Human tissue engineering allows the identification of active miRNA regulators of glioblastoma aggressiveness.

Glioblastoma multiforme (GBM) is among the most aggressive cancers associated with massive infiltration of peritumoral parenchyma by migrating tumor cells. The infiltrative nature of GBM cells, the intratumoral heterogeneity concomitant with redundant signaling pathways likely underlie the inability of conventional and targeted therapies to achieve long-term remissions. In this respect, microRNAs (miRNAs), which are endogenous small non-coding RNAs that play a role in cancer aggressiveness, emerge as possible relevant prognostic biomarkers or therapeutic targets for treatment of malignant gliomas. We previously described a tissue model of GBM developing into a stem cell-derived human Engineered Neural Tissue (ENT) that allows the study of tumor/host tissue interaction. Combined with high throughput sequencing analysis, we took advantage of this human and integrated tissue model to understand miRNAs regulation. Three miRNAs (miR-340, -494 and -1293) active on cell proliferation, adhesion to extracellular matrix and tumor cell invasion were identified in GBM cells developing within ENT, and also confirmed in GBM biopsies. The components of miRNAs regulatory network at the transcriptional and the protein level have been also revealed by whole transcriptome analysis and Tandem Mass Tag in transfected GBM cells. Notably, miR-340 has a clinical relevance and modulates the expression of miR-494 and -1293, emphasizing its biological significance. Altogether, these findings demonstrate that human tissue engineering modeling GBM development in neural host tissue is a suitable tool to identify active miRNAs. Collectively, our study identified miR-340 as a strong modulator of GBM aggressiveness which may constitute a therapeutic target for treatment of malignant gliomas.

Toscana virus meningitis case in Switzerland: an example of the ezVIR bioinformatics pipeline utility for the identification of emerging viruses.

Toscana virus (TOSV) represents a frequent cause of viral meningitis in the Mediterranean Basin that remains neglected in neighbouring countries. We report a documented TOSV meningitis case in a traveller returning from Tuscany to Switzerland. While routine serological and PCR assays could not discriminate between TOSV and Sandfly fever Naples virus infection, a high-throughput sequencing performed directly on the cerebrospinal fluid specimen and analysed with the ezVIR pipeline provided an unequivocal viral diagnostic. TOSV could be unequivocally considered as the aetiological agent, proving the potential of ezVIR to improve standard diagnostics in cases of infection with uncommon or emerging viruses.

Lung function and mortality in the United States: data from the First National Health and Nutrition Examination Survey follow up study.

BACKGROUND: A study was undertaken to define the risk of death among a national cohort of US adults both with and without lung disease. METHODS: Participants in the first National Health and Nutrition Examination Survey (NHANES I) followed for up to 22 years were studied. Subjects were classified using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD) into the following mutually exclusive categories using the forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), FEV(1)/FVC ratio, and the presence of respiratory symptoms: severe COPD, moderate COPD, mild COPD, respiratory symptoms only, restrictive lung disease, and no lung disease. Proportional hazard models were developed that controlled for age, race, sex, education, smoking status, pack years of smoking, years since quitting smoking, and body mass index. RESULTS: A total of 1301 deaths occurred in the 5542 adults in the cohort. In the adjusted proportional hazards model the presence of severe or moderate COPD was associated with a higher risk of death (hazard ratios (HR) 2.7 and 1.6, 95% confidence intervals (CI) 2.1 to 3.5 and 1.4 to 2.0), as was restrictive lung disease (HR 1.7, 95% CI 1.4 to 2.0). CONCLUSIONS: The presence of both obstructive and restrictive lung disease is a significant predictor of earlier death in long term follow up.

The early diagnosis of lung cancer.

