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1
Fasching, Patrick, Stefan Rinnerhofer, Georg Wultsch, Gerhard Tschakert, Peter Hofmann, and Serge P. von Duvillard. "First Lactate Turn Point." Medicine & Science in Sports & Exercise 46 (May 2014): 707. http://dx.doi.org/10.1249/01.mss.0000495599.62004.f2.
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2
Hofmann, Peter, Christian Hartleb, Manfred Wonisch, Guenther Schwaberger, Rochus Pokan, Serge P. von Duvillard, and Serge P. von Duvillard. "Lactate-Minimum and Laktat Turn Point." Medicine & Science in Sports & Exercise 38, Supplement (May 2006): S507—s508. http://dx.doi.org/10.1249/00005768-200605001-02995.
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3
Hofmann, P., R. Pokan, K. Preidler, H. Leitner, D. Szolar, B. Eber, and G. Schwaberger. "Relationship Between Heart Rate Threshold, Lactate Turn Point and Myocardial Function." International Journal of Sports Medicine 15, no. 05 (July 1994): 232–37. http://dx.doi.org/10.1055/s-2007-1021052.
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4
Joglekar, S. S., P. V. Pimpliskar, V. V. Sirdeshmukh, P. S. Alegaonkar, and A. A. Kale. "FITC Embedded ZnO/Silica Nanocomposites as probe for detection of L-lactate: Point-of-Care diagnosis." MRS Advances 4, no. 46-47 (2019): 2533–40. http://dx.doi.org/10.1557/adv.2019.158.
Повний текст джерелаАнотація:
Abstract:A novel Fluorescence Resonance Energy Transfer (FRET) based ‘Turn-ON’ biosensor has been developed using fluorescent ZnO/APTMS-FITC (ZFA) nanoflakes as sensing probe. In this biosensor, Lactate Dehydrogenase (LDH) is used for the detection of L-lactate, a diagnostic marker for abnormal physiological conditions like muscular dystrophy, myocardial infraction, abnormal tissue formation and tissue damage. Lactate Dehydrogeanse (LDH) catalyses the conversion of L-Lactate to L-Pyruvate, in presence of β-NAD reducing to β-NADH. We tried to explore this mechanism with FRET based system for highly sensitive detection of L-Lactate. The fluorescence of these nanoflakes can be reversibly quenched in the presence of β-NAD.
5
Hofmann, Peter, Alexander Mueller, Othmar Moser, Gerhard Tschakert, Sandra J. Wallner-Liebmann, Martina Dieber-Rotheneder, Manuela Konrad, and Kurt Zatloukal. "Mid-point Between Lactate Turn Points Exercise Intensity Prescription Compared to Standard Models in Untrained Females." Medicine & Science in Sports & Exercise 46 (May 2014): 846. http://dx.doi.org/10.1249/01.mss.0000496037.28838.b7.
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Hofmann, Peter, Gerhard Tschakert, Markus Stark, Günther Schwaberger, Rochus Pokan, Manfred Wonisch, Gerhard Smekal, Franz-Josef Seibert, and Serge P. von Duvillard. "Estimation Error When Using The %HRR Method Compared To The Lactate Turn Point." Medicine & Science in Sports & Exercise 41 (May 2009): 34–35. http://dx.doi.org/10.1249/01.mss.0000354670.06780.da.
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7
Cagran, Claus, Gerhard Tschakert, Nikolaus Stühlinger, Rochus Pokan, Serge P. von Duvillard, and Peter Hofmann. "Value Of The D-max Method To Determine The Second Lactate Turn Point." Medicine & Science in Sports & Exercise 43, Suppl 1 (May 2011): 629–30. http://dx.doi.org/10.1249/01.mss.0000401739.14005.11.
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8
Tilp, Markus, Lukas Kitzberger, Gudrun Schappacher-Tilp, Philipp Birnbaumer, and Peter Hofmann. "Electromyographic and Systemic Physiological Thresholds in Single-Joint Elbow Flexion Movements." International Journal of Sports Physiology and Performance 17, no. 2 (February 1, 2022): 241–48. http://dx.doi.org/10.1123/ijspp.2021-0163.
Повний текст джерелаАнотація:
Purpose: Reported relationships between electromyographic (EMG) thresholds and systemic thresholds based on lactate, ventilation, or heart rate are contradictory. This might be related to the complexity of the investigated whole-body movements involving many muscles with different activation patterns. Therefore, the aim of the study was to investigate these relationships during an incremental single-joint exercise. Methods: Eighteen male subjects (29.7 [4.4] y) performed single-arm elbow flexions on a biceps curl machine with loads increasing every minute until exhaustion. EMG signals of the main elbow flexors (short and long head of the biceps brachii, flexor carpi radialis, and brachioradialis) as well as gas exchange variables, blood lactate concentration, and heart rate were measured, and 2 turn points based on a 3-phase model of metabolism were determined for each variable. Results: The first and second turn points for EMG were determined at 32.0% to 33.1% and 64.4% to 66.5% of maximal achieved performance (maximum weight), respectively. Systemic turn points were determined at 33.3% to 34.4% and 65.9% to 66.7% of maximum weight and were not significantly different from EMG turn points. Furthermore, systemic and EMG turn points showed a strong or very strong relationship at the first (ρ = .54–.93, P < .05) and second turn point (ρ = .76–.93, P < .01). Conclusions: A close relationship between EMG and systemic turn points could be confirmed for the applied movement of a small muscle group. The determination of local single muscle thresholds using EMG provides additional muscle-specific information about performance-limiting properties of muscles involved in endurance-type incremental exercise.
9
Tilp, Markus, Lukas Kitzberger, Gudrun Schappacher-Tilp, Philipp Birnbaumer, and Peter Hofmann. "Electromyographic and Systemic Physiological Thresholds in Single-Joint Elbow Flexion Movements." International Journal of Sports Physiology and Performance 17, no. 2 (February 1, 2022): 241–48. http://dx.doi.org/10.1123/ijspp.2021-0163.
Повний текст джерелаАнотація:
Purpose: Reported relationships between electromyographic (EMG) thresholds and systemic thresholds based on lactate, ventilation, or heart rate are contradictory. This might be related to the complexity of the investigated whole-body movements involving many muscles with different activation patterns. Therefore, the aim of the study was to investigate these relationships during an incremental single-joint exercise. Methods: Eighteen male subjects (29.7 [4.4] y) performed single-arm elbow flexions on a biceps curl machine with loads increasing every minute until exhaustion. EMG signals of the main elbow flexors (short and long head of the biceps brachii, flexor carpi radialis, and brachioradialis) as well as gas exchange variables, blood lactate concentration, and heart rate were measured, and 2 turn points based on a 3-phase model of metabolism were determined for each variable. Results: The first and second turn points for EMG were determined at 32.0% to 33.1% and 64.4% to 66.5% of maximal achieved performance (maximum weight), respectively. Systemic turn points were determined at 33.3% to 34.4% and 65.9% to 66.7% of maximum weight and were not significantly different from EMG turn points. Furthermore, systemic and EMG turn points showed a strong or very strong relationship at the first (ρ = .54–.93, P < .05) and second turn point (ρ = .76–.93, P < .01). Conclusions: A close relationship between EMG and systemic turn points could be confirmed for the applied movement of a small muscle group. The determination of local single muscle thresholds using EMG provides additional muscle-specific information about performance-limiting properties of muscles involved in endurance-type incremental exercise.
10
Hofmann, Peter, and Rochus Pokan. "Value of the Application of the Heart Rate Performance Curve in Sports." International Journal of Sports Physiology and Performance 5, no. 4 (December 2010): 437–47. http://dx.doi.org/10.1123/ijspp.5.4.437.
