Digital Commons Network^™

Evidence-Based Medicine Versus Personalized Medicine: Are They Enemies?, Jose De Leon

Psychiatry Faculty Publications

No abstract provided.

Evaluation Of The Training Program Of The Project P.A.T.H.S.: Findings Based On The Perspective Of The Participants From Different Cohorts, Daniel T. L. Shek, Yammy L. Y. Chak

Pediatrics Faculty Publications

Subjective outcome evaluation findings based on the perspective of the participants participating in a 3-day training program of the Project P.A.T.H.S. are reported in this paper. The findings were based on the data collected from the training workshops conducted between 2005 and 2009 (N = 4.167). Results showed that the respondents had good and positive perceptions of the training program and found it very valuable, particularly with respect to training instructors and familiarization with the project. Besides, the training participants were able to acquire attitude, knowledge and skills that are conducive to the successful implementation of the program. Based on …

Subjective Outcome Evaluation And Factors Related To Perceived Effectiveness Of The Project P.A.T.H.S. In Hong Kong, Daniel T. L. Shek, Lu Yu, Vicky Y. T. Ho

Pediatrics Faculty Publications

Based on a sample of 24,457 participated students, the present study investigated participants' subjective evaluation of the Tier 2 Program of the Project P.A.T.H.S. in the 2009/2010 academic year. Participants generally held positive views toward the Tier 2 Program and program instructor and perceived the program to be beneficial to their development. Programs involving adolescents alone were evaluated more positively than programs involving parents and/or teachers. Students' grade and program type did not show significant impact on participants' subjective evaluation of the project. Consistent with previous reports, perceived effectiveness of the program was significantly predicted by students' perceptions about the …

The Project P.A.T.H.S. In Hong Kong--Lessons Learned And Implications For Positive Youth Development Programs, Daniel T. L. Shek, Rachel C. F. Sun

Pediatrics Faculty Publications

The Project P.A.T.H.S. is a positive youth development program which attempts to promote holistic development of junior secondary schools in Hong Kong. It is ground breaking in terms of the number of schools participating in the project and financial resources injected into the project. Based on the experiences gained from the implementation of the project and evaluation data collected from 2005 to 2011, several issues pertinent to the development of positive youth development programs in the Chinese culture are discussed. These issues include complexity of program development, importance of training, identification of factors governing program implementation, need for evaluation, and …

Helping Adolescents With Greater Psychosocial Needs: Subjective Outcome Evaluation Based On Different Cohorts, Daniel T. L. Shek, Tak Yan Lee

Pediatrics Faculty Publications

The Tier 2 Program of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) is designed to help students with greater psychosocial needs. This paper examines nine sets of subjective outcome evaluation data collected from 2005 to 2009 (n = 60, 241 participants). Based on the consolidated data with schools as units, results showed that participants generally had positive perceptions of the program, implementers, and benefits of the program. The subjective outcome evaluation instrument was found to be internally consistent. Multiple regression analysis revealed that perceived qualities of the program and the program implementers predicted perceived effectiveness of the …

Frontal Sinus Osteoma Removal With The Ultrasonic Bone Aspirator., Eric Ehieli, Jaemi Chu, Eli Gordin, Edmund A. Pribitkin

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Osteomas, the most common skull tumors, are typically excised through either an open or endoscopic ostectomy using a high-speed drill, a technically challenging procedure that can result in injury to adjacent soft tissue structures. Osteoma removal through ultrasonic bone emulsification and aspiration (UBA) offers the advantages of decreased blood loss, preservation of adjacent soft tissue structures, and precise bone removal. UBA was used to successfully remove a forehead osteoma without injury to adjacent nerves and with a satisfactory cosmetic outcome. We describe skull osteoma removal with an ultrasonic bone aspirator, which offers potential advantages over conventional bone removal techniques.

