Patient-specific computational fluid dynamics-assessment of aortic hemodynamics in a spectrum of aortic valve pathologies.

OBJECTIVES: The complexity of aortic disease is not fully exposed by aortic dimensions alone, and morbidity or mortality can occur before intervention thresholds are met. Patient-specific computational fluid dynamics (CFD) were used to assess the effect of different aortic valve morphologies on velocity profiles, flow patterns, helicity, wall shear stress (WSS), and oscillatory shear index (OSI) in the thoracic aorta. METHODS: A total of 45 subjects were divided into 5 groups: volunteers, aortic regurgitation-tricuspid aortic valve (AR-TAV), aortic stenosis-tricuspid aortic valve (AS-TAV), aortic stenosis-bicuspid aortic valve right-left cusp fusion (BAV[RL]), and aortic stenosis-right-non cusp fusion (AS-BAV[RN]). Subjects underwent magnetic resonance angiography, with phase-contrast magnetic resonance imaging at the sino-tubular junction to define patient-specific inflow velocity profiles. Hemodynamic recordings were used alongside magnetic resonance imaging angiographic data to run patient-specific CFD. RESULTS: The BAV groups had larger mid-ascending aorta diameters (P < .05). Ascending aorta flow was more eccentric in BAV (flow asymmetry = 78.9% ± 6.5% for AS-BAV(RN), compared with 4.7% ± 2.1% for volunteers, P < .05). Helicity was greater in AS-BAV(RL) (P < .05). Mean WSS was elevated in AS groups, greatest in AS-BAV(RN) (37.1 ± 4.0 dyn/cm2, compared with 9.8 ± 5.4 for volunteers, P < .05). The greater curvature of the ascending aorta experienced highest WSS and lowest OSI in AS patients, most significant in AS-BAV(RN) (P < .05). CONCLUSIONS: BAV displays eccentric flow with high helicity. The presence of AS, particularly in BAV-RN, led to greater WSS and lower OSI in the greater curvature of the ascending aorta. Patient-specific CFD provides noninvasive functional assessment of the thoracic aorta, and may enable development of a personalized approach to diagnosis and management of aortic disease beyond traditional guidelines

Exo70-Mediated Recruitment of Nucleoporin Nup62 at the Leading Edge of Migrating Cells is Required for Cell Migration

Nucleoporin Nup62 localizes at the central channel of the nuclear pore complex and is essential for nucleocytoplasmic transport. Through its FG-repeat domain, Nup62 regulates nuclear pore permeability and binds nuclear transport receptors. Here, we report that Nup62 interacts directly with Exo70 and colocalizes with Exo70 at the leading edge of migrating cells. Nup62 binds the N-terminal domain of Exo70 through its coiled-coil domain but not through its FG-repeat domain. Selective inhibition of leading edge Nup62 using RNA interference significantly reduces cell migration. Furthermore, Exo70 recruits Nup62 at the plasma membrane and at filopodia. Removal of the Exo70-binding domain of Nup62 prevents leading edge localization of Nup62. Analogous to Exo70, Nup62 cycles between the plasma membrane and the perinuclear recycling compartment. Altogether, we propose that Nup62 not solely regulates access to the cell nucleus, but additionally functions in conjunction with Exo70, a key regulator of exocytosis and actin dynamics, at the leading edge of migrating cells

Emx2 as a novel tool to suppress glioblastoma

Glioblastoma is a devastating CNS tumour for which no cure is presently available. We wondered if manipulation of Emx2, which normally antagonizes cortico-cerebral astrogenesis by inhibiting proliferation of astrocyte progenitors, may be employed to counteract it. We found that Emx2 overexpression induced the collapse of seven out of seven in vitro tested glioblastoma cell lines. Moreover, it suppressed four out of four of these lines in vivo. As proven by dedicated rescue assays, the antioncogenic activity of Emx2 originated from its impact on at least six metabolic nodes, which accounts for the robustness of its effect. Finally, in two out of two tested lines, the tumor culture collapse was also achieved when Emx2 was driven by a neural stem cell- specific promoter, likely active within tumor-initiating cells. All that points to Emx2 as a novel, promising tool for therapy of glioblastoma and prevention of its recurrencies