Повний текст джерелаАнотація:
The heart rate performance curve (HRPC) has been shown to be nonlinearly related to work load. This phenomenon has been used to determine a defection point and to be related to the lactate anaerobic threshold. The original method was heavily criticized, and the method was challenged by several authors. However, some authors also demonstrated a high value for this method’s application in various sports conditions. Unfortunately, the HRPC was shown to be not uniform and three different patterns were found. Basic investigations have shown a dependence of the HR-defection on beta1-receptor sensitivity, which gave a plausible explanation of the phenomenon. Important details regarding the testing protocol and the method of turn point determination are given in this review. As a conclusion, we may state that based on numerous studies the method is plausible and valid to determine aerobic exercise performance in various laboratory ergometer and specific sports-related field conditions. Standard protocol conditions adjusted to the exercise performance level of subjects and a computer-supported determination of turn points are necessary to obtain reliable results. Large-scale investigations to validate the heart rate turn point with maximal lactate steady state are still needed. However, from the available literature, the application of this noninvasive method can be recommended to determine aerobic exercise performance in various sports. This noninvasive test is easy to perform repeatedly, which gives interesting possibilities for the monitoring of training adaptation in the short term, such as altitude training or specifc taper forms.
11
Hofmann, P., V. Bunc, H. Leitner, R. Pokan, and G. Gaisl. "Heart rate threshold related to lactate turn point and steady-state exercise on a cycle ergometer." European Journal of Applied Physiology and Occupational Physiology 69, no. 2 (1994): 132–39. http://dx.doi.org/10.1007/bf00609405.
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Eckstein, Max L., Maximilian P. Erlmann, Felix Aberer, Sandra Haupt, Paul Zimmermann, Nadine B. Wachsmuth, Janis Schierbauer, et al. "Glucose and Fructose Supplementation and Their Acute Effects on Anaerobic Endurance and Resistance Exercise Performance in Healthy Individuals: A Double-Blind Randomized Placebo-Controlled Crossover Trial." Nutrients 14, no. 23 (December 2, 2022): 5128. http://dx.doi.org/10.3390/nu14235128.
Повний текст джерелаАнотація:
Background: The effects of glucose, fructose and a combination of these on physical performance have been subject of investigation, resulting in diverse findings. Objective: The aim of this study was to investigate how an individualized amount of glucose, fructose, and a combination of these compared to placebo (sucralose) alter endurance performance on a cycle ergometer, lower and upper body resistance exercise performance at individualized thresholds in healthy young individuals. Methods: A total of 16 healthy adults (9 females) with an age of 23.8 ± 1.6 years and a BMI of 22.6 ± 1.8 kg/m2 (body mass (BM) 70.9 ± 10.8 kg, height 1.76 ± 0.08 m) participated in this study. During the screening visit, the lactate turn point 2 (LTP2) was defined and the weights for chest-press and leg-press were determined. Furthermore, 30 min prior to each exercise session, participants received either 1 g/kg BM of glucose (Glu), 1 g/kg BM of fructose (Fru), 0.5 g/kg BM of glucose/fructose (GluFru) (each), or 0.2 g sucralose (placebo), respectively, which were dissolved in 300 mL of water. All exercises were performed until volitional exhaustion. Time until exhaustion (TTE) and cardio-pulmonary variables were determined for all cycling visits; during resistance exercise, repetitions until muscular failure were counted and time was measured. During all visits, capillary blood glucose and blood lactate concentrations as well as venous insulin levels were measured. Results: TTE in cycling was 449 ± 163 s (s) (Glu), 443 ± 156 s (Fru), 429 ± 160 s (GluFru) and 466 ± 162 s (Pla) (p = 0.48). TTE during chest-press sessions was 180 ± 95 s (Glu), 180 ± 92 s (Fru), 172 ± 78 s (GluFru) and 162 ± 66 s (Pla) (p = 0.25), respectively. Conclusions: Pre-exercise supplementation of Glu, Fru and a combination of these did not have an ergogenic effect on high-intensity anaerobic endurance performance and on upper and lower body moderate resistance exercise in comparison to placebo.
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Mavin, Emily, Bernard Verdon, Sean Carrie, Vinciane Saint-Criq, Jason Powell, Christian A. Kuttruff, Chris Ward, James P. Garnett, and Satomi Miwa. "Real-time measurement of cellular bioenergetics in fully differentiated human nasal epithelial cells grown at air-liquid-interface." American Journal of Physiology-Lung Cellular and Molecular Physiology 318, no. 6 (June 1, 2020): L1158—L1164. http://dx.doi.org/10.1152/ajplung.00414.2019.
Повний текст джерелаАнотація:
Shifts in cellular metabolic phenotypes have the potential to cause disease-driving processes in respiratory disease. The respiratory epithelium is particularly susceptible to metabolic shifts in disease, but our understanding of these processes is limited by the incompatibility of the technology required to measure metabolism in real-time with the cell culture platforms used to generate differentiated respiratory epithelial cell types. Thus, to date, our understanding of respiratory epithelial metabolism has been restricted to that of basal epithelial cells in submerged culture, or via indirect end point metabolomics readouts in lung tissue. Here we present a novel methodology using the widely available Seahorse Analyzer platform to monitor real-time changes in the cellular metabolism of fully differentiated primary human airway epithelial cells grown at air-liquid interface (ALI). We show increased glycolytic, but not mitochondrial, ATP production rates in response to physiologically relevant increases in glucose availability. We also show that pharmacological inhibition of lactate dehydrogenase is able to reduce glucose-induced shifts toward aerobic glycolysis. This method is timely given the recent advances in our understanding of new respiratory epithelial subtypes that can only be observed in vitro through culture at ALI and will open new avenues to measure real-time metabolic changes in healthy and diseased respiratory epithelium, and in turn the potential for the development of novel therapeutics targeting metabolic-driven disease phenotypes.
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Nobbs, T. J., A. Cortés, J. L. Gelpi, J. J. Holbrook, T. Atkinson, M. D. Scawen, and D. J. Nicholls. "Contribution of a buried aspartate residue towards the catalytic efficiency and structural stability of Bacillus stearothermophilus lactate dehydrogenase." Biochemical Journal 300, no. 2 (June 1, 1994): 491–99. http://dx.doi.org/10.1042/bj3000491.
Повний текст джерелаАнотація:
The X-ray structure of lactate dehydrogenase (LDH) shows the side-chain carboxylate group of Asp-143 to be buried in the hydrophobic interior of the enzyme, where it makes hydrogen-bonding interactions with both the side-chain hydroxyl group of Ser-273 and the main-chain amide group of His-195. This is an unusual environment for a carboxylate side-chain as hydrogen bonding normally occurs with water molecules at the surface of the protein. A charged hydrogen-bonding interaction in the interior of a protein would be expected to be much stronger than a similar interaction on the solvent-exposed exterior. In this respect the side-chain carboxylate group of Asp-143 appears to be important for maintaining tertiary structure by providing a common linkage point between three discontinuous elements of the secondary structure, alpha 1F, beta K and the beta-turn joining beta G and beta H. The contribution of the Asp-143 side-chain to the structure and function of Bacillus stearothermophilus LDH was assessed by creating a mutant enzyme containing Asn-143. The decreased thermal stability of both unactivated and fructose-1,6-diphosphate (Fru-1,6-P2)-activated forms of the mutant enzyme support a structural role for Asp-143. Furthermore, the difference in stability of the wild-type and mutant enzymes in guanidinium chloride suggested that the carboxylate group of Asp-143 contributes at least 22 kJ/mol to the conformational stability of the wild-type enzyme. However, there was no alteration in the amount of accessible tryptophan fluorescence in the mutant enzyme, indicating that the mutation caused a structural weakness rather than a gross conformational change. Comparison of the wild-type and mutant enzyme steady-state parameters for various 2-keto acid substrates showed the mutation to have a general effect on catalysis, with an average difference in binding energy of 11 kJ/mol for the transition-state complexes. The different effects of pH and Fru-1,6-P2 on the wild-type and mutant enzymes also confirmed a perturbation of the catalytic centre in the mutant enzyme. As the side-chain of Asp-143 is not sufficiently close to the active site to be directly involved in catalysis or substrate binding it is proposed that the effects on catalysis shown by the mutant enzyme are induced either by a structural change or by charge imbalance at the active site.(ABSTRACT TRUNCATED AT 400 WORDS)
15
Tschakert, Gerhard, and Peter Hofmann. "High-Intensity Intermittent Exercise: Methodological and Physiological Aspects." International Journal of Sports Physiology and Performance 8, no. 6 (November 2013): 600–610. http://dx.doi.org/10.1123/ijspp.8.6.600.
