Discovery of serum biomarkers for diagnosis of tuberculosis by NMR metabolomics including cross-validation with a second cohort.

BACKGROUND: Tuberculosis (TB) is a disease with worldwide presence and a major cause of death in several developing countries. Current diagnostic methodologies often lack specificity and sensitivity, whereas a long time is needed to obtain a conclusive result. METHODS: In an effort to develop better diagnostic methods, this study aimed at the discovery of a biomarker signature for TB diagnosis using a Nuclear Magnetic Resonance based metabolomics approach. In this study, we acquired 1H NMR spectra of blood serum samples of groups of healthy subjects, individuals with latent TB and of patients with pulmonary and extra-pulmonary TB. The resulting data were treated with uni- and multivariate statistical analysis. RESULTS: Six metabolites (inosine, hypoxanthine, mannose, asparagine, aspartate and glutamate) were validated by an independent cohort, all of them related with metabolic processes described as associated with TB infection. CONCLUSION: The findings of the study are according with the WHO Target Product Profile recommendations for a triage test to rule-out active TB.

Low-temperature elastic anomalies in CaTiO3: dynamical characterization.

Pulse-echo ultrasonic measurements of elastic coefficients of CaTiO(3) show anomalous behavior around 200 K, with a notable rise in the attenuation coefficient. Molecular dynamics simulation is used to simulate the elastic response of a mono-domain (MDm) and a poly-domain (PDm) configuration of CaTiO(3) using the Vashishta-Raman interatomic potential. The PDm is obtained by cooling the melt from 3600 to 300 K at a rate of 0.5 K ps(-1), so that it recrystallizes to the PDm orthorhombic configuration. The elastic behavior is simulated in the temperature range from 300 to 20 K. In the MDm, it is observed that the bulk modulus varies linearly with temperature, while in the PDm an anomalous hardening is seen around 210 K. The bulk modulus of the PDm fluctuates strongly and is lower than that of the MDm. Neither the pair correlation function nor the Ti-Ti-O bonding angle indicate a true structural phase transition in this range of temperatures. Given the absence of any apparent change in the structure, a possible explanation for this phenomenon is the emergence of a certain class of dynamical instability associated with domain wall motion. Curiously, the pressure fluctuations in both the MDm and PDm configurations follow a power law distribution f ~ P(-α), with the exponent independent of applied strain and temperature. Time series for pressure are used to analyze the dynamics by time-delay reconstruction techniques. The calculus of embedding and correlation dimension indicates that in the polycrystalline configuration, low-dimension dynamics (<26) appears, which tend to disappear at higher temperatures.