Digital Commons Network^™

Nodal And Planar Cell Polarity Signaling Cooperate To Regulate Zebrafish Convergence And Extension Gastrulation Movements, Margot L.K. Williams, Lilianna Solnica-Krezel

Open Access Publications

During vertebrate gastrulation, convergence and extension (C and E) of the primary anteroposterior (AP) embryonic axis is driven by polarized mediolateral (ML) cell intercalations and is influenced by AP axial patterning. Nodal signaling is essential for patterning of the AP axis while planar cell polarity (PCP) signaling polarizes cells with respect to this axis, but how these two signaling systems interact during C and E is unclear. We find that the neuroectoderm of Nodal-deficient zebrafish gastrulae exhibits reduced C and E cell behaviors, which require Nodal signaling in both cell- and non-autonomous fashions. PCP signaling is partially active in Nodal-deficient …

Cd4+ T Cell Expression Of The Il-10 Receptor Is Necessary For Facial Motoneuron Survival After Axotomy, Elizabeth M Runge, Abhirami K Iyer, Deborah O Setter, Felicia M Kennedy, Virginia M Sanders, Kathryn J Jones

Open Access Publications

BACKGROUND: After peripheral nerve transection, facial motoneuron (FMN) survival depends on an intact CD4+ T cell population and a central source of interleukin-10 (IL-10). However, it has not been determined previously whether CD4+ T cells participate in the central neuroprotective IL-10 cascade after facial nerve axotomy (FNA).

METHODS: Immunohistochemical labeling of CD4+ T cells, pontine vasculature, and central microglia was used to determine whether CD4+ T cells cross the blood-brain barrier and enter the facial motor nucleus (FMNuc) after FNA. The importance of IL-10 signaling in CD4+ T cells was assessed by performing adoptive transfer of IL-10 receptor beta (IL-10RB)-deficient …

The Histone Deacetylase Complex Midac Regulates A Neurodevelopmental Gene Expression Program To Control Neurite Outgrowth, Baisakhi Mondal, Hongjian Jin, Satish Kallappagoudar, Yurii Sedkov, Tanner Martinez, Monica F. Sentmanat, Greg J. Poet, Chunliang Li, Yiping Fan, Shondra M. Pruett-Miller, Hans-Martin Herz

Open Access Publications

The mitotic deacetylase complex (MiDAC) is a recently identified histone deacetylase (HDAC) complex. While other HDAC complexes have been implicated in neurogenesis, the physiological role of MiDAC remains unknown. Here, we show that MiDAC constitutes an important regulator of neural differentiation. We demonstrate that MiDAC functions as a modulator of a neurodevelopmental gene expression program and binds to important regulators of neurite outgrowth. MiDAC upregulates gene expression of pro-neural genes such as those encoding the secreted ligands SLIT3 and NETRIN1 (NTN1) by a mechanism suggestive of H4K20ac removal on promoters and enhancers. Conversely, MiDAC inhibits gene expression by reducing H3K27ac …

Covid-19 Clinical Trials: A Primer For The Cardiovascular And Cardio-Oncology Communities, Bonnie Ky, Douglas L Mann

Open Access Publications

The COVID-19 pandemic has resulted in a proliferation of clinical trials that are designed to slow the spread of SARS-CoV-2, the virus that causes COVID-19. The overwhelming majority of cardiovascular and cancer patients are at increased risk for SARS-CoV-2 infection; accordingly, the cardiovascular and cardio-oncology communities are playing a major role in caring for COVID-19 patients. Many of the therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, drugs that were not effective in Ebola patients, or treatments for malaria that were developed decades ago, and are unlikely to be familiar to the …

Reinforcement Biases Subsequent Perceptual Decisions When Confidence Is Low, A Widespread Behavioral Phenomenon, Armin Lak, Emily Hueske, Junya Hirokawa, Paul Masset, Torben Ott, Anne E. Urai, Tobias H. Donner, Matteo Carandini, Susumu Tonegawa, Naoshige Uchida, Adam Kepecs