Повний текст джерелаАнотація:
High-intensity intermittent exercise (HIIE) has been applied in competitive sports for more than 100 years. In the last decades, interval studies revealed a multitude of beneficial effects in various subjects despite a large variety of exercise prescriptions. Therefore, one could assume that an accurate prescription of HIIE is not relevant. However, the manipulation of HIIE variables (peak workload and peak-workload duration, mean workload, intensity and duration of recovery, number of intervals) directly affects the acute physiological responses during exercise leading to specific medium- and long-term training adaptations. The diversity of intermittent-exercise regimens applied in different studies may suggest that the acute physiological mechanisms during HIIE forced by particular exercise prescriptions are not clear in detail or not taken into consideration. A standardized and consistent approach to the prescription and classification of HIIE is still missing. An optimal and individual setting of the HIIE variables requires the consideration of the physiological responses elicited by the HIIE regimen. In this regard, particularly the intensities and durations of the peak-workload phases are highly relevant since these variables are primarily responsible for the metabolic processes during HIIE in the working muscle (eg, lactate metabolism). In addition, the way of prescribing exercise intensity also markedly influences acute metabolic and cardiorespiratory responses. Turn-point or threshold models are suggested to be more appropriate and accurate to prescribe HIIE intensity than using percentages of maximal heart rate or maximal oxygen uptake.
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Szima, S., G. Balazs, N. Elek, and P. Dahlem. "Pediatric Sepsis: Clinical Markers." Journal of Child Science 07, no. 01 (January 2017): e42-e53. http://dx.doi.org/10.1055/s-0037-1603894.
Повний текст джерелаАнотація:
AbstractPediatric sepsis can be caused by infection agents such as viruses, bacteria, protozoa, or their toxins. Clinical features cover a remarkably wide spectrum. Early recognition of the disease and prompt initiation of therapy substantially improve mortality and the outcome of potential complications. After an initial phase of very mild symptoms, the spread of microbes or toxins in the bloodstream presents as septic shock through vasoregulatory disturbance, absolute or relative intravascular volume loss, and consequential tachycardia and hypotension. The most common accompanying symptom is fever. In physical examination, features such as altered mental status, excess respiratory effort, tachycardia, and prolonged capillary refill time are present at an early stage of the disease. Laboratory tests for the assessment of early stage severity and subsequent monitoring of treatment efficacy include point-of-care arterial blood gas analysis and lactate assay. In early stage disease, it is imperative to promptly start adequate antimicrobial and supportive treatment once bacterial cultures have been taken. Despite the availability of a wide range of laboratory and imaging tests today, diagnosis and severity assessment of sepsis still primarily rely on medical history and clinical examination. In light of this, it is possible for trained care providers to detect the early signs of a septic child during repetitive physical examinations. This is still the mainstay of diagnosis and can provide in all care settings a significant reduction in therapeutic delay; this, in turn, helps to reduce sepsis-related mortality and morbidity.
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Parkin, J. M., M. F. Carey, S. Zhao, and M. A. Febbraio. "Effect of ambient temperature on human skeletal muscle metabolism during fatiguing submaximal exercise." Journal of Applied Physiology 86, no. 3 (March 1, 1999): 902–8. http://dx.doi.org/10.1152/jappl.1999.86.3.902.
Повний текст джерелаАнотація:
To examine the effect of ambient temperature on metabolism during fatiguing submaximal exercise, eight men cycled to exhaustion at a workload requiring 70% peak pulmonary oxygen uptake on three separate occasions, at least 1 wk apart. These trials were conducted in ambient temperatures of 3°C (CT), 20°C (NT), and 40°C (HT). Although no differences in muscle or rectal temperature were observed before exercise, both muscle and rectal temperature were higher ( P < 0.05) at fatigue in HT compared with CT and NT. Exercise time was longer in CT compared with NT, which, in turn, was longer compared with HT (85 ± 8 vs. 60 ± 11 vs. 30 ± 3 min, respectively; P < 0.05). Plasma epinephrine concentration was not different at rest or at the point of fatigue when the three trials were compared, but concentrations of this hormone were higher ( P < 0.05) when HT was compared with NT, which in turn was higher ( P < 0.05) compared with CT after 20 min of exercise. Muscle glycogen concentration was not different at rest when the three trials were compared but was higher at fatigue in HT compared with NT and CT, which were not different (299 ± 33 vs. 153 ± 27 and 116 ± 28 mmol/kg dry wt, respectively; P < 0.01). Intramuscular lactate concentration was not different at rest when the three trials were compared but was higher ( P < 0.05) at fatigue in HT compared with CT. No differences in the concentration of the total intramuscular adenine nucleotide pool (ATP + ADP + AMP), phosphocreatine, or creatine were observed before or after exercise when the trials were compared. Although intramuscular IMP concentrations were not statistically different before or after exercise when the three trials were compared, there was an exercise-induced increase ( P < 0.01) in IMP. These results demonstrate that fatigue during prolonged exercise in hot conditions is not related to carbohydrate availability. Furthermore, the increased endurance in CT compared with NT is probably due to a reduced glycogenolytic rate.
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Black, Matthew I., Joseph C. Handsaker, Sam J. Allen, Stephanie E. Forrester, and Jonathan P. Folland. "Is There an Optimal Speed for Economical Running?" International Journal of Sports Physiology and Performance 13, no. 1 (January 1, 2018): 75–81. http://dx.doi.org/10.1123/ijspp.2017-0015.
Повний текст джерелаАнотація:
The influence of running speed and sex on running economy is unclear and may have been confounded by measurements of oxygen cost that do not account for known differences in substrate metabolism, across a limited range of speeds, and differences in performance standard. Therefore, this study assessed the energy cost of running over a wide range of speeds in high-level and recreational runners to investigate the effect of speed (in absolute and relative terms) and sex (men vs women of equivalent performance standard) on running economy. To determine the energy cost (kcal · kg−1 · km−1) of submaximal running, speed at lactate turn point (sLTP), and maximal rate of oxygen uptake, 92 healthy runners (high-level men, n = 14; high-level women, n = 10; recreational men, n = 35; recreational women, n = 33) completed a discontinuous incremental treadmill test. There were no sex-specific differences in the energy cost of running for the recreational or high-level runners when compared at absolute or relative running speeds (P > .05). The absolute and relative speed–energy cost relationships for the high-level runners demonstrated a curvilinear U shape with a nadir reflecting the most economical speed at 13 km/h or 70% sLTP. The high-level runners were more economical than the recreational runners at all absolute and relative running speeds (P < .05). These findings demonstrate that there is an optimal speed for economical running, there is no sex-specific difference, and high-level endurance runners exhibit better running economy than recreational endurance runners.
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Tschakert, Gerhard, Michael Ofner, Manfred Wonisch, Mario Frei, Wolfgang Domej, Julia Kroepfl, Alexander Mueller, Othmar Moser, and Peter Hofmann. "Determination Of Lactate Turn Points In Normoxic And Hypoxic Conditions." Medicine & Science in Sports & Exercise 46 (May 2014): 427. http://dx.doi.org/10.1249/01.mss.0000494456.36148.72.
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Saldana, Nurys E. "Determination Of Blood Lactate Turn Points By Saliva Lactate And Saliva Alpha-amylase During Incremental Cycle Ergometry." Medicine & Science in Sports & Exercise 37, Supplement (May 2005): S26. http://dx.doi.org/10.1249/00005768-200505001-00155.
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Saldana, Nurys E. "Determination Of Blood Lactate Turn Points By Saliva Lactate And Saliva Alpha-amylase During Incremental Cycle Ergometry." Medicine & Science in Sports & Exercise 37, Supplement (May 2005): S26. http://dx.doi.org/10.1097/00005768-200505001-00155.
