Medicine and Health Sciences Commons^™

Predictors Of Perioperative Blood Loss In Total Joint Arthroplasty., Jai Hyung Park, Mohammad R Rasouli, S M Javad Mortazavi, Anthony T Tokarski, Mitchell G Maltenfort, Javad Parvizi

Rothman Institute Papers

UNLABELLED: UPDATE The print version of this article has errors that have been corrected in the online version of this article. In the Materials and Methods section, the sentence that reads as "During the study period, our institution offered preoperative autologous blood donation to all patients who were scheduling for total joint arthroplasty with a hemoglobin level of no less than 11 mg/dL or a hematocrit level of at least 33%." in the print version now reads as "During the study period, our institution offered preoperative autologous blood donation to all patients who were scheduling for total joint arthroplasty with …

Recommendations For High-Priority Research On Cancer-Related Fatigue In Children And Adults., Andrea M. Barsevick, Michael R. Irwin, Pamela Hinds, Andrew Miller, Ann Berger, Paul Jacobsen, Sonia Ancoli-Israel, Bryce B Reeve, Karen Mustian, Ann O'Mara, Jin-Shei Lai, Michael Fisch, David Cella

Department of Medical Oncology Faculty Papers

Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current …

Randomized Clinical Trial Examining Duration Of Voucher-Based Reinforcement Therapy For Cocaine Abstinence., Kimberly C Kirby, Carolyn M Carpenedo, Karen L Dugosh, Beth J Rosenwasser, Lois A Benishek, Alicia Janik, Rachel Keashen, Elena Bresani, Kenneth Silverman

College of Science & Mathematics Departmental Research

BACKGROUND: This is the first study to systematically manipulate duration of voucher-based reinforcement therapy (VBRT) to see if extending the duration increases abstinence during and following VBRT.

METHODS: We randomized cocaine-dependent methadone-maintained adults to Standard (12 weeks; n=62) or Extended (36 weeks; n=68) VBRT and provided escalating voucher amounts contingent upon urinalysis verification of cocaine abstinence. Urinalysis was scheduled at least every 2 weeks during the 48-week study and more frequently during VBRT (3/week) and 12 weeks of Aftercare (2/week).

RESULTS: Extended VBRT produced longer durations of continuous cocaine abstinence during weeks 1-24 (5.7 vs 2.7 weeks; p=0.003) and proportionally …

Diabetes And Prostate Cancer Screening In Black And White Men, Maureen Sanderson, Jay H. Fowke, Loren Lipworth, Xijing Han, Flora Ukoli, Ann L. Coker, William J. Blot, Margaret K. Hargreaves

CRVAW Faculty Journal Articles

PURPOSE: Prior studies conducted primarily among white men find a reduced risk of prostate cancer associated with time since developing diabetes. While biologic explanations are plausible, the association may in part arise from more frequent prostate cancer screening among those with a diabetes diagnosis. The purpose of the present study was to investigate the association between diabetes and prostate cancer screening.

METHODS: We examined differences in prostate cancer screening (prostate-specific antigen and/or digital rectal examination) testing practices after a diabetes diagnosis among lower-income persons living in the southeastern United States and enrolled in the Southern Community Cohort Study between 2002 …

Sexual Coercion And Sexual Violence At First Intercourse Associated With Sexually Transmitted Infections, Corrine M. Williams, Emily R. Clear, Ann L. Coker

CRVAW Faculty Journal Articles

BACKGROUND: Violence against women has been associated with subsequent risky sexual behaviors and sexually transmitted infections (STIs). We explored whether sexual coercion or violence at first intercourse was associated with self-reported STIs.

METHODS: Using nationally representative data from the 2006 to 2010 National Survey of Family Growth, we analyzed female respondents aged 18 to 44 (n = 9466) who answered questions on coercion at first intercourse (wantedness, voluntariness, and types of force used) and STIs using logistic regression analyses. We explored degrees of coercion, which we label as neither, sexual coercion (unwanted or nonphysical force), or sexual violence (involuntary or …

Retinal Angiogenesis Suppression Through Small Molecule Activation Of P53, Sai H. Chavala, Younghee Kim, Laura Tudisco, Valeria Cicatiello, Till Milde, Nagaraj Kerur, Nidia Claros, Susan Yanni, Victor H. Guaiquil, William W. Hauswirth, John S. Penn, Shahin Rafii, Sandro De Falco, Thomas C. Lee, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels …

Long-Term Outcomes Of Ranibizumab Therapy For Diabetic Macular Edema: The 36-Month Results From Two Phase Iii Trials: Rise And Ride., David M. Brown, Quan Dong Nguyen, Dennis M. Marcus, David S. Boyer, Sunil Patel, Leonard Feiner, Patricio G. Schlottmann, Amy Chen Rundle, Jiameng Zhang, Roman G. Rubio, Anthony P. Adamis, Jason S. Ehrlich, J. Jill Hopkins

Journal Articles: Ophthalmology

PURPOSE: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME).

