Digital Commons Network^™

Emergence Of Bimodal Cell Population Responses From The Interplay Between Analog Single-Cell Signaling And Protein Expression Noise., Marc R Birtwistle, Jens Rauch, Anatoly Kiyatkin, Edita Aksamitiene, Maciej Dobrzyński, Jan B. Hoek, Walter Kolch, Babatunde A Ogunnaike, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Cell-to-cell variability in protein expression can be large, and its propagation through signaling networks affects biological outcomes. Here, we apply deterministic and probabilistic models and biochemical measurements to study how network topologies and cell-to-cell protein abundance variations interact to shape signaling responses.

RESULTS: We observe bimodal distributions of extracellular signal-regulated kinase (ERK) responses to epidermal growth factor (EGF) stimulation, which are generally thought to indicate bistable or ultrasensitive signaling behavior in single cells. Surprisingly, we find that a simple MAPK/ERK-cascade model with negative feedback that displays graded, analog ERK responses at a single cell level can explain the experimentally …

Early Versus Delayed Decompression For Traumatic Cervical Spinal Cord Injury: Results Of The Surgical Timing In Acute Spinal Cord Injury Study (Stascis)., Michael G Fehlings, Alex R. Vaccaro, Jefferson R Wilson, Anoushka Singh, David W Cadotte, James Harrop, Bizhan Aarabi, Christopher Shaffrey, Marcel Dvorak, Charles Fisher, Paul Arnold, Eric M Massicotte, Stephen Lewis, Raja Rampersaud

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical SCI.

METHODS: We performed a multicenter, international, prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study: STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change …

Guided Self-Help Concreteness Training As An Intervention For Major Depression In Primary Care: A Phase Ii Randomized Controlled Trial., E. R. Watkins, R. S. Taylor, R. Byng, C. Baeyens, R. Read, K. Pearson, L. Watson

Peninsula Medical School

BACKGROUND: The development of widely accessible, effective psychological interventions for depression is a priority. This randomized trial provides the first controlled data on an innovative cognitive bias modification (CBM) training guided self-help intervention for depression. METHOD: One hundred and twenty-one consecutively recruited participants meeting criteria for current major depression were randomly allocated to treatment as usual (TAU) or to TAU plus concreteness training (CNT) guided self-help or to TAU plus relaxation training (RT) guided self-help. CNT involved repeated practice at mental exercises designed to switch patients from an unhelpful abstract thinking habit to a helpful concrete thinking habit, thereby targeting …

Osteochondral Tissue Engineering: Scaffolds, Stem Cells And Applications., Patcharakamon Nooeaid, Vehid Salih, Justus P. Beier, Aldo R. Boccaccini

Peninsula Dental School

Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral …

Analysis And Validation Of A Parkinson's Disease Register As A Recruitment Tool For Clinical Studies., Camille Carroll, Amy Palmer, Christine Cosby, John Zajicek

Peninsula Medical School

Promotion of research is a key strategy of the National Health Service (NHS). Currently, many patients are not afforded the opportunity to participate in clinical studies. A register of research-interested patients has the potential to maximise inclusivity. We have established a register of research-interested patients with Parkinson's disease within the South West of England, with pragmatic inclusion criteria and multiple recruitment routes. We undertook an analysis of the register, investigation of its utility as a recruitment tool and a survey of recruiters. There were 529 active participants; 30% were self-referred and 70% were recruited by a healthcare practitioner. Response rate …

Oral Health And Pathology: A Macrophage Account., Rebecca Merry, Louise Belfield, Paul Mcardle, Andrew Mclennan, Stjohn Crean, Andrew Foey

School of Biomedical Sciences

Macrophages are present in healthy oral mucosa and their numbers increase dramatically during disease. They can exhibit a diverse range of phenotypes characterised as a functional spectrum from pro-inflammatory to anti-inflammatory (regulatory) subsets. This review illustrates the role of these subsets in the oral inflammatory disease lichen planus, and the immunosuppressive disease oral squamous cell carcinoma (SCC). We conclude that the role of macrophages in driving progression in oral disease identifies them as potential therapeutic targets for a range of oral pathologies.

