BackgroundIncreased maximal oxygen uptake (V̇O2max) is beneficial in children with cystic fibrosis (CF) but remains lower compared to healthy peers. Intrinsic metabolic deficiencies within skeletal muscle (muscle “quality”) and skeletal muscle size (muscle “quantity”) are both proposed as potential causes for the lower V̇O2max, although exact mechanisms remain unknown. This study utilises gold-standard methodologies to control for the residual effects of muscle size from V̇O2max to address this “quality” vs. “quantity” debate.MethodsFourteen children (7 CF vs. 7 age- and sex-matched controls) were recruited. Parameters of muscle size – muscle cross-sectional area (mCSA) and thigh muscle volume (TMV) were derived from magnetic resonance imaging, and V̇O2max obtained via cardiopulmonary exercise testing. Allometric scaling removed residual effects of muscle size, and independent samples t-tests and effect sizes (ES) identified differences between groups in V̇O2max, once mCSA and TMV were controlled for.ResultsV̇O2max was shown to be lower in the CF group, relative to controls, with large ES being identified when allometrically scaled to mCSA (ES = 1.76) and TMV (ES = 0.92). Reduced peak work rate was also identified in the CF group when allometrically controlled for mCSA (ES = 1.18) and TMV (ES = 0.45).ConclusionsA lower V̇O2max was still observed in children with CF after allometrically scaling for muscle size, suggesting reduced muscle “quality” in CF (as muscle “quantity” is fully controlled for). This observation likely reflects intrinsic metabolic defects within CF skeletal muscle.

BACKGROUND: it remains unclear whether non-animal-derived dietary protein sources (and therefore vegan diets) can support resistance training-induced skeletal muscle remodeling to the same extent as animal-derived protein sources. METHODS: in Phase 1, 16 healthy young adults (m = 8, f = 8; age: 23 ± 1 y; BMI: 23 ± 1 kg/m2) completed a 3-d dietary intervention (high protein, 1.8 g·kg bm-1·d-1) where protein was derived from omnivorous (OMNI1; n = 8) or exclusively non-animal (VEG1; n = 8) sources, alongside daily unilateral leg resistance exercise. Resting and exercised daily myofibrillar protein synthesis (MyoPS) rates were assessed using deuterium oxide. In Phase 2, 22 healthy young adults (m = 11, f = 11; age: 24 ± 1 y; BMI: 23 ± 0 kg/m2) completed a 10 wk, high-volume (5 d/wk), progressive resistance exercise program while consuming an omnivorous (OMNI2; n = 12) or non-animal-derived (VEG2; n = 10) high-protein diet (∼2 g·kg bm-1·d-1). Muscle fiber cross-sectional area (CSA), whole-body lean mass (via DXA), thigh muscle volume (via MRI), muscle strength, and muscle function were determined pre, after 2 and 5 wk, and postintervention. OBJECTIVES: to investigate whether a high-protein, mycoprotein-rich, non-animal-derived diet can support resistance training-induced skeletal muscle remodeling to the same extent as an isonitrogenous omnivorous diet. RESULTS: Daily MyoPS rates were ∼12% higher in the exercised than in the rested leg (2.46 ± 0.27%·d-1 compared with 2.20 ± 0.33%·d-1 and 2.62 ± 0.56%·d-1 compared with 2.36 ± 0.53%·d-1 in OMNI1 and VEG1, respectively; P < 0.001) and not different between groups (P > 0.05). Resistance training increased lean mass in both groups by a similar magnitude (OMNI2 2.6 ± 1.1 kg, VEG2 3.1 ± 2.5 kg; P > 0.05). Likewise, training comparably increased thigh muscle volume (OMNI2 8.3 ± 3.6%, VEG2 8.3 ± 4.1%; P > 0.05), and muscle fiber CSA (OMNI2 33 ± 24%, VEG2 32 ± 48%; P > 0.05). Both groups increased strength (1 repetition maximum) of multiple muscle groups, to comparable degrees. CONCLUSIONS: Omnivorous and vegan diets can support comparable rested and exercised daily MyoPS rates in healthy young adults consuming a high-protein diet. This translates to similar skeletal muscle adaptive responses during prolonged high-volume resistance training, irrespective of dietary protein provenance. This trial was registered at clinicaltrials.gov as NCT03572127.

PURPOSE: 18F-NaF PET is valuable for detecting bone metabolism through osteoblastic activity in the assessment of bone disease. Hawkins, Patlak, and standardised uptake value (SUV) are the most common quantitative measurements used to evaluate bone metabolism. This systematic review evaluates the correlation between quantitative positron emission tomography (PET) methods and to compare their precision. METHODS: a systematic search in Medline, PubMed, SCOPUS, and Web of Science was undertaken to find relevant papers published from 2000. All studies with human adults undergoing 18F-NaF PET, PET/CT, or PET/MRI were included except for subjects diagnosed with non-diffuse metabolic bone disease or malignancy. Quality Assessment Tool for Studies of Diverse Designs (QATSDD) was used to assess risk of bias. A qualitative review and meta-analysis using Hedges random-effect model was used producing summary size effects of the correlation between methods in healthy and unhealthy bone sites and assessing study heterogeneity. RESULTS: 228 healthy and unhealthy participants were included across 12 studies resulted from the systematic search. One-third of studies had a moderate quality percentage while the rest had relatively high quality. The pooled correlation coefficient in meta-analysis showed a high correlation of more than 0.88 (0.71-1.05. 95 %CI) between SUV and Hawkins and more than 0.96 (0.88-1.03. 95 %CI) between Patlak and Hawkins within all subgroups, suggesting all methods yield similar results in healthy and unhealthy bone sites. SUV has the lowest precision error followed by Patlak while Hawkins method showed the highest precision error. CONCLUSION: Patlak is the best within research and SUV is better within clinical practice.

Factors underpinning the time-course of resistance-type exercise training (RET) adaptations are not fully understood. This study hypothesized that consuming a twice-daily protein-polyphenol beverage (PPB; n = 15; age, 24 ± 1 yr; BMI, 22.3 ± 0.7 kg·m-2) previously shown to accelerate recovery from muscle damage and increase daily myofibrillar protein synthesis (MyoPS) rates would accelerate early (10 sessions) improvements in muscle function and potentiate quadriceps volume and muscle fiber cross-sectional area (fCSA) following 30 unilateral RET sessions in healthy, recreationally active, adults. Versus isocaloric placebo (PLA; n = 14; age, 25 ± 2 yr; BMI, 23.9 ± 1.0 kg·m-2), PPB increased 48 h MyoPS rates after the first RET session measured using deuterated water (2.01 ± 0.15 vs. 1.51 ± 0.16%·day-1, respectively; P < 0.05). In addition, PPB increased isokinetic muscle function over 10 sessions of training relative to the untrained control leg (%U) from 99.9 ± 1.8 pretraining to 107.2 ± 2.4%U at session 10 (vs. 102.6 ± 3.9 to 100.8 ± 2.4%U at session 10 in PLA; interaction P < 0.05). Pre to posttraining, PPB increased type II fCSA (PLA: 120.8 ± 8.2 to 109.5 ± 8.6%U; PPB: 92.8 ± 6.2 to 108.4 ± 9.7%U; interaction P < 0.05), but the gain in quadriceps muscle volume was similar between groups. Similarly, PPB did not further increase peak isometric torque, muscle function, or MyoPS measured posttraining. This suggests that although PPB increases MyoPS and early adaptation, it may not influence longer term adaptations to unilateral RET.NEW & NOTEWORTHY Using a unilateral model of resistance training, we show for the first time that a protein-polyphenol beverage increases initial rates of myofibrillar protein synthesis and promotes early functional improvements. Following a prolonged period of training, this strategy also increases type II fiber hypertrophy and causes large individual variation in gains in quadricep muscle cross-sectional area.

Daily protein-polyphenol ingestion increases daily myofibrillar protein synthesis rates and promotes early muscle functional gains during resistance training. Am J Physiol Endocrinol Metab 322: E231-E249, 2022. doi: 10.1152/ajpendo.00328.2021. On page E243, Table 5, the muscle protein and DNA content were reported as "wet"weight when it should have been "dry."

BACKGROUND: Short-term ( 0.05). Immobilization led to 2.3 ± 0.4%, 2.7 ± 0.2%, and 2.0 ± 0.4% decreases in quadriceps muscle volume (P  0.05). Daily MyoPS rates during immobilization were 30 ± 2% (HIGH), 26 ± 3% (LOW), and 27 ± 2% (NO) lower in the immobilized compared with the control leg, with no significant differences between groups (P > 0.05). CONCLUSIONS: Three days of muscle disuse induces considerable declines in muscle mass and daily MyoPS rates. However, daily protein intake does not modulate any of these muscle deconditioning responses.Clinical trial registry number: NCT03797781.

Stress fracture of the second metatarsal is a common and problematic injury for runners. The choice of foot strike pattern is known to affect external kinetics and kinematics but its effect on internal loading of the metatarsals is not well understood. Models of various complexities can be used to investigate the effects of running characteristics on metatarsal stresses. This study aimed to compare second metatarsal stress between habitual rearfoot and non-rearfoot strikers during barefoot running, using a novel participant-specific finite element model, including accurate metatarsal and soft tissue geometry. Synchronised force and kinematic data were collected during barefoot overground running from 20 participants (12 rearfoot strikers). Stresses were calculated using a previously evaluated and published 3D finite element model. Non-rearfoot strikers demonstrated greater external loading and joint contact forces than rearfoot runners, but there were no differences in stresses between groups. Additionally, the study allowed for a qualitative assessment of bone geometries and stresses. No correlation was found between bone volume and stresses, however, there was found to be a large variation in metatarsal shapes, possibly accounting for the lack of difference in stresses. This emphasises the importance of bone geometry when estimating bone stress and supports the suggestion that external forces should not be assumed to be representative of internal loading.

Objective:Poor vascular health is associated with reduced bone strength and increased risk of fragility fracture. However, direct measurement of intraosseous vascular health is difficult due to the density and mineral content of bone. We investigated the feasibility of using a commercially available continuous wave near infrared spectroscopy (NIRS) system for the investigation of vascular haemodynamics in human bonein vivo.Approach:An arterial occlusion (AO) protocol was developed for obtaining haemodynamic measurements of the proximal tibia and lateral calf, including assessment of the protocol’s intra operator reproducibility. For 36 participants, intraosseous haemodynamics derived by NIRS were compared to alternative tests of bone health based on dual x-ray absorptiometry (DXA) testing and MRI.Main Results:Near infrared spectroscopy markers of haemodynamics of the proximal tibia demonstrated acceptable reproducibility, comparable with reproducibility assessments of alternative modalities measuring intraosseous haemodynamics, and the use of NIRS for measuring muscle. Novel associations have been demonstrated between haemodynamic markers of bone measured with NIRS and body composition and bone mineral density (BMD) measurements obtained with both DXA and MRI.Significance:Near infrared spectroscopy provides inexpensive, non-invasive, safe, and real time data on changes in oxygenated and deoxygenated haemoglobin concentration in bone at the proximal tibia. This study has demonstrated the potential for NIRS to contribute to research investigating the pathophysiological role of vascular dysfunction within bone tissue, but also the limitations and need for further development of NIRS technology.

Abstract
. Background
. Left ventricular (LV) hypertrophy (LVH) in uncontrolled hypertension is an independent predictor of mortality, though its regression with treatment improves outcomes. Retrospective data suggest that early control of hypertension provides a prognostic advantage and this strategy is included in the 2018 European guidelines, which recommend treating grade II/III hypertension to target blood pressure (BP) within 3 months. The earliest LVH regression to date was demonstrated by echocardiography at 24 weeks. The effect of a rapid guideline-based treatment protocol on LV remodelling, with very early BP control by 18 weeks remains controversial and previously unreported. We aimed to determine whether such rapid hypertension treatment is associated with improvements in LV structure and function through paired cardiovascular magnetic resonance (CMR) scanning at baseline and 18 weeks, utilising CMR mass and feature tracking analysis.
.
. Methods
. We recruited participants with never-treated grade II/III hypertension, initiating a guideline-based treatment protocol which aimed to achieve BP control within 18 weeks. CMR and feature tracking were used to assess myocardial morphology and function immediately before and after treatment.
.
. Results
. We acquired complete pre- and 18-week post-treatment data for 41 participants. During the interval, LV mass index reduced significantly (43.5 ± 9.8 to 37.6 ± 8.3 g/m2, p &lt; 0.001) following treatment, accompanied by reductions in LV ejection fraction (65.6 ± 6.8 to 63.4 ± 7.1%, p = 0.03), global radial strain (46.1 ± 9.7 to 39.1 ± 10.9, p &lt; 0.001), mid-circumferential strain (− 20.8 ± 4.9 to − 19.1 ± 3.7, p = 0.02), apical circumferential strain (− 26.0 ± 5.3 to − 23.4 ± 4.2, p = 0.003) and apical rotation (9.8 ± 5.0 to 7.5 ± 4.5, p = 0.003).
.
. Conclusions
. LVH regresses following just 18 weeks of intensive antihypertensive treatment in subjects with newly-diagnosed grade II/III hypertension. This is accompanied by potentially advantageous functional changes within the myocardium and supports the hypothesis that rapid treatment of hypertension could improve clinical outcomes.
. Trial registration: ISRCTN registry number: 57475376 (assigned 25/06/2015).
.

Short-term disuse leads to muscle loss driven by lowered daily myofibrillar protein synthesis (MyoPS). However, disuse commonly results from muscle damage, and its influence on muscle deconditioning during disuse is unknown. Twenty-one males [20 ± 1 yr, BMI = 24 ± 1 kg·m-2 (± SE)] underwent 7 days of unilateral leg immobilization immediately preceded by 300 bilateral, maximal, muscle-damaging eccentric quadriceps contractions (DAM; subjects n = 10) or no exercise (CON; subjects n = 11). Participants ingested deuterated water and underwent temporal bilateral thigh MRI scans and vastus lateralis muscle biopsies of immobilized (IMM) and nonimmobilized (N-IMM) legs. N-IMM quadriceps muscle volume remained unchanged throughout both groups. IMM quadriceps muscle volume declined after 2 days by 1.7 ± 0.5% in CON (P = 0.031; and by 1.3 ± 0.6% when corrected to N-IMM; P = 0.06) but did not change in DAM, and declined equivalently in CON [by 6.4 ± 1.1% (5.0 ± 1.6% when corrected to N-IMM)] and DAM [by 2.6 ± 1.8% (4.0 ± 1.9% when corrected to N-IMM)] after 7 days. Immobilization began to decrease MyoPS compared with N-IMM in both groups after 2 days (P = 0.109), albeit with higher MyoPS rates in DAM compared with CON (P = 0.035). Frank suppression of MyoPS was observed between days 2 and 7 in CON (IMM = 1.04 ± 0.12, N-IMM = 1.86 ± 0.10%·day-1; P = 0.002) but not DAM (IMM = 1.49 ± 0.29, N-IMM = 1.90 ± 0.30%·day-1; P > 0.05). Declines in MyoPS and quadriceps volume after 7 days correlated positively in CON (r2 = 0.403; P = 0.035) but negatively in DAM (r2 = 0.483; P = 0.037). Quadriceps strength declined following immobilization in both groups, but to a greater extent in DAM. Prior muscle-damaging eccentric exercise increases MyoPS and prevents loss of quadriceps muscle volume after 2 (but not 7) days of disuse.NEW & NOTEWORTHY We investigated the impact of prior muscle-damaging eccentric exercise on disuse-induced muscle deconditioning. Two and 7 days of muscle disuse per se lowered quadriceps muscle volume in association with lowered daily myofibrillar protein synthesis (MyoPS). Prior eccentric exercise prevented the decline in muscle volume after 2 days and attenuated the decline in MyoPS after 2 and 7 days. These data indicate eccentric exercise increases MyoPS and transiently prevents quadriceps muscle atrophy during muscle disuse.

