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Cardiopulmonary Exercise Testing-Based Algorithm And Its Usefulness In Clinical Cardiology, Mirza Nubair Ahmad, Syed Hasan Yusuf, Rafath Ullah, Mary Ellis, Haroon Yousaf, Timothy E. Paterick, Khawaja Afzal Ammar Nov 2015

Cardiopulmonary Exercise Testing-Based Algorithm And Its Usefulness In Clinical Cardiology, Mirza Nubair Ahmad, Syed Hasan Yusuf, Rafath Ullah, Mary Ellis, Haroon Yousaf, Timothy E. Paterick, Khawaja Afzal Ammar

Journal of Patient-Centered Research and Reviews

Background: Only cardiopulmonary exercise (CPX) testing provides information on the ability of the cardiovascular system to meet the body’s metabolic demands in terms of oxygen consumption (VO2) and carbon dioxide production (VCO2). However, CPX testing is underutilized by cardiologists due to complex diagnostic algorithms involving up to 30 variables as well as lack of validation studies. In addition, CPX also provides oxygen (O2) pulse as a continuous measure of stroke volume, which is its superiority to other stress modalities in which systolic function is measured at peak stress and rest. In the literature, it …


Geographic Distribution Of Infant Death During Birth Hospitalization And Maternal Group B Streptococcus Colonization: Eastern Wisconsin, Jessica J.F. Kram, Dennis J. Baumgardner, Kiley A. Bernhard, Melissa A. Lemke Nov 2015

Geographic Distribution Of Infant Death During Birth Hospitalization And Maternal Group B Streptococcus Colonization: Eastern Wisconsin, Jessica J.F. Kram, Dennis J. Baumgardner, Kiley A. Bernhard, Melissa A. Lemke

Journal of Patient-Centered Research and Reviews

Background: Neonatal death rate in the United States is 4/1,000 live births; infant death rate is 6/1,000. Group B Streptococcus (GBS) may be transmitted from a colonized mother (rates vary from 15% to 35%) to the newborn during a vaginal delivery, and may contribute to neonatal death.

Purpose: To explore the geographic distribution and associated risk factors for maternal GBS colonization and infant death prior to discharge in eastern Wisconsin births.

Methods: Retrospective study of institutional data from PeriData.net, a comprehensive birth registry, utilizing data from 2007 through 2013 at all Aurora medical centers. Categorical variables were analyzed with chi-square …


In Vitro Growth Suppression Of Renal Carcinoma Cells By Curcumin, Santhi D. Konduri, Madhavi Latha Yadav Bangaru, Phu Thanh Do, Shenglin Chen, Jeffrey Woodliff, Sanjay Kansra Nov 2015

In Vitro Growth Suppression Of Renal Carcinoma Cells By Curcumin, Santhi D. Konduri, Madhavi Latha Yadav Bangaru, Phu Thanh Do, Shenglin Chen, Jeffrey Woodliff, Sanjay Kansra

Journal of Patient-Centered Research and Reviews

Purpose

Malignant clear cell renal carcinoma (ccRCC) is an aggressive tumor highly resistant to chemotherapy and radiation. Current therapeutic approaches to management of ccRCC have not significantly improved patient survival, therefore novel therapies are needed. Activated NFκB and STAT3 expression is associated with ccRCC pathogenesis. The dietary polyphenol curcumin is a well-documented antitumor agent and a known inhibitor of NFκB and STAT3 activation. Given the lack of effective therapies that block ccRCC progression, our objective was to examine whether curcumin could suppress the growth and migration of ccRCC cells, and whether this suppression was mediated via inhibition of NFκB and …


Model Assessment And Development Of Risk Stratification Of Surgical Site Infection Following Cesarean Delivery For A High-Risk, Urban Population, Dakisha N. Lewis, Nicole P. Salvo, Kiley A. Bernhard, Danielle M. Greer Nov 2015

Model Assessment And Development Of Risk Stratification Of Surgical Site Infection Following Cesarean Delivery For A High-Risk, Urban Population, Dakisha N. Lewis, Nicole P. Salvo, Kiley A. Bernhard, Danielle M. Greer

Journal of Patient-Centered Research and Reviews

Background: Surgical site infection (SSI) remains a major cause of morbidity despite efforts aimed at prevention and treatment. Risk stratification tools identify patients at greatest risk of SSI. Two models of stratification are: 1) the Centers for Disease Control and Prevention’s National Healthcare Safety Network SSI Risk Index (NHSN), which assigns risk based on surgery duration, surgical wound contamination and physical status; and 2) the New Risk Stratification Schema (NRSS). The NRSS aimed to improve upon NHSN by incorporating five variables: diabetes control, body mass index (BMI), chorioamnionitis, methods of placental extraction and skin closure.

