bluuebunny/crossref_metadata_2025_split huggingface dataset:
70. Supporting IMG integration into residency trainings
Authors: Takahashi S. Glover , Alameddine M. , Martin D. , Verma S. , Edwards S. 
Published: May 2017

This paper is describes the design, development, implementation and evaluation of a preparatory training program for international medical trainees. The program was offered for one week full time shortly before they begin their residency training programs. First the paper reports on the survey and focus groups that guided the learning objectives and the course content. Next the paper describes the curriculum development phase and reports on the topical themes, session goals and objectives and learning materials. Three main themes emerged when developing the program: understanding the educational, health and practice systems in Canada; development of communication skills; and supporting personal success in residency training including self assessment, reflection and personal wellness. Sample lesson plans and handouts from each of the theme areas are illustrated. The comprehensive evaluation of the sessions and the overall program is then also described. The paper then summarizes the identified key issues and challenges in the design and implementation of a preparatory training program for international medical trainees before they begin their residency training programs.
Allan GM, Manca D, Szafran O, Korownyk C. Workforce issues in general surgery. Am Surg. 2007 Feb; 73(2):100-8.
Dauphinee, WD. The circle game: understanding physician migration patterns within Canada. Acad Med. 2006 (Dec); 81(12 Suppl):S49-54.
Spike NA. International medical graduates: the Australian perspective. Academic Medicine. 2006 (Sept); 81(9):842-6.
71. Are video interviews a good alternative to in person interviews in assessing international applicants' skills?
Authors: Alameddine M. , Imrie K. , Akers S. , Verma S. 
Published: May 2017

We developed and administered two questionnaires to assess the interview experience of both interviewers and applicants during postgraduate medical selection interviews. Using a 5 point likert scale, the questionnaires assessed three areas (1) ability to show/assess communication, interpersonal and problem solving skills; (2) ability to know the other side well and (3) level of comfort with the interview. Interviewers and applicants were asked to provide a global rating for the interview. The questionnaires were administered to both candidates and applicants from 6 departments in 18 in-person and 12 video interviews. 30 applicant and 87 interviewer survey forms were collected and analyzed. T-tests were used to compare the means of the two groups and significance levels were analyzed. Both interviewers and applicants had a higher average global satisfaction for video interviews compared to in person interviews. No difference was indicated in the ability of interviewers to assess the applicants’ skills between the two types of interviews. For both interviewers and applicants, video interviews, compared to in person interview, had a lower average score for connecting personally & establishing rapport and for satisfaction with administrative arrangements. Video interviewed applicants had a 50% probability of getting accepted in a program compared to 22% of in person interviewed candidates. We conclude that video interviews appear to be a valuable alternative to in-person interviews, with some sacrifice in personal connection and rapport. Video interviews result in significant time and cost savings for international applicants and have potential implications for the CaRMS process as well.
Sackett KM, Campbell-Heider N, Blyth JB. The evolution and evaluation of videoconferencing technology for graduate nursing education. Comput Inform Nurs. 2004 (Mar-Apr); 22(2):101-6.
Shepherd L, Goldstein D, Whitford H, Thewes B, Brummell V, Hicks M. The utility of videoconferencing to provide innovative delivery of psychological treatment for rural cancer patients: results of a pilot study. J Pain Symptom Manage 2006 (Nov); 32(5):453-61.
Arena J, Dennis N, Devineni T, Maclean R, Meador K. A pilot study of feasibility and efficacy of telemedicine-delivered psychophysiological treatment for vascular headache. Telemed J E Health 2004 (Winter); 10(4):449-54.
The role of THOA in calcium sensitization in human myometrial smooth muscles
Authors: Aguilar Hector , Mitchell B. F. (Peter) 
Published: May 2017

