Comparison of Analytical Methods Of Serum Untargeted Metabolomics

Funding Information: IV. ACKNOWLEDGEMENTS This research was funded by Fundação para a Ciência e a Tecnologia (FCT), grant DSAIPA/DS/0117/2020 and RNEM-LISBOA-01-0145-FEDER-022125 (Portuguese Mass Spectrometry Network). Centro de Química Estrutural is a Research Unit funded by FCT through projects UIDB/00100/2020 and UIDP/00100/2020. Institute of Molecular Sciences is an Associate Laboratory funded by FCT through project LA/P/0056/2020. Publisher Copyright: © 2023 IEEE.Metabolomics has emerged as a powerful tool in the discovery of new biomarkers for medical diagnosis and prognosis. However, there are numerous challenges, such as the methods used to characterize the system metabolome. In the present work, the comparison of two analytical platforms to acquire the serum metabolome of critically ill patients was conducted. The untargeted serum metabolome analysis by ultraperformance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) enabled to identify a set of metabolites statistically different between deceased and discharged patients. This set of metabolites also enabled to develop a very good predictive model, based on linear discriminant analysis (LDA) with a sensitivity and specificity of 80% and 100%, respectively. Fourier Transform Infrared (FTIR) spectroscopy was also applied in a high-throughput, simple and rapid mode to analyze the serum metabolome. Despite this technique not enabling the identification of metabolites, it allowed to identify molecular fingerprints associated to each patient group, while leading to a good predictive model, based on principal component analysis-LDA, with a sensitivity and specificity of 100% and 90%, respectively. Therefore, both analytical techniques presented complementary characteristics, that should be further explored for metabolome characterization and application as for biomarkers discovery for medical diagnosis and prognosis.publishersversionpublishe

Infection Biomarkers Based on Metabolomics

Funding Information: Funding: This work was supported by the project grant DSAIPA/DS/0117/2020 supported by Fundação para a Ciência e a Tecnologia, Portugal; and by the project grant NeproMD/ISEL/2020 financed by Instituto Politécnico de Lisboa.Current infection biomarkers are highly limited since they have low capability to predict infection in the presence of confounding processes such as in non-infectious inflammatory processes, low capability to predict disease outcomes and have limited applications to guide and evaluate therapeutic regimes. Therefore, it is critical to discover and develop new and effective clinical infection biomarkers, especially applicable in patients at risk of developing severe illness and critically ill patients. Ideal biomarkers would effectively help physicians with better patient management, leading to a decrease of severe outcomes, personalize therapies, minimize antibiotics overuse and hospitalization time, and significantly improve patient survival. Metabolomics, by providing a direct insight into the functional metabolic outcome of an organism, presents a highly appealing strategy to discover these biomarkers. The present work reviews the desired main characteristics of infection biomarkers, the main metabolomics strategies to discover these biomarkers and the next steps for developing the area towards effective clinical biomarkers.publishersversionpublishe

The Impact of the Serum Extraction Protocol on Metabolomic Profiling Using UPLC-MS/MS and FTIR Spectroscopy

Funding Information: This research was funded by Fundação para a Ciência e a Tecnologia (FCT), Grants DSAIPA/DS/0117/2020 and RNEM-LISBOA-01-0145-FEDER-022125 (Portuguese Mass Spectrometry Network). The Centro de Química Estrutural is a Research Unit funded by FCT through projects UIDB/00100/2020 and UIDP/00100/2020. The Institute of Molecular Sciences is an Associate Laboratory funded by FCT through project LA/P/0056/2020. Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.Biofluid metabolomics is a very appealing tool to increase the knowledge associated with pathophysiological mechanisms leading to better and new therapies and biomarkers for disease diagnosis and prognosis. However, due to the complex process of metabolome analysis, including the metabolome isolation method and the platform used to analyze it, there are diverse factors that affect metabolomics output. In the present work, the impact of two protocols to extract the serum metabolome, one using methanol and another using a mixture of methanol, acetonitrile, and water, was evaluated. The metabolome was analyzed by ultraperformance liquid chromatography associated with tandem mass spectrometry (UPLC-MS/MS), based on reverse-phase and hydrophobic chromatographic separations, and Fourier transform infrared (FTIR) spectroscopy. The two extraction protocols of the metabolome were compared over the analytical platforms (UPLC-MS/MS and FTIR spectroscopy) concerning the number of features, the type of features, common features, and the reproducibility of extraction replicas and analytical replicas. The ability of the extraction protocols to predict the survivability of critically ill patients hospitalized at an intensive care unit was also evaluated. The FTIR spectroscopy platform was compared to the UPLC-MS/MS platform and, despite not identifying metabolites and consequently not contributing as much as UPLC-MS/MS in terms of information concerning metabolic information, it enabled the comparison of the two extraction protocols as well as the development of very good predictive models of patient’s survivability, such as the UPLC-MS/MS platform. Furthermore, FTIR spectroscopy is based on much simpler procedures and is rapid, economic, and applicable in the high-throughput mode, i.e., enabling the simultaneous analysis of hundreds of samples in the microliter range in a couple of hours. Therefore, FTIR spectroscopy represents a very interesting complementary technique not only to optimize processes as the metabolome isolation but also for obtaining biomarkers such as those for disease prognosis.publishersversionpublishe

