General anaesthetics do not impair developmental expression of the KCC2 potassium-chloride cotransporter in neonatal rats during the brain growth spurt

Background The developmental transition from depolarizing to hyperpolarizing γ-aminobutyric acid-mediated neurotransmission is primarily mediated by an increase in the amount of the potassium-chloride cotransporter KCC2 during early postnatal life. However, it is not known whether early neuronal activity plays a modulatory role in the expression of total KCC2 mRNA and protein in the immature brain. As general anaesthetics are powerful modulators of neuronal activity, the purpose of this study was to explore how these drugs affect KCC2 expression during the brain growth spurt. Methods Wistar rat pups were exposed to either a single dose or 6 h of midazolam, propofol, or ketamine anaesthesia at postnatal days 0, 5, 10, or 15. KCC2 expression was assessed using immunoblotting, immunohistochemistry, or quantitative polymerase chain reaction analysis up to 3 days post-exposure in the medial prefrontal cortex. Results There was a progressive and steep increase in the expression of KCC2 between birth and 2 weeks of age. Exposure to midazolam, propofol, or ketamine up to 6 h at any investigated stages of the brain growth spurt did not influence the expression of this cotransporter protein. Conclusion I.V. general anaesthetics do not seem to influence developmental expression of KCC2 during the brain growth spur

An inductive exploration into the flow experiences of European Tour golfers

© 2014 Taylor & Francis. This study explored perceptions regarding the experience of flow in elite golf; a sport which is different to those studied previously due to its self-paced, stop-start nature. In-depth, semi-structured interviews were conducted with 10 European Tour golfers. Whereas the majority of previous studies have deductively coded data into Csikszentmihalyi’s dimensions, the data in this study were analysed inductively. Thirteen categories were generated which described the flow experiences of these golfers, and these were compared with the original flow dimensions after analysis. In contrast to previous understanding, these golfers reported being aware that they were in flow as it occurred, and seemingly were able to manage their flow experiences. A category describing altered cognitive and kinaesthetic perceptions was also generated which was not accounted for in the existing flow framework, while the participants also suggested that flow was observable (e.g. through changes in behaviour). Findings are discussed in relation to the existing literature, and recommendations made for future research including possible revisions to the flow framework to better describe this experience within golf and other sporting contexts

Sperm morphology, adenosine triphosphate (ATP) concentration and swimming velocity: unexpected relationships in a passerine bird.

The relationship between sperm energetics and sperm function is poorly known, but is central to our understanding of the evolution of sperm traits. The aim of this study was to examine how sperm morphology and ATP content affect sperm swimming velocity in the zebra finch Taeniopygia guttata We exploited the high inter-male variation in this species and created extra experimental power by increasing the number of individuals with very long or short sperm through artificial selection. We found a pronounced quadratic relationship between total sperm length and swimming velocity, with velocity increasing with length up to a point, but declining in the very longest sperm. We also found an unexpected negative association between midpiece length and ATP content: sperm with a short midpiece generally contained the highest concentration of ATP. Low intracellular ATP is therefore unlikely to explain reduced swimming velocity among the very longest sperm (which tend to have a shorter midpiece)

Crib Biting and Equine Gastric Ulceration Syndrome: do horses that display oral stereotypies have altered gastric anatomy and physiology?

Equine Gastric Ulceration Syndrome (EGUS) and Crib biting are two separate conditions suffered by horses. Previous research has hypothesised causal relationships between these two conditions, whereby the behavior is driven by a requirement to stimulate saliva production to buffer gastric juice. However to date there is limited empirical evidence to support this notion. To identify if the anatomy and physiology of the equid stomach differed in crib biting (CB) horses and non-crib biting controls (N-CB) a two part experiment was conducted using cadaver stomachs. Twenty four stomachs (n=12) CB and (n=12) N-CB were collected from an abattoir. Duplicate 1.5 cm squared sections were taken from the fundic and pyloric mucosa for histology and H&E staining to identify gastrin (G) producing cells. Slides were scored using an adapted four point scale. A further 18 stomachs, (n=9) CB and (n=9) N-CB were collected to test the pH of the mucosa and digesta from the fundic and pyloric regions. G cell concentrations were analysed by Mann Whitney U-46 test. Stomach content pH was analysed by one-way ANOVA and L.S.D post hoc. Relationships between digesta and mucosal pH were evaluated by correlation. In both parts of the study there was no difference between the G-cell concentration (P>0.05) and pH (P>0.05) between CB and N-CB horses. There was a positive correlation between digesta and the mucosal surface of pyloric region in CB horses (R2 0.66, P<0.001), but not in N-CB horses. These findings suggest, from cadavers, that CB and N-CB stomachs are not anatomically nor physiologically different. It is plausible that there is no direct inherent link between CB and EGUS rather that both conditions are linked to environmental and physiological stress

