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Epidemiological studies have identified several risk factors for coronary heart disease (CHD), many of which are present in young people. One such risk factor is hypertension. In adults, exercise is thought to have a positive effect on blood pressure levels; however, findings are inconclusive for young people. Despite its association with CHD, obesity is on the increase in Western society's young population; prevention and intervention during early years is needed. An active lifestyle is considered to have a beneficial effect on body fatness. Lipoprotein profiles are directly associated with CHD status. In adults, there is some evidence that physical activity and/or fitness have a favourable effect on lipoprotein levels. Although information regarding the younger population is more ambiguous, it tends to concur with these findings. High levels of lipoprotein(a), are considered an independent risk factor for CHD. Relatively little has been written on young people, although some studies have postulated a favourable relationship with physical activity. An inverse relationship between aerobic fitness and CHD has been confirmed in adults; an association is not as easily verified for young people. Physical activity is similarly deemed to have a beneficial effect on health status. A high-fat diet has been linked to CHD in adults, and evidence to date reports similar findings for young people. Smoking increases the risk of CHD and even moderate smoking during youth could have damaging long-term consequences. There is some evidence that smoking is related to physical activity and fitness levels in young people. In adults, high levels of homocyst(e)ine have been associated with CHD. As yet, little has been written on the relationship between physical activity or physical fitness and homocysteine status in young people. High levels of plasma fibrinogen have been linked to CHD. Several studies have explored the relationship between plasma fibrinogen and physical activity and/or fitness in adults, but findings are inconclusive; for young people, the ambiguity is even greater. C-reactive protein is a molecular marker for CHD but, to date, little attention has been given to this aspect, especially amongst young people. The link between high levels of plasminogen activator inhibitor-1 and CHD has been confirmed, although the essence of this relationship is not established. There is a paucity of data on the younger population and the relevance of collating such information is questionable. For the younger population, most research is limited to the established CHD risk factors and further investigations of recently identified CHD risk factors are needed. [ABSTRACT FROM AUTHOR]

Keyway root cracking and radiolytic weight loss in graphite moderated nuclear reactors may limit future successful operation of the civil nuclear fleet. A novel means of initiating fracture using internally generated stresses has been developed, which uses bromine intercalation to induce fracture in small graphite samples. Successful crack initiation and propagation has been achieved in 1:10 scale reactor components. In situ X-ray Computed Tomography during bromination has enabled observations of failure in real time, allowing the role of microstructure during fracture and weight loss to be determined. Crack paths predicted by models have been assessed. [Display omitted] [ABSTRACT FROM AUTHOR]

Key points: In vitro evidence has identified that coagulation is activated by increased oxidative stress, though the link and underlying mechanism in humans have yet to be established.We conducted the first randomised controlled trial in healthy participants to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise given their synergistic capacity to promote free radical formation.Systemic free radical formation was shown to increase during hypoxia and was further compounded by exercise, responses that were attenuated by antioxidant prophylaxis.In contrast, antioxidant prophylaxis increased thrombin generation at rest in normoxia, and this was normalised only in the face of prevailing oxidation.Collectively, these findings suggest that human free radical formation is an adaptive phenomenon that serves to maintain vascular haemostasis. In vitro evidence suggests that blood coagulation is activated by increased oxidative stress although the link and underlying mechanism in humans have yet to be established. We conducted the first randomised controlled trial to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise. Healthy males were randomly assigned double‐blind to either an antioxidant (n = 20) or placebo group (n = 16). The antioxidant group ingested two capsules/day that each contained 500 mg of l‐ascorbic acid and 450 international units (IU) of dl‐α‐tocopherol acetate for 8 weeks. The placebo group ingested capsules of identical external appearance, taste and smell (cellulose). Both groups were subsequently exposed to acute hypoxia and maximal physical exercise with venous blood sampled pre‐supplementation (normoxia), post‐supplementation at rest (normoxia and hypoxia) and following maximal exercise (hypoxia). Systemic free radical formation (electron paramagnetic resonance spectroscopic detection of the ascorbate radical (A•−)) increased during hypoxia (15,152 ± 1193 AU vs. 14,076 ± 810 AU at rest, P < 0.05) and was further compounded by exercise (16,569 ± 1616 AU vs. rest, P < 0.05), responses that were attenuated by antioxidant prophylaxis. In contrast, antioxidant prophylaxis increased thrombin generation as measured by thrombin–antithrombin complex, at rest in normoxia (28.7 ± 6.4 vs. 4.3 ± 0.2 μg mL−1 pre‐intervention, P < 0.05) and was restored but only in the face of prevailing oxidation. Collectively, these findings are the first to suggest that human free radical formation likely reflects an adaptive response that serves to maintain vascular haemostasis. Key points: In vitro evidence has identified that coagulation is activated by increased oxidative stress, though the link and underlying mechanism in humans have yet to be established.We conducted the first randomised controlled trial in healthy participants to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise given their synergistic capacity to promote free radical formation.Systemic free radical formation was shown to increase during hypoxia and was further compounded by exercise, responses that were attenuated by antioxidant prophylaxis.In contrast, antioxidant prophylaxis increased thrombin generation at rest in normoxia, and this was normalised only in the face of prevailing oxidation.Collectively, these findings suggest that human free radical formation is an adaptive phenomenon that serves to maintain vascular haemostasis. [ABSTRACT FROM AUTHOR]

