Non-invasive diagnostic test for lung cancer using biospectroscopy and variable selection techniques in saliva samples.

Lung cancer is one of the most commonly occurring malignant tumours worldwide. Although some reference methods such as X-ray, computed tomography or bronchoscope are widely used for clinical diagnosis of lung cancer, there is still a need to develop new methods for early detection of lung cancer. Especially needed are approaches that might be non-invasive and fast with high analytical precision and statistically reliable. Herein, we developed a swab "dip" test in saliva whereby swabs were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy harnessed to principal component analysis-quadratic discriminant analysis (QDA) and variable selection techniques employing successive projections algorithm (SPA) and genetic algorithm (GA) for feature selection/extraction combined with QDA. A total of 1944 saliva samples (56 designated as lung-cancer positive and 1888 designed as controls) were obtained in a lung cancer-screening programme being undertaken in North-West England. GA-QDA models achieved, for the test set, sensitivity and specificity values of 100.0% and 99.1%, respectively. Three wavenumbers (1422 cm-1, 1546 cm-1 and 1578 cm-1) were identified using the GA-QDA model to distinguish between lung cancer and controls, including ring C-C stretching, CN adenine, Amide II [δ(NH), ν(CN)] and νs(COO-) (polysaccharides, pectin). These findings highlight the potential of using biospectroscopy associated with multivariate classification algorithms to discriminate between benign saliva samples and those with underlying lung cancer.

ATR-FTIR Spectroscopy with Chemometrics for Analysis of Saliva Samples Obtained in a Lung-Cancer-Screening Programme: Application of Swabs as a Paradigm for High Throughput in a Clinical Setting.

There is an increasing need for inexpensive and rapid screening tests in point-of-care clinical oncology settings. Herein, we develop a swab "dip" test in saliva obtained from consenting patients participating in a lung-cancer-screening programme being undertaken in North West England. In a pilot study, a total of 211 saliva samples (n = 170 benign, 41 designated cancer-positive) were randomly taken during the course of this prospective lung-cancer-screening programme. The samples (sterile Copan blue rayon swabs dipped in saliva) were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. An exploratory analysis using principal component analysis (PCA,) with or without linear discriminant analysis (LDA), was then undertaken. Three pairwise comparisons were undertaken including: (1) benign vs. cancer following swab analysis; (2) benign vs. cancer following swab analysis with the subtraction of dry swab spectra; and (3) benign vs. cancer following swab analysis with the subtraction of wet swab spectra. Consistent and remarkably similar patterns of clustering for the benign control vs. cancer categories, irrespective of whether the swab plus saliva sample was analysed or whether there was a subtraction of wet or dry swab spectra, was observed. In each case, MANOVA demonstrated that this segregation of categories is highly significant. A k-NN (using three nearest neighbours) machine-learning algorithm also showed that the specificity (90%) and sensitivity (75%) are consistent for each pairwise comparison. In detailed analyses, the swab as a substrate did not alter the level of spectral discrimination between benign control vs. cancer saliva samples. These results demonstrate a novel swab "dip" test using saliva as a biofluid that is highly applicable to be rolled out into a larger lung-cancer-screening programme.

Point-of-Care Disease Screening in Primary Care Using Saliva: A Biospectroscopy Approach for Lung Cancer and Prostate Cancer.

Saliva is a largely unexplored liquid biopsy that can be readily obtained noninvasively. Not dissimilar to blood plasma or serum, it contains a vast array of bioconstituents that may be associated with the absence or presence of a disease condition. Given its ease of access, the use of saliva is potentially ideal in a point-of-care screening or diagnostic test. Herein, we developed a swab "dip" test in saliva obtained from consenting patients participating in a lung cancer-screening programme being undertaken in north-west England. A total of 998 saliva samples (31 designated as lung-cancer positive and 17 as prostate-cancer positive) were taken in the order in which they entered the clinic (i.e., there was no selection of participants) during the course of this prospective screening programme. Samples (sterile Copan blue rayon swabs dipped in saliva) were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. In addition to unsupervised classification on resultant infrared (IR) spectra using principal component analysis (PCA), a range of feature selection/extraction algorithms were tested. Following preprocessing, the data were split between training (70% of samples, 22 lung-cancer positive versus 664 other) and test (30% of samples, 9 lung-cancer positive versus 284 other) sets. The training set was used for model construction and the test set was used for validation. The best model was the PCA-quadratic discriminant analysis (QDA) algorithm. This PCA-QDA model was built using 8 PCs (90.4% of explained variance) and resulted in 93% accuracy for training and 91% for testing, with clinical sensitivity at 100% and specificity at 91%. Additionally, for prostate cancer patients amongst the male cohort (n = 585), following preprocessing, the data were split between training (70% of samples, 12 prostate-cancer positive versus 399 other) and test (30% of samples, 5 prostate-cancer positive versus 171 other) sets. A PCA-QDA model, again the best model, was built using 5 PCs (84.2% of explained variance) and resulted in 97% accuracy for training and 93% for testing, with clinical sensitivity at 100% and specificity at 92%. These results point to a powerful new approach towards the capability to screen large cohorts of individuals in primary care settings for underlying malignant disease.