PURPOSE: This study tested the hypothesis that a novel, audio-visual-directed, home-based exercise training intervention would be effective at improving cardiometabolic health and mental well-being in inactive premenopausal women. METHODS: Twenty-four inactive premenopausal women (39 ± 10 years) were randomly assigned to an audio-visual-directed exercise training group (DVD; n = 12) or control group (CON; n = 12). During the 12-week intervention period, the DVD group performed thrice-weekly training sessions of 15 min. Training sessions comprised varying-intensity movements involving multiplanar whole-body accelerations and decelerations (average heart rate (HR) = 76 ± 3% HRmax). CON continued their habitual lifestyle with no physical exercise. A series of health markers were assessed prior to and following the intervention. RESULTS: Following the DVD intervention, HDL cholesterol (pre: 1.83 ± 0.45, post: 1.94 ± 0.46 mmol/L) and mental well-being, assessed via the Warwick Edinburgh Mental Well-Being Scale, improved (P  0.05). There were no pre-post intervention changes in any of the outcome variables in the CON group (P > 0.05). CONCLUSION: the present study suggests that a novel, audio-visual-directed exercise training intervention, consisting of varied-intensity movements interspersed with spinal and lower limb mobility and balance tasks, can improve [HDL cholesterol] and mental well-being in premenopausal women. Therefore, home-based, audio-visual-directed exercise training (45 min/week) appears to be a useful tool to initiate physical activity and improve aspects of health in previously inactive premenopausal women.

Short-term muscle disuse has been reported to lower both postabsorptive and postprandial myofibrillar protein synthesis rates. This study assessed the impact of disuse on daily myofibrillar protein synthesis rates following short-term (2 and 7 days) muscle disuse under free living conditions. Thirteen healthy young men (age: 20 ± 1 yr; BMI: 23 ± 1 kg/m−2) underwent 7 days of unilateral leg immobilization via a knee brace, with the nonimmobilized leg acting as a control. Four days before immobilization participants ingested 400 mL of 70% deuterated water, with 50-mL doses consumed daily thereafter. Upper leg bilateral MRI scans and muscle biopsies were collected before and after 2 and 7 days of immobilization to determine quadriceps volume and daily myofibrillar protein synthesis rates. Immobilization reduced quadriceps volume in the immobilized leg by 1.7 ± 0.3 and 6.7 ± 0.6% after 2 and 7 days, respectively, with no changes in the control leg. Over the 1-wk immobilization period, myofibrillar protein synthesis rates were 36 ± 4% lower in the immobilized (0.81 ± 0.04%/day) compared with the control (1.26 ± 0.04%/day) leg ( P &lt; 0.001). Myofibrillar protein synthesis rates in the control leg did not change over time ( P = 0.775), but in the immobilized leg they were numerically lower during the 0- to 2-day period (16 ± 6%, 1.11 ± 0.09%/day, P = 0.153) and were significantly lower during the 2- to 7-day period (44 ± 5%, 0.70 ± 0.06%/day, P &lt; 0.001) when compared with the control leg. We conclude that 1 wk of muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates in healthy young men.

Abstract
.
. Context
. Anabolic resistance is mechanistically implicated in muscle disuse atrophy.
.
.
. Objective
. The objective of this study is to assess whether anabolic resistance is associated with reduced postprandial amino acid uptake or exacerbated by excess lipid availability.
.
.
. Design, Setting, Participants, and Interventions
. Twenty men underwent 7 days of forearm immobilization while consuming a eucaloric (CON; n = 11) or high-fat overfeeding (HFD; n = 9; 50% excess energy as fat) diet (parallel design) within our Nutritional Physiology Research Unit.
.
.
. Main Outcome Measures
. Preimmobilization and postimmobilization we measured forearm muscle cross-sectional area (aCSA), and postabsorptive and postprandial (3-hour postingestion of a liquid, protein-rich, mixed meal) forearm amino acid metabolism using the arterialized venous-deep venous balance method and infusions of L-[ring-2H5]phenylalanine and L-[1-13C]leucine.
.
.
. Results
. Immobilization did not affect forearm muscle aCSA in either group, but tended to reduce postabsorptive phenylalanine (P =. 07) and leucine (P =. 05) net balances equivalently in CON and HFD. Mixed-meal ingestion switched phenylalanine and leucine net balances from negative to positive (P &amp;lt;. 05), an effect blunted by immobilization (P &amp;lt;. 05) and to a greater extent in HFD than CON (P &amp;lt;. 05). Preimmobilization, meal ingestion increased leucine rates of disappearance (Rd; P &amp;lt;. 05), with values peaking at 191% (from 87 ± 38 to 254 ± 60 µmol·min–1·100 mL forearm volume–1) and 183% (from 141 ± 24 to 339 ± 51 µmol·min–1·100 mL–1) above postabsorptive rates in CON and HFD, respectively, with meal-induced increases not evident postimmobilization in either group (P &amp;gt;. 05).
.
.
. Conclusions
. Disuse impairs the ability of a protein-rich meal to promote positive muscle amino acid balance, which is aggravated by dietary lipid oversupply. Moreover, disuse reduced postprandial forearm amino acid uptake; however, this is not worsened under high-fat conditions.
.

Tibial stress fractures are a problematic injury among runners. Increased loading of the tibia has been observed following prolonged weight‐bearing activity and is suggested to be the result of reduced activity of the plantar flexor muscles. The musculature that spans the tibia contributes to bending of the bone and influences the magnitude of stress on the tibia during running. Participant‐specific models of the tibia can be used as a non‐invasive estimate of tibial stress. This study aimed to quantify tibial stress during running using participant‐specific bone geometry and to compare tibial stress before and after a protocol of repeated muscular contractions of the plantar flexor muscle group. Fourteen participants who run recreationally were included in the final analysis of the study. Synchronized force and kinematic data were collected during overground running before and after an exhaustive, weighted calf‐raise protocol. Bending moments and stress at the distal third of the tibia were estimated using beam theory combined with inverse dynamics and musculoskeletal modeling. Bone geometry was obtained from magnetic resonance images. There was no difference in stress at the anterior, posterior, medial, or lateral peripheries of the tibia after the calf‐raise protocol compared with before. These findings suggest that an exhaustive, repeated calf‐raise protocol did not alter tibial stress during running.

Exhaustive single-leg exercise has been suggested to reduce time to task failure (Tlim) during subsequent exercise in the contralateral leg by exacerbating central fatigue development. We investigated the influence of acetaminophen (ACT), an analgesic that may blunt central fatigue development, on Tlim during single-leg exercise completed with and without prior fatiguing exercise of the contralateral leg. Fourteen recreationally active men performed single-leg severe-intensity knee-extensor exercise to Tlim on the left (Leg1) and right (Leg2) legs without prior contralateral fatigue and on Leg2 immediately following Leg1 (Leg2-CONTRA). The tests were completed following ingestion of 1-g ACT or maltodextrin [placebo (PL)] capsules. Intramuscular phosphorus-containing metabolites and substrates and muscle activation were assessed using 31P-MRS and electromyography, respectively. Tlim was not different between Leg1ACT and Leg1PL conditions (402 ± 101 vs. 390 ± 106 s, P = 0.11). There was also no difference in Tlim between Leg2ACT-CONTRA and Leg2PL-CONTRA (324 ± 85 vs. 311 ± 92 s, P = 0.10), but Tlim was shorter in Leg2ACT-CONTRA and Leg2PL-CONTRA than in Leg2CON (385 ± 104 s, both P < 0.05). There were no differences in intramuscular phosphorus-containing metabolites and substrates or muscle activation between Leg1ACT and Leg1PL and between Leg2ACT-CONTRA and Leg2PL-CONTRA (all P > 0.05). These findings suggest that levels of metabolic perturbation and muscle activation at Tlim are not different during single-leg severe-intensity knee-extensor exercise completed with or without prior fatiguing exercise of the contralateral leg. Despite contralateral fatigue, ACT ingestion did not alter neuromuscular responses, muscle metabolites, or exercise performance.

The following sections 3.5.1 to 3.5.3.2, which previously read.

BACKGROUND: Muscle strength loss following immobilisation has been predominantly attributed to rapid muscle atrophy. However, this cannot fully explain the magnitude of muscle strength loss, so changes in neuromuscular function (NMF) may be involved. OBJECTIVES: We systematically reviewed literature that quantified changes in muscle strength, size and NMF following periods of limb immobilisation in vivo in humans. METHODS: Studies were identified following systematic searches, assessed for inclusion, data extracted and quality appraised by two reviewers. Data were tabulated and reported narratively. RESULTS: Forty eligible studies were included, 22 immobilised lower and 18 immobilised upper limbs. Limb immobilisation ranged from 12 h to 56 days. Isometric muscle strength and muscle size declined following immobilisation; however, change magnitude was greater for strength than size. Evoked resting twitch force decreased for lower but increased for upper limbs. Rate of force development either remained unchanged or slowed for lower and typically slowed for upper limbs. Twitch relaxation rate slowed for both lower and upper limbs. Central motor drive typically decreased for both locations, while electromyography amplitude during maximum voluntary contractions decreased for the lower and presented mixed findings for the upper limbs. Trends imply faster rates of NMF loss relative to size earlier in immobilisation periods for all outcomes. CONCLUSIONS: Limb immobilisation results in non-uniform loss of isometric muscle strength, size and NMF over time. Different outcomes between upper and lower limbs could be attributed to higher degrees of central neural control of upper limb musculature. Future research should focus on muscle function losses and mechanisms following acute immobilisation. REGISTRATION: PROSPERO reference: CRD42016033692.

Flavonoid supplementation improves brachial artery flow-mediated dilation (FMD), but it is not known whether flavonoids protect against vascular dysfunction induced by ischemia-reperfusion (IR) injury and associated respiratory burst. In a randomized, double-blind, placebo-controlled, crossover study, we investigated whether 4 wk supplementation with freeze-dried Montmorency cherry (MC) attenuated suppression of FMD after IR induced by prolonged forearm occlusion. Twelve physically inactive overweight, middle-aged men (52.8 ± 5.8 yr, BMI: 28.1 ± 5.3 kg/m2) consumed MC (235 mg/day anthocyanins) or placebo capsules for 4 wk, with supplementation blocks separated by 4 wk washout. Before and after each supplementation block, FMD responses and plasma nitrate and nitrite ([ NO2- ]) concentrations were measured at baseline and 15, 30, and 45 min after prolonged (20 min) forearm occlusion. FMD response was significantly depressed by the prolonged occlusion ( P < 0.001). After a 45-min reperfusion, FMD was restored to baseline levels after MC (ΔFMD presupplementation: -30.5 ± 8.4%, postsupplementation: -0.6 ± 9.5%) but not placebo supplementation (ΔFMD presupplementation: -11.6 ± 10.6, postsupplementation: -25.4 ± 4.0%; condition × supplement interaction: P = 0.038). Plasma [ NO2- ] decreased after prolonged occlusion but recovered faster after MC compared with placebo (Δ45 min to baseline; MC: presupplementation: -15.3 ± 9.6, postsupplementation: -6.2 ± 8.1; Placebo: presupplementation: -16.3 ± 5.9, postsupplementation: -27.7 ± 11.1 nmol/l; condition × supplement × time interaction: P = 0.033). Plasma peroxiredoxin concentration ([Prx2]) was significantly higher after MC (presupplementation: 22.8 ± 1.4, postsupplementation: 28.0 ± 2.4 ng/ml, P = 0.029) but not after placebo supplementation (presupplementation: 22.1 ± 2.2, postsupplementation: 23.7 ± 1.5 ng/ml). In conclusion, 4 wk MC supplementation enhanced recovery of endothelium-dependent vasodilatation after IR, in parallel with faster recovery of plasma [ NO2- ], suggesting NO dependency. These protective effects seem to be related to increased plasma [Prx2], presumably conferring protection against the respiratory burst during reperfusion. NEW & NOTEWORTHY This is the first study to demonstrate that 4 wk of Montmorency cherry powder supplementation exerted protective effects on endothelium-dependent vasodilation after transient ischemia-reperfusion injury in overweight, physically inactive, nonmedicated, hypertensive middle-aged men. These effects seem to be due to increased nitric oxide availability, as evidenced by higher plasma nitrite concentration and peak arterial diameter during the flow-mediated dilation measurement. This may be a consequence of increased concentration of peroxiredoxin and other antioxidant systems and, hence, reduced reactive oxygen species exposure.

ABSTRACT
.
. Purpose
. Musculoskeletal injuries necessitate periods of disuse (i.e. limb immobilization) during which rapid skeletal muscle atrophy occurs. The relative susceptibility of different muscles of the thigh to disuse atrophy remains uninvestigated. We assessed muscle disuse atrophy of individual thigh muscles throughout 1 wk of unilateral knee immobilization.
.
.
. Methods
. Thirteen healthy, young (20.2 ± 0.6 yr) men underwent 7 d of unilateral leg immobilization via knee bracing. Magnetic resonance imaging scans were performed bilaterally prior to, and following 2 and 7 d of immobilization to determine the volume and anatomical cross-sectional area of the individual muscle groups of the upper legs.
.
.
. Results
. In contrast to the control leg, total thigh muscle volume had decreased by 1.7% ± 0.3% (P &lt; 0.01) and 5.5% ± 0.6% (P &lt; 0.001) in the immobilized leg after 2 and 7 d of disuse, respectively. Muscle loss was significantly greater in the Musculus quadriceps (day 2; 1.7% ± 0.3% (P &lt; 0.05) and day 7; 6.7% ± 0.6%) when compared with the Musculus hamstrings (day 2; 1.4% ± 0.2% (P &lt; 0.01) and day 7; 3.5% ± 0.3%) after 7 d of disuse (P &lt; 0.001). Individual muscles of the thigh exhibited different atrophy rates with the Musculus vastus lateralis anatomical cross-sectional area showing the greater (2.6% ± 0.4% and 7.2% ± 0.8%), and the Musculus gracilis the lesser (1.1% ± 0.7% and 2.3% ± 1.0%) decline following 2 and 7 d of immobilization, respectively (P &lt; 0.01).
.
.
. Conclusions
. Thigh muscle disuse atrophy occurs rapidly and is already evident within 2 d of leg immobilization and progresses at a similar rate over the next 5 d (~0.8% muscle loss per day). M. quadriceps muscle shows more atrophy when compared with the M. hamstrings.
.

It has been reported that mental fatigue decreases exercise performance during high-intensity constant-work-rate exercise (CWR) and self-paced time trials (TT) in recreationally-trained individuals. The purpose of this study was to determine whether performance is impaired following a prolonged cognitive task in individuals trained for competitive sport. Ten trained competitive athletes (ATH) and ten untrained healthy men (UNT) completed a 6-min severe-intensity CWR followed by a 6-min cycling TT immediately following cognitive tasks designed to either perturb (Stroop colour-word task and N-back task; PCT) or maintain a neutral (documentary watching; CON) mental state. UNT had a higher heart rate (75 ± 9 v. 69 ± 7 bpm; P = 0.002) and a lower positive affect PANAS score (19.9 ± 7.5 v. 24.3 ± 4.6; P = 0.036) for PCT compared to CON. ATH showed no difference in heart rate, but had a higher negative affect score for PCT compared to CON (15.1 ± 3.7 v. 12.2 ± 2.7; P = 0.029). Pulmonary O2 uptake during CWR was not different between PCT and CON for ATH or UNT. Work completed during TT was not different between PCT and CON for ATH (PCT 103 ± 12 kJ; CON 102 ± 12 kJ; P > 0.05) or UNT (PCT 75 ± 11 kJ; CON 74 ± 12 kJ; P > 0.05). Compared to CON, during PCT, UNT showed unchanged psychological stress responses, whereas ATH demonstrated increased psychological stress responses. However, regardless of this distinction, exercise performance was not affected by PCT in either competitive athletes or untrained individuals.

The study aimed to explore how both sex and dietary restraint impacts brain activation in response to visual food stimuli in young adolescents (12-13 years) under fed and fasted conditions. Food and non-food images were viewed by 15 boys and 14 girls, while functional magnetic resonance images were acquired. The adolescents were either fasted or in a satiated (fed) state following a randomized crossover study design. When satiation state was not considered, girls showed significantly greater brain activity than boys in regions associated with executive function and decision making, working memory, and self-awareness. In contrast, when either fasted or fed states were considered separately, boys showed significantly increased brain activity in regions linked to executive function, self-awareness, and decision making than the girls. When fasted, compared to unrestrained eaters, restrained individuals showed heightened activation in regions connected to executive function and decision making, with areas associated with self-assessment showing increased activity for unrestrained eaters relative to restrained under fed conditions. These findings highlight important differences in adolescent brain activity and support further investigations to gain greater insight into how these differences might evolve with age.