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Spendier, Florian, Alexander Müller, Markus Korinek, and Peter Hofmann. "Intensity Thresholds and Maximal Lactate Steady State in Small Muscle Group Exercise." Sports 8, no. 6 (May 28, 2020): 77. http://dx.doi.org/10.3390/sports8060077.
Повний текст джерелаАнотація:
The aim of our study is to determine the first (LTP1) and the second (LTP2) lactate turn points during an incremental bicep curl test and to verify these turn points by ventilatory turn points (VT1 and VT2) and constant-load exercise tests. Twelve subjects performed a one-arm incremental bicep curl exercise (IET) after a one repetition maximum (1RM) test to calculate the step rate for the incremental exercise (1RM/45). Workload was increased every min at a rate of 30 reps/min until maximum. To verify LTPs, VT1 and VT2 were determined from spirometric data, and 30 min constant-load tests (CL) were performed at 5% Pmax below and above turn points. Peak load in IET was 5.3 ± 0.9 kg (Lamax: 2.20 ± 0.40 mmol·L−1; HRmax: 135 ± 15 b·min−1; VO2max: 1.15 ± 0.30 L·min−1). LTP1 was detected at 1.9 ± 0.6 kg (La: 0.86 ± 0.36 mmol·L−1; HR 90 ± 13 b·min−1; VO2: 0.50 ± 0.05 L·min−1) and LTP2 at 3.8 ± 0.7 kg (La: 1.38 ± 0.37 mmol·L−1; 106 ± 10 b·min−1; VO2: 0.62 ± 0.11 L·min−1). Constant-load tests showed a lactate steady-state in all tests except above LTP2, with early termination after 16.5 ± 9.1 min. LTP1 and LTP2 could be determined in IET, which were not significantly different from VT1/VT2. Constant-load exercise validated the three-phase concept, and a steady-state was found at resting values below VT1 and in all other tests except above LTP2. It is suggested that the three-phase model is also applicable to small muscle group exercise.
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von Duvillard, Serge P., Jeff Bell, Ines Dieckmann, Jena Hamra, Ken Alford, Frank Miskevich, and John P. Slovak. "Determination of Lactate Turn Points by Gas Exchange, Salivary a-Amylase and Testosterone in Male Subjects." Medicine & Science in Sports & Exercise 39, Supplement (May 2007): S252. http://dx.doi.org/10.1249/01.mss.0000273961.23843.5b.
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Nikolaizik, Wilfried H., Bruno Knöpfli, Ellen Leister, Pieter de Boer, Bettina Sievers, and Martin H. Schöni. "The anaerobic threshold in cystic fibrosis: Comparison of V-slope method, lactate turn points, and Conconi test." Pediatric Pulmonology 25, no. 3 (March 1998): 147–53. http://dx.doi.org/10.1002/(sici)1099-0496(199803)25:3<147::aid-ppul3>3.0.co;2-j.
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Vukovich, Matthew D., Rick L. Sharp, Douglas S. King, and Kellie Kershishnik. "The Effect of Protein Supplementation on Lactate Accumulation during Submaximal and Maximal Exercise." International Journal of Sport Nutrition 2, no. 4 (December 1992): 307–16. http://dx.doi.org/10.1123/ijsn.2.4.307.
Повний текст джерелаАнотація:
Eleven subjects performed a graded exercise test after 1 week of protein supplementation (PRO) or glucose polymer placebo (CON), randomly assigned in a double blind fashion. The exercise consisted of 3-min graded exercise bouts separated by 10 min of active recovery at zero pedal resistance. Subjects then performed a 30-sec Wingate test (WIN) to assess performance during supramaximal exercise. Blood samples were obtained in the last 15 sec of each exercise and recovery period. PRO resulted in a decrease in blood lactate following 120%and WIN, an increase in blood alanine at all time points, and lower postexercise muscle lactate and glycogen. Resting muscle GPT activity was 47% higher during the PRO trial. Mean power output during the WIN did not differ between PRO and CON. The WIN fatigue index was not significantly different between PRO and CON. The increased alanine may reflect increased transamination of pyruvate, thereby reducing the accumulation of lactate, which in turn had a marginal effect on performance during supramaximal exercise.
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Schimassek, H., and Ingrid Meißner. "Glycogen Synthesis in Rat Liver from a Pool of Free Glucose." Zeitschrift für Naturforschung C 48, no. 1-2 (February 1, 1993): 85–91. http://dx.doi.org/10.1515/znc-1993-1-216.
Повний текст джерелаАнотація:
Glycogen synthesis in isolated perfused livers or livers of anesthetized rats (in situ), was studied using radioactively labelled fructose, lactate, and inositol as substrates. The specific radioactivity of glucose and glycogen was measured at various times and compared with that of some intermediates. The results suggest that liver glycogen is formed from the pool of free glucose which in turn is fed by the so-called “direct and indirect pathway” of glycogen synthesis. This points to an important role of glucose-6-phosphatase, an enzyme complex subject to regulation by glucocorticoids, well known promoters of hepatic glycogen synthesis.
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Lauritzen, Martin, Anker Jon Hansen, Dorte Kronborg, and Tadeusz Wieloch. "Cortical Spreading Depression is Associated with Arachidonic Acid Accumulation and Preservation of Energy Charge." Journal of Cerebral Blood Flow & Metabolism 10, no. 1 (January 1990): 115–22. http://dx.doi.org/10.1038/jcbfm.1990.14.
Повний текст джерелаАнотація:
The present study aimed to study the relation between the release of arachidonic acid (AA) and the energy state in cerebral cortices of rats during single episodes of cortical spreading depression (CSD). The changes in concentrations of AA, labile phosphate compounds [ATP, ADP, AMP, and phosphocreatine (PCr)], and glycolytic metabolites (lactate, pyruvate, glucose, and glycogen) were studied during and following the large change of the local direct current (DC) potential. Free AA increased markedly during the DC shift, continued to increase during the subsequent 3 min, and returned to control levels at 4–5 min after CSD. PCr decreased by 38% in the first minutes following the DC shift, while ADP increased by 38%. Both returned to normal within a few minutes. ATP, AMP, and energy charge remained constant throughout the experimental period. Glucose decreased by 47% and glycogen by 34% for a few minutes following CSD, while lactate increased by 105% at 2–3 min and by 77% at 4–5 min after CSD. The metabolites returned to control levels at 10 min after CSD. Considering the constant energy charge at all time points during CSD, it is suggested that the AA rise reflects augmented phospholipase activity due to either increased intracellular [Ca2+] or receptor stimulation or both. The possibility that N-methyl-d-aspartate receptors play a role in the release of AA, and that free AA in turn could be part of the mechanism of CSD, is discussed.
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Wallner, Dietmar, Helmut Simi, Gerhard Tschakert, and Peter Hofmann. "Acute Physiological Response to Aerobic Short-Interval Training in Trained Runners." International Journal of Sports Physiology and Performance 9, no. 4 (July 2014): 661–66. http://dx.doi.org/10.1123/ijspp.2013-0385.
Повний текст джерелаАнотація:
Purpose:To analyze the acute physiological response to aerobic short-interval training (AESIT) at various high-intensity running speeds. A minor anaerobic glycolytic energy supply was aimed to mimic the characteristics of slow continuous runs.Methods:Eight trained male runners (maximal oxygen uptake [VO2max] 55.5 ± 3.3 mL · kg−1 · min−1) performed an incremental treadmill exercise test (increments: 0.75 km · h−1 · min−1). Two lactate turn points (LTP1, LTP2) were determined. Subsequently, 3 randomly assigned AESIT sessions with high-intensity running-speed intervals were performed at speeds close to the speed (v) at VO2max (vVO2max) to create mean intensities of 50%, 55%, and 60% of vLTP1. AESIT sessions lasted 30 min and consisted of 10-s work phases, alternated by 20-s passive recovery phases.Results:To produce mean velocities of 50%, 55%, and 60% of vLTP1, running speeds were calculated as 18.6 ± 0.7 km/h (93.4% vVO2max), 20.2 ± 0.6 km/h (101.9% vVO2max), and 22.3 ± 0.7 km/h (111.0% vVO2max), which gave a mean blood lactate concentration (La) of 1.09 ± 0.31 mmol/L, 1.57 ± 0.52 mmol/L, and 2.09 ± 0.99 mmol/L, respectively. La at 50% of vLTP1 was not significantly different from La at vLTP1 (P = .8894). Mean VO2 was found at 54.0%, 58.5%, and 64.0% of VO2max, while at the end of the sessions VO2 rose to 71.1%, 80.4%, and 85.6% of VO2max, respectively.Conclusion:The results showed that AESIT with 10-s work phases alternating with 20 s of passive rest and a running speed close to vVO2max gave a systemic aerobic metabolic profile similar to slow continuous runs.
