Medicine and Health Sciences Commons^™

Evaluation Of The Use Of An Interactive, Online Resource For Competency-Based Curriculum Development, Patricia S. Beach, Miriam Bar-On, Constance D. Baldwin, Diane Kittredge, R. Franklin Trimm, Rebecca Henry

University Faculty and Staff Publications

Purpose

To evaluate pediatric educators’ use of and satisfaction with the Academic Pediatric Association’s Educational Guidelines for Pediatric Residency.

Method

The authors used customized programming to document all registered users and downloaded files from the Guidelines Web site for a 30-month period after site completion. An online survey of volunteer users was conducted.

Results

Between July 2005 and December 2007, 1,747 individuals registered on the Web site, and 8,754 files were downloaded. Registrants who downloaded files (n = 1,239) represented 97% of the pediatric residency programs in 2008 that were approved by the Accreditation Council for Graduate Medical Education. During …

Detection Of Merkel Cell Carcinoma Polyomavirus In Mucosal Merkel Cell Carcinoma, Karen N. Wu, Md, Peter A. Mccue, Md, Zi-Xuan Wang, Phd, Agnieszka K. Witkiewicz, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Case Report: A 61-year-old-woman with a past medical history significant for hypertension, bipolar disorder, obstructive sleep apnea and chronic obstructive pulmonary disease presented with diffusive lymphadenopathy suspicious for lymphoma. A lymph node in her right groin was biopsied by fine needle aspiration and showed atypical cells, but was not diagnostic. An excisional biopsy of the 2 x 2 cm lymph node demonstrated metastatic Merkel cell carcinoma (MCC). No skin lesions were detected. A CT scan revealed the presence of a large nasopharyngeal mass that following surgical removal was diagnosed as MCC. Treatment with etoposide and cisplatin and radiation were instituted. …

Cd34 And Alpha-Smooth Muscle Actin Distinguish Cryptogenic Organizing Pneumonia From Secondary Bronchiolitis Obliterans-Organizing Pneumonia, Karen N. Wu, Md, Tajender S. Vasu, Md, John L. Farber, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Secondary bronchiolitis obliterans-organizing pneumonia (BOOP) is a reaction to injury, forming granulation tissue with airspaces. Idiopathic cryptogenic organizing pneumonia (COP) and secondary BOOP are histologically similar. COP has been reported to show increased collagen in the granulation plugs and fewer myofibroblasts and capillaries. Using CD34 for capillaries and alpha-smooth muscle actin for myofibroblasts, we assessed these statins to differentiate COP from secondary BOOP.

The Elucidation Of Metabolic Pathways And Their Improvements Using Stable Optimization Of Large-Scale Kinetic Models Of Cellular Systems, Evgeni V. Nikolaev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Metabolic engineering of cellular systems to maximize reaction fluxes or metabolite concentrations still presents a significant challenge by encountering unpredictable instabilities that can be caused by simultaneous or consecutive enhancements of many reaction steps. It can therefore be important to select carefully small subsets of key enzymes for their subsequent stable modification compatible with cell physiology. To address this important problem, we introduce a general mixed integer non-linear problem (MINLP) formulation to compute automatically which enzyme levels should be modulated and which enzyme regulatory structures should be altered to achieve the given optimization goal using non-linear kinetic models of relevant …

Automatic Detection Of Slip-Induced Backward Falls, Jian Liu, Thurmon E. Lockhart

Computer Sciences and Electrical Engineering Faculty Research

Falls are the leading cause of injury deaths among people 65 years and older. The National Safety Council reported that in 2005, 17,700 Americans met their death by falling, and of these deaths, the majority (over 80%) were people over 65 years of age [1]. It is certainly desirable to avoid the fall accidents altogether through developing a comprehensive fall prevention program [2]. However, in case of unavoidable falls, an effective injury-prevention technology is critical to minimize/reduce fall-related physical injuries. Recently, the concept of wearable airbag [3] emerged as one viable and promising injury-prevention approach.

Safe Emergency Management Of Acute Ischemic Stroke: An Academic Community Hospital Decade Experience, John Castaldo, Richard S. Mackenzie Md, Peter J. Barbour Md, Lorraine Spikol, Yevgeniy Isayev, Yuebing Li Phd, Gary Clauser Md, John Margraf Md, Glenn Mackin Md, Faan, Facp, David Richardson, Gavin C. Barr, Jr. Md, Donna Jenny, Susan Nevada, Claranne Mathiesen

Department of Emergency Medicine

No abstract provided.

