Allyl isothiocyanate sensitizes TRPV1 to heat stimulation

The powerful plant-derived irritant allyl isothiocyanate (AITC, aka mustard oil) induces hyperalgesia to heat in rodents and humans through mechanisms that are not yet fully understood. It is generally believed that AITC activates the broadly tuned chemosensory cation channel transient receptor potential cation channel subfamily A member 1 (TRPA1), triggering an inflammatory response that sensitizes the heat sensor transient receptor potential cation channel subfamily V member 1 (TRPV1). In the view of recent data demonstrating that AITC can directly activate TRPV1, we here explored the possibility that this compound sensitizes TRPV1 to heat stimulation in a TRPA1-independent manner. Patch-clamp recordings and intracellular Ca²⁺ imaging experiments in HEK293T cells over-expressing mouse TRPV1 revealed that the increase in channel activation induced by heating is larger in the presence of AITC than in control conditions. The analysis of the effects of AITC and heat on the current–voltage relationship of TRPV1 indicates that the mechanism of sensitization is based on additive shifts of the voltage dependence of activation towards negative voltages. Finally, intracellular Ca²⁺ imaging experiments in mouse sensory neurons isolated from Trpa1 KO mice yielded that AITC enhances the response to heat, specifically in the subpopulation expressing TRPV1. Furthermore, this effect was strongly reduced by the TRPV1 inhibitor capsazepine and virtually absent in neurons isolated from double Trpa1/Trpv1 KO mice. Taken together, these findings demonstrate that TRPV1 is a locus for cross sensitization between AITC and heat in sensory neurons and may help explaining, at least in part, the role of this channel in AITC-induced hyperalgesia to heat.     

Patterns in the prevalence of diabetes and incidence of diabetic complications in people with and without an intellectual disability in Dutch primary care: Insights from a population-based data-linkage study

AimsTo conduct an epidemiological analysis of patterns observed in diabetes care provided to individuals with and without intellectual disabilities (ID) in primary care settings.MethodsAn ID-cohort (N = 21,203) was compared with a control group of similar age and sex from the general Dutch population (N = 267,628). Distinctive data for diabetes (both type 1 and type 2) and related complications were retrieved from national databases.ResultsThe prevalence of diabetes was higher in people with ID than in the general population (9.9% versus 6.6%). Largest differences were seen in younger age groups. Women with ID had diabetes more often than men with ID. Complications were less common in people with ID than in the general population (IR 58.6 vs. 70.4). In particular, cardiological complications were noted less, while surgical interventions and hospitalization occurred more often.ConclusionsAlthough diabetes was 1.5 times more prevalent in people with ID than in other people, related complications were less common, followed different patterns and were more severe than in the general population. Future research is needed to understand of the underlying causal mechanisms and to lower the risk of severe diabetic complications among people with ID.     

Social power and approach-related neural activity

It has been argued that power activates a general tendency to approach whereas powerlessness activates a tendency to inhibit. The assumption is that elevated power involves reward-rich environments, freedom and, as a consequence, triggers an approach-related motivational orientation and attention to rewards. In contrast, reduced power is associated with increased threat, punishment and social constraint and thereby activates inhibition-related motivation. Moreover, approach motivation has been found to be associated with increased relative left-sided frontal brain activity, while withdrawal motivation has been associated with increased right sided activations. We measured EEG activity while subjects engaged in a task priming either high or low social power. Results show that high social power is indeed associated with greater left-frontal brain activity compared to low social power, providing the first neural evidence for the theory that high power is associated with approach-related motivation. We propose a framework accounting for differences in both approach motivation and goal-directed behaviour associated with different levels of power.     

Monodisperse Versus Polydisperse Ultrasound Contrast Agents: Non-Linear Response,Sensitivity, and Deep Tissue Imaging Potential

It has been proposed that monodisperse microbubble ultrasound contrast agents further increase the signal-to-noise ratio of contrast-enhanced ultrasound imaging. Here, the sensitivity of a polydisperse pre-clinical agent was compared experimentally with that of its size- and acoustically sorted derivatives by using narrowband pressure- and frequency-dependent scattering and attenuation measurements. The sorted monodisperse agents had up to a two-orders-of-magnitude increase in sensitivity, that is, in the average scattering cross section per bubble. Moreover, we found, for the first time, that the highly non-linear response of acoustically sorted microbubbles can be exploited to confine scattering and attenuation to the focal region of ultrasound fields used in clinical imaging. This property is a result of minimal pre-focal scattering and attenuation and can be used to minimize shadowing effects in deep tissue imaging. Moreover, it potentially allows for more localized therapy using microbubbles through the spatial control of resonant microbubble oscillations.     

True Dopers or Negligent Athletes? An Analysis of Anti-Doping Rule Violations Reported to the World Anti-Doping Agency 2010–2012

Background: The sanction that an athlete receives when an anti-doping rule violation has been committed depends on the specific circumstances of the case. Anti-doping tribunals decide on the final sanction, following the rules of the World Anti-Doping Code. Objectives: To assess the athletes’ degree of fault based on the length of sanctions imposed on them to feed policy-related discussions. Methods: Analysing data from the results management database of the World Anti-Doping Agency for anonymous information of anti-doping rule violations in eight selected sports covering the years 2010-2012. Results: Four out of ten athletes who committed an anti-doping rule violation received a suspension that was lower than the standard. This is an indication that tribunals in many instances are not convinced that the athletes concerned were completely at fault, that mitigating circumstances were applicable, or that full responsibility of the suspected violation should not be held against them. Anabolic agents, peptide hormones, and hormone modulators lead to higher sanctions, as do combinations of several anti-doping rule violations. Conclusions: This first analysis of information from the World Anti-Doping Agency's results management database indicates that a large proportion of the athletes who commit anti-doping rule violations may have done this unintentionally. Anti-doping professionals should strive to improve this situation in various ways.     

Diffusion‐prepared stimulated‐echo turbo spin echo (DPsti‐TSE): An eddy current‐insensitive sequence for three‐dimensional high‐resolution and undistorted diffusion‐weighted imaging

In this study, we present a new three‐dimensional (3D), diffusion‐prepared turbo spin echo sequence based on a stimulated‐echo read‐out (DPsti‐TSE) enabling high‐resolution and undistorted diffusion‐weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti‐TSE and diffusion‐weighted echo planar imaging (DW‐EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High‐resolution and undistorted DPsti‐TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole‐prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10^?3 versus (1.60 ± 0.02) × 10^?3 mm²/s]. High‐resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10^?3 mm²/s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti‐TSE can serve as a robust 3D diffusion‐weighted sequence and is an attractive alternative to the traditional two‐dimensional DW‐EPI approaches.