Effects of slow- v. fast-digested protein supplementation combined with mixed power training on muscle function and functional capacities in older men.

Ageing leads to a progressive loss of muscle function (MF) and quality (MQ: muscle strength (MS)/lean muscle mass (LM)). Power training and protein (PROT) supplementation have been proposed as efficient interventions to improve MF and MQ. Discrepancies between results appear to be mainly related to the type and/or dose of proteins used. The present study aimed at determining whether or not mixed power training (MPT) combined with fast-digested PROT (F-PROT) leads to greater improvements in MF and MQ in elderly men than MPT combined with slow-digested PROT (S-PROT) or MPT alone. Sixty elderly men (age 69 (sd 7) years; BMI 18-30 kg/m2) were randomised into three groups: (1) placebo + MPT (PLA; n 19); (2) F-PROT + MPT (n 21) and (3) S-PROT + MPT (n 20) completed the intervention. LM, handgrip and knee extensor MS and MQ, functional capacity, serum metabolic markers, skeletal muscle characteristics, dietary intake and total energy expenditure were measured. The interventions consisted in 12 weeks of MPT (3 times/week; 1 h/session) combined with a supplement (30 g:10 g per meal) of F-PROT (whey) or S-PROT (casein) or a placebo. No difference was observed among groups for age, BMI, number of steps and dietary intake pre- and post-intervention. All groups improved significantly their LM, lower limb MS/MQ, functional capacity, muscle characteristics and serum parameters following the MPT. Importantly, no difference between groups was observed following the MPT. Altogether, adding 30 g PROT/d to MPT, regardless of the type, does not provide additional benefits to MPT alone in older men ingesting an adequate (i.e. above RDA) amount of protein per d.

Quantitative proteomic analysis of marine biofilms formed by filamentous cyanobacterium.

Cyanobacterial molecular biology can identify pathways that affect the adhesion and settlement of biofouling organisms and, consequently, obtain novel antifouling strategies for marine applications. Proteomic analyses can provide an essential understanding of how cyanobacteria adapt to different environmental settings. However, only a few qualitative studies have been performed in some cyanobacterial strains. Considering the limited knowledge about protein expression in cyanobacteria in different growing conditions, a quantitative proteomic analysis by LC-MS/MS of biofilm cells from a filamentous strain was performed. Biofilms were also analysed through standard methodologies for following cyanobacterial biofilm development. Biofilms were formed on glass and perspex at two relevant hydrodynamic conditions for marine environments (average shear rates of 4 s-1 and 40 s-1). Biofilm development was higher at 4 s-1 and no significant differences were found between surfaces. Proteomic analysis identified 546 proteins and 41 were differentially expressed. Differences in protein expression were more noticeable between biofilms formed on glass and perspex at 4 s-1. When comparing biofilms formed on different surfaces, results suggest that biofilm development may be related to the expression of several proteins like a beta-propeller domain-containing protein, chaperone DnaK, SLH domain-containing proteins, an OMF family outer membrane protein, and/or additional uncharacterized proteins. Regarding the hydrodynamic effect, biofilm development can be related to SOD enzyme expression, to proteins related to photosynthetic processes and to a set of uncharacterized proteins with calcium binding domains, disordered proteins, and others involved in electron transfer activity. Studies that combine distinct approaches are essential for finding new targets for antibiofilm agents. The characterisation performed in this work provides new insights into how shear rate and surface affect cyanobacterial biofilm development and how cyanobacteria adapt to these different environmental settings from a macroscopic standpoint to a proteomics context.

Calibration of parameters in Dynamic Energy Budget models using Direct-Search methods.

Dynamic Energy Budget (DEB) theory aims to capture the quantitative aspects of metabolism at the individual level, for all species. The parametrization of a DEB model is based on information obtained through the observation of natural populations and experimental research. Currently the DEB toolbox estimates these parameters using the Nelder-Mead Simplex method, a derivative-free direct-search method. However, this procedure presents some limitations regarding convergence and how to address constraints. Framed in the calibration of parameters in DEB theory, this work presents a numerical comparison between the Nelder-Mead Simplex method and the SID-PSM algorithm, a Directional Direct-Search method for which convergence can be established both for unconstrained and constrained problems. A hybrid version of the two methods, named as Simplex Directional Direct-Search, provides a robust and efficient algorithm, able to solve the constrained optimization problems resulting from the parametrization of the biological models.

