Factors that influence the volatile organic compound content in human breath.

BACKGROUND: Thousands of endogenous and exogenous volatile organic compounds (VOCs) are excreted in each breath. Inflammatory and deviant metabolic processes affect the level of endogeneous VOCs, which can serve as specific biomarkers for clinical diagnosis and disease monitoring. Important issues that still need to be tackled are related to potential confounding factors like gender and age and endogenous and exogenous factors, like f.i. smoking. METHODS: The aim of this study was to systematically access the effect of endogenous and exogenous factors on VOC composition of exhaled breath. In the current study breath samples from 1417 adult participants from the LifeLines cohort, a general population cohort in the Netherlands, were collected and the total content of VOCs was measured using gas chromatography-time-of-flight-mass spectrometry. Breath samples were collected in Groningen and transferred to carbon tubes immediately. These samples were then shipped to Maastricht and measured in batches. VOCs profiles were correlated to 14 relevant characteristics of all participants including age, BMI, smoking and blood cell counts and metabolic parameters as well as to 16 classes of medications. RESULTS: VOCs profiles were shown to be significantly influenced by smoking behavior and to a lesser extent by age, BMI and gender. These factors need to be controlled for in breath analysis studies. We found no evidence whatsoever in this 1417 subjects' cohort that white blood cell counts, cholesterol or triglycerides levels have an influence on the VOC profile. Thus they may not have to be controlled for in exhaled breath studies. CONCLUSION: The large cohort of volunteers used here represents a unique opportunity to gauge the factors influencing VOCs profiles in a general population i.e. the most clinically relevant population. Classical clinical parameters and smoking habits clearly influence breath content and should therefore be accounted for in future clinical studies involving breath analysis.

Regularized MANOVA (rMANOVA) in untargeted metabolomics.

Many advanced metabolomics experiments currently lead to data where a large number of response variables were measured while one or several factors were changed. Often the number of response variables vastly exceeds the sample size and well-established techniques such as multivariate analysis of variance (MANOVA) cannot be used to analyze the data. ANOVA simultaneous component analysis (ASCA) is an alternative to MANOVA for analysis of metabolomics data from an experimental design. In this paper, we show that ASCA assumes that none of the metabolites are correlated and that they all have the same variance. Because of these assumptions, ASCA may relate the wrong variables to a factor. This reduces the power of the method and hampers interpretation. We propose an improved model that is essentially a weighted average of the ASCA and MANOVA models. The optimal weight is determined in a data-driven fashion. Compared to ASCA, this method assumes that variables can correlate, leading to a more realistic view of the data. Compared to MANOVA, the model is also applicable when the number of samples is (much) smaller than the number of variables. These advantages are demonstrated by means of simulated and real data examples. The source code of the method is available from the first author upon request, and at the following github repository: https://github.com/JasperE/regularized-MANOVA.

Multivariate curve resolution: a review of advanced and tailored applications and challenges.

Multivariate curve resolution (MCR) is a widespread methodology for the analysis of process data in many different application fields. This article intends to propose a critical review of the recently published works. Particular attention will be paid to situations requiring advanced and tailored applications of multivariate curve resolution, dealing with improvements in preprocessing methods, multi-set data arrangements, tailored constraints, issues related to non-ideal noise structure and deviation to linearity. These analytical issues are tackling the limits of applicability of MCR methods and, therefore, they can be considered as the most challenging ones.

Screening for emphysema via exhaled volatile organic compounds.

Chronic obstructive pulmonary disease (COPD)/emphysema risk groups are well defined and screening allows for early identification of disease. The capability of exhaled volatile organic compounds (VOCs) to detect emphysema, as found by computed tomography (CT) in current and former heavy smokers participating in a lung cancer screening trial, was investigated. CT scans, pulmonary function tests and breath sample collections were obtained from 204 subjects. Breath samples were analyzed with a proton-transfer reaction mass spectrometer (PTR-MS) to obtain VOC profiles listed as ions at various mass-to-charge ratios (m/z). Using bootstrapped stepwise forward logistic regression, we identified specific breath profiles as a potential tool for the diagnosis of emphysema, of airflow limitation or gas-exchange impairment. A marker for emphysema was found at m/z 87 (tentatively attributed to 2-methylbutanal). The area under the receiver operating characteristic curve (ROC) of this marker to diagnose emphysema was 0.588 (95% CI 0.453-0.662). Mass-to-charge ratios m/z 52 (most likely chloramine) and m/z 135 (alkyl benzene) were linked to obstructive disease and m/z 122 (most probably alkyl homologs) to an impaired diffusion capacity. ROC areas were 0.646 (95% CI 0.562-0.730) and 0.671 (95% CI 0.524-0.710), respectively. In the screening setting, exhaled VOCs measured by PTR-MS constitute weak markers for emphysema, pulmonary obstruction and impaired diffusion capacity.

Discrimination between metastasis and glioblastoma multiforme based on morphometric analysis of MR images.