Property measurement of graphite extracted from operational nuclear reactors is vital for forward prediction of the graphite's properties and integrity as part of continued operation and plant life extension assessments. Limited core monitoring material is available, so robust and efficient measurement techniques are required for samples with constrained dimensions. The validation of a technique for measuring electrical resistivity in small graphite samples (largest dimension < 20 mm) is described with an empirical validation of the geometry correction factors. The electrical and thermal characterisation of 175 radiolytically-oxidised Gilsocarbon-grade graphite samples extracted from four advanced gas-cooled reactors (AGRs) is presented, including a subset that were further oxidised in an accelerated-irradiation test programme. The selected material sampled radiolytic-oxidation induced weight losses of up to 59% and doses of up to 193 × 10 20 n.cm −2 equivalent DIDO nickel dose, or ca. 28 displacements per atom. For all the measured oxidation states, a linear correlation between thermal diffusivity and density is demonstrated, with power law functions found to describe the trends in thermal and electrical resistivity with density. The effect of the oxidation on the phenomenologically-different heat and electrical transport mechanisms is considered and electrical resistivity, ρ E , is shown to be an excellent proxy for thermal resistivity, ρ T , with a calibration function ρ E ∝ ρ T 0.66 . For low weight loss samples, including virgin Gilsocarbon, a linear approximation is also described. [ABSTRACT FROM AUTHOR]

The current approach to hydraulic fracturing requires large amounts of industrial hardware to be transported, installed and operated in temporary locations. A significant proportion of this equipment is comprised of the fleet of pumps required to provide the high pressures and flows necessary for well stimulation. Studies have shown that over 90% of the emissions of CO 2 and other pollutants that occur during a hydraulic fracturing operation are associated with these pumps. Pollution and transport concerns are of paramount importance for the emerging hydraulic fracturing industry in Europe, and so it is timely to consider these factors when assessing the design of high pressure pumps for the European resources. This paper gives an overview of the industrial plant required to carry out a hydraulic fracturing operation. This is followed by an analysis of the pump's design space that could result in improved pump efficiency. We find that reducing the plunger diameter and running the pump at higher speeds can increase the overall pump efficiency by up to 4.6%. Such changes to the pump's parameters would results in several environmental benefits beyond the obvious economic gains of lower fuel consumption. The paper concludes with a case study that quantifies these benefits. [ABSTRACT FROM AUTHOR]

• Three-point bend measurement data characterised by ESPI and inverse modelling. • Static Young's modulus, Poisson's ratio and strength determined. • Measurements performed on 218 irradiated graphite beams taken from UK AGR stations. • Graphite samples (6 × 6 × 19 mm) cover dose range to 21.1 DPA and weight loss to 46%. • Modulus and strength correlate well with radiolytic weight loss. The Young's modulus, Poisson's ratio and flexural strength of 218 beams of radiolytically oxidised nuclear graphite have been determined by combining electronic speckle pattern interferometry, ESPI, and inverse finite element modelling techniques. The graphite was extracted from three operational advanced gas cooled reactor stations where it had been subjected to fast neutron irradiation and radiolytic oxidation resulting in mass loss. The 6 × 6 × 19 mm beam samples had densities ranging from 1063 – 1840 kg.m−3, equivalent to weight losses up to 46%, with cumulative neutron doses of up to 161 × 1020 n.cm−2 equivalent Dido nickel dose, or 21.1 displacements per atom, significantly extending the datasets available in the open literature to higher levels of both dose and oxidation. In situ ESPI measurements were collected during three-point bend tests, creating full field displacement maps of the evolving deformation to which simulations were matched by chi-squared minimisation of the elastic properties. Potential loading abnormalities were accounted for in the fitting process to ensure the simulations were representative, with total uncertainties in the determined Young's modulus and Poisson's ratio values of ± 4.5% and ± 0.08, respectively. Consistent trends were observed in the behaviour of the material from the different stations, with strong positive dependences on density for both the flexural strength and Young's modulus. The strength and Young's modulus remained well correlated even to high levels of oxidation mass loss. Conversely, the Poisson's ratio was practically invariant with oxidation with mean values of 0.21 ± 0.03, 0.24 ± 0.05 and 0.25 ± 0.05 for the three stations. The combined ESPI-finite element measurement approach is demonstrated as robust for irradiated small specimens, making it suitable for monitoring graphite in future reactors. The collected data support the safety assessments of the current reactors, enabling predictions of the responses to progressively higher mean core mass loss. [ABSTRACT FROM AUTHOR]

Abstract: The risk-reducing effect of a potential reduced-risk tobacco product (PRRP) can be investigated conceptually in a long-term, prospective study of disease risks among cigarette smokers who switch to a PRRP and in appropriate comparison groups. Our objective was to provide guidance for establishing the fundamental design characteristics of a study intended to (1) determine if switching to a PRRP reduces the risk of lung cancer (LC) compared with continued cigarette smoking, and (2) compare, using a non-inferiority approach, the reduction in LC risk among smokers who switched to a PRRP to the reduction in risk among smokers who quit smoking entirely. Using standard statistical methods applied to published data on LC incidence after smoking cessation, we show that the sample size and duration required for a study designed to evaluate the potential for LC risk reduction for an already marketed PRRP, compared with continued smoking, varies depending on the LC risk-reducing effectiveness of the PRRP, from a 5-year study with 8000–30,000 subjects to a 15-year study with <5000 to 10,000 subjects. To assess non-inferiority to quitting, the required sample size tends to be about 10 times greater, again depending on the effectiveness of the PRRP. [Copyright &y& Elsevier]

Intense exercise is known to cause temporary impairments in immune function. Few studies, however, have investigated the effects of intense competitive exercise on immunoendocrine variables in elite team sport athletes. The aim of this study was to evaluate the time course of changes in selected immunoendocrine and inflammatory markers following an international rugby union game. Blood samples were taken from players (n = 10) on camp entry, the morning of the game (pre), immediately after (post) and 14 and 38 h into a passive recovery period. Players lost 1.4 +/- 0.2 kg of body mass during the game (ambient conditions, 11 degrees C, 45% RH). An acute phase inflammatory response was observed as reflected through immediate increases in serum cortisol and IL-6 (post) followed by delayed increases in serum creatine kinase (CK; 14 h) activity and C-reactive protein (CRP; 38 h); P < 0.05. Decreases in the number of circulating T lympocytes, NK cells and bacteria-stimulated neutrophil degranulation were also observed post-exercise (P < 0.05), indicative of decreased host immune protection. Following a large decrease in serum testosterone to cortisol (T/C) ratio immediately post and 14 h after exercise, T/C values then increased above those observed at camp entry 38 h into recovery (P < 0.05). This rebound anabolic stimulus may represent a physiological requirement for recovery following intense tissue damage resulting from game collisions. The findings also suggest that a game of international rugby elicits disturbances in host immunity, which last up 38 h into the recovery period. [ABSTRACT FROM AUTHOR]

