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The Human Phosphotyrosine Signaling Network: Evolution And Hotspots Of Hijacking In Cancer., Lei Li, Chabane Tibiche, Cong Fu, Tomonori Kaneko, Michael F. Moran, Martin Schiller, Shawn Shun-Cheng Li, Edwin Wang Jul 2012

The Human Phosphotyrosine Signaling Network: Evolution And Hotspots Of Hijacking In Cancer., Lei Li, Chabane Tibiche, Cong Fu, Tomonori Kaneko, Michael F. Moran, Martin Schiller, Shawn Shun-Cheng Li, Edwin Wang

Life Sciences Faculty Research

Phosphotyrosine (pTyr) signaling, which plays a central role in cell-cell and cell-environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 representative …


Analytic Lymph Node Number Establishes Staging Accuracy By Occult Tumor Burden In Colorectal Cancer., Terry Hyslop, David S. Weinberg, Stephanie Schulz, Alan Barkun, Scott A. Waldman Jul 2012

Analytic Lymph Node Number Establishes Staging Accuracy By Occult Tumor Burden In Colorectal Cancer., Terry Hyslop, David S. Weinberg, Stephanie Schulz, Alan Barkun, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND AND OBJECTIVES: Recurrence in lymph node-negative (pN0) colorectal cancer suggests the presence of undetected occult metastases. Occult tumor burden in nodes estimated by GUCY2C RT-qPCR predicts risk of disease recurrence. This study explored the impact of the number of nodes analyzed by RT-qPCR (analytic) on the prognostic utility of occult tumor burden.

METHODS: Lymph nodes (range: 2-159) from 282 prospectively enrolled pN0 colorectal cancer patients, followed for a median of 24 months (range: 2-63), were analyzed by GUCY2C RT-qPCR. Prognostic risk categorization defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk category …


Systemic Sclerosis Disease Modification Clinical Trials Design: Quo Vadis?, Fabian A. Mendoza, Md, Lynette L Keyes-Elstein, Sergio A. Jimenez Jul 2012

Systemic Sclerosis Disease Modification Clinical Trials Design: Quo Vadis?, Fabian A. Mendoza, Md, Lynette L Keyes-Elstein, Sergio A. Jimenez

Scleroderma Center Faculty Papers

The purpose of this manuscript is to discuss relevant aspects of clinical trials for Systemic Sclerosis (SSc) and to identify important considerations for the design of SSc disease modification clinical trials. Placebo randomized controlled trials with appropriate identification of SSc patients with diffuse progressive SSc skin involvement of recent onset, along with a rescue strategy for patients with worsening lung and skin involvement are suggested. If change in skin thickening is a major outcome of the study, the selection of patients with recent onset of disease and a predetermined degree of skin involvement are crucial requirements. The trial duration should …


Reevaluating The Imaging Definition Of Tumor Progression: Perfusion Mri Quantifies Recurrent Glioblastoma Tumor Fraction, Pseudoprogression, And Radiation Necrosis To Predict Survival., Leland S Hu, Jennifer M Eschbacher, Joseph E Heiserman, Amylou C Dueck, William R Shapiro, Seban Liu, John P Karis, Kris A Smith, Stephen W Coons, Peter Nakaji, Robert F Spetzler, Burt G Feuerstein, Josef Debbins, Leslie C Baxter Jul 2012

Reevaluating The Imaging Definition Of Tumor Progression: Perfusion Mri Quantifies Recurrent Glioblastoma Tumor Fraction, Pseudoprogression, And Radiation Necrosis To Predict Survival., Leland S Hu, Jennifer M Eschbacher, Joseph E Heiserman, Amylou C Dueck, William R Shapiro, Seban Liu, John P Karis, Kris A Smith, Stephen W Coons, Peter Nakaji, Robert F Spetzler, Burt G Feuerstein, Josef Debbins, Leslie C Baxter