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Roy, Sukanya, Subhashree Kumaravel, Priyanka Banerjee, Tori K. White, April O’Brien, Catherine Seelig, Rahul Chauhan, et al. "Tumor Lymphatic Interactions Induce CXCR2-CXCL5 Axis and Alter Cellular Metabolism and Lymphangiogenic Pathways to Promote Cholangiocarcinoma." Cells 10, no. 11 (November 9, 2021): 3093. http://dx.doi.org/10.3390/cells10113093.
Повний текст джерелаАнотація:
Cholangiocarcinoma (CCA), or cancer of bile duct epithelial cells, is a very aggressive malignancy characterized by early lymphangiogenesis in the tumor microenvironment (TME) and lymph node (LN) metastasis which correlate with adverse patient outcome. However, the specific roles of lymphatic endothelial cells (LECs) that promote LN metastasis remains unexplored. Here we aimed to identify the dynamic molecular crosstalk between LECs and CCA cells that activate tumor-promoting pathways and enhances lymphangiogenic mechanisms. Our studies show that inflamed LECs produced high levels of chemokine CXCL5 that signals through its receptor CXCR2 on CCA cells. The CXCR2-CXCL5 signaling axis in turn activates EMT (epithelial-mesenchymal transition) inducing MMP (matrix metalloproteinase) genes such as GLI, PTCHD, and MMP2 in CCA cells that promote CCA migration and invasion. Further, rate of mitochondrial respiration and glycolysis of CCA cells was significantly upregulated by inflamed LECs and CXCL5 activation, indicating metabolic reprogramming. CXCL5 also induced lactate production, glucose uptake, and mitoROS. CXCL5 also induced LEC tube formation and increased metabolic gene expression in LECs. In vivo studies using CCA orthotopic models confirmed several of these mechanisms. Our data points to a key finding that LECs upregulate critical tumor-promoting pathways in CCA via CXCR2-CXCL5 axis, which further augments CCA metastasis.
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Kjaer, M., N. H. Secher, F. W. Bach, and H. Galbo. "Role of motor center activity for hormonal changes and substrate mobilization in humans." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 253, no. 5 (November 1, 1987): R687—R695. http://dx.doi.org/10.1152/ajpregu.1987.253.5.r687.
Повний текст джерелаАнотація:
The study evaluated the hypothesis that during exercise autonomic neuroendocrine activity and, in turn, substrate mobilization, is subjected to feed-forward stimulation from motor centers. Eight young healthy men bicycled for two 20-min periods without (control, C) as well as during partial neuromuscular blockade with tubocurarine (Cu). 3-[3H]glucose was infused, and arterialized hand vein blood was sampled. In period 1 O2 consumption (VO2) (56% VO2 max), heart rate, and blood lactate were identical in Cu compared with C experiments, whereas hand grip strength was lower and perceived exertion [14.0 +/- 1.5 vs. 9.1 +/- 1.2 (SE) points, P less than 0.01] higher in Cu experiments, indicating higher motor center activity. Concentrations of norepinephrine [7.39 +/- 1.18 (Cu) vs. 5.14 +/- 1.06 (C) nmol/l], epinephrine (1.69 +/- 0.33 vs 0.87 +/- 0.16 nmol/l), growth hormone (25.9 +/- 7.3 vs. 11.5 +/- 4.7 mU/l), and adrenocorticotropin hormone (11.3 +/- 1.3 vs. 5.5 +/- 0.7 pmol/l) attained higher values in Cu than in C experiments (P less than 0.05). The initial increase in glucose production was enhanced in Cu (8.1 +/- 1.6 mumol.min-1.kg-1) compared with C experiments (3.9 +/- 1.9, P less than 0.05), and plasma glucose only increased in Cu experiments. Free fatty acid (P less than 0.05) and glycerol (P less than 0.1) concentrations were higher in Cu than in C experiments. In period 2 identical perceived exertion was achieved in the two experiments by reducing work load in Cu experiments. In this period hormonal responses were similar in the two experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
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Gupte, Shrikant. "Initiation of IJMBioS." International Journal of Medicine and Biomedical Sciences 1, no. 1 (October 30, 2015): 1–2. http://dx.doi.org/10.55530/ijmbiosnepal.v1i1.2.
Повний текст джерелаАнотація:
It gives me a great pleasure to be a small contributor to the first inaugural issue of “International Journal of Medicine & Biomedical Sciences” being published from Nepal with efforts put in by Nepalese Researches. As the name suggests, this journal is mainly devoted to Biomedical Sciences & Medical sciences and related topics. On this special auspicious occasion I would like to take opportunity to share some of my thoughts. The medical microbiology revolves around three main areas and topics such as type's infectious diseases, diagnosis methods andtreatment options. Over the past decades, major advances in the field of molecular biology, coupled with advances in multiplex real time PCR technologies have facilitated the development of high performing,innovative, low cost and syndrome based tests for the diagnosis of various bacteria, viruses and parasites with the aid of fast track diagnostics. These technologies are particularly specialised in symptoms based disease approach as different pathogens can cause similar clinical pictures while diagnosed for respiratory infections, gastroenteritis, sexually transmitted infections, fever, rash, childhood infections, hepatitis, meningitis, infections of the immune suppressed, tropical fever and many other infections. Fungal infections are increasing worldwide specially with increase in immune compromised patients. Correct and accurate laboratory diagnosis of fungal infections has become an essential part of the laboratory services. After achieving success in diagnosis,it's now a turn of a clinician to give most appropriate antimicrobial treatment from the available armament of antimicrobial agents. At this point the gloomy scenario surfaces. Due to ever increasing number of resistant organisms treatment options for clinicians are very limited. Emergence of MRSA, VRSA, ESBL and MBL including NDM1 and so on have made one time considered most powerful antibiotics blunt in action. The number of strains resistant to different antibiotics and their ever increasing number revealed in several publications worldwide are really scary. The situation is really bad in Asian countries. Lot of discussion goes and finally blame points at uncontrolled misuse of antibiotics. Though it is true, there are certain associated socio-economic issues that need to be considered. The clinician is often forced to go for empirical antibiotic treatment due to high cost of susceptibility tests needed to be performed before starting the appropriate antibiotic treatment and moreover even if he wants, it not easily available particularly in rural areas. Additionally, leading international Pharma companies have either stopped their search for new antibiotics or slowed down and instead prefer to invest in lifestyle diseases such as high blood pressure, diabetes and asthma due to their higher shelf life, unlike that of antibiotics. The safety issues and very high cost of clinical trials coupled with uncertainty of final success have made development of NCEs less rewarding. The art of antibiotic discovery from natural sources such as soil is slowly dying out even though it still has a very high potential to reward. Now days it is possible to give outstanding resultstogether with the help of sophisticated and advanced analytical identification tools and database of known antibiotics, not available during the early days of antibiotic research. Today the countries of the world are fast connected with each other. Any asymptomatic carrier can carry deadly resistant pathogens fromone end of the world to another within less than 24 hours without even his or her knowledge and without any suspect of the regulatory authority. It is very difficult now to stop this spread even in so called isolated advanced countries. Another reason for immergence of antimicrobial resistance is also need to be equally understood. The suboptimal doses when given during the therapy can create antibiotic levels lower than the Mutant Prevention Concentration (MPC) and thereby give chance to slowly growing resistant subpopulation to grow which then increase in number during the same treatment. It is essential that clinician has knowledge of PK-PD effect of antibiotics and by what parameter the antibiotic acts. These are governed by either Cmax /MIC or AUC/MIC or time above MIC. For example Fluoroquinoles act by Cmax/MIC and therefore a single dose once a day is often recommended whereas beta lactams class of antibiotics need longer time above MIC level to act and hence frequent dosing is practised. Any compromise with these parameters could lead to development of resistant strains. The five hours short duration incubation in automated susceptibility test is based on development and measurement of optical density. However, resistant mutants which are few in number compared to a large sensitive population fail to impart turbidity and hence the culture is labelled as sensitive. This is a major error in susceptibility testing. To overcome this problem, E-test MIC method is better option since on 24 hr incubation, the resistant mutants that grow in the form of isolated colonies in the zone of inhibition can clearly show their presence. This observation would help clinician to take informed decision at right time to choose a more efficacious and appropriate antibiotic treatment protocol. This is one of the reasons which results in not only creating reservoir of resistant organisms in patient’s body and its subsequent spread but could also result in mortality. The national level antibiotic resistance surveillance program if undertaken on regular intervals of time would help draw correct picture of gravity of alarming situation and also to judge the effectiveness of program implemented to control AMR. It is a joint responsibility of Pharma companies to refrain themselves from introducing irrational antibiotic combinations without understanding the PK –PD of an individual partner. In antimicrobial therapy, the concentration of an individual component at the site of infection when present together during the therapy is critical as observed in in-vitro evaluation experiments. Similarly, MIC results in in-vitro combination study must show MICs of resistant strains falling in the sensitive range as recommended by CLSI guideline. Researchers have to keep in mind that the outcome of quality research should lead to new findings, better understanding or insight into earlier findings or ideally suggesting a better treatment option. The publication of reconfirmation of known data is sometimes essential. However, these type of publication when very frequently appear in journals do not lead to advancement of science. Finally I congratulate IJMBioS team a good success in this noble endeavour.
