BRIEF REPORT: Brief Instrument to Assess Geriatrics Knowledge of Surgical and Medical Subspecialty House Officers

Initiatives are underway to increase geriatrics training in nonprimary care disciplines. However, no validated instrument exists to measure geriatrics knowledge of house officers in surgical specialties and medical subspecialties. METHODS : A 23-item multiple-choice test emphasizing inpatient care and common geriatric syndromes was developed through expert panels and pilot testing, and administered to 305 residents and fellows at 4 institutions in surgical disciplines (25% of respondents), emergency medicine (29%), medicine subspecialties (19%), internal medicine (12%), and other disciplines (15%). RESULTS : Three items decreased internal reliability. The remaining 20 items covered 17 topic areas. Residents averaged 62% correct on the test. Internal consistency was appropriate (Cronbach's Α coefficient=0.60). Validity was supported by the use of expert panels to develop content, and by overall differences in scores by level of training ( P <.0001) and graded improvement in test performance, with 58%, 63%, 62%, and 69% correct responses among HO1, HO2, HO3, and HO4s, respectively. CONCLUSIONS : This reliable, valid measure of clinical geriatrics knowledge can be used by a wide variety of surgical and medical graduate medical education programs to guide curriculum reform or evaluate program performance to meet certification requirements. The instrument is now available on the web.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73902/1/j.1525-1497.2006.00433.x.pd

Matrix metalloproteinases in subjects with type 1 diabetes

<p>Abstract</p> <p>Background</p> <p>Nephropathy is serious complication of diabetes. We have previously shown that level of the proteoglycan syndecan-1 in blood is associated with ultrastructural kidney changes in young persons with type 1 diabetes. Dysregulation of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) may contribute to the development of nephropathy. The aim of this study was to investigate if the levels of MMPs in blood samples are potential markers of early nephropathy in type 1 diabetes.</p> <p>Methods</p> <p>Blood samples were collected from type 1 diabetes patients after 11 years of diabetes (n = 15) and healthy volunteers (n = 12) and stored at ÷80°C until measurement. Levels and activities of serum MMP-2, MMP-9, TIMP-1 and TIMP- 2 were analyzed and compared to those of control individuals using ELISA, SDS-PAGE gelatin zymography, and Western blot analysis.</p> <p>Results</p> <p>The serum levels of both MMP-9 and MMP-2 were significantly higher in subjects with type 1 diabetes, compared to controls (p = 0.016 and p = 0.008 respectively). Western blotting revealed no differences between the two groups in the levels of TIMP-1 or TIMP-2, respectively.</p> <p>Conclusion</p> <p>Our MMP analysis of serum from a limited number of patients with type 1 diabetes suggest that such analysis is potentially useful as markers in studies of people at risk of progression to chronic kidney disease.</p

Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

Effect of a Dipeptidyl Peptidase-IV Inhibitor, Des-Fluoro-Sitagliptin, on Neointimal Formation after Balloon Injury in Rats

Background: Recently, it has been suggested that enhancement of incretin effect improves cardiac function. We investigated the effect of a DPP-IV inhibitor, des-fluoro-sitagliptin, in reducing occurrence of restenosis in carotid artery in response to balloon injury and the related mechanisms. Methods and Findings: Otsuka Long-Evans Tokushima Fatty rats were grouped into four: control (normal saline) and sitagliptin 100, 250 and 500 mg/kg per day (n = 10 per group). Sitagliptin or normal saline were given orally from 1 week before to 2 weeks after carotid injury. After 3 weeks of treatment, sitagliptin treatment caused a significant and dose-dependent reduction in intima-media ratio (IMR) in obese diabetic rats. This effect was accompanied by improved glucose homeostasis, decreased circulating levels of high-sensitivity C-reactive protein (hsCRP) and increased adiponectin level. Moreover, decreased IMR was correlated significantly with reduced hsCRP, tumor necrosis factor-$\alpha$ and monocyte chemoattractant protein-1 levels and plasminogen activator inhibitor-1 activity. In vitro evidence with vascular smooth muscle cells (VSMCs) demonstrated that proliferation and migration were decreased significantly after sitagliptin treatment. In addition, sitagliptin increased caspase-3 activity and decreased monocyte adhesion and NFκB activation in VSMCs. Conclusions: Sitagliptin has protective properties against restenosis after carotid injury and therapeutic implications for treating macrovascular complications of diabetes

Effects of combined treatment with rapamycin and cotylenin A, a novel differentiation-inducing agent, on human breast carcinoma MCF-7 cells and xenografts