DESIGN: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection-controlled for 2 years.

PARTICIPANTS: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥ 275 μm on optical coherence tomography.

METHODS: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser …

Evidence-Based Practice In Occupational Therapy Curricula., Tina Angelis, Edd, Otr/L, Thomas G Dimarco, Susan Toth-Cohen, Edd, Otr/L

Department of Occupational Therapy Faculty Papers

The purpose of this study is to describe currently used educational strategies for teaching evidence-based practice (EBP) in entry-level master's degree occupational therapy programs in the United States. Fifty-eight entry-level occupational therapy program directors completed a survey. Results showed that occupational therapy programs consistently use a wide variety of EBP resources for teaching EBP including database searches, literature reviews, and the development of a research proposal. Less commonly used strategies include the use of case stories and journal clubs. The current study provides a baseline of existing strategies taught in entry level programs that may be built upon to gather …

A Population-Based Case–Control Study Of Urinary Arsenic Species And Squamous Cell Carcinoma In New Hampshire, Usa, Diane Gilbert-Diamond, Zhigang Li, Ann E. Perry, Steven K. Spencer, A Jay Gandolfi, Margaret R. Karagas

Dartmouth Scholarship

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States.

Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population.

Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and …

Generating Hypotheses About Care Needs Of High Utilizers: Lessons From Patient Interviews., Dawn B Mautner, Hauchie Pang, Jeffrey C Brenner, Judy A Shea, Kennen S Gross, Rosemary Frasso, Carolyn C Cannuscio

Department of Family & Community Medicine Faculty Papers

Informed by a largely secondary and quantitative literature, efforts to improve care and outcomes for complex patients with high levels of emergency and hospital-based health care utilization have offered mixed results. This qualitative study identifies psychosocial factors and life experiences described by these patients that may be important to their care needs. Semi-structured interviews were conducted with 19 patients of the Camden Coalition of Healthcare Providers' Care Management Team. Investigators coded transcripts using a priori and inductively-derived codes, then identified 3 key themes: (1) Early-life instability and traumas, including parental loss, unstable or violent relationships, and transiency, informed many participants' …

Outdated Dermatologic Drug Samples And Obligations To The Patient., Jordan Wang, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

CASE SCENARIO

A 37-year-old man with a slightly raised, red, scaly patch on his left arm is seen in the clinic of an academic teaching hospital by a young dermatologist. Following examination and biopsy, he is found to have squamous cell carcinoma in situ. The patient was recently laid off from work and had lost access to his health insurance. He is struggling to make ends meet for his family, so it would be difficult for him to cover any extraneous health-related expenses. Upon relaying this information to the dermatologist, the patient is provided with a full course of 5-fluorouracil …

Factors Impacting Echocardiographic Imaging After The Fontan Procedure: A Report From The Pediatric Heart Network Fontan Cross-Sectional Study., Richard V. Williams, Renee Margossian, Minmin Lu, Andrew M. Atz, Timothy J. Bradley, Michael Jay Campbell, Steven D. Colan, Dianne Gallagher, Wyman W. Lai, Gail D. Pearson, Ashwin Prakash, Girish S. Shirali, Meryl S. Cohen, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Echocardiographic image quality in Fontan survivors may be limited by a variety of factors. We sought to describe echocardiographic quality and factors associated with study quality in subjects participating in the Pediatric Heart Network Fontan Cross-Sectional Study. Echocardiograms were obtained at 7 clinical sites using a standard protocol. Quality grading and analysis were performed by a core laboratory. Univariate and multivariable modeling were performed to assess factors associated with quality and ability to obtain images sufficient for prespecified quantitative analysis. A total of 543 echocardiograms were obtained. The quality of echocardiograms improved over the duration of the study. The great …

