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Biological variability dominates and influences analytical variance in HPLC-ECD studies of the human plasma metabolome
Yevgeniya I Shurubor, Wayne R Matson, Walter C Willett, Susan E Hankinson, Bruce S Kristal
BMC Clinical Pathology , 2007, DOI: 10.1186/1472-6890-7-9
Abstract: Human plasma samples were biochemically analyzed using HPLC separations coupled with coulometric electrode array detection.We identified these markers/metabolites in human plasma, and then used them to determine which human samples represent blinded duplicates with 100% accuracy (N = 30 of 30). At least 47 of 61 metabolites tested were sufficiently stable for use even after 48 hours of exposure to shipping conditions. Stability of some metabolites differed between individuals (N = 10 at 0, 24, and 48 hours), suggesting the influence of some biological factors on parameters normally considered as analytical.Overall analytical precision (mean median CV, ~9%) and total between-person variation (median CV, ~50–70%) appear well suited to enable use of metabolomics markers in human clinical trials and epidemiological studies, including studies of the effect of caloric intake and balance on long-term cancer risk.After tobacco, over-nutrition is, arguably, the major cause of excess morbidity in developed countries, affecting a broad spectrum of diseases including cancer, cardio-/cerebrovascular disease, and type II diabetes. This association may be seen in both broad demographic groups, such as the American Cancer Society study group (900,000 U.S. adults)[1] and in more narrowly defined demographic groups, such as the Nurses' Health Study (NHS) group (122,000 U.S. female registered nurses) [2]. The difficulty of accurately assessing caloric intake and energy expenditure [3] has hampered studies relating to energy restriction, caloric balance, and caloric intake in both epidemiology and clinical nutrition. Several of the major hurdles in identifying biomarkers to address this and similar epidemiological problems are related to analytical (the lack of useful measurement standards) and methodological (the inability to distinguish individual physiology) issues [4-13]. Recent results have suggested the advantage of metabolomics approaches in clarifying these situations, at least
Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder – Possible Role for Methoxyindole Pathway
Hongjie Zhu, Mikhail B. Bogdanov, Stephen H. Boyle, Wayne Matson, Swati Sharma, Samantha Matson, Erik Churchill, Oliver Fiehn, John A. Rush, Ranga R. Krishnan, Eve Pickering, Marielle Delnomdedieu, Rima Kaddurah-Daouk, Pharmacometabolomics Research Network
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068283
Abstract: Therapeutic response to selective serotonin (5-HT) reuptake inhibitors in Major Depressive Disorder (MDD) varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective of this study was to analyze changes within methoxyindole and kynurenine (KYN) branches of tryptophan pathway to determine whether differential regulation within these branches may contribute to mechanism of variation in response to treatment. Metabolomics approach was used to characterize early biochemical changes in tryptophan pathway and correlated biochemical changes with treatment outcome. Outpatients with MDD were randomly assigned to sertraline (n = 35) or placebo (n = 40) in a double-blind 4-week trial; response to treatment was measured using the 17-item Hamilton Rating Scale for Depression (HAMD17). Targeted electrochemistry based metabolomic platform (LCECA) was used to profile serum samples from MDD patients. The response rate was slightly higher for sertraline than for placebo (21/35 [60%] vs. 20/40 [50%], respectively, χ2(1) = 0.75, p = 0.39). Patients showing a good response to sertraline had higher pretreatment levels of 5-methoxytryptamine (5-MTPM), greater reduction in 5-MTPM levels after treatment, an increase in 5-Methoxytryptophol (5-MTPOL) and Melatonin (MEL) levels, and decreases in the (KYN)/MEL and 3-Hydroxykynurenine (3-OHKY)/MEL ratios post-treatment compared to pretreatment. These changes were not seen in the patients showing poor response to sertraline. In the placebo group, more favorable treatment outcome was associated with increases in 5-MTPOL and MEL levels and significant decreases in the KYN/MEL and 3-OHKY/MEL; changes in 5-MTPM levels were not associated with the 4-week response. These results suggest that recovery from a depressed state due to treatment with drug or with placebo could be associated with preferential utilization of serotonin for production of melatonin and 5-MTPOL.
S. Go, Marine Insurance in the Netherlands 1600-1870: A Comparative Institutional Approach
C. Matson
BMGN : Low Countries Historical Review , 2011,
Homeostatic Imbalance of Purine Catabolism in First-Episode Neuroleptic-Na?ve Patients with Schizophrenia
Jeffrey K. Yao,George G. Dougherty Jr.,Ravinder D. Reddy,Matcheri S. Keshavan,Debra M. Montrose,Wayne R. Matson,Joseph McEvoy,Rima Kaddurah-Daouk
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009508
Abstract: Purine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology.
Metabolomic Profiling in LRRK2-Related Parkinson's Disease
Krisztina K. Johansen,Lei Wang,Jan O. Aasly,Linda R. White,Wayne R. Matson,Claire Henchcliffe,M. Flint Beal,Mikhail Bogdanov
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007551
Abstract: Mutations in LRRK2 gene represent the most common known genetic cause of Parkinson's disease (PD).
Associations between Purine Metabolites and Clinical Symptoms in Schizophrenia
Jeffrey K. Yao, Ruth Condray, George G. Dougherty, Matcheri S. Keshavan, Debra M. Montrose, Wayne R. Matson, Joseph McEvoy, Rima Kaddurah-Daouk, Ravinder D. Reddy
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042165
Abstract: Background The antioxidant defense system, which is known to be dysregulated in schizophrenia, is closely linked to the dynamics of purine pathway. Thus, alterations in the homeostatic balance in the purine pathway may be involved in the pathophysiology of schizophrenia. Methodology/Principal Findings Breakdown products in purine pathway were measured using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system for 25 first-episode neuroleptic-na?ve patients with schizophrenia at baseline and at 4-weeks following initiation of treatment with antipsychotic medication. Associations between these metabolites and clinical and neurological symptoms were examined at both time points. The ratio of uric acid and guanine measured at baseline predicted clinical improvement following four weeks of treatment with antipsychotic medication. Baseline levels of purine metabolites also predicted clinical and neurological symtpoms recorded at baseline; level of guanosine was associated with degree of clinical thought disturbance, and the ratio of xanthosine to guanosine at baseline predicted degree of impairment in the repetition and sequencing of actions. Conclusions/Significance Findings suggest an association between optimal levels of purine byproducts and dynamics in clinical symptoms and adjustment, as well as in the integrity of sensory and motor processing. Taken together, alterations in purine catabolism may have clinical relevance in schizophrenia pathology.
The Effect of the 12-micrometer Band: Comparing GOES-11 and GOES-12 Data Using the 3-Channel Volcanic Ash Algorithm
Emily M. Matson
Physics , 2006,
Abstract: The 12-micrometer channel on GOES-11 has been replaced by the 13.3-micrometer channel on the latest geosynchronous satellite, GOES-12. There has been concern that this 13.3-micrometer channel will not be as accurate in detecting volcanic ash. Volcanic ash is highlighted using a special volcanic ash algorithm, an arithmetic combination of the brightness temperatures as measured by three channels, yielding a unitless brightness count whose values comprise an IR image. Degradation in cloud detection, especially low clouds, was also expected. IR data from GOES-11 and GOES-12 for two Mexican volcanoes, Colima and Popocatepetl, was analyzed. The data indicates that, in general, the GOES-11 volcanic ash algorithm with the 12-micrometer band provides much better data for various types of clouds. It emphasizes the importance of the 12-micrometer band and provides scope for future research in this area.
A Reliable Methodology for Quantitative Extraction of Fruit and Vegetable Physiological Amino Acids and Their Subsequent Analysis with Commonly Available HPLC Systems  [PDF]
Wayne W. Fish
Food and Nutrition Sciences (FNS) , 2012, DOI: 10.4236/fns.2012.36115
Abstract: Many of the extraction and amino acid analysis methodologies currently employed do not provide complete analysis of all the physiological amino acids and biogenic amines. Extraction procedures frequently employ dilute acid which partially converts gln and asn to glu and asp. A commonly used pre-column derivatizing agent, o-phthalaldehyde, does not react with the imino acids, pro and hydroxypro. The purpose of this investigation was to integrate extraction and analysis procedures into a reliable method for measuring the complete physiological amino acid profiles of fruit and vegetables using HPLC instrumentation commonly available to most laboratories. Water extraction of ground, frozen-thawed tissues effected complete recovery of the physiological amino acids as demonstrated by spiking experiments and tissue combination experiments. HPLC of dabsyl derivatives of the free amino acids allowed their quantification in a selection of fruit and vegetables. Physiological amino acid levels were determined for peach, apple, potato, onion, tomato, bell pepper, broccoli, and seven types of cucurbits. The coefficient of variation for estimation of an amino acid level generally fell in the range of 5% to 7%. Because of marked variability in physiological amino acid content as a result of growing conditions, cultural practices, and inherent cultivar differences, comparisons of results with literature values were not possible.
Engineering Intelligent Racing Concepts Using Design Research Methods  [PDF]
Trevor Hyman, Wayne Li
World Journal of Engineering and Technology (WJET) , 2018, DOI: 10.4236/wjet.2018.62026
Abstract: The automotive seat market is positioned to significantly grow over the next five years. Research into how sensor implementation in every day driver cars can enhance driver wellness is becoming increasingly popular and visible in the automotive seat industry. However, in the competitive race car industry,drivers prioritize driving ability over wellness. To further examine this phenomenon, the Human-Machine InteractionLab at the Georgia Institute of Technology took a unique approach to developing strong use cases for implementing sensor technology to improve driving ability for race car drivers by combining qualitative and quantitative research data obtained through modern design research and planning methodology. Following a process relying heavily on user-centered design methods, the authors developed a business case conceptfora sensor-based seat accessory that acts as a competitive racer’s?driving coach?that is able to identify the mechanics of braking, turning, and accelerating through pressure sensors in the driver’s seat pan surface. This technology allows drivers to precisely understand when and how hard to brake, turn, or accelerate out of turns, thus reducing heat times and financial burden for drivers.
Obstetric Hemorrhage and Hypothermia: Chilling Facts  [PDF]
Wayne R. Cohen
Open Journal of Obstetrics and Gynecology (OJOG) , 2018, DOI: 10.4236/ojog.2018.813128
Abstract: Objective: This clinical perspective reviews the causes, prevention and treatment of accidental hypothermia in severe obstetric hemorrhage. Results: Hypothermia commonly accompanies hemorrhagic shock. Hypothermia can inhibit blood coagulation, reduce cardiac contractility, predispose to arrhythmias, contribute to acidosis, and suppress immune function. Several techniques for warming a patient or reducing heat loss are available. Keeping the patient dry, covering her with blankets, and raising the ambient temperature in the room are valuable. Methods to transmit heat actively are more effective. Forced warm air blowers are efficient. Heating intravenous fluids is important, and warm fluid lavage of the open abdomen can be effective. Conclusion: Monitoring core temperature in the operating room and choosing therapy is a shared responsibility of surgeon and anesthesiologist.
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