An implementation of the maximum-caliber principle by replica-averaged time-resolved restrained simulations

Inferential methods can be used to integrate experimental informations and molecular simulations. The maximum entropy principle provides a framework for using equilibrium experimental data and it has been shown that replica-averaged simulations, restrained using a static potential, are a practical and powerful implementation of such principle. Here we show that replica-averaged simulations restrained using a time-dependent potential are equivalent to the principle of maximum caliber, the dynamic version of the principle of maximum entropy, and thus may allow to integrate time-resolved data in molecular dynamics simulations. We provide an analytical proof of the equivalence as well as a computational validation making use of simple models and synthetic data. Some limitations and possible solutions are also discussed

Pruritus: a useful sign for predicting the haemodynamic changes that occur following administration of vancomycin

INTRODUCTION: The aim of this study was to investigate the haemodynamic changes that follow the appearance of pruritus during vancomycin administration. METHODS: We studied 50 patients scheduled for coronary artery bypass surgery, and we compared data from patients who exhibited pruritus with those from patients who did not. After the monitoring devices had been positioned, vancomycin (15 mg/kg) was continuously infused at a constant rate over 30 min, before induction of anaesthesia. Haemodynamic profiles were recorded before vancomycin infusion (time point 1); at 15 (time point 2) and 30 min (time point 3) after the beginning of vancomycin infusion; and 15 min after vancomycin infusion had been stopped (time point 4). At each time arterial and mixed venous blood samples were drawn to calculate the shunt fraction (Qsp/Qt). RESULTS: In patients who exhibited pruritus (group A, n = 17) at time point 3 versus time point 1, systemic vascular resistance index (SVRI) and arterial oxygen tension (PaO(2)) decreased significantly; cardiac index (CI), stroke volume index (SVI) and Qsp/Qt increased significantly; and mean systemic pressure and heart rate were stable. Those changes were observed only in patients not treated with a β-blocker before surgery, whereas no change occurred in patients treated with the drug. In the patients who were free from pruritus (group B, n = 28), we did not observe any significant change. CONCLUSION: The appearance of pruritus during vancomycin administration indicates that SVRI is declining, thus exposing the patient to risk for hypotension. Therapy with a β-blocker appears to confer protection against this hemodynamic reaction

Detraining effects prevention: a new rising challenge for athletes

[no abstract available

High intensity interval training does not have compensatory effects on physical activity levels in older adults

Exercise has beneficial effects on older adults, but controversy surrounds the purported "compensatory effects" that training may have on total daily physical activity and energy expenditure in the elderly. We wanted to determine whether 8 weeks of high-intensity interval training (HIIT) induced such effects on physical activity and energy expenditure in healthy, active older adult men

Resting Energy Expenditure in Anorexia Nervosa: Measured versus Estimated

Introduction. Aim of this study was to compare the resting energy expenditure (REE) measured by the Douglas bag method with the REE estimated with the FitMate method, the Harris-Benedict equation, and the Müller et al. equation for individuals with BMI < 18.5 kg/m2 in a severe group of underweight patients with anorexia nervosa (AN). Methods. 15 subjects with AN participated in the study. The Douglas bag method and the FitMate method were used to measure REE and the dual energy X-ray absorptiometry to assess body composition after one day of refeeding. Results. FitMate method and the Müller et al. equation gave an accurate REE estimation, while the Harris-Benedict equation overestimated the REE when compared with the Douglas bag method. Conclusion. The data support the use of the FitMate method and the Müller et al. equation, but not the Harris-Benedict equation, to estimate REE in AN patients after short-term refeeding

Energetics of running in top-level marathon runners from Kenya

On ten top-level Kenyan marathon runners (KA) plus nine European controls (EC, equivalent to KA), we measured maximal oxygen consumption ( $$\dot{V}{\text{O}}_{{ 2 {\text{max}}}}$$ ) and the energy cost of running (C r) on track during training camps at moderate altitude, to better understand the KA dominance in the marathon. At each incremental running speed, steady-state oxygen consumption ( $$\dot{V}{\text{O}}_{ 2}$$ ) was measured by telemetric metabolic cart, and lactate by electro-enzymatic method. The speed requiring $$\dot{V}{\text{O}}_{ 2} = \dot{V}{\text{O}}_{{ 2 {\text{max}}}}$$ provided the maximal aerobic velocity (v max). The energy cost of running was calculated by dividing net $$\dot{V}{\text{O}}_{ 2}$$ by the corresponding speed. The speed at lactate threshold (v ΘAN) was computed from individual Lâb versus speed curves. The sustainable $$\dot{V}{\text{O}}_{{ 2 {\text{max}}}}$$ fraction (F d) at v ΘAN (F ΘAN) was computed dividing v ΘAN by v max. The F d for the marathon (F mar) was determined as F mar=0.92 F ΘAN. Overall, $$\dot{V}{\text{O}}_{{ 2 {\text{max}}}}$$ (64.9±5.8 vs. 63.9±3.7mlkg−1min−1), v max (5.55±0.30 vs. 5.41±0.29ms−1) and C r (3.64±0.28 vs. 3.63±0.31Jkg−1m−1) resulted the same in KA as in EC. In both groups, C r increased linearly with the square of speed. F ΘAN was 0.896±0.054 in KA and 0.909±0.068 in EC; F mar was 0.825±0.050 in KA and 0.836±0.062 in EC (NS). Accounting for altitude, running speed predictions from present data are close to actual running performances, if F ΘAN instead of F mar is taken as index of F d. In conclusion, both KA and EC did not have a very high $$\dot{V}{\text{O}}_{{ 2 {\text{max}}}}$$ , but had extremely high F d, and low C r, equal between them. The dominance of KA over EC cannot be explained on energetic ground

