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Objective: The purpose of this study was to test the hypothesis that perfluorinated alkylate substance (PFAS) exposures are associated with body weight increases in a dietary intervention study. Methods: In the DioGenes trial, adults with obesity first lost at least 8% of their body weight and then completed at least 26 weeks on a specific diet. Concentrations of five major PFASs were assessed in plasma samples from study baseline. Results: In 381 participants with complete data, plasma concentrations averaged 2.9 ng/mL and 1.0 ng/mL for perfluorooctanoic acid (PFOA) and perfluorohexanesulfonic acid (PFHxS), respectively. A doubling in plasma PFOA was associated with an increase in weight at 26 weeks by 1.50 kg (95% CI: 0.88–2.11), with an increase of 0.91 kg (95% CI: 0.54–1.27) for PFHxS, independent of diet groups and sex. Associations for other PFASs were in the same direction and significant, although not after adjustment for PFOA and PFHxS. Weight changes associated with elevated PFAS exposures were similar to or larger than average changes ascribed to the different diet groups. Conclusions: Elevated plasma concentrations of PFOA and PFHxS were associated with increased weight gain that exceeded those related to the diets. Obesogenic PFASs may cause weight gain and thus contribute to the obesity pandemic.

Background: This study tested the hypothesis that training reduces resting sympathetic activity and improves baroreflex control in both hypertensive and normotensive men but reduces blood pressure only in hypertensive men.Methods: Middle-aged/older un-medicated stage-1 hypertensive males (mean age 55±3 yrs; n=13) and normotensive controls (mean age 60±5 yrs; n=12) participated in 8 weeks of supervised high-intensity interval spinning training. Before and after training, muscle sympathetic nerve activity (MSNA) and blood pressure were measured at rest and during a sympatho-excitatory cold pressor test (CPT). Based on the measurements, baroreceptor sensitivity and baroreceptor threshold were calculated.Results: Resting MSNA and baroreceptor sensitivity were similar for the hypertensive and the normotensive groups. Training lowered MSNA (ppp>0.05) alter the MSNA or blood pressure response to CPT or increase baroreceptor sensitivity but reduced (pConclusion: The dissociation between the training induced changes in resting MSNA, lack of change in baroreflex sensitivity and the change in blood pressure, suggests that MSNA is not a main cause of the blood pressure reduction with exercise training in un-medicated middle-aged/older men.

Background: Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID-19. Few studies have investigated regulators of iron metabolism in the context of COVID-19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community-acquired pneumonia (CAP) caused by SARS-CoV-2 compared to CAP caused by bacteria or influenza virus in hospitalized patients.Methods: A cross-sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C-reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin.Results: Median (IQR) hepcidin was higher in SARS-CoV-2 with 143.8 (100.7-180.7) ng/mL compared to bacterial and influenza infection with 78.8 (40.1-125.4) and 53.5 (25.2-125.8) ng/mL, respectively. The median ferritin level was more than 2-fold higher in patients with SARS-CoV-2 compared to the other etiologies (pConclusion: Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS-CoV-2 compared to those infected with bacteria indicate alterations in iron metabolism in patients with SARS-CoV-2 infection.

Objective: Several tissues produce and release interleukin-6 (IL-6) in response to beta2-adrenergic stimulation with selective agonists (beta2-agonists). Moreover, exercise stimulates muscle IL-6 production, but whether beta2-agonists regulate skeletal muscle production and release of IL-6 in humans, in association with exercise remains to be clarified. Thus, we investigated leg IL-6 release in response to beta2-agonist salbutamol in lean young men at rest and in recovery from resistance exercise.Design: The study employed a randomized controlled crossover design, where 12 men ingested either salbutamol (16 mg) or placebo for 4 days, followed by the last dose (24 mg) administered 1½ h before exercise. Arterial and femoral venous plasma IL-6 as well as femoral artery blood flow was measured before and ½-5 h in recovery from quadriceps muscle resistance exercise. Furthermore, vastus lateralis muscle biopsies were collected ½ and 5 h after exercise for determination of mRNA levels of IL-6 and Tumor Necrosis Factor (TNF)-α.Results: Average leg IL-6 release was 1.7-fold higher (p=0.01) for salbutamol than placebo, being 138±76 and 79±66 pg∙min-1 (mean±SD) for salbutamol and placebo, respectively, but IL-6 release was not significantly different between treatments within specific sampling points at rest and after exercise. Muscle IL-6 mRNA was 1.5 and 1.7-fold higher (p=0.001) for salbutamol than placebo ½ and 5 h after exercise, respectively, whereas no significant treatment differences were observed for TNF-α mRNA.Conclusions: Beta2-adrenergic stimulation with high doses of the selective beta2-agonist salbutamol, preceeded by 4 consecutive daily doses, induces transcription of IL-6 in skeletal muscle in response to resistance exercise and increases muscle IL-6 release in lean individuals.

Rodent studies highlight enhancement of glucose tolerance and insulin sensitivity as potential clinically relevant effects of chronic beta2-agonist treatment. However, the doses administered to rodents are incomparable with the therapeutic doses used for humans. Thus, we investigated the physiological effects of prolonged beta2-agonist treatment at inhaled doses resembling those used in respiratory diseases on insulin-stimulated whole-body glucose disposal and putative mechanisms in skeletal muscle and adipose tissue of healthy men. Utilizing a randomized placebo-controlled parallel-group design, we assigned 21 healthy men to 4 weeks daily inhalation of terbutaline (TER; 4 mg×day-1 , n = 13) or placebo (PLA, n = 8). Before and after treatments, we assessed subjects' whole-body insulin-stimulated glucose disposal and body composition, and collected vastus lateralis muscle and abdominal adipose tissue biopsies. Glucose infusion rate increased by 27% (95% CI: 80 to 238 mg×min-1 , P = 0.001) in TER, whereas no significant changes occurred in PLA (95% CI: -37 to 195 mg×min-1 , P = 0.154). GLUT4 content in muscle or adipose tissue did not change nor hexokinase II content or markers of mitochondrial volume in muscle. Change in lean mass was associated with change in glucose infusion rate in TER (r = 0.59, P = 0.03). Beta2-agonist treatment in close-to-therapeutic doses may augment whole-body insulin-stimulated glucose disposal in healthy young men and part of the change is likely explained by muscle hypertrophy. These findings highlight the therapeutic potential of beta2 -agonists for improving insulin sensitivity.

