Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, ...thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).
CYP2D6
and
CYP2C19
polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and ...others by both polymorphic enzymes (e.g., amitriptyline, clomipramine, doxepin, imipramine, and trimipramine). Evidence is presented for
CYP2D6
and
CYP2C19
genotype-directed dosing of TCAs. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for
CYP2D6
and
CYP2C19
Genotypes and Dosing of Tricyclic Antidepressants.
The response to exercise training (trainability) has been shown to have a strong heritable component. There is growing evidence suggesting that traits such as trainability do not only depend on the ...genetic code, but also on epigenetic signals. Epigenetic signals play an important role in the modulation of gene expression, through mechanisms such as DNA methylation and histone modifications. There is an emerging evidence to show that physical activity influences DNA methylation in humans. The present review aims to summarize current knowledge on the link between DNA methylation and physical activity in humans. We have critically reviewed the literature and only papers focused on physical activity and its influence on DNA methylation status were included; a total of 25 papers were selected. We concluded that both acute and chronic exercises significantly impact DNA methylation, in a highly tissue‐ and gene‐specific manner. This review also provides insights into the molecular mechanisms of exercise‐induced DNA methylation changes, and recommendations for future research.
The bryozoan
Schizoporella japonica
Ortmann (1890) was first recorded in European waters in 2010 and has since been reported from further locations in Great Britain (GB) and Norway. This paper ...provides a new earliest European record for the species from 2009, a first record from Ireland and presence and absence records from a total of 231 marinas and harbours across GB, Ireland, the Isle of Man, France and Portugal. This species is typically associated with human activity, including commercial and recreational vessels, aquaculture equipment, and both wave and tidal energy devices. It has also been observed in the natural environment, fouling rocks and boulders. The species has an extensive but widely discontinuous distribution in GB and Ireland. Although found frequently in marinas and harbours in Scotland, it inhabits only a few sites in England, Wales and Ireland, interspersed with wide gaps that are well documented as genuine absences. This appears to be a rare example of a southward-spreading invasion in GB and Ireland. The species has been reported from the Isle of Man and Norway but has not been found in France or Portugal. In the future we expect
S. japonica
to spread into suitable sections of the English, Welsh and Irish coasts, and further within Europe. The species’ capability for long-distance saltatory spread and potential for negative impact on native ecosystems and economic activity suggests that
S. japonica
should now be considered invasive in GB and Ireland. As such, it is recommended that biosecurity procedures alongside effective surveillance and monitoring should be prioritised for regions outside the species’ current distribution.
Although reduced-intensity conditioning (RIC) and non-myeloablative (NMA)-conditioning regimens have been used for over a decade, their relative efficacy vs myeloablative (MA) approaches to ...allogeneic hematopoietic cell transplantation in patients with AML and myelodysplasia (MDS) is unknown. We compared disease status, donor, graft and recipient characteristics with outcomes of 3731 MA with 1448 RIC/NMA procedures performed at 217 centers between 1997 and 2004. The 5-year univariate probabilities and multivariate relative risk outcomes of relapse, TRM, disease-free survival (DFS) and OS are reported. Adjusted OS at 5 years was 34, 33 and 26% for MA, RIC and NMA transplants, respectively. NMA conditioning resulted in inferior DFS and OS, but there was no difference in DFS and OS between RIC and MA regimens. Late TRM negates early decreases in toxicity with RIC and NMA regimens. Our data suggest that higher regimen intensity may contribute to optimal survival in patients with AML/MDS, suggesting roles for both regimen intensity and graft vs leukemia in these diseases. Prospective studies comparing regimens are needed to confirm this finding and determine the optimal approach to patients who are eligible for either MA or RIC/NMA conditioning.
School of Sport and Exercise Sciences, Loughborough University, Leicestershire, United Kingdom
Submitted 8 July 2006
; accepted in final form 6 March 2007
Ghrelin is an orexigenic hormone secreted ...from endocrine cells in the stomach and other tissues. Acylation of ghrelin is essential for appetite regulation. Vigorous exercise induces appetite suppression, but this does not appear to be related to suppressed concentrations of total ghrelin. This study examined the effect of exercise and feeding on plasma acylated ghrelin and appetite. Nine male subjects aged 1925 yr participated in two, 9-h trials (exercise and control) in a random crossover design. Trials began at 0800 in the morning after an overnight fast. In the exercise trial, subjects ran for 60 min at 72% of maximum oxygen uptake between 0800 and 0900. After this, they rested for 8 h and consumed a test meal at 1100. In the control trial, subjects rested for 9 h and consumed a test meal at 1100. Area under the curve values for plasma acylated ghrelin concentration (assessed from venous blood samples) were lower over the first 3 h and the full 9 h of the exercise trial compared with the control trial: 317 ± 135 vs. 510 ± 186 pg·ml 1 ·3 h and 917 ± 342 vs. 1,401 ± 521 pg·ml 1 ·9 h (means ± SE) respectively ( P <0.05). Area under the curve values for hunger (assessed using a visual scale) were lower over the first 3 h of the exercise trial compared with the control trial ( P = 0.013). These findings demonstrate that plasma acylated ghrelin concentration and hunger are suppressed during running.
running; appetite; hunger
Address for reprint requests and other correspondence: D. J. Stensel, School of Sport and Exercise Sciences, Loughborough Univ., Leicestershire LE11 3TU, UK (e-mail: D.J.Stensel{at}lboro.ac.uk )
Relaxor ferroelectrics exemplify a class of functional materials where interplay between disorder and phase instability results in inhomogeneous nanoregions. Although known for about 30 years, there ...is no definitive explanation for polar nanoregions (PNRs). Here we show that ferroelectric phonon localization drives PNRs in relaxor ferroelectric PMN-30%PT using neutron scattering. At the frequency of a preexisting resonance mode, nanoregions of standing ferroelectric phonons develop with a coherence length equal to one wavelength and the PNR size. Anderson localization of ferroelectric phonons by resonance modes explains our observations and, with nonlinear slowing, the PNRs and relaxor properties. Phonon localization at additional resonances near the zone edges explains competing antiferroelectric distortions known to occur at the zone edges. Our results indicate the size and shape of PNRs that are not dictated by complex structural details, as commonly assumed, but by phonon resonance wave vectors. This discovery could guide the design of next generation relaxor ferroelectrics.
Sprint performance under heat stress: A review Girard, O.; Brocherie, F.; Bishop, D. J.
Scandinavian journal of medicine & science in sports,
June 2015, Letnik:
25, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
Training and competition in major track‐and‐field events, and for many team or racquet sports, often require the completion of maximal sprints in hot (>30 °C) ambient conditions. Enhanced short‐term ...(<30 s) power output or single‐sprint performance, resulting from transient heat exposure (muscle temperature rise), can be attributed to improved muscle contractility. Under heat stress, elevations in skin/core temperatures are associated with increased cardiovascular and metabolic loads in addition to decreasing voluntary muscle activation; there is also compelling evidence to suggest that large performance decrements occur when repeated‐sprint exercise (consisting of brief recovery periods between sprints, usually <60 s) is performed in hot compared with cool conditions. Conversely, poorer intermittent‐sprint performance (recovery periods long enough to allow near complete recovery, usually 60–300 s) in hotter conditions is solely observed when exercise induces marked hyperthermia (core temperature >39 °C). Here we also discuss strategies (heat acclimatization, precooling, hydration strategies) employed by “sprint” athletes to mitigate the negative influence of higher environmental temperatures.
PDF