Arterial endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and predisposes individuals to the deposition of unstable atherosclerotic plaques. It can also lead to increased arterial stiffness, which is an accepted cause of increased arterial pulse wave velocity (APWV). Endothelial dysfunction is reversed by recombinant human growth hormone (rhGH) therapy in patients with growth hormone (GH) deficiency (GHD), favorably influencing the risk for atherogenesis. Endogenous human growth hormone (hGH), secreted by the anterior pituitary, and levels of insulin-like growth factor-I (IGF-I), produced in response to hGH stimulation of the liver, peak during early adulthood, but decline throughout adulthood. It is suspected that low-grade inflammatory cardiovascular pathophysiologic markers such as homocysteine, nitric oxide, C-reactive protein (CRP), and fibrinogen and plasminogen activator inhibitor along with changes in lipid and glucose metabolism may all contribute to GHD-associated metabolic and cardiovascular complications. These effects are associated with increased APWV, but are attenuated by rhGH therapy in GHD. GH replacement increases IGF-I levels and reduces CRP and large-artery stiffness. Reviews of rhGH in the somatopause have not been overtly favorable. Whereas reviews of rhGH/rhIGF-I combinations in GH resistance are more positive than those for rhGH alone, their combined use in the somatopause is limited. Senescent individuals may benefit from such a combination. [ABSTRACT FROM AUTHOR]

This study investigated the effect of repeated bouts of short-term, high-intensity cycling exercise on the salivary cortisol, testosterone and immunoglobulin (A) concentrations of 15-16 year old boys. Seventeen apparently healthy schoolchildren (aged 15.5 +/- 0.4 years) participated in this study. All participants completed 6 x 8 s sprints, interspersed with 30 s recovery intervals on a cycle ergometer. Using the passive drool method, salivary samples were taken before, and 5 min after, exercise. The group mean for peak power output was 723.1 +/- 180.3 s. There were significant changes (p < or = 0.05) in both SalT and SalC, 5 min after completing 6 x 8 s cycle sprints. No significant differences (p > 0.05) were recorded for SIg(A). The increases in SalT and SalC reported in this study confirm that repeated bouts of short-term, high-intensity exercise produces significant physiological hormonal responses in adolescent boys, but does not affect mucosal immune function. [ABSTRACT FROM AUTHOR]

The article reports on the results of research which was conducted in an effort to evaluate the physiologic demands of two rugby players by using global positioning system tracking software. Researchers found that players covered on average 6,953 meters during 83 minutes of play and that players spent 37% of that distance standing and walking, 27% on jogging, 10% cruising, 14% striding, 5% high-intensity running, and 6% sprinting.

The article reports on plasma volume response to 30-s cycle ergometry. This study aims to compare power profiles, changes in plasma volume (PV), and plasma lipid and lipoprotein concentrations immediately after, and 24 hours after exercise. In this study, subjects took on two 30-s, high-intensity cycle ergometer protocols after optimization of resistive loads measured from fat-free mass (FFM) and total body mass (TBM). It was established that short-duration, high-intensity cycle ergometer exercise tests can promote PV decreases in untrained subjects, which may influence the interpretation of bloodborne biochemical parameters.

Central fatigue, such as that found in chronic fatigue syndrome, is a state in which cognition and action require increasing effort and performance is impaired without evidence for reduced peripheral motor responsiveness. Previous studies identified functional changes in subcortical regions in patients who experience central fatigue but did not address neural correlates of the subjective experience of fatigue. This study investigated responses to acute tryptophan feeding (after administration of 30 mg/kg body mass) using functional magnetic resonance imaging to investigate neural correlates of central fatigue during a cognitively demanding exercise, the counting Stroop task. In a double-blind, cross-over study, eight subjects ingested l-tryptophan (Trp) or placebo (Plac) on two separate test days. Neutral (N) and interference (I) Stroop tasks were carried out. Plasma-free tryptophan (p[FT]) increased tenfold after l-Trp administration ( P < 0.01). Although reaction times were longer after Trp (mean±SD, Plac-Neut 669 ± 163 ms, I 715 ± 174 ms, P < 0.01; Trp-Neut 712 ± 193 ms, I 761 ± 198 ms, P < 0.05), the Stroop effect was not significantly different between Plac and Trp. l-Trp administration was associated with relatively decreased activation in regions, including the left postcentral, angular, inferior frontal, and the lateral orbital gyri and the inferior frontal sulcus relative to Plac. Relatively increased activation was found after Trp in the left precuneus and in the posterior cingulate gyrus. Thus, Trp administration before the Stroop task caused distributed functional changes in primary sensory and in multimodal neocortex, including changes in a brain region, the activity of which has been shown previously to vary with conscious awareness (precuneus). Previous reports suggest that primary mechanisms of central fatigue may be predominantly subcortical. The present results demonstrate that neocortical activity changes are also found. Whether this activity contributes to the primary mechanisms underlying central fatigue or not, the neocortical activity changes may provide an index of the conscious experience. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) have been implicated in the cellular membrane damage and postoperative morbidity associated with obligatory ischemia–reperfusion (I-R) during vascular surgery. Thus, a clinical study was undertaken to evaluate the effects of ascorbate prophylaxis on ROS exchange kinetics in 22 patients scheduled for elective abdominal aortic aneurysm (AAA) or infra-inguinal bypass (IIB) repair. Patients were assigned double-blind to receive intravenous sodium ascorbate (2 g vitamin C, n=10) or placebo (0.9% saline, n=12) administered 2 h prior to surgery. Blood samples were obtained from the arterial and venous circulation proximal to the respective sites of surgical repair (local) and from an antecubital vein (peripheral) during cross-clamping (ischemia) and within 60 s of clamp release (reperfusion). Ascorbate supplementation increased the venoarterial concentration difference (v–adiff) of lipid hydroperoxides (LH), interleukin (IL)-6 and vascular endothelial growth factor (VEGF) protein during ischemia. This increased the peripheral concentration of LH, total creatine phosphokinase (CPK), and VEGF protein during reperfusion (P<0.05 vs placebo). Electron paramagnetic resonance (EPR) spectroscopy confirmed that free iron was available for oxidative catalysis in the local ischemic venous blood of supplemented patients. An increased concentration of the ascorbate radical (A•−) and α-phenyl-tert-butylnitrone (PBN) adducts assigned as lipid-derived alkoxyl (LO•) and alkyl (LC•) species were also detected in the peripheral blood of supplemented patients during reperfusion (P<0.05 vs ischemia). In conclusion, these findings suggest that ascorbate prophylaxis may have promoted iron-induced oxidative lipid damage via a Fenton-type reaction initiated during the ischemic phase of surgery. The subsequent release of LH into the systemic circulation may have catalyzed formation of second-generation radicals implicated in the regulation of vascular permeability and angiogenesis. [Copyright &y& Elsevier]