Ethane-beta-Sultam Modifies the Activation of the Innate Immune System Induced by Intermittent Ethanol Administration in Female Adolescent Rats

Intermittent ethanol abuse or ‘binge drinking’ during adolescence induces neuronal damage, which may be associated with cognitive dysfunction. To investigate the neurochemical processes involved, rats were administered either 1 g/kg or 2 g/kg ethanol in a ‘binge drinking’ regime. After only 3 weeks, significant activation of phagocytic cells in the peripheral (alveolar macrophages) and the hippocampal brain region (microglia cells) was present,as exemplified by increases in the release of pro-inflammatory cytokines in the macrophages and of iNOS in the microglia. This was associated with neuronal loss in the hippocampus CA1 region. Daily supplementation with a taurine prodrug, ethane-β-sultam, 0.028 g/kg, during the intermittent ethanol loading regime, supressed the release of the pro-inflammatory cytokines and of reactive nitrogen species, as well as neuronal loss, particularly in the rats administered the lower dose of ethanol, 1 g/kg. Plasma, macrophage and hippocampal taurine levels increased marginally after ethane-β-sultam supplementation. The ‘binge drinking’ ethanol rats administered 1 g/kg ethanol showed increased latencies to those of the control rats in their acquisition of spacial navigation in the Morris Water Maze, which was normalised to that of the controls values after ethane-β-sultam administration. Such results confirm that the administration of ethane-β-sultam to binge drinking rats reduces neuroinflammation in both the periphery and the brain, suppresses neuronal loss, and improved working memory of rats in a water maze study

Exploring views on satisfaction with life in young children with chronic illness: an innovative approach to the collection of self-report data from children under 11

The objective of this study was to explore young children’s views on the impact of chronic illness on their life in order to inform future development of a patient-based self-report health outcome measure. We describe an approach to facilitating self-report views from young children with chronic illness. A board game was designed in order to obtain qualitative data from 39 children with a range of chronic illness conditions and 38 healthy controls ranging in age from 3 to 11 years. The format was effective in engaging young children in a self-report process of determining satisfaction with life and identified nine domains. The board game enabled children aged 5–11 years with chronic illness to describe the effects of living with illness on home, family, friends, school and life in general. It generated direct, non-interpreted material from children who, because of their age, may have been considered unable or limited their ability to discuss and describe how they feel. Obtaining this information for children aged 4 and under continues to be a challenge

Discovery of Novel Adenosine Receptor Agonists That Exhibit Subtype Selectivity.

A series of N(6)-bicyclic and N(6)-(2-hydroxy)cyclopentyl derivatives of adenosine were synthesized as novel A1R agonists and their A1R/A2R selectivity assessed using a simple yeast screening platform. We observed that the most selective, high potency ligands were achieved through N(6)-adamantyl substitution in combination with 5'-N-ethylcarboxamido or 5'-hydroxymethyl groups. In addition, we determined that 5'-(2-fluoro)thiophenyl derivatives all failed to generate a signaling response despite showing an interaction with the A1R. Some selected compounds were also tested on A1R and A3R in mammalian cells revealing that four of them are entirely A1R-selective agonists. By using in silico homology modeling and ligand docking, we provide insight into their mechanisms of recognition and activation of the A1R. We believe that given the broad tissue distribution, but contrasting signaling profiles, of adenosine receptor subtypes, these compounds might have therapeutic potential.This study was supported by the Swiss National Science Foundation (SNSF professorship PP00P2_123536 and PP00P2_146321 to M.L.), the BBSRC (G.L., BB/G01227X/1 and BB/M00015X/1), an MRC Doctoral Training Partnership (I.W. MR/J003964/1), and the EPSRC (A.K., EP/G500045/1).This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/acs.jmedchem.5b0140