Long Lasting Recruitment Of Immune Cells And Altered Epiperineurial Thickness In Focal Nerve Inflammation Induced By Complete Freund's Adjuvant, Geoffrey M. Bove

Biomedical Sciences Faculty Publications

Immune-mediated nerve inflammation is involved in many painful states in humans, and causes axonal and behavioral changes in rats. While models of nerve inflammation have been characterized using electrophysiological and behavioral methods, the presence of immune cells has not been fully assessed. We inflamed rat sciatic nerves using complete Freund's adjuvant and quantified the presence of ED-1 macrophages and TCR-αβ T-cells for up to 12 weeks. We report that these immune cells are prominent extraneurally up to 12 weeks following the induction of inflammation. This observation does not easily correlate with inflammation-induced axonal mechanical sensitivity, which peaks within 1 week …

Jnk1 Activation Predicts The Prognostic Outcome Of The Human Hepatocellular Carcinoma, Qingshan Chang, Jianguo Chen, Kevin J. Beezhold, Vince Castranova, Xianglin Shi, Fei Chen

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with an extremely poor prognosis. The classification of HCC based on the molecular signature is not well-established.

RESULTS: In the present study, we reported HCC signature genes based on the JNK1 activation status in 31 HCC specimens relative to the matched distal noncancerous liver tissue from 31 patients. The HCCs with high JNK1 (H-JNK1) and low JNK1 (L-JNK1) were sub-grouped. Two different signature gene sets for both H-JNK1 and L-JNK1 HCC were identified through gene expression profiling. A striking overlap of signature genes was observed between the H-JNK1 …

Aging And Environmental Exposures Alter Tissue-Specific Dna Methylation Dependent Upon Cpg Island Context, Brock C. Christensen, E Andres Houseman, Carmen J. Marsit, Shichun Zheng, Margaret R. Wrensch, Joseph L. Wiemels, Heather H. Nelson, Margaret R. Karagas

Dartmouth Scholarship

Epigenetic control of gene transcription is critical for normal human development and cellular differentiation. While alterations of epigenetic marks such as DNA methylation have been linked to cancers and many other human diseases, interindividual epigenetic variations in normal tissues due to aging, environmental factors, or innate susceptibility are poorly characterized. The plasticity, tissue-specific nature, and variability of gene expression are related to epigenomic states that vary across individuals. Thus, population-based investigations are needed to further our understanding of the fundamental dynamics of normal individual epigenomes. We analyzed 217 non-pathologic human tissues from 10 anatomic sites at 1,413 autosomal CpG loci …

Uncoupling Scavenger Receptor A-Mediated Phagocytosis Of Bacteria From Endotoxic Shock Resistance, Eyal Amiel, Julie L. Acker, Ryan M. Collins, Brent Berwin

Dartmouth Scholarship

Unresolved infection by gram-negative bacteria can result in the potentially lethal condition known as endotoxic shock, whereby uncontrolled inflammation can lead to multiple organ failure and death of the infected host. Previous results have demonstrated that animals deficient in class A scavenger receptor (SRA), a trafficking receptor for bacteria and bacterium-derived molecules, are more susceptible to endotoxic shock. This has been proposed to be a result of impaired SRA-dependent phagocytic clearance of bacteria resulting in stronger proinflammatory stimuli. In this report, we test the hypothesis that there is an obligate reciprocal relationship between SRA-mediated phagocytosis of bacteria and susceptibility to …

Mutations To Antibiotic Resistance During Stringent Response In B. Subtilis, Chad Hansen, Ronald E. Yasbin, Eduardo A. Robleto

Undergraduate Research Opportunities Program (UROP)

The relA gene in Bacillus subtilis controls a variety of factors during the stringent response which is a response to starvation of amino acids. The stringent response inhibits DNA synthesis and transcription of genes of tRNA, rRNA, and ribosomal proteins and promotes synthesis of the required amino acids. The objective of my project is to determine if a strain of B. subtilis that has a knockout mutation for the relA gene will accumulate a higher number of mutations that confer resistance to antibiotics that inhibit translation. It is proposed that because the relA gene inhibits transcription of ribosomal proteins, a …

Inaugural Target Discovery World Congress 2009: Interactive Cardiovascular And Thoracic Surgery, Michael Holinstat, Ph.D.

Department of Medicine Faculty Papers

Dr. Michael Holinstat advocated a preferred therapeutic approach to treatment of platelet clot formation: to target signaling components downstream of receptor activation.

