Anabolic effects of oral leucine-rich protein with and without ß-hydroxybutyrate on muscle protein metabolism in a novel clinical model of systemic inflammation-a randomized crossover trial.

BACKGROUND: ß-lactoglobulin (BLG) stimulates muscle protein synthesis and ß-hydroxybutyrate (BHB) inhibits muscle breakdown. Whether combining the 2 can additively attenuate disease-induced muscle loss is unknown. OBJECTIVE: Based on previous observations of anticatabolic effects of protein and ketone bodies during inflammation, and using a novel model combining ongoing systemic inflammation, fasting, and immobilization, we tested whether the anticatabolic muscle response to oral amino acids is altered compared with control conditions, as well as whether coadministration of oral BHB and BLG further improves the muscle anabolic response. Muscle net balance (NBphe) was the primary outcome and intramyocellular signals were assessed. METHODS: In a randomized crossover design, 8 young men underwent either preconditioning with LPS (prestudy day: 1 ng/kg, study day: 0.5 ng/kg) combined with a 36-h fast and bed rest to mimic catabolic inflammatory disease (CAT) or an overnight fast (control [CTR]) prior to isocaloric nutritional interventions on 3 occasions separated by ∼6 wk (range 42 to 83 d). RESULTS: NBphe increased similarly upon all conditions (interaction P = 0.65). From comparable baseline rates, both Rdphe [muscle synthesis, median ratio (95% CI): 0.44 (0.23, 0.86) P = 0.017] and Raphe [muscle breakdown, median ratio (95% CI): 0.46 (0.27, 0.78) P = 0.005] decreased following BHB + BLG compared with BLG. BLG increased Rdphe more under CAT conditions compared with CTR (interaction P = 0.02). CAT increased inflammation, energy expenditure, and lipid oxidation and decreased Rdphe and anabolic signaling [mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E-binding protein 1 (4EPB1) phosphorylation]. CONCLUSION: In contrast to our initial hypothesis, NBphe increased similarly following BLG during CAT and CTR conditions; CAT however, specifically stimulated the BLG-mediated increase in protein synthesis, whereas BHB coadministration did not affect NBphe, but distinctly dampened the BLG-induced increase in muscle amino acid fluxes thereby liberating circulating amino acids for anabolic actions elsewhere.

Radiative Energy Budgets in a Microbial Mat Under Different Irradiance and Tidal Conditions.

Irradiance and temperature variations during tidal cycles modulate microphytobenthic primary production potentially by changing the radiative energy balance of photosynthetic mats between immersion and emersion and thus sediment daily net metabolism. To test the effect of tidal stages on the radiative energy budget, we used microsensor measurements of oxygen, temperature, and scalar irradiance to estimate the radiative energy budget in a coastal photosynthetic microbial mat during immersion (constant water column of 2 cm) and emersion under increasing irradiance. Total absorbed light energy was higher in immersion than emersion, due to a lower reflectance of the microbial mat, while most (> 97%) of the absorbed light energy was dissipated as heat irrespective of tidal conditions. During immersion, the upward heat flux was higher than the downward one, whereas the opposite occurred during emersion. At highest photon irradiance (800 µmol photon m-2 s-1), the sediment temperature increased ~ 2.5 °C after changing the conditions from immersion to emersion. The radiative energy balance showed that less than 1% of the incident light energy (PAR, 400-700 nm) was conserved by photosynthesis under both tidal conditions. At low to moderate incident irradiances, the light use efficiency was similar during the tidal stages. In contrast, we found an ~ 30% reduction in the light use efficiency during emersion as compared to immersion under the highest irradiance likely due to the rapid warming of the sediment during emersion and increased non-photochemical quenching. These changes in the photosynthetic efficiency and radiative energy budget could affect both primary producers and temperature-dependent bacterial activity and consequently daily net metabolism rates having important ecological consequences.

Computational neuroimaging strategies for single patient predictions.

Neuroimaging increasingly exploits machine learning techniques in an attempt to achieve clinically relevant single-subject predictions. An alternative to machine learning, which tries to establish predictive links between features of the observed data and clinical variables, is the deployment of computational models for inferring on the (patho)physiological and cognitive mechanisms that generate behavioural and neuroimaging responses. This paper discusses the rationale behind a computational approach to neuroimaging-based single-subject inference, focusing on its potential for characterising disease mechanisms in individual subjects and mapping these characterisations to clinical predictions. Following an overview of two main approaches - Bayesian model selection and generative embedding - which can link computational models to individual predictions, we review how these methods accommodate heterogeneity in psychiatric and neurological spectrum disorders, help avoid erroneous interpretations of neuroimaging data, and establish a link between a mechanistic, model-based approach and the statistical perspectives afforded by machine learning.

