Expression Pattern of Kv11 (Ether à-go-go-Related Gene; erg) K+ Channels in the Mouse Retina

In response to light, most retinal neurons exhibit gradual changes in membrane potential. Therefore K+ channels that mediate threshold currents are well-suited for the fine-tuning of signal transduction. In the present study we demonstrate the expression of the different Kv11 (ether-à-go-go related gene; erg) channel subunits in the human and mouse retina by RT PCR and quantitative PCR, respectively. Immunofluorescence analysis with cryosections of mouse retinae revealed the following local distribution of the three Kv11 subunits: Kv11.1 (m-erg1) displayed the most abundant expression with the strongest immunoreactivity in rod bipolar cells. In addition, immunoreactivity was found in the inner part of the outer plexiform layer (OPL), in the inner plexiform layer (IPL) and in the inner segments of photoreceptors. Immunoreactivity for Kv11.2 (m-erg2) was observed in the outer part of the OPL and throughout the IPL. Double-labeling for vGluT1 or synaptophysin indicated a mainly presynaptic localization of Kv11.2. While no significant staining for Kv11.3 (m-erg3) was detected in the neuronal retina, strong Kv11.3 immunoreactivity was present in the apical membrane of the retinal pigment epithelium. The different expression levels were confirmed by real-time PCR showing almost equal levels of Kv11.1 and Kv11.2, while Kv11.3 mRNA expression was significantly lower. The two main splice variants of Kv11.1, isoforms a and b were detected in comparable levels suggesting a possible formation of cGMP/cGK-sensitive Kv11.1 channels in photoreceptors and rod bipolar cells. Taken together, the immunohistological results revealed different expression patterns of the three Kv11 channels in the mouse retina supposing distinct physiological roles

The use of contextualised standardised client simulation to develop clinical reasoning in final year veterinary students

Clinical reasoning is an important skill for veterinary students to develop before graduation. Simulation has been studied in medical education as a method for developing clinical reasoning in students, but evidence supporting it is limited. This study involved the creation of a contextualized, standardized client simulation session that aimed to improve the clinical reasoning ability and confidence of final-year veterinary students. Sixty-eight participants completed three simulated primary-care consultations, with the client played by an actor and the pet by a healthy animal. Survey data showed that all participants felt that the session improved their clinical decision-making ability. Quantitative clinical reasoning self-assessment, performed using a validated rubric, triangulated this finding, showing an improvement in students’ perception of several components of their clinical reasoning skill level from before the simulation to after it. Blinded researcher analysis of the consultation video recordings found that students showed a significant increase in ability on the history-taking and making-sense-of-data (including formation of a differential diagnosis) components of the assessment rubric. Thirty students took part in focus groups investigating their experience with the simulation. Two themes arose from thematic analysis of these data: variety of reasoning methods and “It’s a different way of thinking.” The latter highlights differences between the decision making students practice during their time in education and the decision making they will use once they are in practice. Our findings suggest that simulation can be used to develop clinical reasoning in veterinary students, and they demonstrate the need for further research in this area

Potassium Channel and NKCC Cotransporter Involvement in Ocular Refractive Control Mechanisms

Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/−10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5mM Ba2+ and 10−5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba2+ but significant change only for negative lens defocus with bumetanide ; ; ; ; ; ). Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a possible common mechanism. The selective inhibition of refractive compensation to negative lens in chick by loop diuretics such as bumetanide suggests that these drugs may be effective in the therapeutic management of human myopia

Transfer of learning between unimanual and bimanual rhythmic movement coordination: transfer is a function of the task dynamic.

Under certain conditions, learning can transfer from a trained task to an untrained version of that same task. However, it is as yet unclear what those certain conditions are or why learning transfers when it does. Coordinated rhythmic movement is a valuable model system for investigating transfer because we have a model of the underlying task dynamic that includes perceptual coupling between the limbs being coordinated. The model predicts that (1) coordinated rhythmic movements, both bimanual and unimanual, are organised with respect to relative motion information for relative phase in the coupling function, (2) unimanual is less stable than bimanual coordination because the coupling is unidirectional rather than bidirectional, and (3) learning a new coordination is primarily about learning to perceive and use the relevant information which, with equal perceptual improvement due to training, yields equal transfer of learning from bimanual to unimanual coordination and vice versa [but, given prediction (2), the resulting performance is also conditioned by the intrinsic stability of each task]. In the present study, two groups were trained to produce 90° either unimanually or bimanually, respectively, and tested in respect to learning (namely improved performance in the trained 90° coordination task and improved visual discrimination of 90°) and transfer of learning (to the other, untrained 90° coordination task). Both groups improved in the task condition in which they were trained and in their ability to visually discriminate 90°, and this learning transferred to the untrained condition. When scaled by the relative intrinsic stability of each task, transfer levels were found to be equal. The results are discussed in the context of the perception–action approach to learning and performance

The 50s cliff: perceptuo-motor learning rates across the lifespan.