Flagellum-Mediated Biofilm Defense Mechanisms Of Pseudomonas Aeruginosa Against Host-Derived Lactoferrin, Jeff G. Leid, Mathias Kerr, Candice Selgado, Chelsa Johnson, Gabriel Moreno, Alyssa Smith, Mark E. Shirtliff, Georg A. O'Toole, Emily K. Cope

Dartmouth Scholarship

Chronic infection with the gram-negative organism Pseudomonas aeruginosa is a leading cause of morbidity and mortality in human patients, despite high doses of antibiotics used to treat the various diseases this organism causes. These infections are chronic because P. aeruginosa readily forms biofilms, which are inherently resistant to antibiotics as well as the host's immune system. Our laboratory has been investigating specific mutations in P. aeruginosa that regulate biofilm bacterial susceptibility to the host. To continue our investigation of the role of genetics in bacterial biofilm host resistance, we examined P. aeruginosa biofilms that lack the flgK gene. This mutant …

Role Of Cd4+Cd25+ Regulatory T Lymphocytes In Experimental Toxoplasmosis, Sanjay Varikuti

Masters Theses & Specialist Projects

Toxoplasmosis is an important cause of congenital disease, and it is one of the most common opportunistic infections in patients with acquired immunodeficiency syndrome. The need for a reliable experimental model of this infection is crucial not only for achieving a better understanding of the patho-physiology of the disease, but also for developing better methods for evaluating new therapeutic regimens. The purpose of the present study was to investigate the role of CD4+CD25+ T regulatory lymphocytes in mice infected with Toxoplasma gondii. T regulatory (Treg) cells have been shown to play an important role in our immune system in …

Cloning And Expression Of A Putative Exported Protein Coding Gene Sas1089 From An Invasive Community Associated Staphylococcus Aureus Strain Mssa476, Nailah Alzaki

All-Inclusive List of Electronic Theses and Dissertations

Originally, methicillin resistant Staphylococcus aureus (MRSA) occurred primarily in the hospital setting and was designated hospital- associated MRSA (HA-MRSA). In recent years, isolates of Staphylococcus aureus from the community (CA-MRSA), found to be methicillin resistant, are not as resistant tooth~ antibiotics as HA-MRSA. However, community strains are noted for their invasiveness causing soft tissue infections with propensity for invasion to deeper sites.

Micrornas Involved In Tumor Suppressor And Oncogene Pathways: Implications For Hepatobiliary Neoplasia., Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

MicroRNAs are a class of small regulatory RNAs that function to modulate protein expression. This control allows for fine-tuning of the cellular phenotype, including regulation of proliferation, cell signaling, and apoptosis; not surprisingly, microRNAs contribute to liver cancer biology. Recent investigations in human liver cancers and tumor-derived cell lines have demonstrated decreased or increased expression of particular microRNAs in hepatobiliary cancer cells. Based on predicted and validated protein targets as well as functional consequences of altered expression, microRNAs with decreased expression in liver tumor cells may normally aid in limiting neoplastic transformation. Conversely, selected microRNAs that are up-regulated in liver …

Cd19 Signaling Is Impaired In Murine Peritoneal And Splenic B-1 B Lymphocytes, Trivikram Dasu, Vishal Sindhava, Stephen H. Clarke, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells reside predominantly within the coelomic cavities, tonsils, Peyer's patches, spleen (a minor fraction – ∼5%) and are absent in the lymph nodes. They are the primary sources of natural IgM in the body. B-1 cells express polyreactive B cell receptors (BCRs) that cross react with self-antigens and are thus implicated in auto-immune disorders. Previously, we reported that peritoneal B-1 cells are deficient in CD19-mediated intracellular signals leading to Ca²⁺ mobilization. Here, we find that splenic B-1 cells, like peritoneal B-1 cells, are defective in Ca²⁺ release upon B cell activation by co-cross-linking BCR and CD19. In …

Is Chaalia/Pan Masala Harmful For Health? Practices And Knowledge Of Children Of Schools In Mahmoodabad And Chanesar Goth, Karachi, Sameena Shah, Riaz Qureshi, Iqbal Azam Syed

Department of Family Medicine

OBJECTIVE: To determine the practices and knowledge of harmful effects regarding use of Chaalia and Pan Masala in three schools of Mahmoodabad and Chanesar Goth, Jamshed Town, Karachi, Pakistan.