The physiological and exercise performance adaptations to sprint interval training (SIT) may be modified by dietary nitrate ([Formula: see text]) supplementation. However, it is possible that different types of [Formula: see text] supplementation evoke divergent physiological and performance adaptations to SIT. The purpose of this study was to compare the effects of 4-wk SIT with and without concurrent dietary [Formula: see text] supplementation administered as either [Formula: see text]-rich beetroot juice (BR) or potassium [Formula: see text] (KNO3). Thirty recreationally active subjects completed a battery of exercise tests before and after a 4-wk intervention in which they were allocated to one of three groups: 1) SIT undertaken without dietary [Formula: see text] supplementation (SIT); 2) SIT accompanied by concurrent BR supplementation (SIT + BR); or 3) SIT accompanied by concurrent KNO3 supplementation (SIT + KNO3). During severe-intensity exercise, V̇o2peak and time to task failure were improved to a greater extent with SIT + BR than SIT and SIT + KNO3 ( P < 0.05). There was also a greater reduction in the accumulation of muscle lactate at 3 min of severe-intensity exercise in SIT + BR compared with SIT + KNO3 ( P < 0.05). Plasma [Formula: see text] concentration fell to a greater extent during severe-intensity exercise in SIT + BR compared with SIT and SIT + KNO3 ( P < 0.05). There were no differences between groups in the reduction in the muscle phosphocreatine recovery time constant from pre- to postintervention ( P > 0.05). These findings indicate that 4-wk SIT with concurrent BR supplementation results in greater exercise capacity adaptations compared with SIT alone and SIT with concurrent KNO3 supplementation. This may be the result of greater NO-mediated signaling in SIT + BR compared with SIT + KNO3. NEW & NOTEWORTHY We compared the influence of different forms of dietary nitrate supplementation on the physiological and performance adaptations to sprint interval training (SIT). Compared with SIT alone, supplementation with nitrate-rich beetroot juice, but not potassium [Formula: see text], enhanced some physiological adaptations to training.

BACKGROUND: Heterozygous mutations in the HNF1B gene are the most common monogenic cause of developmental kidney disease. Extrarenal phenotypes frequently occur, including diabetes mellitus and pancreatic hypoplasia; the latter is associated with subclinical exocrine dysfunction. We measured faecal elastase-1 in patients with HNF1B-associated disease regardless of diabetes status and assessed the degree of symptoms associated with pancreatic exocrine deficiency. METHODS: Faecal elastase-1 was measured in 29 patients with a known HNF1B mutation. We defined a low faecal elastase-1 concentration based on the 2.5 percentile of 99 healthy control individuals (410 μg/g stool). Symptoms related to pancreatic exocrine dysfunction were assessed and a subset of the HNF1B cohort (n  =  6) underwent pancreatic imaging. RESULTS: Faecal elastase-1 was below the 2.5 percentile of the control cohort in 18/29 (62%) patients with HNF1B-associated renal disease. A total of 8/29 (28%) had a measurement suggestive of exocrine pancreatic insufficiency at  

Purpose: Repeated cycles of endothelial ischemia–reperfusion injury and the resulting respiratory burst contribute to the irreversible pathophysiology of vascular diseases, and yet, the effects of ischemia reperfusion on vascular function, oxidative stress, and nitric oxide (NO) bioavailability have not been assessed simultaneously. Therefore, this study sought to examine the effects of prolonged forearm occlusion and subsequent reperfusion on NO-dependent brachial artery endothelial function. Methods: Flow-mediated dilatation was measured at baseline and 15, 30, and 45 min after 20-min forearm occlusion in 14 healthy, but physically inactive middle-aged men (53.7 ± 1.2 years, BMI: 28.1 ± 0.1 kg m−2). Venous blood samples collected from the occluded arm were analyzed for NO metabolites and markers of oxidative stress. Results: FMD was significantly depressed after the prolonged occlusion compared to baseline, with a significant reduction 15-min post-occlusion (6.6 ± 0.7 to 2.9 ± 0.4%, p < 0.001); FMD remained depressed after 30 min (4.1 ± 0.6%, p = 0.001), but was not significantly different to baseline after 45-min recovery (5.4 ± 0.7%, p = 0.079). Plasma nitrate (main time effect: p = 0.015) and nitrite (main time effect: p = 0.034) concentrations were significantly reduced after prolonged occlusion. Plasma catalase activity was significantly elevated at 4- (p = 0.016) and 45-min (p = 0.001) post-occlusion, but plasma peroxiredoxin 2 and protein carbonyl content did not change. Conclusions: Prolonged forearm occlusion resulted in acute impairment of endothelium-dependent vasodilatation of the brachial artery for at least 30 min after reperfusion. We demonstrate that this vascular dysfunction is associated with oxidative stress and reduced NO bioavailability following reperfusion.

Purpose: to investigate the influence of β-alanine (BA) supplementation on muscle carnosine content, muscle pH and the power-duration relationship (i.e. critical power and W'). Methods: in a double-blind, randomized, placebo-controlled study, 20 recreationally-active males (22 ± 3 y, V°O2peak 3.73 ± 0.44 L·min-1) ingested either BA (6.4 g/d for 28 d) or placebo (PL) (6.4 g/d) for 28 d. Subjects completed an incremental test and two 3-min all-out tests separated by 1-min on a cycle ergometer pre- and post-supplementation. Muscle pH was assessed using 31P-magnetic resonance spectroscopy (MRS) during incremental (INC KEE) and intermittent knee-extension exercise (INT KEE). Muscle carnosine content was determined using 1H-MRS. Results: There were no differences in the change in muscle carnosine content from pre- to post-intervention (PL: 1 ± 16% vs. BA: -4 ± 25%) or in muscle pH during INC KEE or INT KEE (P > 0.05) between PL and BA, but blood pH (PL: -0.06 ± 0.10 vs. BA: 0.09 ± 0.13) during the incremental test was elevated post-supplementation in the BA group only (P < 0.05). The changes from pre- to post-supplementation in critical power (PL: -8 ± 18 W vs. BA: -6 ± 17 W) and W' (PL: 1.8 ± 3.3 kJ vs. BA: 1.5 ± 1.7 kJ) were not different between groups. No relationships were detected between muscle carnosine content and indices of exercise performance. Conclusions: BA supplementation had no significant effect on muscle carnosine content and no influence on intramuscular pH during incremental or high-intensity intermittent knee-extension exercise. The small increase in blood pH following BA supplementation was not sufficient to significantly alter the power-duration relationship or exercise performance.

Measurement of hemodynamic wall shear stress (WSS) is important in investigating the role of WSS in the initiation and progression of atherosclerosis. Echo particle image velocimetry (echo PIV) is a novel ultrasound-based technique for measuring WSS in vivo that has previously been validated in vitro using the standard optical PIV technique. We evaluated the repeatability and reproducibility of echo PIV for measuring WSS in the human common carotid artery. We measured WSS in 28 healthy participants (18 males and 10 females, mean age: 56 ± 12 y). Echo PIV was highly repeatable, with an intra-observer variability of 1.0 ± 0.1 dyn/cm2 for peak systolic (maximum), 0.9 dyn/cm2 for mean and 0.5 dyn/cm2 for end-diastolic (minimum) WSS measurements. Likewise, echo PIV was reproducible, with a low inter-observer variability (max: 2.0 ± 0.2 dyn/cm2, mean: 1.3 ± 0.1 dyn/cm2, end-diastolic: 0.7 dyn/cm2) and more variable inter-scan (test-retest) variability (max: 7.1 ± 2.3 dyn/cm2, mean: 2.9 ± 0.4 dyn/cm2, min: 1.5 ± 0.1 dyn/cm2). We compared echo PIV with the reference method, phase-contrast magnetic resonance imaging (PC-MRI); echo PIV-based WSS measurements agreed qualitatively with PC-MRI measurements (r = 0.89, p 

PURPOSE: to compare the effects of self-paced high-intensity interval and continuous cycle training on health markers in premenopausal women. METHODS: Forty-five inactive females were randomised to a high-intensity interval training (HIIT; n = 15), continuous training (CT; n = 15) or an inactive control (CON; n = 15) group. HIIT performed 5 × 5 min sets comprising repetitions of 30-s low-, 20-s moderate- and 10-s high-intensity cycling with 2 min rest between sets. CT completed 50 min of continuous cycling. Training was completed self-paced, 3 times weekly for 12 weeks. RESULTS: Peak oxygen uptake (16 ± 8 and 21 ± 12%), resting heart rate (HR) (-5 ± 9 and -4 ± 7 bpm) and visual and verbal learning improved following HIIT and CT compared to CON (P 

Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties. High flavonoid intakes attenuate age-related cognitive decline, but data from human intervention studies are sparse. We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion, task-related activation, and cognitive function in healthy older adults. Participants were randomised to consume either 30 mL blueberry concentrate providing 387 mg anthocyanidins (5 female, 7 male; age 67.5 ± 3.0 y; body mass index, 25.9 ± 3.3 kg·m-2) or isoenergetic placebo (8 female, 6 male; age 69.0 ± 3.3 y; body mass index, 27.1 ± 4.0 kg·m-2). Pre- and postsupplementation, participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5T magnetic resonance imaging scanner while functional magnetic resonance images were continuously acquired. Quantitative resting brain perfusion was determined using an arterial spin labelling technique, and blood biomarkers of inflammation and oxidative stress were measured. Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/21/40/44/45, precuneus, anterior cingulate, and insula/thalamus (p < 0.001) as well as significant improvements in grey matter perfusion in the parietal (5.0 ± 1.8 vs -2.9 ± 2.4%, p = 0.013) and occipital (8.0 ± 2.6 vs -0.7 ± 3.2%, p = 0.031) lobes. There was also evidence suggesting improvement in working memory (2-back test) after blueberry versus placebo supplementation (p = 0.05). Supplementation with an anthocyanin-rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.

Background: Third metatarsal stress fractures are relatively common during Royal Marines recruit training; however, their aetiology is poorly understood. Mathematical modelling of the third metatarsal may aid in understanding risk factors for stress fracture, particularly if the influence of footwear on peak bending stresses can be determined. This study built on previous models of metatarsal bending stress by integrating individual metatarsal geometry and gait data. Methods: Data from five males with size 11 (UK) feet were acquired. MRI images were digitised to determine cross-sectional bone parameters. Gait variables included vertical ground reaction forces, plantar pressure and foot orientation. The magnitude and location of peak bending stresses were calculated for barefoot running, before standard issue combat boots and trainers were compared. Findings: Estimated peak compressive, tensile and torsional stresses were greater in combat assault boots than in trainers (p < 0.05) with medium effect sizes but wide confidence intervals. However, differences in bone geometry between individuals had a much greater influence on estimated peak stresses. Interpretation: Results suggest that bone geometry has a greater influence on third metatarsal stress fracture risk than footwear. Future bone stress simulations should account for bone geometry. Further development of the model in a variety of participants should proceed to verify these suggestions.

We hypothesized that 4 wk of dietary nitrate supplementation would enhance exercise performance and muscle metabolic adaptations to sprint interval training (SIT). Thirty-six recreationally active subjects, matched on key variables at baseline, completed a series of exercise tests before and following a 4-wk period in which they were allocated to one of the following groups: 1) SIT and [Formula: see text]-depleted beetroot juice as a placebo (SIT+PL); 2) SIT and [Formula: see text]-rich beetroot juice (~13 mmol [Formula: see text]/day; SIT+BR); or 3) no training and [Formula: see text]-rich beetroot juice (NT+BR). During moderate-intensity exercise, pulmonary oxygen uptake was reduced by 4% following 4 wk of SIT+BR and NT+BR (P < 0.05) but not SIT+PL. The peak work rate attained during incremental exercise increased more in SIT+BR than in SIT+PL (P < 0.05) or NT+BR (P < 0.001). The reduction in muscle and blood [lactate] and the increase in muscle pH from preintervention to postintervention were greater at 3 min of severe-intensity exercise in SIT+BR compared with SIT+PL and NT+BR (P < 0.05). However, the change in severe-intensity exercise performance was not different between SIT+BR and SIT+PL (P > 0.05). The relative proportion of type IIx muscle fibers in the vastus lateralis muscle was reduced in SIT+BR only (P < 0.05). These findings suggest that BR supplementation may enhance some aspects of the physiological adaptations to SIT.NEW & NOTEWORTHY We investigated the influence of nitrate-rich and nitrate-depleted beetroot juice on the muscle metabolic and physiological adaptations to 4 wk of sprint interval training. Compared with placebo, dietary nitrate supplementation reduced the O2 cost of submaximal exercise, resulted in greater improvement in incremental (but not severe-intensity) exercise performance, and augmented some muscle metabolic adaptations to training. Nitrate supplementation may facilitate some of the physiological responses to sprint interval training.

We tested the hypothesis that dietary nitrate (NO3-)-rich beetroot juice (BR) supplementation could partially offset deteriorations in O2 transport and utilization and exercise tolerance after blood donation. Twenty-two healthy volunteers performed moderate-intensity and ramp incremental cycle exercise tests prior to and following withdrawal of ∼450 ml of whole blood. Before donation, all subjects consumed seven 70-ml shots of NO3--depleted BR [placebo (PL)] in the 48 h preceding the exercise tests. During the 48 h after blood donation, subjects consumed seven shots of BR (each containing 6.2 mmol of NO3-, n = 11) or PL (n = 11) before repeating the exercise tests. Hemoglobin concentration and hematocrit were reduced by ∼8-9% following blood donation (P < 0.05), with no difference between the BR and PL groups. Steady-state O2 uptake during moderate-intensity exercise was ∼4% lower after than before donation in the BR group (P < 0.05) but was unchanged in the PL group. The ramp test peak power decreased from predonation (341 ± 70 and 331 ± 68 W in PL and BR, respectively) to postdonation (324 ± 69 and 322 ± 66 W in PL and BR, respectively) in both groups (P < 0.05). However, the decrement in performance was significantly less in the BR than PL group (2.7% vs. 5.0%, P < 0.05). NO3- supplementation reduced the O2 cost of moderate-intensity exercise and attenuated the decline in ramp incremental exercise performance following blood donation. These results have implications for improving functional capacity following blood loss.

Nitric oxide alters gastric blood flow, improves vascular function, and mediates glucose uptake within the intestines and skeletal muscle. Dietary nitrate, acting as a source of nitric oxide, appears to be a potential low-cost therapy that may help maintain glucose homeostasis. In a randomized, double-blind, placebo-controlled crossover study, 31 young and older adult participants had a standardized breakfast, supplemented with either nitrate-rich beetroot juice (11.91 mmol nitrate) or nitrate-depleted beetroot juice as placebo (0.01 mmol nitrate). MRI was used to assess apparent diffusion coefficient (ADC), portal vein flux, and velocity. Plasma glucose, incretin, and C-peptide concentrations and blood pressure were assessed. Outcome variables were measured at baseline and hourly for 3 h. Compared with a placebo, beetroot juice resulted in a significant elevation in plasma nitrate and plasma nitrite concentration. No differences were seen for the young or older adult cohorts between placebo and beetroot juice for ADC, or portal vein flux. There was an interaction effect in the young adults between visits for portal vein velocity. Nitrate supplementation did not reduce plasma glucose, active GLP-1, total GLP-1, or plasma C-peptide concentrations for the young or older adult cohorts. Despite a significant elevation in plasma nitrite concentration following an acute dose of (11.91 mmol) nitrate, there was no effect on hepatic blood flow, plasma glucose, C-peptide, or incretin concentration in healthy adults.