Children with weight-for-age z-score (WAZ)

We combined game activity analyses with skeletal muscle phenotypes and comprehensive physiological testing to elucidate factors of importance for physical performance in elite women's football. GPS-data from an experimental game, sprint and endurance testing, and muscle tissue analysis of metabolic enzyme activity, protein expression and fiber type composition were completed for international top-level women players (n = 20; age; 23 ± 4 yrs, height; 166 ± 10 cm, weight; 60 ± 8 kg; VO2max ; 51 ± 6 ml/min/kg). Muscle monocarboxylate transporter 4 (MCT4) protein expression explained 46% of the variance in total game distance, while the ability to maintain high-intensity running (HIR) during the final 15 min of the game correlated to myosin heavy chain 1 (MHCI) and Na+-K+ ATPase β1, FXYD1 (phospholemman) and superoxide dismutase 2 (SOD2) protein expression (range: r = 0.51-0.71; all p < 0.05). Total HIR distance correlated with (MHCIIa) protein expression (r = 0.51; p < 0.05), while muscle Na+/H+ exchanger 1 (NHE1) protein explained 36% of the variance in game sprint distance (p < 0.05). Total game accelerations (actions >4 m/s2) correlated with platelet endothelial cell adhesion molecule (PECAM-1) protein expression (r = 0.51; p < 0.05), while concentric knee flexor strength explained 42-62% of the variance in intense decelerations (>4 m/s2). In conclusion, for elite women players' game endurance performance and resistance to end-game fatigue were affected by monocarboxylate transporter expression and myosin heavy chain profile. HIR was also correlated to ion transporter expression and muscle antioxidative capacity. Finally, the importance of functional strength and measures of muscle vascularization in relation to total game decelerations and accelerations, respectively, illustrates the complex physiological demands in elite women's football.

This study aimed to determine and compare the perception, painfulness, and usability of the minimally invasive Dried Blood Spot (DBS) collections from fingertip vs. upper arm from different athlete populations: males and females representing sports dependent on hand/arm, sports less dependent on hand/arm and para-athletes. To accomplish this, 108 national level athletes from Denmark were recruited (♀ = 49, ♂ = 59, 25 ± 6 years; mean±SD) and 11 Doping Control Officers (DCOs) collected manual fingerprick DBS (HemaSpot HF) and automated upper-arm DBS (Tasso-M20) from each athlete. Athletes and DCOs responded to questionnaires regarding the perception of sample collection procedures. On a 0-10 scale, the athletes reported a low pain score and a very good general experience for both sampling sites but following upper-arm DBS collection the associated pain was rated lower (-0.4 ± 1.6, p < 0.05) and the general experience rated better (+0.6 ± 2.3, p ≤ 0.001) than after the fingerprick DBS collection. The DCOs rated the general experience with the upper-arm DBS collection better (+1.6 ± 1.1, p ≤ 0.01) than the fingerprick DBS collection, partly because problems occurred more frequently during the DBS collection from the fingertip (28%) than from the upper arm (6%). In conclusion, it appears that DBS sampling is affiliated with minimal sensation of pain and is preferred by both DCOs and athletes, independent of gender and discipline, over conventional sample collection methods. Collection of DBS from the upper arm was preferred over fingerprick by both athletes and DCOs.

While misuse of testosterone esters is widespread in elite and recreational sports, direct detection of intact testosterone esters in doping control samples is hampered by the rapid hydrolysis by esterases present in the blood. With dried blood spot (DBS) as sample matrix, continued degradation of the esters is avoided due to inactivation of the hydrolase enzymes in dried blood. Here we have developed the method further for detection of testosterone esters in DBS with focus on robustness and applicability in doping control. To demonstrate the method's feasibility, DBS samples from men receiving two intramuscular injections of Sustanon® 250 (n = 9) or placebo (n = 10), were collected, transported and stored prior to analysis, to mimic a doping control scenario. The presented nanoLC-HRMS/MS method appeared reliable and suitable for direct detection of four testosterone esters (testosterone decanoate, isocaproate, phenylpropionate and propionate) after extraction from DBS. Sustanon® was detected in all subjects for at least five days, with detection window up to 14 days for three of the esters. Evaluation of analyte stability showed that while storage at room temperature is tolerated well for a few days, testosterone esters are highly stable (> 18 months) in DBS when stored in frozen conditions. Collectively, these findings demonstrate the applicability of DBS sampling in doping control for detection of steroid esters. The fast collection and reduced shipment costs of DBS compared to urine and standard blood samples, respectively, will allow more frequent and/or large-scale testing to increase detection and deterrence.

A series of five intramolecularly hydrogen-bonded arylhydrazone (aryl = phenol, p-nitrophenol, anisole, quinoline) derived molecular switches have been synthesized and characterized by NMR and HRMS techniques. It was found that the compounds exist as different isomers in solution. An investigation of both conformational and/or configurational changes of the azo-hydrazone compounds was carried out by 1D 1 H- and 13 C- spectra, 2D NOESY, COSY, HSQC, and HMBC techniques. It was found that these stimuli-responsive molecular switches exist mainly in the E form by intramolecularly hydrogen bonded between NH and the pyridine nitrogen at equilibrium. Deprotonation of the neutral E form yields the E' deprotonated isomer. Prediction of 13 C-NMR chemical shifts was achieved by DFT quantum mechanical calculations. Anions have traditionally been difficult to calculate correctly, so calculations of the anion using different functionals, basis sets, and solvent effects are also included. Deuterium isotope effects on the 13 C-NMR chemical shifts were employed in the assignments and furthermore utilized as indicators of intramolecular hydrogen bonding. Studies in various organic solvents including CDCl3 , CD3 CN, and DMSO-d6 were also performed aiming to monitor dynamic changes over several days. The effect of the hydrogen bonded solvents leads to Z forms.

We investigated whether immature reticulocyte fraction (IRF) and immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive biomarkers for low-dose recombinant human erythropoietin (rhEpo) treatment at sea-level (SL) and moderate altitude (AL) and whether multi (FACS) or single (Sysmex-XN) fluorescence flow cytometry is superior for IRF and IR/RBC determination. Thirty-nine participants completed two interventions, each containing a four-week baseline, a four-week SL or AL (2,230m) exposure and a four-week follow-up. During exposure, rhEpo (20 IU·kg-1) or placebo (PLA) was injected at SL (SLrhEpo n = 25, SLPLA n = 9) and AL (ALrhEpo n = 12, ALPLA n = 27) every second day for three weeks. Venous blood was collected weekly. Sysmex measurements revealed that IRF and IR/RBC was up to ~70% (P < 0.01) and ~190% (P < 0.001) higher in SLrhEpo than SLPLA during treatment and up to ~45% (P < 0.001) and ~55% (P < 0.01) lower post-treatment, respectively. Compared with ALPLA, IRF and IR/RBC was up to ~20% (P < 0.05) and ~45% (P < 0.001) lower post-treatment in SLrhEpo, respectively. In ALrhEpo, IRF and IR/RBC was up to ~40% (P < 0.05) and ~110% (P < 0.001) higher during treatment and up to ~25% (P < 0.05) and ~40% (P < 0.05) lower post-treatment, respectively, compared with ALPLA. Calculated thresholds provided ~90% sensitivity for both biomarkers at SL and 33% (IRF) and 66% (IR/RBC) at AL. Specificity was >99%. Single-fluorescence flow cytometry coefficient of variation was >twofold higher at baseline (P < 0.001), and provided larger or similar changes compared to multi-fluorescence, albeit with smaller precision. In conclusion, IRF and IR/RBC were sensitive and specific biomarkers for low-dose rhEpo misuse at SL and AL.