The purpose of this study was to compare power outputs, and blood concentrations of lipid hydroperoxides (LH), malondialdehyde (MDA), creatine kinase (CK), myoglobin (Mb) and lactate ([La-]B) following 30 s of maximal cycle ergometry when resistive forces were derived from total-body mass (TBM) or fat-free mass (FFM). Alpha-tocopherol (AT), retinol (R) and uric acid (UA) concentrations were also measured to qualify the activity of antioxidants. Cardiac troponin levels were determined to exclude myocardial damage and to verify that any CK was predominantly derived from skeletal muscle. Differences (P<0.05) in peak power output, pedal velocity and resistive forces were observed when the TBM and FFM protocols were compared [953 (114) W vs 1,020 (134) W; 134 (8) rpm vs 141 (7) rpm; 6 (1) kg vs 5 (1) kg respectively). LH and MDA concentrations increased immediately post-exercise during the TBM protocol only (P<0.05) and were greater when compared to FFM (P<0.05). LH and MDA values decreased 24 h post-exercise. Increases in CK concentrations were recorded immediately post-exercise for both the TBM and FFM protocols with greater concentrations recorded for TBM (P<0.05). Decreases were observed 24 h post-exercise. Mb concentrations were greater immediately post-exercise for the TBM protocol and were greater than those recorded for FFM (P<0.05). Values decreased 24 h later (P<0.05). AT and UA concentrations decreased immediately post-exercise for both protocols (P<0.05) and increased 24 h later (P<0.05). There were no changes observed in R concentrations at any of the blood sampling stages. [La-]B increased (P<0.05) immediately post-exercise for both protocols, and decreased 24 h later (P<0.05). The results of the study suggest that greater power outputs are obtainable with significantly less oxidative stress and muscle disruption when resistive forces reflect FFM mass as opposed to TBM. [ABSTRACT FROM AUTHOR]

Background: Recent studies have revealed that many discharged patients with COVID-19 experience ongoing symptoms months later. Rehabilitation interventions can help address the consequences of COVID-19, including medical, physical, cognitive, and psychological problems. To our knowledge, no studies have investigated the effects of rehabilitation following discharge from hospital for patients with COVID-19., Objective: The specific aims of this project are to investigate the effects of a 12-week exercise program on pulmonary fibrosis in patients recovering from COVID-19. A further aim will be to examine how Chinese herbal medicines as well as the gut microbiome and its metabolites regulate immune function and possibly autoimmune deficiency in the rehabilitation process., Methods: In this triple-blinded, randomized, parallel-group, controlled clinical trial, we will recruit adult patients with COVID-19 who have been discharged from hospital in Hong Kong and are experiencing impaired lung function and pulmonary function. A total of 172 eligible patients will be randomized into four equal groups: (1) cardiorespiratory exercise plus Chinese herbal medicines group, (2) cardiorespiratory exercise only group, (3) Chinese herbal medicines only group, and (4) waiting list group (in which participants will receive Chinese herbal medicines after 24 weeks). These treatments will be administered for 12 weeks, with a 12-week follow-up period. Primary outcomes include dyspnea, fatigue, lung function, pulmonary function, blood oxygen levels, immune function, blood coagulation, and related blood biochemistry. Measurements will be recorded prior to initiating the above treatments and repeated at the 13th and 25th weeks of the study. The primary analysis is aimed at comparing the outcomes between groups throughout the study period with an α level of .05 (two-tailed)., Results: The trial has been approved by the university ethics committee following the Declaration of Helsinki (approval number: REC/19-20/0504) in 2020. The trial has been recruiting patients. The data collection will be completed in 24 months, from January 1, 2021, to December 31, 2022., Conclusions: Given that COVID-19 and its sequelae would persist in human populations, important findings from this study would provide valuable insights into the mechanisms and processes of COVID-19 rehabilitation., Trial Registration: ClinicalTrials.gov NCT04572360; https://clinicaltrials.gov/ct2/show/NCT04572360., International Registered Report Identifier (irrid): PRR1-10.2196/25556., (©Yang Gao, Linda L D Zhong, Binh Quach, Bruce Davies, Garrett I Ash, Zhi-Xiu Lin, Yibin Feng, Benson W M Lau, Peter D Wagner, Xian Yang, Yike Guo, Wei Jia, Zhaoxiang Bian, Julien S Baker. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.05.2021.)