Arterial spin labelling (ASL) provides a potential method to non-invasively determine muscle blood flow and examine the impact of interventions such as supplementation and training. However, it's a method with intrinsically low signal, leading to limitations in accuracy and temporal resolution. To examine these limitations, the current study measured perfusion via ASL on three occasions in the rectus femoris of 10 healthy adults, during light and moderate exercise, over three different exercise durations. For data sampled over 9 min, light intensity exercise gave an average perfusion of 35.0 ± 5.1 ml/min.100g−1 with a coefficient of variation (COV) of 16% and single intraclass correlation coefficient (ICC) of 0.67. For the moderate bout, perfusion was 51.3 ± 5.6 ml/min.100g−1 (COV 10%, ICC 0.82). When the same data were analyzed over 5 min 24 s, perfusion was 37.8 ± 11.13 (COV 30%, ICC 0.13) during light and 49.5 ± 8.8 ml/min.100g−1 (COV 18%, ICC 0.52) during moderate exercise. When sampling was reduced to 1 min 48 s, perfusion was 41.2 ± 13.7 (COV 33%, ICC 0.26) during light and 49.5 ± 13.6 ml/min.100g−1 (COV 28%, ICC 0.04) during moderate exercise. For 9 min a significant perfusion difference was found between the exercise intensities; however, this was not the case for sampling over 5 min 24 s or 1 min 48 s. Such findings illustrate the potential of ASL to non-invasively monitor muscle perfusion under steady-state conditions, but highlight that extended exercise protocols are necessary in order to generate date of sufficient reliability to be able to discriminate intervention dependent perfusion differences.

Arterial spin labelling (ASL) provides a potential method to non-invasively determine muscle blood flow and examine the impact of interventions such as supplementation and training. However, it's a method with intrinsically low signal, leading to limitations in accuracy and temporal resolution. To examine these limitations, the current study measured perfusion via ASL on three occasions in the rectus femoris of 10 healthy adults, during light and moderate exercise, over three different exercise durations. For data sampled over 9 min, light intensity exercise gave an average perfusion of 35.0 ± 5.1 ml/min.100g(-1) with a coefficient of variation (COV) of 16% and single intraclass correlation coefficient (ICC) of 0.67. For the moderate bout, perfusion was 51.3 ± 5.6 ml/min.100g(-1) (COV 10%, ICC 0.82). When the same data were analyzed over 5 min 24 s, perfusion was 37.8 ± 11.13 (COV 30%, ICC 0.13) during light and 49.5 ± 8.8 ml/min.100g(-1) (COV 18%, ICC 0.52) during moderate exercise. When sampling was reduced to 1 min 48 s, perfusion was 41.2 ± 13.7 (COV 33%, ICC 0.26) during light and 49.5 ± 13.6 ml/min.100g(-1) (COV 28%, ICC 0.04) during moderate exercise. For 9 min a significant perfusion difference was found between the exercise intensities; however, this was not the case for sampling over 5 min 24 s or 1 min 48 s. Such findings illustrate the potential of ASL to non-invasively monitor muscle perfusion under steady-state conditions, but highlight that extended exercise protocols are necessary in order to generate date of sufficient reliability to be able to discriminate intervention dependent perfusion differences.

We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n=56) were randomized to complete a single bout of short (FG15) or long duration (FG60) small sided football or low magnitude whole body vibration training (VIB). Procollagen type 1 amino-terminal propeptide (P1NP) was increased during exercise for FG15 (51.6±23.0 to 56.5±22.5 μg·L-1, mean ± SD, P

The study examined which of a number of different magnetic resonance (MR) methods were sensitive to detecting muscle damage induced by eccentric exercise. Seventeen healthy, physically active participants, with muscle damage confirmed by non-MR methods were tested 24 h after performing eccentric exercise. Techniques investigated whether damage could be detected within the quadriceps muscle as a whole, and individually within the rectus femoris, vastus lateralis (VL), vastus medialis (VM), and vastus intermedius (VI). Relative to baseline values, significant changes were seen in leg and muscle cross-sectional areas and volumes and the resting inorganic phosphate concentration. Significant time effects over all muscles were also seen in the transverse relaxation time (T2) and apparent diffusion coefficient (ADC) values, with individually significant changes seen in the VL, VM, and VI for T2 and in the VI for ADC. A significant correlation was found between muscle volume and the average T2 change (r = 0.59) but not between T2 and ADC or Pi alterations. There were no significant time effects over all muscles for magnetization transfer contrast images, for baseline pH, phosphocreatine (PCr), phosphodiester, or ATP metabolite concentrations or the time constant describing the rate of PCr recovery following exercise.

The study examined which of a number of different magnetic resonance (MR) methods were sensitive to detecting muscle damage induced by eccentric exercise. Seventeen healthy, physically active participants, with muscle damage confirmed by non-MR methods were tested 24h after performing eccentric exercise. Techniques investigated whether damage could be detected within the quadriceps muscle as a whole, and individually within the rectus femoris, vastus lateralis (VL), vastus medialis (VM), and vastus intermedius (VI). Relative to baseline values, significant changes were seen in leg and muscle cross-sectional areas and volumes and the resting inorganic phosphate concentration. Significant time effects over all muscles were also seen in the transverse relaxation time (T2) and apparent diffusion coefficient (ADC) values, with individually significant changes seen in the VL, VM, and VI for T2 and in the VI for ADC. A significant correlation was found between muscle volume and the average T2 change (r=0.59) but not between T2 and ADC or Pi alterations. There were no significant time effects over all muscles for magnetization transfer contrast images, for baseline pH, phosphocreatine (PCr), phosphodiester, or ATP metabolite concentrations or the time constant describing the rate of PCr recovery following exercise.

UNLABELLED: it is possible that dietary nitrate (NO3 (-)) supplementation may improve both physical and cognitive performance via its influence on blood flow and cellular energetics. PURPOSE: to investigate the effects of dietary NO3 (-) supplementation on exercise performance and cognitive function during a prolonged intermittent sprint test (IST) protocol, which was designed to reflect typical work patterns during team sports. METHODS: in a double-blind randomised crossover study, 16 male team-sport players received NO3 (-)-rich (BR; 140 mL day(-1); 12.8 mmol of NO3 (-)), and NO3 (-)-depleted (PL; 140 mL day(-1); 0.08 mmol NO3 (-)) beetroot juice for 7 days. On day 7 of supplementation, subjects completed the IST (two 40-min "halves" of repeated 2-min blocks consisting of a 6-s "all-out" sprint, 100-s active recovery and 20 s of rest), on a cycle ergometer during which cognitive tasks were simultaneously performed. RESULTS: Total work done during the sprints of the IST was greater in BR (123 ± 19 kJ) compared to PL (119 ± 17 kJ; P < 0.05). Reaction time of response to the cognitive tasks in the second half of the IST was improved in BR compared to PL (BR first half: 820 ± 96 vs. second half: 817 ± 86 ms; PL first half: 824 ± 114 vs. second half: 847 ± 118 ms; P < 0.05). There was no difference in response accuracy. CONCLUSIONS: These findings suggest that dietary NO3 (-) enhances repeated sprint performance and may attenuate the decline in cognitive function (and specifically reaction time) that may occur during prolonged intermittent exercise.

Purpose: the primary purpose of this investigation was to compare the recovery of the W′ to the recovery of intramuscular substrates and metabolites using 31P- and 1H-magnetic resonance spectroscopy. Methods: Ten healthy recreationally trained subjects were tested to determine critical power (CP) and W′ for single-leg-extensor exercise. They subsequently exercised in the bore of a 1.5-T MRI scanner at a supra-CP work rate. Following exhaustion, the subjects rested in place for 1, 2, 5 or 7 min, and then repeated the effort. The temporal course of W′ recovery was estimated, which was then compared to the recovery of creatine phosphate [PCr], pH, carnosine content, and to the output of a novel derivation of the W′BAL model. Results: W′ recovery closely correlated with the predictions of the novel model (r = 0.97, p = 0.03). [PCr] recovered faster (Formula presented.) than W′(Formula presented.) the W′ available for the second exercise bout was directly correlated with the difference between [PCr] at the beginning of the work bout and [PCr] at exhaustion (r = 0.99, p = 0.005). Nonlinear regression revealed an inverse curvilinear relationship between carnosine concentration and the W′t1/2 (r2 = 0.55). Conclusion: the kinetics of W′ recovery in single-leg-extensor exercise is comparable to that observed in whole-body exercise, suggesting a conserved mechanism. The extent to which the recovery of the W′ can be directly attributed to the recovery of [PCr] is unclear. The relationship of the W′ to muscle carnosine content suggests novel future avenues of investigation.

PURPOSE: the primary purpose of this investigation was to compare the recovery of the W' to the recovery of intramuscular substrates and metabolites using (31)P- and (1)H-magnetic resonance spectroscopy. METHODS: Ten healthy recreationally trained subjects were tested to determine critical power (CP) and W' for single-leg-extensor exercise. They subsequently exercised in the bore of a 1.5-T MRI scanner at a supra-CP work rate. Following exhaustion, the subjects rested in place for 1, 2, 5 or 7 min, and then repeated the effort. The temporal course of W' recovery was estimated, which was then compared to the recovery of creatine phosphate [PCr], pH, carnosine content, and to the output of a novel derivation of the W' BAL model. RESULTS: W' recovery closely correlated with the predictions of the novel model (r = 0.97, p = 0.03). [PCr] recovered faster [Formula: see text] than W' [Formula: see text] the W' available for the second exercise bout was directly correlated with the difference between [PCr] at the beginning of the work bout and [PCr] at exhaustion (r = 0.99, p = 0.005). Nonlinear regression revealed an inverse curvilinear relationship between carnosine concentration and the W' t 1/2 (r (2) = 0.55). CONCLUSION: the kinetics of W' recovery in single-leg-extensor exercise is comparable to that observed in whole-body exercise, suggesting a conserved mechanism. The extent to which the recovery of the W' can be directly attributed to the recovery of [PCr] is unclear. The relationship of the W' to muscle carnosine content suggests novel future avenues of investigation.

© 2015 Springer-Verlag Berlin Heidelberg Purpose: Magnetically controlled growth rods (MCGRs) are a new technology for the management of early-onset pediatric deformity enabling guided spinal growth by controlling the curvature. These rods contain a rare earth magnet and are contraindicated for MRI. We have investigated the behavior MCGRs to determine whether MRI adversely affects rod properties and to determine the extent of image distortion. Methods: This is an in vitro experiment using two magnetic growth rods secured in a 1.5 T MRI. A gradient echo sequence MRI was performed to evaluate whether the rods elongated, contracted or rotated during scanning and a phantom model was used to evaluate the amount of artifact induced. Results: the rod was not activated or subsequently impaired by the process of MRI. Image distortion of 28.9 cm along the long axis of the magnet and 20.1 cm perpendicular to this was seen with extension 10.6 cm cranial to the magnet housing. No negative effect was demonstrated on the magnetic rod elongation mechanism. Conclusions: This study has demonstrated that there are no detrimental effects of MRI on the MCGR and imaging of the head and neck phantom can still be interpreted. Further in vivo study is warranted.

We tested the hypothesis that the time constants (τ) of postexercise T2. MRI signal intensity (an index of O2 delivery) and muscle [PCr] (an index of metabolic perturbation, measured by (31)P-MRS) in hypoxia would be accelerated after dietary nitrate (NO3 (-)) supplementation. In a double-blind crossover design, eight moderately trained subjects underwent 5 days of NO3 (-) (beetroot juice, BR; 8.2 mmol/day NO3 (-)) and placebo (PL; 0.003 mmol/day NO3 (-)) supplementation in four conditions: normoxic PL (N-PL), hypoxic PL (H-PL; 13% O2), normoxic NO3 (-) (N-BR), and hypoxic NO3 (-) (H-BR). The single-leg knee-extension protocol consisted of 10 min of steady-state exercise and 24 s of high-intensity exercise. The [PCr] recovery τ was greater in H-PL (30 ± 4 s) than H-BR (22 ± 4 s), N-PL (24 ± 4 s) and N-BR (22 ± 4 s) (P < 0.05) and the maximal rate of mitochondrial ATP resynthesis (Qmax) was lower in the H-PL (1.12 ± 0.16 mM/s) compared with H-BR (1.35 ± 0.26 mM/s), N-PL (1.47 ± 0.28 mM/s), and N-BR (1.40 ± 0.21 mM/s) (P < 0.05). The τ of postexercise T2. signal intensity was greater in H-PL (47 ± 14 s) than H-BR (32 ± 10 s), N-PL (38 ± 9 s), and N-BR (27 ± 6 s) (P < 0.05). The postexercise [PCr] and T2. recovery τ were correlated in hypoxia (r = 0.60; P < 0.05), but not in normoxia (r = 0.28; P > 0.05). These findings suggest that the NO3 (-)-NO2 (-)-NO pathway is a significant modulator of muscle energetics and O2 delivery during hypoxic exercise and subsequent recovery.

BACKGROUND: in this substudy of the effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes, we report the development of a novel nitrate depleted beetroot juice for use clinical trials and determine if dietary nitrate supplementation improved cognitive function in patients with type 2 diabetes mellitus. METHODS: Beetroot juice was treated with the anion exchange resin Purolite A520e. UV-vis-spectrophotometry, and a blind taste test were performed along with determination of sugar content, measurement of ascorbate and dehydroascorbate, the ionic composition of juice and Proton NMR. Subsequently, 27 patients, age 67.2±4.9 years, (18 male) were recruited for a double blind, randomised, placebo-controlled crossover trial. Participants were randomised to begin in either order beetroot juice (nitrate content 7.5 mmol per 250 ml) or placebo (nitrate depleted beetroot juice nitrate content 0.002 mmol per 250 ml). At the end of each 2 week supplementation period cognitive function was assessed using E-prime, E-Studio software with 5 separate tests being performed. The tests utilised in the present study have been adapted from the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: the differences in the UV-vis spectra were comparable to the natural variation found in differing cultivars. There were no discernable differences in taste, sugar content, or Proton NMR. Ascorbate and dehydroascorbate were undetectable in either juice. After 2 weeks of beetroot juice simple reaction time was significantly quicker in the active arm at 327±40 ms versus 341.8±52.7 ms in the placebo arm, mean difference 13.9±25.6 ms (95% CI 3.8-24.0 ms), p=0.009. No other measures of cognitive function differed between treatment arms. CONCLUSION: We have developed an effective placebo beetroot juice for use in trials of supplementation of dietary nitrate. Two weeks supplementation of the diet with 7.5 mmol of nitrate per day caused a significant improvement in simple reaction time in individuals with T2DM.

Purpose: the present study investigated the effects of 16 weeks of small-volume, small-sided soccer training soccer group (SG, n=13) and oscillating whole-body vibration training vibration group (VG, n=17) on body composition, aerobic fitness, and muscle PCr kinetics in healthy inactive premenopausal women in comparison with an inactive control group (CO, n=14). Methods: Training for SG and VG consisted of twice-weekly 15-min sessions with average heart rates (HRs) of ~155 and 90bpm respectively. Pre- and post-measurements of body composition (DXA), phosphocreatine (PCr) on- and off-kinetics, and HR measurements during standardised submaximal exercise were performed. Results: After 16 weeks of training in SG, fat percentage was lowered (p=0.03) by 1.7%±2.4% from 37.5%±6.9% to 35.8%±6.2% and the PCr decrease in the quadriceps during knee-extension ramp exercise was attenuated (4%±8%, p=0.04), with no changes in VG or CO (time-group effect: p=0.03 and p=0.03). Submaximal exercise HR was also reduced in SG after 16 weeks of training (6%±5% of HRmax, p=0.01). Conclusion: Short duration soccer training for 16 weeks appears to be sufficient to induce favourable changes in body composition and indicators of aerobic fitness and muscle oxidative capacity in untrained premenopausal women.

PURPOSE: During constant work rate exercise above the lactate threshold (LT), the initial rapid phase of pulmonary oxygen uptake (VO₂) kinetics is supplemented by an additional VO₂ slow component (VO₂Sc) which reduces the efficiency of muscular work. The VO₂Sc amplitude has been shown to increase with maturation but the mechanisms are poorly understood. We utilized the transverse relaxation time (T₂) of muscle protons from magnetic resonance imaging (MRI) to test the hypothesis that a lower VO₂ slow component (VO₂Sc) amplitude in children would be associated with a reduced muscle recruitment compared to adults. METHODS: Eight boys (mean age 11.4 ± 0.4) and eight men (mean age 25.3 ± 3.3 years) completed repeated step transitions of unloaded-to-very heavy-intensity (U → VH) exercise on a cycle ergometer. MRI scans of the thigh region were acquired at rest and after VH exercise up to the VO₂Sc time delay (ScTD) and after 6 min. T₂ for each of eight muscles was adjusted in relation to cross-sectional area and then summed to provide the area-weighted ΣT₂ as an index of thigh recruitment. RESULTS: There were no child/adult differences in the relative VO₂Sc amplitude [Boys 14 ± 7 vs. Men 18 ± 3 %, P = 0.15, effect size (ES) = 0.8] during which the change (∆) in area-weighted ΣT₂ between the ScTD and 6 min was not different between groups (Boys 1.6 ± 1.2 vs. Men 2.3 ± 1.1 ms, P = 0.27, ES = 0.6). A positive and strong correlation was found between the relative VO₂Sc amplitude and the magnitude of the area-weighted ∆ΣT₂ in men (r = 0.92, P = 0.001) but not in boys (r = 0.09, P = 0.84). CONCLUSIONS: This study provides evidence to show that progressive muscle recruitment (as inferred from T₂ changes) contributes to the development of the VO₂Sc during intense submaximal exercise independent of age.