Profiling The Ethnic Characteristics Of Domestic Injuries In Children Younger Than Age 5 Years., Tolulope A. Oyetunji, Adrienne A. Stevenson, Aderonke O. Oyetunji, Sharon K. Onguti, Sarah A. Ames, Adil H. Haider, Benedict C. Nwomeh

Manuscripts, Articles, Book Chapters and Other Papers

The home remains a very common location for deadly injuries among children younger than 5 years. The aim of this study is to describe the demographic and injury characteristics of domestic injuries in children younger than 5 years. The National Trauma Data Bank's National Sample Program data set was queried for children younger than 5 years with the injury site classified as home. Bivariate analysis was performed to determine unadjusted differences by ethnicity. Appropriate weight was applied to the sample to determine accurate national estimates. A total of 7,364 children, representing 32,033 children, were analyzed. Overall mortality was 1.6 per …

Essential Role Of Caveolin-3 In Adiponectin Signalsome Formation And Adiponectin Cardioprotection., Yajing Wang, Xiaoliang Wang, Jean-François Jasmin, Wayne Bond Lau, Rong Li, Yuexin Yuan, Wei Yi, Kurt Chuprun, Michael P. Lisanti, Walter J Koch, Erhe Gao, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

METHODS AND RESULTS: Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery; P

CONCLUSIONS: Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.

Frontal Sinus Osteoma Removal With The Ultrasonic Bone Aspirator., Eric Ehieli, Jaemi Chu, Eli Gordin, Edmund A Pribitkin

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Osteomas, the most common skull tumors, are typically excised through either an open or endoscopic ostectomy using a high-speed drill, a technically challenging procedure that can result in injury to adjacent soft tissue structures. Osteoma removal through ultrasonic bone emulsification and aspiration (UBA) offers the advantages of decreased blood loss, preservation of adjacent soft tissue structures, and precise bone removal. UBA was used to successfully remove a forehead osteoma without injury to adjacent nerves and with a satisfactory cosmetic outcome. We describe skull osteoma removal with an ultrasonic bone aspirator, which offers potential advantages over conventional bone removal techniques.

Thickened Ascending Aortic Wall Mimicking Intramural Hematoma., Kentaro Yamane, Hitoshi Hirose, Benjamin A. Youdelman, James Diehl

Department of Surgery Faculty Papers

A 45-year-old Hispanic woman presented with a 3-day history of ‘‘burning’’ chest pain. A computed tomo- graphic angiogram of the chest revealed the ascending aorta had a maximum diameter of 40 mm with marked thickening of the aortic wall (Figure 1), which we con- cluded was an intramural hematoma. On entering the pericardium, a milky-white plaque-like area on the ascending aorta was encountered (Figure 2). The ascending aorta was firm to palpation. Intraoperative transesophageal echocardiography and epiaortic ultra- sound showed a hyperechoic aortic wall with no find- ings compatible with aortic dissection. The ascending aorta had an irregular surface contour, …

Effect Of Obstructive Sleep Apnea On Mitral Valve Tenting., Gregg S. Pressman, Vincent M. Figueredo, Abel Romero-Corral, Ganesan Murali, Morris N Kotler

Division of Cardiology Faculty Papers

Obstructive apneas produce high negative intrathoracic pressure which imposes an afterload burden on the left ventricle. Such episodes might produce structural changes in the left ventricle over time. Doppler echocardiograms were obtained within 2 months of attended polysomnography. Patients were grouped according to apnea-hypopnea index (AHI): mild/no OSA (AHI < 15) and mod/severe OSA (AHI ≥ 15). Mitral valve tenting height and area, left ventricular (LV) long and short axis, and LV end-diastolic volume (LVEDV), were measured along with tissue Doppler parameters. Comparisons of measurements at baseline and follow up between and within groups were obtained; correlations between absolute changes (deltas) in echocardiographic parameters were also performed. After a mean follow up of 240 days mitral valve tenting height increased significantly (1.17 ± 0.12 cm to 1.28 ± 0.17 cm, p=0.001) in mod/severe OSA as did tenting area (2.30 ± 0.41 cm² to 2.66 ± 0.60 cm², p=0.0002); delta tenting height correlated with delta LVEDV (rho 0.43, p=0.01) and delta tenting area (rho 0.35, p=0.04). In mild/no OSA patients there was no significant change in tenting height; there was a borderline significant increase in tenting area (2.20 ± 0.44 cm …

