A pilot study comparing the metabolic profiles of elite-level athletes from different sporting disciplines

Background: The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Methods: Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Results: Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. Conclusions: This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes’ elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications

Plastic shrinkage cracking of concrete - Roles of osmotic suction

Plastic shrinkage cracking of concrete occurs when the stresses arising in the concrete, due to a combination of suction and restraints of deformation such as reinforcement or formwork, equal its strength. However, three different types of suctions should be distinguished, namely total, matric and osmotic suctions. Although the total suction comprises matric and osmotic suctions, it is often used interchangeably with matric suction, with the underlying unconfirmed assumption that either the osmotic suction or its effect is negligible. In this paper, after a discussion of the pore moisture suctions and strength of unsaturated early-age concrete, experimental investigations of the suctions arising in, and the tensile strength and shear strength of, fly ash mixed with solutions of different osmotic suctions are described. It was found that osmotic suction has negligible effect on the shear and tensile strength, and hence, by inference, the inter-particle stresses in the fly ash mixture and early-age concrete. This strongly suggests that the role played by osmotic suction in the plastic shrinkage cracking of concrete is minimal and, accordingly, justifies the focus of earlier researchers on matric suction only

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein

Phase I Evaluation of STA-1474, a Prodrug of the Novel HSP90 Inhibitor Ganetespib, in Dogs with Spontaneous Cancer

The novel water soluble compound STA-1474 is metabolized to ganetespib (formerly STA-9090), a potent HSP90 inhibitor previously shown to kill canine tumor cell lines in vitro and inhibit tumor growth in the setting of murine xenografts. The purpose of the following study was to extend these observations and investigate the safety and efficacy of STA-1474 in dogs with spontaneous tumors.This was a Phase 1 trial in which dogs with spontaneous tumors received STA-1474 under one of three different dosing schemes. Pharmacokinetics, toxicities, biomarker changes, and tumor responses were assessed. Twenty-five dogs with a variety of cancers were enrolled. Toxicities were primarily gastrointestinal in nature consisting of diarrhea, vomiting, inappetence and lethargy. Upregulation of HSP70 protein expression was noted in both tumor specimens and PBMCs within 7 hours following drug administration. Measurable objective responses were observed in dogs with malignant mast cell disease (n = 3), osteosarcoma (n = 1), melanoma (n = 1) and thyroid carcinoma (n = 1), for a response rate of 24% (6/25). Stable disease (>10 weeks) was seen in 3 dogs, for a resultant overall biological activity of 36% (9/25).This study provides evidence that STA-1474 exhibits biologic activity in a relevant large animal model of cancer. Given the similarities of canine and human cancers with respect to tumor biology and HSP90 activation, it is likely that STA-1474 and ganetespib will demonstrate comparable anti-cancer activity in human patients

Evolutionary factors affecting Lactate dehydrogenase A and B variation in the Daphnia pulex species complex

Background: Evidence for historical, demographic and selective factors affecting enzyme evolution can be obtained by examining nucleotide sequence variation in candidate genes such as Lactate dehydrogenase (Ldh). Two closely related Daphnia species can be distinguished by their electrophoretic Ldh genotype and habitat. Daphnia pulex populations are fixed for the S allele and inhabit temporary ponds, while D. pulicaria populations are fixed for the F allele and inhabit large stratified lakes. One locus is detected in most allozyme surveys, but genome sequencing has revealed two genes, LdhA and LdhB. Results: We sequenced both Ldh genes from 70 isolates of these two species from North America to determine if the association between Ldh genotype and habitat shows evidence for selection, and to elucidate the evolutionary history of the two genes. We found that alleles in the pond-dwelling D. pulex and in the lake-dwelling D. pulicaria form distinct groups at both loci, and the substitution of Glutamine (S) for Glutamic acid (F) at amino acid 229 likely causes the electrophoretic mobility shift in the LDHA protein. Nucleotide diversity in both Ldh genes is much lower in D. pulicaria than in D. pulex. Moreover, the lack of spatial structuring of the variation in both genes over a wide geographic area is consistent with a recent demographic expansion of lake populations. Neutrality tests indicate that both genes are under purifying selection, but the intensity is much stronger on LdhA. Conclusions: Although lake-dwelling D. pulicaria hybridizes with the other lineages in the pulex species complex, it remains distinct ecologically and genetically. This ecological divergence, coupled with the intensity of purifying selection on LdhA and the strong association between its genotype and habitat, suggests that experimental studies would be useful to determine if variation in molecular function provides evidence that LDHA variants are adaptive

Modeling the Population-Level Effects of Male Circumcision as an HIV-Preventive Measure: A Gendered Perspective

BACKGROUND: Evidence from biological, epidemiological, and controlled intervention studies has demonstrated that male circumcision (MC) protects males from HIV infection, and MC is now advocated as a public-health intervention against HIV. MC provides direct protection only to men, but is expected to provide indirect protection to women at risk of acquiring HIV from heterosexual transmission. How such indirect protection interacts with the possibility that MC campaigns will lead to behavior changes, however, is not yet well understood. Our objective here is to investigate the link between individual-level effects of MC campaigns and long-term population-level outcomes resulting from disease dynamics, looking at both genders separately, over a broad range of parameters. METHODS AND FINDINGS: We use simple mathematical models of heterosexual transmission to investigate the potential effects of a circumcision scale-up, combined with possible associated behavioral disinhibition. We examine patterns in expected long-term prevalence using a simple equilibrium model based on transmission factors, and validate our results with ODE-based simulations, focusing on the link between effects on females and those on males.We find that the long-term population-level effects on females and males are not strongly linked: there are many possible ways in which an intervention which reduces prevalence in males might nonetheless increase prevalence in females. CONCLUSIONS: Since an intervention that reduces long-term male prevalence could nonetheless increase long-term female prevalence, MC campaigns should explicitly consider both the short-term and long-term effects of MC interventions on females. Our findings strongly underline the importance of pairing MC programs with education, support programs and HIV testing and counseling, together with other prevention measures

Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts

Background: Prostate tumours are commonly poorly oxygenated which is associated with tumour progression and development of resistance to chemotherapeutic drugs and radiotherapy. Fibroblast growth factor 8b (FGF8b) is a mitogenic and angiogenic factor, which is expressed at an increased level in human prostate tumours and is associated with a poor prognosis. We studied the effect of FGF8b on tumour oxygenation and growth parameters in xenografts in comparison with vascular endothelial growth factor (VEGF)-expressing xenografts, representing another fast growing and angiogenic tumour model. Methods: Subcutaneous tumours of PC-3 cells transfected with FGF8b, VEGF or empty (mock) vectors were produced and studied for vascularity, cell proliferation, glucose metabolism and oxygenation. Tumours were evaluated by immunohistochemistry (IHC), flow cytometry, use of radiolabelled markers of energy metabolism ([F-18] FDG) and hypoxia ([F-18] EF5), and intratumoral polarographic measurements of pO(2). Results: Both FGF8b and VEGF tumours grew rapidly in nude mice and showed highly vascularised morphology. Perfusion studies, pO(2) measurements, [F-18] EF5 and [F-18] FDG uptake as well as IHC staining for glucose transport protein (GLUT1) and hypoxia inducible factor (HIF) 1 showed that VEGF xenografts were well-perfused and oxygenised, as expected, whereas FGF8b tumours were as hypoxic as mock tumours. These results suggest that FGF8b-induced tumour capillaries are defective. Nevertheless, the growth rate of hypoxic FGF8b tumours was highly increased, as that of well-oxygenised VEGF tumours, when compared with hypoxic mock tumour controls. Conclusion: FGF8b is able to induce fast growth in strongly hypoxic tumour microenvironment whereas VEGF-stimulated growth advantage is associated with improved perfusion and oxygenation of prostate tumour xenografts

The Accumulation of Organic Carbon in Mineral Soils by Afforestation of Abandoned Farmland

The afforestation of abandoned farmland significantly influences soil organic carbon (OC). However, the dynamics between OC inputs after afforestation and the original OC are not well understood. To learn more about soil OC dynamics after afforestation of farmland, we measured the soil OC content in paired forest and farmland plots in Shaanxi Province, China. The forest plots had been established on farmland 18, 24, 48, 100, and 200 yr previously. The natural 13C abundance of soil organic matter was also analyzed to distinguish between crop- and forest-derived C in the afforested soils. We observed a nonlinear accumulation of total OC in the 0–80 cm depth of the mineral soil across time. Total soil OC accumulated more rapidly under forest stands aged 18 to 48 yr than under forest stands aged 100 or 200 yrs. The rate of OC accumulation was also greater in the 0–10 cm depth than in the 10–80 cm depth. Forest-derived OC in afforested soils also accumulated nonlinearly across time, with the greatest increase in the 0–20 cm depth. Forest-derived OC in afforest soils accounted for 52–86% of the total OC in the 0–10 cm depth, 36–61% of the total OC in the 10–20 cm depth, and 11–50% of the total OC in the 20–80 cm depth. Crop-derived OC concentrations in the 0–20 cm depth decreased slightly after afforestation, but there was no change in crop-derived OC concentrations in the 20–80 cm depth. The results of our study support the claim that afforestation of farmland can sequester atmospheric CO2 by increasing soil OC stocks. Changes in the OC stocks of mineral soils after afforestation appear to be influenced mainly by the input of forest-derived C rather than by the loss of original OC

Studying Public Health Law::Principles, Politics, and Populations as Patients

Public health law is firmly establishing itself as a crucial area of scholarly inquiry. Its vital importance has been sharply underscored following the outbreak of COVID-19, in response to which we have seen the institution of extreme legal measures—suchas the UK’s Coronavirus Act 2020—in efforts to control and contain the spread ofthe disease. The pandemic has also starkly exposed the complex nature of the regulatory challenges, nationally, internationally, and globally, to which such public health problems give rise. In approaching these, and other questions concerning the public’s health, such as non-communicable disease, public health law, as a field, brings notable distinctive features: these include a practical focus on populations, institutions, the prevention of ill health, protection of good health, and thepromotion of positive states of well-being; and concomitant critical approaches rooted in theories of social justice as contrasted with more narrow biomedical ethics. Such features make it in some senses atypical territory within the field of health law. Furthermore, the inherent role of political institutions places law conceptually within public health in a way that may be seen as distinguishable from law’s relationship with clinical medicine. This chapter explains how the broad reach and distinct features of public health require a commensurately broad approach to conceptualising public health law, and how distinct practical and theoretical features may be integrated into academic public health law. It also shows how public health law, with its distinct conceptualisations concerning ‘the body’ of medical jurisprudence, can both challenge and enrich medico-legal studies, and bring important perspectives within the broader field of health law