This study aimed to investigate sickle cell trait (SCT) associations with physical activity, markers of insulin secretion and resistance, and glucose among people living with HIV infection (PLWH), both antiretroviral therapy (ART) naïve and experienced, and HIV-uninfected adults. This was a cross-sectional study conducted in Mwanza, north-western Tanzania. We used data of 668 participants attained from two sub-studies of CICADA study. Mean age was 40 (SD 11.5) years, 402 (61.7 %) were females and 157 (24.1 %) had SCT. PLWH were 422 (64.7 %), of these, 80 (18.9 %) were on ART. People with SCT had higher risk of having an isolated β-cell dysfunction compared to those without SCT (RRR=1.82, CI: 1.10, 3.01, P=0.02). People with SCT but without HIV infection had lower average acceleration on the trunk longitudinal axis (ACCx) and higher level of self-reported physical activity. 30 min oral glucose tolerance test among PLWH on ART was higher in those with SCT compared to those without SCT. People with SCT are at higher risk of having β-cell dysfunction and those with SCT on ART are at more risk of developing diabetes. Future studies to investigate the interaction between SCT and HIV/ART on risk of diabetes should be considered.

KEY POINTS Patients with renal failure undergoing maintenance haemodialysis are associated with insulin resistance and protein metabolism dysfunction. Novel research suggests that disruption to the transmembrane protein linkage between the cytoskeleton and the extracellular matrix in skeletal muscle may contribute to reduced amino acid metabolism and insulin resistance in haemodialysis. ILK, PINCH1 and pFAKTyr397 were significantly decreased in haemodialysis compared to controls, whereas Rac1 and Akt2 showed no different between groups. Rac1 deletion in the Rac1 knockout model did not alter the expression of integrin-associated proteins. Phenylalanine kinetics were reduced in the haemodialysis group at 30 and 60 min post meal ingestion compared to controls; both groups showed similar levels of insulin sensitivity and β-cell function. Key proteins in the integrin-cytoskeleton linkage are reduced in haemodialysis patients, suggesting for the first time that integrin-associated proteins dysfunction may contribute to reduced phenylalanine flux without affecting insulin resistance in haemodialysis patients. ABSTRACT Muscle atrophy, insulin resistance and reduced muscle phosphoinositide 3-kinase-Akt signalling are common characteristics of patients undergoing maintenance haemodialysis (MHD). Disruption to the transmembrane protein linkage between the cytoskeleton and the extracellular matrix in skeletal muscle may contribute to reduced amino acid metabolism and insulin resistance in MHD patients. Eight MHD patients (age: 56 ± 5 years: body mass index: 32 ± 2 kg m-2 ) and non-diseased controls (age: 50 ± 2 years: body mass index: 31 ± 1 kg m-2 ) received primed continuous l-[ring-2 H5 ]phenylalanine before consuming a mixed meal. Phenylalanine metabolism was determined using two-compartment modelling. Muscle biopsies were collected prior to the meal and at 300 min postprandially. In a separate experiment, skeletal muscle tissue from muscle-specific Rac1 knockout (Rac1 mKO) was harvested to investigate whether Rac1 depletion disrupted the cytoskeleton-integrin linkage, allowing for cross-model examination of proteins of interest. ILK, PINCH1 and pFAKTyr397 were significantly lower in MHD (P

BackgroundSkeletal muscle wasting is often associated with insulin resistance. A major regulator of muscle mass is the transforming growth factor β (TGF-β) superfamily, including activin A, which causes atrophy. TGF-β superfamily ligands also negatively regulate insulin-sensitive proteins, but whether this pathway contributes to insulin action remains to be determined.MethodsTo elucidate if TGF-β superfamily ligands regulate insulin action we used an adeno-associated virus gene editing approach to overexpress the activin A inhibitor, follistatin (Fst288) in mouse muscle of lean and diet-induced obese mice. We determined basal and insulin-stimulated 2 deoxy-glucose uptake using isotopic tracers in vivo. Furthermore, to evaluate whether circulating Fst and activin A concentrations are associated with obesity, insulin resistance, and weight loss in humans we analysed serum from morbidly obese subjects before, 1 week, and 1 year after Roux-en-Y gastric bypass (RYGB).ResultsFst288 muscle overexpression markedly increased in vivo insulin-stimulated (but not basal) glucose uptake (+75%, pConclusionsWe here present evidence that Fst is a potent regulator of insulin action in muscle and in addition to AKT and p70S6K, we identify TBC1D1, TBC1D4 and PAK1 as Fst targets. A possible role for Fst in regulating glycemic control is suggested because circulating Fst more than doubled post RYGB surgery, a treatment that markedly improved insulin sensitivity. These findings demonstrate the therapeutic potential of inhibiting TGF-β superfamily ligands to improve insulin action and Fst’s relevance to muscle wasting associated insulin resistant conditions in mice and humans.

Running economy (RE) at a given submaximal running velocity is defined as oxygen consumption per minute per kg body mass. We investigated RE in a group of 12 male elite runners of national class. In addition to RE at 14 and 18 km h−1 we measured the maximal oxygen consumption (VO2max) and anthropometric measures including the moment arm of the Achilles tendon (L Ach), shank and foot volumes, and muscular fascicle lengths. A 3‐D biomechanical movement analysis of treadmill running was also conducted. RE was on average 47.8 and 62.3 ml O2 min−1 kg−1 at 14 and 18 km h−1. Maximal difference between the individual athletes was 21% at 18 km h−1. Mechanical work rate was significantly correlated with VO2 measured in L min−1 at both running velocities. However, RE and relative work rate were not significantly correlated. L Ach was significantly correlated with RE at 18 km h−1 implying that a short moment arm is advantageous regarding RE. Neither foot volume nor shank volume were significantly correlated to RE. Relative muscle fascicle length of m. soleus was significantly correlated with RE at 18 km h−1. Whole body stiffness and leg stiffness were significantly correlated with L Ach indicating that a short moment arm coincided with high stiffness. It is concluded that a short L Ach is correlated with RE. Probably, a short L Ach allows for storage of a larger amount of elastic energy in the tendon and influences the force–velocity relation toward a lower contraction velocity., Running economy was found to be significantly related to Achilles tendon moment arm, foot length ratio, whole body stiffness and leg stiffness, and muscular fascicle length.