Purpose: Our objectives were to: …


Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan Nov 2015

Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan

Journal of Patient-Centered Research and Reviews

Background: Congestive heart failure afflicts 5.7 million people in the United States with annual incidence of 600,000 and mortality of 280,000. Heart failure accounts for greater than 1 million hospitalizations annually and the single largest inpatient Medicare expense. As the U.S. population ages and greater emphasis is placed on population health as a means to bend projected health care expenditures, large health care organizations will need to develop algorithms to identify patients at high risk with heart failure and possibly preempt hospitalizations. Doppler echocardiography is routinely performed in clinical assessment of severe heart failure.

Purpose: We sought to determine echocardiographic …


Stent Thrombosis: Regional Prevalence, Risk Factors, And Outcomes, Andrew M. Ayers, Chi C. Cho, Robyn Shearer, M. Fuad Jan, Anjan Gupta Nov 2015

Stent Thrombosis: Regional Prevalence, Risk Factors, And Outcomes, Andrew M. Ayers, Chi C. Cho, Robyn Shearer, M. Fuad Jan, Anjan Gupta

Journal of Patient-Centered Research and Reviews

Background: Stent thrombosis is an infrequent but catastrophic complication of percutaneous coronary intervention (PCI). Many studies usually involve few stent thrombosis patients, generally less than 60, given its prevalence. While dual antiplatelet therapy has decreased stent thrombosis significantly in the general population, there are still patients who present with occurrence and recurrence of stent thrombosis.

Purpose: We sought to define the prevalence of site-specific stent thrombosis in a larger cohort of patients by specific coronary territories and determine if this had an effect on cardiovascular outcomes. In addition we sought to elucidate the role of previous coronary artery bypass grafting …


In Vitro Growth Suppression Of Renal Carcinoma Cells By Curcumin, Santhi Konduri, Madhavi Latha Yadav Bangaru, Phu Thanh Do, Shenglin Chen, Jeffrey Woodliff, Sanjay Kansra Nov 2015

In Vitro Growth Suppression Of Renal Carcinoma Cells By Curcumin, Santhi Konduri, Madhavi Latha Yadav Bangaru, Phu Thanh Do, Shenglin Chen, Jeffrey Woodliff, Sanjay Kansra

Journal of Patient-Centered Research and Reviews

Background: Malignant clear cell renal carcinoma (ccRCC) is an aggressive tumor that is highly resistant to chemotherapy and radiation. Current therapeutic approaches to management of ccRCC have not significantly improved patient survival, therefore novel therapies are needed. The von Hippel-Lindau tumor suppressor gene is frequently mutated in ccRCC resulting in unregulated transcriptional activity of hypoxia-inducible factors (HIF) 1α and 2α. HIF-mediated transcription leads to increased growth factor expression and growth factor receptor (GFR)-mediated signaling. NFκB and STAT3 are phosphorylated in response to GFR activation and modulate gene expression, which promotes cell growth and invasion. Activated NFκB and STAT3 expression is …


Tertiary Center Experience Of Catheter-Directed Thrombolysis For Immediately Threatened Acute Lower Limb Ischemia Of Native Vessels And Bypass Graft Thrombosis, Hani Hashim, M. Fuad Jan, Maharaj Singh, Suhail Allaqaband, Tanvir Bajwa, Anjan Gupta Nov 2015

Tertiary Center Experience Of Catheter-Directed Thrombolysis For Immediately Threatened Acute Lower Limb Ischemia Of Native Vessels And Bypass Graft Thrombosis, Hani Hashim, M. Fuad Jan, Maharaj Singh, Suhail Allaqaband, Tanvir Bajwa, Anjan Gupta

Journal of Patient-Centered Research and Reviews

Background: Catheter-directed thrombolysis (CDT) is an effective therapy and a class I indication for patients with acute limb ischemia (ALI, Rutherford categories I and IIa) of less than 14 days duration, and class IIb indication for ALI (Rutherford category IIb) with symptoms more than 14 days duration. However, there is no consensus on the initial management option for ALI (Rutherford category IIb) with symptoms less than 14 days duration.