Analyzing The Health Care Cost Curve: A Case Study., Robert D. Lieberthal

College of Population Health Faculty Papers

This case study uses data from a self-insured employer plan to perform an analysis into the properties of the health care cost curve. The analysis shows that one statistical property of the health care cost curve is that costs rise continuously, not on an annual or monthly basis. Graphical analysis indicates that managed care techniques used to restrain costs can also smooth utilization, producing the continuously growing cost curve observed. The analysis further illustrates that there is no one "cost curve"-analysis must be segmented by population. Finally, the power of predictive models to fit the cost curve varies by population. …

Multi-Criteria Decision Analysis As An Innovative Approach To Managing Zoonoses: Results From A Study On Lyme Disease In Canada, Cécile Aenishaenslin, Valérie Hongoh, Hassane D. Cissé, Anne Gatewood Hoen

Dartmouth Scholarship

ackground: Zoonoses are a growing international threat interacting at the human-animal-environment interface and call for transdisciplinary and multi-sectoral approaches in order to achieve effective disease management. The recent emergence of Lyme disease in Quebec, Canada is a good example of a complex health issue for which the public health sector must find protective interventions. Traditional preventive and control interventions can have important environmental, social and economic impacts and as a result, decision-making requires a systems approach capable of integrating these multiple aspects of interventions. This paper presents the results from a study of a multi-criteria decision analysis (MCDA) approach for …

Impact Of Treatment Response Metrics On Photodynamic Therapy Planning And Outcomes In A Three-Dimensional Model Of Ovarian Cancer, Sriram Anbil, Imran Rizvi, Jonathan P. Celli, Nermina Alagic, Brian W. Pogue, Tayyaba Hasan

Dartmouth Scholarship

Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching …

De Novo Frameshift Mutation In Asxl3 In A Patient With Global Developmental Delay, Microcephaly, And Craniofacial Anomalies., Darrell L. Dinwiddie, Sarah E. Soden, Carol J. Saunders, Neil A. Miller, Emily G. Farrow, Laurie D. Smith, Stephen F. Kingsmore

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Currently, diagnosis of affected individuals with rare genetic disorders can be lengthy and costly, resulting in a diagnostic odyssey and in many patients a definitive molecular diagnosis is never achieved despite extensive clinical investigation. The recent advent and use of genomic medicine has resulted in a paradigm shift in the clinical molecular genetics of rare diseases and has provided insight into the causes of numerous rare genetic conditions. In particular, whole exome and genome sequencing of families has been particularly useful in discovering de novo germline mutations as the cause of both rare diseases and complex disorders.

CASE PRESENTATION: …

A Study On The Geophylogeny Of Clinical And Environmental Vibrio Cholerae In Kenya, J. Kiiru, A. Mutreja, A. A. Mohamed, R. W. Kimani, J. Mwituria, R. O. Sanaya, J. Muyodi, Gunturu Revathi, J. Parkhill, N. Thomson, G. Dougan, S. Kariuki

Pathology, East Africa

Cholera remains a significant public health challenge in many sub-Saharan countries including Kenya. We have performed a combination of phylogenetic and phenotypic analysis based on whole genome DNA sequences derived from 40 environmental and 57 clinical V. cholerae from different regions of Kenya isolated between 2005 and 2010. Some environmental and all clinical isolates mapped back onto wave three of the monophyletic seventh pandemic V. cholerae El Tor phylogeny but other environmental isolates were phylogenetically very distinct. Thus, the genomes of the Kenyan V. cholerae O1 El Tor isolates are clonally related to other El Tor V. cholerae isolated elsewhere …

Psmb9 Codon 60 Polymorphisms Have No Impact On The Activity Of The Immunoproteasome Catalytic Subunit B1i Expressed In Multiple Types Of Solid Cancer, Ji Eun Park, Lin Ao, Zachary Miller, Kyungbo Kim, Ying Wu, Eun Ryoung Jang, Eun Young Lee, Kyung Bo Kim, Wooin Lee

Pharmaceutical Sciences Faculty Publications

The proteasome is a key regulator of cellular protein homeostasis and is a clinically validated anticancer target. The immunoproteasome, a subtype of proteasome expressed mainly in hematopoietic cells, was initially recognized for its role in antigen presentation during the immune response. Recently, the immunoproteasome has been implicated in several disease conditions including cancer and autoimmune disorders, but many of the factors contributing to these pathological processes remain unknown. In particular, the codon 60 polymorphism of the PSMB9 gene encoding the β1i immunoproteasome catalytic subunit has been investigated in the context of a variety of diseases. Despite this, previous studies have …