Objectives: National dietary guidelines were introduced in 1977 and 1983, by the USA and UK governments to reduce coronary heart disease (CHD) mortality by reducing dietary fat intake. Our 2015 systematic review examined randomised controlled trial (RCT) evidence available to the dietary committees at the time; we found no support for the recommendations to restrict dietary fat. What epidemiological evidence was available to the dietary guideline committees in 1983?, Methods: A systematic review of prospective cohort studies, published prior to 1983, which examined the relationship between dietary fat, serum cholesterol and the development of CHD., Results: Across 6 studies, involving 31 445 participants, there were 1521 deaths from all-causes and 360 deaths from CHD during the mean follow-up of 7.5±6.2 years. The death rates were 4.8% and 1.1% from all-causes and CHD respectively. One study included men with previous heart disease. The death rate from CHD for those with, and without previous myocardial infarction was 20.9% and 1.0% respectively. None of the six studies found a significant relationship between CHD deaths and total dietary fat intake. One of the six studies found a correlation between CHD deaths and saturated dietary fat intake across countries; none found a relationship between CHD deaths and saturated dietary fat in the same population., Conclusions: 1983 dietary recommendations for 220 million US and 56 million UK citizens lacked supporting evidence from RCT or prospective cohort studies. The extant research had been undertaken exclusively on males, so lacked generalisability for population-wide guidelines., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: National dietary guidelines were introduced in 1977 and 1983, by the US and UK governments to reduce coronary heart disease (CHD) mortality by reducing dietary fat intake. Our 2016 systematic review examined the epidemiological evidence available to the dietary committees at the time; we found no support for the recommendations to restrict dietary fat. The present investigation extends our work by re-examining the totality of epidemiological evidence currently available relating to dietary fat guidelines., Methods: A systematic review and meta-analysis of prospective cohort studies currently available, which examined the relationship between dietary fat, serum cholesterol and the development of CHD, were undertaken., Results: Across 7 studies, involving 89 801 participants (94% male), there were 2024 deaths from CHD during the mean follow-up of 11.9±5.6 years. The death rate from CHD was 2.25%. Eight data sets were suitable for inclusion in meta-analysis; all excluded participants with previous heart disease. Risk ratios (RRs) from meta-analysis were not statistically significant for CHD deaths and total or saturated fat consumption. The RR from meta-analysis for total fat intake and CHD deaths was 1.04 (95% CI 0.98 to 1.10). The RR from meta-analysis for saturated fat intake and CHD deaths was 1.08 (95% CI 0.94 to 1.25)., Conclusions: Epidemiological evidence to date found no significant difference in CHD mortality and total fat or saturated fat intake and thus does not support the present dietary fat guidelines. The evidence per se lacks generalisability for population-wide guidelines., Competing Interests: Competing interests: ZH receives income from writing and from two small self-employment businesses: The Harcombe Diet Co. and Columbus Publishing., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

This study evaluated the effect of game venue and starting status on precompetitive psychophysiological measures in elite rugby union. Saliva samples were taken from players (starting XV, n = 15, and nonstarters, n = 9) on a control day and 90 min before 4 games played consecutively at home and away venues against local rivals and league leaders. Precompetition psychological states were assessed using the Competitive State Anxiety Inventory-2. The squad recorded 2 wins (home) and 2 losses (away) over the study period. Calculated effect sizes (ESs) showed higher pregame cortisol- (C) and testosterone- (T) difference values before all games than on a baseline control day (ES 0.7-1.5). Similar findings were observed for cognitive and somatic anxiety. Small between-venues C differences were observed in starting XV players (ES 0.2-0.25). Conversely, lower home T- (ES 0.95) and higher away C- (ES 0.6) difference values were observed in nonstarters. Lower T-difference values were apparent in nonstarters (vs starting XV) before home games, providing evidence of a between-groups effect (ES 0.92). Findings show an anticipatory rise in psychophysiological variables before competition. Knowledge of starting status appears a moderating factor in the magnitude of player endocrine response between home and away games.

Even though intense exercise has traditionally been associated with a statistically significant accumulation of blood-borne biomarkers of free radical-mediated lipid peroxidation, it remains to be determined if the oxidative stress response is biologically significant. To examine biological significance, we calculated the critical difference of selected biomarkers of oxidants-antioxidants in the peripheral circulation of ten male subjects aged 24±3 years. Venous blood was drawn in the resting supine position every hour over an 8-h period (Study 1). As proof-of-concept, supine venous blood was also obtained at rest and following maximal cycling exercise in a separate group of 13 males, mean age 22±3 years (Study 2). The critical difference of electron paramagnetic resonance spin-trapped alkoxyl free radicals, lipid hydroperoxides, malondialdehyde, ascorbic acid, retinol, lycopene, α-tocopherol, β-carotene and α-carotene was calculated as 121%, 28%, 50%, 9%, 29%, 106%, 13%, 28% and 107%, respectively (Study 1). Maximal exercise was associated with a statistically significant (P<0.05 vs. rest) reduction in α-tocopherol and retinol, and a corresponding rise in alkoxyl free radicals and lipid hydroperoxides (Study 2). However, these changes were all within the critical difference percentage value. In conclusion, these findings highlight the importance of distinguishing biological from statistical significance when assessing the physiological and clinical impact of exercise-induced oxidative stress.

The non-therapeutic use of androgenic anabolic steroids (AAS) is associated with sudden cardiac death. Despite this, there is no proposed mechanism by which this may occur. Signal-averaged ECG (SAECG) allows the assessment of cardiac electrical stability, reductions of which are a known risk factor for cardiac arrhythmias. The aim of the present study was to examine cardiac electrical stability using SAECG in a group (n = 15) of long-term AAS users (AAS use 21.3 ± 3.1 years) compared with a group (n = 15) of age-matched weight lifters (WL) and age-matched sedentary controls [C (n = 15)]. AS, WL and C underwent SAECG analysis at rest and following an acute bout of exercise to volitional exhaustion. SAECGs were analyzed using a 40 Hz filter and were averaged over 200 beats. Results indicate a non-significant trend for increased incidence of abnormal SAECG measures at rest in AS (P = 0.55). However, AS demonstrated a significantly higher incidence of abnormalities of SAECG following exercise than C or WL (P < 0.05). In conclusion, the higher incidence of abnormal SAECG measurements immediately post-exercise in the AAS group places them at a greater risk of sudden death. The present study provides a strong contraindication to the use of AAS.