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

Conditionally reprogrammed primary airway epithelial cells maintain morphology, lineage and disease specific functional characteristics

© 2017 The Author(s). Current limitations to primary cell expansion led us to test whether airway epithelial cells derived from healthy children and those with asthma and cystic fibrosis (CF), co-cultured with an irradiated fibroblast feeder cell in F-medium containing 10 µM ROCK inhibitor could maintain their lineage during expansion and whether this is influenced by underlying disease status. Here, we show that conditionally reprogrammed airway epithelial cells (CRAECs) can be established from both healthy and diseased phenotypes. CRAECs can be expanded, cryopreserved and maintain phenotypes over at least 5 passages. Population doublings of CRAEC cultures were significantly greater than standard cultures, but maintained their lineage characteristics. CRAECs from all phenotypes were also capable of fully differentiating at air-liquid interface (ALI) and maintained disease specific characteristics including; defective CFTR channel function cultures and the inability to repair wounds. Our findings indicate that CRAECs derived from children maintain lineage, phenotypic and importantly disease-specific functional characteristics over a specified passage range

Classification, diagnosis, and approach to treatment for angioedema: Consensus report from the Hereditary Angioedema International Working Group

Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Cigarette Smoking and Erectile Dysfunction: Focus on NO Bioavailability and ROS Generation

Introduction.  Thirty million men in the United States suffer from erectile dysfunction (ED) and this number is expected to double by 2025. Considered a major public health problem, which seriously affects the quality of life of patients and their partners, ED becomes increasingly prevalent with age and chronic smoking is a major risk factor in the development of ED. Aim.  To review available evidence concerning the effects of cigarette smoking on vascular changes associated with decreased nitric oxide (NO) bioavailability and increased reactive oxygen species (ROS) generation. Methods.  We examined epidemiological and clinical data linking cigarette smoking and ED, and the effects of smoking on vascular NO bioavailability and ROS generation. Main Outcome Measures.  There are strong parallels between smoking and ED and considerable evidence supporting the concept that smoking-related ED is associated with reduced bioavailability of NO because of increased ROS. Results.  Cigarette smoking-induced ED in human and animal models is associated with impaired arterial flow to the penis or acute vasospasm of the penile arteries. Long-term smoking produces detrimental effects on the vascular endothelium and peripheral nerves and also causes ultrastructural damage to the corporal tissue, all considered to play a role in chronic smoking-induced ED. Clinical and basic science studies provide strong indirect evidence that smoking may affect penile erection by the impairment of endothelium-dependent smooth muscle relaxation or more specifically by affecting NO production via increased ROS generation. Whether nicotine or other products of cigarette smoke mediate all effects related to vascular damage is still unknown. Conclusions.  Smoking prevention represents an important approach for reducing the risk of ED. The characterization of the components of cigarette smoke leading to ED and the mechanisms by which these components alter signaling pathways activated in erectile responses are necessary for a complete comprehension of cigarette smoking-associated ED. Tostes RS, Carneiro FS, Lee AJ, Giachini FRC, Leite R, Osawa Y, and Clinton Webb R. Cigarette smoking and erectile dysfunction: Focus on NO bioavailability and ROS generation. J Sex Med 2008;5:1284–1295.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75024/1/j.1743-6109.2008.00804.x.pd

Evaluation of a new community-based curriculum in disaster medicine for undergraduates

BACKGROUND: Nowadays, many medical schools include training in disaster medicine in undergraduate studies. This study evaluated the efficacy of a disaster medicine curriculum recently designed for Saudi Arabian medical students. METHODS: Participants were 15 male and 14 female students in their fourth, fifth or sixth year at Jazan University Medical School, Saudi Arabia. The course was held at the Research Center in Emergency and Disaster Medicine and Computer Sciences Applied to the Medical Practice in Novara, Italy. RESULTS: The overall mean score on a test given before the course was 41.0 % and it increased to 67.7 % on the post-test (Wilcoxon test for paired samples: z = 4.71, p < 0.0001). There were no significant differences between the mean scores of males and females, or between students in their fourth, fifth or sixth year of medical school. CONCLUSIONS: These results show that this curriculum is effective for teaching disaster medicine to undergraduate medical students. Adoption of this course would help to increase the human resources available for dealing with disaster situations

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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