Improved understanding of the regulation of contractions of uterine smooth muscle (myometrium) is essential to develop more successful strategies for prevention of premature birth, which remains the most common cause of infant death and disability. Oxytocin (OT) and prostaglandin (PG) F2a are potent myometrial stimulants which induce an increase in intracellular Ca++. This activates myosin light chain kinase (MLCK) and subsequently the cell’s contractile machinery. However, there is poor correlation between the rise in Ca++ and the strength of the myometrial contraction. Contractile strength greatly increases at the time of parturition partly due to Ca++-independent factors that sensitize the muscle to the rise in intracellular Ca++. In vascular smooth muscle, one key regulator in this process of Ca++ sensitization is the monomeric G-protein, RhoA which in turn activates Rho-associated kinase (ROK). Studies in the rat myometrium have shown that RhoA and ROK are involved in enhancing OT-induced contractions. The potential role of the RhoA/ROK system in uterine contractility at the time of parturition has not been investigated in the human myometrium or in human cell lines.
We propose to investigate the role of RhoA/ROK in the human myometrium using molecular cloning techniques. We have constructed expression plasmids for wild type, dominant positive (constitutively active), and dominant negative (constitutively inactive) isoforms of RhoA and synthesized purified proteins using a bacterial (BL21) translation system. These constructs will be introduced into primary and immortalized human myocytes using the protein transduction domain (TAT) derived from the HIV virus, which is capable of introducing whole proteins into mammalian cells. RhoA activation/translocation to the plasma membrane will be visualized using real time confocal microscopy in experiments where the RhoA proteins have been tagged with green fluorescent protein (GFP). Following introduction of the normal and mutant G-proteins, the downstream targets of activated ROK will be assayed for phosphorylation status using near infrared (NIR) fluorescence imaging of western blots or in-cell westerns. These targets include the myosin binding subunit (MBS) of myosin light chain phosphatase (MLCP), and two peptide phosphatase inhibitors of MLCP, CPI-17 and PHI-1. In addition, we propose to measure ROK activity directly using a direct enzyme assay. We will monitor calcium transients using fluorescence microscopy to verify the calcium independence of our measurements. These experiments will determine the role of the RhoA/ROK system in the mechanisms that may determine human uterine contractility. This information may direct new strategies to prevent or treat preterm labour.
Effects of maternal nutrient restriction on placental morphology and insulin-like growth factor system expressions
Authors: Albion C , Dixon S , Nygard K , Reid C , Han V 
Published: May 2017

Uteroplacental insufficiency is one of the major causes of fetal growth restriction (FGR) in developed countries. The pathophysiology is likely the result of fetal undernutrition due to the impairment of nutrient and substrate transfer from the mother to the fetus. Fetal undernutrition due to maternal undernutrition is not a major cause of FGR in developed countries compared to developing countries. However, FGR can be reproducibly created in experimental animals by maternal undernutrition, and is commonly utilized to study the pathophysiology of fetal undernutrition in the fetus and the placenta. The insulin-like growth factor (IGF) system is the principal growth factor involved in regulating normal fetal and placental growth and its aberrant expression is associated with the development of FGR. We hypothesized that placenta undergoes adaptive changes in pregnancies with maternal undernutrition, the effects of which are mediated by the IGF system.
Methods: A mouse model of FGR was generated in CD-1 mice using maternal total caloric nutrient restriction. At 6.5 days of pregnancy, mice were randomly assigned to the control group (ad libitum diet) or global nutrient restriction (GNR) diet group (70% of predetermined food intake of each gestational day). FGR can be reproducibly induced in the fetuses without effect in litter size. Placentae were collected at 18.5 days and were fixed in 4% paraformaldehyde. Five mm tissue sections were prepared by standard techniques and were stained with hematoxylin & eosin for morphometry, PAS for glycogen staining, and immunohistochemistry against IGF-I and –II, IGFBP-1, -2 and –3 using specific antisera for cell-specific expression of the IGF system. The morphology of the placentae was analyzed using a computerized image analysis system.
Results: Placentae were significantly smaller in FGR mice compared to controls (94±4 mg SEM vs 72±3 mg SEM). Preliminary results demonstrate changes in FGR mouse placentae tended to be a result of a reduction in spongiotrophoblast layer (p = 0.066, one-tailed t-test) while the labyrinthine trophoblast layer was maintained. Morphometric analysis of the labyrinth demonstrated an increase in the diameter of both maternal and fetal vessels with a reduction in the thickness of the interchorial layer. The IGF-I and –II, IGFBP-1, IGFBP-2 and IGFBP-3 immunoreactivity were all reduced in FGR placentae compared to the controls.
Conclusion: These findings suggest that maternal nutrient restriction induces changes in the placenta that may potentially lead to improved nutrient and substrate transfer from mother to fetus, in an attempt to maintain fetal viability. However, these compensatory changes are not sufficient to maintain growth. These changes may result from the alteration of expression of the IGF system genes.
Global gene expression analyses in early experimental osteoarthritis reveal novel players in articular cartilage degenerations
Authors: Appleton Tom , Usmani Shirine , Pitelka Vasek , Henry Jim , Bernier Suzanne , Beier Frank 
Published: May 2017