High Metabolic Potential May Contribute To The Success Of St131 Uropathogenic Escherichia Coli., Tarek M. Gibreel, Andrew R. Dodgson, John Cheesbrough, Frederick J. Bolton, Andrew J. Fox, Mathew Upton

School of Biomedical Sciences

Uropathogenic Escherichia coli (UPEC) is the predominant cause of urinary tract infection in both hospital and community settings. The recent emergence of multidrug-resistant clones like the O25b:H4-ST131 lineage represents a significant threat to health, and numerous studies have explored the virulence potential of these organisms. Members of the ST131 clone have been described as having variable carriage of key virulence factors, and it has been suggested that additional unidentified factors contribute to virulence. Here we demonstrated that ST131 isolates have high metabolic potential and biochemical profiles that distinguish them from isolates of many other sequence types (STs). A collection of …

Prevalence And Risk Factors Of Major Depressive Disorder In Hiv/Aids As Seen In Semi-Urban Entebbe District, Uganda, Eugene Kinyanda, Susan Hoskins, Juliet Nakku, Saira Nawaz, Vikram Patel

Dartmouth Scholarship

Background:

Not much is known about the risk factors of major depressive disorder (MDD) in HIV/AIDS in the African socio-cultural context. Therefore a study was undertaken to examine the prevalence and risk factors of MDD in HIV/AIDS in semi-urban Uganda.

Methods:

A cross-sectional study was undertaken among 618 respondents attending two HIV clinics in Uganda.

Results:

Prevalence of MDD was 8.1%. Factors associated with MDD at univariate analysis only were female gender, family history of mental illness, negative coping style, alcohol dependency disorder, food insecurity and stress; not associated with MDD were social support, neurocognitive impairment, CD4 counts and BMI. …

Partition Decoupling For Multi-Gene Analysis Of Gene Expression Profiling Data, Rosemary Braun, Gregory Leibon, Scott Pauls, Daniel Rockmore

Dartmouth Scholarship

Background:

Multi-gene interactions likely play an important role in the development of complex phenotypes, and relationships between interacting genes pose a challenging statistical problem in microarray analysis, since the genes involved in these interactions may not exhibit marginal differential expression. As a result, it is necessary to develop tools that can identify sets of interacting genes that discriminate phenotypes without requiring that the classification boundary between phenotypes be convex.

Results:

We describe an extension and application of a new unsupervised statistical learning technique, known as the Partition Decoupling Method (PDM), to gene expression microarray data. This method may be used …

Cd2ap Regulates Sumoylation Of Cin85 In Podocytes, Irini Tossidou, Rainer Niedenthal, Malte Klaus, Beina Teng, Kirstin Worthmann, Benjamin King, Kevin Peterson

Dartmouth Scholarship

Podocytes are highly differentiated and polarized epithelial cells located on the visceral side of the glomerulus. They form an indispensable component of the glomerular filter, the slit diaphragm, formed by several transmembrane proteins and adaptor molecules. Disruption of the slit diaphragm can lead to massive proteinuria and nephrotic syndrome in mice and humans. CD2AP is an adaptor protein that is important for the maintenance of the slit diaphragm. Together with its paralogue, CIN85, CD2AP belongs to a family of adaptor proteins that are primarily described as being involved in endocytosis and downregulation of receptor tyrosine kinase activity. We have shown …

A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional …

Rice Consumption Contributes To Arsenic Exposure In Us Women, Diane Gilbert-Diamond, Kathryn L. Cottingham, Joann F. Gruber, Tracy Punshon, Vicki Sayarath, A. Jay Gandolfi, Emily R. Baker, Brian P. Jackson, Carol L. Folt, Margaret R. Karagas

Dartmouth Scholarship

Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n …

A Perceptual Metric For Photo Retouching, Eric Kee, Hany Farid

Dartmouth Scholarship

In recent years, advertisers and magazine editors have been widely criticized for taking digital photo retouching to an extreme. Impossibly thin, tall, and wrinkle- and blemish-free models are routinely splashed onto billboards, advertisements, and magazine covers. The ubiquity of these unrealistic and highly idealized images has been linked to eating disorders and body image dissatisfaction in men, women, and children. In response, several countries have considered legislating the labeling of retouched photos. We describe a quantitative and perceptually meaningful metric of photo retouching. Photographs are rated on the degree to which they have been digitally altered by explicitly modeling and …

Project P.A.T.H.S. In Hong Kong: New Curriculum In Response To Adolescent Developmental Issues, Hing Keung Ma, Daniel T. L. Shek, Joav Merrick

Pediatrics Faculty Publications

No abstract.