Background: This study aimed to investigate the putative role of the Triglyceride-glucose index (TyG index) computed as ln[TG (mg/dL) × glucose (mg/dL)/2] and derived proxies as predictors of adiposity and weight loss changes after a low calorie diet (LCD) intervention.Methods: A total of 744 adult participants from the multicenter DIOGenes intervention study were prescribed a LCD (800 kcal/day) during 8 weeks. Body composition and fat content at baseline and after 8 weeks were estimated by DEXA/BIA. A multivariate analysis approach was used to estimate the difference in ∆Weight1-2 (kg), ∆BMI1-2 (kg/m2) or ∆Fat1-2 (%) between the basal value (point 1) and after 8 weeks following a LCD (point 2), respectively. The TyG index at baseline (TyG1), after following the LCD for 8 weeks (TyG2), or the TyG index differences between both time points (∆TyG1-2) were analyzed as predictors of weight and fat changes.Results: TyG1 was associated with ∆Weight1-2 (kg) and ∆BMI1-2 (kg/m2), with β=0.812 (p = 0.017) and β=0.265 (p = 0.018), respectively. Also, TyG2 values were inversely related to ∆Fat1-2 (%), β=-1.473 (p = 0.015). Moreover, ∆TyG1-2 was associated with ∆Weight1-2 (kg) and ∆Fat1-2 (%), β= 0.689 (p = 0.045) and β=1.764 (p = 0.002), respectively. Furthermore, an association between TyG2 and resistance to fat loss was found (p = 0.015).Conclusion: TyG1 index is a good predictor of weight loss induced by LCD. Moreover, TyG2 was closely related to resistance to fat loss, while ∆TyG1-2 values were positively associated with body fat changes. Therefore, TyG index and derived estimations could be used as markers of individualized responses to energy restriction and a surrogate of body composition outcomes in clinical/epidemiological settings in obesity conditions.

The influence of glucose and palmitic acid (PA) on mitochondrial respiration and emission of hydrogen peroxide (H2O2) was determined in skeletal muscle‐derived microvascular endothelial cells. Measurements were assessed in intact and permeabilized (cells treated with 0.025% saponin) low passage endothelial cells with acute‐or prolonged (3 days) incubation with regular (1.7 mM) or elevated (2.2 mM) PA concentrations and regular (5 mM) or elevated (11 mM) glucose concentrations. In intact cells, acute incubation with 1.7 mM PA alone or with 1.7 mM PA + 5 mM glucose (p, This study investigated and compared the impact of glucose and palmitic acid on mitochondrial respiration and emission of hydrogen peroxide measured simultaneously in low passage microvascular endothelial cells derived from rat skeletal muscle. The study shows for the first time that acute and prolonged lipid availability and prolonged hyperglycemia, as seen in lifestyle‐related diseases, lower mitochondrial respiration and enhance hydrogen peroxide emission in primary microvascular endothelial cells.

Purpose: We tested the hypothesis that participation in small-sided team handball training could provide beneficial effects on cardiovascular and metabolic parameters in overweight premenopausal women with special focus on the importance of prior team handball experience.Methods: A 16-week RCT training intervention was conducted in overweight premenopausal women randomized into three groups; a team handball training group without prior experience (UN; n=13), a team handball group with prior experience (EXP; n=10), and an inactive control group (CON; n=9). Both UN and EXP completed 1.6±0.3 training sessions per week with average heart rates of 84±5 and 85±9% of maximal heart rate, respectively. Cardiovascular and metabolic parameters were assessed before and after the intervention.Results: Compared to CON, UN had significant increases in VO2max (7±4%) and intermittent endurance performance (26±14%) as well as reduced total fat mass (4±6%), total fat percentage (4±5%) and android fat mass (7±12%), respectively (all ppp>0.05).Conclusion: Small-sided team handball training in overweight premenopausal women resulted in improvement of VO2max and body composition for participants with minimal team handball experience, indicating that prior team handball experience is not a prerequisite for improving physiological parameters of importance for health. Furthermore, EXP displayed cardiac adaptations, including enhanced left ventricular mass and left ventricular mass index.

Formoterol is a long-acting beta2-adrenoceptor agonist (LABA) used for treatment of asthma and exercise-induced bronchoconstriction. Formoterol is usually administered as a racemic (rac-) mixture of (R,R)- and (S,S)-enantiomers. While formoterol is restricted by the World Anti-Doping Agency (WADA), inhalation of formoterol is permitted to a predetermined dose (54 μg/24 hours) and a urine threshold of 40 ng/mL. However, chiral switch enantiopure (R,R)-formoterol is available, effectively doubling the therapeutic advantage for the same threshold. The aim of this study was to investigate whether formoterol exhibits enantioselective urinary pharmacokinetics following inhalation. Six healthy volunteers were administered a 12 μg inhaled dose of rac-formoterol. Urine was collected over 24-hours and analysed by enantioselective UPLC-MS/MS assay. Total (free drug plus conjugated metabolite) median (min-max) rac-formoterol urine levels following inhalation were 1.96(1.05-13.4) ng/mL, 1.67(0.16-9.67) ng/mL, 0.45(0.16-1.51) ng/mL, 0.61(0.33-0.78) ng/mL, and 0.17(0.08-1.06) ng/mL at 2, 4, 8, 12 and 24 hours, respectively, well below the 2019 urine threshold. The proportion of conjugation differed between enantiomers with glucuronide conjugation much greater for (R,R)-formoterol (around 30-60% of total) compared to (S,S)-formoterol (0-30%). There was clear evidence of inter-individual enantioselectivity observed in the ratios of (R,R):(S,S)-formoterol, where (S,S)- was predominant in free formoterol, and (R,R)- predominant in the conjugated metabolite. In conclusion, rac-formoterol delivered by inhalation exhibits enantioselective elimination in urine following single dose administration. Enantioselective assays should be employed in doping control to screen for banned beta2-agonist chiral switch products such as (R,R)-formoterol, and total hydrolysed rac-formoterol is warranted to account for inter-individual differences in enantioselective glucuronidation.

