Digital Commons Network^™

Effect Of Oxidative Stress On Protein Tyrosine Phosphatase 1b In Scleroderma Dermal Fibroblasts., Pei-Suen Tsou, Nadine N. Talia, Adam J. Pinney, Ann Kendzicky, Sonsoles Piera-Velazquez, Sergio A. Jimenez, James R. Seibold, Kristine Phillips, Alisa E Koch

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Platelet-derived growth factor (PDGF) and its receptor, PDGFR, promote fibrosis in systemic sclerosis (SSc; scleroderma) dermal fibroblasts, and such cells in scleroderma skin lesions produce excessive reactive oxygen species (ROS). PDGFR is phosphorylated upon PDGF stimulation, and is dephosphorylated by protein tyrosine phosphatases (PTPs), including PTP1B. This study was undertaken to determine whether the thiol-sensitive PTP1B is affected by ROS in SSc dermal fibroblasts, thereby enhancing the phosphorylation of PDGFR and synthesis of type I collagen. This study also sought to investigate the effect of a thiol antioxidant, N-acetylcysteine (NAC), in SSc.

METHODS: Fibroblasts were isolated from the skin …

Does The Load-Sharing Classification Predict Ligamentous Injury, Neurological Injury, And The Need For Surgery In Patients With Thoracolumbar Burst Fractures?: Clinical Article., Kristen Radcliff, Christopher K Kepler, Todd A Rubin, Motasem Maaieh, Alan S Hilibrand, James Harrop, Jeffrey A Rihn, Todd J Albert, Alexander R Vaccaro

Department of Orthopaedic Surgery Faculty Papers

OBJECT: The load-sharing score (LSS) of vertebral body comminution is predictive of results after short-segment posterior instrumentation of thoracolumbar burst fractures. Some authors have posited that an LSS > 6 is predictive of neurological injury, ligamentous injury, and the need for surgical intervention. However, the authors of the present study hypothesized that the LSS does not predict ligamentous or neurological injury.

METHODS: The prospectively collected spinal cord injury database from a single institution was queried for thoracolumbar burst fractures. Study inclusion criteria were acute (< 24 hours) burst fractures between T-10 and L-2 with preoperative CT and MRI. Flexion-distraction injuries and pathological fractures were excluded. Four experienced spine surgeons determined the LSS and posterior ligamentous complex (PLC) integrity. Neurological status was assessed from a review of the medical records.

RESULTS: Forty-four patients were included in the study. There were 4 patients for whom all observers …

Resolution Of Bilateral Ptosis After Reduction Of Unilaterally Elevated Intraocular Pressure In A Child With Axenfeld-Reiger Spectrum Disorder., Ketki Soin, Alex V. Levin

Wills Eye Hospital Papers

We report a 9-month-old boy with bilateral pseudoptosis associated with elevated IOP. The patient had previously undergone bilateral trabeculectomies and Ahmed tube placement and right cataract extraction and penetrating keratoplasty. At presentation, the right eye IOP was 24 mm Hg and the left eye IOP was 32 mm Hg. Approximately 2 weeks after dorzolamide was added to the treatment regimen for the left eye, the mother reported that the ptosis had resolved. We suggest several explanations for the resolution of the ptosis.

Technical Desiderata For The Integration Of Genomic Data Into Electronic Health Records., Daniel R Masys, Gail P Jarvik, Neil F Abernethy, Nicholas R Anderson, George J Papanicolaou, Dina N Paltoo, Mark A Hoffman, Isaac S Kohane, Howard P Levy

Manuscripts, Articles, Book Chapters and Other Papers

The era of "Personalized Medicine," guided by individual molecular variation in DNA, RNA, expressed proteins and other forms of high volume molecular data brings new requirements and challenges to the design and implementation of Electronic Health Records (EHRs). In this article we describe the characteristics of biomolecular data that differentiate it from other classes of data commonly found in EHRs, enumerate a set of technical desiderata for its management in healthcare settings, and offer a candidate technical approach to its compact and efficient representation in operational systems.

Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Mitochondria Take Center Stage., Shey-Shing Sheu, Robert T Dirksen, Edward N Pugh

Center for Translational Medicine Faculty Papers

No abstract provided.

Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Molecular Identities Of Mitochondrial Ca2+ Influx Mechanism: Updated Passwords For Accessing Mitochondrial Ca2+-Linked Health And Disease., Jin O-Uchi, Shi Pan, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

No abstract provided.

Management Of Hyperglycemia In Type 2 Diabetes: A Patient-Centered Approach: Position Statement Of The American Diabetes Association (Ada) And The European Association For The Study Of Diabetes (Easd)., Silvio E Inzucchi, Richard M Bergenstal, John B Buse, Michaela Diamant, Ele Ferrannini, Michael Nauck, Anne L Peters, Apostolos Tsapas, Richard Wender, David R. Matthews

Department of Family & Community Medicine Faculty Papers

No abstract provided.

The Quest For The Perfect Prostate Biopsy Continues, Leonard G. Gomella

Kimmel Cancer Center Faculty Papers

No abstract provided.

Acceptability Of Narratives To Promote Colorectal Cancer Screening In An Online Community, Kevin O Hwang, Amber W Trickey, Amanda L Graham, Eric J Thomas, Richard L Street, Jennifer L Kraschnewski, Sally W Vernon

Faculty, Staff and Student Publications

OBJECTIVE: To assess the acceptability of narratives to promote colorectal cancer (CRC) screening among members of an online weight loss community.

METHOD: Members of online weight loss community completed an Internet survey in 2010. Multiple logistic regression models examined demographic and attitudinal correlates of interest in sharing and receiving CRC screening narratives.

RESULTS: Participants (n=2386) were 92% female with mean (SD) age 58 (6) years; 68% were up-to-date with CRC screening. Among those who were up-to-date, 39% were interested in sharing their narratives with other members. African-Americans were more likely than other racial groups to be interested in sharing narratives …

Collaborative Learning About E-Health For Mental Health Professionals And Service Users In A Structured Anonymous Online Short Course: Pilot Study., Emily J. Ashurst, Ray B. Jones, Graham R. Williamson, Tobit Emmens, Jon Perry

School of Nursing and Midwifery

BACKGROUND: Professionals are interested in using e-health but implementation of new methods is slow. Barriers to implementation include the need for training and limited awareness or experience. Research may not always convince mental health professionals (MHPs). Adding the 'voice' of mental health service users (MHSUs) in collaborative learning may help. Involving MHSUs in face-face education can be difficult. We had previously been unable to engage MHPs in online discussion with MHSUs. Here we assessed the feasibility of short online courses involving MHSUs and MHPs. METHODS: We ran three e-health courses, comprising live interactive webcast, week's access to a discussion forum, …

Does Initial Shunt Type For The Norwood Procedure Affect Echocardiographic Measures Of Cardiac Size And Function During Infancy?: The Single Vventricle Reconstruction Trial., Peter C. Frommelt, Lin T. Guey, L Luann Minich, Majeed Bhat, Tim J. Bradley, Steve D. Colan, Greg Ensing, Jessica Gorentz, Haleh Heydarian, J Blaine John, Wyman W. Lai, Jami C. Levine, William T. Mahle, Stephen G. Miller, Richard G. Ohye, Gail D. Pearson, Girish S. Shirali, Pierre C. Wong, Meryl S. Cohen, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Pediatric Heart Network trial comparing outcomes in 549 infants with single right ventricle undergoing a Norwood procedure randomized to modified Blalock-Taussig shunt or right ventricle-pulmonary artery shunt (RVPAS) found better 1-year transplant-free survival in those who received RVPAS. We sought to compare the impact of shunt type on echocardiographic indices of cardiac size and function up to 14 months of age.