Muscle adaptation in response to a high-intensity interval training in obese older adults: effect of daily protein intake distribution.

BACKGROUND: Aging is associated with declines in muscle mass, strength and quality, leading to physical impairments. An even protein distribution in daily meals has recently been proposed along with adequate total protein intake as important modulators of muscle mass. In addition, due to its short duration, high-intensity interval training (HIIT) has been highlighted as a promising intervention to prevent physical deterioration. However, the interaction between daily protein intake distribution and HIIT intervention in elderlies remain unknown. OBJECTIVE: To investigate muscle adaptation following HIIT in older adults according to daily protein intake distribution. METHODS: Thirty sedentary obese subjects who completed a 12-week elliptical HIIT program were matched [criteria: age (± 2 years), sex, BMI (± 2 kg/m2)] and divided a posteriori into 2 groups according to the amount of protein ingested at each meal: < 20 g in at least one meal (P20-, n = 15, 66.8 ± 3.7 years) and ≥ 20 g in each meal (P20+, n = 15, 68.1 ± 4.1 years). Body composition, functional capacity, muscle strength, muscle power, physical activity level, and nutritional intakes were measured pre- and post-intervention. A two way repeated ANOVA was used to determine the effect of the intervention (HIIT) and protein distribution (P20- vs P20+, p < 0.05). RESULTS: No difference was observed at baseline between groups. Following the HIIT intervention, we observed a significant decrease in waist and hip circumferences and improvements in functional capacities in both P20- and P20 + group (p < 0.05). However, no protein distribution effect was observed. CONCLUSION: A 12-week HIIT program is achievable and efficient to improve functional capacities as well as body composition in obese older adults. However, consuming at least 20 g of proteins in every meal does not further enhance muscle performance in response to a 12-week HIIT intervention.

[The Confusion Assessment Method: Transcultural adaptation of a French version]. / Adaptation transculturelle francophone de la Confusion Assessment Method.

INTRODUCTION: The Confusion Assessment Method (CAM) is a validated key tool in clinical practice and research programs to diagnose delirium and assess its severity. There is no validated French version of the CAM training manual and coding guide (Inouye SK). The aim of this study was to establish a consensual French version of the CAM and its manual. METHODS: Cross-cultural adaptation to achieve equivalence between the original version and a French adapted version of the CAM manual. RESULTS: A rigorous process was conducted including control of cultural adequacy of the tool's components, double forward and back translations, reconciliation, expert committee review (including bilingual translators with different nationalities, a linguist, highly qualified clinicians, methodologists) and pretesting. A consensual French version of the CAM was achieved. CONCLUSION: Implementation of the CAM French version in daily clinical practice will enable optimal diagnosis of delirium diagnosis and enhance communication between health professionals in French speaking countries. Validity and psychometric properties are being tested in a French multicenter cohort, opening up new perspectives for improved quality of care and research programs in French speaking countries.

Coevolution between flight morphology, vertical stratification and sexual dimorphism: what can we learn from tropical butterflies?

Occurrence patterns are partly shaped by the affinity of species with habitat conditions. For winged organisms, flight-related attributes are vital for ecological performance. However, due to the different reproductive roles of each sex, we expect divergence in flight energy budget, and consequently different selection responses between sexes. We used tropical frugivorous butterflies as models to investigate coevolution between flight morphology, sex dimorphism and vertical stratification. We studied 94 species of Amazonian fruit-feeding butterflies sampled in seven sites across 3341 ha. We used wing-thorax ratio as a proxy for flight capacity and hierarchical Bayesian modelling to estimate stratum preference. We detected a strong phylogenetic signal in wing-thorax ratio in both sexes. Stouter fast-flying species preferred the canopy, whereas more slender slow-flying species preferred the understorey. However, this relationship was stronger in females than in males, suggesting that female phenotype associates more intimately with habitat conditions. Within species, males were stouter than females and sexual dimorphism was sharper in understorey species. Because trait-habitat relationships were independent from phylogeny, the matching between flight morphology and stratum preference is more likely to reflect adaptive radiation than shared ancestry. This study sheds light on the impact of flight and sexual dimorphism on the evolution and ecological adaptation of flying organisms.

