Search PubMed⌕ Search

Biomedical subjects

Paul Worley

Publications and source records attributed to Paul Worley.

13 recordsLinked to original sources
PubMed2006

Neuronal pentraxins mediate synaptic refinement in the developing visual system.

Neuronal pentraxins (NPs) define a family of proteins that are homologous to C-reactive and acute-phase proteins in the immune system and have been hypothesized to be involved in activity-dependent synaptic plasticity. To investigate the role of NPs in vivo, we generated mice that lack one, two, or all three NPs. NP1/2 knock-out mice exhibited defects in the segregation of eye-specific retinal ganglion cell (RGC) projections to the dorsal lateral geniculate nucleus, a process that involves activity-dependent synapse formation and elimination. Retinas from mice lacking NP1 and NP2 had cholinergically driven waves of activity that occurred at a frequency similar to that of wild-type mice, but several other parameters of retinal activity were altered. RGCs cultured from these mice exhibited a significant delay in functional maturation of glutamatergic synapses. Other developmental processes, such as pathfinding of RGCs at the optic chiasm and hippocampal long-term potentiation and long-term depression, appeared normal in NP-deficient mice. These data indicate that NPs are necessary for early synaptic refinements in the mammalian retina and dorsal lateral geniculate nucleus. We speculate that NPs exert their effects through mechanisms that parallel the known role of short pentraxins outside the CNS.

Animals↗
PubMed2006

Empirical evidence for symbiotic medical education: a comparative analysis of community and tertiary-based programmes.

BACKGROUND: Flinders University has developed the Parallel Rural Community Curriculum (PRCC), a full year clinical curriculum based in rural general practice in South Australia. The examination performance of students on this course has been shown to be higher than that of their tertiary hospital-based peers. AIM: To compare the learning experiences of students in the community-based programme with those of students in the tertiary hospital in order to explain these improved academic outcomes. METHOD: A case study was undertaken, using an interpretivist perspective, with 3 structured interviews carried out over 2 academic years with each of 6 students from the community-based programme and 16 students from the tertiary hospital. The taped interviews were transcribed and analysed thematically using NUD*IST software. RESULTS: The community-based programme was successful in immersing the students in the clinical environment in a meaningful way. Four key themes were found in the data. These represented clear differences between the experiences of the community-based and hospital-based students. These differences involved: the value that students perceived they were given by supervising doctors and their patients; the extent to which the student's presence realised a synergy between the work of the university and the health service; opportunities for students to meet the aspirations of both the community and government policy, and opportunities for students to learn how professional expectations can mesh with their own personal values. CONCLUSION: This study has provided empirical evidence for the importance of the concept of symbiosis in understanding quality in medical education.

Attitude of Health Personnel↗
PubMed2005

The impact of medical students on rural general practitioner preceptors.

INTRODUCTION: As universities rely more heavily on rural GPs to precept medical students, the formation of symbiotic partnerships benefiting students, universities and GPs, becomes imperative. In order to develop and consolidate these partnerships universities must understand who their rural GP preceptors are and how precepting impacts on them. METHODS: A review of the literature was undertaken to determine the significant themes of student impacts from articles where conclusions were clearly based on empirical findings. RESULTS: Forty-three articles were included in the final review, but only nine specifically looked at impacts on rural GPs. Impacts were categorized into six domains: personal; time; patient care; professional relationships and professional development; business and infrastructure; and recognition and remuneration. CONCLUSIONS: Literature specifically addressing the impact of precepting on rural GPs is scarce. Further studies are required to evaluate the relationship between the quality of teaching delivered to students, the type and length of student attachments and the likely impacts on rural GPs.

Australia↗
PubMed2004

Cohort study of examination performance of undergraduate medical students learning in community settings.

OBJECTIVES: To determine whether moving clinical medical education out of the tertiary hospital into a community setting compromises academic standards. DESIGN: Cohort study. SETTING: Flinders University four year graduate entry medical course. In their third year, students are able to choose to study at the tertiary teaching hospital in Adelaide, in rural general practices, or at Royal Darwin Hospital, a regional secondary referral hospital. PARTICIPANTS: All 371 medical students who did their year 3 study from 1998-2002. MAIN OUTCOME MEASURES: Mean student examination score (%) at the end of year 3. RESULTS: The unadjusted mean year 3 scores at each location differed significantly (P < 0.001); the mean score was 65.2 (SE = 0.43) for Adelaide students, 68.2 (0.83) for Darwin students, and 69.3 (0.97) for students on the rural programme. Mean year 2 scores were similar for each location. Post hoc tests of means adjusted for sex, age, year 2 score, and cohort year showed that the rural and Darwin groups had a significantly improved score in year 3 compared with the Adelaide group (adjusted mean difference = 3.08, 95% confidence interval 1.25 to 4.90, P < 0.001 for rural group; 1.91, 0.47 to 3.36, P = 0.001 for Darwin group). CONCLUSIONS: These findings show that the concern that student academic performance in the tertiary hospital would be better than that of students in the regional hospital and community settings is not justified. This challenges the orthodoxy of a tertiary hospital education being the gold standard for undergraduate medical students.