INTRODUCTION: Rapamycin, an inhibitor of the serine/threonine kinase target of rapamycin, induces G(1 )arrest and/or apoptosis. Although rapamycin and its analogues are attractive candidates for cancer therapy, their sensitivities with respect to growth inhibition differ markedly among various cancer cells. Using human breast carcinoma cell line MCF-7 as an experimental model system, we examined the growth-inhibitory effects of combinations of various agents and rapamycin to find the agent that most potently enhances the growth-inhibitory effect of rapamycin. METHOD: We evaluated the growth-inhibitory effect of rapamycin plus various agents, including cotylenin A (a novel inducer of differentiation of myeloid leukaemia cells) to MCF-7 cells, using either MTT assay or trypan blue dye exclusion test. The cell cycle was analyzed using propidium iodide-stained nuclei. Expressions of several genes in MCF-7 cells with rapamycin plus cotylenin A were studied using cDNA microarray analysis and RT-PCR. The in vitro results of MCF-7 cells treated with rapamycin plus cotylenin A were further confirmed in vivo in a mouse xenograft model. RESULTS: We found that the sensitivity of rapamycin to MCF-7 cells was markedly affected by cotylenin A. This treatment induced growth arrest of the cells at the G(1 )phase, rather than apoptosis, and induced senescence-associated β-galactosidase activity. We examined the gene expression profiles associated with exposure to rapamycin and cotylenin A using cDNA microarrays. We found that expressions of cyclin G(2), transforming growth factor-β-induced 68 kDa protein, BCL2-interacting killer, and growth factor receptor-bound 7 were markedly induced in MCF-7 cells treated with rapamycin plus cotylenin A. Furthermore, combined treatment with rapamycin and cotylenin A significantly inhibited the growth of MCF-7 cells as xenografts, without apparent adverse effects. CONCLUSION: Rapamycin and cotylenin A cooperatively induced growth arrest in breast carcinoma MCF-7 cells in vitro, and treatment with rapamycin and cotylenin A combined more strongly inhibited the growth of MCF-7 cells as xenografts in vivo than treatment with rapamycin or cotylenin A alone, suggesting that this combination may have therapeutic value in treating breast cancer. We also identified several genes that were markedly modulated in MCF-7 cells treated with rapamycin plus cotylenin A

Inhibition of Hypoxia-Inducible Factor-1α (HIF-1α) Protein Synthesis by DNA damage inducing agents

10.1371/journal.pone.0010522PLoS ONE55

The mechanism of impact of summative assessment on medical students’ learning

It has become axiomatic that assessment impacts powerfully on student learning, but there is a surprising dearth of research on how. This study explored the mechanism of impact of summative assessment on the process of learning of theory in higher education. Individual, in-depth interviews were conducted with medical students and analyzed qualitatively. The impact of assessment on learning was mediated through various determinants of action. Respondents’ learning behaviour was influenced by: appraising the impact of assessment; appraising their learning response; their perceptions of agency; and contextual factors. This study adds to scant extant evidence and proposes a mechanism to explain this impact. It should help enhance the use of assessment as a tool to augment learning

Acute and chronic kidney disease in elderly patients with hip fracture: prevalence, risk factors and outcome with development and validation of a risk prediction model for acute kidney injury

Background Hip fracture is a common injury in older people with a high rate of postoperative morbidity and mortality. This patient group is also at high risk of acute kidney injury (AKI) and chronic kidney disease (CKD), but little is known of the impact of kidney disease on outcome following hip fracture. Methods An observational cohort of consecutive patients with hip fracture in a large UK secondary care hospital. Predictive modelling of outcomes using development and validation datasets. Inclusion: all patients admitted with hip fracture with sufficient serum creatinine measurements to define acute kidney injury. Main outcome measures – development of acute kidney injury during admission; mortality (in hospital, 30-365 day and to follow-up); length of hospital stay. Results Data were available for 2848 / 2959 consecutive admissions from 2007-2011; 776 (27.2%) male. Acute kidney injury occurs in 24%; development of acute kidney injury is independently associated with male sex (OR 1.48 (1.21 to 1.80), premorbid chronic kidney disease stage 3B or worse (OR 1.52 (1.19 to 1.93)), age (OR 3.4 (2.29 to 5.2) for >85 years) and greater than one major co-morbidities (OR 1.61 (1.34 to 1.93)). Acute kidney injury of any stage is associated with an increased hazard of death, and increased length of stay (Acute kidney injury: 19.1 (IQR 13 to 31) days; no acute kidney injury 15 (11 to 23) days). A simplified predictive model containing Age, CKD stage (3B-5), two or more comorbidities, and male sex had an area under the ROC curve of 0.63 (0.60 to 0.67). Conclusions Acute kidney injury following hip fracture is common and associated with worse outcome and greater hospital length of stay. With the number of people experiencing hip fracture predicted to rise, recognition of risk factors and optimal perioperative management of acute kidney injury will become even more important

Neuronal differentiation of hair-follicle-bulge-derived stem cells co-cultured with mouse cochlear modiolus explants

Stem-cell-based repair of auditory neurons may represent an attractive therapeutic option to restore sensorineural hearing loss. Hair-follicle-bulge-derived stem cells (HFBSCs) are promising candidates for this type of therapy, because they (1) have migratory properties, enabling migration after transplantation, (2) can differentiate into sensory neurons and glial cells, and (3) can easily be harvested in relatively high numbers. However, HFBSCs have never been used for this purpose. We hypothesized that HFBSCs can be used for cell-based repair of the auditory nerve and we have examined their migration and incorporation into cochlear modiolus explants and their subsequent differentiation. Modiolus explants obtained from adult wild-type mice were cultured in the presence of EF1α-copGFP-transduced HFBSCs, constitutively expressing copepod green fluorescent protein (copGFP). Also, modiolus explants without hair cells were co-cultured with DCX-copGFP-transduced HFBSCs, which demonstrate copGFP upon doublecortin expression during neuronal differentiation. Velocity of HFBSC migration towards modiolus explants was calculated, and after two weeks, co-cultures were fixed and processed for immunohistochemical staining. EF1α-copGFP HFBSC migration velocity was fast: 80.5 ± 6.1 μm/h. After arrival in the explant, the cells formed a fascicular pattern and changed their phenotype into an ATOH1-positive neuronal cell type. DCX-copGFP HFBSCs became green-fluorescent after integration into the explants, confirming neuronal differentiation of the cells. These results show that HFBSC-derived neuronal progenitors are migratory and can integrate into cochlear modiolus explants, while adapting their phenotype depending on this micro-environment. Thus, HFBSCs show potential to be employed in cell-based therapies for auditory nerve repair