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Jones, Andrew M., Brett S. Kirby, Ida E. Clark, Hannah M. Rice, Elizabeth Fulkerson, Lee J. Wylie, Daryl P. Wilkerson, Anni Vanhatalo, and Brad W. Wilkins. "Physiological demands of running at 2-hour marathon race pace." Journal of Applied Physiology, November 5, 2020. http://dx.doi.org/10.1152/japplphysiol.00647.2020.
Повний текст джерелаАнотація:
The requirements of running a 2 hour marathon have been extensively debated but the actual physiological demands of running at ~21.1 km/h have never been reported. We therefore conducted laboratory-based physiological evaluations and measured running economy (O2 cost) while running outdoors at ~21.1 km/h, in world-class distance runners as part of Nike's 'Breaking 2' marathon project. On separate days, 16 male distance runners (age, 29 ± 4 years; height, 1.72 ± 0.04 m; mass, 58.9 ± 3.3 kg) completed an incremental treadmill test for the assessment of V̇O2peak, O2 cost of submaximal running, lactate threshold and lactate turn-point, and a track test during which they ran continuously at 21.1 km/h. The laboratory-determined V̇O2peak was 71.0 ± 5.7 ml/kg/min with lactate threshold and lactate turn-point occurring at 18.9 ± 0.4 and 20.2 ± 0.6 km/h, corresponding to 83 ± 5 % and 92 ± 3 % V̇O2peak, respectively. Seven athletes were able to attain a steady-state V̇O2 when running outdoors at 21.1 km/h. The mean O2 cost for these athletes was 191 ± 19 ml/kg/km such that running at 21.1 km/h required an absolute V̇O2 of ~4.0 L/min and represented 94 ± 3 % V̇O2peak. We report novel data on the O2 cost of running outdoors at 21.1 km/h, which enables better modelling of possible marathon performances by elite athletes. Using the value for O2 cost measured in this study, a sub-2 hour marathon would require a 59 kg runner to sustain a V̇O2 of approximately 4.0 L/min or 67 ml/kg/min.
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Ahn, Chong H., Jin-Woo Choi, Sanghyo Kim, Young-Soo Sohn, Aniruddha Puntambekar, Suresh Murugesan, Gregory Beaucage, and Joseph H. Nevin. "Disposable Smart Plastic Biochips For Clinical Diagnostics." MRS Proceedings 729 (2002). http://dx.doi.org/10.1557/proc-729-u1.8.
Повний текст джерелаАнотація:
AbstractThis paper presents an overview of the development of novel disposable smart plastic fluidic biochips for clinical diagnostic applications. The biochip is manufactured using a low-cost, rapid turn around injection molding/embossing process on a plastic substrate. The plastic fluidic biochip uses a novel sPROMs (structurally programmable microfluidic system) approach to achieve passive control of fluidic sequencing [1-2]. The plastic biochip also uses an on-chip pressurized air source for fluidic movement thus eliminating the need for active driving mechanisms and allowing for a truly disposable approach. Furthermore, electrochemical biosensors are also integrated on-chip to analyze various metabolically significant parameters such as PO2(partial pressure of oxygen), Glucose, Lactate,and pH. The fluidic biochip is being developed for point-of-care health monitoring applications where parameters such as small size, simplicity of operation, disposability, reduced cross-contamination are vital. The issues mentioned above are successfully addressed using the approach of this work and are discussed in this paper.
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Ferreira, Gonçalo Rafael Marques, Joana Correia, João Fiuza, João Miguel Santos, Vanda Neto, Joana Cunha, Filipe Fernandes, Inês Pires, Bruno Marmelo, and Costa Cabral. "Clinical Case 15—Warburg effect and pulmonary embolism: a confounding clinical case." Cardiovascular Research 118, Supplement_2 (October 1, 2022). http://dx.doi.org/10.1093/cvr/cvac157.133.
Повний текст джерелаАнотація:
Abstract Presentation A 61 year old man with a history of multiple lymph node metastasis of unknown primary cancer was admitted in the Emergency Room with sudden dyspnea preceded by left leg swelling. Physical examination revealed a blood pressure of 91/70mmHg, tachycardia, tachypnea and signs of deep vein thrombosis (DVT). Diagnosis and management Blood analysis showed increased serum lactate (SL) (5,5 mmol/L), a slight increase of cardiac enzymes and hypoglycemia, and imagiologic tests showed signs of bilateral pulmonary embolism (PE) and an increase of the right cardiac chambers. The patient was hospitalized with the diagnosis of intermediate-high risk PE. Because the patient presented persistent elevated SL and borderline hypotension, fibrinolysis was performed. However, the patient maintained high SL levels and hypotensive profile. After receiving the lymph node's biopsy result, which pointed towards a follicular lymphoma, the persistent hyperlactatemia, together with the hypoglycemic profile, was interpreted as a consequence of the Warburg Effect. Luckily, the patient didn't had any side effects of the fibrinolytic treatment. Learning points Acute high risk PE is marked by the presence of haemodynamic instability at presentation, and the finding of increased SL suggests peripheral hypoperfusion. Systemic thrombolytic therapy is indicated in most of patients with high risk PE. However, there are other causes of hyperlactatemia which the physician must be aware, as it can act as a confounder of PE risk assessment. The Warburg Effect may cause elevated SL in patients with cancer, which in turn are at risk of developing PE.
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Vita, Angelina Jessica A., Seth Rice, Owen Albin, Twisha S. Patel, Charles N. Styron, Keith S. Kaye та Jason M. Pogue. "424. Risk Factors for Infection or Colonization with Piperacillin-tazobactam (TZP) Resistant P. aeruginosa (PSA) with Increasing Degrees of β-lactam Resistance". Open Forum Infectious Diseases 9, Supplement_2 (1 грудня 2022). http://dx.doi.org/10.1093/ofid/ofac492.499.