We recently found that older adults show reduced learning rates when learning a new pattern of coordinated rhythmic movement. The purpose of this study was to extend that finding by examining the performance of all ages across the lifespan from the 20 s through to the 80 s to determine how learning rates change with age. We tested whether adults could learn to produce a novel coordinated rhythmic movement (90° relative phase) in a visually guided unimanual task. We determined learning rates to quantify changes in learning with age and to determine at what ages the changes occur. We found, as before, that learning rates of participants in their 70 s and 80 s were half those of participants in their 20 s. We also found a gradual slow decline in learning rate with age until approximately age 50, when there was a sudden drop to a reduced learning rate for the 60 though 80 year olds. We discuss possible causes for the "50 s cliff" in perceptuo-motor learning rates and suggest that age related deficits in perception of complex motions may be the key to understanding this result

The internal consistency and validity of the Self-assessment parkinsons's Disease Disability Scale

OBJECTIVE: To test the consistency and validity of the Self-assessment Parkinson's Disease Disability Scale in patients with Parkinson's disease living at home. DESIGN: Patients with Parkinson's disease responded to a set of questionnaires. In addition, an observation of the performance of daily activities was carried out on a subgroup. SETTING AND SUBJECTS: Patients with Parkinson's disease living at home (n = 142). MEASURES: The Self-assessment Parkinson's Disease Disability Scale (SPDDS), the Hoehn & Yahr Rating Scale (H&Y), and the Sickness Impact Profile (SIP68). The observation concerned nine activities that correspond to items of the SPDDS questionnaire. RESULTS: Internal consistency of the SPDDS was very high (Cronbach's alpha = 0.97; reliability rho = 0.97). The items of the SPDDS are hierarchical (Loevinger's H = 0.64): patients had least difficulty with 'washing' and 'brushing teeth' and most difficulty with 'turning in bed', 'travelling by public transport' and 'writing a letter'. Validity of the SPDDS was good: the relationship between the SPDDS questionnaire and the H&Y rating scale, the SIP68 and the results of the observation was strong and significant. CONCLUSION: The SPDDS is a unidimensional instrument measuring disabilities in Parkinson's disease patients living at home

Survival of stroke patients after introduction of the 'Dutch Transmural Protocol TIA/CVA'

<p>Background: Earlier research showed that healthcare in stroke could be better organized, aiming for improved survival and less comorbidity. Therefore, in 2004 the Dutch College of General Practitioners (NHG) and the Dutch Association of Neurology (NVN) introduced the 'Dutch Transmural Protocol TIA/CVA' (the LTA) to improve survival, minimize the risk of stroke recurrence, and increase quality of life after stroke. This study examines whether survival improved after implementation of the new protocol, and whether there was an increase in contacts with the general practitioner (GP)/nurse practitioner, registration of comorbidity and prescription of medication.</p><p>Methods: From the primary care database of the Registration Network Groningen (RNG) two cohorts were composed: one cohort compiled before and one after introduction of the LTA. Cohort 1 (n = 131, first stroke 2001-2002) was compared with cohort 2 (n = 132, first stroke 2005-2006) with regard to survival and the secondary outcomes.</p><p>Results: Comparison of the two cohorts showed no significant improvement in survival. In cohort 2, the number of contacts with the GP was significantly lower and with the nurse practitioner significantly higher, compared with cohort 1. All risk factors for stroke were more prevalent in cohort 2, but were only significant for hypercholesterolemia. In both cohorts more medication was prescribed after stroke, whereas ACE inhibitors were prescribed more frequently only in cohort 2.</p><p>Conclusion: No major changes in survival and secondary outcomes were apparent after introduction of the LTA. Although, there was a small improvement in secondary prevention, this study shows that optimal treatment after introduction of the LTA has not yet been achieved.</p>

The coordination patterns observed when two hands reach-to-grasp separate objects

What determines coordination patterns when both hands reach to grasp separate objects at the same time? It is known that synchronous timing is preferred as the most stable mode of bimanual coordination. Nonetheless, normal unimanual prehension behaviour predicts asynchrony when the two hands reach towards unequal targets, with synchrony restricted to targets equal in size and distance. Additionally,suffciently separated targets require sequential looking. Does synchrony occur in all cases because it is preferred in bimanual coordination or does asynchrony occur because of unimanual task constraints and the need for sequential looking? We investigated coordinative timing when participants (n = 8) moved their right (preferred) hand to the same object at a fixed distance but the left hand to objects of diVerent width (3, 5, and 7 cm) and grip surface size (1, 2, and 3 cm) placed at diVerent distances (20, 30, and 40 cm) over 270 randomised trials. The hand movements consisted of two components: (1) an initial component (IC) during which the hand reached towards the target while forming an appropriate grip aperture, stopping at (but not touching the object; (2) a completion component (CC) during which the Wnger and thumb closed on the target. The two limbs started the IC together but did not interact until the deceleration phase when evidence of synchronisation began to appear. Nonetheless, asynchronous timing was present at the end of the IC and preserved through the CC even with equidistant targets. Thus, there was synchrony but requirements for visual information ultimately yielded asynchronous coordinative timing