Introduction: Articular cartilage degeneration is a hallmark of osteoarthritis (OA). We sought to identify dysregulated genes in degenerating cartilage and hypothesized that altered growth factor expression causes cartilage degradation in OA.
Methods: Genome-wide microarray analysis of RNA harvested directly from sham (control) and degenerating articular cartilage was performed using our previously characterized pre-clinical rat model of knee OA1. Known OA genes were validated using RNA samples (real-time PCR) and histological sections (immunofluorescence) from independent animals. Functional studies in chondrocytes and articular cartilage explants investigated the effects of one identified factor (transforming growth factor alpha (TGF-α)) on cartilage degeneration. The effects of TGF-α on primary chondrocyte morphology, proliferation, gene expression, and SOX9 transcription factor expression were assessed.
Results: Dysregulated gene expression profiles in degenerating cartilage included known OA genes2. Microarray expression profiles were consistently validated at RNA and protein levels by alternative methods. Several genes previously unstudied in OA cartilage were upregulated, including growth factors (e.g. TGF-α and kit ligand), cell surface receptors (e.g. endothelin type A receptor), and proteases (e.g. cathepsin S). Functional studies demonstrated that TGF-α alters chondrocyte morphology through re-organization of the actin cytoskeleton. TGF-α also stimulated primary chondrocyte proliferation and chondrocyte cluster formation in cartilage explants. Chondrocyte expression of anabolic genes and total collagen protein levels were reduced by TGF-α, while expression of catabolic factors increased. Finally, TGF-α reduced both the expression of total SOX9 and levels of phosphorylated (active) SOX9.
Conclusions: Our microarray study identified numerous factors previously unstudied in OA cartilage, including increased levels of TGF-α. Functional studies determined that TGF-α promotes cartilage degeneration through chondrocyte proliferation and catabolic factor expression. Further, TGF-α inhibits chondrocyte anabolism, likely through a mechanism involving suppression of SOX9.
References:
1C.T.G. Appleton et al. (2007). Arthritis Res Ther 9(1):R13. 2C.T.G. Appleton et al. (2007), Arthritis Rheum In Press.
The character of anti-HCV T cell responses differs between spontaneous and treatment-induced viral clearance s
Authors: Barrett L , Hirsch G , Gallant M , Howley C , Peltekian K , Grant M 
Published: May 2017