Patients' participation in and evaluation of a follow-up program following intensive care.

BACKGROUND: Patients' difficulties following critical illness and the willingness of intensive care units (ICU) to take an expanded responsibility during the recovery period have led to the development of different follow-up programs. The aim of this study was to explore and describe patients' participation in and evaluation of a follow-up program at a nurse-led clinic (NLC). METHODS: Patients with a length of stay ≥72 h, discharged from the ICU, participated in a follow-up program based on three contacts, as a visit to the NLC, telephone contact, ward visit or as an indirect contact, during a 6-month period. A specially developed database recorded information regarding patients' participation and questionnaires were used to obtain patients' views of the follow-up program. RESULTS: Of 96 study patients, 51% visited the NLC once or twice. These patients were younger (P<0.001) and had lower Acute Physiology and Chronic Health Evaluation II (P=0.017) compared with those who did not visit the clinic. The most common reason for not visiting the clinic was not enough strength, chiefly physical. In the evaluation, patients answered that they received advice and information, an opportunity to talk, increased knowledge and re-evaluated memories and experiences from the ICU stay. Patients appreciated the follow-up and expressed gratitude to the competent and obliging staff. CONCLUSION: The current follow-up program, adjusted to individual patients' conditions and needs in terms of different types of contacts and continuity, was found to be of great value. Effects of the program other than the patient perspective are also relevant to evaluate.

The influence of ionic strength and pH on the aggregation properties of zinc-free insulin studied by static and dynamic laser light scattering.

The aggregation properties of zinc-free insulin have been studied using static and dynamic light scattering. The aggregation has been investigated as a function of three parameters, the concentration of sodium chloride (in the range 10-100 mM), the pH value (in the range pH 7.5-10.5), and the insulin concentration (1.8-13.4 mg/mL). The measured homodyne autocorrelation function was used to determine the apparent mean hydrodynamic diameter as well as the apparent weight-averaged molar mass of the insulin species in solution. A method of data analysis was employed, which allows the separation of light scattering contributions from the insulin oligomers and from irrelevant macromolecules and possible impurities present in the sample solutions. Also, a simple phenomenological equilibrium model describing the association of oligomers of insulin is presented. One aspect of this model is that it makes it possible to determine weight average molar masses corrected for virial effects on the Rayleigh ratio. This was necessary because virial effects cannot be isolated and corrected for by dilution since this would change the equilibrium distribution of oligomers. The basis of the model is a positive contribution to Gibbs free energy from charge repulsion depending on the protein charge and the number of monomers in the oligomers, and an assumed constant negative contribution to Gibbs free energy arising from either an entropic gain or hydrogen bonding upon association. The equilibrium model gives a good description of both the apparent weight average molar masses and the apparent hydrodynamic diameters, when the effect of the insulin concentration is taken into account by including virial effects arising from charge-charge repulsion (Donnan effect). The result shows that the association of insulin as a function of pH and ionic strength can be described by an effective charge equal to the charge derived from proton titration reduced by the number of sodium ions binding to insulin. At the lowest pH and highest salt concentration (pH 7.5, 100 mM NaCl, 12 mg/mL insulin), the weight average molar mass is close to that of the hexamer, and at the highest pH and lowest salt concentration (pH 10.5, 10 mM NaCl, 1.9 mg/mL), the weight average molar mass is close to that of the monomer. In all cases, however, a distribution of oligomers is present with a relative Gaussian width of about 30%.(ABSTRACT TRUNCATED AT 400 WORDS)

Indirect determination of traces of thiosulphate by differential-pulse polarography.

Two methods are reported for the indirect determination of thiosulphate down to ca. 0.02 microg/ml by differential-pulse polarography. Both methods involve prior oxidation of thiosulphate with iodine, either in acidic medium to tetrathionate or in alkaline medium to sulphate, whereby ultimately one and eight equivalents of iodate are obtained, respectively. The concentration of iodate in the resulting solution is then measured by differential-pulse polarography under optimum conditions. The average recovery for each method amounted to 100.1%, and the relative standard deviations were 1.3 and 1.4% for the two methods.