Potentially harmful advantage to athletes: a putative connection between UGT2B17 gene deletion polymorphism and renal disorders with prolonged use of anabolic androgenic steroids

ABSTRACT: BACKGROUND AND OBJECTIVE: With prolonged use of anabolic androgenic steroids (AAS), occasional incidents of renal disorders have been observed. Independently, it has also been established that there are considerable inter-individual and inter-ethnic differences, in particular with reference to the uridine diphosphate-glucuronosyltransferase 2B17 (UGT2B17) gene, in metabolising these compounds. This report postulates the association of deletion polymorphism in the UGT2B17 gene with the occurrence of renal disorders on chronic exposure to AAS. PRESENTATION OF THE HYPOTHESIS: The major deactivation and elimination pathway of AASs is through glucuronide conjugation, chiefly catalyzed by the UGT2B17 enzyme, followed by excretion in urine. Excretion of steroids is affected in individuals with a deletion mutation in the UGT2B17 gene. We hypothesize that UGT2B17 deficient individuals are more vulnerable to developing renal disorders with prolonged use of AAS owing to increases in body mass index and possible direct toxic effects of steroids on the kidneys. Elevated serum levels of biologically active steroids due to inadequate elimination can lead to prolonged muscle build up. An increase in body mass index may cause renal injuries due to sustained elevated glomerular pressure and flow rate. TESTING THE HYPOTHESIS: In the absence of controlled clinical trials in humans, observational studies can be carried out. Real time PCR with allelic discrimination should be employed to examine the prevalence of different UGT2B17 genotypes in patients with impaired renal function and AAS abuse. In individuals with the UGT2B17 deletion polymorphism, blood tests, biofluid analyses, urinalysis, and hair analyses following the administration of an anabolic steroid can be used to determine the fate of the substance once in the body. IMPLICATIONS OF THE HYPOTHESIS: If the hypothesis is upheld, anabolic steroid users with a deletion mutation in the UGT2B17 gene may be exposed to an increased risk of developing renal disorders. In the current detecting - sanctioning anti-doping system, athletes motivated by the potential to evade detection owing to their unique genetic make-up could subject themselves to a serious health consequence. More research on AAS metabolism in the presence of UGT2B17 gene deletion is required. Benefit - harm evaluations in therapeutic use of anabolic steroids should also consider this potential link between UGT2B17 gene deletion polymorphism and renal disorders

Military spending and economic growth in China: a regime-switching analysis

This article has been made available through the Brunel Open Access Publishing Fund.This article investigates the impact of military spending changes on economic growth in China over the period 1953 to 2010. Using two-state Markov-switching specifications, the results suggest that the relationship between military spending changes and economic growth is state dependent. Specifically, the results show that military spending changes affect the economic growth negatively during a slower growth-higher variance state, while positively within a faster growth-lower variance one. It is also demonstrated that military spending changes contain information about the growth transition probabilities. As a policy tool, the results indicate that increases in military spending can be detrimental to growth during slower growth-higher growth volatility periods. © 2014 © 2014 The Author(s). Published by Taylor & Francis

Correlated Persistent Tunneling Currents in Glasses

Low temperature properties of glasses are derived within a generalized tunneling model, considering the motion of charged particles on a closed path in a double-well potential. The presence of a magnetic induction field B violates the time reversal invariance due to the Aharonov-Bohm phase, and leads to flux periodic energy levels. At low temperature, this effect is shown to be strongly enhanced by dipole-dipole and elastic interactions between tunneling systems and becomes measurable. Thus, the recently observed strong sensitivity of the electric permittivity to weak magnetic fields can be explained. In addition, superimposed oscillations as a function of the magnetic field are predicted.Comment: 4 page

Magnetic Determination of Hc2H_{c2} under Accurate Alignment in (TMTSF)2_2ClO4_4

Cantilever magnetometry has been used to measure the upper critical magnetic field $H_{c2}$ of the quasi-one dimensional molecular organic superconductor (TMTSF)$_2$ClO$_4$. From simultaneous resistivity and torque magnetization experiments conducted under precise field alignment, $H_{c2}$ at low temperature is shown to reach 5T, nearly twice the Pauli paramagnetic limit imposed on spin singlet superconductors. These results constitute the first thermodynamic evidence for a large $H_{c2}$ in this system and provide support for spin triplet pairing in this unconventional superconductorComment: Submitted July 1, 2003, Accepted December 9, 2003, Physical Review Letter

Polarization Dependence of Bulk Ion Acceleration from Ultrathin Foils Irradiated by High-Intensity Ultrashort Laser Pulses

The acceleration of ions from ultrathin (10-100 nm) carbon foils has been investigated using intense (∼ 6 x1020 Wcm-2), ultrashort (45 fs) laser pulses, highlighting a strong dependence of the ion beam parameters on the laser polarization, with circularly polarized (CP) pulses producing the highest energies for both protons and carbons (25-30 MeV/nucleon); carbon ion energies obtained employing CP pulses were signicantly higher (∼2.5 times) than for irradiations employing linearly polarized (LP) pulses. Particle-in-cell simulations indicate that Radiation Pressure Acceleration becomes the dominant mechanism for the thinnest targets and CP pulses