METHODS AND RESULTS: A core laboratory measured indices of cardiac size and function from protocol exams: early after Norwood procedure (age 22.5 ± 13.4 days), before stage II procedure (age 4.8 ± 1.8 months), and at 14 …

Cdc42-Dependent Activation Of Nadph Oxidase Is Involved In Ethanol-Induced Neuronal Oxidative Stress, Xin Wang, Zunji Ke, Gang Chen, Mei Xu, Kimberly A. Bower, Jacqueline A. Frank, Zhuo Zhang, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

It has been suggested that excessive reactive oxygen species (ROS) and oxidative stress play an important role in ethanol-induced damage to both the developing and mature central nervous system (CNS). The mechanisms underlying ethanol-induced neuronal ROS, however, remain unclear. In this study, we investigated the role of NADPH oxidase (NOX) in ethanol-induced ROS generation. We demonstrated that ethanol activated NOX and inhibition of NOX reduced ethanol-promoted ROS generation. Ethanol significantly increased the expression of p47^phox and p67^phox, the essential subunits for NOX activation in cultured neuronal cells and the cerebral cortex of infant mice. Ethanol caused serine …

Process Evaluation Of A Positive Youth Development Program In Hong Kong Based On Different Cohorts, Ben M. F. Law, Daniel T. L. Shek

Pediatrics Faculty Publications

There are only a few process evaluation studies on positive youth development programs, particularly in the Chinese context. This study aims to examine the quality of implementation of a positive youth development program (the Project P.A.T.H.S.: Positive Adolescent Training through Holistic Social Programmes) and investigate the relationships among program adherence, process factors, implementation quality, and perceived program success. Process evaluation of 97 classroom-based teaching units was conducted in 62 schools from 2005 to 2009. Findings based on different cohorts generally showed that there were high overall program adherence and implementation quality. Program adherence and implementation process were highly correlated with …

Interim Evaluation Of The Project P.A.T.H.S.: Findings Based On Different Datasets, Daniel T. L. Shek, Lu Yu

Pediatrics Faculty Publications

Interim evaluation studies were carried out in order to examine the implementation details of the Tier 1 Program of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong. Quantitative results of the interim evaluation findings based on eight datasets collected from 2006 to 2009 are reported in this paper. Three hundred and seventy-eight schools were randomly selected to provide information on the implementation details of the program via face-to-face interviews, telephone interviews, and self-completed questionnaires. Results showed that a majority of the workers perceived that the students had positive responses to the program and the program …

Qualitative Evaluation Of Project P.A.T.H.S.: An Integration Of Findings Based On Program Participants, Daniel T. L. Shek, Rachel C. F. Sun

Pediatrics Faculty Publications

An integration of the qualitative evaluation findings collected in different cohorts of students who participated in Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) (n = 252 students in 29 focus groups) was carried out. With specific focus on how the informants described the program, results showed that the descriptions were mainly positive in nature, suggesting that the program was well received by the program participants. When the informants were invited to name three metaphors that could stand for the program, positive metaphors were commonly used. Beneficial effects of the program in different psychosocial domains were also voiced by …

Quantitative Patterns Of Stylistic Influence In The Evolution Of Literature, James M. Hughes, Nicholas J. Foti, David C. Krakauer, Daniel N. Rockmore

Dartmouth Scholarship

Literature is a form of expression whose temporal structure, both in content and style, provides a historical record of the evolution of culture. In this work we take on a quantitative analysis of literary style and conduct the first large-scale temporal stylometric study of literature by using the vast holdings in the Project Gutenberg Digital Library corpus. We find temporal stylistic localization among authors through the analysis of the similarity structure in feature vectors derived from content-free word usage, nonhomogeneous decay rates of stylistic influence, and an accelerating rate of decay of influence among modern authors. Within a given time …

Imaging Prior Information In The Brain, Scott Gorlin, Ming Meng, Jitendra Sharma, Hiroki Sugihara

Dartmouth Scholarship

In making sense of the visual world, the brain's processing is driven by two factors: the physical information provided by the eyes (“bottom-up” data) and the expectancies driven by past experience (“top-down” influences). We use degraded stimuli to tease apart the effects of bottom-up and top-down processes because they are easier to recognize with prior knowledge of undegraded images. Using machine learning algorithms, we quantify the amount of information that brain regions contain about stimuli as the subject learns the coherent images. Our results show that several distinct regions, including high-level visual areas and the retinotopic cortex, contain more information …

Shoc2 Is Targeted To Late Endosomes And Required For Erk1/2 Activation In Egf-Stimulated Cells, Emilia Galperin, Lina Abdelmoti, Alexander Sorkin