METHODS: To achieve the objective a cross-sectional design was used in three government schools of Mahmoodabad and Chanesar Goth, Jamshed Town, Karachi. Students of either gender drawn from these schools fulfilling the inclusion and exclusion criteria were interviewed using a pre-coded structured questionnaire. Along with demographic data, questions regarding frequency of Chaalia and Pan Masala use, practices of this habit in friends and family and place of procurement of these substances, …

Performance Of A Hip Protector Depends On Its Position During A Fall, Woochol J. Choi, Joaquin A. Hoffer, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

"Hip protectors are designed to attenuate and redistribute the force applied to the hip region during a fall, and thereby reduce risk for hip fracture [1]. However, little information exists on the effectiveness of hip protectors in achieving these goals, and how this is altered by displacement of the hip protector relative to the greater trochanter (GT). In the current study, we tested these issues."

Effectiveness Of A Clinical Decision Support System To Identify Heparin Induced Thrombocytopenia., Jeffrey M. Riggio, Md, Msc, Mandelin K. Cooper, Pharmd, Benjamin E. Leiby, Phd, Jeanine M. Walenga, Phd, Geno J. Merli, Md, Jonathan E. Gottlieb, Md

Department of Medicine Faculty Papers

BACKGROUND: Subtle decreases in platelet count may impede timely recognition of heparin-induced thrombocytopenia (HIT), placing the patient at increased risk of thrombotic events.

OBJECTIVE: A clinical decision support system (CDSS) was developed to alert physicians using computerized provider order entry when a patient with an active order for heparin experienced platelet count decreases consistent with HIT.

METHODS: Comparisons for timeliness of HIT identification and treatment were evaluated for the year preceding and year following implementation of the CDSS in patients with laboratory confirmation of HIT.

RESULTS: During the intervention time period, the CDSS alert occurred 41,922 times identifying 2,036 patients …

An Iterative Strategy Combining Biophysical Criteria And Duration Hidden Markov) Models For Structural Predictions Of Chlamydia Trachomatis S66 Promoters, Ronna R. Mallios, David M. Ojcius, David H. Ardell

All Dugoni School of Dentistry Faculty Articles

Background: Promoter identification is a first step in the quest to explain gene regulation in bacteria. It has been demonstrated that the initiation of bacterial transcription depends upon the stability and topology of DNA in the promoter region as well as the binding affinity between the RNA polymerase σ-factor and promoter. However, promoter prediction algorithms to date have not explicitly used an ensemble of these factors as predictors. In addition, most promoter models have been trained on data from Escherichia coli. Although it has been shown that transcriptional mechanisms are similar among various bacteria, it is quite possible that the …

Didox Modulates Reactive Oxygen Species Production And Inflammatory Events Induced By Lipopolysaccharide (Lps) And Aryl Hydrocarbon Receptor (Ahr) Ligands In Raw 264.7 Murine Macrophages., Thabe Matsebatlela

All Dissertations

Aberrant activation of macrophages during inflammation results in oxidative burst release of reactive oxygen and reactive nitrogen species (ROS/RNS) which are widely accepted to participate in pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. It is demonstrated here that Didox (3,4-Dihydroxybenzohydroxamic acid) possesses antioxidative and anti-inflammatory properties that can protect against inflammation and oxidative stress induced by lipopolysaccharide (LPS) and aryl hydrocarbon receptor (AHR) ligands (PCB126, E804, and IO) in Raw 264.7 murine macrophages. In brief, it is demonstrated here that Didox inhibits LPS-induced oxidative stress, …

Intra-Tumor Heterogeneity Of Mlh1 Promoter Methylation Revealed By Deep Single Molecule Bisulfite Sequencing., Katherine E Varley, David G Mutch, Tina B Edmonston, Paul J Goodfellow, Robi D Mitra

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A single tumor may contain cells with different somatic mutations. By characterizing this genetic heterogeneity within tumors, advances have been made in the prognosis, treatment and understanding of tumorigenesis. In contrast, the extent of epigenetic intra-tumor heterogeneity and how it influences tumor biology is under-explored. We have characterized epigenetic heterogeneity within individual tumors using next-generation sequencing. We used deep single molecule bisulfite sequencing and sample-specific DNA barcodes to determine the spectrum of MLH1 promoter methylation across an average of 1000 molecules in each of 33 individual samples in parallel, including endometrial cancer, matched blood and normal endometrium. This first glimpse, …

Matrix Metalloproteinase Inhibitor, Cts-1027, Attenuates Liver Injury And Fibrosis In The Bile Duct-Ligated Mouse., Alisan Kahraman, Steven F. Bronk, Sophie Cazanave, Nathan W. Werneburg, Justin L. Mott, Patricia C. Contreras, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