Open Access Publications

Learning from successes and failures often improves the quality of subsequent decisions. Past outcomes, however, should not influence purely perceptual decisions after task acquisition is complete since these are designed so that only sensory evidence determines the correct choice. Yet, numerous studies report that outcomes can bias perceptual decisions, causing spurious changes in choice behavior without improving accuracy. Here we show that the effects of reward on perceptual decisions are principled: past rewards bias future choices specifically when previous choice was difficult and hence decision confidence was low. We identified this phenomenon in six datasets from four laboratories, across mice, …

Damage To The Shortest Structural Paths Between Brain Regions Is Associated With Disruptions Of Resting-State Functional Connectivity After Stroke, Joseph C Griffis, Nicholas V Metcalf, Maurizio Corbetta, Gordon L Shulman

Open Access Publications

Focal brain lesions disrupt resting-state functional connectivity, but the underlying structural mechanisms are unclear. Here, we examined the direct and indirect effects of structural disconnections on resting-state functional connectivity in a large sample of sub-acute stroke patients with heterogeneous brain lesions. We estimated the impact of each patient's lesion on the structural connectome by embedding the lesion in a diffusion MRI streamline tractography atlas constructed using data from healthy individuals. We defined direct disconnections as the loss of direct structural connections between two regions, and indirect disconnections as increases in the shortest structural path length between two regions that lack …

Sex Differences In Cancer Mechanisms, Joshua B Rubin, Joseph S Lagas, Lauren Broestl, Jasmin Sponagel, Nathan Rockwell, Gina Rhee, Sarah F Rosen, Si Chen, Robyn S Klein, Princess Imoukhuede, Jingqin Luo

Open Access Publications

We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex …

Human Ipsc-Derived Neurons And Cerebral Organoids Establish Differential Effects Of Germline Nf1 Gene Mutations, Corina Anastasaki, Michelle L Wegscheid, Kelly Hartigan, Jason B Papke, Nathan D Kopp, Jiayang Chen, Olivia Cobb, Joseph D Dougherty, David H Gutmann

Open Access Publications

Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder caused by a spectrum of distinct germline NF1 gene mutations, traditionally viewed as equivalent loss-of-function alleles. To specifically address the issue of mutational equivalency in a disease with considerable clinical heterogeneity, we engineered seven isogenic human induced pluripotent stem cell lines, each with a different NF1 patient NF1 mutation, to identify potential differential effects of NF1 mutations on human central nervous system cells and tissues. Although all mutations increased proliferation and RAS activity in 2D neural progenitor cells (NPCs) and astrocytes, we observed striking differences between NF1 mutations on 2D NPC …

A Phase Ii Study Of Axalimogene Filolisbac For Patients With Previously Treated, Unresectable, Persistent/Recurrent Loco-Regional Or Metastatic Anal Cancer, Cathy Eng, Marwan Fakih, Manik Amin, Van Morris, Howard S. Hochster, Patrick M. Boland, Hope Uronis

Open Access Publications

Squamous cell carcinoma of the anorectal canal (SCCA) is a rare HPV-related malignancy that is steadily increasing in incidence. A high unmet need exists for patients with persistent loco-regional and metastatic disease. Axalimogene filolisbac (ADXS11-001) is an investigational immunotherapy that stimulates tumor-specific responses against HPV-associated cancers, and has demonstrated benefit in metastatic cervical cancer. We conducted this single-arm, multicenter, phase 2 trial in patients with persistent/recurrent, loco-regional or metastatic SCCA. Patients received ADXS11-001, 1 × 10

Divergent Effects Of Dnmt3a And Tet2 Mutations On Hematopoietic Progenitor Cell Fitness, Elizabeth L Ostrander, Ashley C Kramer, Cates Mallaney, Hamza Celik, Won Kyun Koh, Jake Fairchild, Emily Haussler, Christine R C Zhang, Grant A Challen