BACKGROUND AND PURPOSE: Solitary MET and GBM are difficult to distinguish by using MR imaging. Differentiation is useful before any metastatic work-up or biopsy. Our hypothesis was that MET and GBM tumors differ in morphology. Shape analysis was proposed as an indicator for discriminating these 2 types of brain pathologies. The purpose of this study was to evaluate the accuracy of this approach in the discrimination of GBMs and brain METs. MATERIALS AND METHODS: The dataset consisted of 33 brain MR imaging sets of untreated patients, of which 18 patients were diagnosed as having a GBM and 15 patients, as having solitary metastatic brain tumor. The MR imaging was segmented by using the K-means algorithm. The resulting set of classes (also called "clusters") represented the variety of tissues observed. A morphology-based approach allowed discrimination of the 2 types of tumors. This approach was validated by a leave-1-patient-out procedure. RESULTS: A method was developed for the discrimination of GBMs and solitary METs. Two masses out of 33 were wrongly classified; the overall results were accurate in 93.9% of the observed cases. CONCLUSIONS: A semiautomated method based on a morphologic analysis was developed. Its application was found to be useful in the discrimination of GBM from solitary MET.

Multivariate curve resolution of rapid-scan FTIR difference spectra of quinone photoreduction in bacterial photosynthetic membranes.

Photosynthetic reaction centres and membranes are systems of particular interest and are often taken as models to investigate the molecular mechanisms of selected bioenergetic reactions. In this work, a multivariate curve resolution by alternating least squares procedure is detailed for resolution of time-resolved difference FTIR spectra probing the evolution of quinone reduction in photosynthetic membranes from Rhodobacter sphaeroides under photoexcitation. For this purpose, different data sets were acquired in the same time range and spectroscopic domain under slightly different experimental conditions. To enable resolution and provide meaningful results the different data sets were arranged in an augmented matrix. This strategy enabled recovery of three different species despite rank-deficiency conditions. It also results in better definition (identity and evolution) of the contributions. From the resolved spectra, the species have been attributed to: 1. the formation of ubiquinol, more precisely the disappearance of Q/appearance of QH(2); 2. conformational change of the protein in the surrounding biological medium; 3. oxidation of diaminodurene, a redox mediator. Because, moreover, results obtained from augmented data sets strategies enable quantitative and qualitative interpretation of concentration profiles, other effects, for example the consequence of repeated light excitation of the same sample, choice of illumination power, or the number of spectra accumulated could be compared and discussed.

[Loneliness among young people: collation of writings]. / La solitude chez les jeunes: recension des écrits.

Contrary to the popular belief that loneliness is typically associated with adults, and especially with older persons, this state can occur early in life. In fact, an increasing number of studies indicate that an important proportion of adolescents experience an intense episode of loneliness. This literature review describes loneliness among younger persons. We discuss the ampleness of the problem, the definition of the phenomenon, the feeling associated with loneliness, precipitating and predisposating factors and, finally, coping strategies to deal with this experience.

Effect of two models of portal hypertension on splanchnic organ blood flow in the rat.

Splanchnic organ blood flow and cardiac output were measured by the microsphere method in fasted rats with prehepatic portal hypertension due to portal vein stenosis, in rats with intrahepatic portal hypertension due to bile duct ligation, and in unoperated normal rats. Portal venous pressure was higher in both groups of portal hypertensive rats than in normal rats. Cardiac output was significantly higher in portal hypertensive rats than in normal rats. In rats with portal vein stenosis, splanchnic blood flow was higher than in controls. This increase was caused by increased perfusion of all organs drained by the portal vein, and by increased hepatic arterial blood flow. In rats with bile duct ligation, splanchnic blood flow was not significantly higher than in normal rats: haemoperfusion of all organs contributing to the portal circulation decreased, whereas hepatic arterial blood flow increased. As cardiac output rose similarly, the differences observed between the two types of portal hypertension depend mainly on the difference in distribution of flow within the splanchnic bed.

Intercellular bridges in ovaries of the newborn gerbil.

This study describes intercellular bridges in the ovaries of neonatal gerbils. Electron microscopy has revealed the presence of true intercellular bridges, connecting oogonia or oocytes, in ovaries of newborn gerbils. The cytoplasm of the intercellular channels is similar to that of the connected cells, with mitochondria, smooth and rough endoplasmic reticulum, and free ribosomes present. Lysosomes are also occasionally present in the intercellular bridges and they may be involved in early waves of oocyte atresia. An electron-dense substance, 350-500 A thick, is located immediately beneath the unit membrane of the intercellular bridges. Accumulation of electron-dense material increases the thickness of the walls of the intercellular bridges, supporting and maintaining the patency of the channels. It is suggested that the intercellular channels probably allow the interchange of nutrients, organelles, and possibly regulatory materials as well.

Effects of methyl methacrylate monomer vapors on respiration and circulation in unanesthetized rats.

A study was conducted in which two groups of female rats were exposed to vaporized MMA-m for a period of 20 minutes daily for 21 and 42 days, respectively. Systolic blood pressure, heart rate, respiration, and ECG were monitored for 5 minutes prior to MMA-m exposure and then during a 20-minute exposure to MMA-m. On the twenty-first and forty-second day, respectively, the aforementioned vectors were monitored again. During the first exposure 63% of the experimental animals displayed marked changes in respiration ranging from a modified Cheyne-Stokes type to periods of very shallow breathing followed by deep breathing. Thirty-eight percent showed ECG changes ranging from premature ventricular contractions and altered QRS complexes to markedly depressed T waves. Continued exposure resulted in an initial decrease followed by an increased systolic blood pressure with an increased respiratory and heart rate. At the final testing period all animals showed abnormal respiratory patterns and ECG changes and demonstrated a heart block pattern. In all animals systolic blood pressure increased the longer they were exposed to MMA-m.