Controlling the atomic distribution in PtPd nanoparticles: thermal stability and reactivity during NO abatement.

In situ X-ray absorption spectroscopy and mass spectrometry measurements were employed to simultaneously probe the atom specific short range order and reactivity of Pd and PtPd nanoparticles towards NO decomposition at 300 °C. The nanoparticles were synthesized by a well controlled, eco-friendly wet chemical reduction of metal salts and later supported on activated carbon. Particularly for the bimetallic PtPd samples, distinct atomic arrangements were achieved using a seeding growth method, which allowed producing a random nanoalloy, or nanoparticles with Pt- or Pd-rich core. X-ray photoelectron spectroscopy, transmission electron microscopy, and X-ray diffraction provided additional insights on their electronic, morphological and long range order structural properties. The results revealed that the higher the thermal induced atomic migration observed within the nanoparticles during thermal treatments, the least were their reactivity for NO abatement.

Lactation performance of Holstein cows treated with 2 formulations of recombinant bovine somatotropin in a large commercial dairy herd in Brazil.

The objectives of this controlled study were to compare the effects of 2 different formulations of recombinant bovine somatotropin (rbST) on milk yield, milk composition (fat and protein), milk somatic cell count, and body condition score (BCS) among dairy cattle in a large commercial herd. Regulatory approved 500-mg zinc sesame oil base rbST (ZSO-rbST; Elanco Animal Health, Greenfield, IN) and vitamin E lecithin base rbST (VEL-rbST; LG Life Sciences, Seoul, South Korea) formulations were administered per the manufacturers' recommendations every 14 d over 17 injection cycles starting at 57 to 70 d of lactation (90 cows per rbST group). Control cows (n = 60) received no rbST. Somatotropin-treated animals (VEL-rbST and ZSO-rbST combined) had increased average milk yield and protein percentage and lower average BCS compared with control cows. For primiparous cows, average milk yield was 37.75 kg/d with the ZSO-rbST treatment and 35.72 kg/d with the VEL-rbST treatment. For multiparous cows, average milk yield was 40.13 kg/d with the ZSO-rbST treatment and 38.81 kg/d with the VEL-rbST treatment. There were no differences in milk fat percentage between VEL-rbST and ZSO-rbST treatments, but milk protein content was greater with VEL-rbST treatment than with ZSO-rbST treatment. Nonetheless, cows treated with ZSO-rbST yielded more kilograms of fat and protein per day than cows treated with VEL-rbST. No significant differences in BCS were found between both rbST treatment groups. The differential increase in milk yield between cows treated with ZSO-rbST and VEL-rbST was driven by rbST response differences both within the 14-d cycle and throughout the 17 injection cycles. The cows treated with VEL-rbST demonstrated a more variable 14-d milk yield response curve, with more pronounced valleys between injections compared with the ZSO-rbST formulation. In addition, only the ZSO-rbST treatment was effective in modifying the lactation persistency compared with control cows. Compared with the VEL-rbST formulation, the ZSO-rbST formulation yielded more kilograms of milk, fat, and protein with less milk variation throughout the seventeen 14-d lactation cycles for both primiparous and multiparous cows.

Polyandrous behavior in an overexploited giant South American turtle (Podocnemis expansa) population in Central Amazon, Brazil.

The aim of the present study was to investigate the reproductive behavior of the giant Amazon River turtle (Podocnemis expansa) in the Amazon. This was carried out by estimating the degree of polymorphism in five DNA microsatellites in a sample of 359 hatchlings from 12 nests in the Mamirauá Sustainable Development Reserve in the municipality of Tefé, state of Amazonas, Brazil. An analysis of allele frequency and variation in the five microsatellite loci allowed for determination of multiple paternity in all nests sampled. Contributions of at least four male turtles to one nest, three male turtles to six nests, and two male turtles to five nests were identified. Knowledge on the reproductive behavior of P. expansa can assist in the establishment of management and conservation strategies for the population in the Mamirauá Reserve.

Thyroid Function in Human Obesity: Underlying Mechanisms.