Molecular and Cellular Biochemistry Faculty Publications

Shoc2 is the putative scaffold protein that interacts with RAS and RAF, and positively regulates signaling to extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). To elucidate the mechanism by which Shoc2 regulates ERK1/2 activation by the epidermal growth factor (EGF) receptor (EGFR), we studied subcellular localization of Shoc2. Upon EGFR activation, endogenous Shoc2 and red fluorescent protein tagged Shoc2 were translocated from the cytosol to a subset of late endosomes containing Rab7. The endosomal recruitment of Shoc2 was blocked by overexpression of a GDP-bound H-RAS (N17S) mutant and RNAi knockdown of clathrin, suggesting the requirement of RAS activity and …

Between Utopia And Dystopia, Zhe Ren

Student Theses and Dissertations

I watch the city. I am fascinated by the swift change and goings on of metropolitan life. I think of it as a collective performance and exemplary of basic human nature. The urban space also frightens me because it is expanding so fast that it disrupts the relationship between human civilization and the natural balance. My work is an exploration of this coexistence between humans and nature. As populations continue to expand and energy becomes rare, we find new ways to cohabitate. While creating new life forms both naturally and scientifically, humans become parasitic to their surroundings. Population growth is …

Interleukin-1Β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion Through The Activation Of Ccaat Enhancer Binding Protein Β, Brenda L. Petrella, Matthew P. P. Vincenti

Dartmouth Scholarship

Effective treatment of metastatic renal cell carcinoma (RCC) remains a major medical concern, as these tumors are refractory to standard therapies and prognosis is poor. Although molecularly targeted therapies have shown some promise in the treatment of this disease, advanced RCC tumors often develop resistance to these drugs. Dissecting the molecular mechanisms underlying the progression to advanced disease is necessary to design alternative and improved treatment strategies. Tumor-associated macrophages (TAMs) found in aggressive RCC tumors produce a variety of inflammatory cytokines, including interleukin-1 b (IL-1b). Moreover, the presence of TAMs and high serum levels of IL-1b in RCC patients correlate …

Deciphering Mechanisms Of Staphylococcal Biofilm Evasion Of Host Immunity., Mark L. Hanke, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilms are adherent communities of bacteria contained within a complex matrix. Although host immune responses to planktonic staphylococcal species have been relatively well-characterized, less is known regarding immunity to staphylococcal biofilms and how they modulate anti-bacterial effector mechanisms when organized in this protective milieu. Previously, staphylococcal biofilms were thought to escape immune recognition on the basis of their chronic and indolent nature. Instead, we have proposed that staphylococcal biofilms skew the host immune response away from a proinflammatory bactericidal phenotype toward an anti-inflammatory, pro-fibrotic response that favors bacterial persistence. This possibility is supported by recent studies from our laboratory using …

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.

Improved Tumor Contrast Achieved By Single Time Point Dual-Reporter Fluorescence Imaging, Kenneth M. Tichauer, Kimberley S. Samkoe, Kristian J. Sexton, Jason R. Gunn, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

In this study, we demonstrate a method to quantify biomarker expression that uses an exogenous dual-reporter imaging approach to improve tumor signal detection. The uptake of two fluorophores, one nonspecific and one targeted to the epidermal growth factor receptor (EGFR), were imaged at 1 h in three types of xenograft tumors spanning a range of EGFR expression levels (n  =  6 in each group). Using this dual-reporter imaging methodology, tumor contrast-to-noise ratio was amplified by >6 times at 1 h postinjection and >2 times at 24 h. Furthermore, by as early as 20 min postinjection, the dual-reporter imaging signal …

Factor Structure Of A Multidimensional Gender Identity Scale In A Sample Of Chinese Elementary School Children, Lu Yu, Dong Xie, Daniel T. L. Shek

Pediatrics Faculty Publications

This study examined the factor structure of a scale based on the four-dimensional gender identity model (Egan and Perry, 2001) in 726 Chinese elementary school students. Exploratory factor analyses suggested a three-factor model, two of which corresponded to "Felt Pressure" and "Intergroup Bias" in the original model. The third factor "Gender Compatibility" appeared to be a combination of "Gender Typicality" and "Gender Contentment" in the original model. Follow-up confirmatory factor analysis (CFA) indicated that, relative to the initial four-factor structure, the three-factor model fits the current Chinese sample better. These results are discussed in light of cross-cultural similarities and differences …

