Effect of medical student preference on rural clinical school experience and rural career intentions

Introduction: The key parameter for rural clinical schools (RCSs) is to provide at least 1 year of clinical training in rural areas for 25% of Australian Commonwealth supported medical students with the intent to influence future rural medical workforce outcomes. The objective of this study was to describe the association between a medical student’s selection preference and their RCS experience and rural career intent. Methods: Medical students completing an RCS placement in 2012 and 2013 were encouraged to complete a survey regarding their experience and future career intent. Data were analysed to compare medical students for whom the RCS was their first choice with students who described the RCS as other than their first preference. Results: Students for whom RCS was their first choice (724/1092) were significantly more likely to be female, come from a rural background and be from an undergraduate program. These students reported more positive experiences of all aspects of the RCS program (costs, access, support and networks, safety) and were 2.36 times more likely to report intentions to practice in a non-metropolitan area (odds ratio(OR)=2.36 (95% confidence interval(CI)=1.82–3.06), p\u3c0.001). This was true for students of rural (OR=3.11 (95%CI=1.93–5.02), p\u3c0.001) and metropolitan backgrounds (OR=2.07 (95%CI=1.48–2.89), p\u3c0.001). More students in the first-choice group (68.8%) intended to practice in a regional area (not a capital or major city), significantly higher than the 48.4% of participants in the other-preference group (χ2 (1) 42.79, p\u3c0.001). Conclusions: The decision to choose an RCS placement is a marker of rural career intention and a positive rural training experience for students of both rural and metropolitan backgrounds. It may be important to identify other-preference students and their specific social support needs to ensure a positive perception of a future rural career

Characterization of a far-red analog of ghrelin for imaging GHS-R in P19-derived cardiomyocytes.

Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as measured in HEK293 cells overexpressing GHS-R1a was within an order of magnitude of that of fluorescein-ghrelin and native human ghrelin, while the des-acyl Cy5-ghrelin did not bind GHS-R1a. Live cell imaging in HEK293/GHS-R1a cells showed cell surface labeling that was displaced by excess ghrelin. Interestingly, Cy5-ghrelin, but not the des-acyl analog, showed concentration-dependent binding in mouse heart tissue sections. We then used Cy5-ghrelin to track GHS-R expression in P19-derived cardiomyocytes. Live cell imaging at different time points after DMSO-induced differentiation showed that GHS-R expression preceded that of the differentiation marker aMHC and tracked with the contractility marker SERCA 2a. Our far-red analog of ghrelin adds to the tools we are developing to map GHS-R in developing and diseased cardiac tissues

Distribution of pollutants from a new paper plant in southern Lake Champlain, Vermont and New York

From November of 1973 to May of 1974, 15 arrays of sediment traps were placed along 33 km of southern Lake Champlain to sample the distribution of effluent from a large paper plant located on the western shore which had commenced operation in 1971. In the arrays located near the effluent diffuser pipeline as much as 2.3 cm of sediment accumulated, whereas elsewhere in the lake less than 1 cm accumulated. In the area of accelerated accumulation, sediments contained high concentrations of several components used in or derived from paper manufacturing. Values for kaolinite, expressed as the ratio of kaolinite to chlorite, for example, were as high as 1.4, anatase (TiO 2 ) concentrations were as high as 0.8%, organic carbon 8.7%, and phosphorus 254 µg/g; all were more abundant than in sediments collected in traps to the south or north. In surficial bottom sediments collected near each array organic carbon and phosphorus were also higher (4.2% and 127 µg/g respectively) near the diffuser than elsewhere. Thus, the new plant after three years of production measurably affected the composition of suspended sediment and surficial bottom sediment despite the construction and use of extensive facilities to reduce the flow of pollutants to the lake.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46764/1/254_2006_Article_BF02380502.pd

Psychiatric services utilization in completed suicides of a youth centres population

BACKGROUND: From a retrospective study of youth centres (YCs) and coroner's files, we investigated youths' history of medical service utilization who died by suicide. This is the second of two papers on YCs population, the first paper having shown that the rate of psychopathology was higher in the YCs population compared to the general adolescent population. METHODS: From 1995 to 2000, 422 youths, aged 18 years and younger, died as a result of suicide in Quebec. More than one-third received services from YCs at some point. Using the provincial physician payment and hospitalization database, we examined physical and psychiatric service utilization according to time intervals, as well as hospitalization for psychiatric reasons in the individuals' lifetime and in the year preceding suicide. Suicides were matched to living YCs youths for age, sex, and geographic area. YCs controls were then subdivided into two groups based on file information pertaining to the presence or absence of suicidal behavior or ideation. RESULTS: Compared to living YCs youths, suicides had a higher rate of psychiatric service utilization in the week, month, 90 days, and year preceding suicide, as well as higher levels of lifetime hospitalization for psychiatric reasons than controls with or without a history of suicidal behavior or ideation. We found that 28.3% YCs suicides made use of psychiatric services in the year preceding suicide. CONCLUSION: The rate of psychiatric service utilization by YCs youth suicides is substantially inferior to the needs of this population. Our study underscores the need for appropriate recognition of psychiatric and suicidal problems among YCs population by social and psycho-educational professionals. At the same time, it highlights the issues of general practitioners' risk identification, psychiatric referral and treatment. Our findings suggest the need for improved organization and coordination of psychiatric services to ameliorate treatment delivery

A dietary feedback system for the delivery of consistent personalized dietary advice in the web-based multicenter Food4Me study

Background: Despite numerous healthy eating campaigns, the prevalence of diets high in saturated fatty acids, sugar, and salt and low in fiber, fruit, and vegetables remains high. With more people than ever accessing the Internet, Web-based dietary assessment instruments have the potential to promote healthier dietary behaviors via personalized dietary advice. Objective: The objectives of this study were to develop a dietary feedback system for the delivery of consistent personalized dietary advice in a multicenter study and to examine the impact of automating the advice system. Methods: The development of the dietary feedback system included 4 components: (1) designing a system for categorizing nutritional intakes; (2) creating a method for prioritizing 3 nutrient-related goals for subsequent targeted dietary advice; (3) constructing decision tree algorithms linking data on nutritional intake to feedback messages; and (4) developing personal feedback reports. The system was used manually by researchers to provide personalized nutrition advice based on dietary assessment to 369 participants during the Food4Me randomized controlled trial, with an automated version developed on completion of the study. Results: Saturated fatty acid, salt, and dietary fiber were most frequently selected as nutrient-related goals across the 7 centers. Average agreement between the manual and automated systems, in selecting 3 nutrient-related goals for personalized dietary advice across the centers, was highest for nutrient-related goals 1 and 2 and lower for goal 3, averaging at 92%, 87%, and 63%, respectively. Complete agreement between the 2 systems for feedback advice message selection averaged at 87% across the centers. Conclusions: The dietary feedback system was used to deliver personalized dietary advice within a multi-country study. Overall, there was good agreement between the manual and automated feedback systems, giving promise to the use of automated systems for personalizing dietary advice

Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder

<p>Abstract</p> <p>Background</p> <p>The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide), and major depressive disorder (MDD). We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls.</p> <p>Methods</p> <p>Four different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared.</p> <p>Results</p> <p>The MAOA 4R allele was more frequent in males with MDD than in male community controls (χ²= 4.182, p = 0.041). Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively). Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p < 0.001; β = 0.15, p = 0.026; β = 1.11, p < 0.001). Structural equation modeling (SEM) showed that nongenetic factors, such as age, paternal overprotection, and somatic symptoms, were associated with MDD, whereas depressed suicide were associated with severity of depression, personality traits, age, marital status, and inversely associated with anxiety symptoms. However, depression did not affect suicidal behavior in the community group.</p> <p>Conclusion</p> <p>The MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the relationships among MAOA uVNTR polymorphism, symptom profiles, and suicidal behavior.</p

Rapid-acting antidepressants and the regulation of TrkB neurotrophic signalling-Insights from ketamine, nitrous oxide, seizures and anaesthesia

Increased glutamatergic neurotransmission and synaptic plasticity in the prefrontal cortex have been associated with the rapid antidepressant effects of ketamine. Activation of BDNF (brain-derived neurotrophic factor) receptor TrkB is considered a key molecular event for antidepressant-induced functional and structural synaptic plasticity. Several mechanisms have been proposed to underlie ketamine's effects on TrkB, but much remains unclear. Notably, preliminary studies suggest that besides ketamine, nitrous oxide (N2O) can rapidly alleviate depressive symptoms. We have shown nitrous oxide to evoke TrkB signalling preferentially after the acute pharmacological effects have dissipated (ie after receptor disengagement), when slow delta frequency electroencephalogram (EEG) activity is up-regulated. Our findings also demonstrate that various anaesthetics and sedatives activate TrkB signalling, further highlighting the complex mechanisms underlying TrkB activation. We hypothesize that rapid-acting antidepressants share the ability to regulate TrkB signalling during homeostatically evoked slow-wave activity and that this mechanism is important for sustained antidepressant effects. Our observations urge the examination of rapid and sustained antidepressant effects beyond conventional receptor pharmacology by focusing on brain physiology and temporally distributed signalling patterns spanning both wake and sleep. Potential implications of this approach for the improvement of current therapies and discovery of novel antidepressants are discussed.Peer reviewe

Specific Inhibition of Phosphodiesterase-4B Results in Anxiolysis and Facilitates Memory Acquisition

Cognitive dysfunction is a core feature of dementia and a prominent feature in psychiatric disease. As non-redundant regulators of intracellular cAMP gradients, phosphodiesterases (PDE) mediate fundamental aspects of brain function relevant to learning, memory, and higher cognitive functions. Phosphodiesterase-4B (PDE4B) is an important phosphodiesterase in the hippocampal formation, is a major Disrupted in Schizophrenia 1 (DISC1) binding partner and is itself a risk gene for psychiatric illness. To define the effects of specific inhibition of the PDE4B subtype, we generated mice with a catalytic domain mutant form of PDE4B (Y358C) that has decreased ability to hydrolyze cAMP. Structural modelling predictions of decreased function and impaired binding with DISC1 were confirmed in cell assays. Phenotypic characterization of the PDE4BY358C mice revealed facilitated phosphorylation of CREB, decreased binding to DISC1, and upregulation of DISC1 and β-Arrestin in hippocampus and amygdala. In behavioural assays, PDE4BY358C mice displayed decreased anxiety and increased exploration, as well as cognitive enhancement across several tests of learning and memory, consistent with synaptic changes including enhanced long-term potentiation and impaired depotentiation ex vivo. PDE4BY358C mice also demonstrated enhanced neurogenesis. Contextual fear memory, though intact at 24 hours, was decreased at 7 days in PDE4BY358C mice, an effect replicated pharmacologically with a non-selective PDE4 inhibitor, implicating cAMP signalling by PDE4B in a very late phase of consolidation. No effect of the PDE4BY358C mutation was observed in the pre-pulse inhibition and forced swim tests. Our data establish specific inhibition of PDE4B as a promising therapeutic approach for disorders of cognition and anxiety, and a putative target for pathological fear memory