Purpose: During constant work rate exercise above the lactate threshold (LT), the initial rapid phase of pulmonary oxygen uptake ([Formula Presented]O2) kinetics is supplemented by an additional [Formula Presented]O2 slow component ([Formula Presented]O2Sc) which reduces the efficiency of muscular work. The [Formula Presented]O2Sc amplitude has been shown to increase with maturation but the mechanisms are poorly understood. We utilized the transverse relaxation time (T2) of muscle protons from magnetic resonance imaging (MRI) to test the hypothesis that a lower [Formula Presented]O2 slow component ([Formula Presented]O2Sc) amplitude in children would be associated with a reduced muscle recruitment compared to adults.

During constant work rate exercise above the
lactate threshold (LT ), the initial rapid phase of pulmonary
oxygen uptake (˙V O2) kinetics is supplemented by an
additional ˙V O2 slow component (˙V O2Sc) which reduces
the efficiency of muscular work. The ˙V O2Sc amplitude has
been shown to increase with maturation but the mechanisms
are poorly understood. We utilized the transverse
relaxation time (T2) of muscle protons from magnetic resonance
imaging (MRI) to test the hypothesis that a lower
˙V
O2 slow component (˙V O2Sc) amplitude in children would
be associated with a reduced muscle recruitment compared
to adults.
Methods Eight boys (mean age 11.4 ± 0.4) and eight
men (mean age 25.3 ± 3.3 years) completed repeated step
transitions of unloaded-to-very heavy-intensity (U → VH)
exercise on a cycle ergometer. MRI scans of the thigh
region were acquired at rest and after VH exercise up to
the ˙V O2Sc time delay (ScTD) and after 6 min. T2 for each of eight muscles was adjusted in relation to cross-sectional
area and then summed to provide the area-weighted ΣT2 as
an index of thigh recruitment.
Results T here were no child/adult differences in the relative
˙VO2Sc amplitude [Boys 14 ± 7 vs. Men 18 ± 3 %,
P = 0.15, effect size (ES) = 0.8] during which the change
(Δ) in area-weighted ΣT2 between the ScTD and 6 min
was not different between groups (Boys 1.6 ± 1.2 vs. Men
2.3 ± 1.1 ms, P = 0.27, ES = 0.6). A positive and strong
correlation was found between the relative ˙V O2Sc amplitude
and the magnitude of the area-weighted ΔΣT2 in men
(r = 0.92, P = 0.001) but not in boys (r = 0.09, P = 0.84).
Conclusions T his study provides evidence to show
that progressive muscle recruitment (as inferred from T2
changes) contributes to the development of the ˙V O2Sc during
intense submaximal exercise independent of age.

Children and adolescents are less susceptible to muscle fatigue during repeated bouts of high-intensity exercise than adults, but the physiological basis for these differences is not clear. The purpose of the current investigation was to investigate the muscle metabolic responses, using 31-phosphorus magnetic resonance spectroscopy, during fatiguing isometric quadriceps exercise in 13 adolescents (7 females) and 14 adults (8 females). Participants completed 30 maximal voluntary contractions (6-s duration) separated by 6 s of rest. Fatigue was quantified as the relative decrease in force over the test. Fatigue was not significantly different with age (p = 0.20) or sex (p = 0.63). Metabolic perturbation (change in phosphocreatine, inorganic phosphate, and ADP concentrations) was significantly greater in adults compared with adolescents; no sex effects were present. Muscle pH did not differ with age or sex. Phosphocreatine recovery following exercise was not significantly different with age (p = 0.27) or sex (p = 0.97) but a significant interaction effect was present (p = 0.04). Recovery tended to be faster in boys than men but slower in girls than women, though no significant group differences were identified. The results of this study show that at a comparable level of muscle fatigue, the metabolic profile is profoundly different between adolescents and adults.

Phosphorous magnetic resonance spectroscopy (31P-MRS) and near-infra red spectroscopy (NIRS) provide methods for measuring spinal muscle function non-invasively but their reliability is not established. The aim of this study was assess the reliability (ICC) and error magnitude (CV%) of measurements of muscle phosphocreatine (PCr), tissue oxygenation index (TOI), and muscle deoxyhaemoglobin (HHb) acquired during fatigue and in recovery after 24 s exercise in the lumbar muscles. Ten healthy participants (19-25 years, 5 male, 5 female) performed exercise that involved holding the upper body unsupported in slight extension until fatigue and then, after 30 minutes of rest, for repeated bursts of 24 seconds. ICCs indicated good to excellent reliability of baseline measures (TOI:0.75) and of amplitude changes during fatigue (PCr:0.73, TOI:0.69, HHb:0.80), and recovery (HHb:0.96) and poor to fair reliability for time constants describing rates of change during fatigue (PCr:0.11) and recovery (PCr:0.31, HHb:0.47). CV% indicated varying relative measurement error across baseline measures (TOI:5%), amplitude changes during fatigue (PCr:7%, TOI:38%, HHb:31%) and recovery (HHb:31%), and in time constants for fatigue (PCr:39%) and recovery (PCr:20%, HHb:37%). The results suggested that reliability would be sufficient for future studies on spinal muscle function but that measurement error may be too large to evaluate individuals.

The phosphocreatine (PCr) recovery time constant (τ) following exercise provides a measure of mitochondrial oxidative capacity. The purpose of this investigation was to use 2 different protocols to determine τ in adolescent females. 31P-MR spectra were collected during 2 exercise tests in 6 adolescent girls (13.8 ± 0.3 y) and 7 women (23.2 ± 3.4 y). The first test consisted of 23 repeated 4 seconds maximal isometric calf contractions separated by 12-second recovery; PCr recovery between the final 18 contractions was used to calculate τ. The second test was a sustained 20-second maximal contraction; recovery was fitted with an exponential function to measure τ. PCr τ did not significantly differ between groups: (gated exercise: 4 girls: 16 ± 5 s, 7 women: 17 ± 5 s, p; sustained exercise: 6 girls: 19 ± 6 s, 7 women: 19 ± 4 s). Bland-Altman analysis demonstrated a close agreement between sustained and gated exercise. Both gated and sustained exercise appear feasible in a pediatric population, and offer a noninvasive evaluation of mitochondrial oxidative capacity.

DNA polymerase δ, whose catalytic subunit is encoded by POLD1, is responsible for lagging-strand DNA synthesis during DNA replication. It carries out this synthesis with high fidelity owing to its intrinsic 3'- to 5'-exonuclease activity, which confers proofreading ability. Missense mutations affecting the exonuclease domain of POLD1 have recently been shown to predispose to colorectal and endometrial cancers. Here we report a recurring heterozygous single-codon deletion in POLD1 affecting the polymerase active site that abolishes DNA polymerase activity but only mildly impairs 3'- to 5'-exonuclease activity. This mutation causes a distinct multisystem disorder that includes subcutaneous lipodystrophy, deafness, mandibular hypoplasia and hypogonadism in males. This discovery suggests that perturbing the function of the ubiquitously expressed POLD1 polymerase has unexpectedly tissue-specific effects in humans and argues for an important role for POLD1 function in adipose tissue homeostasis. © 2013 Nature America, Inc. All rights reserved.

DNA polymerase δ, whose catalytic subunit is encoded by POLD1, is responsible for lagging-strand DNA synthesis during DNA replication. It carries out this synthesis with high fidelity owing to its intrinsic 3'- to 5'-exonuclease activity, which confers proofreading ability. Missense mutations affecting the exonuclease domain of POLD1 have recently been shown to predispose to colorectal and endometrial cancers. Here we report a recurring heterozygous single-codon deletion in POLD1 affecting the polymerase active site that abolishes DNA polymerase activity but only mildly impairs 3'- to 5'-exonuclease activity. This mutation causes a distinct multisystem disorder that includes subcutaneous lipodystrophy, deafness, mandibular hypoplasia and hypogonadism in males. This discovery suggests that perturbing the function of the ubiquitously expressed POLD1 polymerase has unexpectedly tissue-specific effects in humans and argues for an important role for POLD1 function in adipose tissue homeostasis.

Dietary nitrate (NO(3)(-)) supplementation has been shown to reduce resting blood pressure and alter the physiological response to exercise in young adults. We investigated whether these effects might also be evident in older adults. In a double-blind, randomized, crossover study, 12 healthy, older (60-70 yr) adults supplemented their diet for 3 days with either nitrate-rich concentrated beetroot juice (BR; 2 × 70 ml/day, ∼9.6 mmol/day NO(3)(-)) or a nitrate-depleted beetroot juice placebo (PL; 2 × 70 ml/day, ∼0.01 mmol/day NO(3)(-)). Before and after the intervention periods, resting blood pressure and plasma [nitrite] were measured, and subjects completed a battery of physiological and cognitive tests. Nitrate supplementation significantly increased plasma [nitrite] and reduced resting systolic (BR: 115 ± 9 vs. PL: 120 ± 6 mmHg; P < 0.05) and diastolic (BR: 70 ± 5 vs. PL: 73 ± 5 mmHg; P < 0.05) blood pressure. Nitrate supplementation resulted in a speeding of the Vo(2) mean response time (BR: 25 ± 7 vs. PL: 28 ± 7 s; P < 0.05) in the transition from standing rest to treadmill walking, although in contrast to our hypothesis, the O(2) cost of exercise remained unchanged. Functional capacity (6-min walk test), the muscle metabolic response to low-intensity exercise, brain metabolite concentrations, and cognitive function were also not altered. Dietary nitrate supplementation reduced resting blood pressure and improved Vo(2) kinetics during treadmill walking in healthy older adults but did not improve walking or cognitive performance. These results may have implications for the enhancement of cardiovascular health in older age.

Dietary nitrate supplementation, which enhances nitric oxide (NO) bioavailability, has previously been shown to contribute to improved exercise performance by reducing both oxygen cost and energy expenditure. In contrast, previous studies have indicated that NO can lower force production in vitro. To examine the role of dietary nitrates in regulating force generation under normal physiological conditions, we undertook an extended nitrate supplementation regime and determined force output and energy cost with a repeated isometric maximum voluntary contraction (MVC) protocol. In a double-blind, randomized, crossover design, eight participants received 0.5 l/day of nitrate-rich (BR) or nitrate-depleted (PL) beetroot juice for 15 days and completed an exercise protocol consisting of 50 MVCs at 2.5 h, 5 days and 15 days after the beginning of the supplementation period. No significant reduction in force output was determined for BR relative to PL for the peak contraction, the mean or the end force, and no significant time effect was found over the course of the supplementation period. There was a reduction in the mean PCr cost of exercise averaged over the BR supplementation trials, but this did not reach statistical significance for end exercise (BR 15.10 ± 4.14 mM, PL 17.10 ± 5.34 mM, P = 0.06) or the mean throughout the protocol (BR 15.96 ± 4.14 mM, PL 17.79 ± 4.51 mM, P = 0.06). However, a significant reduction in PCr cost per unit force output was found for BR at end exercise (P = 0.04). These results indicate that, under normal physiological conditions, increased NO bioavailability is not associated with a reduction of force-generating capability in human skeletal muscle and confirm that nitrate supplementation reduces the PCr cost of force production. © 2013 Springer-Verlag Berlin Heidelberg.

Dietary nitrate supplementation, which enhances nitric oxide (NO) bioavailability, has previously been shown to contribute to improved exercise performance by reducing both oxygen cost and energy expenditure. In contrast, previous studies have indicated that NO can lower force production in vitro. To examine the role of dietary nitrates in regulating force generation under normal physiological conditions, we undertook an extended nitrate supplementation regime and determined force output and energy cost with a repeated isometric maximum voluntary contraction (MVC) protocol. In a double-blind, randomized, crossover design, eight participants received 0.5 l/day of nitrate-rich (BR) or nitrate-depleted (PL) beetroot juice for 15 days and completed an exercise protocol consisting of 50 MVCs at 2.5 h, 5 days and 15 days after the beginning of the supplementation period. No significant reduction in force output was determined for BR relative to PL for the peak contraction, the mean or the end force, and no significant time effect was found over the course of the supplementation period. There was a reduction in the mean PCr cost of exercise averaged over the BR supplementation trials, but this did not reach statistical significance for end exercise (BR 15.10 ± 4.14 mM, PL 17.10 ± 5.34 mM, P = 0.06) or the mean throughout the protocol (BR 15.96 ± 4.14 mM, PL 17.79 ± 4.51 mM, P = 0.06). However, a significant reduction in PCr cost per unit force output was found for BR at end exercise (P = 0.04). These results indicate that, under normal physiological conditions, increased NO bioavailability is not associated with a reduction of force-generating capability in human skeletal muscle and confirm that nitrate supplementation reduces the PCr cost of force production.

Intermittent hypoxic training (IHT) is sometimes used by athletes to enhance nonhematological physiological adaptations to simulated altitude. We investigated whether IHT would result in greater improvements in muscle energetics and exercise tolerance compared with work-matched intermittent normoxic training (INT). Nine physically active men completed 3 wk of intensive, single-leg knee-extensor exercise training. Each training session consisted of 25 min of IHT (FiO2 14.5 ± 0.1%) with the experimental leg and 25 min of INT with the alternate leg, which served as a control. Before and after the training intervention, subjects completed a test protocol consisting of a bout of submaximal constant-work-rate exercise, a 24-s high-intensity exercise bout to quantify the phosphocreatine recovery time constant ([PCr]-τ), and an incremental test to the limit of tolerance. The tests were completed in normoxia and hypoxia in both INT and IHT legs. Muscle metabolism was assessed noninvasively using (31)P-magnetic resonance spectroscopy. Improvements in the time-to-exhaustion during incremental exercise were not significantly different between training conditions either in normoxia (INT, 28 ± 20% vs. IHT, 25 ± 9%; P = 0.86) or hypoxia (INT, 21 ± 10% vs. IHT, 15 ± 11%; P = 0.29). In hypoxia, [PCr]-τ was speeded slightly but significantly more post-IHT compared with post-INT (-7.3 ± 2.9 s vs. -3.7 ± 1.7 s; P < 0.01), but changes in muscle metabolite concentrations during exercise were essentially not different between IHT and INT. Under the conditions of this investigation, IHT does not appreciably alter muscle metabolic responses or incremental exercise performance compared with INT.

We tested the hypothesis that muscle high-energy phosphate compounds and metabolites related to the fatigue process would be recovered after exhaustion during recovery exercise performed below but not above critical power (CP) and that these changes would influence the capacity to continue exercise. Eight male subjects completed single-leg, knee-extension exercise to exhaustion (for ∼180 s) on three occasions, followed by a work-rate reduction to severe-intensity exercise, heavy-intensity exercise (CP differ according to whether the recovery exercise is performed below or above the CP. These findings confirm the importance of the CP as an intramuscular metabolic threshold that dictates the accumulation of fatigue-related metabolites and the capacity to tolerate high-intensity exercise.