Lung cancer is the most common fatal malignancy in both men and women, both in the United States and elsewhere in the world. Today, lung cancer is most often diagnosed on the basis of symptoms of advanced disease or when chest x-rays are taken for a variety of purposes unrelated to lung cancer detection. Unfortunately, in the United States no society or governmental agency recommends screening, even for patients with high risks, such as smokers with airflow obstruction or people with occupational exposures, including asbestos. The origins of this negative attitude toward lung cancer screening are found in 3 studies sponsored by the National Cancer Institute in the mid-1970s and conducted at Johns Hopkins University School of Medicine, the Mayo Clinic, and the Memorial Sloan-Kettering Center. These studies concluded that early identification of lung cancer through chest x-rays and cytologic diagnosis of sputum did not alter disease-specific mortality. However, patients with earlier stage disease were found through screening, which resulted in a higher resectability rate and improved survival in the screening group compared with a control group of patients receiving ordinary care. Patients in the control group often received annual chest x-rays during the course of this study, which was the standard of care at the time. Thus no true nonscreening control group resulted. The patients at highest risk were not enrolled in this study. No specific amount of pack-years of smoking intensity was required. Only men were screened. The studies were inadequately powered to show an improvement in mortality rate of less than 50%. Ninety percent of lung cancer occurs in smokers. The prevalence of lung cancer is 4 to 6 times greater when smokers have airflow obstruction than with normal airflow, when all other background factors, including smoking history, occupational risk, and family history, are the same. Screening heavy smokers (ie, > or = 30 pack-years) with airflow obstruction (forced expiratory volume in one second < 70% of normal) will yield 2% or more patients with lung cancer (prevalence cases) and, over the course of 5 years, probably from 2% to 3% of patients with additional cancers, yielding an overall incidence of 5%. New technologies include low-dose helical computed tomographic scans for small peripheral adenocarcinomas that cannot yet be visualized by standard chest x-rays and cytologic diagnosis of sputum for central squamous cell lesions. These tests are complementary. A new health care initiative, the National Lung Health Education Program, recommends spirometric testing for all smokers 45 years or older, as well as for patients with symptoms of lung cancer. Screening for lung cancer in such patients will find many cancers at an early stage when they are amenable to cure. Today, we have the knowledge and the technology that could change the outcome of lung cancer.

Addressing oral disease--the case for tobacco cessation services.

There is strong scientific evidence from clinical and epidemiological studies that tobacco use, particularly cigarette smoking, is linked to periodontal disease as well as other serious but less common oral health diseases. Given the strength of this evidence, dentists must include tobacco cessation services (TCS) as part of their routine care. This paper describes barriers to the adoption of TCS as identified by Alberta dentists participating in a randomized intervention trial and discusses strategies for overcoming these barriers. As well, suggestions are made to professional associations and educational institutes on ways to increase the incorporation of tobacco cessation into professional practice standards.

Partnering for optimal respiratory home care: physicians working with respiratory therapists to optimally meet respiratory home care needs.

The need for respiratory care services continues to increase, reimbursement for those services has decreased, and cost-containment measures have increased the frequency of home health care. Respiratory therapists are well qualified to provide home respiratory care, reduce misallocation of respiratory services, assess patient respiratory status, identify problems and needs, evaluate the effect of the home setting, educate the patient on proper equipment use, monitor patient response to and complications of therapy, monitor equipment functioning, monitor for appropriate infection control procedures, make recommendations for changes to therapy regimen, and adjust therapy under the direction of the physician. Teamwork benefits all parties and offers cost and time savings, improved data collection and communication, higher job satisfaction, and better patient monitoring, education, and quality of life. Respiratory therapists are positioned to optimize treatment efficacy, maximize patient compliance, and minimize hospitalizations among patients receiving respiratory home care.

Early detection for lung cancer. New tools for casefinding.