Introduction: Hepatitis C virus (HCV) is a common infection with approximately 170 million individuals infected worldwide. The majority of exposed individuals develop chronic infection, with viral clearance being the exception to the rule. Even with antiviral therapy, only 50-75% of treated individuals become HCV RNA negative. The role of the adaptive immune response, and particularly T cells, has been well established in other viral infections but its function in HCV infection is unclear, making it difficult to develop either prophylactic or therapeutic vaccine strategies.
Objectives: Compare the breadth, specificity, and magnitude of anti-HCV T cell responses in individuals who are chronically HCV-infected with those who clear HCV spontaneously or after antiviral treatment.
Methods: We assessed T cell responses in 3 groups of HCV exposed individuals: 18 people who were chronically HCV infected (anti-HCV antibody and HCV RNA positive), 5 who were exposed to HCV but cleared the virus without treatment (antibody positive, RNA negative), and 17 who responded to anti-HCV treatment (antibody positive but RNA negative after treatment). CD4+ T cell responses to HCV and recall antigens were measured by standard 3H-thymidine proliferation assay, and CD8+ T cell responses were evaluated by incubating peripheral blood mononuclear cells (PBMC) overnight with 15-mer peptides spanning the entire HCV-1a genome. The number of HCV-specific interferon-gamma (IFN-g)-producing cells per million PBMC was estimated by ELISPOT.
Results: Anti-HCV CD4+ T cell responses were uncommon, and of low magnitude in all groups. Responses were only to peptides in the core region. The overall breadth of the anti-HCV CD8+ response was greatest in treated responders (average 43/44 peptide pools tested positive) and least in those who failed treatment (average 11/44). All clearers had responses to the NS5 region. The magnitude of the CD8+ response tended to be highest in the treated responders, but there was no significant difference between groups.
Conclusions: The character of the anti-HCV T cell response differs not just between chronic infection and clearance, but also between spontaneous versus treatment-associated HCV clearance. This suggests that it is likely a combination of T cell breadth, magnitude and specificity that results in viral clearance. Based on these results, development of therapeutic and prophylactic vaccine strategies may need to target different T cell responses.
Through the looking-glass: Objectivity, interpretation, and the construction of social kinds as emerging issues in research ethicss
Authors: Berkhout S G , Tyndall M W , Anderson S 
Published: May 2017

Background: Access to the means of knowledge production is severely limited for many individuals who are socially, politically, and economically disadvantaged. Of particular concern, largely overlooked in bioethics discourse, is the manner by which surveillance, identification, and classification contribute to the creation of particular populations based on harmful social identities, and the subsequent stigmatization of the individuals subject to analysis.
Methods: Drawing from a range of philosophical and sociological literature, including Hans-Georg Gadamer, Charles Taylor, Bruno Latour, and Deborah Lupton, as well as public health discourse, this paper gives an analysis of a challenging metaphysical and ethical problem related to research practices and public health interventions in vulnerable communities. The themes of objectivism and stigmatization are illuminated by focusing on research related to HIV infection among survival sex workers in Vancouver’s downtown eastside.
Results: Reductionist models of human behaviour presuppose a clear distinction between description and evaluation, contributing to an understanding of social reality as structured by objective, base level data, and misconstruing modes of social relations as individual action. In the context of HIV risk, an ethical problem emerges: describing individual actions as “data,” or “fact,” serves to construct and reinforce transgressive social identities. Given that stigmatization is itself part of the context of adverse health outcomes and HIV infection, practices relying on methods that presume representational authority and fail to critically interpret human action are ethically problematic. Resolving difficulties within the methodological underpinnings of public health and HIV behavioural research requires an understanding of many social science methods as hermeneutical, while enabling the contribution of disparate standpoints to the production of scientific knowledge.
Conclusions: The implications of presumed objectivity and representational authority demand a reconsideration of how research in vulnerable communities might be conducted, such that it produces results that are scientifically rigorous and socially responsible.
Rapid electrical pacing of cardiomyocytes alters the behavior of cardiac fibroblasts: Implications for atrial fibrillations
Authors: Burstein Brett , Qi Xiao-Yan , Calderone Angelino , Nattel Stanley 
Published: May 2017