We investigated the responses of intramuscular phosphate-linked metabolites and pH (as assessed by (31)P-MRS) during intermittent high-intensity exercise protocols performed with different recovery-interval durations. Following estimation of the parameters of the power-duration relationship, i.e. the critical power (CP) and curvature constant (W'), for severe-intensity constant-power exercise, nine male subjects completed three intermittent exercise protocols to exhaustion where periods of high-intensity constant-power exercise (60 s) were separated by different durations of passive recovery (18 s, 30 s and 48 s). The tolerable duration of exercise was 304 ± 68 s, 516 ± 142 s, and 847 ± 240 s for the 18-s, 30-s, and 48-s recovery protocols, respectively (P < 0.05). The work done >CP (W>CP) was significantly greater for all intermittent protocols compared with the subjects' W', and this difference became progressively greater as recovery-interval duration was increased. The restoration of intramuscular phosphocreatine concentration during recovery was greatest, intermediate, and least for 48 s, 30 s, and 18 s of recovery, respectively (P < 0.05). The W>CP in excess of W' increased with greater durations of recovery, and this was correlated with the mean magnitude of muscle phosphocreatine reconstitution between work intervals (r = 0.61; P < 0.01). The results of this study show that during intermittent high-intensity exercise, recovery intervals allow intramuscular homeostasis to be restored, with the degree of restoration being related to the duration of the recovery interval. Consequently, and consistent with the intermittent CP model, the ability to perform W>CP during intermittent high-intensity exercise and, therefore, exercise tolerance, increases when recovery-interval duration is extended.

A previous modelling study predicted that the forces applied by the extensor muscles to stabilise the lumbar spine would be greater in spines that have a larger sagittal curvature (lordosis). Because the force-generating capacity of a muscle is related to its size, it was hypothesised that the size of the extensor muscles in a subject would be related to the size of their lumbar lordosis. Magnetic resonance imaging (MRI) data were obtained, together with age, height, body mass and back pain status, from 42 female subjects. The volume of the extensor muscles (multifidus and erector spinae) caudal to the mid-lumbar level was estimated from cross-sectional area measurements in axial T1-weighted MRIs spanning the lumbar spine. Lower lumbar curvature was determined from sagittal T1-weighted images. A stepwise linear regression model was used to determine the best predictors of muscle volume. The mean lower lumbar extensor muscle volume was 281cm3 (SD=49cm3). The mean lower lumbar curvature was 30° (SD=7°). Five subjects reported current back pain and were excluded from the regression analysis. Nearly half the variation in muscle volume was accounted for by the variables age (standardised coefficient, B=-3.2, P=0.03) and lower lumbar curvature (B=0.47, P=0.002). The results support the hypothesis that extensor muscle volume in the lower lumbar spine is related to the magnitude of the sagittal curvature; this has implications for assessing muscle size as an indicator of muscle strength. © 2013 Anatomical Society.

The purpose of this investigation was to determine the influence of heat stress on the dynamics of muscle metabolic perturbation during high-intensity exercise. Seven healthy males completed single-legged knee-extensor exercise until the limit of tolerance on two separate occasions. In a randomized order the subjects underwent 40 min of lowerbody immersion in warm water at 42°C prior to exercise (HOT) or received no prior thermal manipulation (CON). Following the intervention, muscle metabolism was measured at rest and throughout exercise using 31P-MRS. The tolerable duration of high-intensity exercise was reduced by 36% after passive heating (CON:474 ± 146 vs. HOT:303 ± 76 s; P = 0.005). Intramuscular pH was lower over the first 60 s of exercise (CON:7.05 ± 0.02 vs. HOT:7.00 ± 0.03; P = 0.019) in HOT compared to CON. The rate of muscle [PCr] degradation during exercise was greater in the HOT condition (CON: -0.17 ± 0.08 vs. HOT: -0.25 ± 0.10% s-1; P = 0.006) and pH also tended to change more rapidly in HOT (P = 0.09). Muscle [PCr] (CON:26 ± 14 vs. HOT:29 ± 10%), [Pi] (CON:504 ± 236 vs. HOT:486 ± 186%) and pH (CON:6.84 ± 0.13 vs. HOT:6.80 ± 0.14; P>0.05) were not statistically different at the limit of tolerance (P>0.05 for all comparisons). These results suggest that the reduced time-to-exhaustion during high-intensity knee-extensor exercise following lower-body heating might be related, in part, to accelerated rates of change of intramuscular [PCr] and pH towards 'critical' values that limit muscle function. © Springer-Verlag 2012.

The purpose of this investigation was to determine the influence of heat stress on the dynamics of muscle metabolic perturbation during high-intensity exercise. Seven healthy males completed single-legged knee-extensor exercise until the limit of tolerance on two separate occasions. In a randomized order the subjects underwent 40 min of lower-body immersion in warm water at 42°C prior to exercise (HOT) or received no prior thermal manipulation (CON). Following the intervention, muscle metabolism was measured at rest and throughout exercise using (31)P-MRS. The tolerable duration of high-intensity exercise was reduced by 36% after passive heating (CON: 474 ± 146 vs. HOT: 303 ± 76 s; P = 0.005). Intramuscular pH was lower over the first 60 s of exercise (CON: 7.05 ± 0.02 vs. HOT: 7.00 ± 0.03; P = 0.019) in HOT compared to CON. The rate of muscle [PCr] degradation during exercise was greater in the HOT condition (CON: -0.17 ± 0.08 vs. HOT: -0.25 ± 0.10% s(-1); P = 0.006) and pH also tended to change more rapidly in HOT (P = 0.09). Muscle [PCr] (CON: 26 ± 14 vs. HOT: 29 ± 10%), [Pi] (CON: 504 ± 236 vs. HOT: 486 ± 186%) and pH (CON: 6.84 ± 0.13 vs. HOT: 6.80 ± 0.14; P > 0.05) were not statistically different at the limit of tolerance (P > 0.05 for all comparisons). These results suggest that the reduced time-to-exhaustion during high-intensity knee-extensor exercise following lower-body heating might be related, in part, to accelerated rates of change of intramuscular [PCr] and pH towards 'critical' values that limit muscle function.

We investigated whether abnormalities in the structural organization of the corpus callosum in the presence of curvilinear lipoma are associated with increased facilitation of response time to bilateral stimuli, an effect known as the redundancy gain (RG). A patient (A.J.) with a curvilinear lipoma of the corpus callosum, his genetically-identical twin, and age-matched control participants made speeded responses to luminant stimuli. Structural organization of callosal regions was assessed with diffusion-tensor imaging. A.J. was found to have reduced structural integrity in the splenium of the corpus callosum and produced a large RG suggestive of neural summation.

Exercise in hypoxia is associated with reduced muscle oxidative function and impaired
exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases
plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia
on muscle metabolism and oxidative function. In a double-blind, randomised crossover study,
nine healthy subjects completed knee-extension exercise to the limit of tolerance (Tlim), once
in normoxia (20.9% O2; CON) and twice in hypoxia (14.5% O2). During 24 h prior to the
hypoxia trials, subjects consumed 0.75 L of nitrate-rich beetroot juice (9.3 mmol nitrate; HBR)
or 0.75 L of nitrate-depleted beetroot juice as a placebo (0.006 mmol nitrate; H-PL).
Muscle metabolism was assessed using calibrated 31P-MRS. Plasma [nitrite] was elevated
(P

Dietary supplementation with beetroot juice (BR) has been shown to reduce resting blood pressure and the O(2) cost of submaximal exercise and to increase tolerance to high-intensity cycling. We tested the hypothesis that the physiological effects of BR were consequent to its high NO(3)(-) content per se, and not the presence of other potentially bioactive compounds. We investigated changes in blood pressure, mitochondrial oxidative capacity (Q(max)), and physiological responses to walking and moderate- and severe-intensity running following dietary supplementation with BR and NO(3)(-)-depleted BR [placebo (PL)]. After control (nonsupplemented) tests, nine healthy, physically active male subjects were assigned in a randomized, double-blind, crossover design to receive BR (0.5 l/day, containing ∼6.2 mmol of NO(3)(-)) and PL (0.5 l/day, containing ∼0.003 mmol of NO(3)(-)) for 6 days. Subjects completed treadmill exercise tests on days 4 and 5 and knee-extension exercise tests for estimation of Q(max) (using (31)P-magnetic resonance spectroscopy) on day 6 of the supplementation periods. Relative to PL, BR elevated plasma NO(2)(-) concentration (183 ± 119 vs. 373 ± 211 nM, P < 0.05) and reduced systolic blood pressure (129 ± 9 vs. 124 ± 10 mmHg, P < 0.01). Q(max) was not different between PL and BR (0.93 ± 0.05 and 1.05 ± 0.22 mM/s, respectively). The O(2) cost of walking (0.87 ± 0.12 and 0.70 ± 0.10 l/min in PL and BR, respectively, P < 0.01), moderate-intensity running (2.26 ± 0.27 and 2.10 ± 0.28 l/min in PL and BR, respectively, P < 0.01), and severe-intensity running (end-exercise O(2) uptake = 3.77 ± 0.57 and 3.50 ± 0.62 l/min in PL and BL, respectively, P < 0.01) was reduced by BR, and time to exhaustion during severe-intensity running was increased by 15% (7.6 ± 1.5 and 8.7 ± 1.8 min in PL and BR, respectively, P < 0.01). In contrast, relative to control, PL supplementation did not alter plasma NO(2)(-) concentration, blood pressure, or the physiological responses to exercise. These results indicate that the positive effects of 6 days of BR supplementation on the physiological responses to exercise can be ascribed to the high NO(3)(-) content per se.

Noninvasive, easy-to-use and accurate measurements of wall shear stress (WSS) in human blood vessels have always been challenging in clinical applications. Echo particle image velocimetry (Echo PIV) has shown promise for clinical measurements of local hemodynamics and wall shear rate. Thus far, however, the method has only been validated under simple flow conditions. In this study, we validated Echo PIV under in vitro and in vivo conditions. For in vitro validation, we used an anatomically correct, compliant carotid bifurcation flow phantom with pulsatile flow conditions, using optical particle image velocimetry (optical PIV) as the reference standard. For in vivo validation, we compared Echo PIV-derived 2-D velocity fields obtained at the carotid bifurcation in five normal subjects against phase-contrast magnetic resonance imaging (PC-MRI)-derived velocity measurements obtained at the same locations. For both studies, time-dependent, 2-D, two-component velocity vectors; peak/centerline velocity, flow rate and wall shear rate (WSR) waveforms at the common carotid artery (CCA), carotid bifurcation and distal internal carotid artery (ICA) were examined. Linear regression, correlation analysis and Bland-Altman analysis were used to quantify the agreement of different waveforms measured by the two techniques. In vitro results showed that Echo PIV produced good images of time-dependent velocity vector maps over the cardiac cycle with excellent temporal (up to 0.7 ms) and spatial (∼0.5 mm) resolutions and quality, comparable with optical PIV results. Further, good agreement was found between Echo PIV and optical PIV results for velocity and WSR measurements. In vivo results also showed good agreement between Echo PIV velocities and phase contrast MRI velocities. We conclude that Echo PIV provides accurate velocity vector and WSR measurements in the carotid bifurcation and has significant potential as a clinical tool for cardiovascular hemodynamics evaluation.

We used ³¹P-magnetic resonance spectroscopy to test the hypothesis that exercise-induced muscle damage (EIMD) alters the muscle metabolic response to dynamic exercise, and that this contributes to the observed reduction in exercise tolerance following EIMD in humans. Ten healthy, physically active men performed incremental knee extensor exercise inside the bore of a whole body 1.5-T superconducting magnet before (pre) and 48 h after (post) performing 100 squats with a load corresponding to 70% of body mass. There were significant changes in all markers of muscle damage [perceived muscle soreness, creatine kinase activity (434% increase at 24 h), and isokinetic peak torque (16% decrease at 24 h)] following eccentric exercise. Muscle phosphocreatine concentration ([PCr]) and pH values during incremental exercise were not different pre- and post-EIMD (P > 0.05). However, resting inorganic phosphate concentration ([P(i)]; pre: 4.7 ± 0.8; post: 6.7 ± 1.7 mM; P < 0.01) and, consequently, [P(i)]/[PCr] values (pre: 0.12 ± 0.02; post: 0.18 ± 0.05; P < 0.01) were significantly elevated following EIMD. These mean differences were maintained during incremental exercise (P < 0.05). Time to exhaustion was significantly reduced following EIMD (519 ± 56 and 459 ± 63 s, pre- and post-EIMD, respectively, P < 0.001). End-exercise pH (pre: 6.75 ± 0.04; post: 6.83 ± 0.04; P < 0.05) and [PCr] (pre: 7.2 ± 1.7; post: 14.5 ± 2.1 mM; P < 0.01) were higher, but end-exercise [P(i)] was not significantly different (pre: 19.7 ± 1.9; post: 21.1 ± 2.6 mM, P > 0.05) following EIMD. The results indicate that alterations in phosphate metabolism, specifically the elevated [P(i)] at rest and throughout exercise, may contribute to the reduced exercise tolerance observed following EIMD.

There are reports of abnormal pulmonary oxygen uptake (Vo(2)) and deoxygenated hemoglobin ([HHb]) kinetics in individuals with Type 2 diabetes (T2D) below 50 yr of age with disease durations of

The aim of this investigation was to examine the adaptation of the muscle phosphates (e.g. phosphocreatine (PCr) and ADP) implicated in regulating oxidative phosphorylation, and oxygenation at the onset of high intensity exercise in children and adults. The hypotheses were threefold: primary PCr kinetics would be faster in children than adults; the amplitude of the PCr slow component would be attenuated in children; and the amplitude of the deoxyhaemoglobin/myoglobin (HHb) slow component would be reduced in children. Eleven children (5 girls, 6 boys, 13 +/- 1 years) and 11 adults (5 women, 6 men, 24 +/- 4 years) completed two to four constant work rate exercise tests within a 1.5 T MR scanner. Quadriceps muscle energetics during high intensity exercise were monitored using (31)P-MRS. Muscle oxygenation was monitored using near-infrared spectroscopy. The time constant for the PCr response was not significantly different in boys (31 +/- 10 s), girls (31 +/- 10 s), men (44 +/- 20 s) or women (29 +/- 14 s, main effects: age, p = 0.37, sex, p = 0.25). The amplitude of the PCr slow component relative to end-exercise PCr was not significantly different between children (23 +/- 23%) and adults (17 +/- 13%, p = 0.47). End-exercise [PCr] was significantly lower, and [ADP] higher, in females (18 +/- 4 mM and 53 +/- 16 microM) than males (23 +/- 4 mM, p = 0.02 and 37 +/- 11 microM, p = 0.02), but did not differ with age ([PCr]: p = 0.96, [ADP]: p = 0.72). The mean response time for muscle tissue deoxygenation was significantly faster in children (22 +/- 4 s) than adults (27 +/- 7 s, p = 0.01). The results of this study show that the control of oxidative metabolism at the onset of high intensity exercise is adult-like in 13-year-old children, but that matching of oxygen delivery to extraction is more precise in adults.

The purpose of this study was to elucidate the mechanistic bases for the reported reduction in the O(2) cost of exercise following short-term dietary nitrate (NO(3)(-)) supplementation. In a randomized, double-blind, crossover study, seven men (aged 19-38 yr) consumed 500 ml/day of either nitrate-rich beet root juice (BR, 5.1 mmol of NO(3)(-)/day) or placebo (PL, with negligible nitrate content) for 6 consecutive days, and completed a series of low-intensity and high-intensity "step" exercise tests on the last 3 days for the determination of the muscle metabolic (using (31)P-MRS) and pulmonary oxygen uptake (Vo(2)) responses to exercise. On days 4-6, BR resulted in a significant increase in plasma [nitrite] (mean +/- SE, PL 231 +/- 76 vs. BR 547 +/- 55 nM; P < 0.05). During low-intensity exercise, BR attenuated the reduction in muscle phosphocreatine concentration ([PCr]; PL 8.1 +/- 1.2 vs. BR 5.2 +/- 0.8 mM; P < 0.05) and the increase in Vo(2) (PL 484 +/- 41 vs. BR 362 +/- 30 ml/min; P < 0.05). During high-intensity exercise, BR reduced the amplitudes of the [PCr] (PL 3.9 +/- 1.1 vs. BR 1.6 +/- 0.7 mM; P < 0.05) and Vo(2) (PL 209 +/- 30 vs. BR 100 +/- 26 ml/min; P < 0.05) slow components and improved time to exhaustion (PL 586 +/- 80 vs. BR 734 +/- 109 s; P < 0.01). The total ATP turnover rate was estimated to be less for both low-intensity (PL 296 +/- 58 vs. BR 192 +/- 38 microM/s; P < 0.05) and high-intensity (PL 607 +/- 65 vs. BR 436 +/- 43 microM/s; P < 0.05) exercise. Thus the reduced O(2) cost of exercise following dietary NO(3)(-) supplementation appears to be due to a reduced ATP cost of muscle force production. The reduced muscle metabolic perturbation with NO(3)(-) supplementation allowed high-intensity exercise to be tolerated for a greater period of time.

