Trainability of cold induced vasodilatation in fingers and toes

Subjects that repeatedly have to expose the extremities to cold may benefit from a high peripheral temperature to maintain dexterity and tissue integrity. Therefore, we investigated if repeated immersions of a hand and a foot in cold water resulted in increased skin temperatures. Nine male and seven female subjects (mean 20.4; SD 2.2 years) immersed their right (trained) hand and foot simultaneously in 8°C water, 30 min daily for 15 days. During the pre and post-test (days 1 and 15, respectively) the left (untrained) hand and foot were immersed as well. Pain, tactile sensitivity and skin temperatures were measured every day. Mean (SD) toe temperature of the trained foot increased from 9.49°C (0.89) to 10.03°C (1.38) (p < 0.05). The trained hand, however, showed a drop in mean finger temperature from 9.28°C (0.54) to 8.91°C (0.44) (p < 0.001) and the number of cold induced vasodilation (CIVD) reactions decreased from 52% during the first test to 24% during the last test. No significant differences occurred in the untrained extremities. Pain diminished over time and tactile sensitivity decreased with skin temperature. The combination of less CIVD responses in the fingers after training, reduced finger skin temperatures in subjects that did show CIVD and the reduced pain and tactile sensitivity over time may lead to an increased risk for finger cold injuries. It is concluded that repeated cold exposure of the fingers does not lead to favorable adaptations, but may instead increase the injury risk

Difference in balance measures between patients with chronic ankle instability and patients after an acute ankle inversion trauma

Neuromuscular control of the ankle is disturbed in patients with chronic ankle instability due to an initial ankle inversion trauma. Static balance is assumed to be a measure for this disturbance. Functional (ankle) scores are another way to evaluate ankle impairment. The hypothesis was that there is a difference in static balance measures between small groups of healthy subjects, patients after an acute ankle inversion trauma and patients with chronic ankle instability and that static balance measures correlate well with functional scores. Static balance in healthy subjects (N = 15), patients after a primary ankle inversion injury (N = 14) and patients with chronic ankle instability (N = 23) was tested with a single leg test on a force plate (Postural Sway test) and on a compliant floor (Simple Balance test). Functional impairment was evaluated with the Karlsson, AOFAS and SF-36 (ankle) scores. There was a statistically significant and clinically relevant difference in functional (ankle) scores, but not a statistically significant difference in balance measures between the groups. Balance measures did not correlate to the functional scores. It was concluded that, despite a clinically relevant difference in functional outcome measures between the groups, static balance measures do not appear to be useful for clinical application in the individual patient

A novel hybrid promoter responsive to pathophysiological and pharmacological regulation

The aim of this study was to construct a promoter containing DNA motifs for an endogenous transcription factor associated with inflammation along with motifs for pharmacological regulation factors. We demonstrate in transfected cells that expression of a gene of interest is induced by hypoxic conditions or through pharmacological induction, and also show pharmacological repression. In vivo studies utilised electroporation of plasmid to mouse paws, a delivery method shown to be effective by bioluminescence imaging. For gene therapy, the promoter was used to drive expression of IL-1Ra in a paw inflammation model with therapeutic effect observed which was further enhanced when the promoter was additionally induced with a pharmacological activator. One of the most important observations from this study was that promoter induction by hypoxia or inflammation could be prevented by the pharmacological repressor in the absence of doxycycline. These studies demonstrate that hybrid promoters enable pharmacological adjustment to the pathophysiological level of gene expression and, importantly, that they allow termination of gene expression even in the presence of pathophysiological stimuli

Can Motivation Normalize Working Memory and Task Persistence in Children with Attention-Deficit/Hyperactivity Disorder? The Effects of Money and Computer-Gaming

Visual-spatial Working Memory (WM) is the most impaired executive function in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Some suggest that deficits in executive functioning are caused by motivational deficits. However, there are no studies that investigate the effects of motivation on the visual-spatial WM of children with- and without ADHD. Studies examining this in executive functions other than WM, show inconsistent results. These inconsistencies may be related to differences in the reinforcement used. The effects of different reinforcers on WM performance were investigated in 30 children with ADHD and 31 non-ADHD controls. A visual-spatial WM task was administered in four reinforcement conditions: Feedback-only, 1 euro, 10 euros, and a computer-game version of the task. In the Feedback-only condition, children with ADHD performed worse on the WM measure than controls. Although incentives significantly improved the WM performance of children with ADHD, even the strongest incentives (10 euros and Gaming) were unable to normalize their performance. Feedback-only provided sufficient reinforcement for controls to reach optimal performance, while children with ADHD required extra reinforcement. Only children with ADHD showed a decrease in performance over time. Importantly, the strongest incentives (10 euros and Gaming) normalized persistence of performance in these children, whereas 1 euro had no such effect. Both executive and motivational deficits give rise to visual-spatial WM deficits in ADHD. Problems with task-persistence in ADHD result from motivational deficits. In ADHD-reinforcement studies and clinical practice (e.g., assessment), reinforcement intensity can be a confounding factor and should be taken into account. Gaming can be a cost-effective way to maximize performance in ADHD

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004

Learning efficacy of explicit visuomotor sequences in children with attention-deficit/hyperactivity disorder and Asperger syndrome