Open Access Publications

The DNA methylation regulators DNMT3A and TET2 are recurrently mutated in hematological disorders. Despite possessing antagonistic biochemical activities, loss-of-function murine models show overlapping phenotypes in terms of increased hematopoietic stem cell (HSC) fitness. Here, we directly compared the effects of these mutations on hematopoietic progenitor function and disease initiation. In contrast to Dnmt3a-null HSCs, which possess limitless self-renewal in vivo, Tet2-null HSCs unexpectedly exhaust at the same rate as control HSCs in serial transplantation assays despite an initial increase in self-renewal. Moreover, loss of Tet2 more acutely sensitizes hematopoietic cells to the addition of a common co-operating mutation (Flt3

Assessment Of Biological Role And Insight Into Druggability Of The Plasmodium Falciparum Protease Plasmepsin V, Alexander J Polino, Armiyaw S Nasamu, Jacquin C Niles, Daniel E Goldberg

Open Access Publications

Upon infecting a red blood cell (RBC), the malaria parasite

Tbk1 And Ikkε Act Redundantly To Mediate Sting-Induced Nf-Κb Responses In Myeloid Cells, Katherine R Balka, Amber M Smith, Jonathan J Miner, Et Al

Open Access Publications

Stimulator of Interferon Genes (STING) is a critical component of host innate immune defense but can contribute to chronic autoimmune or autoinflammatory disease. Once activated, the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS)-STING pathway induces both type I interferon (IFN) expression and nuclear factor-κB (NF-κB)-mediated cytokine production. Currently, these two signaling arms are thought to be mediated by a single upstream kinase, TANK-binding kinase 1 (TBK1). Here, using genetic and pharmacological approaches, we show that TBK1 alone is dispensable for STING-induced NF-κB responses in human and mouse immune cells, as well as in vivo. We further demonstrate that …

Proportion Of Upper Extremity Musculoskeletal Disorders Attributable To Personal And Occupational Factors: Results From The French Pays De La Loire Study, Aboubakari Nambiema, Sandrine Bertrais, Julie Bodin, Natacha Fouquet, Agnès Aublet-Cuvelier, Bradley Evanoff, Alexis Descatha, Yves Roquelaure

Open Access Publications

BACKGROUND: Upper extremity musculoskeletal disorders (UEMSD) are one of the most common and costly occupational health problems. We aimed to assess the population-attributable fraction (PAF) of personal and occupational risk factors associated with incident UEMSD in a working population.

METHODS: From 2002 to 2005, a random sample of 3710 workers from the Pays de la Loire region in France, aged 20-59 were included by occupational physicians (OPs). Between 2007 and 2010, 1611 workers were re-examined by their OPs. Subjects free from UEMSD at baseline were included in this study (1275 workers, mean age: 38.2 years). Cox regression models with equal …

Cd300lf Is The Primary Physiologic Receptor Of Murine Norovirus But Not Human Norovirus, Vincent R. Graziano, Forrest C. Walker, Elizabeth A. Kennedy, Ebrahim Hassan, Arthur S. Kim, Megan T. Baldridge, Et Al.

Open Access Publications

Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. The bona fide receptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for MNoV. Interestingly, its paralogue CD300ld was also sufficient for MNoV infection in vitro. Here we explored whether CD300lf is the sole physiologic receptor in vivo and whether HNoV can use a CD300 ortholog as an entry receptor. We report that both CD300ld and CD300lf are sufficient for infection by diverse MNoV strains …

Care Of Patients With Pulmonary Arterial Hypertension During The Coronavirus (Covid-19) Pandemic, John J Ryan, Lana Melendres-Groves, Roham T Zamanian, Ronald J Oudiz, Murali Chakinala, Erika B Rosenzweig, Mardi Gomberg-Maitland

Open Access Publications

The COVID-19 pandemic presents many unique challenges when caring for patients with pulmonary hypertension. The COVID-19 pandemic has altered routine standard of care practice and the acute management particularly for those patients with pulmonary arterial hypertension, where pulmonary arterial hypertension-specific treatments are used. It is important to balance the ongoing care and evaluation of pulmonary arterial hypertension patients with "exposure risk" to COVID-19 for patients coming to clinic or the hospital. If there is a morbidity and mortality benefit from starting pulmonary arterial hypertension therapies, for example in a patient with high-likelihood of pulmonary arterial hypertension, then it remains important …