Exercise training improves peripheral insulin sensitivity and leads to molecular adaptations in the skeletal muscle. We investigated changes in the expression of key muscle proteins in the glucose metabolic pathway following active commuting by bike or leisure‐time exercise at two different intensities. In addition, potential associations between insulin sensitivity and muscle protein expression were examined. This per‐protocol analysis included 72 out of 130 physically inactive, healthy women and men (20–45 years) with overweight/obesity (BMI: 25–35 kg/m2) who completed 6 months of no intervention (CON, n = 12), active commuting by bike (BIKE, n = 14), or leisure‐time exercise of moderate (MOD, n = 28) or vigorous (VIG, n = 18) intensity. Exercise was prescribed 5 days/week with a weekly exercise energy expenditure of 1,600 kcal for women and 2,100 kcal for men. Insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp and skeletal muscle biopsies were obtained from m. vastus lateralis and analyzed for protein expression at baseline and after 3 and 6 months of intervention. We found an increased expression of pyruvate dehydrogenase (PDH) in the exercise groups compared with the control group following 6 months of training. No differential effects were observed on the protein expression following moderate versus vigorous intensity exercise. In addition, we found a positive association between insulin sensitivity and the expression of glucose transporter type 4 as well as PDH. The positive association and the increase in expression of PDH after exercise training points toward a role for PDH in the training‐induced enhancement of insulin sensitivity., Associations between the expression of key muscle glucoregulatory proteins and insulin sensitivity, indicate that pyruvate dehydrogenase regulates insulin sensitivity after exercise training in humans.

This narrative review aims to provide an interdisciplinary perspective on actors that link global aquatic food production systems with fish consumption and nutritional status, with a special focus on adolescent girls in Bangladesh. The writing of this narrative perspective was undertaken within the framework of the Aquatic Food for Health and Nutrition (AQN) project that aimed to develop a metric for assessing the impacts on nutrition and health of agroecosystems producing farmed seafood. Previous studies evaluating links between agricultural ecosystems, aquaculture, food security and human health have systemically ignored the importance of diet and nutrition. Such studies have also ignored the importance of local communities, cultural norms and household composition and behaviours to identify vulnerable groups such as adolescent girls. This narrative review presents our current understanding of the relationships between aquaculture, fish production and consumption patterns, food security, optimal nutrition and health. It also highlights the importance of research into aquaculture food systems, linking aquatic food production systems with nutritional status, health and socioeconomic prosperity, which would help to develop more integrated and relevant food policies.

High infant weight increases the risk of childhood overweight, while breastfeeding may reduce the risk. However, some infants have a very high weight gain even though they are exclusively breastfed. We examined the risk of a high body mass index (BMI) and overweight in childhood for infants ≥2.5 SD above the median weight-for-age (WAZ) at age 5 months according to duration of exclusive breastfeeding (≤2, >2 to 2 to

Malnutrition impairs cognitive, communication, and motor development, but it is not known how nutrition and health are associated with development in children with moderate acute malnutrition (MAM). We aimed to describe motor and language development of children with MAM and explore its nutrition and health‐related correlates. This cross‐sectional study used baseline data from a nutritional trial in children with MAM aged 6–23 months in Burkina Faso. Motor and language skills were assessed using the Malawi Development Assessment Tool (MDAT). Linear mixed models were used to explore potential correlates of MDAT including socio‐economic status, anthropometry, body composition, whole‐blood polyunsaturated fatty acids (PUFA), haemoglobin (Hb), iron status, and morbidity. We also assessed child and caregiver participation during MDAT procedures and their associations with correlates and development. MDAT data were available for 1.608 children. Mean (95% CI) MDAT z‐scores were −0.39 (−0.45, −0.34) for gross motor, 0.54 (0.48, 0.59) for fine motor, and −0.91 (−0.96, −0.86) for language skills. Children with higher mid‐upper arm circumference, weight‐for‐height, height‐for‐age, fat‐free mass, n‐3 PUFAs, Hb, and iron status had better MDAT z‐scores, whereas children with more fat mass index, anaemia, illness, and inflammation had poorer z‐scores. In addition, children living in larger households or with an unmarried mother had poorer MDAT z‐scores. Associations between morbidity and z‐scores were largely explained by children's poorer participation during MDAT assessment. The identified factors associated with child development may inform interventions needed to stimulate development during or after management of MAM.

We assessed prevalence of concurrently wasted and stunted (WaSt) and explored the overlaps between wasted, stunted, underweight and low mid-upper arm circumference (MUAC) among children aged 6-59 months in Karamoja, Uganda. We also determined optimal weight-for-age (WAZ) and MUAC thresholds for detecting WaSt. We conducted secondary data analysis with 2015-2018 Food Security and Nutrition Assessment (FSNA) cross-sectional survey datasets from Karamoja. Wasting, stunting and underweight were defined as

Outpatient therapeutic feeding protocols for the treatment of uncomplicated severe acute malnutrition in children were initially based on weight gain data from inpatient settings and expert knowledge of the physiological requirements during recovery. However, weight gain and energy requirements from historic inpatient settings may differ from modern outpatient settings and therefore may not be appropriate to guide current therapeutic feeding protocols. We calculated the weight gain and average estimated total daily energy requirement of children successfully treated for uncomplicated severe acute malnutrition as outpatients in Niger (n = 790). Mean energy provided by six therapeutic feeding protocols was calculated and compared with average estimated energy requirements in the study population. Overall weight gain was 5.5 g·kg-1 ·day-1 among recovered children. Average energy requirements ranged from 92 to 110 kcal·kg-1 ·day-1 depending on the estimation approach. Two current therapeutic feeding protocols were found to provide an excess of energy after the first week of treatment in our study population, whereas four research protocols tended to provide less energy than the estimated requirement after the first week of treatment. Alternative feeding protocols have the potential to simplify and lead to important savings for programmes but should be evaluated to show adequacy to meet the energy needs of children under treatment, as well as feasibility and cost efficiency. Our findings rely on theoretical calculations based on several assumptions and should be confirmed in field studies.

5´AMP–activated protein kinase (AMPK) is a mediator of a healthy metabolic phenotype in skeletal muscle. Metformin may exacerbate the energy disturbances observed during exercise leading to enhanced AMPK activation, and these disturbances may provoke early muscular fatigue. We studied acute (1 day) and short‐term (4 days) effects of metformin treatment on AMPK and its downstream signaling network, in healthy human skeletal muscle and adipose tissue at rest and during exercise, by applying a randomized blinded crossover study design in 10 lean men. Muscle and fat biopsies were obtained before and after the treatment period at rest and after a single bout of exercise. Metformin treat ment elicited peak plasma and muscle metformin concentrations of 31 μM and 11 μM, respectively. Neither of the treatments affected AMPK activity in skeletal muscle and adipose at rest or during exercise. In contrast, whole‐body stress during exercise was elevated as indicated by increased plasma lactate and adrenaline concentrations as well as increased heart rate and rate of perceived exertion. Also whole‐body insulin sensitivity was enhanced by 4 days metformin treatment, that is reduced fasting plasma insulin and HOMA‐IR. In conclusion, acute and short‐term metformin treatment does not affect energy homeostasis and AMPK activation at rest or during exercise in skeletal muscle and adipose tissue of healthy subjects. However, metformin treatment is accompanied by slightly enhanced perceived exertion and whole‐body stress which may provoke a lesser desire for physical activity in the metformin‐treated patients., Acute or short‐term metformin treatment did not affect the energy status and 5´AMP–activated protein kinase activation at rest or during exercise in skeletal muscle and adipose tissue of healthy subject. However, the metformin treatment was accompanied by enhanced whole‐body stress.

This study examined cardiovascular adaptations in 8- to 10-year-old schoolchildren after 10 months (a full school year) of 3 × 40 minute per week of small-sided ball games (SSG, including football, basketball, and/or floorball) or circuit strength training (CST). The study involved 291 Danish schoolchildren, 8-10 years old, cluster-randomized to SSG (n = 93, 4 schools, 5 classes), CST (n = 83, 4 schools, 4 classes), or a control group (CON, n = 115, 2 schools, 5 classes). Before and after the 10-month intervention, resting heart rate and blood pressure measurements were performed as well as comprehensive transthoracic echocardiography and peripheral arterial tonometry (PAT). Analysis of baseline-to-10-months changes showed between-group differences (P < 0.05) after both training interventions in diastolic blood pressure (delta scores: SSG -2.1 ± 6.0 mm Hg; CST -3.0 ± 7.1 mm Hg; CON 0.2 ± 5.3 mm Hg). Moreover, there were between-group differences in delta scores (P < 0.05) in interventricular septum thickness (SSG 0.17 ± 0.87 mm; CST 0.30 ± 0.94 mm; CON -0.15 ± 0.68 mm), left-atrial volume index (SSG 0.32 ± 5.13 mL/m2 ; CON 2.60 ± 5.94 mL/m2 ), and tricuspid annular plane systolic excursion (SSG -0.4 ± 3.3 mm; CON: 0.1 ± 3.6 mm). No significant between-group differences were observed for the PAT-derived reactive hyperemia index. In conclusion, 10 months of 3 × 40 minutes per week of SSG and CST in 8- to 10-year-old children decreased diastolic blood pressure and elicited discrete cardiac adaptations, suggesting that intense physical exercise in school classes can have effects on cardiovascular health in children.

Scope. To explore the effect of a healthy Nordic diet on the global transcriptome profile in peripheral blood mononuclear cells (PBMCs) of subjects with metabolic syndrome. Methods and results. Subjects with metabolic syndrome undergo a 18/24 week randomized intervention study comparing an isocaloric healthy Nordic diet with an average habitual Nordic diet served as control (SYSDIET study). Altogether, 68 participants are included. PBMCs are obtained before and after intervention and total RNA is subjected to global transcriptome analysis. 1302 probe sets are differentially expressed between the diet groups (p‐value < 0.05). Twenty‐five of these are significantly regulated (FDR q‐value < 0.25) and are mainly involved in mitochondrial function, cell growth, and cell adhesion. The list of 1302 regulated probe sets is subjected to functional analyses. Pathways and processes involved in the mitochondrial electron transport chain, immune response, and cell cycle are downregulated in the healthy Nordic diet group. In addition, gene transcripts with common motifs for 42 transcription factors, including NFR1, NFR2, and NF‐κB, are downregulated in the healthy Nordic diet group. Conclusion. These results suggest that benefits of a healthy diet may be mediated by improved mitochondrial function and reduced inflammation. The project was funded by NordForsk Nordic Centre of Excellencein Food, Nutrition and Health project 070014 (SYSDIET [Systems Biologyin Controlled Dietary Interventions and Cohort Studies]) and further, OsloMetropolitan University-OsloMet (Norway), University of Oslo (Norway),Throne Holst Foundation (Norway), Academy of Finland, SwedishResearch Council, Svenska Diabetesf ̈orbundet, SRP Diabetes, FinnishDiabetes Research Foundation, Finnish Foundation for CardiovascularResearch, the Sigrid Juselius Foundation, EVO funding from KuopioUniversity Hospital (Finland), the Druvan Foundation, Sk ̊ane UniversityHospital, the Heart-Lung Foundation, Diabetesfonden and FoundationCerealia (Sweden), the Danish Obesity Research Centre (DanORC,www.danorc.dk), the Danish Council for Strategic Research (DairyHealth,BioFunCarb) (Denmark), the Agricultural Productivity Fund, and theResearch Fund of the University of Iceland (Iceland).

Prediction of chemical shifts in organic cations is known to be a challenge. In this article we meet this challenge for α-protonated alkylpyrroles, a class of compounds not yet studied in this context, and present a combined experimental and theoretical study of the 13C and 1H chemical shifts in three selected pyrroles. We have investigated the importance of the solvation model, basis set and quantum chemical method with the goal of developing a simple computational protocol, which allows prediction of 13C and 1H chemical shifts with a sufficient accuracy for identification of such compounds in mixtures. We find that density functional theory with the B3LYP functional is not sufficient for reproducing all 13C chemical shifts, while already the simplest correlated wave function model, Møller-Plesset perturbation theory (MP2), leads to almost perfect agreement with the experimental data. Treatment of solvent effects generally improves somewhat the agreement with experiment and can in most cases be accomplished by a simple polarizable continuum model. The only exception is the N-H proton, which requires inclusion of explicit solvent molecules in the calculation.