Neurosurgery

INTRODUCTION: Contrast-enhanced MRI (CE-MRI) represents the current mainstay for monitoring treatment response in glioblastoma multiforme (GBM), based on the premise that enlarging lesions reflect increasing tumor burden, treatment failure, and poor prognosis. Unfortunately, irradiating such tumors can induce changes in CE-MRI that mimic tumor recurrence, so called post treatment radiation effect (PTRE), and in fact, both PTRE and tumor re-growth can occur together. Because PTRE represents treatment success, the relative histologic fraction of tumor growth versus PTRE affects survival. Studies suggest that Perfusion MRI (pMRI)-based measures of relative cerebral blood volume (rCBV) can noninvasively estimate histologic tumor fraction to predict …


Parent Or Community: Where Do 20-Month-Olds Exposed To Two Accents Acquire Their Representation Of Words?, Caroline Floccia, Luche C Delle, Samantha Durrant, Joseph Butler, Jeremy Goslin Jul 2012

Parent Or Community: Where Do 20-Month-Olds Exposed To Two Accents Acquire Their Representation Of Words?, Caroline Floccia, Luche C Delle, Samantha Durrant, Joseph Butler, Jeremy Goslin

School of Psychology

The recognition of familiar words was evaluated in 20-month-old children raised in a rhotic accent environment to parents that had either rhotic or non-rhotic accents. Using an Intermodal Preferential Looking task children were presented with familiar objects (e.g. 'bird') named in their rhotic or non-rhotic form. Children were only able to identify familiar words pronounced in a rhotic accent, irrespective of their parents' accent. This suggests that it is the local community rather than parental input that determines accent preference in the early stages of acquisition. Consequences for the architecture of the early lexicon and for models of word learning …


Intermediate-Term Mortality And Cardiac Transplantation In Infants With Single-Ventricle Lesions: Risk Factors And Their Interaction With Shunt Type., James S. Tweddell, Lynn A. Sleeper, Richard G. Ohye, Ismee A. Williams, Lynn Mahony, Christian Pizarro, Victoria L. Pemberton, Peter C. Frommelt, Scott M. Bradley, James F. Cnota, Jennifer Hirsch, Paul M. Kirshbom, Jennifer S. Li, Nancy Pike, Michael Puchalski, Chitra Ravishankar, Jeffrey P. Jacobs, Peter C. Laussen, Brian W. Mccrindle, Pediatric Heart Network Investigators, Girish S. Shirali Jul 2012

Intermediate-Term Mortality And Cardiac Transplantation In Infants With Single-Ventricle Lesions: Risk Factors And Their Interaction With Shunt Type., James S. Tweddell, Lynn A. Sleeper, Richard G. Ohye, Ismee A. Williams, Lynn Mahony, Christian Pizarro, Victoria L. Pemberton, Peter C. Frommelt, Scott M. Bradley, James F. Cnota, Jennifer Hirsch, Paul M. Kirshbom, Jennifer S. Li, Nancy Pike, Michael Puchalski, Chitra Ravishankar, Jeffrey P. Jacobs, Peter C. Laussen, Brian W. Mccrindle, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The study objective was to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor the modified Blalock-Taussig shunt or a right ventricle-to-pulmonary artery shunt.

METHODS: We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors.

RESULTS: Data from 549 subjects (follow-up, 2.7 ± 0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated …


B-Vitamin Deficiency In Patients Treated With Antiepileptic Drugs., Scott Mintzer, Christopher T Skidmore, Michael R Sperling Jul 2012

B-Vitamin Deficiency In Patients Treated With Antiepileptic Drugs., Scott Mintzer, Christopher T Skidmore, Michael R Sperling