Mixedness and entanglement for two-mode Gaussian states

We analytically exploit the two-mode Gaussian states nonunitary dynamics. We show that in the zero temperature limit, entanglement sudden death (ESD) will always occur for symmetric states (where initial single mode compression is $z_0$) provided the two mode squeezing $r_0$ satisfies $0 < r_0 < 1/2 \log (\cosh (2 z_0)).$ We also give the analytical expressions for the time of ESD. Finally, we show the relation between the single modes initial impurities and the initial entanglement, where we exhibit that the later is suppressed by the former.Comment: Accepted for publication in Optics Communication

Hyperbaric oxygen therapy to treat acute sport-related traumatic brain injuries: A case series

We report on hyperbaric oxygen (HBO2) therapy used to improve postinjury outcomes in eight acutely concussed high school student-athletes (5 males, 3 females, mean age = 16.0 ± 1.2 years). Patients were randomly assigned into one of three intervention groups: (a) HBO2 therapy; (b) hyperbaric therapy with compressed medical-grade air (HBA); or (c) normobaric 100% O2 therapy. All patients completed five 1-hr treatments within the first 10 days following his or her concussion. Main outcome measures included mental status examination, symptom burden, and the number of days from injury until the physician permitted the student-athlete to return to activity. Patients receiving HBO2 treatment experienced the greatest absolute symptom reduction over the five treatment sessions. No meaningful differences were found in mental status examination. All participants returned to activity in a similar timeframe. HBO2 therapy may be an effective option for the acute treatment of postconcussion symptoms, particularly in young athletes presenting with a high symptom burden

4D gravity on a non-BPS bent dilatonic brane

We investigate the localization of metastable four-dimensional gravity around a bent dilatonic brane, embedded into a five-dimensional space, that exists only up to distances sufficiently small compared to a crossover scale. Far from such scale, five-dimensional effects strongly deviate the Newtonian potential. We study this effect by considering localization of massive gravity on a non-BPS bent dilatonic 3-brane solution of a five-dimensional supergravity. Our results show that the cosmological constant on the bent brane controls the size of the crossover scale. For sufficiently small positive cosmological constant, that is in accord with the present observations, the crossover scale becomes very large.Comment: 7 pages, version to appear in JCA

Efeitos da salinidade em algodoeiros tratados com produtos químicos

Studies were carried out to establish the effects of spray of polyethylene polysulfide (5%), oxyethylene docosanol (5%) and succinic acid-2,2-dimethylhydrazide (2,000 ppm), in the growth of cotton 'IAC-RM3', under application of N-P-K (5:10:5) and irrigation with solution of NaCl - CaCl2 - MgCl2 (1.00:0.85:0.15). The antitranspirants promote increase in leaf area of cotton; and the growth retardant causes diminution in the leaf area in relation to check in salinity conditions. The chemicals promote increase in the dry weight in relation to check. The net assimilation rate and the relative growth rate were superior in the plots that received the chemicals in relation to check in salinity conditions. It was not verified differences between the plants treated with antitranspirants and the check in relation to the leaf area ratio; that parameter was inferior in the treatment with the growth retardant.Estudaram-se os efeitos de polissulfeto de polietileno (0,5%), o-xietileno docosanol (5%) e ácido succínico - 2,2-dimetil-hidrazida (2000 ppm), aplicados em pulverização, no desenvolvimento de algo-doeiro cultivar 'IAC-RM3', submetido à adubação N-P-K (5:10 5) e à irrigação com solução de NaCl - CaCl2 - MgCl2 (1,000,85:0,15). Os antitranspirantes permitiram aumento em área foliar do algo-doeiro; sendo que o retardador de crescimento provocou redução na área foliar com relação ao controle, em condições de salinidade. Os produtos químicos promoveram maior aumento no peso seco em relação ao controle. A taxa assimilatória líquida e a taxa de crescimento relativo mostraram-se mais altas nas plantas tratadas com produtos químicos em relação ao controle, nas condições de salinidade. N ao ocorreram diferenças marcantes entre as plantas tratadas com antitranspirantes e o controle, com relação à razão de área foliar; sendo que este parâmetro mostrou-se inferior no tratamento com retardador de crescimento

Nonvalidated home blood pressure devices dominate the online marketplace in Australia: major implications for cardiovascular risk management

Self-home blood pressure (BP) monitoring is recommended to guide clinical decisions on hypertension and is used worldwide for cardiovascular risk management. People usually make their own decisions when purchasing BP devices, which can be made online. If patients purchase nonvalidated devices (those not proven accurate according to internationally accepted standards), hypertension management may be based on inaccurate readings resulting in under- or over-diagnosis or treatment. This study aimed to evaluate the number, type, percentage validated, and cost of home BP devices available online. A search of online businesses selling devices for home BP monitoring was conducted. Multinational companies make worldwide deliveries, so searches were restricted to BP devices available for one nation (Australia) as an example of device availability through the global online marketplace. Validation status of BP devices was determined according to established protocols. Fifty nine online businesses, selling 972 unique BP devices were identified. These included 278 upper-arm cuff devices (18.3% validated), 162 wrist-cuff devices (8.0% validated), and 532 wrist-band wearables (0% validated). Most BP devices (92.4%) were stocked by international e-commerce businesses (eg, eBay, Amazon), but only 5.5% were validated. Validated cuff BP devices were more expensive than nonvalidated devices: median (interquartile range) of 101.1 (75.0–151.5) versus 67.4 (30.4–112.8) Australian Dollars. Nonvalidated BP devices dominate the online marketplace and are sold at lower cost than validated ones, which is a major barrier to accurate home BP monitoring and cardiovascular risk management. Before purchasing a BP device, people should check it has been validated at https://www.stridebp.org