Histone Deacetylase Inhibitor Valproic Acid Suppresses The Growth And Increases The Androgen Responsiveness Of Prostate Cancer Cells., Yu-Wei Chou, Nagendra K. Chaturvedi, Shougiang Ouyang, Fen-Fen Lin, Dharam Kaushik, Jue Wang, Isaac Kim, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments …

Effects Of Prenatal Food And Micronutrient Supplementation On Child Growth From Birth To 54 Months Of Age: A Randomized Trial In Bangladesh, Ashraful Islam Khan, Iqbal Kabir, Eva-Charlotte Ekström, Kajsa Åsling-Monemi, Dewan Shamsul Alam, Edward A. Frongillo Jr., Md Yunus, Shams Arifeen, Lars-Åke Persson

Faculty Publications

Background: There is a lack of information on the optimal timing of food supplementation to malnourished pregnant women and possible combined effects of food and multiple micronutrient supplementations (MMS) on their offspring's growth. We evaluated the effects of prenatal food and micronutrient interventions on postnatal child growth. The hypothesis was that prenatal MMS and early invitation to food supplementation would increase physical growth in the offspring during 0-54 months and a combination of these interventions would further improve these outcomes.

Methods: In the large, randomized MINIMat trial (Maternal and Infant Nutrition Interventions in Matlab), Bangladesh, 4436 pregnant women were enrolled …

Changes In Spirituality Partly Explain Health-Related Quality Of Life Outcomes After Mindfulness-Based Stress Reduction., Jeffrey M Greeson, Daniel M Webber, Moria J Smoski, Jeffrey G Brantley, Andrew G Ekblad, Edward C Suarez, Ruth Quillian Wolever

College of Science & Mathematics Departmental Research

Mindfulness-Based Stress Reduction is a secular behavioral medicine program that has roots in meditative spiritual practices. Thus, spirituality may partly explain Mindfulness-Based Stress Reduction outcomes. Participants (N = 279; M (SD) age = 45(12); 75% women) completed an online survey before and after an 8-week Mindfulness-Based Stress Reduction program. Structural equation modeling was used to test the hypothesis that, following Mindfulness-Based Stress Reduction, the relationship between enhanced mindfulness and improved health-related quality of life is mediated by increased daily spiritual experiences. Changes in both spirituality and mindfulness were significantly related to improvement in mental health. Although the initial mediation hypothesis …

An Integrative Model Of Excessive Reassurance Seeking And Negative Feedback Seeking In The Development And Maintenance Of Depression., Lyndsay E Evraire, David J A Dozois

Psychology Publications

Depression and interpersonal dysfunction are inextricably linked. Interpersonal behaviors in individuals with depression, specifically excessive reassurance seeking (ERS) and negative feedback seeking (NFS), have recently emerged as possible risk factors for interpersonal rejection and future depression. However, existing models integrating ERS and NFS in individuals with depression lack empirical support and fail to provide an adequate explanation for the negative social and psychological consequences that concurrent ERS and NFS create. The proposed model, based on the bias and accuracy literature in close relationships, suggests that individuals with depression desire and elicit global enhancement (through ERS) and specific verification (through NFS) …

Perceived Parental Attachment And Achievement Motivation, Mena Bal, Imants Barušs

Psychology

A significant amount of research in attachment theory has been devoted to factors affecting academic achievement, but less attention has been given to the role of attachment in the relation between academic achievement and achievement motivation. The current preliminary study examined the role of perceived parental attachment in achievement motivation. Self-report data obtained from the Parental Attachment Questionnaire, Achievement Goals Questionnaire, and the Performance Failure Appraisal Inventory were collected from 50 university students with a mean age of 18.8 yr. Correlation and regression analyses indicated that parental facilitation of independence correlated significantly and negatively with fear of failure. Results yielded …

The Evolution Of Cauterization: From The Hot Iron To The Bovie., Michelle F. Deleon, Ms, Charles J. Yeo, Md, Pinckney Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

The Bovie electrocautery has become a fundamental tool of modern-day surgery, particularly for its integral role in hemostasis, yet despite this landmark invention and its widespread use, there is very little said about the man behind the machine: William T. Bovie. It would be thousands of years from the inception of cautery in medicine until the birth of Dr. Bovie and his device. However, his work in biophysics and collaboration with Dr. Harvey Cushing would revolutionize surgical practice in the early 20th century and forever ingrain his name into the field of surgery.