Department of Neurology Faculty Papers

Enzyme-inducing antiepileptic drugs (AEDs) produce many alterations in metabolism, including vitamin levels. Whether they produce clinically relevant deficiency of B vitamins has rarely been assessed. We obtained B-vitamin levels in patients who were being converted from an inducing AED (phenytoin or carbamazepine) to a non-inducing AED (levetiracetam, lamotrigine, or topiramate), with measurements both before and ≥ 6 weeks after the switch. A group of normal subjects underwent the same studies. Neither folate nor B12 deficiency was seen in any patient. Vitamin B6 deficiency was found in 16/33 patients (48%) taking inducers, compared to 1/11 controls (9%; p=0.031). After switch to …


Associations Between Toenail Arsenic Concentration And Dietary Factors In A New Hampshire Ppopulation, Joann F. Gruber, Margaret R. Karagas, Diane Gilbert-Diamond, Pamela J. Bagley, M Scot Zens, Vicki Sayarath, Tracy Punshon, J Steven Morris, Kathryn L. Cottingham Jun 2012

Associations Between Toenail Arsenic Concentration And Dietary Factors In A New Hampshire Ppopulation, Joann F. Gruber, Margaret R. Karagas, Diane Gilbert-Diamond, Pamela J. Bagley, M Scot Zens, Vicki Sayarath, Tracy Punshon, J Steven Morris, Kathryn L. Cottingham

Dartmouth Scholarship

Background: Dietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown.

Methods: As part of a population-based case-control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We …


Loss Of Intranetwork And Internetwork Resting State Functional Connections With Alzheimer's Disease Progression, Mathew R. Brier, Jewell B. Thomas, Abraham Z. Snyder, Tammie L. Benzinger, Dongyang Zhang, Marcus E. Raichle, David M. Holtzman, John C. Morris, Beau M. Ances Jun 2012

Loss Of Intranetwork And Internetwork Resting State Functional Connections With Alzheimer's Disease Progression, Mathew R. Brier, Jewell B. Thomas, Abraham Z. Snyder, Tammie L. Benzinger, Dongyang Zhang, Marcus E. Raichle, David M. Holtzman, John C. Morris, Beau M. Ances

Open Access Publications

Alzheimer's disease (AD) is the most common cause of dementia. Much is known concerning AD pathophysiology but our understanding of the disease at the systems level remains incomplete. Previous AD research has used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to assess the integrity of functional networks within the brain. Most studies have focused on the default-mode network (DMN), a primary locus of AD pathology. However, other brain regions are inevitably affected with disease progression. We studied rs-fcMRI in five functionally defined brain networks within a large cohort of human participants of either gender (n = 510) that ranged in …


Resilience In The Face Of Disaster: Prevalence And Longitudinal Course Of Mental Disorders Following Hurricane Ike, Robert H. Pietrzak, Melissa Tracy, Sandro Galea, Dean G. Kilpatrick, Kenneth J. Ruggiero, Jessica L. Hamblen, Steven M. Southwick, Fran H. Norris Jun 2012

Resilience In The Face Of Disaster: Prevalence And Longitudinal Course Of Mental Disorders Following Hurricane Ike, Robert H. Pietrzak, Melissa Tracy, Sandro Galea, Dean G. Kilpatrick, Kenneth J. Ruggiero, Jessica L. Hamblen, Steven M. Southwick, Fran H. Norris

Dartmouth Scholarship

Objectives: Natural disasters may increase risk for a broad range of psychiatric disorders, both in the short- and in the medium-term. We sought to determine the prevalence and longitudinal course of posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), depression, and suicidality in the first 18 months after Hurricane Ike.

Methods: Six hundred fifty-eight adults representative of Galveston and Chambers Counties, Texas participated in a random, population-based survey. The initial assessment was conducted 2 to 5 months after Hurricane Ike struck Galveston Bay on September 13, 2008. Follow-up assessments were conducted at 5 to 9 and 14 …


What's New In Spine Surgery., Keith H Bridwell, Paul A Anderson, Scott D Boden, Alexander R Vaccaro, Jeffrey C Wang Jun 2012

What's New In Spine Surgery., Keith H Bridwell, Paul A Anderson, Scott D Boden, Alexander R Vaccaro, Jeffrey C Wang

Rothman Institute Papers

No abstract provided.