Glanzmann Thrombasthenia: Genetic Basis And Clinical Correlates, Juliana Perez Botero, Kristy Lee, Brian R. Branchford, Paul F. Bray, Kathleen Freson, Michele P. Lambert, Minjie Luo, Shruthi Mohan, Justyne E Ross, Wolfgang Bergmeier, Jorge Di Paola, Clingen Platelet Disorder Variant Curation Expert Panel

Open Access Publications

Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet aggregation caused by quantitative or qualitative defects in integrins αIIb and β3. These integrins are encoded by the

Endoscopic Extraction Of A Buried Bumper By Use Of An Insulation-Tipped Knife And A Sphincterotome, Michael Weaver, Vladimir Kushnir

Open Access Publications

No abstract provided.

Assessing Clinical Research Coordinator Knowledge Of Good Clinical Practice: An Evaluation Of The State Of The Art And A Test Validation Study, James M Dubois, Jessica T Mozersky, Alison L Antes, Kari Baldwin, Michelle Jenkerson

Open Access Publications

This paper describes the development and validation of a new 32-item test of knowledge of good clinical practice (GCP) administered to 625 clinical research coordinators. GCP training is mandated by study sponsors including the US National Institutes of Health. The effectiveness of training is rarely assessed, and the lack of validated tests is an obstacle to assessment. The GCP knowledge test was developed following evaluation of two existing widely used GCP tests to ensure it accurately reflects the content of current training. The final GCP knowledge test demonstrated good reliability (

Insights Into The Intracellular Localization, Protein Associations And Artemisinin Resistance Properties Of Plasmodium Falciparum K13, Nina F. Gnädig, Barbara H. Stokes, Rachel L. Edwards, Gavreel F. Kalantarov, Kim C. Heimsch, Michal Kuderjavy, Audrey Crane, Marcus C. S. Lee, Judith Straimer, Katja Becker, Ilya N. Trakht, Audrey R. Odom John, Sachel Mok, David A. Fidock

Open Access Publications

The emergence of artemisinin (ART) resistance in Plasmodium falciparum intra-erythrocytic parasites has led to increasing treatment failure rates with first-line ART-based combination therapies in Southeast Asia. Decreased parasite susceptibility is caused by K13 mutations, which are associated clinically with delayed parasite clearance in patients and in vitro with an enhanced ability of ring-stage parasites to survive brief exposure to the active ART metabolite dihydroartemisinin. Herein, we describe a panel of K13-specific monoclonal antibodies and gene-edited parasite lines co-expressing epitope-tagged versions of K13 in trans. By applying an analytical quantitative imaging pipeline, we localize K13 to the parasite endoplasmic reticulum, Rab-positive …

Analytical Performance Of An Immunoprofiling Assay Based On Rna Models, Ian Schillebeeckx, Jon R Armstrong, Jason T Forys, Jeffrey Hiken, Jon Earls, Kevin C Flanagan, Tiange Cui, Jarret I Glasscock, David N Messina, Eric J Duncavage

Open Access Publications

As immuno-oncology drugs grow more popular in the treatment of cancer, better methods are needed to quantify the tumor immune cell component to determine which patients are most likely to benefit from treatment. Methods such as flow cytometry can accurately assess the composition of infiltrating immune cells; however, they show limited use in formalin-fixed, paraffin-embedded (FFPE) specimens. This article describes a novel hybrid-capture RNA sequencing assay, ImmunoPrism, that estimates the relative percentage abundance of eight immune cell types in FFPE solid tumors. Immune health expression models were generated using machine learning methods and used to uniquely identify each immune cell …

Chordoma With Lung Metastases At Initial Presentation Of A Pediatric Patient, Samiat Agunbiade, Ayman Nada, Sudhir Bhimaniya, Matthew T Whitehead, Eman S Mahdi

Open Access Publications

Chordomas are rare, slow growing malignant tumors derived from notochord remnants that can arise anywhere along the neuronal axis. Chordomas are particularly rare in patients under 20 years of age and tend to be intracranial in location, as opposed to sacrococcygeal in adults. Metastasis at initial presentation is uncommon in all age groups and is exceedingly rare in the absence of local recurrence of the primary tumor. We report a case of advanced clival chordoma with marked nasopharyngeal disease extension and lung metastases at the time of presentation in a pediatric patient.