Developmental disorders such as attention-deficit/hyperactivity disorder (ADHD) and Asperger syndrome (AS) are often associated with learning disabilities. This study investigated the explicit learning of visuomotor sequences in 17 ADHD children (mean age 12.1), 21 AS children (mean age 12.7), and 15 typically developing children (mean age: 12.3). The participants were required to explore a hidden sequence of button presses by trial and error and elaborate the learned sequence (2 × 10 task: Hikosaka et al. 1996). The results indicated that although ADHD and AS children had a tendency of repeating the same errors and took longer to complete a sequence, both showed a degree and pattern of improvement in accuracy and speed similar to that of typically developing children. These results suggest that the explicit learning of visuomotor sequence in ADHD and AS patients is largely unimpaired

No association of TNFRSF1B variants with type 2 diabetes in Indians of Indo-European origin

<p>Abstract</p> <p>Background</p> <p>There has been no systematic evaluation of the association between genetic variants of type 2 receptor for TNFα (TNFR2) and type 2 diabetes, despite strong biological evidence for the role of this receptor in the pathogenesis of this complex disorder. In view of this, we performed a comprehensive association analysis of <it>TNFRSF1B </it>variants with type 2 diabetes in 4,200 Indo-European subjects from North India.</p> <p>Methods</p> <p>The initial phase evaluated association of seven SNPs viz. rs652625, rs496888, rs6697733, rs945439, rs235249, rs17883432 and rs17884213 with type 2 diabetes in 2,115 participants (1,073 type 2 diabetes patients and 1,042 control subjects). Further, we conducted replication analysis of three associated SNPs in 2,085 subjects (1,047 type 2 diabetes patients and 1,038 control subjects).</p> <p>Results</p> <p>We observed nominal association of rs945439, rs235249 and rs17884213 with type 2 diabetes (<it>P </it>< 0.05) in the initial phase. Haplotype CC of rs945439 and rs235249 conferred increased susceptibility for type 2 diabetes [OR = 1.19 (95%CI 1.03-1.37), <it>P </it>= 0.019/<it>P</it>_perm= 0.076] whereas, TG haplotype of rs235249 and rs17884213 provided protection against type 2 diabetes [OR = 0.83 (95%CI 0.72-0.95, <it>P </it>= 7.2 × 10^-3/<it>P</it>_perm= 0.019]. We also observed suggestive association of rs496888 with plasma hsCRP levels [<it>P </it>= 0.042]. However, the association of rs945439, rs235249 and rs17884213 with type 2 diabetes was not replicated in the second study population. Meta-analysis of the two studies also failed to detect any association with type 2 diabetes.</p> <p>Conclusions</p> <p>Our two-stage association analysis suggests that <it>TNFRSF1B </it>variants are not the determinants of genetic risk of type 2 diabetes in North Indians.</p

Reduced levels of dopamine and altered metabolism in brains of HPRT knock-out rats: a new rodent model of Lesch-Nyhan Disease

Lesch-Nyhan disease (LND) is a severe neurological disorder caused by loss-of-function mutations in the gene encoding hypoxanthine phosphoribosyltransferase (HPRT), an enzyme required for efficient recycling of purine nucleotides. Although this biochemical defect reconfigures purine metabolism and leads to elevated levels of the breakdown product urea, it remains unclear exactly how loss of HPRT activity disrupts brain function. As the rat is the preferred rodent experimental model for studying neurobiology and diseases of the brain, we used genetically-modified embryonic stem cells to generate an HPRT knock-out rat. Male HPRT-deficient rats were viable, fertile and displayed normal caged behaviour. However, metabolomic analysis revealed changes in brain biochemistry consistent with disruption of purine recycling and nucleotide metabolism. Broader changes in brain biochemistry were also indicated by increased levels of the core metabolite citrate and reduced levels of lipids and fatty acids. Targeted MS/MS analysis identified reduced levels of dopamine in the brains of HPRT-deficient animals, consistent with deficits noted previously in human LND patients and HPRT knock-out mice. The HPRT-deficient rat therefore provides a new experimental platform for future investigation of how HPRT activity and disruption of purine metabolism affects neural function and behaviour

Reward and Punishment Sensitivity in Children with ADHD: Validating the Sensitivity to Punishment and Sensitivity to Reward Questionnaire for Children (SPSRQ-C)

This study validates the Sensitivity to Punishment and Sensitivity to Reward Questionnaire for children (SPSRQ-C), using a Dutch sample of 1234 children between 6–13 years old. Factor analysis determined that a 4-factor and a 5-factor solution were best fitting, explaining 41% and 50% of the variance respectively. The 4-factor model was highly similar to the original SPSRQ factors found in adults (Punishment Sensitivity, Reward Responsivity, Impulsivity/Fun-Seeking, and Drive). The 5-factor model was similar to the 4-factor model, with the exception of a subdivision of the Punishment Sensitivity factor into a factor with ‘social-fear’ items and a factor with ‘anxiety’ items. To determine external validity, scores of three groups of children with attention deficit hyperactivity disorder (ADHD) were compared on the EFA models: ADHD-only (n = 34), ADHD and autism spectrum disorder (ADHD+ASD; n = 22), ADHD and oppositional defiant disorder (ADHD+ODD; n = 22). All ADHD groups scored higher than typical controls on Reward Responsivity and on the ‘anxiety’ factor (n = 75). The ADHD-only and ADHD+ODD group scored higher than other groups on Impulsivity/Fun-Seeking and Drive, while the ADHD+ASD group scored higher on Punishment Sensitivity. The findings emphasize the value of the SPSRQ-C to quickly and reliably assess a child’s sensitivity to reinforcement, with the aim to provide individually-tailored behavioral interventions that utilize reward and reprimands