Live-Cell Monitoring Of Periodic Gene Expression In Synchronous Human Cells Identifies Forkhead Genes Involved In Cell Cycle Control, Gavin D. Grant, Joshua Gamsby, Viktor Martyanov, Lionel Brooks, Lacy K. George, J. Matthew Mahoney, Jennifer J. Loros, Jay C. Dunlap, Michael L. Whitfield Jun 2012

Live-Cell Monitoring Of Periodic Gene Expression In Synchronous Human Cells Identifies Forkhead Genes Involved In Cell Cycle Control, Gavin D. Grant, Joshua Gamsby, Viktor Martyanov, Lionel Brooks, Lacy K. George, J. Matthew Mahoney, Jennifer J. Loros, Jay C. Dunlap, Michael L. Whitfield

Dartmouth Scholarship

We developed a system to monitor periodic luciferase activity from cell cycle-regulated promoters in synchronous cells. Reporters were driven by a minimal human E2F1 promoter with peak expression in G1/S or a basal promoter with six Forkhead DNA-binding sites with peak expression at G2/M. After cell cycle synchronization, luciferase activity was measured in live cells at 10-min intervals across three to four synchronous cell cycles, allowing unprecedented resolution of cell cycle-regulated gene expression. We used this assay to screen Forkhead transcription factors for control of periodic gene expression. We confirmed a role for FOXM1 and identified two novel cell cycle …


Consumption Of Pornographic Materials Among Hong Kong Early Adolescents: A Replication, Daniel T. L. Shek, Cecilia M. S. Ma Jun 2012

Consumption Of Pornographic Materials Among Hong Kong Early Adolescents: A Replication, Daniel T. L. Shek, Cecilia M. S. Ma

Pediatrics Faculty Publications

Consumption of pornographic materials was examined in 3,638 secondary 2 students in Hong Kong. Results showed that over 80% of the respondents had never consumed pornographic materials in the past year. Internet pornography was the most common medium that adolescents used when viewing pornographic materials. Males reported a higher level of pornography consumption than did females. Participants who were born in mainland China were more likely to consume pornographic materials than their Hong Kong counterparts. Regardless of the types of pornographic materials, the levels of pornography consumption significantly increased over time. Results also showed that higher levels of positive youth …


Internet Addiction Phenomenon In Early Adolescents In Hong Kong, Daniel T. L. Shek, Lu Yu Jun 2012

Internet Addiction Phenomenon In Early Adolescents In Hong Kong, Daniel T. L. Shek, Lu Yu

Pediatrics Faculty Publications

The present study investigated the prevalence and demographic correlates of Internet addiction in Hong Kong adolescents as well as the change in related behavior at two time points over a one-year interval. Two waves of data were collected from a large sample of students (Wave 1: 3,328 students, age = 12.59 ± 0.74 years; Wave 2: 3,580 students, age = 13.50 ± 0.75 years) at 28 secondary schools in Hong Kong. Comparable to findings at Wave 1 (26.4%), 26.7% of the participants met the criterion of Internet addiction at Wave 2 as measured by Young's 10-item Internet Addiction Test. The …


Autophagy And Senescence In Cancer-Associated Fibroblasts Metabolically Supports Tumor Growth And Metastasis Via Glycolysis And Ketone Production., Claudia Capparelli, Carmela Guido, Diana Whitaker-Menezes, Phd, Gloria Bonuccelli, Renee Balliet, Timothy G Pestell, Allison F Goldberg, Richard Pestell, Anthony Howell, Sharon Sneddon, Ruth Birbe, Aristotelis Tsirigos, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P. Lisanti Jun 2012