Pre-Exposure Prophylaxis For Preventing Acquisition Of Hiv: A Cross-Sectional Study Of Patients, Prescribers, Uptake, And Spending In The United States, 2015-2016, Stephanie S. Chan, Andre R. Chappel, Karen E. Joynt Maddox, Karen W. Hoover, Ya-Lin A. Huang, Weiming Zhu, Stacy M. Cohen, Pamela W. Klein, Nancy De Lew

Open Access Publications

BACKGROUND: In 2015, there were approximately 40,000 new HIV diagnoses in the United States. Pre-exposure prophylaxis (PrEP) is an effective strategy that reduces the risk of HIV acquisition; however, uptake among those who can benefit from it has lagged. In this study, we 1) compared the characteristics of patients who were prescribed PrEP with individuals newly diagnosed with HIV infection, 2) identified the specialties of practitioners prescribing PrEP, 3) identified metropolitan statistical areas (MSAs) within the US where there is relatively low uptake of PrEP, and 4) reported median amounts paid by patients and third-party payors for PrEP.

METHODS AND …

Association Between Immune-Related Adverse Events And Recurrence-Free Survival Among Patients With Stage Iii Melanoma Randomized To Receive Pembrolizumab Or Placebo: A Secondary Analysis Of A Randomized Clinical Trial, Alexander M M Eggermont, Leonel Hernandez-Aya, Et Al

Open Access Publications

Importance: Whether immune-related adverse events (irAEs) indicate drug activity in patients treated with immune checkpoint inhibitors remains unknown.

Objective: To investigate the association between irAEs and recurrence-free survival (RFS) in the double-blind EORTC 1325/KEYNOTE-054 clinical trial comparing pembrolizumab therapy and placebo for the treatment of patients with high-risk stage III melanoma.

Design, Setting, and Participants: A total of 1019 adults with stage III melanoma were randomly assigned on a 1:1 ratio to receive treatment with pembrolizumab therapy or placebo. Eligible patients were adults 18 years and older with complete resection of cutaneous melanoma metastatic to lymph nodes, classified with stage …

Reduced Neurosteroid Potentiation Of Gabaa Receptors In Epilepsy And Depolarized Hippocampal Neurons, Suchitra Joshi, William H Roden, Jaideep Kapur, Laura A Jansen

Open Access Publications

OBJECTIVE: Neurosteroids regulate neuronal excitability by potentiating γ-aminobutyric acid type-A receptors (GABARs). In animal models of temporal lobe epilepsy, the neurosteroid sensitivity of GABARs is diminished and GABAR subunit composition is altered. We tested whether similar changes occur in patients with epilepsy and if depolarization-induced increases in neuronal activity can replicate this effect.

METHODS: We determined GABAR α4 subunit expression in cortical tissue resected from pediatric epilepsy patients. Modulation of human GABARs by allopregnanolone and Ro15-4513 was measured in Xenopus oocytes using whole-cell patch clamp. To extend the findings obtained using tissue from epilepsy patients, we evaluated GABAR expression and …

Double Lung Transplantation For End-Stage Kartagener Syndrome: A Case Report And Literature Review, Bo Wang, Xinghua Zhang, Wenyang Jiang, Jie Huang, Jingyu Chen, Daniel Kreisel, Jose Luis J Danguilan, Michael Hsin, Huiqing Lin

Open Access Publications

Kartagener syndrome (KS) is an autosomal recessive disorder characterized by situs inversus, paranasal sinusitis and bronchiectasis. We report the successful use of double lung transplant (DLTx) to treat end-stage KS. A 49-year-old Han woman was admitted to Renmin Hospital (Wuhan University, China) in September 2017 with a ≥15 year history of chronic productive cough that had worsened during the past year. Clinical examination and imaging investigations revealed respiratory failure and situs inversus consistent with KS. The patient was successfully treated with DLTx involving bilateral bronchial anastomoses. DLTx is a feasible treatment option for end-stage KS.