Повний текст джерелаАнотація:
Abstract Background Resistance to β-lactams amongst PSA is common with roughly 20% of isolates demonstrating resistance to TZP. This can lead to delays in the time to appropriate empiric therapy. While rapid diagnostics can identify PSA at earlier time points, they fail to detect common β-lactam resistance mechanisms in this pathogen. Though risk factors for TZP resistance (TZP-R) amongst PSA have been identified, co-resistance amongst traditional anti-PSA β-lactams is common, so decisions to turn to other traditional anti-PSA or novel agents in the presence of such predictors are unclear. This study aims to find predictors unique to varying degrees of β-lactam resistance amongst TZP-R PSA to inform these decisions. Methods This was a retrospective case-case-case-control study of all non-cystic fibrosis patients with PSA isolated from a culture from 2015-2021 at Michigan Medicine. Four study groups were created based on the susceptibility profile of PSA: TZP susceptible (TZP-S), resistance to TZP only (TZP-R ONLY), resistance to TZP in addition to 1 or 2 other traditional anti-PSA β-lactams (TZP-R PLUS), and resistance to all traditional anti-PSA β-lactams (pan β-lactam resistance, PBR). Bivariate and multivariate analyses were performed to compare each degree of TZP resistance to the TZP-S group. Results were then compared across models to assess uniqueness to a given resistant phenotype. Results 2365 patients were included, and results of the multivariate analyses are listed in the table. The sole predictor of TZP-R ONLY was recent ceftriaxone or cefotaxime use. Independent predictors unique to TZP-R PLUS were community acquired infection, recent ICU residence, and recent exposure to TZP or aztreonam. Most risk factors identified were either unique to PBR or shared between PBR and TZP-R PLUS including history of PSA, history of TZP-R PSA, and recent exposure to multiple antibiotics. Multivariate Models for TZP-R ONLY, TZP-R PLUS, and PBR Conclusion This analysis demonstrates that previously identified risk factors for TZP-R P. aeruginosa are predictors of PSA with greater degrees of resistance. Given these findings, consideration needs to be given to escalation to novel agents in the presence of risk factors at the time of PSA isolation, rather than to other traditional anti-PSA β-lactams. Disclosures Owen Albin, MD, Charles River Laboratory: Advisor/Consultant|Cipla Pharmaceuticals: Advisor/Consultant|Shionogi Inc: Advisor/Consultant Keith S. Kaye, MD, GSK: Advisor/Consultant|merck: Advisor/Consultant|merck: Stocks/Bonds|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant jason M. Pogue, PharmD, consultant to Venatorx, Merck, Shionogi, QPex Biopharma, Utility, GSK, and Entasis.: Advisor/Consultant.
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Heibel, Jessica J., Eric M. Graham, Aurelie Roux, David Graham, Cedric Manlhiot, and Allen D. Everett. "Abstract 13920: Improved Outcome Prediction Modelling in Neonatal Congenital Heart Disease With Metabolomic Feature Clustering." Circulation 142, Suppl_3 (November 17, 2020). http://dx.doi.org/10.1161/circ.142.suppl_3.13920.
Повний текст джерелаАнотація:
Introduction: Neonatal heart surgery requiring cardiopulmonary bypass (CPB) is associated with significant morbidity and mortality. Methods to improve outcome prediction are lacking. Hypothesis: Targeted metabolic profiling can identify critical metabolites associated with important post-operative clinical outcomes. These in turn could be integrated into clinical prediction models. Methods: Secondary analysis of serum samples from the neonatal congenital cardiac surgery with CPB methylprednisolone trial, which evaluated effects of steroids on outcomes. Samples were from pre-op, immediate post-CPB, and 12 hrs post op. Outcomes were a cardiac dysfunction composite (death, ECMO, cardiac arrest and lactate) and low cardiac output syndrome (LCOS). Metabolite levels were determined with targeted mass spectrometry (LC/MS/MS). Principal component (PC) analysis and multivariable regression analysis with bootstrapping were used to assess the association between metabolic profiles and outcomes. Results: Total cohort had 149 patients. PC analysis identified 6 PCs (PC1-PC6) that explained 51% of variance. When PCs and metabolites were added to a base clinical model, model fit for the cardiac dysfunction composite outcome was significantly improved (c-stat 0.819 vs 0.902, p<0.001) as well as LCOS (c-stat 0.576 vs. 0.803, p=0.76 vs. p=0.01). Using adjusted regression models, metabolites (some of which are included in PCs) significantly associated with cardiac dysfunction composite outcome were proline (p=0.004) and leucine (p=0.01). Metabolites associated with LCOS were n-acetyltryptophan (p=0.01), glycocholic acid (p=0.001), cortisol (p=0.02), nicotinamide (p=0.04), methyladenosine (p=0.01) and methionine (p=0.01). For cardiac composite outcome, cumulative and post op values were significant, whereas all time points were for LCOS. Conclusions: Combining metabolic profiles with patient characteristics revealed significant pre-op metabolites associated with important clinical outcomes. Given that the association held true for all time points, these observations could be used to design molecular signature for post-operative cardiac complications or, to create prediction models based on pre-operative metabolic profiles.
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Belkić, Dževad, and Karen Belkić. "High-resolution at 3T for in vivo derivative NMR spectroscopy in medical diagnostics of ovarian tumor: exact quantification by shape estimations." Journal of Mathematical Chemistry, September 8, 2021. http://dx.doi.org/10.1007/s10910-021-01283-x.
Повний текст джерелаАнотація:
AbstractTime signals are measured experimentally throughout sciences, technologies and industries. Of particular interest here is the focus on time signals encoded by means of magnetic resonance spectroscopy (MRS). The great majority of generic time signals are equivalent to auto-correlation functions from quantum physics. Therefore, a quantum-mechanical theory of measurements of encoded MRS time signals is achievable by performing quantum-mechanical spectral analysis. When time signals are measured, such an analysis becomes an inverse problem (harmonic inversion) with the task of reconstruction of the fundamental frequencies and the corresponding amplitudes. These complex-valued nodal parameters are the building blocks of the associated resonances in the frequency spectrum. Customarily, the MRS literature reports on fitting some ad hoc mathematical expressions to a set of resonances in a Fourier spectrum to extract their positions, widths and heights. Instead, an alternative would be to diagonalize the so-called data matrix with the signal points as its elements and to extract the resonance parameters without varying any adjusting, free constants as these would be absent altogether. Such a data matrix (the Hankel matrix) is from the category of the evolution matrix in the Schrödinger picture of quantum mechanics. Therefore, the spectrum of this matrix, i.e. the eigenvalues and the corresponding amplitudes, as the Cauchy residues (that are the squared projections of the full wave functions of the system onto the initial state) are equivalent to the sought resonance parameters, just mentioned. The lineshape profile of the frequency-dependent quantum-mechanical spectral envelope is given by the Heaviside partial fraction sum. Each term (i.e. every partial fraction) in this summation represents a component lineshape to be assigned to a given molecule (metabolite) in the tissue scanned by MRS. This is far reaching, since such a procedure allows reconstruction of the most basic quantum-mechanical entities, e.g. the total wave function of the investigated system and its ’Hamiltonian’ (a generator of the dynamics), directly from the encoded time signals. Since quantum mechanics operates with abstract objects, it can be applied to any system including living species. For example, time signals measured from the brain of a human being can be analyzed along these lines, as has actually been done e.g. by own our research. In this way, one can arrive at a quantum-mechanical description of the dynamics of vital organs of the patient by retrieving the interactions as the most important parts of various pathways of the tissue functions and metabolism. Of practical importance is that the outlined quantum-mechanical prediction of the frequency spectrum coincides with the Padé approximant, which is in signal processing alternatively called the fast Padé transform (FPT) for nonderivative estimations. Further, there is a novelty called the derivative fast Padé transform (dFPT). The FPT and dFPT passed the test of time with three fundamentally different time signals, synthesized (noise-free, noise-contaminated) as well as encoded from phantoms and from patients. Such systematics are necessary as they permit robust and reliable benchmarkings of the theory in a manner which can build confidence of the physician, while interpreting the patient’s data and making the appropriate diagnosis. In the present study, we pursue further this road paved earlier by applying the FPT and dFPT (both as shape and parameter estimators) to time signals encoded by in vivo proton MRS from an ovarian tumor. A clinical 3T scanner is used for encoding at a short echo time (30 ms) at which most resonances have not reached yet their decay mode and, as such, could be detected to assist with diagnostics. We have two goals, mathematical and clinical. First, we want to find out whether particularly the nonparametric dFPT, as a shape estimator, can accurately quantify. Secondly, we want to determine whether this processor can provide reliable information for evaluating an ovarian tumor. From the obtained results, it follows that both goals have met with success. The nonparametric dFPT, from its onset as a shape estimator, transformed itself into a parameter estimator. Its quantification capabilities are confirmed by reproducing the components reconstructed by the parametric dFPT. Thereby, fully quantified information is provided to such a precise extent that a large number of sharp resonances (more than 160) appear as being well isolated and, thus, assignable to the known metabolites with no ambiguities. Importantly, some of these metabolites are recognized cancer biomarkers (e.g. choline, phosphocholine, lactate). Also, broader resonances assigned to macromolecules are quantifiable by a sequential estimation (after subtracting the formerly quantified sharp resonances and processing the residual spectrum by the nonparametric dFPT). This is essential too as the presence of macromolecules in nonoderivative envelopes deceptively exaggerates the intensities of sharper resonances and, hence, can be misleading for diagnostics. The dFPT, as the quantification-equipped shape estimator, rules out such possibilities as wider resonances can be separately quantified. This, in turn, helps make adequate assessment of the true yield from sharp resonances assigned to metabolites of recognized diagnostic relevance.