Following an application from Specialised Nutrition Europe (SNE), submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to carbohydrate solutions and contribute to the improvement of physical performance during a high-intensity and long-lasting physical exercise. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is carbohydrate solutions containing glucose, mixtures of glucose and fructose, sucrose and/or maltodextrins. The Panel considers that carbohydrate solutions are sufficiently characterised in relation to the claimed effect. The claimed effect proposed by the applicant is 'contribute to the improvement of physical performance during a high-intensity and long-lasting physical exercise', which is considered by the Panel as a beneficial physiological effect. The Panel concludes that a cause and effect relationship has been established between the consumption of carbohydrate solutions and the improvement of physical performance during high-intensity and long-lasting physical exercise. The target population is healthy trained adults performing high-intensity (at least at 65% of the VO2max) and long-lasting (at least 60 min) physical exercise. (c) 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to provide a supplementary dietary exposure and safety assessment of synthetic l-ergothioneine for those groups of the population which had been excluded by the applicant in the original application, i.e. infants and young children (i.e. toddlers), pregnant and breastfeeding women. Thus, intake estimates were calculated for these population groups and the following maximum anticipated daily intakes of l-ergothioneine from the NF, in addition to the background diet, were calculated: 2.82 mg/kg body weight (bw) per day for infants, 3.39 mg/kg bw per day for toddlers and 1.31 mg/kg bw per day for adults including pregnant and breastfeeding women. The Panelconsiders that based on the overall toxicological data the no-observed-adverse-effect level (NOAEL) of 800 mg/kg bw per day as established in the original assessment also pertains to pregnant and breastfeeding women as well as to young children (i.e. toddlers) and infants. The corresponding margins of exposure (i.e. the ratio between the NOAEL and the maximum anticipated daily intakes) are 284 for infants, 236 for young children and 610 for pregnant and breastfeeding women. These margins of exposure are considered sufficient. The Panelconcludes that the novel food, synthetic l-ergothioneine, is safe under the proposed uses and use levels for infants, young children (i.e. toddlers) and pregnant and breastfeeding women. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

Following an application from Loc Troi group, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Vibigaba (germinated brown rice) and contribution to the maintenance of normal blood cholesterol concentrations. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is Vibigaba. The Panel considers that the germinated brown rice Vibigaba is sufficiently characterised. The claimed effect proposed by the applicant is ‘contribution to the maintenance of normal blood cholesterol levels’. The Panel considers that maintenance of normal blood cholesterol concentrations is a beneficial physiological effect. The Panel notes that the applicant did not perform a comprehensive literature search to identify human intervention studies which could be pertinent to the claim. The applicant did not reply to a specific request from EFSA to provide this information. The applicant identified one human intervention study as being pertinent to the claim. The Panel notes the important methodological limitations of the study (e.g. statistical methods used for data analysis not appropriate for the study design) and that the information provided on the design and conduct of the study is insufficient for a complete scientific evaluation. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of Vibigaba (germinated brown rice) and maintenance of normal blood cholesterol concentration.

Following an application from Cargill R&D Centre Europe, submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on thescientific substantiation of a health claim related to sugar-free hard confectionery with at least 90% erythritol and reduction of dental plaque which reduces the risk of caries. The food proposed by the applicant as the subject of the health claim, sugar-free hard confectionery with at least 90% erythritol, is sufficiently characterised. In the context of this application, the weight of dental plaque, and/or the counts of Streptococcus mutans in dental plaque, and/or the concentration of organic acids in plaque (primarily acetic acid and lactic acid) can be considered as risk factor(s) in the development of dental caries, as long as evidence is provided that the consumption of the food that is the subject of the health claim reduces one or more of the proposed risk factors and the incidence of dental caries. One human intervention study did not show an effect of sugar-free hard confectionery with at least 90% erythritol on the incidence of dental caries in children on either mixed or permanent dentition. The Panel concludes that a cause and effect relationship has not been established between the consumption of sugar-free hard confectionery with at least 90% erythritol and reduction of dental plaque which reduces the risk of dental caries.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to provide scientific and technical guidance for the preparation and presentation of applications for authorisation of infant and/or follow‐on formula manufactured from protein hydrolysates. This guidance document addresses the information and data to be submitted to EFSA on infant and follow‐on formulae manufactured from protein hydrolysates with respect to the safety and suitability of the specific formula and/or the formula's efficacy in reducing the risk of developing allergy to milk proteins. The guidance will be further reviewed and updated with the experience gained from the evaluation of specific applications for authorisation, and in the light of future Community guidelines and legislation. The NDA Panel endorsed a draft of this scientific opinion on 14 December 2016 for public consultation. The draft document has been revised and updated according to the comments received, where appropriate., This publication is linked to the following EFSA Supporting Publications article: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2017.EN-1214/full

Environmental history is an interdisciplinary pursuit that has developed as a form of conscience to counter an increasingly powerful, forward-looking liberal theory of the environment. It deals with the relations between environmental ideas and materialities, from the work of the geographers George Perkins Marsh, Carl Sauer, and Clarence Glacken, to more recent global-scale assessments of the impact of the “great acceleration” since 1950. Today’s “runaway world” paradoxically embraces risk management in an attempt to determine its own future whilst generating a whole new category of “manufactured risks”. These are exposed by environmental history’s focus on long-run analysis and its narrative form that identifies the stories that we tell ourselves about nature. How a better understanding of past environmental transformations helps to analyse society and agency, and what this can mean for solutions and policies, is the agenda for an engaged environmental history from now on.

Landscape ecology is an interdisciplinary field of research and practice that deals with the mutual association between the spatial configuration and ecological functioning of landscapes, exploring and describing processes involved in the differentiation of spaces within landscapes, and the ecological significance of the patterns which are generated by such processes. In landscape ecology, perspectives drawn from existing academic disciplines are integrated based on a common, spatially explicit mode of analysis developed from classical holistic geography, emphasizing spatial and landscape pattern analysis and ecological interaction of land units. The landscape is seen as a holon: an assemblage of interrelated phenomena, both cultural and biophysical, that together form a complex whole. Enduring challenges to landscape ecology include the need to develop a systematic approach able to translate positivist readings of the environment and hermeneutical perspectives on socioecological interaction into a common framework or terminology.