Obesity is associated with several metabolic and endocrine disorders; and changes in plasma concentrations, secretion patterns, and clearance of various hormones are observed in obese patients. In this context, recent research has shown that overweight can influence the function of the thyroid gland, usually leading to increased thyrotropin concentrations and changes in the ratio between the hormones triiodothyronine and thyroxine, though within the normal range. The etiology of these changes is still unclear; however, several mechanisms have been proposed including the adaptive process to increase energy expenditure, hyperleptinemia, changes in the activity of deiodinases, the presence of thyroid hormones resistance, chronic low-grade inflammation, and insulin resistance. Although the clinical implications have not been clarified, studies suggest that these changes in the thyroid function of obese individuals may contribute to the worsening of metabolic complications and the development of diseases in the thyroid gland.

Pharmacological and Toxicological Studies of Essential Oil of Lavandula stoechas subsp. luisieri.

The present study was carried out to evaluate the chemical and pharmacological properties of the essential oil of Lavandula stoechas subsp. luisieri, which is a spontaneous shrub widespread in Alentejo (Portugal). Oxygenated monoterpenes, such as 1,8-cineole, lavandulol, and necrodane derivatives, are the main components of essential oil. It revealed important antioxidant activity with a high ability to inhibit lipid peroxidation and showed an outstanding effect against a wide spectrum of microorganisms, such as gram-positive and gram-negative bacteria and pathogenic yeasts. The analgesic effect studied in rats was dose dependent, reaching a maximum of 67 % at 60 min with the dose of 200 mg/kg and the anti-inflammatory activity with this dose caused an inhibition in carrageenan-induced rat paw oedema (83 %) that is higher than dexamethasone 1 mg/Kg (69 %). Besides, animals exhibited normal behaviour after essential oil administration, revealing low toxicity. The essential oil of L. luisieri from Alentejo presents important pharmacological properties and low toxicity, and is a promised candidate to be used as a food supplement or in pharmaceutical applications.

Hydrodynamic profile of young swimmers: changes over a competitive season.

The aim of this study was to analyze the changes in the hydrodynamic profile of young swimmers over a competitive season and to compare the variations according to a well-designed training periodization. Twenty-five swimmers (13 boys and 12 girls) were evaluated in (a) October (M1); (b) March (M2); and (c) June (M3). Inertial and anthropometrical measures included body mass, swimmer's added water mass, height, and trunk transverse surface area. Swimming efficiency was estimated by the speed fluctuation, stroke index, and approximate entropy. Active drag was estimated with the velocity perturbation method and the passive drag with the gliding decay method. Hydrodynamic dimensionless numbers (Froude and Reynolds numbers) and hull velocity (i.e., speed at Froude number = 0.42) were also calculated. No variable presented a significant gender effect. Anthropometrics and inertial parameters plus dimensionless numbers increased over time. Swimming efficiency improved between M1 and M3. There was a trend for both passive and active drag increase from M1 to M2, but being lower at M3 than at M1. Intra-individual changes between evaluation moments suggest high between- and within-subject variations. Therefore, hydrodynamic changes over a season occur in a non-linear fashion way, where the interplay between growth and training periodization explain the unique path flow selected by each young swimmer.

Aortic pulse wave velocity and HeartSCORE: improving cardiovascular risk stratification. a sub-analysis of the EDIVA (Estudo de DIstensibilidade VAscular) project.