Adult↗
PubMed2004

Homer2 gene deletion in mice produces a phenotype similar to chronic cocaine treated rats.

Addiction to cocaine results from changes in brain function arising from a combination of pharmacology, environmental circumstances, as well as genetic vulnerability. One change is a reduction in Homer protein in the nucleus accumbens. In this report we summarize the behavioral and neurochemical effects of Homer2 gene deletion in mice and compare this with the effects of chronic cocaine treatment in rats. It was shown that Homer2 KO mice demonstrate enhanced locomotor stimulant and conditioned place preference responses to cocaine. Homer2 deletion also caused mice to show reduced basal extracellular glutamate in the nucleus accumbens and a sensitized increase in extracellular glutamate in response to a cocaine injection. In contrast to glutamate, Homer2 KO mice showed a normal increase in extracellular dopamine following a cocaine challenge injection. The parallel between the effect of Homer2 gene deletion and chronic cocaine administration on behavioral and glutamatergic neurochemical responses to cocaine supports involvement of Homer proteins and glutamate transmission in the sensitization of behavior produced by repeated cocaine.

Animals↗
PubMed2004

What do medical students actually do on clinical rotations?

As medical schools make use of an increasing variety of clinical teaching settings, it is of interest to find that that there is very little published research that explores the actual learning activities undertaken by students in different environments. This study was designed to describe and analyse a typical week for students learning the same curricular material in one of three Australian settings: an urban tertiary teaching hospital, a remote secondary referral hospital and a rural community-based programme. Twenty-eight students completed week-long learning logs in weeks 9 and 35 of a 40-week academic year. Each student recorded his or her activity in 15-minute intervals for each week. Analysis of these data revealed that, compared with the hospital-based students, the community-based students reported greater patient contact, more time spent in clinical settings and increased time supervised by experienced clinicians. Whilst the community-based students valued their learning in clinical settings more highly than the learning they undertook at their home, the opposite was found for the tertiary hospital-based students. This study, the first to compare student activity in these three prototypical settings in the medical education literature, provides empirical evidence supporting community-based programmes as credible alternatives to traditional teaching hospital-based environments.

Adult↗
PubMed2003

Narp and NP1 form heterocomplexes that function in developmental and activity-dependent synaptic plasticity.

Narp is a neuronal immediate early gene that plays a role in excitatory synaptogenesis. Here, we report that native Narp in brain is part of a pentraxin complex that includes NP1. These proteins are covalently linked by disulfide bonds into highly organized complexes, and their relative ratio in the complex is dynamically dependent upon the neuron's activity history and developmental stage. Complex formation is dependent on their distinct N-terminal coiled-coil domains, while their closely homologous C-terminal pentraxin domains mediate association with AMPA-type glutamate receptors. Narp is substantially more effective in assays of cell surface cluster formation, coclustering of AMPA receptors, and excitatory synaptogenesis, yet their combined expression results in supraadditive effects. These studies support a model in which Narp can regulate the latent synaptogenic activity of NP1 by forming mixed pentraxin assemblies. This mechanism appears to contribute to both activity-independent and activity-dependent excitatory synaptogenesis.

Amino Acid Sequence↗
PubMed2002

Differing mechanisms for glutamate receptor aggregation on dendritic spines and shafts in cultured hippocampal neurons.

We have explored the ability of axons from spinal and hippocampal neurons to aggregate NMDA- and AMPA-type glutamate receptors on each other as a way of exploring the molecular differences between their presynaptic elements. Spinal axons, which normally cluster only AMPA-type glutamate receptors on other spinal neurons, cluster both AMPA- and NMDA-type glutamate receptors on the dendritic shafts of hippocampal interneurons but are ineffective at clustering either subtype of glutamate receptor on the dendritic spines of hippocampal pyramidal neurons. Conversely, hippocampal axons appear to be multipotent, capable of clustering both AMPA- and NMDA-type glutamate receptors on hippocampal interneurons and pyramidal cells. The secretion of the neuronal activity-regulated pentraxin (Narp) by hippocampal axons is restricted to contacts with interneurons. Exogenous application of Narp to cultured hippocampal neurons results in clusters of both NMDA- and AMPA-type glutamate receptors on hippocampal interneurons but not hippocampal pyramidal neurons. Because Narp displays no ability to directly aggregate NMDA receptors, we propose that Narp aggregates NMDA receptors in hippocampal interneurons indirectly through cytoplasmic coupling to synaptic AMPA receptors. Furthermore, our data suggest the existence of a novel molecule(s), capable of forming excitatory synapses on dendritic spines.