Introduction: We developed an automated sampling system to allow multiple, discrete blood samples from a human participant to be collected rapidly and immediately following cigarette smoke exposure. We reported the details of the sampling system along with the results of a pilot study for evaluation of the system., Methods: Components of the system include silastic tubing, solenoid pinch valves, a peristaltic pump, and a fraction collector. This system incorporates a smoking machine that allows precise delivery of cigarette smoke through a mouthpiece and intricate timing to correlate blood samples with smoke inhalation. All components are controlled via integration from a user interface and are fully customizable. We performed several tests to evaluate the equipment, including tubing dead volume, leakage tests, and sample reproducibility. We also performed a pilot study with 6 adult smokers, who received 6 controlled puffs of a research test cigarette. Each inhalation was followed by radial arterial blood collection (1 sample per second tapered to 1 sample every 4 s) for 1 min. Samples were evaluated for nicotine via liquid chromatography-tandem mass spectrometric methods., Results: Sampling times and volumes were sufficient for nicotine analysis. No adverse effects were seen in the pilot study, and a 30-min washout period was deemed appropriate between puffs. A significant rise in plasma nicotine levels above baseline after inhalation of smoke was consistently detected in all participants., Discussion: The unique advantage of this system is to allow rapid blood sampling after a puff of cigarette smoke, with the benefits of reproducibility, reduction in labor intensity, and high temporal resolution.

Athletes have enjoyed almost a thirty year amnesty of rhGH abuse, which they consider has contributed to the winning of medals and the breaking of world records. Such a reprieve is almost at an end, since WADA have identified a method to detect rhGH abuse. Or have they? The anecdotal word "on the street" is that rhGH is still undetectable and athletes believe that the benefits, at the dosages they administer, far outweigh the risks! Scientists are aware that in a hormone deficiency condition, replacement can halt and in certain situations reverse some of the adverse effects. Growth hormone deficiency can lead to a loss of skeletal muscle mass and an increase in abdomino-visceral obesity, which is reversed on replacement with rhGH. Since the availability of GH, athletes have been trying to extrapolate these effects from the deficiency state to the healthy corpus and increase their sporting prowess. Past confessions from athletes, such as Ben Johnson, Kelly White, Tim Montgomery, Marion Jones and currently Dwain Chambers have demonstrated that they are prepared to tread the very fine lines that separate the "men from the boys". Rewards are so great, that anonymous surveys have identified that athletes will risk ill health, if they believe they can cheat, win and not get caught. The question that still needs to be answered is, "does growth hormone enhance performance"? Recent research suggests that it could. There is also a suspicion that in "cycled" low supraphysiological doses, it is no where near as harmful as WADA claim it to be.

Anabolic-androgenic steroids (AAS) were the first identified doping agents that have ergogenic effects and are being used to increase muscle mass and strength in adult males. Consequently, athletes are still using them to increase physical performance and bodybuilders are using them to improve size and cosmetic appearance. The prevalence of AAS use has risen dramatically over the last two decades and filtered into all aspects of society. Support for AAS users has increased, but not by the medical profession, who will not accept that AAS use dependency is a psychiatric condition. The adverse effects and potential dangers of AAS use have been well documented. AAS are used in sport by individuals who have acquired knowledge of the half-lives of specific drugs and the dosages and cycles required to avoid detection. Conversely, they are used by bodybuilders in extreme dosages with the intention of gaining muscle mass and size, with little or no regard for the consequences. Polypharmacy by self-prescription is prevalent in this sector. Most recently, AAS use has filtered through to 'recreational street drug' users and is the largest growth of drugs in this subdivision. They are taken to counteract the anorexic and cachectic effects of the illegal psychotropic street drugs. Screening procedures for AAS in World Anti-Doping Agency accredited laboratories are comprehensive and sensitive and are based mainly on gas chromatography-mass spectrometry, although liquid chromatography-mass spectrometry is becoming increasingly more valuable. The use of carbon isotope mass spectrometry is also of increasing importance in the detection of natural androgen administration, particularly to detect testosterone administration. There is a degree of contentiousness in the scenario of AAS drug use, both within and outside sport. AAS and associated doping agents are not illegal per se. Possession is not an offence, despite contravening sporting regulations and moral codes. Until AAS are classified in the same capacity as street drugs in the UK, where possession becomes a criminal offence, they will continue to attract those who want to win at any cost. The knowledge acquired by such work can only assist in the education of individuals who use such doping agents, with a view to minimizing health risks and hopefully once again create a level playing field in sport.

Objectives: To determine whether 6 days recombinant human growth hormone (rhGH) administration, in an abstinent anabolic-androgenic steroid (AAS) using group had any respiratory, endurance exercise and biochemical effects compared with an abstinent AAS control group., Methods: Male subjects (n=48) were randomly divided, using a single blind procedure into two groups: (1) control group (C) n=24, means+/-SD, age 32+/-11 years; height 1.8+/-0.06 m; (2) rhGH using group (0.019 mg kg(-1) day(-1)) (GH) n=24, means+/-SD, age 32+/-9 years; height 1.8+/-0.07 m. Anthropometry, respiratory muscle function and endurance exercise were investigated. Respiratory measurements examined, were forced expiratory volume in one second, forced vital capacity, maximum inspiratory pressure and maximum expiratory pressure. Endurance exercise was assessed by measuring peak oxygen uptake (VO(2)peak). Biochemical analysis included; haemoglobin, packed cell volume, glucose, sodium, urea, creatinine, total protein, albumin, testosterone and insulin like growth factor-I (IGF-I)., Results: Forced expiratory volume in one second/forced vital capacity, maximum inspiratory pressure, maximum expiratory pressure, and IGF-I significantly increased compared with the control group (all P<0.05). Body mass index, fat free mass index, peak oxygen uptake, maximum inspiratory pressure, maximum expiratory pressure, IGF-I and serum sodium significantly increased, whilst body fat, total protein and albumin, significantly decreased within the GH group (all P<0.017)., Conclusion: The findings of this study indicated that short-term high dose rhGH increased aerobic performance and respiratory muscle strength in former AAS users.