BACKGROUND: HeartSCORE is a tool for assessing cardiovascular risk, basing its estimates on the relative weight of conventional cardiovascular risk factors. However, new markers of cardiovascular risk have been identified, such as aortic pulse wave velocity (PWV). The purpose of this study was to evaluate to what extent the incorporation of PWV in HeartSCORE increases its discriminative power of major cardiovascular events (MACE). METHODS AND RESULTS: This study is a sub-analysis of the EDIVA project, which is a prospective cohort, multicenter and observational study involving 2200 individuals of Portuguese nationality (1290 men and 910 women) aged between 18 and 91 years (mean 46.33 ± 13.76 years), with annual measurements of PWV (Complior). Only participants above 35 years old were included in the present re-analysis, resulting in a population of 1709 participants. All MACE - death, cerebrovascular accident, coronary accidents (coronary heart disease), peripheral arterial disease and renal failure - were recorded. During a mean follow-up period of 21.42 ± 10.76 months, there were 47 non-fatal MACE (2.1% of the sample). Cardiovascular risk was estimated in all patients based on the HeartSCORE risk factors. For the analysis, the refitted HeartSCORE and PWV were divided into three risk categories. The event-free survival at 2 years was 98.6%, 98.0% and 96.1%, respectively in the low-, intermediate- and high-risk categories of HeartSCORE (log-rank p < 0.001). The multi-adjusted hazard ratio (HR) per 1 - standard deviation (SD) of MACE was 1.86 (95% CI 1.37-2.53, p < 0.001) for PWV. The risk of MACE by tertiles of PWV and risk categories of the HeartSCORE increased linearly, and the risk was particularly more pronounced in the highest tertile of PWV for any category of the HeartSCORE, demonstrating an improvement in the prediction of cardiovascular risk. It was clearly depicted a high discriminative capacity of PWV even in groups of apparent intermediate cardiovascular risk. Measures of model fit, discrimination and calibration revealed an improvement in risk classification when PWV was added to the risk-factor model. The C statistics improved from 0.69 to 0.78 (adding PWV, p = 0.005). The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were also determined, and indicated further evidence of improvements in discrimination of the outcome when including PWV in the risk-factor model (NRI = 0.265; IDI = 0.012). CONCLUSION: The results clearly illustrate the benefits of integrating PWV in the risk assessment strategies, as advocated by HeartSCORE, insofar as it contributes to a better discriminative capacity of global cardiovascular risk, particularly in individuals with low or moderate cardiovascular risk.

SBS-managed high-peak-power nanosecond-pulse fiber-based master oscillator power amplifier.

We report on a compactly packaged Yb-doped fiber-based laser architecture featuring an actively pulse controlled, single-longitudinal-mode seeder and multistage amplifier chain terminated by a "folded" rod-type photonic crystal fiber. In this laser source, stimulated Brillouin scattering (SBS) is the power-limiting factor, but is managed by phase modulating the seeder with a pseudo-random noise signal. Pulse energy/peak power of ~2 mJ/1.5 MW at 10 kHz repetition rate are thus obtained within ~1.55 ns pulses of peak spectral brightness >20 kW cm(-2) sr(-1) Hz(-1).

Handgrip strength predicts survival and is associated with markers of clinical and functional outcomes in advanced cancer patients.

PURPOSE: Handgrip strength (HGS) has been shown to predict survival and is associated with changes in body composition, nutritional status, inflammation, and functional ability in several chronic disease conditions. Whether similar relationships exist between HGS and clinical outcomes in patients with advanced cancer are currently unknown. We evaluated the association between HGS and survival as well as several key markers of body composition (e.g., sarcopenia), subjective performance measures (e.g., quality of life), and muscle strength (e.g., isokinetic torque of the quadriceps) in patients with advanced forms of non-small cell lung and gastrointestinal cancers. METHODS: A consecutive cohort of 203 patients with advanced cancer was enrolled and categorized into three HGS percentiles (e.g., ≥50th, 25th, and ≤10th) according to published normative values. Multivariate regression analyses were used to test for independent associations between HGS and survival, sarcopenia, quality of life (QoL), and lower extremity muscle strength as well as key biological markers (e.g., hemoglobin, albumin, and C-reactive protein) while controlling for age, gender, cancer diagnosis, treatment (chemotherapy/radiotherapy), medications, and time from diagnosis to assessment. RESULTS: When compared to HGS ≥50th, patients in the HGS ≤10th percentile had lower BMI (B, -2.5 kg/m(2); 95% CI, -4.5 to -0.45), shorter survival (hazard ratio, 3.2; 2.0-5.1), lower hemoglobin (-19.70 g/L; -27.28 to -12.13) and albumin (-4.99 g/L; -7.85 to -2.13), greater occurrence of sarcopenia (odds ratio, 9.53; 1.95-46.55), lower isokinetic torque of the quadriceps at both 60°/s (-30.6 Nm; -57.9 to -3.3) and 120°/s (-25.1 Nm; -46.4 to -3.7), lower QoL (-1.6 on McGill Quality of Life Questionnaire scale; -2.5 to -0.6), higher levels of fatigue (18.8 on Brief Fatigue Inventory scale; 4.7 -32.9), poorer performance status (0.75 on Eastern Cooperative Oncology Group Performance Status scale; 0.34-1.15), lower fat mass (-7.4 kg; -14.4 to -0.5), and lower lean body mass (-6.5 kg; -10.3 to -2.8). CONCLUSIONS: HGS is independently associated with survival and important biological, functional, and quality of life characteristics in advanced cancer patients. Patients presenting with very low percentiles with respect to their handgrip assessment may require timely referral to supportive and/or palliative care services.

