Genotoxicants Target Distinct Molecular Networks in Neonatal Neurons

BACKGROUND: Exposure of the brain to environmental agents during critical periods of neuronal development is considered a key factor underlying many neurologic disorders. OBJECTIVES: In this study we examined the influence of genotoxicants on cerebellar function during early development by measuring global gene expression changes. METHODS: We measured global gene expression in immature cerebellar neurons (i.e., granule cells) after treatment with two distinct alkylating agents, methylazoxymethanol (MAM) and nitrogen mustard (HN2). Granule cell cultures were treated for 24 hr with MAM (10–1,000 μM) or HN2 (0.1–20 μM) and examined for cell viability, DNA damage, and markers of apoptosis. RESULTS: Neuronal viability was significantly reduced (p < 0.01) at concentrations > 500 μM for MAM and > 1.0 μM for HN2; this correlated with an increase in both DNA damage and markers of apoptosis. Neuronal cultures treated with sublethal concentrations of MAM (100 μM) or HN2 (1.0 μM) were then examined for gene expression using large-scale mouse cDNA microarrays (27,648). Gene expression results revealed that a) global gene expression was predominantly up-regulated by both genotoxicants; b) the number of down-regulated genes was approximately 3-fold greater for HN2 than for MAM; and c) distinct classes of molecules were influenced by MAM (i.e, neuronal differentiation, the stress and immune response, and signal transduction) and HN2 (i.e, protein synthesis and apoptosis). CONCLUSIONS: These studies demonstrate that individual genotoxicants induce distinct gene expression signatures. Further study of these molecular networks may explain the variable response of the developing brain to different types of environmental genotoxicants

'It gives you an understanding you can't get from any book.' The relationship between medical students' and doctors' personal illness experiences and their performance: a qualitative and quantitative study

Background: anecdotes abound about doctors' personal illness experiences and the effect they have on their empathy and care of patients. We formally investigated the relationship between doctors' and medical students' personal illness experiences, their examination results, preparedness for clinical practice, learning and professional attitudes and behaviour towards patients.Methods: newly-qualified UK doctors in 2005 (n = 2062/4784), and two cohorts of students at one London medical school (n = 640/749) participated in the quantitative arm of the study. 37 Consultants, 1 Specialist Registrar, 2 Clinical Skills Tutors and 25 newly-qualified doctors participated in the qualitative arm. Newly-qualified doctors and medical students reported their personal illness experiences in a questionnaire. Doctors' experiences were correlated with self-reported preparedness for their new clinical jobs. Students' experiences were correlated with their examination results, and self-reported anxiety and depression. Interviews with clinical teachers, newly-qualified doctors and senior doctors qualitatively investigated how personal illness experiences affect learning, professional attitudes, and behaviour.Results: 85.5% of newly-qualified doctors and 54.4% of medical students reported personal illness experiences. Newly-qualified doctors who had been ill felt less prepared for starting work (p &lt; 0.001), but those who had only experienced illness in a relative or friend felt more prepared (p = 0.02). Clinical medical students who had been ill were more anxious (p = 0.01) and had lower examination scores (p = 0.006). Doctors felt their personal illness experiences helped them empathise and communicate with patients. Medical students with more life experience were perceived as more mature, empathetic, and better learners; but illness at medical school was recognised to impede learning.Conclusion: the majority of the medical students and newly qualified doctors we studied reported personal illness experiences, and these experiences were associated with lower undergraduate examination results, higher anxiety, and lower preparedness. However reflection on such experiences may have improved professional attitudes such as empathy and compassion for patients. Future research is warranted in this area