Objectives: To determine whether six days recombinant human growth hormone (rhGH) in an abstinent anabolic-androgenic steroid (AAS) group had any cardiovascular and biochemical effects compared with a control group., Methods: Male subjects (n=48) were randomly divided, using a single blind procedure into two groups: (1) control group (C) n=24, mean+/-SD, age 32+/-11 years; height 1.8+/-0.06m; (2) rhGH using group (0.058IUkg(-1)day(-1)) (GH) n=24, mean+/-SD, age 32+/-9 years; height 1.8+/-0.07m. Physiological responses, anthropometry, arterial pulse wave velocity (APWV), blood pressure (BP), heart rate (HR), peak oxygen uptake (VO(2) peak) and biochemical indices were investigated., Results: Body mass index, fat-free mass index and VO(2) peak significantly increased while body fat significantly decreased within GH (all P<0.017). Insulin like growth factor-I significantly increased within GH (P<0.017) and compared with C (P<0.05). Serum sodium significantly increased (P<0.017) and serum homocysteine, high sensitivity C-reactive protein, thyroid stimulating hormone and tetra-iodothyronine (T(4)), significantly decreased within GH (all P<0.017). T(4) significantly decreased compared with C (P<0.05). Arterial pulse wave velocity, peak and recovery systolic and diastolic BP, significantly decreased compared with C (P<0.05). Resting HR and rate pressure product (RPP) significantly increased compared with C (P<0.05)., Conclusion: The findings of this study suggest that short term use of rhGH may have beneficial effects on endothelial function and specific inflammatory markers of cardiovascular disease in abstinent AAS users, but may have an adverse effect on the cardiovascular system, as evidenced by the increase in resting RPP.

The purpose of this study was to examine relationships between aerobic fitness (AF), fatness, and coronary-heart-disease (CHD) risk factors in 12- to 13-year-olds. The data were obtained from 208 schoolchildren (100 boys; 108 girls) ages 12.9 +/- 0.3 years. Measurements included AF, indices of obesity, blood pressure, blood lipids and lipoproteins, fibrinogen, homocysteine, and C-reactive protein. An inverse relationship was found between AF and fatness (p

This study examined whether six days recombinant human growth hormone (rhGH) affected psychological profile in an abstinent androgenic-anabolic steroid (AAS) abusing group, compared with an abstinent AAS control group. Male subjects (n = 48) were assigned in a random fashion into one of two groups: (1): (n=24) control group (C); (2): (n=24) rhGH group (GH). A hospital anxiety scale (HADS) questionnaire was completed by all subjects. Physiological responses investigated included anthropometry. Biochemical markers examined included; serum glucose, sodium, urea, lipid profile, high sensitivity C-reactive protein (hsCRP), homocysteine (HCY), tetra-iodothyronine (T4), thyroid stimulating (TSH), luteinising (LH) and follicle stimulating (FSH) hormones, testosterone (T), prolactin (PRL), cortisol and insulin like growth factor-1 (IGF-I). HADS questionnaire significantly decreased in both anxiety (A) and depression (D) symptoms within GH (P<0.017) and compared with C (P<0.05). Body mass index (BMI) and fat-free mass index (FFMI) significantly increased (both P<0.017) while body fat significantly decreased within GH (P<0.017). IGF-I significantly increased within GH (P<0.017) and significantly increased compared with C (P<0.05). Serum sodium significantly increased (P<0.017) and serum HCY, hsCRP, TSH and T4, significantly decreased within GH (all P<0.017). PRL significantly increased and T4 significantly decreased compared with C (both P<0.05). The findings of this study suggest that short term use of rhGH has beneficial effects on mental state in individuals who were previous abusers of AAS and appeared to have a beneficial effect on cardiovascular risk markers associated with adverse mental health.

The purpose of this study was to measure power values generated in elite karate fighters during brief high intensity cycle ergometry when resistive forces were derived from total - body mass (TBM) or fat - free mass (FFM). Male international karate practitioners volunteered as participants (n = 11). Body density was calculated using hydrostatic weighing procedures with fat mass ascertained from body density values. Participants were required to pedal maximally on a cycle ergometer (Monark 864) against randomly assigned loads ranging from 70 g·kg(-1) - 95 g·kg(-1) (using a TBM or FFM protocol) for 8 seconds. The resistive force that produced the highest peak power output (PPO) for each protocol was considered optimal. Differences (p < 0.05) in peak power outputs were found between the TBM and FFM experimental condition (1164 ± 137 W vs. 1289 ± 145 W respectively). Differences were also recorded (p < 0.01) between pedal velocity and applied resistive forces (127 ± 8 rpm vs. 142 ± 7 rpm; 6.6 ± 1 kg vs. 5.5 ± 1 kg, respectively). No differences (p > 0.05) were observed between time to PPO, or heart rate when the TBM and FFM protocols were compared. The findings of this study suggest that when high intensity cycle ergometer resistive forces are derived from FFM, greater peak powers can be obtained consistently in karate athletes. Resistive forces that relate to the active muscle tissue utilised during this type of exercise may need to be explored in preference to protocols that include both lean and fat masses. The findings have implications for both exercise prescription and the evaluation of experimental results concerning karate athletes. Key PointsMethods for quantifying and measuring high intensity performance using high intensity cycle ergometry have received considerable attention in recent years.The assumption has been that the relationship between total - body mass (TBM) and fat - free mass (FFM) is the same.However, variations in body composition between participants may under or over estimate cradle resistive forces used in high intensity cycle ergometry power assessment.This may lead to spurious calculations of power.The findings of this study demonstrate that the total capacity, power and relative contribution of the energy systems involved during experimental high intensity cycle ergometer exercise need re - evaluating.

