A comparison of medetomidine and its active enantiomer dexmedetomidine when administered with ketamine in mice

Medetomidine-ketamine (MK) and dexmedetomidine-ketamine (DK) are widely used to provide general anaesthesia in laboratory animals, but have not been compared directly in many of these species, including rodents. This study aimed to compare the onset and depth of anaesthesia, and changes in vital signs, after intraperitoneal (IP) or subcutaneous (SC) administration of ketamine (75 mg kg-1) combined with medetomidine (1 mg kg-1) or dexmedetomidine (0.5 mg kg-1) using a randomised semi-crossover design with >= 48 hours between treatments in 10 male and 10 female mice. Each mouse was anaesthetised twice using the same administration route (IP or SC): once with each drug-ketamine combination. Anaesthetised mice were monitored on a heating pad without supplemental oxygen for 89 minutes; atipamezole was administered for reversal. The times that the righting reflex was lost post-injection and returned post-reversal were analysed using general linear models. Tail-pinch and pedal reflexes were examined using binomial generalized linear models. Pulse rate (PR), respiratory rate (fr), and arterial haemoglobin saturation (SpO2) were compared using generalized additive mixed models. There were no significant differences among treatments for the times taken for loss and return of the righting reflex, or response of the tail-pinch reflex. The pedal withdrawal reflex was abolished more frequently with MK than DK over time (P = 0.021). The response of PR and SpO2 were similar among treatments, but fr was significantly higher with MK than DK (P <= 0.0005). Markedly low SpO2 concentrations occurred within 5 minutes post-injection (83.8 +/- 6.7 %) in all treatment groups and were most severe after 89 minutes lapsed (66.7 +/- 7.5 %). No statistical differences were detected in regards to administration route (P <= 0.94). This study failed to demonstrate clinical advantages of the enantiomer dexmedetomidine over medetomidine when combined with ketamine to produce general anaesthesia in mice. At the doses administered, deep surgical anaesthesia was not consistently produced with either combination; therefore, anaesthetic depth must be assessed before performing surgical procedures. Supplemental oxygen should always be provided during anaesthesia to prevent hypoxaemia

Seawater acidification more than warming presents a challenge for two Antarctic macroalgal-associated amphipods

Elevated atmospheric pCO2 concentrations are triggering seawater pH reductions and seawater temperature increases along the western Antarctic Peninsula (WAP). These factors in combination have the potential to influence organisms in an antagonistic, additive, or synergistic manner. The amphipods Gondogeneia antarctica and Paradexamine fissicauda represent prominent members of macroalgal-associated mesograzer assemblages of the WAP. Our primary objective was to investigate amphipod behavioral and physiological responses to reduced seawater pH and elevated temperature to evaluate potential cascading ecological impacts. For 90 d, amphipods were exposed to combinations of seawater conditions based on present ambient (pH 8.0, 1.5°C) and predicted end-of-century conditions (pH 7.6, 3.5°C). We recorded survival, molt frequency, and macroalgal consumption rates as well as change in wet mass and proximate body composition (protein and lipid). Survival for both species declined significantly at reduced pH and co-varied with molt frequency. Consumption rates in G. antarctica were significantly higher at reduced pH and there was an additive pH-temperature effect on consumption rates in P. fissicauda. Body mass was reduced for G. antarctica at elevated temperature, but there was no significant effect of pH or temperature on body mass in P. fissicauda. Exposure to the pH or temperature levels tested did not induce significant changes in whole body biochemical composition of G. antarctica, but exposure to elevated temperature resulted in a significant increase in whole body protein content of P. fissicauda. Our study indicates that while elevated temperature causes sub-lethal impacts on both species of amphipods, reduced pH causes significant mortality

Randomised controlled trial comparing rubber band ligation with stapled haemorrhoidopexy for Grade II circumferential haemorrhoids : Long-term results