OBJECTIVE: To review data from published population trials and clinical practice guidelines on screening for lung cancer to provide a recommendation for early detection of lung cancer. QUALITY OF EVIDENCE: Literature was searched via MEDLINE using the MeSH headings "lung neoplasm," "mass screening," "thoracic radiography," and "sputum." Only prospective randomized controlled trials with large numbers of subjects were selected. MAIN MESSAGE: Risk of lung cancer among long-term heavy smokers continues even years after stopping smoking. Risk is highest in smokers with chronic obstructive pulmonary disease. Canadian clinical practice guidelines currently recommend that sputum cytology examination and chest radiography (CXR) not be used for lung cancer screening. This guideline was deducted from four randomized population trials in the 1970s that have serious limitations and applies to asymptomatic adults only. A CXR and sputum cytology examination are indicated in symptomatic current and former smokers older than 45 years with a smoking history of 30 pack-years or more and airflow obstruction defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of 70% or less and a FEV1 lower than 70%. Curative treatment is available for early lung cancer. Substantial advances in innovative technologies for early detection using low-dose spiral CT and newer sputum tests have been made in the last three decades. Additional studies are under way to evaluate these new technologies. CONCLUSION: Primary care physicians have an important role in identifying people at risk of developing lung cancer and in supporting research to evaluate new screening technology.

Preliminary observations of transtracheal augmented ventilation for chronic severe respiratory disease.

OBJECTIVE: Evaluate the potential safety and efficacy of transtracheal augmented ventilation (TTAV), which is the transtracheal delivery of high flows of a humidified air-oxygen blend. METHODS: The first of 2 observational studies evaluated patients before and after a 3-month intervention with the nocturnal (Noc) administration of TTAV at 10 L/min. Resting physiologic studies evaluated standard low-flow transtracheal oxygen (LFTTO), TTAV, and breathing without transtracheal flow via mouthpiece (MP). Patients also underwent nocturnal polysomnography, bronchoscopy, ventilatory drive evaluation, and treadmill exercise. The second study assessed the safety of Noc TTAV for up to 60 months. Each study evaluated 15 different transtracheal patients with severe lung disease. RESULTS: Pleural pressure-time index and respiratory duty cycle were significantly lower (p < 0.05) when comparing MP to TTAV. TTAV contributed more (p < 0.05) than LFTTO to the total volume delivered to the lung (V(L)). Arterial blood gases and (V(L)) were unaltered by TTAV. Sleep quality and nocturnal oxygenation with TTAV were similar to LFTTO, and Noc TTAV had no effect on ventilatory drive. Bronchoscopy showed no evidence of substantial injury. Treadmill exercise tests showed a longer exercise time (p < 0.005) and greater total work (p < 0.05) following Noc TTAV. During exercise, the changes in slope for heart rate and pH were less steep (p < 0.05) following Noc TTAV. The 3-month study and a long-term evaluation showed that Noc TTAV was well-tolerated and safe, with a reported high compliance. CONCLUSIONS: Patients with chronic hypoxemia and severe respiratory insufficiency may benefit from Noc TTAV.

Commentary: quality of spirometry testing.

Spirometry is necessary for the diagnosis and monitoring of both obstructive and restrictive lung diseases. Today, the most rapidly growing health problem in the United States is chronic obstructive pulmonary disease (COPD). COPD is now the fourth most common cause of death and the only cause of death that is rising among the top ten causes. There is also an increasing prevalence of interstitial lung diseases. Both obstructive and interstitial lung diseases are identified and monitored by spirometry.

Simple office spirometry.

Spirometric measurements are as fundamental to medicine as are measurements of pulse, blood pressure, temperature, height, and weight. Spirometric measurements should be considered important vital signs. Any deviations from "normal" measurements can point primary care physicians toward the use of behavioral modification or effective pharmacologic agents to prevent or forestall their patients' premature morbidity and mortality from many disease states, including premature deaths from all causes.

COPD. Interventions for smoking cessation and improved ventilatory function.

Chronic obstructive pulmonary disease (COPD) is a spectrum of smoking-related diseases that includes chronic bronchitis, emphysema, and asthmatic bronchitis. Smoking injures airways and alveoli, which invokes inflammatory processes in the respiratory tract that are mediated by oxidants, proteases, and inflammatory cytokines. Early identification of respiratory function loss and intervention are necessary to prevent progression to the disabling stages of COPD. Spirometry is a useful tool for assessing responses to smoking cessation and bronchoactive drugs. Anti-inflammatory drugs and antibiotics are useful to deal with exacerbations of bronchitis. Patient education and oxygen can improve the quality and duration of life in early and advanced stages of COPD.