Animals↗
PubMed2002

Synaptically targeted narp plays an essential role in the aggregation of AMPA receptors at excitatory synapses in cultured spinal neurons.

Neuronal activity regulated pentraxin (Narp) has been implicated in the aggregation of AMPA-type glutamate receptors (GluR) at excitatory synapses. In the present paper, we examine the role of endogenous Narp in excitatory synapse formation by using novel, dominant-negative Narp mutants (dnNarp) that selectively bind endogenous Narp and prevent its accumulation at synapses. Axons from neurons transfected with wild-type Narp showed an increase in their ability to cluster AMPA receptors on spinal neurons, whereas axons from neurons transfected with dnNarp showed a marked decrease in their ability to induce GluR1 clusters on contacted dendrites. Despite their marked effect at excitatory synapses, dnNarp and wild-type Narp had no effect on the postsynaptic clustering of the inhibitory protein gephyrin or the percentage of contacts associated with staining for the presynaptic vesicle proteins GAD or synaptophysin. Use of the dnNarp mutants to suppress endogenous Narp expression by postsynaptic dendrites showed a complementary role for dendritic Narp in the clustering of synaptic AMPA receptors, as well as a reduction in the total number of excitatory synapses on transfected neurons. Together these experiments suggest an important role for Narp in the formation of excitatory synapses in cultured spinal neurons.

Animals↗
PubMed2002

Local synthesis of proteins at synaptic sites on dendrites: role in synaptic plasticity and memory consolidation?

Long-lasting forms of memory are thought to be mediated by modifications in synapses that are induced by particular patterns of activity, take time to be established (consolidated), and involve new gene expression. The molecular mechanisms underlying such long-lasting synaptic modifications remain to be defined. Here, we focus on new findings regarding synapse-specific gene expression and especially the intracellular transport and synaptic targeting of the mRNA for a recently identified immediate early gene called activity-regulated cytoskeleton-associated protein (Arc). Arc mRNA is transported into dendrites after episodes of neuronal activation. The newly synthesized Arc mRNA localizes selectively at synapses that have experienced particular patterns of activity, and this targeting depends on NMDA receptor activation. Arc protein is assembled into the postsynaptic junction, and Arc expression is strongly induced by brief behavioral experiences in select populations of neurons. These features of Arc induction and trafficking reveal novel cellular mechanisms that are well suited to mediate long-term synapse-specific modifications. We will review findings from other laboratories that both LTP and memory are disrupted when Arc induction is blocked, and we will discuss the possibility that Arc protein may play a key role in activity-dependent synaptic modification.

Cytoskeletal Proteins↗
PubMed2002

Integrity: the key to quality in community-based medical education? (Part two).

Relationships do matter! In fact, medicine cannot be learned without them, and community-based medical education (CBME) curricula that ignore them or take them for granted do so at their students peril! Could these assertions provide a key to quality in CBME curricula? In a previous paper, I provided evidence for a simple model of four key relationships, the four Rs, to act as a framework to analyse CBME. These four Rs are the relationships between (1) clinicians and patients, (2) health service and university research, (3) government and community, and (4) personal principles and professional expectations. In this paper I describe a key to discerning quality in this model. This key is integrity - that coalition of soundness and interdependence that enables the quality of the whole to be greater than the sum of the parts. I will also discuss the implications of this model for CBME with particular reference to reform of student selection, curricular goals, course structure, and assessment. Whilst further research based on this model is needed, as a result of this synthesis of the current medical education literature, I propose that it is its capacity to produce clinical, social, institutional and interpersonal integrity in its graduates that makes community-based medical education such an attractive alternative. Relationships do matter!

Journal Article↗
PubMed2002

Relationships: a new way to analyse community-based medical education? (Part one).

Relationships do matter! In fact, medicine cannot be learned without them, and community-based medical education (CBME) curricula that ignore them or take them for granted do so at their students' peril. As CBME is becoming more popular, there is a need to develop appropriate frameworks for describing quality in CBME to ensure that it remains a principle-driven, not format-driven, initiative. In this paper, I provide evidence for a simple model of four key relationships, the four Rs, in which the medical student must be immersed to facilitate high quality learning. These four Rs are the relationships between (1) clinicians and patients, (2) health service and university research, (3) government and community, and (4) personal principles and professional expectations. As a result of this synthesis of the current medical education literature, I propose that this model of clinical, social, institutional and interpersonal relationships is a valid framework for articulating the important principles in CBME, and that it describes why community-based medical education is such an attractive alternative. Relationships do matter!

Journal Article↗