It is well established that tobacco smokers have reduced levels of monoamine oxidase activities both in the brain and peripheral organs. Furthermore, extensive evidence suggests that smokers are less prone to develop Parkinson's disease. These facts, plus the observation that inhibition of monoamine oxidase B protects against the parkinsonian inducing effects of the nigrostriatal neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have prompted studies to identify monoamine oxidase inhibitors in the tobacco plant and tobacco cigarette smoke. Our previous efforts on cured tobacco leaf extracts have led to the characterization of 2,3,6-trimethyl-1,4-naphthoquinone, a non-selective monoamine oxidase inhibitor, and farnesylacetone, a selective monoamine oxidase B inhibitor. We now have extended these studies to tobacco smoke constituents. Fractionation of the smoke extracts has confirmed and extended the qualitative results of an earlier report [J. Korean Soc. Tob. Sci.1997, 19, 136] demonstrating the inhibitory activity of the terpene trans,trans-farnesol on rat brain MAO-B. In the present study, K(i) values for the inhibition of human, baboon, monkey, dog, rat, and mouse liver MAO-B have been determined. Noteworthy is the absence of inhibitory effects on human placental MAO-A and beef liver MAO-B. A limited structure-activity relationship study of analogs of trans,trans-farnesol is reported. Although the health hazards associated with the use of tobacco products preclude any therapeutic opportunities linked to smoking, these results suggest the possibility of identifying novel structures of compounds that could lead to the development of neuroprotective agents.

This study assesses the prevalence of recently identified coronary heart disease (CHD) risk factors in young people of differing socioeconomic status (SES). From November 2001 through March 2002, 100 boys and 108 girls, of age 12.9 +/- 0.3 years, selected from differing SES were assessed for CHD risk factors. Measurements included fibrinogen (Fg), homocyst(e)ine (Hcy), and C-reactive protein (CRP). Fibrinogen was significantly greater among boys from a higher SES compared with those from a low SES (P < or = 0.05). Differences according to sex (P < or = 0.05) were identified for Fg and CRP. The data indicate the prevalence of recently identified CHD risk factors in this cohort of British schoolchildren. For the purpose of this article, the phrase "young people" embraces both children and adolescents., (Copyright 2005 Wiley-Liss, Inc)

Purpose: The purpose of this study was to examine the upper-body contribution via handgrip to power profiles and blood lactate concentrations during high-intensity cycle ergometry., Methods: Nine trained male subjects each completed a 20-s high-intensity cycle ergometer test twice, in a random manner, using two protocols, with a handgrip (WG), and without handgrip (WOHG). Capillary (earlobe) blood samples were obtained pre- and post-exercise. Blood samples were corrected for plasma volume changes and analyzed to determine blood lactate concentrations., Results: In the WG protocol, mean (+/-SEM) blood lactate concentrations sampled over the three conditions were 0.98 +/- 0.33 mmol.L-1, 5.68 +/- 0.46 mmol.L-1, and 9.14 +/- 0.38 mmol.L-1, respectively. During the WOHG protocol, blood lactate values recorded were 0.99 +/- 0.26 mmol.L-1, 5.58 +/- 0.58 mmol.L-1, and 7.62 +/- 0.65 mmol.L-1, respectively. Differences were found (P < 0.05) from rest to 4 min after exercise for both groups. Differences in concentrations were also observed between groups at the 4-min postexercise blood-sampling stage. Peak power output values recorded using the WG protocol were also greater (1461 +/- 94 W vs 1136 +/- 88 W; P < 0.05). No differences were recorded for mean power output (MPO), fatigue index (FI), or work done (WD)., Conclusion: Results indicate significant differences in power output and blood lactate concentrations between protocols. These findings suggest that the performance of traditional style leg-cycle ergometry requires a muscular contribution from the whole body. As such, researchers should consider this, both in terms of the allocation of ergometer loads, and in the analysis of blood-borne metabolites.

The relationship between somatotype and somatotype components with coronary artery disease (CAD) and regional adiposity was considered in 58 males (age 60.2 +/- 9.4 years) undergoing investigative coronary angiography for suspected atherosclerotic CAD. Severity of CAD was determined in terms of both the degree of stenosis and the anatomical position of the lesions on the coronary arteries (myocardial score). Six patients had negative angiographic findings but three of these had impaired left ventricular function as determined by left ventriculography. The mean (+/-SD) somatotype of the group was 5.7 / 5.6 / 1.2 (1.7 / 1.4 / 1.0), illustrating a clear dominance of the first two somatotype components. Canonical correlation analysis showed that somatotype was not significantly related to the angiography results (P > 0.05). However, correlations between the somatotype components and the angiography results with their respective first canonical variates showed that the somatotype variate was one of high mesomorphy and low ectomorphy and the angiography variate was essentially one of a high myocardial score. After adjustment for the confounding interrelationship among the somatotype components, endomorphy was significantly correlated with abdominal circumference (r = 0.65, P < 0.001), the abdomen-to-hip ratio (r = 0.53, P < 0.001) and the abdominal sagittal diameter (r = 0.60, P < 0.001). Mesomorphy was not related to these indicators of android or abdominal adiposity following partial adjustment. Ectomorphy was inversely related to the indices of general and regional adiposity. This study suggests that adiposity and muscularity are important features in terms of increased CAD risk, whereas linearity is beneficial. Am. J. Hum. Biol. 12:128-138, 2000. Copyright 2000 Wiley-Liss, Inc.