Peer reviewedPostprin

Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating

Sedentary aging results in a diminished rapid cutaneous vasodilator response to local heating. We investigated whether this diminished response was due to altered contributions of noradrenergic sympathetic nerves; assessing 1) the age-related decline and, 2) the effect of aerobic fitness. We measured skin blood flow (SkBF)(laser-Doppler flowmetry) in young (24±1 yr) and older (64±1 yr) endurance-trained and sedentary men (n=7 per group) at baseline and during 35 min of local skin heating to 42 °C at three forearm sites: 1) untreated; 2) bretylium tosylate (BT), preventing neurotransmitter release from noradrenergic sympathetic nerves; and 3) yohimbine and propranolol (YP), antagonising α- and β-adrenergic receptors. SkBF was converted to cutaneous vascular conductance (CVC) (SkBF/mean arterial pressure) and normalized to maximal CVC (%CVCmax) achieved by skin heating to 44 °C. Pharmacological agents were administered using microdialysis. In the young trained, the rapid vasodilator response was reduced at the BT and YP sites (P0.05) but treatment with BT did (P>0.05). Neither BT nor YP treatments affected the rapid vasodilator response in the older sedentary group (P>0.05). These data suggest that the age-related reduction in the rapid vasodilator response is due to an impairment of sympathetic-dependent mechanisms, which can be partly attenuated with habitual aerobic exercise. Rapid vasodilation involves noradrenergic neurotransmitters in young trained men, and non-adrenergic sympathetic cotransmitters (e.g., neuropeptide Y) in young sedentary and older trained men, possibly as a compensatory mechanism. Finally, in older sedentary men, the rapid vasodilation appears not to involve the sympathetic system

Disorder and interactions in one-dimensional systems

Published versio

Functional network changes and cognitive control in schizophrenia

Cognitive control is a cognitive and neural mechanism that contributes to managing the complex demands of day-to-day life. Studies have suggested that functional impairments in cognitive control associated brain circuitry contribute to a broad range of higher cognitive deficits in schizophrenia. To examine this issue, we assessed functional connectivity networks in healthy adults and individuals with schizophrenia performing tasks from two distinct cognitive domains that varied in demands for cognitive control, the RiSE episodic memory task and DPX goal maintenance task. We characterized general and cognitive control-specific effects of schizophrenia on functional connectivity within an expanded frontal parietal network (FPN) and quantified network topology properties using graph analysis. Using the network based statistic (NBS), we observed greater network functional connectivity in cognitive control demanding conditions during both tasks in both groups in the FPN, and demonstrated cognitive control FPN specificity against a task independent auditory network. NBS analyses also revealed widespread connectivity deficits in schizophrenia patients across all tasks. Furthermore, quantitative changes in network topology associated with diagnostic status and task demand were observed. The present findings, in an analysis that was limited to correct trials only, ensuring that subjects are on task, provide critical insights into network connections crucial for cognitive control and the manner in which brain networks reorganize to support such control. Impairments in this mechanism are present in schizophrenia and these results highlight how cognitive control deficits contribute to the pathophysiology of this illness

Quantum gears: a simple mechanical system in the quantum regime

Abstract. The quantum mechanics of a simple mechanical system is considered. A group of gears can serve as a model for several different systems such as an artifically constructed nanomechanical device or a group of ring molecules. It is shown that the classical motion of the gears in which the angular velocities are locked together does not correspond to

Better by design: Rethinking interventions for better environmental regulation

etter regulation seeks to extend existing policy and regulatory outcomes at less burden for the actors involved. No single intervention will deliver all environmental outcomes. There is a paucity of evidence on what works why, when and with whom. We examine how a sample (n=33) of policy makers select policy and regulatory instruments, through a case study of the Department for Environment, Food and Rural Affairs (Defra), UK. Policy makers have a wide range of instruments at their disposal and are seeking ways to harness the influence of non-governmental resources to encourage good environmental behaviour. The relevance of each influence varies as risk and industry characteristics vary between policy areas. A recent typology of policy and regulatory instruments has been refined. Direct regulation is considered necessary in many areas, to reduce environmental risks with confidence and to tackle poor environmental performance. Co-regulatory approaches may provide important advantages to help accommodate uncertainty for emerging policy problems, providing a mechanism to develop trusted evidence and to refine objectives as problems are better understood