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Gilbert R.J.C.,University of Oxford | Mikelj M.,University of Ljubljana | Dalla Serra M.,National Research Council Italy | Froelich C.J.,NorthShore University HealthSystem Research Institute | And 2 more authors.
Cellular and Molecular Life Sciences | Year: 2013

Recent work on the MACPF/CDC superfamily of pore-forming proteins has focused on the structural analysis of monomers and pore-forming oligomeric complexes. We set the family of proteins in context and highlight aspects of their function which the direct and exclusive equation of oligomers with pores fails to explain. Starting with a description of the distribution of MACPF/CDC proteins across the domains of life, we proceed to show how their evolutionary relationships can be understood on the basis of their structural homology and re-evaluate models for pore formation by perforin, in particular. We furthermore highlight data showing the role of incomplete oligomeric rings (arcs) in pore formation and how this can explain small pores generated by oligomers of proteins belonging to the family. We set this in the context of cell biological and biophysical data on the proteins' function and discuss how this helps in the development of an understanding of how they act in processes such as apicomplexan parasites gliding through cells and exiting from cells. © 2012 Springer Basel AG.

Wang E.E.,NorthShore University HealthSystem | Dyne P.L.,View Medical | Du H.,NorthShore University HealthSystem Research Institute
Academic Emergency Medicine | Year: 2011

Objectives: The development of robust Accreditation Council for Graduate Medical Education (ACGME) systems-based practice (SBP) training and validated evaluation tools has been generally challenging for emergency medicine (EM) residency programs. The purpose of this paper is to report the results of a consensus workgroup session of the 2010 Council of Emergency Medicine Residency Directors (CORD) Academic Assembly with the following objectives: 1) to discuss current and preferred local and regional methods for teaching and assessing SBP and 2) to develop consensus within the CORD community using the modified Delphi method with respect to EM-specific SBP domains and link these domains to specific SBP educational and evaluative methods. Methods: Consensus was developed using a modified Delphi method. Previously described taxonomy generation methodology was used to create a SBP taxonomy of EM domain-specific knowledge, skills, and attitudes (KSA). The steps in the process consisted of: 1) an 11-question preconference survey, 2) a vetting process conducted at the 2010 CORD Academic Assembly, and 3) the development and ranking of domain-specific SBP educational activities and evaluation criteria for the specialty of EM. Results: Rank-order lists were created for preferred SBP education and evaluation methods. Expert modeling, informal small group discussion, and formal small group activities were considered to be the optimal methods to teach SBP. Kruskal-Wallis testing revealed that these top three items were rated significantly higher than self-directed learning projects and lectures (p = 0.0317). Post hoc test via permutation testing revealed that the difference was significant between expert modeling and formal small group activity (adjusted p = 0.028), indicating that expert modeling was rated significantly higher than formal small group activity. Direct observation methods were the preferred methods for evaluation. Multiple barriers to training and evaluation were elucidated. We developed a consensus taxonomy of domains that were felt to be most essential and reflective of the practice of EM: multitasking, disposition, and patient safety. Learning formats linked to the domains were created and specific examples of local best practices collected. Domain-specific anchors of observable actions for the three domains were created. Conclusions: This consensus process resulted in the development of a taxonomy of EM-specific domains for teaching and observable tasks for evaluating SBP. The concept of SBP is interlinked with the other general competencies and difficult to separate. Rather than develop specific SBP evaluation tools to measure the competency directly, SBP competency evaluation should be considered one element of a coordinated effort to teach and evaluate the six ACGME general competencies. © 2011 by the Society for Academic Emergency Medicine.