Costs And Difficulties Of Recruiting Patients To Provide E-Health Support: Pilot Study In One Primary Care Trust., Ray B. Jones, Anita O'Connor, Jade Brelsford, Neil Parsons, Heather Skirton

School of Nursing and Midwifery

BACKGROUND: Better use of e-health services by patients could improve outcomes and reduce costs but there are concerns about inequalities of access. Previous research in outpatients suggested that anonymous personal email support may help patients with long term conditions to use e-health, but recruiting earlier in their 'journey' may benefit patients more. This pilot study explored the feasibility and cost of recruiting patients for an e-health intervention in one primary care trust. METHODS: The sample comprised 46 practices with total patient population of 250,000. We approached all practices using various methods, seeking collaboration to recruit patients via methods agreed with …

Oxidative Stress In Hpv-Driven Viral Carcinogenesis: Redox Proteomics Analysis Of Hpv-16 Dysplastic And Neoplastic Tissues, Federico De Marco, Elona Bucaj, Cesira Foppoli, Ada Fiorini, Carla Blarzino, Kozeta Filipi, Alessandra Giorgi, Maria Eugenia Schininà, Fabio Di Domenico, Raffaella Coccia, D. Allan Butterfield, Marzia Perluigi

Chemistry Faculty Publications

Genital infection by high risk Human Papillomavirus (HR-HPV), although recognized as the main etio-pathogenetic factor of cervical cancer, is not per se sufficient to induce tumour development. Oxidative stress (OS) represents an interesting and under-explored candidate as a promoting factor in HPV-initiated carcinogenesis. To gain insight into the role of OS in cervical cancer, HPV-16 positive tissues were collected from patients with invasive squamous cervical carcinoma, from patients with High Grade dysplastic HPV lesions and from patients with no clinical evidence of HPV lesions. After virological characterization, modulation of proteins involved in the redox status regulation was investigated. ERp57 and …

Unfakeable Facial Configurations Affect Strategic Choices In Trust Games With Or Without Information About Past Behavior, Constantin Rezlescu, Brad Duchaine, Christopher Y. Olivola, Nick Chater

Dartmouth Scholarship

Background:

Many human interactions are built on trust, so widespread confidence in first impressions generally favors individuals with trustworthy-looking appearances. However, few studies have explicitly examined: 1) the contribution of unfakeable facial features to trust-based decisions, and 2) how these cues are integrated with information about past behavior.

Methodology/Principal Findings:

Using highly controlled stimuli and an improved experimental procedure, we show that unfakeable facial features associated with the appearance of trustworthiness attract higher investments in trust games. The facial trustworthiness premium is large for decisions based solely on faces, with trustworthy identities attracting 42% more money (Study 1), and remains …

Hyccin, The Molecule Mutated In The Leukodystrophy Hypomyelination And Congenital Cataract (Hcc), Is A Neuronal Protein., Elisabetta Gazzerro, Simona Baldassari, Caterina Giacomini, Veronica Musante, Floriana Fruscione, Veronica La Padula, Roberta Biancheri, Sonia Scarfì, Valeria Prada, Federica Sotgia, Ian D Duncan, Federico Zara, Hauke B Werner, Michael P Lisanti, Lucilla Nobbio, Anna Corradi, Carlo Minetti

Kimmel Cancer Center Faculty Papers

"Hypomyelination and Congenital Cataract", HCC (MIM #610532), is an autosomal recessive disorder characterized by congenital cataract and diffuse cerebral and peripheral hypomyelination. HCC is caused by deficiency of Hyccin, a protein whose biological role has not been clarified yet. Since the identification of the cell types expressing a protein of unknown function can contribute to define the physiological context in which the molecule is explicating its function, we analyzed the pattern of Hyccin expression in the central and peripheral nervous system (CNS and PNS). Using heterozygous mice expressing the b-galactosidase (LacZ) gene under control of the Hyccin gene regulatory elements, …