Relationship Between Vancomycin Trough Concentrations And Nephrotoxicity: A Prospective Multicenter Trial, John A. Bosso, Jean Nappi, Celeste Rudisill, Marlea Wellein, P Brandon Bookstaver, Jenna Swindler, Patrick D. Mauldin

Faculty Publications

Several single-center studies have suggested that higher doses of vancomycin, aimed at producing trough concentrations of >15 mg/liter, are associated with increased risk of nephrotoxicity. We prospectively assessed the relative incidence of nephrotoxicity in relation to trough concentration in patients with documented methicillin-resistant Staphylococcus aureus (MRSA) infections at seven hospitals throughout South Carolina. Adult patients receiving vancomycin for at least 72 h with at least one vancomycin trough concentration determined under steady-state conditions were prospectively studied. The relationship between vancomycin trough concentrations of >15 mg/ml and the occurrence of nephrotoxicity was assessed using univariate and multivariate analyses, controlling for age, …

Widespread Regulation Of Mirna Biogenesis At The Dicer Step By The Cold-Inducible Rna-Binding Protein, Rbm3, Julie Pilotte, Esther E. Dupont-Versteegden, Peter W. Vanderklish

Physical Therapy Faculty Publications

MicroRNAs (miRNAs) play critical roles in diverse cellular events through their effects on translation. Emerging data suggest that modulation of miRNA biogenesis at post-transcriptional steps by RNA-binding proteins is a key point of regulatory control over the expression of some miRNAs and the cellular processes they influence. However, the extent and conditions under which the miRNA pathway is amenable to regulation at posttranscriptional steps are poorly understood. Here we show that RBM3, a cold-inducible, developmentally regulated RNA-binding protein and putative protooncogene, is an essential regulator of miRNA biogenesis. Utilizing miRNA array, Northern blot, and PCR methods, we observed that over …

B1b Lymphocyte-Derived Antibodies Control Borrelia Hermsii Independent Of Fcα/Μ Receptor And In The Absence Of Host Cell Contact., Matthew J. Colombo, David Abraham, Akira Shibuya, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

The critical role of IgM in controlling pathogen burden has been demonstrated in a variety of infection models. In the murine model of Borrelia hermsii infection, IgM is necessary and sufficient for the rapid clearance of bacteremia. Convalescent, but not naïve, B1b cells generate a specific IgM response against B. hermsii, but the mechanism of IgM-mediated protection is unknown. Here, we show that neither Fcα/μR, a high-affinity receptor for IgM, nor IgM-dependent complement activation is required for controlling B. hermsii. Bacteria in diffusion chambers with a pore size impermeable to cells were killed when diffusion chambers were implanted into either …

Factors Affecting Growth In Infants With Single Ventricle Physiology: A Report From The Pediatric Heart Network Infant Single Ventricle Trial., Richard V. Williams, Victor Zak, Chitra Ravishankar, Karen Altmann, Jeffrey Anderson, Andrew M. Atz, Carolyn Dunbar-Masterson, Nancy Ghanayem, Linda Lambert, Karen Lurito, Barbara Medoff-Cooper, Renee Margossian, Victoria L. Pemberton, Jennifer Russell, Mario Stylianou, Daphne Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To describe growth patterns in infants with single ventricle physiology and determine factors influencing growth.

STUDY DESIGN: Data from 230 subjects enrolled in the Pediatric Heart Network Infant Single Ventricle Enalapril Trial were used to assess factors influencing change in weight-for-age z-score (z) from study enrollment (0.7 ± 0.4 months) to pre-superior cavopulmonary connection (SCPC; 5.1 ± 1.8 months, period 1) and pre-SCPC to final study visit (14.1 ± 0.9 months, period 2). Predictor variables included patient characteristics, feeding regimen, clinical center, and medical factors during neonatal (period 1) and SCPC hospitalizations (period 2). Univariate regression analysis was performed, …

Probiotic Bacterial Strains Differentially Modulate Macrophage Cytokine Production In A Strain-Dependent And Cell Subset-Specific Manner., N. Habil, W. Al-Murrani, J. Beal, A. D. Foey