Autophagy And Senescence In Cancer-Associated Fibroblasts Metabolically Supports Tumor Growth And Metastasis Via Glycolysis And Ketone Production., Claudia Capparelli, Carmela Guido, Diana Whitaker-Menezes, Phd, Gloria Bonuccelli, Renee Balliet, Timothy G Pestell, Allison F Goldberg, Richard Pestell, Anthony Howell, Sharon Sneddon, Ruth Birbe, Aristotelis Tsirigos, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P. Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Senescent fibroblasts are known to promote tumor growth. However, the exact mechanism remains largely unknown. An important clue comes from recent studies linking autophagy with the onset of senescence. Thus, autophagy and senescence may be part of the same physiological process, known as the autophagy-senescence transition (AST). To test this hypothesis, human fibroblasts immortalized with telomerase (hTERT-BJ1) were stably transfected with autophagy genes (BNIP3, CTSB or ATG16L1). Their overexpression was sufficient to induce a constitutive autophagic phenotype, with features of mitophagy, mitochondrial dysfunction and a shift toward aerobic glycolysis, resulting in L-lactate and ketone body production. Autophagic fibroblasts also showed …


Amygdala Responses To Averted Vs Direct Gaze Fear Vary As A Function Of Presentation Speed, Reginald B. Adams, Robert G. Franklin Jr, Kestutis Kveraga, Nalini Ambady, Robert E. Kleck, Paul J. Whalen, Nouchine Hadjikhani, Anthony J. Nelson Jun 2012

Amygdala Responses To Averted Vs Direct Gaze Fear Vary As A Function Of Presentation Speed, Reginald B. Adams, Robert G. Franklin Jr, Kestutis Kveraga, Nalini Ambady, Robert E. Kleck, Paul J. Whalen, Nouchine Hadjikhani, Anthony J. Nelson

Dartmouth Scholarship

We examined whether amygdala responses to rapidly presented fear expressions are preferentially tuned to averted vs direct gaze fear and conversely whether responses to more sustained presentations are preferentially tuned to direct vs averted gaze fear. We conducted three functional magnetic resonance imaging (fMRI) studies to test these predictions including: Study 1: a block design employing sustained presentations (1 s) of averted vs direct gaze fear expressions taken from the Pictures of Facial Affect; Study 2: a block design employing rapid presentations (300 ms) of these same stimuli and Study 3: a direct replication of these studies in the context …


Neurological Soft Signs In Persons With Amnestic Mild Cognitive Impairment And The Relationships To Neuropsychological Functions, Hui-Jie Li, Peng-Yun Wang, Yang Jiang, Raymond C.K. Chan, Hua-Li Wang, Juan Li Jun 2012

Neurological Soft Signs In Persons With Amnestic Mild Cognitive Impairment And The Relationships To Neuropsychological Functions, Hui-Jie Li, Peng-Yun Wang, Yang Jiang, Raymond C.K. Chan, Hua-Li Wang, Juan Li

Behavioral Science Faculty Publications

BACKGROUND: Neurological abnormalities have been reported in people with amnestic mild cognitive impairment (aMCI). The current study aimed to examine the prevalence of neurological soft signs (NSS) in this clinical group and to examine the relationship of NSS to other neuropsychological performances.

METHODS: Twenty-nine people with aMCI and 28 cognitively healthy elderly people were recruited for the present study. The NSS subscales (motor coordination, sensory integration, and disinhibition) of the Cambridge Neurological Inventory and a set of neuropsychological tests were administered to all the participants.

RESULTS: People with aMCI exhibited significantly more motor coordination signs, disinhibition signs, and total NSS …


School Day Segmented Physical Activity Patterns Of High And Low Active Children, Stuart J. Fairclough, Aaron Beighle, Heather Erwin, Nicola D. Ridgers Jun 2012

School Day Segmented Physical Activity Patterns Of High And Low Active Children, Stuart J. Fairclough, Aaron Beighle, Heather Erwin, Nicola D. Ridgers

Kinesiology and Health Promotion Faculty Publications

BACKGROUND: Variability exists in children's activity patterns due to the association with environmental, social, demographic, and inter-individual factors. This study described accelerometer assessed physical activity patterns of high and low active children during segmented school week days whilst controlling for potential correlates.

METHODS: Two hundred and twenty-three children (mean age: 10.7 ± 0.3 yrs, 55.6% girls, 18.9% overweight/obese) from 8 north-west England primary schools wore ActiGraph GT1M accelerometers for 7 consecutive days during autumn of 2009. ActiGraph counts were converted to minutes of moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) physical activity. Children were classified as high active (HIGH) or …


Is Mri Better Than Ct For Detecting A Vascular Component To Dementia? A Systematic Review And Meta-Analysis., Rebecca Beynon, Jonathan A.C. Sterne, Gordon Wilcock, Marcus Likeman, Roger M. Harbord, Margaret Astin, Margaret Burke, Alysson Bessell, Yoav Ben-Shlomo, James Hawkins, William Hollingworth, Penny Whiting Jun 2012

Is Mri Better Than Ct For Detecting A Vascular Component To Dementia? A Systematic Review And Meta-Analysis., Rebecca Beynon, Jonathan A.C. Sterne, Gordon Wilcock, Marcus Likeman, Roger M. Harbord, Margaret Astin, Margaret Burke, Alysson Bessell, Yoav Ben-Shlomo, James Hawkins, William Hollingworth, Penny Whiting

School of Psychology

BACKGROUND: Identification of causes of dementia soon after symptom onset is important, because appropriate treatment of some causes of dementia can slow or halt its progression or enable symptomatic treatment where appropriate. The accuracy of MRI and CT, and whether MRI is superior to CT, in detecting a vascular component to dementia in autopsy confirmed and clinical cohorts of patients with VaD, combined AD and VaD ("mixed dementia"), and AD remain unclear. We conducted a systematic review and meta-analysis to investigate this question. METHODS: We searched eight databases and screened reference lists to identify studies addressing the review question. We …


Human Genome-Wide Association And Mouse Knockout Approaches Identify Platelet Supervillin As An Inhibitor Of Thrombus Formation Under Shear Stress., Leonard C. Edelstein, Elizabeth J. Luna, Ian B. Gibson, Molly Bray, Ying Jin, Altaf Kondkar, Srikanth Nagalla, Nacima Hadjout-Rabi, Tara C. Smith, Daniel Covarrubias, Stephen N. Jones, Firdos Ahmad, Moritz Stolla, Xianguo Kong, Zhiyou Fang, Wolfgang Bergmeier, Chad Shaw, Suzanne M. Leal, Paul Bray Jun 2012

Human Genome-Wide Association And Mouse Knockout Approaches Identify Platelet Supervillin As An Inhibitor Of Thrombus Formation Under Shear Stress., Leonard C. Edelstein, Elizabeth J. Luna, Ian B. Gibson, Molly Bray, Ying Jin, Altaf Kondkar, Srikanth Nagalla, Nacima Hadjout-Rabi, Tara C. Smith, Daniel Covarrubias, Stephen N. Jones, Firdos Ahmad, Moritz Stolla, Xianguo Kong, Zhiyou Fang, Wolfgang Bergmeier, Chad Shaw, Suzanne M. Leal, Paul Bray

Department of Medicine Faculty Papers

BACKGROUND: High shear force critically regulates platelet adhesion and thrombus formation during ischemic vascular events. To identify genetic factors that influence platelet thrombus formation under high shear stress, we performed a genome-wide association study and confirmatory experiments in human and animal platelets.

METHODS AND RESULTS: Closure times in the shear-dependent platelet function analyzer (PFA)-100 were measured on healthy, nondiabetic European Americans (n=125) and blacks (n=116). A genome-wide association (P

CONCLUSIONS: We show for the first time that (1) platelets contain supervillin; (2) platelet thrombus formation in the PFA-100 is associated with human SVIL variants and low SVIL expression; and (3) …


Participants' Evaluation Of The Project P.A.T.H.S.: Are Findings Based On Different Datasets Consistent?, Daniel T. L. Shek, Rachel C. F. Sun Jun 2012

Participants' Evaluation Of The Project P.A.T.H.S.: Are Findings Based On Different Datasets Consistent?, Daniel T. L. Shek, Rachel C. F. Sun

Pediatrics Faculty Publications

Subjective outcome evaluation findings based on the perspective of the participants of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in nine datasets collected from 2005 to 2009 (n = 206, 313 program participants) were examined in this paper. Based on the consolidated data with schools as units, results showed that the participants generally had positive perceptions of the program, implementers, and benefits of the program. More than four-fifths of the participants regarded the program as beneficial to their holistic development. Multiple regression analysis revealed that the perceived qualities of the program and the program implementers predicted perceived …


Selective Impact Of Hiv Disease Progression On The Innate Immune System In The Human Female Reproductive Tract, Timothy Lahey, Mimi Ghosh, John V. Fahey, Zheng Shen, Lucy R. Mukura, Yan Song, Susan Cu-Uvin, Kenneth H. Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira Jun 2012

Selective Impact Of Hiv Disease Progression On The Innate Immune System In The Human Female Reproductive Tract, Timothy Lahey, Mimi Ghosh, John V. Fahey, Zheng Shen, Lucy R. Mukura, Yan Song, Susan Cu-Uvin, Kenneth H. Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira

Dartmouth Scholarship

Background: We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.

Methods: CVL from 57 HIV-infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/µl, 200-500 cells/µl, or <200 cells/µl of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti-gp160 HIV IgG antibodies were measured by ELISA and Luminex.


A Prospective Observational Study Of Mycophenolate Mofetil Treatment In Progressive Diffuse Cutaneous Systemic Sclerosis Of Recent Onset., Fabian A. Mendoza, Md, Sarah J. Nagle, Jason B. Lee, Md, Sergio A. Jimenez Jun 2012

A Prospective Observational Study Of Mycophenolate Mofetil Treatment In Progressive Diffuse Cutaneous Systemic Sclerosis Of Recent Onset., Fabian A. Mendoza, Md, Sarah J. Nagle, Jason B. Lee, Md, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

OBJECTIVE: A prospective observational study of mycophenolate mofetil (MMF) treatment in patients with diffuse progressive cutaneous systemic sclerosis (SSc) of recent onset.

METHODS: Twenty-five previously untreated consecutive patients with recent-onset (< 24 mo) diffuse progressive cutaneous SSc received MMF as the only disease-modifying therapy. Modified Rodnan skin score (mRSS) and affected body surface area (BSA) were compared from initiation of MMF to study end. Pulmonary function tests performed at the same institution before therapy and at study end were available in 15 patients. Histopathology and real-time PCR assessment of fibrosis-related gene expression were performed before and after treatment in skin biopsies from 3 patients.

RESULTS: At 18.2 ± 8.73 months of MMF therapy (median 2000 mg/day) the mRSS decreased from 24.56 ± 8.62 to 14.52 ± 10.9 (p = 0.0004) and the affected BSA from 36% ± 16% to 14% ± 13.3% (p = 0.00001). Pulmonary function tests remained stable from initiation of MMF to the end of the study. Skin histopathology showed a remarkable reduction in accumulation of fibrotic tissue. Real-time PCR …


Resolution Of Bilateral Ptosis After Reduction Of Unilaterally Elevated Intraocular Pressure In A Child With Axenfeld-Reiger Spectrum Disorder., Ketki Soin, Alex V. Levin Jun 2012

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.


Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Mitochondria Take Center Stage., Shey-Shing Sheu, Robert T Dirksen, Edward N Pugh Jun 2012

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.


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 Jun 2012

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 …


The Quest For The Perfect Prostate Biopsy Continues, Leonard G. Gomella Jun 2012

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 Jun 2012

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 …


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 Jun 2012

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.


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 Jun 2012

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.