CONCLUSIONS This study demonstrated that low PMA, CCI score ≥ 2 and bowel resection were independent risk factors for postoperative complications in patients with AMI. Preoperative assessment of frailty using PMA and the evaluation of comorbidity status using CCI may serve as helpful tools in preoperative risk assessment and should be integrated into scoring systems for surgically treated AMI. Beginning with the discovery more than 35 years ago that oxygen chemoreceptors of the fish gill are enriched with serotonin, numerous studies have examined the importance of this, and other neuroendocrine factors in piscine chemoreceptor function, and in particular on the chemoreceptor-mediated reflex control of breathing. However, despite these studies, there is continued debate as to the role of neuroendocrine factors in the initiation or modulation of breathing during environmental disturbances or physical activity. In this review, we summarize the state-of-knowledge surrounding the neuroendocrine control of oxygen chemoreception in fish and the associated reflex adjustments to ventilation. We focus on neurohumoral substances that either are present in chemosensory cells or those that are localised elsewhere but have also been implicated in the direct control of breathing. These substances include serotonin, catecholamines (adrenaline and noradrenaline), acetylcholine, purines and gaseous neurotransmitters. Despite the growing indirect evidence for an involvement of these neuroendocrine factors in chemoreception and ventilatory control, direct evidence awaits the incorporation of novel methods currently under development. BACKGROUND Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) particle containing apolipoprotein(a) (apo(a)) covalently linked to apolipoprotein B-100 (apoB). 12-O-Tetradecanoylphorbol-13-acetate purchase Statin-treated patients with elevated Lp(a) have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Recent trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition decreases Lp(a) and cardiovascular events, particularly in high risk patients with elevated Lp(a). We investigated the kinetic mechanism whereby alirocumab, a PCSK9 inhibitor, lowers Lp(a) in statin-treated patients with high Lp(a) and ASCVD. METHODS The effects of 12-week alirocumab treatment (150 mg every 2 weeks) on apo(a) kinetics were studied in 21 patients with elevated Lp(a) concentration (>0.5 g/L). Apo(a) fractional catabolic rate (FCR) and production rate (PR) were determined using intravenous D3-leucine administration, mass spectrometry and compartmental modelling. All patients were on long-term statin treatment. RESULTS Alirocumab significantly decreased plasma concentrations of total cholesterol (-39%), LDL-cholesterol (-67%), apoB (-56%), apo(a) (-25%) and Lp(a) (-22%) (P less then 0.001 for all). Alirocumab also significantly lowered plasma apo(a) pool size (-26%, P less then 0.001) and increased the FCR of apo(a) (+28%, P less then 0.001), but did not alter apo(a) PR, which remained significantly higher relative to a reference group of patients on statins with normal Lp(a) (P less then 0.001). CONCLUSIONS In statin-treated patients, alirocumab lowers elevated plasma Lp(a) concentrations by accelerating the catabolism of Lp(a) particles. This may be consequent on marked upregulation of hepatic receptors (principally for LDL) and/or reduced competition between Lp(a) and LDL particles for these receptors; the mechanism could contribute to the benefit of PCSK9 inhibition with alirocumab on cardiovascular outcomes. BACKGROUND An adequate metabolic and hormonal response to the switch from rest to exercise is critical for the health benefits of exercise interventions. Previous work suggests that this response is impaired with overweight/obesity but the specific differences between overweight/obese and lean individuals remain unclear. METHODS We compared glucose and non-esterified fatty acid (NEFA) regulation and the changes of key homeostatic hormones during 45 min of moderate exercise between 17 overweight/obese and 28 lean premenopausal women. For this comparison, we implemented an exercise protocol at 60% of individual peak oxygen uptake, with frequent blood sampling and under fasting conditions. RESULTS We found that at the same exercise intensity in the overweight/obese and the lean group of women, the metabolic and hormonal response differed. In contrast to the lean group, the overweight/obese group portrayed an activation in the stress axis (adrenocorticotropic hormone (ACTH)/cortisol) and a lower growth hormone (hGH) response and exercise-increase of plasma NEFA. Both groups, however, displayed increased insulin sensitivity during exercise that was accompanied by a normalization of the elevated fasting glucose in the overweight/obese group after 15-20 min. CONCLUSION We conclude that the response to exercise in overweight/obese subjects indeed differs from that in lean individuals. Additionally, we demonstrate that exercise can elicit beneficial (improved glucose regulation) and unwanted effects (stress axis activation) in overweight/obese subjects at the same time. This second finding suggests that exercise interventions for overweight/obese subjects need careful consideration of intensity and dose in order to achieve the intended results and avoid acute, undesired reactions. This study investigates changes with respect to increasing protein levels in dystrophic nerves of two mdx mouse models of Duchenne muscular dystrophy (DMD). We propose that these nerve changes result from progressive ongoing damage to neuromuscular junctions (NMJs) due to repeated intrinsic bouts of necrosis in dystrophic muscles. We compared sciatic nerves from classic mdx mice aged 13, 15 and 18 months (M), with D2.mdx mice (on DBA2 background) aged 9 and 13 M, using immunoblotting to quantify levels of 7 proteins. The neuronal proteins S100β and Tau5 were increased by 13 M in mdx nerves (compared with WT), indicating ongoing myonecrosis in this strain. In striking contrast there was no difference in levels of these neuronal proteins for D2.mdx and D2.WT sciatic nerves at 13 M, indicating reduced myonecrosis over this time in D2.mdx mice compared with mdx. These novel changes in mdx sciatic nerves by 13 M, suggest early denervation or neurodegeneration of dystrophic nerves that is likely irreversible and progressive.