Role Of Yttrium-90 Selective Internal Radiation Therapy In The Treatment Of Liver-Dominant Metastatic Colorectal Cancer: An Evidence-Based Expert Consensus Algorithm, D Rohan Jeyarajah, Maria B Majella Doyle, N Joseph Espat, Paul D Hansen, David A Iannitti, Joseph Kim, Thavam Thambi-Pillai, Brendan C. Visser

Open Access Publications

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a …

Differences In The Chitinolytic Activity Of Mammalian Chitinases On Soluble And Insoluble Substrates, Benjamin A Barad, Lin Liu, Roberto E Diaz, Ralp Basilio, Steven J Van Dyken, Richard M Locksley, James S Fraser

Open Access Publications

Chitin is an abundant polysaccharide used by many organisms for structural rigidity and water repulsion. As such, the insoluble crystalline structure of chitin poses significant challenges for enzymatic degradation. Acidic mammalian chitinase, a processive glycosyl hydrolase, is the primary enzyme involved in the degradation of environmental chitin in mammalian lungs. Mutations to acidic mammalian chitinase have been associated with asthma, and genetic deletion in mice increases morbidity and mortality with age. We initially set out to reverse this phenotype by engineering hyperactive acidic mammalian chitinase variants. Using a screening approach with commercial fluorogenic substrates, we identified mutations with consistent increases …

Mining Reported Adverse Events Induced By Potential Opioid-Drug Interactions, Jinzhao Chen, Gaoyu Wu, Andrew Michelson, Zachary Vesoulis, Jennifer Bogner, John D Corrigan, Philip R O Payne, Fuhai Li

Open Access Publications

OBJECTIVE: Opioid-based analgesia is routinely used in clinical practice for the management of pain and alleviation of suffering at the end of life. It is well-known that opioid-based medications can be highly addictive, promoting not only abuse but also life-threatening overdoses. The scope of opioid-related adverse events (AEs) beyond these well-known effects remains poorly described. This exploratory analysis investigates potential AEs from drug-drug interactions between opioid and nonopioid medications (ODIs).

MATERIALS AND METHODS: In this study, we conduct an initial exploration of the association between ODIs and severe AEs using millions of AE reports available in FDA Adverse Event Reporting …

Pharmacologic Inhibition Of Rgd-Binding Integrins Ameliorates Fibrosis And Improves Function Following Kidney Injury, Jeannine Basta, Lynn Robbins, Lisa Stout, Michael J Prinsen, David W Griggs, Michael Rauchman

Open Access Publications

Fibrosis is a final common pathway for many causes of progressive chronic kidney disease (CKD). Arginine-glycine-aspartic acid (RGD)-binding integrins are important mediators of the pro-fibrotic response by activating latent TGF-β at sites of injury and by providing myofibroblasts information about the composition and stiffness of the extracellular matrix. Therefore, blockade of RGD-binding integrins may have therapeutic potential for CKD. To test this idea, we used small-molecule peptidomimetics that potently inhibit a subset of RGD-binding integrins in a murine model of kidney fibrosis. Acute kidney injury leading to fibrosis was induced by administration of aristolochic acid. Continuous subcutaneous administration of CWHM-12, …

Use Of Extended Realities In Cardiology, Michael K Southworth, Jonathan R Silva, Jennifer N Avari Silva

Open Access Publications

Recent miniaturization of electronic components and advances in image processing software have facilitated the entry of extended reality technology into clinical practice. In the last several years, the number of applications in cardiology has multiplied, with many promising to become standard of care. We review many of these applications in the areas of patient and physician education, cardiac rehabilitation, pre-procedural planning and intraprocedural use. The rapid integration of these approaches into the many facets of cardiology suggests that they will one day become an every-day part of physician practice.