The Flexible Fairness: Equality, Earned Entitlement, And Self-Interest, Chunliang Feng, Yi Luo, Ruolei Gu, Lucas S. Broster, Xueyi Shen, Tengxiang Tian, Yue-Jia Luo, Frank Krueger

Behavioral Science Faculty Publications

The current study explored whether earned entitlement modulated the perception of fairness in three experiments. A preliminary resource earning task was added before players decided how to allocate the resource they jointly earned. Participants' decision in allocation, their responses to equal or unequal offers, whether advantageous or disadvantageous, and subjective ratings of fairness were all assessed in the current study. Behavioral results revealed that participants proposed more generous offers and showed enhanced tolerance to disadvantageous unequal offers from others when they performed worse than their presumed "partners," while the reverse was true in the better-performance condition. The subjective ratings also …

Mapping Disease At An Approximated Individual Level Using Aggregate Data: A Case Study Of Mapping New Hampshire Birth Defects, Xun Shi, Stephanie Miller, Kevin Mwenda, Akikazu Onda

Dartmouth Scholarship

Limited by data availability, most disease maps in the literature are for relatively large and subjectively-defined areal units, which are subject to problems associated with polygon maps. High resolution maps based on objective spatial units are needed to more precisely detect associations between disease and environmental factors. Method: We propose to use a Restricted and Controlled Monte Carlo (RCMC) process to disaggregate polygon-level location data to achieve mapping aggregate data at an approximated individual level. RCMC assigns a random point location to a polygon-level location, in which the randomization is restricted by the polygon and controlled by the background (e.g., …

Molecular Signatures In Urologic Tumors, Spencer Larkin, Natasha Kyprianou

Surgery Faculty Publications

Urologic tumors continue to represent a huge fraction of cancer cases in the United States, with over 376,310 estimated new diagnoses in 2013. As with many types of tumors, urologic tumors vary greatly in their phenotype, ranging from minimally invasive to malignancies possessing great metastatic potential. The increasing need for more efficient and less invasive methods of cancer detection, as well as the ability to predict severity of the disease phenotype is readily evident--yet reliable methods remain elusive in a clinical setting today. Comprehensive panels of gene clusters are being developed toward the generation of molecular signatures in order to …

Aspirin And Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage In Hyperhomocysteinemic Women., Pratip Chakraborty, Sayani Banerjee, Piyali Saha, Shyam Sundar Nandi, Sunita Sharma, Sourendra K. Goswami, Baidyanath Chakravarty, Syed N. Kabir

Journal Articles: Cellular & Integrative Physiology

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 …

Patterning In Placental 11-B Hydroxysteroid Dehydrogenase Methylation According To Prenatal Socioeconomic Adversity, Allison A. Appleton, David A. Armstrong, Corina Lesseur, Joyce Lee, James F. Padbury, Barry M. Lester

Dartmouth Scholarship

Background:

Prenatal socioeconomic adversity as an intrauterine exposure is associated with a range of perinatal outcomes although the explanatory mechanisms are not well understood. The development of the fetus can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol thereby protecting the developing fetus from this exposure. This gene is regulated by DNA methylation, and this methylation and the expression it controls has been shown to be susceptible to a variety of stressors from …

Patchy ‘Coherence’: Using Normalization Process Theory To Evaluate A Multi-Faceted Shared Decision Making Implementation Program (Magic), Amy Lloyd, Natalie Joseph-Williams, Adrian Edwards, Andrew Rix, Glyn Elwyn

Dartmouth Scholarship

Implementing shared decision making into routine practice is proving difficult, despite considerable interest from policy-makers, and is far more complex than merely making decision support interventions available to patients. Few have reported successful implementation beyond research studies. MAking Good Decisions In Collaboration (MAGIC) is a multi-faceted implementation program, commissioned by The Health Foundation (UK), to examine how best to put shared decision making into routine practice. In this paper, we investigate healthcare professionals' perspectives on implementing shared decision making during the MAGIC program, to examine the work required to implement shared decision making and to inform future efforts. The MAGIC …

Patients With Atrial Fibrillation Undergoing Total Joint Arthroplasty Increase Hospital Burden., Vinay K Aggarwal, Eric H Tischler, Zachary D Post, Ian Kane, Fabio R Orozco, Alvin Ong

Rothman Institute Papers

BACKGROUND: More than 3 million people in the United States have atrial fibrillation, most of whom are being managed with anticoagulation therapy for life. The goal of the present study was to examine the effect of chronic anticoagulation therapy on patients with atrial fibrillation who undergo total joint arthroplasty.