School of Biomedical Sciences

Gut mucosal macrophages play a pivotal role in driving mucosal immune responses, resulting in either activation of inflammatory immune responses to pathogenic challenge or tolerance to beneficial luminal contents such as food and commensal bacteria. Macrophage responses elicited are dependent on tissue environment and the resulting cell subset, where homeostatic macrophages resemble the M2 macrophage subset and inflammatory macrophages resemble M1s. Probiotics can modulate macrophage function with outcome dependent on subset present. Using a THP-1 monocyte cell line-derived model of CD14high/low M1 and M2 macrophages, the aim of this study was to investigate the immunomodulatory effects of a panel of …

Switches, Excitable Responses And Oscillations In The Ring1b/Bmi1 Ubiquitination System., Lan K Nguyen, Javier Muñoz-García, Helene Maccario, Aaron Ciechanover, Walter Kolch, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots …

Autoimmune Enteropathy With A Cd8+ Cd7- T-Cell Small Bowel Intraepithelial Lymphocytosis: Case Report And Literature Review, Shrinivas Bishu, Violeta Arsenescu, Eun Y. Lee, H. David Vargas, Willem J. S. De Villiers, Razvan Arsenescu

Surgery Faculty Publications

Background

Adult onset autoimmune enteropathy (AIE) is a rare condition characterized by diarrhea refractory to dietary therapy diagnosed in patients with evidence of autoimmune conditions. Auto-antibodies to gut epithelial cells and other tissues are commonly demonstrated. Despite increasing awareness, the pathogenesis, histologic, immunologic and clinical features of AIE remain uncertain. There remains controversy regarding the diagnostic criteria, the frequency and types of auto-antibodies and associated autoimmune conditions, and the extent and types of histologic and immunologic abnormalities. CD4+ T-cells are thought to at least responsible for this condition; whether other cell types, including B- and other T-cell subsets are involved, …

Planning Combinatorial Disulfide Cross-Links For Protein Fold Determination, Fei Xiong, Alan M Friedman, Chris Bailey-Kellogg

Dartmouth Scholarship

Fold recognition techniques take advantage of the limited number of overall structural organizations, and have become increasingly effective at identifying the fold of a given target sequence. However, in the absence of sufficient sequence identity, it remains difficult for fold recognition methods to always select the correct model. While a native-like model is often among a pool of highly ranked models, it is not necessarily the highest-ranked one, and the model rankings depend sensitively on the scoring function used. Structure elucidation methods can then be employed to decide among the models based on relatively rapid biochemical/biophysical experiments.

A Brief Overview Of Adolescent Developmental Problems In Hong Kong, Daniel T. L. Shek, Hing Keung Ma, Rachel C. F. Sun

Pediatrics Faculty Publications

Several adolescent developmental problems in Hong Kong are briefly reviewed in this paper. First, rising adolescent substance abuse trends are described. Second, Internet use problems and Internet addiction among young people are examined. Third, worrying trends in adolescent sexuality are identified. Fourth, phenomena on bullying among young people are reviewed. Finally, phenomena related to adolescent materialistic orientation are focused upon. With reference to these adolescent developmental problems, possible solutions are briefly discussed particularly with reference to the ecological perspective. It is argued that the related scientific literature provides useful pointers for designing the curriculum in the extension phase of the …

Percutaneous Implantation Of The Edwards Sapien Transcatheter Heart Valve For Conduit Failure In The Pulmonary Position: Early Phase 1 Results From An International Multicenter Clinical Trial., Damien Kenny, Ziyad M. Hijazi, Saibal Kar, John Rhodes, Michael Mullen, Raj Makkar, Girish S. Shirali, Mark Fogel, John Fahey, Mary G. Heitschmidt, Christopher Cain

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: The purpose of this study was to evaluate the safety and effectiveness of the Edwards SAPIEN transcatheter heart valve (Edwards Lifesciences LLC, Irvine, California) in the pulmonary position in patients with moderate to severe pulmonary regurgitation with or without stenosis.

BACKGROUND: Transcatheter pulmonary valve replacement is evolving, but to date, experience has been limited to the Melody valve (Medtronic Inc., Minneapolis, Minnesota).

METHODS: Eligible patients with dysfunctional right ventricle-to-pulmonary artery conduits were screened if body weight was ≥35 kg and the in situ conduit diameter was ≥16 mm and ≤24 mm. Standardized implantation and follow-up protocols were used.

RESULTS: …