Association of social network and social support with health-related quality of life and fatigue in long-term survivors of Hodgkin lymphoma.

PURPOSE: As the number of survivors of Hodgkin's lymphoma (HL) increases, there has been a growing interest in long-term treatment-related side effects and their impact on the quality of life (QoL). The aim of this study was to assess the association of social network and social support with the QoL and fatigue among long-term HL survivors. METHODS: A total of 200 HL survivors were included. The generic Short Form-12 (SF-12) questionnaire, the QoL cancer survivor's questionnaire (QOL-CS), and the Multidimensional Fatigue Inventory were used to assess QoL and fatigue. Social network and social support were evaluated with the Social Support Survey. RESULTS: Social network and all social support measures were favorably associated with two or more SF-12 scales, mainly with physical functioning and the mental health scales. Social network and social support dimensions were also associated with better QOL-CS scores. Affective support, informational support, positive interaction, and emotional support were associated with less fatigue. CONCLUSIONS: Both social network and social support are associated with better QoL and lower levels of fatigue in HL survivors. This information may be useful to health professionals and community organizations in implementing effective interventions to improve these patients' quality of life.

Lack of association of tumor-associated macrophages with clinical outcome in patients with classical Hodgkin's lymphoma.

BACKGROUND: A recent study demonstrated that an increased number of CD68+ macrophages were correlated with primary treatment failure, shortened progression-free survival (PFS) and disease-specific survival (DSS) in patients with classical Hodgkin's lymphoma (cHL). PATIENTS AND METHODS: The aim of the present study was to verify the relationship between the number of CD68+ and CD163+ macrophages with clinical outcomes in a cohort of 265 well-characterized patients with cHL treated uniformly with the standard doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy regimen. Two pairs of hematopathologists carried out independent pathological evaluations of tissue microarray slides. RESULTS: There were no associations between clinical characteristics and the expression of CD68 or CD163. However, higher levels of CD68 and CD163 expression were correlated with the presence of Epstein-Barr virus-positive Hodgkin tumor cells (P = 0.01 and 0.037, respectively). The expression of CD68 or CD163 was not associated with either the PFS or the DSS. CONCLUSION: CD68 and CD163 expression require further evaluation before their use can be recommended for prognostic stratification of patients with cHL.

Postprandial hyperaminoacidaemia overcomes insulin resistance of protein anabolism in men with type 2 diabetes.

AIMS/HYPOTHESIS: Although protein is usually ignored when considering insulin resistance, we have shown resistance of protein concurrent with glucose metabolism in men with type 2 diabetes during a hyperinsulinaemic clamp at euglycaemia and fasting aminoacidaemia. We hypothesised that this resistance is even worse during conditions that simulate the postprandial state, when anabolism should be maximal. METHODS: Eight overweight and obese men with type 2 diabetes underwent a hyperinsulinaemic-hyperglycaemic (8 mmol/l) clamp, first with plasma amino acids at postabsorptive (Hyper-2) then at postprandial concentrations (Hyper-3). Whole-body protein kinetics were assessed using L-: [1-(13)C]leucine. Hyper-2 results were compared with those of diabetic men whose plasma glucose was lowered to 5.5 mmol/l and fasting aminoacidaemia maintained during the hyperinsulinaemic clamp (Hyper-1). RESULTS: In Hyper-2 vs Hyper-1 clamps, leucine flux (2.99 ± 0.16 vs 2.62 ± 0.06 µmol kg [fat-free mass (FFM)](-1) min(-1)), rates of synthesis (2.31 ± 0.15 vs 1.98 ± 0.06) and breakdown (2.38 ± 0.16 vs 2.00 ± 0.07) were higher (p < 0.05), but leucine oxidation and net balance did not differ. In Hyper-3 vs Hyper-2 clamps, leucine flux and synthesis and oxidation rates increased markedly as did net balance (0.84 ± 0.09 vs -0.07 ± 0.04 µmol [kg FFM](-1) min(-1), p < 0.0001). CONCLUSIONS/INTERPRETATION: In type 2 diabetic men, insulin resistance of protein metabolism is of the same magnitude at 8 vs 5.5 mmol/l, but turnover rates are higher with hyperglycaemia. Contrary to our hypothesis, sustained postprandial-level hyperaminoacidaemia stimulated positive net protein balance comparable with that previously found in lean non-diabetic men. This was sufficient to overcome the insulin resistance of protein anabolism.