Developing An Online Learning Community For Mental Health Professionals And Service Users: A Discursive Analysis., Janet Smithson, Ray B. Jones, Emily Ashurst

School of Nursing and Midwifery

BACKGROUND: There is increasing interest in online collaborative learning tools in health education, to reduce costs, and to offer alternative communication opportunities. Patients and students often have extensive experience of using the Internet for health information and support, and many health organisations are increasingly trying out online tools, while many healthcare professionals are unused to, and have reservations about, online interaction. METHODS: We ran three week-long collaborative learning courses, in which 19 mental health professionals (MHPs) and 12 mental health service users (MHSUs) participated. Data were analysed using a discursive approach to consider the ways in which participants interacted, and …

Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers

Markey Cancer Center Faculty Publications

Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of …

Development And Functional Analysis Of Novel Genetic Promoters Using Dna Shuffling, Hybridization And A Combination Thereof, Rajiv Ranjan, Sunita Patro, Bhubaneswar Pradhan, Alok Kumar, Indu B. Maiti, Nrisingha Dey

Kentucky Tobacco Research and Development Center Faculty Publications

BACKGROUND: Development of novel synthetic promoters with enhanced regulatory activity is of great value for a diverse range of plant biotechnology applications.

METHODOLOGY: Using the Figwort mosaic virus full-length transcript promoter (F) and the sub-genomic transcript promoter (FS) sequences, we generated two single shuffled promoter libraries (LssF and LssFS), two multiple shuffled promoter libraries (LmsFS-F and LmsF-FS), two hybrid promoters (FuasFScp and FSuasFcp) and two hybrid-shuffled promoter libraries (LhsFuasFScp and LhsFSuasFcp). Transient expression activities of approximately 50 shuffled promoter clones from each of these libraries were assayed in tobacco (Nicotiana tabacum cv. Xanthi) protoplasts. It was observed that most …

Gender-Sensitive Reporting In Medical Research., Shirin Heidari, Quarraisha Abdool Karim, Judith D Auerbach, Simone E Buitendijk, Pedro Cahn, Mirjam J Curno, Catherine Hankins, Elly Katabira, Susan Kippax, Richard Marlink, Joan Marsh, Ana Marusic, Heidi M Nass, Julio Montaner, Elizabeth Pollitzer, Maria Teresa Ruiz-Cantero, Lorraine Sherr, Papa Salif Sow, Kathleen Squires, Mark A Wainberg

Department of Medicine Faculty Papers

Sex and gender differences influence the health and wellbeing of men and women. Although studies have drawn attention to observed differences between women and men across diseases, remarkably little research has been pursued to systematically investigate these underlying sex differences. Women continue to be underrepresented in clinical trials, and even in studies in which both men and women participate, systematic analysis of data to identify potential sex-based differences is lacking. Standards for reporting of clinical trials have been established to ensure provision of complete, transparent and critical information. An important step in addressing the gender imbalance would be inclusion of …

Fibrinogen, Chronic Obstructive Pulmonary Disease (Copd) And Outcomes In Two United States Cohorts, Deepa Valvi, David M. Mannino, Hana Müllerova, Ruth Tal-Singer

Preventive Medicine and Environmental Health Faculty Publications

BACKGROUND: Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD).

METHODS: We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations.