Aim: Excessive matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of acute and chronic liver injury. CTS-1027 is an MMP inhibitor, which has previously been studied in humans as an anti-arthritic agent. Thus, our aim was to assess if CTS-1027 is hepato-protective and anti-fibrogenic during cholestatic liver injury. Methods: C57/BL6 mice were subjected to bile duct ligation (BDL) for 14 days. Either CTS-1027 or vehicle was administered by gavage. Results: BDL mice treated with CTS-1027 demonstrated a threefold reduction in hepatocyte apoptosis as assessed by the TUNEL assay or immunohistochemistry for caspase 3/7-positive cells as compared to vehicle-treated …

Chaperone Expression And Effects Of Its Inhibition On Breast Cancer Sensitization, Malissa Diehl

Theses and Dissertations

Breast cancer is one of the most prevalent and deadly forms of cancer in women and is not restricted by race or ethnicity. Although a wealth of knowledge has been amassed on the biology of breast cancer, including its risk factors, diagnosis, prognosis, prevention, and treatment, it remains a serious health concern and active area of research. Initial response to standard chemotherapeutic and radiotherapeutic regimens is generally strong for many patients, yet breast tumors often recur, leading to more aggressive and resistant tumors. Because recurrence is such a clinical issue, more effective therapeutic approaches are needed to eliminate partial clinical …

Behavioral And Molecular Analysis Of Individual Variation In Ethanol Drinking, Jennifer Wolstenholme

Theses and Dissertations

A majority of Americans regularly consume alcohol, but the risk factors leading to excessive drinking and alcohol abuse are unevenly distributed throughout the population. Genetic differences can account for only 40-60% of this variability. While variations in ethanol preference drinking in rodent models have been reported, the neurobiological factors underlying these behaviors are still not completely understood. Thus, these studies were designed to determine behavioral and molecular factors associated with the initiation of ethanol drinking preference in an inbred mouse model. We harnessed the power of inter-individual variation of ethanol drinking within an inbred mouse strain to essentially eliminate genetic …

Chaperone Association With Telomere Binding Proteins, Amy Depcrynski

Theses and Dissertations

The Hsp90 chaperone complex associates with the telomerase enzyme, facilitating the assembly of the ribonucleoprotein complex. While previous data from our laboratory indicate that Hsp90 and p23 remain stably associated with (functionally active) telomerase, more recent experiments suggest that these chaperones associate with telomeres independent of telomerase, presumably through a specific interaction with telomere binding proteins. The current study examines the novel interactions between TRF2, TRF1, TIN2 and TPP1 and molecular chaperones (Hsp90, Hsp70, p23). In vitro and in cell experiments have shown an interaction between TRF1 and TRF2 and the molecular chaperones Hsp90 and Hsp70. Inhibition of Hsp90 using …

Exploring The Methylation Status Of Rai1 And The Rai1 Consensus Binding Sequence, Eri Kamura

Theses and Dissertations

Smith Magenis Syndrome (SMS) is a multiple congenital anomalies/ mental retardation disorder caused by deletion or mutation of the RAI1 gene on chromosome 17p11.2. The majority of patients with SMS phenotypes have a deletion or mutation of RAI1. However, some patients have been observed with SMS-like phenotypes and yet have no deletions or mutations in the RAI1 gene. One possible explanation could be aberrant methylation of RAI1 since RAI1 is present and yet may be silenced. In order to study this possibility, patient cell lines were treated with 5-Aza-2’-deoxycytidine. RNA was extracted and real-time PCR was used to check the …

Retinoic Acid Induced 1 Gene Analysis In Humans And Zebrafish, Bijal Vyas

Theses and Dissertations

Smith-Magenis syndrome (SMS) is a complex mental retardation syndrome caused by deletion of 17p11.2 region or mutation of the RAI1 gene (retinoic acid induced 1). Individuals with SMS typically exhibit speech and motor delays, mental retardation, characteristic craniofacial and skeletal anomalies, and a distinct neurobehavioral phenotype that includes sleep disturbances, stereotypes, and maladaptive and self-injurious behaviors. RAI1 is thought to be a transcription factor modulating the expression of genes involved in a variety of cellular functions. Previous studies have shown the RAI1 gene being induced by retinoic acid (RA), a derivative of vitamin A. RA plays a significant role in …

Lipid Nanoparticles With Accessible Nickel As A Vaccine Delivery System For Single And Multiple His-Tagged Hiv Antigens, Weili Yan, Anekant Jain, Ronan O'Carra, Jerold Woodward, Wenxue Li, Guanhan Li, Avindra Nath, Russell J. Mumper

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the HIV his-tagged Tat protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by s.c. injection with his-Tat/Ni-NP formulation (1.5 μg Tat-his/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific IgG titer with his-Tat/Ni-NP was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity …