Comparative attainment of 5-year undergraduate and 4-year graduate entry medical students moving into foundation training

Background Graduate entry medicine is a recent innovation in UK medical training. Evidence is sparse at present as to progress and attainment on these programmes. Shared clinical rotations, between an established 5-year and a new graduate entry course, provide the opportunity to compare achievement on clinical assessments. To compare completion and attainment on clinical phase assessments between students on a 4-year graduate entry course and an established 5-year undergraduate medicine course. Methods Overall completion rates for the 4 and 5 year courses, fails at first attempt, and scores on 14 clinical assessments, were compared between 171 graduate-entry and 450 undergraduate medical students at the University of Nottingham, comprising two graduating cohorts. Percentage assessment marks were converted to z-scores separately for each graduating year and the normalised marks then combined into a single dataset. Z-score transformed percentage marks were analysed by multivariate analysis of variance and univariate analyses of variance for each summative assessment. Numbers of fails at first attempt were analysed aggregated across all assessments initially, then separately for each assessment using χ2. Results Completion rates were around 90% overall and significantly higher in the graduate entry course. Failures of assessments overall were similar, but a higher proportion of graduate entry students failed the final OSLER. Mean performance on clinical assessments showed a significant overall difference, made up of lower performance on 4 of 5 knowledge-based exams (as well as higher performance on the first exam) by the graduate entry group, but similar levels of performance on all the skills-based and attitudinal assessments. Conclusions High completion rates are encouraging. The lower performance in some knowledge-based exams may reflect lower prior educational attainment, a substantially different demographic profile (age, gender), or an artefact of the first 2 years of a new graduate entry programme

GPs’ strategies in exploring the preschool child’s wellbeing in the paediatric consultation

Background: Although General Practitioners (GPs) are uniquely placed to identify children with emotional, social, and behavioural problems, they succeed in identifying only a small number of them. The aim of this article is to explore the strategies, methods, and tools employed by GPs in the assessment of the preschool child’s emotional, mental, social, and behavioural health. We look at how GPs address parental care of the child in general and in situations where GPs have a particular awareness of the child. Method: Twenty-eight Danish GPs were purposively selected to take part in a qualitative study which combined focus-group discussions, observation of child consultations, and individual interviews with GPs. Results: Analysis of the data suggests that GPs have developed a set of methods, and strategies to assess the preschool child and parental care of the child. They look beyond paying narrow attention to the physical health of the child and they have expanded their practice to include the relations and interactions in the consultation room. The physical examination of the child continues to play a central role in doctor-child communication. Conclusion: The participating GPs’ strategies helped them to assess the wellbeing of the preschool child but they often find it difficult to share their impressions with parents

Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

An exploratory study on the contribution of graduate entry students personality to the diversity of medical student populations

Studies conducted in medical education show that personality influences undergraduate medical students academic and clinical performances and also their career interests. Our aims with this exploratory study were: to assess the contribution of graduate entry students to the diversity of personality in medical student populations; to assess whether eventual differences may be explained by programme structure or student age and sex. We performed a cross-sectional study underpinned by the five-factor model of personality, with students attending three medical schools in Portugal. The five personality dimensions were assessed with the Portuguese version of the NEO-Five Factor Inventory. MANOVA and MANCOVA analyses were performed to clarify the contributions of school, programme structure, age and sex. Student personality dimensions were significantly different between the three medical schools [F (10,1026)  = 3.159, p < .001, [Formula: see text] = 0.03, π = 0.987]. However, taking sex and age into account the differences became non-significant. There were institutional differences in personality dimensions. However, those were primarily accounted for by sex and age effects and not by the medical school attended. Diversifying age and sex of the admitted students will diversify the personality of the medical student population

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Effects of childhood socioeconomic position on subjective health and health behaviours in adulthood: how much is mediated by adult socioeconomic position?

<p>Abstract</p> <p>Background</p> <p>Adult socioeconomic position (SEP) is one of the most frequently hypothesised indirect pathways between childhood SEP and adult health. However, few studies that explore the indirect associations between childhood SEP and adult health systematically investigate the mediating role of multiple individual measures of adult SEP for different health outcomes. We examine the potential mediating role of individual measures of adult SEP in the associations of childhood SEP with self-rated health, self-reported mental health, current smoking status and binge drinking in adulthood.</p> <p>Methods</p> <p>Data came from 10,010 adults aged 25-64 years at Wave 3 of the Survey of Family, Income and Employment in New Zealand. The associations between childhood SEP (assessed using retrospective information on parental occupation) and self-rated health, self-reported psychological distress, current smoking status and binge drinking were determined using logistic regression. Models were adjusted individually for the mediating effects of education, household income, labour market activity and area deprivation.</p> <p>Results</p> <p>Respondents from a lower childhood SEP had a greater odds of being a current smoker (OR 1.70 95% CI 1.42-2.03), reporting poorer health (OR 1.82 95% CI 1.39-2.38) or higher psychological distress (OR 1.60 95% CI 1.20-2.14) compared to those from a higher childhood SEP. Two-thirds to three quarters of the association of childhood SEP with current smoking (78%), and psychological distress (66%) and over half the association with poor self-rated health (55%) was explained by educational attainment. Other adult socioeconomic measures had much smaller mediating effects.</p> <p>Conclusions</p> <p>This study suggests that the association between childhood SEP and self-rated health, psychological distress and current smoking in adulthood is largely explained through an indirect socioeconomic pathway involving education. However, household income, area deprivation and labour market activity are still likely to be important as they are intermediaries in turn, in the socioeconomic pathway between education and health.</p

IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study

Idiopathic pulmonary fibrosis (IPF) is a rare and devastating lung disease of unknown aetiology. Genetic variations in the IL1RN gene, encoding the interleukin-1 receptor antagonist (IL-1Ra), have been associated with IPF susceptibility. Several studies investigated the variable number tandem repeat (VNTR) or single nucleotide polymorphisms rs408392, rs419598 and rs2637988, with variable results. The aim of this study was to elucidate the influence of polymorphisms in IL1RN on IPF susceptibility and mRNA expression. We performed a meta-analysis of the five case–control studies that investigated an IL1RN polymorphism in IPF in a Caucasian population. In addition, we investigated whether IL1RN mRNA expression was influenced by IL1RN polymorphisms. The VNTR, rs408392 and rs419598 were in tight linkage disequilibrium, with D′ > 0.99. Furthermore, rs2637988 was in linkage disequilibrium with the VNTR (D′ = 0.90). A haploblock of VNTR*2 and the minor alleles of rs408392and rs419598 was constructed. Meta-analysis revealed that this VNTR*2 haploblock is associated with IPF susceptibility both with an allelic model (odds ratio = 1.42, p = 0.002) and a carriership model (odds ratio = 1.60, p = 0.002). IL1RN mRNA expression was significantly influenced by rs2637988, with lower levels found in carriers of the (minor) GG genotype (p < 0.001). From this meta-analysis, we conclude that the VNTR*2 haploblock is associated with susceptibility to IPF. In addition, polymorphisms in IL1RN influence IL-1Ra mRNA expression, suggesting that lower levels of IL-1Ra predispose to developing IPF. Together these findings demonstrate that the cytokine IL-1Ra plays a role in IPF pathogenesis