We investigated the physiological consequences of one of the most extreme exercises realized by humans in race conditions: a 166-km mountain ultra-marathon (MUM) with 9500 m of positive and negative elevation change. For this purpose, (i) the fatigue induced by the MUM and (ii) the recovery processes over two weeks were assessed. Evaluation of neuromuscular function (NMF) and blood markers of muscle damage and inflammation were performed before and immediately following (n = 22), and 2, 5, 9 and 16 days after the MUM (n = 11) in experienced ultra-marathon runners. Large maximal voluntary contraction decreases occurred after MUM (−35% [95% CI: −28 to −42%] and −39% [95% CI: −32 to −46%] for KE and PF, respectively), with alteration of maximal voluntary activation, mainly for KE (−19% [95% CI: −7 to −32%]). Significant modifications in markers of muscle damage and inflammation were observed after the MUM as suggested by the large changes in creatine kinase (from 144±94 to 13,633±12,626 UI L−1), myoglobin (from 32±22 to 1,432±1,209 µg L−1), and C-Reactive Protein (from <2.0 to 37.7±26.5 mg L−1). Moderate to large reductions in maximal compound muscle action potential amplitude, high-frequency doublet force, and low frequency fatigue (index of excitation-contraction coupling alteration) were also observed for both muscle groups. Sixteen days after MUM, NMF had returned to initial values, with most of the recovery process occurring within 9 days of the race. These findings suggest that the large alterations in NMF after an ultra-marathon race are multi-factorial, including failure of excitation-contraction coupling, which has never been described after prolonged running. It is also concluded that as early as two weeks after such an extreme running exercise, maximal force capacities have returned to baseline.

Pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38) are neuropeptides of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon family. PACAP receptors are expressed in different brain regions, including cerebellum. We used primary culture of rat cerebellar granule neurons to study the effect of PACAP-38 on apoptosis induced by potassium deprivation. We demonstrated that PACAP-38 increased survival of cerebellar neurons in a dose-dependent manner by decreasing the extent of apoptosis estimated by DNA fragmentation. PACAP-38 induced activation of the extracellular signal-regulated kinase (ERK)-type of mitogen-activated protein (MAP) kinase through a cAMP-dependent pathway. PD98059, an inhibitor of MEK (MAP kinase kinase), completely abolished the antiapoptotic effect of PACAP-38, suggesting that MAP kinase pathway activation is necessary for PACAP-38 action.

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This experiment investigated the fatigue induced by a 24-h running exercise (24TR) and particularly aimed at testing the hypothesis that the central component would be the main mechanism responsible for neuromuscular fatigue. Neuromuscular function evaluation was performed before, every 4 h during, and at the end of the 24TR on 12 experienced ultramarathon runners. It consisted of a determination of the maximal voluntary contractions (MVC) of the knee extensors (KE) and plantar flexors (PF), the maximal voluntary activation (%VA) of the KE and PF, and the maximal compound muscle action potential amplitude (Mmax) on the soleus and vastus lateralis. Tetanic stimulations also were delivered to evaluate the presence of low-frequency fatigue and the KE maximal muscle force production ability. Strength loss occurred throughout the exercise, with large changes observed after 24TR in MVC for both the KE and PF muscles (-40.9+/-17.0 and -30.3+/-12.5%, respectively; P<0.001) together with marked reductions of %VA (-33.0+/-21.8 and -14.8+/-18.9%, respectively; P<0.001). A reduction of Mmax amplitude was observed only on soleus, and no low-frequency fatigue was observed for any muscle group. Finally, KE maximal force production ability was reduced to a moderate extent at the end of the 24TR (-10.2%; P<0.001), but these alterations were highly variable (+/-15.7%). These results suggest that central factors are mainly responsible for the large maximal muscle torque reduction after ultraendurance running, especially on the KE muscles. Neural drive reduction may have contributed to the relative preservation of peripheral function and also affected the evolution of the running speed during the 24TR.

This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.