Severe-intensity constant-work-rate exercise results in the attainment of maximal oxygen uptake, but the muscle metabolic milieu at the limit of tolerance (T(lim)) for such exercise remains to be elucidated. We hypothesized that T(lim) during severe-intensity exercise would be associated with the attainment of consistently low values of intramuscular phosphocreatine ([PCr]) and pH, as determined using (31)P magnetic resonance spectroscopy, irrespective of the work rate and the inspired O(2) fraction. We also hypothesized that hyperoxia would increase the asymptote of the hyperbolic power-duration relationship (the critical power, CP) without altering the curvature constant (W). Seven subjects (mean +/- s.d. age 30 +/- 9 years) completed four constant-work-rate knee-extension exercise bouts to the limit of tolerance (range, 3-10 min) both in normoxia (N) and in hyperoxia (H; 70% O(2)) inside the bore of 1.5 T superconducting magnet. The [PCr] (approximately 5-10% of resting baseline) and pH (approximately 6.65) at the limit of tolerance during each of the four trials was not significantly different either in normoxia or in hyperoxia. At the same fixed work rate, the overall rate at which [PCr] fell with time was attenuated in hyperoxia (mean response time: N, 59 +/- 20 versus H, 116 +/- 46 s; P < 0.05). The CP was higher (N, 16.1 +/- 2.6 versus H, 18.0 +/- 2.3 W; P < 0.05) and the W was lower (N, 1.92 +/- 0.70 versus H, 1.48 +/- 0.31 kJ; P < 0.05) in hyperoxia compared with normoxia. These data indicate that T(lim) during severe-intensity exercise is associated with the attainment of consistently low values of muscle [PCr] and pH. The CP and W parameters of the power-duration relationship were both sensitive to the inspiration of hyperoxic gas.

Metabolic transitions from rest to high-intensity exercise were divided into two discrete steps (i.e. rest-to-moderate-intensity (R-->M) and moderate-to-high-intensity (M-->H)) to explore the effect of prior high-intensity 'priming' exercise on intramuscular [PCr] and pulmonary VO₂ kinetics for different sections of the motor unit pool. It was hypothesized that [PCr] and VO₂ kinetics would be unaffected by priming during R-->M exercise, but that the time constants (tau) describing the fundamental [PCr] response and the phase II VO₂ response would be significantly reduced by priming for M-->H exercise. On three separate occasions, six male subjects completed two identical R-->M/M-->H 'work-to-work' prone knee-extension exercise bouts separated by 5min rest. Two trials were performed with measurement of pulmonary VO₂ and the integrated electromyogram (iEMG) of the right m. vastus lateralis. The third trial was performed within the bore of a 1.5-T superconducting magnet for (31)P-MRS assessment of muscle metabolic responses. Priming did not significantly affect the [PCr] or VO₂ tau during R-->M ([PCr] tau Unprimed: 24+/-16 vs. Primed: 22+/-14s; VO₂ tau Unprimed: 26+/-8 vs. Primed: 25+/-9s) or M-->H transitions ([PCr] tau Unprimed: 30+/-5 vs. Primed: 32+/-7s; VO₂ tau Unprimed: 37+/-5 vs. Primed: 38+/-9s). However, it did reduce the amplitudes of the [PCr] and VO₂ slow components by 50% and 46%, respectively, during M-->H (PH exercise after priming. It is concluded that the tau for the initial exponential change of muscle [PCr] and pulmonary VO₂ following the transition from moderate-to-high-intensity prone knee-extension exercise is not altered by priming exercise.

PURPOSE: This study tested the hypothesis that the muscle metabolic responses of 9- to 12-yr-old children and young adults during incremental quadriceps exercise are dependent on age and sex. METHODS: Fifteen boys, 18 girls, 8 men, and 8 women completed a quadriceps step-incremental test to exhaustion inside a magnetic resonance scanner for determination of the muscle metabolic responses using P-magnetic resonance spectroscopy. Quadriceps muscle mass was determined using magnetic resonance imaging scans enabling comparison of metabolic data at a normalized power output. RESULTS: the power output and the energetic state at the Pi/PCr and pH intracellular thresholds (IT) were independent of age and sex. The rate of change in Pi/PCr against power output after the ITPi/PCr (S2) was lower in boys (0.158 +/- 0.089) and girls (0.257 +/- 0.110) compared with men (0.401 +/- 0.114, P < 0.001) and women (0.391 +/- 0.133, P = 0.014), respectively, with sex differences present for children only (P = 0.003). Above the ITpH, S2 was more rapid in the men (-0.041 +/- 0.022, P = 0.003) and girls (-0.030 +/- 0.013, P = 0.011) compared with boys (-0.019 +/- 0.007), with no differences between the girls and the women (-0.035 +/- 0.015, P = 0.479). The increase in Pi/PCr at exhaustion was lower in boys (0.85 +/- 0.38) than that in men (1.86 +/- 0.65, P < 0.001) and in girls (1.78 +/- 1.25) than that in women (4.97 +/- 3.52, P = 0.003), with sex differences in both the child (P = 0.005) and the adult groups (P = 0.019). CONCLUSIONS: During moderate-intensity exercise, muscle metabolism appears adult-like in 9- to 12-yr-old children, although both age- and sex-related differences in the "anaerobic" energy turnover are present during high-intensity exercise.

It is not possible to attain a metabolic steady state during exercise above the so-called critical force or critical power. We tested the hypothesis that the muscle metabolic perturbations at the end of a bout of maximal isometric contractions, which yield a stable end-test force (equal to the critical force), would be similar to that at task failure following submaximal contractions performed above the critical force. Eight healthy subjects (four female) performed isometric single knee-extension exercise in the bore of a 1.5 T superconducting magnet on two occasions. Following familiarization, subjects performed the following exercises: (1) 60 maximal contractions (3 s contraction, 2 s rest); and (2) submaximal contractions (the same contraction regime performed at 54 +/- 8% maximal voluntary contraction) to task failure. Phosphocreatine (PCr), inorganic phosphate (P(i)) and diprotonated phosphate (H(2)PO(4)()) concentrations and pH were determined using (31)P magnetic resonance spectroscopy throughout both tests. During the maximal contractions, force production fell from 213 +/- 33 N to reach a plateau in the last 30 s of the test at 100 +/- 20 N. The muscle metabolic responses at the end of each test were substantial, but not different between conditions: [PCr] was reduced (to 21 +/- 12 and 17 +/- 7% of baseline for maximal and submaximal contractions, respectively; P = 0.17), [P(i)] was elevated (to 364 +/- 98 and 363 +/- 135% of baseline, respectively; P = 0.98) and pH reduced (to 6.64 +/- 0.16 and 6.69 +/- 0.17, respectively; P = 0.43). The [H(2)PO(4)()] was also elevated at the end of both tests (to 607 +/- 252 and 556 +/- 269% of baseline, respectively; P = 0.22). These data suggest that the exercise-induced metabolic perturbations contributing to force depression in all-out exercise are the same as those contributing to task failure during submaximal contractions.

We hypothesized that increasing skeletal muscle total creatine (Cr) content through dietary Cr supplementation would result in slower muscle phosphocreatine concentration ([PCr]) kinetics, as assessed using (31)P magnetic resonance spectroscopy, following the onset and offset of both moderate-intensity (Mod) and heavy-intensity (Hvy) exercise. Seven healthy males (age 29 +/- 6 yr, mean +/- SD) completed a series of square-wave transitions to Mod and Hvy knee extensor exercise inside the bore of a 1.5-T superconducting magnet both before and after a 5-day period of Cr loading (4x 5 g/day of creatine monohydrate). Cr supplementation resulted in an approximately 8% increase in the resting muscle [PCr]-to-[ATP] ratio (4.66 +/- 0.27 vs. 5.04 +/- 0.22; P < 0.05), consistent with a significant increase in muscle total Cr content consequent to the intervention. The time constant for muscle [PCr] kinetics was increased following Cr loading for Mod exercise (control: 15 +/- 8 vs. Cr: 25 +/- 9 s; P < 0.05) and subsequent recovery (control: 14 +/- 8 vs. Cr: 27 +/- 8 s; P < 0.05) and for Hvy exercise (control: 54 +/- 18 vs. Cr: 72 +/- 30 s; P < 0.05), but not for subsequent recovery (control: 41 +/- 11 vs. Cr: 44 +/- 6 s). The magnitude of the increase in [PCr] following Cr loading was correlated (P < 0.05) with the extent of the slowing of the [PCr] kinetics for the moderate off-transient (r = 0.92) and the heavy on-transient (r = 0.71). These data demonstrate, for the first time in humans, that an increase in muscle [PCr] results in a slowing of [PCr] dynamics in exercise and subsequent recovery.

Wall shear stress (WSS) has been shown to be important to endothelial cell function and gene expression. Previous studies have shown that fluid dynamics might be closely related to the initialization of atherosclerotic plaques which preferentially originate in areas of disturbed flow in human vessels, where WSS is low or oscillatory. We recently developed a novel ultrasound-based technique, termed echo particle image velocimetry (echo PIV), by which the multi-component hemodynamic information in human cardiovascular system could be assessed. In this paper, we show that echo PIV was successfully employed to measure hemodynamic information in the right common carotid artery (rCCA) of ten healthy volunteers and that the values show good agreement with phase-contrast magnetic resonance imaging (PC-MRI) measurements with mean absolute differences (mean±SD) of 10.0%±9.8%, 10.1%±8.8% and 17.0%±15.3% for velocity, flow rate and WSS, respectively. In particular, the mean WSS (dynes/cm∧2) in rCCA of ten volunteers was found to be 9.2±2.0 by echo PIV, and 8.0±1.4 by PC-MRI, both in agreement with published data. We further showed that calculating WSS by either peak/mean velocity or flow rate together with arterial diameter was invalid for in-vivo measurements due to invalidity of assuming parabolic velocity profile in carotid artery. We found that the peak velocity across radial direction in rCCA was about 1.6 times of the mean velocity, not 2 times as it should be in parabolic distribution. In conclusion, echo PIV demonstrated several advantages over traditional techniques in terms of both temporal and spatial resolution when measuring WSS in human vessels. ©2009 IEEE.

Although functional magnetic resonance imaging is a technique that is widely used in adult populations, its use within a fetal environment has been extremely limited. Problems associated with movement and technical scanning issues have limited its effectiveness in providing reliable and spatially accurate details of fetal brain activity. However, initial research has indicated that it is a viable tool for assessing functional maturation in the fetus, and recent advances in echo-planar imaging sequences on the abdomen at 3-T provide the potential for more reliable activation detection and higher resolution spatial information. If the technique can be further developed such that a similar reliability in activity patterns is observed as in conventional functional MRI, then fetal functional MRI could offer a useful contribution at a clinical level as well as at a research one in the assessment of brain development and maturation.

(31)Phosphate-magnetic resonance spectroscopy and near infrared spectroscopy (NIRS) were used for the simultaneous assessment of changes in quadriceps muscle metabolism and oxygenation during consecutive bouts of high-intensity exercise. Six male subjects completed two 6 min bouts of single-legged knee-extension exercise at 80% of the peak work rate separated by 6 min of rest while positioned inside the bore of a 1.5 T superconducting magnet. The total haemoglobin and oxyhaemoglobin concentrations in the area of the quadriceps muscle interrogated with NIRS were significantly higher in the baseline period prior to the second compared with the first exercise bout, consistent with an enhanced muscle oxygenation. Intramuscular phosphorylcreatine concentration ([PCr]) dynamics were not different over the fundamental region of the response (time constant for bout 1, 51 +/- 15 s versus bout 2, 52 +/- 17 s). However, the [PCr] dynamics over the entire response were faster in the second bout (mean response time for bout 1, 72 +/- 16 s versus bout 2, 57 +/- 8 s; P < 0.05), as a consequence of a greater fall in [PCr] in the fundamental phase and a reduction in the magnitude of the 'slow component' in [PCr] beyond 3 min of exercise (bout 1, 10 +/- 6% versus bout 2, 5 +/- 3%; P < 0.05). These data suggest that the increased muscle O(2) availability afforded by the performance of a prior bout of high-intensity exercise does not significantly alter the kinetics of [PCr] hydrolysis at the onset of a subsequent bout of high-intensity exercise. The greater fall in [PCr] over the fundamental phase of the response following prior high-intensity exercise indicates that residual fatigue acutely reduces muscle efficiency.

The kinetics of pulmonary O(2) uptake is known to be substantially slower when exercise is initiated from a baseline of lower-intensity exercise rather than from rest. However, it is not known whether putative intracellular regulators of mitochondrial respiration (and in particular the phosphocreatine concentration, [PCr]) show similar non-linearities in their response dynamics. The purpose of this study was therefore to investigate the influence of baseline metabolic rate on muscle [PCr] kinetics (as assessed using (31)P-magnetic resonance spectroscopy) following the onset of exercise. Seven male subjects completed 'step' tests to heavy-intensity exercise (80% of peak work-rate) from a resting baseline and also from a baseline of moderate-intensity exercise (40% of peak work-rate) using a single-leg knee-extensor ergometer situated inside the bore of a 1.5 T super-conducting magnet. The time constant describing the kinetics of the initial exponential-like fall in [PCr] was significantly different between rest-to-moderate (25 +/- 14 s), rest-to-heavy (48 +/- 11 s) and moderate-to-heavy exercise (95 +/- 40 s) (P < 0.05 for all comparisons). A delayed-onset 'slow component' in the [PCr] response was observed in all subjects during rest-to-heavy exercise, but was attenuated in the moderate-to-heavy exercise condition. These data indicate that muscle [PCr] kinetics does not conform to 'linear, first-order' behaviour during dynamic exercise, and thus have implications for understanding the regulation of muscle oxidative metabolism.

We tested the hypothesis that the asymptote of the hyperbolic relationship between work rate and time to exhaustion during muscular exercise, the "critical power" (CP), represents the highest constant work rate that can be sustained without a progressive loss of homeostasis [as assessed using (31)P magnetic resonance spectroscopy (MRS) measurements of muscle metabolites]. Six healthy male subjects initially completed single-leg knee-extension exercise at three to four different constant work rates to the limit of tolerance (range 3-18 min) for estimation of the CP (mean +/- SD, 20 +/- 2 W). Subsequently, the subjects exercised at work rates 10% below CP (CP) for as long as possible, while the metabolic responses in the contracting quadriceps muscle, i.e. phosphorylcreatine concentration ([PCr]), P(i) concentration ([P(i)]), and pH, were estimated using (31)P-MRS. All subjects completed 20 min of CP exercise was 14.7 +/- 7.1 min. During CP exercise, however, [PCr] continued to fall to the point of exhaustion and [P(i)] and pH changed precipitously to values that are typically observed at the termination of high-intensity exhaustive exercise (end-exercise values = 26 +/- 16% of baseline [PCr], 564 +/- 167% of baseline [P(i)], and pH 6.87 +/- 0.10, all P < 0.05 vs.

To further understand the mechanism(s) explaining the faster pulmonary oxygen uptake (pVO2) kinetics found in children compared to adults, this study examined whether the phase II pVO2 kinetics in children are mechanistically linked to the dynamics of intramuscular PCr, which is known to play a principal role in controlling mitochondrial oxidative phosphorylation during metabolic transitions. On separate days, 18 children completed repeated bouts of moderate intensity constant work-rate exercise for determination of (1) PCr changes every 6 s during prone quadriceps exercise using 31P-magnetic resonance spectroscopy, and (2) breath by breath changes in pVO2 during upright cycle ergometry. Only subjects (n = 12) with 95% confidence intervals ≤±7 s for all estimated time constants were considered for analysis. No differences were found between the PCr and phase II pVO2 time constants at the onset (PCr 23 ± 5 vs. pVO2 or offset (PCr 28 ± 5 vs. pVO2 of exercise. The average difference between the PCr and phase II pVO2 time constants was 4 ± 4 s for the onset and offset responses. Pooling of the exercise onset and offset responses revealed a significant correlation between the PCr and pVO2 time constants (r = 0.459, P = 0.024). The close kinetic coupling between the pVO2 and PCr responses at the onset and offset of exercise in children is consistent with our current understanding of metabolic control and suggests that an age-related modulation of the putative phosphate linked controller(s) of mitochondrial oxidative phosphorylation may explain the faster pVO2 kinetics found in children compared to adults. © Springer-Verlag 2007.