Background: Atrial fibrillation (AF) produces atrial tachycardia-related changes in atrial electrophysiology, providing a possible explanation for the progressive nature of the arrhythmia. Structural remodeling results from ventricular dysfunction due to a rapid response to AF, but whether AF itself can cause atrial fibrosis remains unclear. This study investigated the hypothesis that rapid atrial cardiomyocyte activation produces factors that influence atrial fibroblast proliferation and secretory functions.
Methods: Cultured canine atrial fibroblasts were treated with medium from rapidly-paced atrial cardiomyocytes (group 5Hz), non-paced cardiomyocytes (group NP) and cardiomyocyte pacing medium alone (group Ø), and analyzed by [3H]thymidine incorporation, Western-blot and real-time RT-PCR.
Results: Rapidly-paced cardiomyocyte-conditioned medium had a potent anti-proliferative effect, reducing [3H]thymidine uptake compared to non-paced cardiomyocyte-conditioned medium and medium alone (2,143±1,490** vs. 15,870±3,343 and 16,440±4,193 respectively, **P < 0.01 vs. both NP and Ø). Conditioned medium from rapidly-paced cardiomyocytes increased αSMA protein reflecting an activated myofibroblast phenotype (1.62±0.20** vs. 1.08±0.26 and 1.01±0.24), collagen-1 (2.41±0.22* vs. 1.49±0.33 and 1.10±0.19, *P < 0.05 both NP and Ø) and fibronectin-1 (3.05±0.28* vs. 1.80±0.45 and 1.20±0.19) mRNA expression compared to control cells. Treatment of the conditioned medium with the AT1 receptor blocker valsartan, partially attenuated the pacing-induced αSMA increase but had no effect on fibroblast proliferation. Atrial tissue from 1-week atrial-tachypaced dogs with AV block/ventricular pacing to control ventricular rate similarly showed upregulation of collagen-1 (2.6±0.5 vs. 0.7±0.3, P < 0.01) and fibronectin-1 (4.9±0.6 vs. 1.1±0.4, P < 0.001) mRNA versus unpaced shams. Conclusion: Rapidly-paced cardiomyocytes release substances that profoundly alter cardiac fibroblast function and induce an activated myofibroblast phenotype that is reflected by altered ECM-gene expression in vivo. These findings are consistent with recent observations that AF per se causes ECM remodeling and may have important consequences for understanding and preventing the mechanisms underlying AF progression.
The metalloproteinase ADAM10 is required for retinal ganglion cell axon guidance in the developing visual systems
Authors: Chen Y. Y. , Hehr C. L. , Atkinson-Leadbeater K. , Hocking J. C. , McFarlane S. 
Published: May 2017

Background: The growth cone interprets cues in its environment in order to reach its target. We want to identify molecules that regulate growth cone behaviour in the developing embryo. We investigated the role of A disintegrin and metalloproteinase 10 (ADAM10) in axon guidance in the developing visual system of African frog, Xenopus laevis.
Methods: We first examined the expression patterns of adam10 mRNA by in situ hybridization. We then exposed the developing optic tract to an ADAM10 inhibitor, GI254023X, in vivo. Lastly, we inhibited ADAM10 function in diencephalic neuroepithelial cells (through which retinal ganglion cell (RGC) axons extend) or RGCs by electroporating or transfecting an ADAM10 dominant negative (dn-adam10).
Results: We show that adam10 mRNA is expressed in the dorsal neuroepithelium over the time RGC axons extend towards their target, the optic tectum. Second, pharmacological inhibition of ADAM10 in an in vivo exposed brain preparation causes the failure of RGC axons to recognize their target at low concentrations (0.5, 1 μM), and the failure of the axons to make a caudal turn in the mid-diencephalon at higher concentration (5 μM). Thus, ADAM10 function is required for RGC axon guidance at two key guidance decisions. Finally, molecular inhibition of ADAM10 function by electroporating dn-adam10 in the brain neuroepithelium causes defects in RGC axon target recognition (57%) and/or defects in caudal turn (12%), as seen with the pharmacological inhibitor. In contrast, molecular inhibition of ADAM10 within the RGC axons has no effect. Conclusions: These data argue strongly that ADAM10 acts cell non-autonomously within the neuroepithelium to regulate the guidance of RGC axons. This study shows for the first time that a metalloproteinase acts in a cell non-autonomous fashion to direct vertebrate axon growth. It will provide important insights into candidate molecules that could be used to reform nerve connections if destroyed because of injury or disease.
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