The aim of this study was to identify the mechanisms that contribute to the decline in knee extensor (KE) muscles strength after a prolonged running exercise. During the 2 days preceding a 30-km running race [duration 188.7 +/- 27.0 (SD) min] and immediately after the race, maximal percutaneous electrical stimulations (single twitch, 0.5-s tetanus at 20 and 80 Hz) were applied to the femoral nerve of 12 trained runners. Superimposed twitches were also delivered during isometric maximal voluntary contraction (MVC) to determine the level of voluntary activation (%VA). The vastus lateralis electromyogram was recorded. KE MVC decreased from pre- to postexercise (from 188.1 +/- 25.2 to 142.7 +/- 29.7 N x m; P < 0.001) as did %VA (from 98.8 +/- 1.8 to 91.3 +/- 10.7%; P < 0.05). The changes from pre- to postexercise in these two variables were highly correlated (R = 0.88; P < 0.001). The modifications in the mechanical response after the 80-Hz stimulation and M-wave peak-to-peak amplitude were also significant (P < 0.001 and P < 0.05, respectively). It can be concluded that 1) central fatigue, neuromuscular propagation, and muscular factors are involved in the 23.5 +/- 14.9% reduction in MVC after a prolonged running bout at racing pace and 2) runners with the greatest KE strength loss experience large activation deficit.

Diabetes Care 2019;42:777-788 | https://doi.org/10.2337/dc18-0836 OBJECTIVEThe long-term impact of intentional weight loss on cardiovascular events remains unknown. We describe 12-month changes in body weight and cardiovascular risk factors in PREvención con DIeta MEDiterránea (PREDIMED)-Plus, a trial designed to evaluate the long-term effectiveness of an intensive weight loss lifestyle intervention on primary cardiovascular prevention. RESEARCH DESIGN AND METHODSOverweight/obese adults with metabolic syndrome aged 55-75 years (n = 626) were randomized to an intensive weight loss lifestyle intervention based on an energyrestricted Mediterranean diet, physical activity promotion, and behavioral support (IG) or a control group (CG). The primary and secondary outcomes were changes in weight and cardiovascular risk markers, respectively. RESULTSDiet and physical activity changes were in the expected direction, with significant improvements in IG versus CG. After 12 months, IG participants lost an average of 3.2 kg vs. 0.7 kg in the CG (P < 0.001), a mean difference of 22.5 kg (95% CI 23.1 to 21.9). Weight loss ‡5% occurred in 33.7% of IG participants compared with 11.9% in the CG (P < 0.001). Compared with the CG, cardiovascular risk factors, including waist circumference, fasting glucose, triglycerides, and HDL cholesterol, significantly improved in IG participants (P < 0.002). Reductions in insulin resistance, HbA 1c , and circulating levels of leptin, interleukin-18, and MCP-1 were greater in IG than CG participants (P < 0.05). IG participants with prediabetes/diabetes significantly improved glycemic control and insulin sensitivity, along with triglycerides and HDL cholesterol levels compared with their CG counterparts. CONCLUSIONSPREDIMED-Plus intensive lifestyle intervention for 12 months was effective in decreasing adiposity and improving cardiovascular risk factors in overweight/obese older adults with metabolic syndrome, as well as in individuals with or at risk for diabetes.Clinical trial reg. no. ISRCTN89898870, www .isrctn.org This article contains Supplementary Data online at

Neuromuscular fatigue of the knee extensor (KE) and plantar flexor (PF) muscles was characterized after a 65-km ultramarathon race in nine well-trained runners by stimulating the femoral and tibial nerves, respectively. One week before and immediately after the ultramarathon, maximal twitches were elicited from the relaxed KE and PF. Electrically evoked superimposed twitches of the KE were also elicited during maximal voluntary contractions (MVCs) to determine maximal voluntary activation. MVC and maximal voluntary activation decreased significantly after the ultramarathon (-30.2 +/- 18.0% and -27.7 +/- 13.0%, respectively; P < 0.001). Surprisingly, peak twitch increased after the ultramarathon from 15.8 +/- 6.3 to 19.7 +/- 3.3 N. m for PF (P < 0.01) and from 131.9 +/- 21.2 to 157.1 +/- 35.9 N for KE (P < 0.05). Also, shorter contraction and half-relaxation times were observed for both muscles. The compound muscle action potentials (M wave) were not significantly altered by the ultramarathon with the exception of the soleus, which showed a slightly higher M-wave amplitude after the running. From these results, it can be concluded that 65 km of running 1) severely depressed the maximal voluntary force capacity mainly because of a decrease in maximal voluntary activation, 2) potentiated the twitch mechanical response, and 3) did not change significantly the M-wave characteristics.