The Tlo Proteins Are Stoichiometric Components Of Candida Albicans Mediator Anchored Via The Med3 Subunit, Anda Zhang, Kostadin O. Petrov, Emily R. Hyun, Zhongle Liu, Scott A. Gerber, Lawrence C. Myers

Dartmouth Scholarship

The amplification of the TLO (for telomere-associated) genes in Candida albicans, compared to its less pathogenic, close relative Candida dubliniensis, suggests a role in virulence. Little, however, is known about the function of the Tlo proteins. We have purified the Mediator coactivator complex from C. albicans (caMediator) and found that Tlo proteins are a stoichiometric component of caMediator. Many members of the Tlo family are expressed, and each is a unique member of caMediator. Protein expression analysis of individual Tlo proteins, as well as the purification of tagged Tlo proteins, demonstrate that there is a large free population of Tlo …

Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan

Dartmouth Scholarship

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two …

The Meaning Of Parenteral Hydration To Family Caregivers And Patients With Advanced Cancer Receiving Hospice Care., Marlene Z. Cohen, Isabel Torres-Vigil, Beth E. Burbach, Allison De La Rosa, Eduardo Bruera

Journal Articles: College of Nursing

CONTEXT: In the U.S., patients with advanced cancer who are dehydrated or have decreased oral intake almost always receive parenteral hydration in acute care facilities but rarely in the hospice setting.

OBJECTIVES: To describe the meaning of hydration for terminally ill cancer patients in home hospice care and for their primary caregivers.

METHODS: Phenomenological interviews were conducted at two time points with 85 patients and 84 caregivers enrolled in a randomized, double-blind, controlled trial examining the efficacy of parenteral hydration in patients with advanced cancer receiving hospice care in the southern U.S. Transcripts were analyzed hermeneutically by the interdisciplinary research …

Prevention Of Stone Migration With The Accordion During Endoscopic Ureteral Lithotripsy., Christopher J Pagnani, Magdy El Akkad, Demetrius H Bagley

Department of Urology Faculty Papers

BACKGROUND AND PURPOSE: Endoscopic lithotripsy is often prolonged secondary to the retrograde migration of calculous fragments. Various balloons, baskets, and other devices have been used to prevent this migration. Our purpose is to analyze the effect of the Accordion(®) on stone migration and overall efficiency during lithotripsy.

PATIENTS AND METHODS: We prospectively evaluated 21 patients with a total of 23 distal ureteral stones. Patients underwent lithotripsy using an endoscopic impact lithotriptor. The Accordion was randomly used in 11 of these 21 patients. Data were collected regarding stone migration, stone size, stone ablation, ureteral clearing, and lengths of time for various …

Program Implementers' Evaluation Of The Project P.A.T.H.S.: Findings Based On Different Datasets Over Time, Daniel T. L. Shek, Cecilia M. S. Ma

Pediatrics Faculty Publications

This paper integrates the evaluation findings based on program implementers in nine datasets collected from 2005 to 2009 (244 schools and 7,926 implementers). Using consolidated data with schools as the unit of analysis, results showed that program implementers generally had positive perceptions of the program, themselves, and benefits of the program, with more than four-fifths of the implementers regarding the program as beneficial to the program participants. The subjective outcome evaluation instrument was found to be internally consistent. Multiple regression analyses revealed that perceived qualities of the program and program implementers predicted perceived effectiveness of the program. In conjunction with …

Recognition For Positive Behavior As A Critical Youth Development Construct: Conceptual Bases And Implications On Youth Service Development, Ben M. F. Law, Andrew M. H. Siu, Daniel T. L. Shek

Pediatrics Faculty Publications

Recognition for positive behavior is an appropriate response of the social environment to elicit desirable external behavior among the youth. Such positive responses, rendered from various social systems, include tangible and intangible reinforcements. The following theories are used to explain the importance of recognizing positive behavior: operational conditioning, observational learning, self-determination, and humanistic perspective. In the current work, culturally and socially desirable behaviors are discussed in detail with reference to Chinese adolescents. Positive behavior recognition is especially important to adolescent development because it promotes identity formation as well as cultivates moral reasoning and social perspective thinking from various social systems. …