling surgery is presented here. A urinary bladder stone had formed on an eroded, nonabsorbable suture that had been used in the previous operation. Before identifying the underlying cause, the patient suffered from lower urinary tract symptoms and had undergone a prolonged course of antibiotic therapy for 3 years. Following removal of the suture, the UTI symptoms were rapidly resolved and only a short course of antibiotics was needed after the operation

Is there any relationship between producer price index and consumer price index in the Czech Republic?

This article tests the expenditure-switching model in the Czech Republic to inspect the causal link between the Producer Price Index (P.P.I.) and Consumer Price Index (C.P.I.). The results of the co-movement between the P.P.I. and C.P.I. in the period indicate a positive relationship across the chosen period. We notice that in the frequency domain, the two variables have a relationship in higher spectrums (short-term). The results also show that comovements exist during structural reforms and financial crises, which in turn supports the expenditure-switching model. The C.P.I. and P.P.I. are sensitive to variations in exchange rates, which pass through prices at the domestic level. Exchange rate shocks lead to inflationary pressure; therefore, long-term oriented intervention policies of the central banks will be more efficient. This article provides substantial information to exporters about price adjustments to exchange rate fluctuation

Liquid biopsy genotyping in lung cancer: ready for clinical utility?

Liquid biopsy is a blood test that detects evidence of cancer cells or tumor DNA in the circulation. Despite complicated collection methods and the requirement for technique-dependent platforms, it has generated substantial interest due, in part, to its potential to detect driver oncogenes such as epidermal growth factor receptor (EGFR) mutants in lung cancer. This technology is advancing rapidly and is being incorporated into numerous EGFR tyrosine kinase inhibitor (EGFR-TKI) development programs. It appears ready for integration into clinical care. Recent studies have demonstrated that biological fluids such as saliva and urine can also be used for detecting EGFR mutant DNA through application other user-friendly techniques. This review focuses on the clinical application of liquid biopsies to lung cancer genotyping, including EGFR and other targets of genotype-directed therapy and compares multiple platforms used for liquid biopsy

Prevalence of Pediculus Capitis Infestation Among School Children of Chinese Refugees Residing in Mountainous Areas of Northern Thailand

An epidemiologic survey of Pediculus capitis infestation among Akka aboriginal and Han children of Chinese refugees living in mountainous areas at elevations of 1,100 to 1,400 m in Chiang-Rai Province of northern Thailand was conducted during January 2003. Of the 303 children examined, 43 (14.2%) had P. capitis infestation. The overall infestation rate for P. capitis in Akka children (29.3%, 12/41) was significantly higher than that in Han children (11.8%, 31/262; c2 = 8.161, p = 0.002). The prevalence in Akka (52.2%, 12/23) and Han girls (19.7%, 31/157) was higher than that in Akka (0%) and Han boys (0%), respectively (p < 0.001), and the prevalence was higher in Akka girls than in Han girls (c2 = 10.978, p = 0.001). The high prevalence of P. capitis infestation among these girls was possibly due to poor environmental hygiene and unavailability of sufficient water

Web-based computer adaptive assessment of individual perceptions of job satisfaction for hospital workplace employees

<p>Abstract</p> <p>Background</p> <p>To develop a web-based computer adaptive testing (CAT) application for efficiently collecting data regarding workers' perceptions of job satisfaction, we examined whether a 37-item Job Content Questionnaire (JCQ-37) could evaluate the job satisfaction of individual employees as a single construct.</p> <p>Methods</p> <p>The JCQ-37 makes data collection via CAT on the internet easy, viable and fast. A Rasch rating scale model was applied to analyze data from 300 randomly selected hospital employees who participated in job-satisfaction surveys in 2008 and 2009 via non-adaptive and computer-adaptive testing, respectively.</p> <p>Results</p> <p>Of the 37 items on the questionnaire, 24 items fit the model fairly well. Person-separation reliability for the 2008 surveys was 0.88. Measures from both years and item-8 job satisfaction for groups were successfully evaluated through item-by-item analyses by using <it>t</it>-test. Workers aged 26 - 35 felt that job satisfaction was significantly worse in 2009 than in 2008.</p> <p>Conclusions</p> <p>A Web-CAT developed in the present paper was shown to be more efficient than traditional computer-based or pen-and-paper assessments at collecting data regarding workers' perceptions of job content.</p

Signal transducer and activator of transcription 3 activation up-regulates interleukin-6 autocrine production: a biochemical and genetic study of established cancer cell lines and clinical isolated human cancer cells