RESULTS: Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period. The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels >393.0 mg/dL. Subjects with Stage …

Robotic Surgery Training With Commercially Available Simulation Systems In 2011: A Current Review And Practice Pattern Survey From The Society Of Urologic Robotic Surgeons., Costas D Lallas, John W Davis And Members Of The Society Of Urologic Robotic Surgeons

Department of Urology Faculty Papers

Abstract Objectives: Virtual reality (VR) simulation has the potential to standardize surgical training for robotic surgery. We sought to evaluate all commercially available VR robotic simulators. Materials and Methods: A MEDLINE(®) literature search was performed of all applicable keywords. Available VR simulators were evaluated with regard to face, content, and construct validation. Additionally, a survey was e-mailed to all members of the Endourological Society, querying the pervasiveness of VR simulators in robotic surgical training. Finally, each company was e-mailed to ask for a price quote for their respective system. Results: There are four VR robotic surgical simulators currently available: RoSS™, …

The Economic, Institutional, And Political Determinants Of Public Health Delivery System Structures, Richard C. Ingram, F. Douglas Scutchfield, Glen P. Mays, Michelyn W. Bhandari

Preventive Medicine and Environmental Health Faculty Publications

OBJECTIVES: A typology of local public health systems was recently introduced, and a large degree of structural transformation over time was discovered in the systems analyzed. We present a qualitative exploration of the factors that determine variation and change in the seven structural configurations that comprise the local public health delivery system typology.

METHODS: We applied a 10-item semistructured telephone interview protocol to representatives from the local health agency in two randomly selected systems from each configuration--one that had maintained configuration over time and one that had changed configuration over time. We assessed the interviews for patterns of variation between …

Effect Of Level Of Farm Mechanization Early In Life On Bone Later In Life, Lacey A. Mccormack, Teresa L. Binkley, Bonny Specker

Health and Nutritional Sciences Faculty Publications

OBJECTIVE: To determine whether an active rural lifestyle during childhood and adolescence, defined as low farm mechanization, was associated with bone measures later in life.
METHODS: DXA bone data from total body, hip and spine, and pQCT data from 4% and 20% distal radius were obtained on 330 individuals (157 women) aged 20-66 years who farmed at least 75% of their lives. Primary bone outcomes included areal bone mineral density (aBMD), aBMD Z-scores, cortical and trabecular volumetric BMD, cortical thickness and periosteal circumference. Relationship between bone and recall of level of farm mechanization as a child was determined after stratifying …

Interactions Between Antiepileptics And Second-Generation Antipsychotics, Jose De Leon, Vincenza Santoro, Concetta D'Arrigo, Edoardo Spina

Psychiatry Faculty Publications

INTRODUCTION: Pharmacokinetic and pharmacodynamic drug interactions (DIs) can occur between antiepileptics (AEDs) and second-generation antipsychotics (SGAPs). Some AED and SGAP pharmacodynamic mechanisms are poorly understood. AED-SGAP combinations are used for treating comorbid illnesses or increasing efficacy, particularly in bipolar disorder.

AREAS COVERED: This article provides a comprehensive review of the interactions between antiepileptics and second-generation antipsychotics. The authors cover pharmacokinetic AED-SGAP DI studies, the newest drug pharmacokinetics in addition to the limited pharmacodynamic DI studies.

EXPERT OPINION: Dosing correction factors and measuring SGAP levels can help to compensate for the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone. Further studies …

Integrating An Automated Diabetes Management System Into The Family Management Of Children With Type 1 Diabetes: Results From A 12-Month Randomized Controlled Technology Trial., Tammy Toscos Phd, Stephen W Ponder, Barbara J Anderson, Mayer B Davidson, Martin L Lee, Elaine Montemayor-Gonzalez, Patricia Reyes, Eric Link, Kevin L Mcmahon

Health Services and Informatics Research

OBJECTIVE: The study objective was to evaluate how the use of a pervasive blood glucose monitoring (BGM) technology relates to glycemic control, report of self-care behavior, and emotional response to BGM of children with type 1 diabetes and their parents.

RESEARCH DESIGN AND METHODS: Forty-eight children aged less than 12 years (mean 8.8 years) with type 1 diabetes were randomly assigned to one of two study groups, a control group (conventional care without technology) or an experimental group (conventional care with technology), and followed for 12 months. Families in the experimental group were given the Automated Diabetes Management System (ADMS), …

Invited Commentary On: Orthotopic Heart Transplantation In Patients With Metabolic Risk Factors, Nicholas C. Cavarocchi, Paul Mather

Department of Surgery Faculty Papers

This is invited commentary to the following article:

Kilic, A., Conte, J. V., Shah, A. S., & Yuh, D. D. (2012). Orthotopic heart transplantation in patients with metabolic risk factors. Annals of Thoracic Surgery, 93(3), 718-724.