The splitting of muscle phosphocreatine (PCr) plays an integral role in the regulation of muscle O2 utilization during a "step" change in metabolic rate. This study tested the hypothesis that the kinetics of muscle PCr would be faster in children compared with adults both at the onset and offset of moderate-intensity exercise, in concert with the previous demonstration of faster phase II pulmonary O2 uptake kinetics in children. Eighteen peri-pubertal children (8 boys, 10 girls) and 16 adults (8 men, 8 women) completed repeated constant work-rate exercise transitions corresponding to 80% of the Pi/PCr intracellular threshold. The changes in quadriceps [PCr], [Pi], [ADP], and pH were determined every 6 s using 31P-magnetic resonance spectroscopy. No significant (P>0.05) age- or sex-related differences were found in the PCr kinetic time constant at the onset (boys, 21+/-4 s; girls, 24+/-5 s; men, 26+/-9 s; women, 24+/-7 s) or offset (boys, 26+/-5 s; girls, 29+/-7 s; men, 23+/-9 s; women 29+/-7 s) of exercise. Likewise, the estimated theoretical maximal rate of oxidative phosphorylation (Qmax) was independent of age and sex (boys, 1.39+/-0.20 mM/s; girls, 1.32+/-0.32 mM/s; men, 2.36+/-1.18 mM/s; women, 1.51+/-0.53 mM/s). These results are consistent with the notion that the putative phosphate-linked regulation of muscle O2 utilization is fully mature in peri-pubertal children, which may be attributable to a comparable capacity for mitochondrial oxidative phosphorylation in child and adult muscle.

We hypothesized that a period of endurance training would result in a speeding of muscle phosphocreatine concentration ([PCr]) kinetics over the fundamental phase of the response and a reduction in the amplitude of the [PCr] slow component during high-intensity exercise. Six male subjects (age 26 +/- 5 yr) completed 5 wk of single-legged knee-extension exercise training with the alternate leg serving as a control. Before and after the intervention period, the subjects completed incremental and high-intensity step exercise tests of 6-min duration with both legs separately inside the bore of a whole-body magnetic resonance spectrometer. The time-to-exhaustion during incremental exercise was not changed in the control leg [preintervention group (PRE): 19.4 +/- 2.3 min vs. postintervention group (POST): 19.4 +/- 1.9 min] but was significantly increased in the trained leg (PRE: 19.6 +/- 1.6 min vs. POST: 22.0 +/- 2.2 min; P < 0.05). During step exercise, there were no significant changes in the control leg, but end-exercise pH and [PCr] were higher after vs. before training. The time constant for the [PCr] kinetics over the fundamental exponential region of the response was not significantly altered in either the control leg (PRE: 40 +/- 13 s vs. POST: 43 +/- 10 s) or the trained leg (PRE: 38 +/- 8 s vs. POST: 40 +/- 12 s). However, the amplitude of the [PCr] slow component was significantly reduced in the trained leg (PRE: 15 +/- 7 vs. POST: 7 +/- 7% change in [PCr]; P < 0.05) with there being no change in the control leg (PRE: 13 +/- 8 vs. POST: 12 +/- 10% change in [PCr]). The attenuation of the [PCr] slow component might be mechanistically linked with enhanced exercise tolerance following endurance training.

PURPOSE: to quantify T(1), T(2), and regional tissue perfusion in uterine tissues, with MR imaging in clinically feasible imaging times, using echo planar imaging (EPI) techniques over a single menstrual cycle. MATERIALS AND METHODS: a total of 24 healthy ovulating women were scanned; however, complete data sets through the menstrual cycle were not obtained from all women. Three scans were performed to coincide prospectively with the follicular, periovulatory, and luteal phases of the cycle. T(1) and perfusion were measured simultaneously using flow alternating inversion recovery (FAIR), while T(2) was measured using a single Hahn spin-echo (SE) EPI sequence. RESULTS: Between the follicular and periovulatory phases, statistically significant increases (P < 0.05) were seen for the T(2) of the endometrium and perfusion of the myometrium as well as the T(2)/T(1) ratio for both endometrium and myometrium. A statistically significant decrease was seen in the endometrial T(2) between the periovulatory and luteal phases of the cycle. Tissue differentiation was achieved using the parameters measured, with T(1) and T(2) being statistically greater for the endometrium than for the myometrium, and endometrial perfusion being statistically lower than myometrial perfusion. CONCLUSION: These results show the feasibility of using these techniques to measure T(1), T(2), and perfusion in uterine tissues and of extending this work to study pathological conditions.

This study examined the reliability of (31)P-magnetic resonance spectroscopy (MRS) to measure parameters of muscle metabolic function in children. On separate days, 14 children (7 boys and 7 girls) completed three knee-extensor incremental tests to exhaustion inside a whole-body scanner (1.5 T, Phillips). The dynamic changes in the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) and intracellular muscle pH were resolved every 30 s. Using plots of Pi/PCr and pH against power output (W), intracellular thresholds (ITs) for each variable were determined using both subjective and objective procedures. The IT(Pi/PCr) and IT(pH) were observed subjectively in 93 and 81% of their respective plots, whereas the objective method identified the IT(Pi/PCr) in 88% of the plots. The IT(pH) was undetectable using the objective method. End exercise (END) END(Pi/PCr), END(pH), IT(Pi/PCr) and IT(pH) were examined using typical error statistics expressed as a % coefficient of variation (CV) across all three exercise tests. The CVs for the power output at the subjectively determined IT(Pi/PCr) and IT(pH) were 10.6 and 10.3%, respectively. Objective identification of the IT(Pi/PCr) had a CV of 16.3%. CVs for END(pH) and END(Pi/PCr) were 0.9 and 50.0%, respectively. MRS provides a valuable window into metabolic changes during exercise in children. During knee-extensor exercise to exhaustion, END(pH) and the subjectively determined IT(Pi/PCr) and IT(pH) demonstrate good reliability and thus stable measures for the future study of developmental metabolism. However, the objectively determined IT(Pi/PCr) and END(Pi/PCr) displayed poor reliability.

OBJECTIVE: to determine the ability of air displacement plethysmography (ADP) to predict visceral adipose tissue (VAT) volume in children. RESEARCH METHODS AND PROCEDURES: Fifty-five (33 boys/22 girls) white children 13 to 14 years old were studied. Anthropometric measures were collected for body mass, stature, BMI, and waist-to-hip ratio (WHR), and body fat percentage was estimated from triceps and subscapular skinfolds, bioelectrical impedance analysis, and ADP. VAT volume was determined using magnetic resonance imaging, using a multiple slice protocol at levels L1 to L5. RESULTS: Boys had significantly (p < or = 0.05) less VAT volume than girls [645.1 (360.5) cm(3) vs. 1035.8 (717.3) cm(3)]. ADP explained the greatest proportion of the variance in VAT volume compared with the other anthropometric measures. Multiple regression analysis indicated that VAT volume was best predicted by ADP body fat percentage in boys [r(2) = 0.81, SE of the estimate (SEE) = 160.1, SEE coefficient of variation = 25%] and by WHR and BMI in girls (r(2) = 0.80, SEE = 337.71, SEE coefficient of variation = 33%). DISCUSSION: Compared with the other anthropometric measures, ADP explains the greatest proportion of the variance in VAT volume in children 13 to 14 years old. For boys, ADP is the tool of choice to predict VAT volume, yet using the more simply collected measures of BMI and WHR is recommended for girls. However, large SE of the estimates remained, suggesting that if precision is needed, there is no surrogate for direct imaging of VAT.

OBJECTIVE: High-resolution magnetic resonance imaging (MRI) was used to monitor both uterine endometrial and junctional zone morphometry during the normal menstrual cycle. STUDY DESIGN: Twenty-four healthy, ovulating women were studied during a single menstrual cycle. Three scans were performed to prospectively coincide with the follicular, periovulatory, and luteal phases of the cycle. RESULTS: MRI data showed a significant increase in endometrial and junctional zone volume, between the follicular and periovulatory phases, with a significant decrease in endometrial volume observed from the periovulatory to luteal phases. The regularity index, which is a novel subjective assessment of junctional zone structure, varied significantly and demonstrated a less regular junctional zone in the luteal phase. CONCLUSION: This study has quantified the normal developmental changes of uterine tissue during the menstrual cycle with MRI. Junctional zone data from MRI may play a major role in future studies that investigate menstrual disorders, subfertility, and pathologic changes.

Previous studies have demonstrated the use of functional magnetic resonance imaging (fMRI) to assess fetal brain activity. To extend these studies, a fetal fMRI experiment using a visual stimulus has been performed at 0.5 T. This used a block fMRI paradigm with a bright, constant-intensity light source being shone at the maternal abdomen for 8 sec followed by 16 sec of darkness. This was repeated typically 40 times on nine subjects all of whom were greater than 36 weeks gestational age. of these, one could not be analysed due to motion, three did not show significant activation, and five showed significant activation (P < 0.0085). In all cases, activation was localised within the frontal cortex. Exact localisation was difficult but this may correspond to the frontal eye fields and dorsolateral prefontal cortex. In no cases was significant activation present within the occipital region as would have been expected and was observed in 2/8 adult subjects. Hum. Brain Mapping 20:239-245, 2003.

OBJECTIVES: (1) to investigate a possible association between myometrial and placental artery vasoreactivity and perfusion at the basal and chorionic plates, respectively. (2) to confirm that myometrial arteries from women with pre-eclampsia and intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response. METHODS: Women with normal pregnancy, pre-eclampsia and intrauterine growth restriction had a magnetic resonance scan to assess placental perfusion using a technique called intravoxel incoherent motion. At delivery, myometrial and chorionic plate placental arteries were assessed on a wire myograph. Vessels were pre-constricted with the thromboxane mimetic U46619 and dilated with incremental doses of bradykinin. RESULTS: Pre-constricted myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibited an attenuated vasodilatory response to bradykinin, compared with normal pregnancy (P < 0.0001). Pre-constricted placental arteries exhibited a minimal vasodilatory response in all three groups of women (P = 0.10). Maximal constrictor and vasodilatory responses of myometrial arteries were not associated with the perfusing fraction at the basal plate. Maximal constrictor and vasodilatory responses of chorionic plate placental arteries were not associated with the perfusing fraction at the chorionic plate. CONCLUSION: We confirm that myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response. Apart from vasoreactivity of small arteries, other factors may be involved in the control of placental perfusion.

The signature DNA lesion induced by ionizing radiation is clustered DNA damage. Gamma radiation-induced clustered DNA damage containing base lesions was investigated in plasmid DNA under cell mimetic conditions and in two cell lines, V79-4 (hamster) and HF19 (human), using bacterial endonucleases Nth (endonuclease III) and Fpg (formamidopyrimidine DNA glycosylase). Following irradiation with 60Co gamma-rays, induction of double-strand breaks (DSB) and clustered DNA damage, revealed as DSB by the proteins, was determined in plasmid using the plasmid-nicking assay and in cells by either conventional pulsed field gel electrophoresis or a hybridization assay, in which a 3 Mb restriction fragment of the X chromosome is used as a radioactive labeled probe. Enzyme concentrations (30-60 ng/microg DNA) were optimized to minimize visualization of background levels of endogenous DNA damage and DSB produced by non-specific cutting by Fpg and Nth in cellular DNA. 60Co gamma-radiation produces a 1.8-fold increase in the yields of both types of enzyme sensitive sites, visualized as DSB compared with that of prompt DSB in plasmid DNA. In mammalian cells, the increase in yields of clustered DNA damage containing either Fpg or Nth sensitive sites compared with that of prompt DSB is 1.4-2.0- and 1.8-fold, respectively. Therefore, clustered DNA damage is induced in cells by sparsely ionizing radiation and their yield is significantly greater than that of prompt DSB.

Functional magnetic resonance imaging (fMRI) is now a well-established technique for directly identifying adult brain activity. This study builds on earlier pilot work that showed that fMRI could provide direct evidence of fetal brain cortical activation in response to an auditory stimulus. The new work presented here aims to assess the sensitivity of this technique in a larger sample group. This article includes a specific discussion of the methodology required for fetal fMRI. Sixteen pregnant subjects were scanned between 37 and 41 weeks gestation, 12 had an auditory stimulus applied to the maternal abdomen (study group) and 4 had an auditory stimulus applied to the mother's ears (control group). Two of twelve (2/12) study-group patients experienced back pain so that the experiment was abandoned; 4/12 showed significant activation (P < 0.005) in one or both of the temporal lobes; 1/12 showed significant activation in the frontal lobe. A susceptibility artifact at the interface between the maternal bowel and the fetus affected 3/12 data sets. No significant activation was found in 3/4 of the control cases, and 1/4 could not be analyzed due to a susceptibility artifact. © 2001 Wiley-Liss, Inc.

Functional magnetic resonance imaging (fMRI) is now a well-established technique for directly identifying adult brain activity. This study builds on earlier pilot work that showed that fMRI could provide direct evidence of fetal brain cortical activation in response to an auditory stimulus. The new work presented here aims to assess the sensitivity of this technique in a larger sample group. This article includes a specific discussion of the methodology required for fetal fMRI. Sixteen pregnant subjects were scanned between 37 and 41 weeks gestation, 12 had an auditory stimulus applied to the maternal abdomen (study group) and 4 had an auditory stimulus applied to the mother's ears (control group). Two of twelve (2/12) study-group patients experienced back pain so that the experiment was abandoned; 4/12 showed significant activation (P < 0.005) in one or both of the temporal lobes; 1/12 showed significant activation in the frontal lobe. A susceptibility artifact at the interface between the maternal bowel and the fetus affected 3/12 data sets. No significant activation was found in 3/4 of the control cases, and 1/4 could not be analyzed due to a susceptibility artifact.

Biophysical modeling of radiation-induced DNA damage shows that significant yields of clustered DNA damage are formed after energy deposition by a single radiation track. To date, the majority of studies on radiation-induced DNA damage in cells have concentrated on determination of the yields of single- and double-strand breaks (DSBs), the latter representing one type of clustered DNA damage. It was recognized, however, that clustered DNA damage, which does not contain a DSB, might contain a combination of DNA base lesions and single-strand breaks in proximity. This mini-review discusses some of the recent experimental data confirming the induction of non-DSB, clustered DNA damage by radiation.

PURPOSE: to compare experimental yields of single strand breaks (SSB) and double strand breaks (DSB) induced in plasmid DNA in aqueous solution by alpha-particles and Al(K) ultrasoft X-rays (USX) with the corresponding yields, generated via computer simulations, for a range of mean diffusion distances of the hydroxyl radical (*OH). MATERIALS AND METHODS: Aerobic, aqueous solutions of plasmid DNA were irradiated at 277K with 238Pu alpha-particles or USX in the presence of 10(-4) to 0.33 mol dm(-3) Tris and the yields of SSB and DSB determined by gel electrophoresis. Computer simulations, using Monte Carlo track-structure codes for 1.5keV electrons (CPA100) and 3.2MeV alpha-particle track segments (PITS), were used to obtain yields of DNA SSB and DSB at different. OH scavenger conditions. RESULTS: the experimental yield of SSB and DSB induced by AlK USX and SSB induced by alpha-particles and the dependences on the mean diffusion distance of the. OH are in reasonable agreement with the corresponding simulated yields and their corresponding dependences. However, for DSB induced by alpha-particles, a significant systematic difference exists between the simulated and experimental yields over the full. OH scavenging range, with the simulated yields being a factor of two to three greater than the experimental values. CONCLUSION: That the simulated yields of strand breaks are generally in reasonable agreement with those determined experimentally over a wide range of. OH scavenging capacities, increases confidence in the use of these simulations as a valuable source of quantitative, mechanistic information on DNA damage induced at very low radiation doses.