<p>Abstract</p> <p>Background</p> <p>Spontaneous interleukin-6 (IL-6) production has been observed in various tumors and implicated in the pathogenesis, progression and drug resistance in cancer. However, the regulation of IL-6 autocrine production in cancer cells is not fully understood. IL-6 is auto-regulated in many types of cell. Two of the three major downstream pathways of IL-6, MEK/extracellular signal-related kinase (Erk) pathway and phosphatidylinositol 3-kinase (PI3-K)/Akt pathway, have been shown to regulate IL-6 expression through the activation of AP-1 and NF-κB. However, it is not clear what the role of Janus kinase (Jak) 2/signal transducer and activator of transcription (Stat) 3 pathway. This study was designed to determine the role of Jak2/Stat3 pathway in the regulation of IL-6 autocrine production in cancer cells.</p> <p>Results</p> <p>Inhibitors of Jak2/Stat3, MEK/Erk and PI3-K/Akt pathways down-regulated IL-6 secretion in the lung adenocarcinoma PC14PE6/AS2 (AS2) cells, which spontaneously secreted IL-6 and possessed constitutively activated Stat3. Transfection with dominant-negative Stat3, Stat3 siRNA, or Stat3 shRNA decreased IL-6 expression in AS2 cells. Conversely, transfection with constitutively-activated Stat3 increased the production of IL-6. In AS2 derived cells, resistance to paclitaxel was positively correlated with Stat3 activation status and the expression of IL-6, which is commonly secreted in drug resistant cancer cells. The pharmacological inhibition of NF-κB, PI3-K/Akt and MEK/Erk and the pharmacological inhibition and genetic inhibition (Stat3 siRNA) of Jak2/Stat3 pathway decreased IL-6 autocrine production in various drug resistant cancer cell lines and similarly decreased IL-6 autocrine production in clinically isolated lung cancer cells.</p> <p>Conclusions</p> <p>This study is the first to directly address the role Stat3 plays on the autocrine production of IL-6, which occurs through a positive-feedback loop. Our biochemical and genetic studies clearly demonstrated that Jak2/Stat3, in combination with other IL-6 downstream pathways, contributed frequently and substantially to IL-6 autocrine production in a broad spectrum of cancer cell lines as well as in clinical cancer samples. Our findings suggest that Stat3 could potentially be regulated to suppress IL-6 autocrine production in cancer cells to inhibit the progression of cancer and reduce drug resistance.</p

Signal transducer and activator of transcription 3 activation up-regulates interleukin-6 autocrine production: a biochemical and genetic study of established cancer cell lines and clinical isolated human cancer cells

<p>Abstract</p> <p>Background</p> <p>Spontaneous interleukin-6 (IL-6) production has been observed in various tumors and implicated in the pathogenesis, progression and drug resistance in cancer. However, the regulation of IL-6 autocrine production in cancer cells is not fully understood. IL-6 is auto-regulated in many types of cell. Two of the three major downstream pathways of IL-6, MEK/extracellular signal-related kinase (Erk) pathway and phosphatidylinositol 3-kinase (PI3-K)/Akt pathway, have been shown to regulate IL-6 expression through the activation of AP-1 and NF-κB. However, it is not clear what the role of Janus kinase (Jak) 2/signal transducer and activator of transcription (Stat) 3 pathway. This study was designed to determine the role of Jak2/Stat3 pathway in the regulation of IL-6 autocrine production in cancer cells.</p> <p>Results</p> <p>Inhibitors of Jak2/Stat3, MEK/Erk and PI3-K/Akt pathways down-regulated IL-6 secretion in the lung adenocarcinoma PC14PE6/AS2 (AS2) cells, which spontaneously secreted IL-6 and possessed constitutively activated Stat3. Transfection with dominant-negative Stat3, Stat3 siRNA, or Stat3 shRNA decreased IL-6 expression in AS2 cells. Conversely, transfection with constitutively-activated Stat3 increased the production of IL-6. In AS2 derived cells, resistance to paclitaxel was positively correlated with Stat3 activation status and the expression of IL-6, which is commonly secreted in drug resistant cancer cells. The pharmacological inhibition of NF-κB, PI3-K/Akt and MEK/Erk and the pharmacological inhibition and genetic inhibition (Stat3 siRNA) of Jak2/Stat3 pathway decreased IL-6 autocrine production in various drug resistant cancer cell lines and similarly decreased IL-6 autocrine production in clinically isolated lung cancer cells.</p> <p>Conclusions</p> <p>This study is the first to directly address the role Stat3 plays on the autocrine production of IL-6, which occurs through a positive-feedback loop. Our biochemical and genetic studies clearly demonstrated that Jak2/Stat3, in combination with other IL-6 downstream pathways, contributed frequently and substantially to IL-6 autocrine production in a broad spectrum of cancer cell lines as well as in clinical cancer samples. Our findings suggest that Stat3 could potentially be regulated to suppress IL-6 autocrine production in cancer cells to inhibit the progression of cancer and reduce drug resistance.</p

Vocal cord dysfunction diagnosed by four-dimensional dynamic volume computed tomography in patients with difficult-to-treat asthma: A case series

Patients with asthma may also have vocal cord dysfunction (VCD), which leads to poor control of the asthma. Once patients are diagnosed with difficult-to-treat asthma with poor control, VCD should be excluded or treated accordingly. The gold standard for diagnosis of VCD is to perform a laryngoscopy. However, this procedure is invasive and may not be suitable for patients with difficult-to-treat asthma. Four-dimensional (4D) dynamic volume computed tomography (CT) is a noninvasive method for quantification of laryngeal movement, and can serve as an alternative for the diagnosis of VCD. Herein, we present a series of five cases with difficult-to-treat asthma patients who were diagnosed with VCD by 4D dynamic volume CT. Clinicians should be alert to the possibility of VCD when poor control is noted in patients with asthma. Early diagnosis by noninvasive 4D dynamic volume CT can decrease excessive doses of inhaled corticosteroids