Evaluation Of Lay Support In Pregnant Women With Social Risk (Elsips): A Randomised Controlled Trial, Sara Kenyon, Kate Jolly, Karla Hemming, Lucy Annang Ingram Phd, Nicola Gale, Sophie-Anna Dann, Jacky Chambers, Christine Macarthur

Faculty Publications

BACKGROUND: Maternal, neonatal and child health outcomes are worse in families from black and ethnic minority groups and disadvantaged backgrounds. There is little evidence on whether lay support improves maternal and infant outcomes among women with complex social needs within a disadvantaged multi-ethnic population in the United Kingdom (UK). METHOD/DESIGN: The aim of this study is to evaluate a lay Pregnancy Outreach Worker (POW) service for nulliparous women identified as having social risk within a maternity service that is systematically assessing social risks alongside the usual obstetric and medical risks. The study design is a randomised controlled trial (RCT) in …

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, Alexander Vaccaro, Jefferson R. Wilson, Anoushka Singh, David W. Cadotte, James S. Harrop, Bizhan Aarabi, Christopher Shaffrey, Marcel Dvorak, Charles Fisher, Paul Arnold, Eric M. Massicotte, Stephen Lewis, Raja Rampersaud

Department of Neurosurgery 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 (,24 hours after 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 …

Gucy2c Opposes Systemic Genotoxic Tumorigenesis By Regulating Akt-Dependent Intestinal Barrier Integrity, Jieru Egeria Lin, Adam Eugene Snook, Peng Li, Brian Arthur Stoecker, Gilbert Won Kim, Michael Sullivan Magee, Alex Vladimir Mejia Garcia, Michael Anthony Valentino, Terry Hyslop, Stephanie Schulz, Scott Arthur Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The barrier separating mucosal and systemic compartments comprises epithelial cells, annealed by tight junctions, limiting permeability. GUCY2C recently emerged as an intestinal tumor suppressor coordinating AKT1-dependent crypt-villus homeostasis. Here, the contribution of GUCY2C to barrier integrity opposing colitis and systemic tumorigenesis is defined. Mice deficient in GUCY2C (Gucy2c^−/−) exhibited barrier hyperpermeability associated with reduced junctional proteins. Conversely, activation of GUCY2C in mice reduced barrier permeability associated with increased junctional proteins. Further, silencing GUCY2C exacerbated, while activation reduced, chemical barrier disruption and colitis. Moreover, eliminating GUCY2C amplified, while activation reduced, systemic oxidative DNA damage. This genotoxicity was associated …

Ovarian Cancer Progression Is Controlled By Phenotypic Changes In Dendritic Cells, Uciane K. Scarlett, Melanie R. Rutkowski, Adam M. Rauwerdink, Jennifer Fields, Ximena Escovar-Fadul, Jason Baird, Juan R. Cubillos-Ruiz, Ana C. Jacobs, Jorge L. Gonzalez, John Weaver, Steven Fiering, Jose R. Conejo-Garcia

Dartmouth Scholarship

We characterized the initiation and evolution of the immune response against a new inducible p53-dependent model of aggressive ovarian carcinoma that recapitulates the leukocyte infiltrates and cytokine milieu of advanced human tumors. Unlike other models that initiate tumors before the development of a mature immune system, we detect measurable antitumor immunity from very early stages, which is driven by infiltrating dendritic cells (DCs) and prevents steady tumor growth for prolonged periods. Coinciding with a phenotypic switch in expanding DC infiltrates, tumors aggressively progress to terminal disease in a comparatively short time. Notably, tumor cells remain immunogenic at advanced stages, but …