Phase Diagram for Charge Density Waves in a Magnetic Field

The influence of an external magnetic field on a quasi one-dimensional system with a charge density wave (CDW) instability is treated within the random phase approximation which includes both CDW and spin density wave correlations. We show that the CDW is sensitive to both orbital and Pauli effects of the field. In the case of perfect nesting, the critical temperature decreases monotonously with the field, and the wave vector of the instability starts to shift above some critical value of magnetic field. Depending on the ratio between the spin and charge coupling constants and on the direction of the applied magnetic field, the wave vector shift is either parallel ($CDW_x$ order) or perpendicular ($CDW_y$ order) to the most conducting direction. The $CDW_x$ order is a field dependent linear combination of the charge and spin density waves and is sensible only to the Pauli effect. The wave vector shift in $CDW_y$ depends on the interchain coupling, but the critical temperature does not. This order is affected by the confinement of the electronic orbits. By increasing the relative strength of the orbital effect with respect to the Pauli effect, one can destroy the $CDW_y$, establishing either a $CDW_x$, or a $CDW_0$ (corresponding to perfect nesting wave vector). We also show that by increasing the imperfect nesting parameter, one passes from the regime where the critical temperature decreases with the field to the regime where it is initially enhanced by the orbital effect and eventually suppressed by the Pauli effect. For a bad nesting, the quantized phases of the field-induced CDW appear.Comment: 30 pages (LaTeX) + 15 figure

Direct access:how is it working?

AimThe aim of this study was to identify and survey dental hygienists and therapists working in direct access practices in the UK, obtain their views on its benefits and disadvantages, establish which treatments they provided, and what barriers they had encountered.MethodThe study used a purposive sample of GDC-registered hygienists and therapists working in practices offering direct access, identified through a ‘Google’ search. An online survey was set up through the University of Edinburgh, and no-responses followed up by post.ResultsThe initial search identified 243 individuals working in direct access practices. Where a practice listed more than one hygienist/therapist, one was randomly selected. This gave a total of 179 potential respondents. Eighty six responses were received, representing a response rate of 48%. A large majority of respondents (58, 73%) were favourable in their view of the GDC decision to allow direct access, and most thought advantages outnumbered disadvantages for patients, hygienists, therapists and dentists. There were no statistically significant differences in views between hygienists and therapists. Although direct access patients formed a small minority of their caseload for most respondents, it is estimated that on average respondents saw approximately 13 per month. Treatment was mainly restricted to periodontal work, irrespective of whether the respondent was singly or dually qualified. One third of respondents reported encountering barriers to successful practice, including issues relating to teamwork and dentists’ unfavourable attitudes. However, almost two thirds(64%) felt that direct access had enhanced their job satisfaction, and 45% felt their clinical skills had increased.DiscussionComments were mainly positive, but sometimes raised worrying issues, for example in respect to training, lack of dental nurse support and the limited availability of periodontal treatment under NHS regulations

Destruction of density-wave states by a pseudo-gap in high magnetic fields: application to (TMTSF)2_2ClO4_4

A model is presented for the destruction of density-wave states in quasi-one-dimensional crystals by high magnetic fields. The model is consistent with previously unexplained properties of the organic conductors (TMTSF)$_2$ClO$_4$ and (BEDT-TTF)$_2$MHg(SCN)$_4$ (M=K,Rb,Tl). As the magnetic field increases quasi-one-dimensional density-wave fluctuations increase, producing a pseudo-gap in the electronic density of states near the transition temperature. When the pseudo-gap becomes larger than the mean-field transition temperature formation of a density-wave state is not possible.Comment: 4 pages, RevTeX, 2 figures in uuencoded compressed tar file. Small changes to text and Figure 1. Final version to appear in Physical Review Letter

Role of the dimerized gap due to anion ordering in spin-density wave phase of (TMTSF)2_2ClO4_4 at high magnetic fields

Magnetoresistance measurements have been carried out along the highly conducting a axis in the FISDW phase of hydrogened and deuterated (TMTSF)$_2$ClO$_4$ for various cooling rates through the anion ordering temperature. With increasing the cooling rate, a) the high field phase boundary $\beta_{\rm {HI}}$, observed at 27 T in hydrogened samples for slowly cooled, is shifted towards a lower field, b) the last semimetallic SDW phase below $\beta_{\rm {HI}}$ is suppressed, and c) the FISDW insulating phase above $\beta_{\rm {HI}}$ is enhanced in both salts. The cooling rate dependence of the FISDW transition and of $\beta_{\rm {HI}}$ in both salts can be explained by taking into account the peculiar SDW nesting vector stabilized by the dimerized gap due to anion ordering.Comment: 6pages,6figures(EPS), accepted for publication in PR