Time course and differential responses of the major heat shock protein families in human skeletal muscle following acute nondamaging treadmill exercise.

The exercise-induced expression of heat shock proteins (HSPs) in rodent models is relatively well defined. In contrast, comparable data from human studies are limited and the exercise-induced stress response of human skeletal muscle is far from understood. This study has characterized the time course and magnitude of the HSP response in the skeletal muscles of a healthy active, but untrained, young male population following a running exercise protocol. Eight subjects performed 45 min of treadmill running at a speed corresponding to their lactate threshold (11.7 +/- 0.5 km/h; 69.8 +/- 4.8% maximum O2 uptake). Muscle biopsies were obtained from the vastus lateralis muscle immediately before and at 24 h, 48 h, 72 h, and 7 days postexercise. Exercise induced a significant (P < 0.05) but variable increase in HSP70, heat shock cognate (HSC) 70, and HSP60 expression with peak increases (typically occurring at 48 h postexercise) to 210, 170, and 139% of preexercise levels, respectively. In contrast, exercise did not induce a significant increase in either HSP27, alphaB-crystallin, SOD 2 (MnSOD) protein content, or the activity of SOD and catalase. When examining baseline protein levels, HSC70, HSP27, and alphaB-crystallin appeared consistently expressed between subjects, whereas HSP70 and MnSOD displayed marked individual variation of up to 3- and 1.5-fold, respectively. These data are the first to define the time course and extent of HSP production in human skeletal muscle following a moderately demanding and nondamaging running exercise protocol. Data demonstrate a differential effect of aerobic exercise on specific HSPs.

Effects of equipment and technique on peak flow measurements.

BACKGROUND: Different lung function equipment and different respiratory manoeuvres may produce different Peak Expiratory Flow (PEF) results. Although the PEF is the most common lung function test, there have been few studies of these effects and no previous study has evaluated both factors in a single group of patients. METHODS: We studied 36 subjects (PEF range 80-570 l/min). All patients recorded PEF measurements using a short rapid expiration following maximal inspiration (PEF technique) or a forced maximal expiration to residual volume (FVC technique). Measurements were made using a Wright's peak flow meter, a turbine spirometer and a Fleisch pneumotachograph spirometer. RESULTS: The mean PEF was 8.7% higher when the PEF technique was used (compared with FVC technique, p < 0.0001). The mean PEF recorded with the turbine spirometer was 5.5% lower than the Wright meter reading. The Fleisch spirometer result was 19.5% lower than the Wright reading. However, adjustment of the Wrights measurements from the traditional Wright's scale to the new EU Peak Flow scale produced results that were only 7.2% higher than the Fleisch pneumotachograph measurements. CONCLUSION: Peak flow measurements are affected by the instruction given and by the device and Peak Flow scale used. Patient management decisions should not be based on PEF measurement made on different instruments.

Exogenous glutamine: the clinical evidence.

We know that critically ill patients suffering from undernutrition with a limited nutritional reserve have a poorer outcome. Furthermore, having a low body mass index has been shown to be an independent predictor of excess mortality in multiple organ failure. Therefore, nutritional support has gained increasing interest in critical illness with the hope of preventing or attenuating the effects of malnutrition. A negative nitrogen balance is the characteristic metabolic feature in critical illness, with the major protein loss derived from skeletal muscle. In particular, glutamine concentrations are rapidly reduced in plasma and muscle. Over the last 20 yrs or so, increasing evidence is emerging to support the use of glutamine supplementation in critical illness. Clinical trials have found a mortality and morbidity advantage with glutamine supplementation. The advantage appears to be greater the more glutamine is given and greater again when given parenterally. Various modes of action have been postulated. Glutamine seems to have an effect on the immune system, antioxidant status, glucose metabolism, and heat shock protein response. However, the benefit of exogenous glutamine on morbidity and mortality is not universally accepted. This review critically appraises the current clinical evidence regarding glutamine supplementation in critical illness.

Are there any real differences between enteral feed formulations used in the critically ill?

PURPOSE OF REVIEW: We know that adequate nutritional support is essential in the treatment of critically ill patients, because it can, if applied appropriately, improve the clinical outcome. Increasing evidence seems to suggest that malnutrition itself is a predictor of poor outcome in intensive care, and significant underfeeding during intensive care stay increases the risk of bloodstream infections. The purpose of this review is to highlight recent advances in enteral nutrition in the critically ill adult patient. RECENT FINDINGS: Recent studies suggest that tight glycaemic control is associated with improved outcome. Enteral feeding should be encouraged, using simple feeding protocols, and started early if safe to do so. Gastric residual volumes do not correlate with the risk of aspiration, and therefore should be used with caution in feeding protocols. Conflicting evidence exists for supplementation with antioxidant and immunonutrition in the critically ill. Glutamine and fish oil/borage oil should be considered for burns patients and patients with adult respiratory distress syndrome, respectively. SUMMARY: This review offers information regarding the latest developments in nutritional support via the enteral route. Further research is needed to clarify the role of enteral supplements such as antioxidants and 'immune modulating substances'.