METHODS: We retrospectively reviewed all patients undergoing aseptic primary or revision total joint arthroplasty at our facility from March 2007 to August 2011. One hundred and sixty-one patients with atrial fibrillation (Group A) were compared with 161 matched controls (Group B). A total of 112 hips and 210 knees underwent 239 …

Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell

Department of Cancer Biology Faculty Papers

The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated. Herein, genome-wide expression profiling conducted of 17β-estradiol-treated castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1 determines estrogen-dependent gene expression for 88% of estrogen-responsive genes in vivo. In addition, expression profiling of 17β-estradiol-stimulated cyclin …

Samuel D. Gross, M.D. (1805-1884): An Innovator, Even In Death., Peter R. Bucciarelli, B.S., John C. Kairys, Md, Ernest L. Rosato, Md, Charles J. Yeo, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

Dr. Samuel Gross' contributions to the field of surgery are well known and range from numerous clinical advances to pioneering scholarship and professional activities. Dr. Gross was ceaselessly ambitious and even remarked in his autobiography that his ‘‘conviction has always been that is far better for a man to wear out than to rust out.’’1 It is through this frame of motivation that Dr. Gross lived his life.

The Effect Of Malnutrition On Patients Undergoing Elective Joint Arthroplasty., Ronald Huang, Md, Max Greenky, Bs, Glenn J. Kerr, Md, Mathew S. Austin, Md, Javad Parvizi, Md, Frcs

Rothman Institute Papers

Malnutrition has been linked to serious complications in patients undergoing elective total joint arthroplasty (TJA). This study prospectively evaluated 2,161 patients undergoing elective TJA for malnutrition as defined by either an abnormal serum albumin or transferrin. The overall incidence of malnutrition was 8.5% (184 of 2,161) and the rate of overall complications in the malnourished group was 12% as compared to 2.9% in patients with normal parameters (P55years-old undergoing TJA and is associated with a significant increase in post-operative complications.

Occupational Exposure To Hepatitis C Virus: Early T-Cell Responses In The Absence Of Seroconversion In A Longitudinal Cohort Study., Theo Heller, Jens Martin Werner, Fareed Rahman, Eishiro Mizukoshi, Yuji Sobao, Ann Marie Gordon, Arlene Sheets, Averell H. Sherker, Ellen Kessler, Kathleen S. Bean, Steven K. Herrine, M'Lou Stevens, James Schmitt, Barbara Rehermann

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: T-cell responses have been described in seronegative patients who test negative for hepatitis C virus (HCV) RNA despite frequent HCV exposure. However, the cross-sectional design of those studies did not clarify whether T cells were indeed induced by low-level HCV exposure without seroconversion or whether they resulted from regular acute infection with subsequent antibody loss.

METHODS: Over a 10-year period, our longitudinal study recruited 72 healthcare workers with documented HCV exposure. We studied viremia and antibody and T-cell responses longitudinally for 6 months.

RESULTS: All healthcare workers remained negative for HCV RNA and antibodies. However, 48% developed proliferative T-cell …

Conservation Of Structure And Mechanism By Trm5 Enzymes., Thomas Christian, Howard Gamper, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Enzymes of the Trm5 family catalyze methyl transfer from S-adenosyl methionine (AdoMet) to the N¹ of G37 to synthesize m¹ G37-tRNA as a critical determinant to prevent ribosome frameshift errors. Trm5 is specific to eukaryotes and archaea, and it is unrelated in evolution from the bacterial counterpart TrmD, which is a leading anti-bacterial target. The successful targeting of TrmD requires detailed information on Trm5 to avoid cross-species inhibition. However, most information on Trm5 is derived from studies of the archaeal enzyme Methanococcus jannaschii (MjTrm5), whereas little information is available for eukaryotic enzymes. Here we use human Trm5 (Homo sapiens; HsTrm5) …