Minimum joint space width and tibial cartilage morphology in the knees of healthy individuals: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The clinical use of minimum joint space width (mJSW) and cartilage volume and thickness has been limited to the longitudinal measurement of disease progression (i.e. change over time) rather than the diagnosis of OA in which values are compared to a standard. This is primarily due to lack of establishment of normative values of joint space width and cartilage morphometry as has been done with bone density values in diagnosing osteoporosis. Thus, the purpose of this pilot study is to estimate reference values of medial joint space width and cartilage morphometry in healthy individuals of all ages using standard radiography and peripheral magnetic resonance imaging.</p> <p>Design</p> <p>For this cross-sectional study, healthy volunteers underwent a fixed-flexion knee X-ray and a peripheral MR (pMR) scan of the same knee using a 1T machine (ONI OrthOne™, Wilmington, MA). Radiographs were digitized and analyzed for medial mJSW using an automated algorithm. Only knees scoring ≤1 on the Kellgren-Lawrence scale (no radiographic evidence of knee OA) were included in the analyses. All 3D SPGRE fat-sat sagittal pMR scans were analyzed for medial tibial cartilage morphometry using a proprietary software program (Chondrometrics GmbH).</p> <p>Results</p> <p>Of 119 healthy participants, 73 were female and 47 were male; mean (SD) age 38.2 (13.2) years, mean BMI 25.0 (4.4) kg/m². Minimum JSW values were calculated for each sex and decade of life. Analyses revealed mJSW did not significantly decrease with increasing decade (p > 0.05) in either sex. Females had a mean (SD) medial mJSW of 4.8 (0.7) mm compared to males with corresponding larger value of 5.7 (0.8) mm. Cartilage morphometry results showed similar trends with mean (SD) tibial cartilage volume and thickness in females of 1.50 (0.19) μL/mm²and 1.45 (0.19) mm, respectively, and 1.77 (0.24) μL/mm²and 1.71 (0.24) mm, respectively, in males.</p> <p>Conclusion</p> <p>These data suggest that medial mJSW values do not decrease with aging in healthy individuals but remain fairly constant throughout the lifespan with "healthy" values of 4.8 mm for females and 5.7 mm for males. Similar trends were seen for cartilage morphology. Results suggest there may be no need to differentiate a t-score and a z-score in OA diagnosis because cartilage thickness and JSW remain constant throughout life in the absence of OA.</p

The impact of trained patient educators on musculoskeletal clinical skills attainment in pre-clerkship medical students

<p>Abstract</p> <p>Background</p> <p>Despite the high burden of musculoskeletal (MSK) diseases, few generalists are comfortable teaching MSK physical examination (PE) skills. Patient Partners^®in Arthritis (PP^®IA) is a standardized patient educator program that could potentially supplement current MSK PE teaching. This study aims to determine if differences exist in MSK PE skills between non-MSK specialist physician and PP^®IA taught students.</p> <p>Methods</p> <p>Pre-clerkship medical students attended 2-hour small group MSK PE teaching by either non-MSK specialist physician tutors or by PP^®IA. All students underwent an MSK OSCE and completed retrospective pre-post questionnaires regarding comfort with MSK PE and interest in MSK.</p> <p>Results</p> <p>83 students completed the OSCE (42 PP^®IA, 41 physician taught) and 82 completed the questionnaire (42 PP^®IA, 40 physician taught). There were no significant differences between groups in OSCE scores. For all questionnaire items, post-session ratings were significantly higher than pre-session ratings for both groups. In exploratory analysis PP^®IA students showed significantly greater improvement in 12 of 22 questions including three of five patient-centred learning questions.</p> <p>Conclusions</p> <p>PP^®IA MSK PE teaching is as good as non-MSK specialist physician tutor teaching when measured by a five station OSCE and provide an excellent complementary resource to address current deficits in MSK PE teaching.</p

Diagnosis and management of adhesive capsulitis

Adhesive capsulitis is a musculoskeletal condition that has a disabling capability. This review discusses the diagnosis and both operative and nonoperative management of this shoulder condition that causes significant morbidity. Issues related to medications, rehabilitation, and post surgical considerations are discussed

Developing Graduate Employability: The CareerEDGE Model and the Importance of Emotional Intelligence

This chapter discusses a model of graduate employability development, the CareerEDGE model (Dacre Pool and Sewell 2007) which includes Emotional Intelligence (EI) as a key component. Although previous models and theories of employability (e.g. Fugate et al. 2004; Knight and Yorke 2004) have alluded to adaptive emotional functioning as an aspect of employability, CareerEDGE was the first to give EI such prominence. There is scope for EI to have a direct impact on graduate employability but also an indirect impact via other aspects of employability development

Using the Living CV to help students take ownership of their learning gain

There is an increasing emphasis on embedding employability skills and experience within the higher education curriculum to address new concepts of ‘learning gain’ and the perceived student demand for a value for money experience. An exploratory study, at a southern university in the UK, found that students articulated an improved work readiness when they were presented the ‘Living CV’, an initiative that connects programme learning outcomes into CV outputs. During 2018, a larger, mixed methods study (n=127) was conducted across all three years of fashion degrees. Students completed a pre and post questionnaire before and after a presentation on the Living CV and their views were further explored in a focus group and interviews. Results found that the Living CV presentation heightened students’ awareness of the applicability of their programme learning to their future employability and how they could use their academic learning outcomes on their CV as a tool to achieve this. The study recommends that personalised and explicit coaching on ‘work literacy’ should be integrated into university programmes at all levels to include the Living CV, discussion about and experience in the world of work, increased employer engagement and preparation for interview