Bio adipic acid production from sodium muconate and muconic acid: a comparison of two systems

sodium muconate and trans,trans‐muconic acid were heterogeneously hydrogenated to adipic acid, a strategic intermediate for the industry of polyamides and high performance polymers. Hydrogen pressure, metal to substrate ratio, substrate concentration and reaction temperature were varied to study the effect of these parameters on the reaction products. Commercial Pd/AC 5 % was used as catalyst and characterized by TEM, BET and XPS analyses. The results revealed that temperature is the parameter which mainly affect the reaction. Moreover, hydrogenation of trans,trans‐muconic acid is faster than sodium muconate reduction. Full conversion and full yield toward adipic acid was obtained using trans,trans‐muconic acid as substrate after 60 min at the following operating conditions: temperature=70 °C, metal/substrate=1/200 (molPd/molsub), trans,trans‐muconic acid concentration=1.42E‐02M and hydrogen pressure=1 bar. In all reactions (2E)hexenedioic acid was detected as main intermediate

Effects of acceleration in the Gz axis on human cardiopulmonary responses to exercise

The aim of this paper was to develop a model from experimental data allowing a prediction of the cardiopulmonary responses to steady-state submaximal exercise in varying gravitational environments, with acceleration in the Gz axis (a g) ranging from 0 to 3g. To this aim, we combined data from three different experiments, carried out at Buffalo, at Stockholm and inside the Mir Station. Oxygen consumption, as expected, increased linearly with a g. In contrast, heart rate increased non-linearly with a g, whereas stroke volume decreased non-linearly: both were described by quadratic functions. Thus, the relationship between cardiac output and a g was described by a fourth power regression equation. Mean arterial pressure increased with a g non linearly, a relation that we interpolated again with a quadratic function. Thus, total peripheral resistance varied linearly with a g. These data led to predict that maximal oxygen consumption would decrease drastically as a g is increased. Maximal oxygen consumption would become equal to resting oxygen consumption when a g is around 4.5g, thus indicating the practical impossibility for humans to stay and work on the biggest Planets of the Solar Syste

ASCs-exosomes recover coupling efficiency and mitochondrial membrane potential in an in vitro model of ALS

The amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motoneurons death. Mutations in the superoxide dismutase 1 (SOD1) protein have been identified to be related to the disease. Beyond the different altered pathways, the mitochondrial dysfunction is one of the major features that leads to the selective death of motoneurons in ALS. The NSC-34 cell line, overexpressing human SOD1(G93A) mutant protein [NSC-34(G93A)], is considered an optimal in vitro model to study ALS. Here we investigated the energy metabolism in NSC-34(G93A) cells and in particular the effect of the mutated SOD1(G93A) protein on the mitochondrial respiratory capacity (complexes I-IV) by high resolution respirometry (HRR) and cytofluorimetry. We demonstrated that NSC-34(G93A) cells show a reduced mitochondrial oxidative capacity. In particular, we found significant impairment of the complex I-linked oxidative phosphorylation, reduced efficiency of the electron transfer system (ETS) associated with a higher rate of dissipative respiration, and a lower membrane potential. In order to rescue the effect of the mutated SOD1 gene on mitochondria impairment, we evaluated the efficacy of the exosomes, isolated from adipose-derived stem cells, administrated on the NSC-34(G93A) cells. These data show that ASCs-exosomes are able to restore complex I activity, coupling efficiency and mitochondrial membrane potential. Our results improve the knowledge about mitochondrial bioenergetic defects directly associated with the SOD1(G93A) mutation, and prove the efficacy of adipose-derived stem cells exosomes to rescue the function of mitochondria, indicating that these vesicles could represent a valuable approach to target mitochondrial dysfunction in ALS

Avoidable blindness and value based healthcare: more value with a population approach

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