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Dahiya, Sandeep, Vera Saulite, Frieder Kleemann, Sateesh Nagumantry, and Simon Bulley. "P19 A case of pyrexia of unknown origin - wrong way round!" Rheumatology Advances in Practice 6, Supplement_1 (September 26, 2022). http://dx.doi.org/10.1093/rap/rkac067.019.
Повний текст джерелаАнотація:
Abstract Introduction/Background We present a case of a 43-year-old female with a long-standing psoriatic arthritis (PsA) and background diagnosis of undifferentiated connective tissues disease (uCTD), treated with methotrexate and ixekizumab. She developed systemic symptoms of fever, photosensitive rash, recurrent renal impairment, and was found to have pancytopenia with rapidly rising ferritin. During the course of her disease, her dsDNA antibodies became positive by Crithidia. Bone marrow biopsy showed prominent haemophagocytosis. Coupled with raised soluble CD25 receptor and triglycerides levels, this established the diagnosis of macrophage activation syndrome secondary to either uCTD progression or ixekizumab. Description/Method A 43-year-old female nurse with PsA and uCTD (strongly positive ANA, anti-Ro and Anti-La), but no clinical features of CTD, has been treated with methotrexate with good response since 2011. In 2019 she was started on ustekinumab for psoriasis with excellent response. In April 2020 her biologic therapy was changed to ixekizumab due to secondary failure. In July 2020 she presented with a thigh abscess, upper airway swelling and acute kidney injury. Investigations demonstrated leucopenia, CRP 18mmol/l, and ferritin 764mmol/l. She was treated with oral prednisolone, antibiotics, fluids and underwent incision and drainage of thigh abscess. Repeat tests showed lymphopenia, ESR of 98mm/hr and polyclonal gammaglobulinaemia. MRI thigh ruled out osteomyelitis. In August 2020 she was readmitted with high fever, florid photosensitive rash and productive cough. Thorough infection screen was negative. Antibiotics were not effective. dsDNA antibodies were now positive by Crithidia. Differential was either natural progression of CTD or secondary to ixekizumab. A bone marrow biopsy showed no evidence of malignancy. Symptoms settled with high dose oral steroids. She was readmitted two weeks later with recurrence of symptoms, renal impairment, pancytopenia, ferritin >8000mmol/l, raised lactate dehydrogenase and triglycerides. A CT chest, abdomen and pelvis was largely unremarkable. Repeat bone marrow biopsy demonstrated prominent haemophagocytosis. A diagnosis of macrophage activation syndrome (MAS) secondary to CTD was made. Genetic HLH testing (perforin) was normal, soluble CD25R (sCD25R) was markedly raised. She was treated with IV methylprednisolone, followed by dexamethasone and cyclosporine. Her symptoms settled, cytopenia resolved and ferritin improved. Due to new renal impairment, cyclosporine was discontinued. Renal biopsy demonstrated immunologically mediated glomerulonephritis, likely secondary to CTD. There was mild glomerular damage. Mycophenolate mofetil was added with good response; prednisolone dose was reduced successfully. There was no recurrence of fever or other systemic symptoms, renal function remains stable. Discussion/Results MAS is part of a diverse group of inflammatory hyperferritinaemic syndromes. It is considered a secondary form of haemophagocytic lymphohistiocytosis (HLH) developing in patients with autoimmune conditions. Typically MAS is triggered by systemic lupus erythematosus (SLE). To our knowledge, there are no case reports in the literature describing the onset of MAS on the background of PsA. The diagnosis of MAS is invariably challenging due to lack of early biomarkers and non-specific presenting features. This case illustrates a rare presentation of MAS in a patient with overlapping CTD, psoriasis, and PsA. This patient developed features of lupus as well as a change in her immune profile with positive dsDNA and renal histology in keeping with lupus. This was further complicated by the development of MAS. Renal function decline was noted prior to starting cyclosporine, and kidney biopsy was not typical for acute interstitial nephritis, making cyclosporine an unlikely culprit. Mild glomerular damage did not warrant immunosuppression beyond steroids. Fortunately, the patient responded well to IV methylprednisolone and later mycophenolate mofetil. Therefore, anakinra, cyclophosphamide and rituximab were not considered necessary. There is paucity of data on the treatment choices in MAS, with the commonly used HLH 2004 protocol (etoposide, dexamethasone and cyclosporine) showing disappointing results. With her overlapping immune conditions, the choice of immunosuppressive therapies might also be challenging in future should her symptoms of psoriasis and PsA reoccur after further steroid reduction. Key learning points/Conclusion HLS and MAS are poorly understood conditions, thought to be caused by exaggerated inflammatory response to defective granule-mediated cytotoxicity and uncontrolled T-cell activation. This response, in turn, leads to cytokine storm, consequent tissue damage and multi-organ failure. Hystiocytosis Society has developed diagnostic criteria for HLH, which include a molecular diagnosis consistent with HLH (pathological mutations of PRF1, UNC13D, or STX11), or at least five of eight criteria: fever, splenomegaly, cytopenia, hypertriglyceridaemia/hypofibrinogenaemia, haemophagocytosis on biopsy, low/absent natural killer (NK) cell activity, hyperferritinaemia, elevated sCD25R. Our patient fulfilled six out of eight criteria, making the diagnosis certain. It should however be noted that these criteria were developed based on paediatric population and their specificity and sensitivity is not tested in adults. Furthermore, haemophagocytosis may not be present in the initial stages of HLH, as in our case, and is not essential for diagnosis. To complicate matters further, haemophagocytosis can be found in bone marrow in other conditions, such as infections and bone marrow disorders. Extreme hyperferritinaemia is a characteristic feature of HLH, and can be found in only a handful of other conditions, which aids the diagnostic process. These include SLE, hepatocellular injury, adult onset Still’s disease (AOSD), and haematological malignancies. Interestingly, the patient also meets Yamaguchi criteria for diagnosis of AOSD due to having fever, rash, abnormal liver function tests, minor lymphadenopathy, and arthralgia. This fact illustrates that clinicians should avoid using diagnostic criteria as a tick-box exercise in the search for diagnosis. By presenting this case at the Case-Based Conference we are aiming to raise awareness about MAS in the context of PsA and learn how other teams approach patients with known autoimmune conditions and fever of unknown origin. The authors received no financial support for the research, authorship, and publication of this article.