Silva A.K.,University of Chicago | Lapin B.,NorthShore University HealthSystem Research Institute | Yao K.A.,NorthShore University HealthSystem | Song D.H.,University of Chicago | Sisco M.,NorthShore University HealthSystem
Annals of Surgical Oncology | Year: 2015

Background: Women with breast cancer are increasingly choosing to undergo contralateral prophylactic mastectomy (CPM) despite questionable survival benefit and limited data on added risks. Little is known about differences in perioperative complications between women who undergo bilateral mastectomy (BM) versus unilateral mastectomy (UM) with reconstruction. Methods: The American College of Surgeons National Surgery Quality Improvement Program Participant Use Files (2005–2013) were used to identify women with unilateral breast cancer who underwent UM or BM with reconstruction. Adjusted 30-day complications were compared between UM and BM groups using logistic regression models. Results: A total of 20,501 patients were identified, of whom 35.3 % underwent BM. Of these, 84.3 % had implant reconstruction and 15.7 % had autologous reconstruction. For all women, BM was associated with longer hospital stays (adjusted odds ratio [aOR] 1.98–2.09, p < 0.001) and a higher transfusion rate than UM (aOR 2.52–3.06, p < 0.001). BM with implant reconstruction was associated with a modestly increased reoperation rate (aOR 1.15, p = 0.029). BM with autologous reconstruction was associated with a higher wound disruption rate (aOR 2.51, p = 0.015). Surgical site infections, prosthesis failure, and medical complications occurred at similar rates in UM and BM groups. Conclusions: CPM is associated with significant increases in some, but not all, surgical site complications. CPM does not increase the likelihood of medical complications, which are generally infrequent. © 2015, Society of Surgical Oncology.

Northshore University Healthsystem Research Institute and Siemens AG | Date: 2014-04-02

A method for operating a Magnetic Resonance (MR) imaging system including generating radio frequency (RF) excitation pulses in a volume of patient anatomy that includes a patients heart to provide subsequent acquisition of associated RF echo data and generating slice select magnetic field gradients for phase encoding and readout RF data acquisition in the volume of patient anatomy. The method also includes acquiring a plurality of slices of an image of the volume of patient anatomy within a plurality of cycles representing time period between successive beats of the patients heart. The method also includes causing, by a control processor, accelerated acquisition of two or more slices of the plurality of slices within a quiescent phase of each of the plurality of cycles. The method further includes applying, by the control processor, one or more saturation areas proximate to a target volume of the patient anatomy.

Halin S.,Umea University | Rudolfsson S.H.,Umea University | Doll J.A.,NorthShore University HealthSystem Research Institute | Crawford S.E.,NorthShore University HealthSystem Research Institute | And 2 more authors.
Neoplasia | Year: 2010

Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis but whether it has additional effects on the tumor microenvironment is largely unexplored. We show that overexpression of PEDF in orthotopic MatLyLu rat prostate tumors increased tumor macrophage recruitment. The fraction of macrophages expressing inducible nitric oxide synthase, a marker of cytotoxic M1 macrophages, was increased, suggesting that PEDF could enhance antitumor immunity. In addition, PEDF overexpression reduced vascular growth both in the tumor and in the surrounding normal tissue, slowed tumor growth, and decreased lymph node metastasis. Contrary, extratumoral lymphangiogenesis was increased. PEDF expression is, for reasons unknown, often decreased or lost during prostate tumor progression. When AT-1 rat prostate tumor cells, expressing high levels of PEDF messenger RNA (mRNA) and protein, were injected into the prostate, PEDF is markedly downregulated, suggesting that factors in the microenvironment suppressed its expression. One such factor could be macrophage-derived tumor necrosis factor α (TNFα). A fraction of the accumulating macrophages expressed TNFα, and TNFα treatment downregulated the expression of PEDF protein and mRNA in prostate AT-1 tumor cells in vitro and in the rat ventral prostate in vivo. PEDF apparently has multiple effects in prostate tumors: it suppresses angiogenesis and metastasis, but it also causes macrophage accumulation. Accumulating macrophages may inhibit tumor growth, but they may also suppress PEDF and enhance lymph angiogenesis and, in this way, eventually enhance tumor growth. © 2010 Neoplasia Press, Inc.

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