Following the adoption of Regulation (EU) 2015/2283 of the European Parliament and of the Council on novel foods, the European Commission requested EFSA to update and develop scientific and technical guidance for the preparation and presentation of applications for authorisation of novel foods. This guidance presents a common format for the organisation of the information to be presented in order to assist the applicant in preparing a well‐structured application to demonstrate the safety of the novel food. The application should be comprehensive and complete. This guidance outlined the data needed for the safety assessments of novel foods. Requirements which should be covered in all applications relate to the description of the novel food, production process, compositional data, specification, proposed uses and use levels, and anticipated intake of the novel food. Further sections on the history of use of the novel food and/or its source, absorption, distribution, metabolism, excretion, nutritional information, toxicological information and allergenicity should be considered by the applicant by default. If not covered in the application, this should be justified. The applicant should integrate the data presented in the different sections to provide their overall considerations on how the information supports the safety of the novel food under the proposed conditions of use. Where potential health hazards have been identified, they should be discussed in relation to the anticipated intakes of the novel food and the proposed target populations. On the basis of the information provided, EFSA will assess the safety of the novel food under the proposed conditions of use.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on the energy conversion factor of d‐tagatose to be used for calculating the energy value of foods to be declared in nutrition labelling. Energy conversion factors for nutrients for the purpose of nutrition labelling have been set based on the concept of metabolisable energy (ME). The same methodology has been applied to calculate the energy conversion factor for d‐tagatose in this opinion. The assessment is based on a dossier prepared for Nutrilab NV and submitted by Bioresco Ltd. At present, data are insufficient to derive an accurate ME value for d‐tagatose. Relying on the human data indicating a mean absorption rate of 80% (range 69–88%) and a urinary excretion of either 1% or 5%, the corresponding energy values for d‐tagatose would be 2.8 kcal/g (11.8 kJ/g) and 2.96 kcal/g (12.4 kJ/g), respectively. Taking into account that the remaining 20% of d‐tagatose which is not absorbed in the small intestine is fermented in the colon and may deliver at least some energy, e.g. in form of short‐chain fatty acids, the Panel concludes that a rounded estimate of the energy conversion factor for d‐tagatose based on the available data and calculated as ME would be 3 kcal/g (12.5 kJ/g). The Panel considers that additional data on the absorption, distribution, metabolism and excretion of d‐tagatose in humans would help in the calculation of a more accurate energy conversion factor for d‐tagatose based on the concept of ME.

Following an application from Ecopharma BVBA, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Fabenol® Max and ‘reduces the absorption of carbohydrates’. The Panel considers that Fabenol® Max, which is an aqueous extract from Phaseolus vulgaris L. standardised by its content of α-amylase inhibitor, is sufficiently characterised. According to the applicant, consumption of the food ‘offers potential benefits in the maintenance of healthy blood sugar levels’. The meaning of ‘healthy blood sugar levels’ was not specified. The target population proposed by the applicant is ‘the general population that wants to manage their carbohydrate intake (for the maintenance of healthy blood sugar levels or optimal body composition)’. The Panel notesthat the claimed effect was not sufficiently defined and that the applicant did not provide any further information. The Panel concludes that a cause and effect relationship cannot be established between the consumption of Fabenol® Max and a beneficial physiological effect.

Regular exercise plays an important role in the prevention and treatment of type 2 diabetes (T2D). The synthesis and secretion of myokines in response to contraction may contribute to the beneficial metabolic effects of exercise. However, some exercise-induced responses may be attenuated in T2D. Here, we investigated whether the effect of acute exercise on selected myokines are impaired in T2D. Skeletal muscle biopsies and blood samples were obtained from 13 men with T2D and 14 weight-matched, glucose-tolerant men before, immediately after and 3-h after acute exercise (60 min cycling) to examine muscle expression and plasma/serum levels of selected myokines. One-hour of exercise increased muscle expression of IL6, FGF21, ANGPTL4, CHI3L1, CTGF and CYR61, of which FGF21, ANGPTL4 and CHI3L1 increased further 3-h into recovery, whereas expression of IL6, CYR61, and CTGF returned to baseline levels. There was no immediate effect of exercise on IL15 expression, but it decreased 3-h into recovery. Plasma IL-6 increased robustly, whereas circulating levels of FGF21, ANGPTL4, IL-15, and CHI3L1 increased only modestly in response to exercise. All returned toward baseline levels 3-h into recovery except for plasma ANGPTL4, which increased further. No significant differences in these responses to exercise were observed between the groups. Our results demonstrate that muscle expression and circulating levels of selected known and putative myokines were equally regulated by acute exercise in patients with T2D and weight-matched controls. This suggests that the potential beneficial metabolic effects of these myokines are not impaired in patients with T2D.

AimWe analysed the variation of species richness in the European freshwater faunaacross latitude. In particular, we compared latitudinal patterns in species richnessandß-diversity among species adapted to different habitat types.LocationEurope.MethodsWe compiled data on occurrence for 14,020 animal species across 25pre-defined biogeographical regions of European freshwaters from theLimnofaunaEuropaea. Furthermore, we extracted information on the habitat preferences ofspecies. We assigned species to three habitat types: species adapted to groundwater,lotic (running water) and lentic (standing water) habitats. We analysed latitudinalpatterns of species richness, the proportion of lentic species andß-diversity.ResultsOnly lentic species showed a significant species-area relationship. Wefound a monotonic decline of species richness with latitude for groundwater andlotic habitats, but a hump-shaped relationship for lentic habitats. The proportion oflentic species increased from southern to northern latitudes.ß-Diversity declinedfrom groundwater to lentic habitats and from southern to northern latitudes.Main conclusionsThe differences in the latitudinal variation of species richnessamong species adapted to different habitat types are in part due to differences in thepropensity for dispersal. Since lentic habitats are less persistent than lotic or groundwaterhabitats, lentic species evolved more efficient strategies for dispersal. Thedispersal propensity of lentic species facilitated the recolonization of central Europeafter the last glaciation. Overall, we stress the importance of considering the historyof regions and lineages as well as the ecological traits of species for understandingpatterns of biodiversity.

Stable strontium isotope ratios in archaeological finds have frequently been used to determine their place of origin, in order to reconstruct migration and trade. Peat bogs offer favourable burial conditions for the preservation of organic remains such as woollen textiles and leather by a natural tanning process. However, these finds are impregnated by peat substances including contaminant strontium which is likely to mask the original 87Sr/86Sr isotopic ratio of the specimens. In this paper, we present a pilot study analysing stable strontium isotopic ratios from Iron Age textile and leather finds from the Thorsberg peat bog, focusing on a sample processing method which permits the quantitative removal of contaminating strontium from the specimens. Copyright © 2007 John Wiley & Sons, Ltd.

��������� � �� ���������� The pattern, pace and extent of the evolutionary radiation of modern birds (Neornithes) by the end-Cretaceous (65 Ma) has long been debated. Well-dated, taphonomically understood and phylogenetically constrained fossil birds from both sides of the Cretaceous–Paleogene (K–Pg) boundary are required to quantify the shape of this radiation, but have largely been lacking. Here we report on a large collection of fossil birds from the Lower Eocene of Denmark (ca. 54 Ma) that includes three-dimensionally preserved, articulated specimens from carbonate concretions as well as skeletal imprints and feathers. These birds are from a marine diatomite sequence (the Fur Formation), a low-energy deep-water preservational environment unique to the Cretaceous and Paleogene avian fossil record. We present taphonomic and palaeoecological information gleaned from these birds that in combination with phylogenetic data have implications for unravelling avian survivorship across the K–Pg boundary as well as for the pattern of the neornithine evolutionary radiation. Copyright # 2009 John Wiley & Sons, Ltd.