Hyperaminoacidaemia at postprandial levels does not modulate glucose metabolism in type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Hyperaminoacidaemia attenuates glucose disposal during hyperinsulinaemic clamps in healthy lean individuals, an effect thought to be mediated by negative feedback on insulin signalling, downstream of the mammalian target of rapamycin (mTOR) signalling pathway. This has been interpreted as amino acids causing insulin resistance in healthy people, and contributing to it in type 2 diabetes. However, the effect of hyperaminoacidaemia on glucose disposal in type 2 diabetic individuals remains to be determined. METHODS: Eight obese men with type 2 diabetes underwent a two-step hyperinsulinaemic-hyperglycaemic (8 mmol/l) clamp, first with amino acids at postabsorptive concentrations, followed by postprandial concentrations. Whole-body glucose turnover was assessed using D: -[3-(3)H]glucose. Vastus lateralis biopsies were obtained at baseline and during each step of the clamp to determine the phosphorylation states of AKT, mTOR, ribosomal protein (rp) S6, and insulin receptor substrate (IRS)-1. RESULTS: Rates of glucose infusion (1.30 ± 0.19 vs 1.15 ± 0.13 mmol/min), endogenous glucose production (0.48 ± 0.06 vs 0.53 ± 0.05 mmol/min) and disposal (1.24 ± 0.17 vs 1.17 ± 0.14 mmol/min) did not differ between postabsorptive and postprandial amino acid concentrations (p > 0.05). Whereas phosphorylation of AKT(Ser473), AKT(Thr308) mTOR(Ser2448) and rpS6(Ser235/236) increased (p < 0.05) with elevated amino acids, that of IRS-1(Ser636/639) and IRS-1(Ser1101) did not change. CONCLUSIONS/INTERPRETATION: Postprandial circulating amino acid concentrations do not worsen the already attenuated glucose disposal in hyperglycaemic type 2 diabetic men, and cell-signalling events are consistent with this. Our results do not support recommendations to restrict dietary protein in type 2 diabetes.

Budesonide/formoterol vs. salmeterol/fluticasone in COPD: a systematic review and adjusted indirect comparison of pneumonia in randomised controlled trials.

AIMS: This analysis was designed to provide a comparison between budesonide/formoterol and salmeterol/fluticasone for the relative incidence of pneumonia adverse events, pneumonia serious adverse events and pneumonia-related mortality in patients being treated for chronic obstructive pulmonary disease. METHODS: An initial literature search revealed no suitable head-to-head trials between budesonide/formoterol and salmeterol/fluticasone and therefore a systematic review was conducted to find randomised controlled trials providing data for input into an adjusted indirect comparison of the two combination treatments using placebo as a common comparator. The Bucher adjusted indirect comparison method was used to calculate odds ratios and 95% confidence intervals. RESULTS: Eight salmeterol/fluticasone trials and four budesonide/formoterol trials were identified as being relevant for the analyses. The proportion of patients experiencing a pneumonia adverse event was significantly lower with budesonide/formoterol than salmeterol/fluticasone (odds ratio, 0.47; 95% confidence interval, 0.28-0.80). The proportion of patients experiencing a pneumonia serious adverse event was also significantly lower with budesonide/formoterol than salmeterol/fluticasone (odds ratio, 0.41; 95% confidence interval, 0.19-0.86). However, there were too few events to draw any firm conclusions on pneumonia-related mortality. CONCLUSIONS: The results of the indirect comparison support the hypothesis that budesonide/formoterol is associated with fewer pneumonia events than salmeterol/fluticasone in chronic obstructive pulmonary disease. The limitations of the analysis are that the results from a single study, TORCH, have a large bearing on the overall findings of the analysis, and that there is heterogeneity in the length and the dosing of the included studies, although it does not appear that heterogeneity affected the reported results. Another important limitation is the lack of predefined diagnostic standards for pneumonia in these studies.