Purpose: To evaluate the safety, efficacy and outcome of CDT, with or without bailout Angiojet mechanical thrombectomy, in patients with immediately threatened acute lower extremity ischemia (Rutherford category IIb) as a …


Disease-Management In Family Medicine Clinics Through The Addition Of A Health Coach: A Pilot Study, Crystal Y. Cichon, Jessica J.F. Kram, Tiffany A. Mullen, Pamela Voelkers, Kristin J. Magliocco, Kiley A. Bernhard, Dennis J. Baumgardner Nov 2015

Disease-Management In Family Medicine Clinics Through The Addition Of A Health Coach: A Pilot Study, Crystal Y. Cichon, Jessica J.F. Kram, Tiffany A. Mullen, Pamela Voelkers, Kristin J. Magliocco, Kiley A. Bernhard, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Background: In the United States, more than 80% of health care spending is focused on the management of chronic illnesses such as hypertension, diabetes and hyperlipidemia. Controlling these chronic diseases can lead to better health outcomes and decrease the number of preventable deaths. Patient self-management has shown to improve clinical outcomes. In a primary care setting, a multidisciplinary approach can more effectively educate patients on improving their health.

Purpose: To assess the impact of a health coach in a primary care setting as it relates to clinical outcomes.

Methods: Patients from two Aurora family medicine clinics were referred to a …


Aligning Asthma Education Across The Continuum Of Physician Education: Impact On Clinical Metrics, Lisa Sullivan Vedder, Deborah Simpson, Jacob L. Bidwell, John R. Brill, Theresa Frederick Nov 2015

Aligning Asthma Education Across The Continuum Of Physician Education: Impact On Clinical Metrics, Lisa Sullivan Vedder, Deborah Simpson, Jacob L. Bidwell, John R. Brill, Theresa Frederick

Journal of Patient-Centered Research and Reviews

Background: All trainees entering family medicine residency training programs after June 1, 2012, must complete the same American Board of Family Medicine (ABFM) Maintenance of Certification (MOC) requirements as practicing physicians. These shared requirements provide an opportunity to align physician education initiatives across the continuum focused around a clinical care topic to improve health care system metrics.

Purpose: To assess the initial effectiveness of an ABFM Asthma Part IV approved MOC module, aligned to meet residency and medical student program accreditation requirements, on health care system metrics.

Methods: An ABFM Asthma Part IV MOC module was implemented for family medicine …


Feasibility Of Atrial Delivery And Tracking Of Stem Cells In A Porcine Model, Nina Garlie, Timothy Hacker, Eric G. Schmuck, Jill Koch, Jayant Khitha, Amish Raval, Indrajit Choudhuri Nov 2015

Feasibility Of Atrial Delivery And Tracking Of Stem Cells In A Porcine Model, Nina Garlie, Timothy Hacker, Eric G. Schmuck, Jill Koch, Jayant Khitha, Amish Raval, Indrajit Choudhuri

Journal of Patient-Centered Research and Reviews

Background: Many patients undergoing open heart surgery have sinus node dysfunction and atrial fibrillation, leading to adverse outcomes. Mesenchymal stem cells (MSC) delivered at the time of surgery may have a reparative effect on atrial tissue, thereby improving sinus node function and reducing or preventing atrial fibrillation. Stem cell delivery to the atrium is entirely unstudied. This is a significant gap in medical research, as atrial disease contributes significantly to health care costs.

Purpose: The purpose of this pilot study is to establish a technique to deliver MSC to the atria through an open-chest model, to assess the safety of …


The Effect Of Percutaneous Closure Of Large Atrial Septal Defects On Right Ventricular Function In Adults, Armaan Shaikh, Alejandro Lopez-Mas, Suhail Allaqaband, Bijoy K. Khandheria, Abraham Getenet, Matt M. Umland, Maharaj Singh, Tanvir Bajwa Nov 2015

The Effect Of Percutaneous Closure Of Large Atrial Septal Defects On Right Ventricular Function In Adults, Armaan Shaikh, Alejandro Lopez-Mas, Suhail Allaqaband, Bijoy K. Khandheria, Abraham Getenet, Matt M. Umland, Maharaj Singh, Tanvir Bajwa

Journal of Patient-Centered Research and Reviews

Background: Percutaneous closure of atrial septal defects has been shown to be a safe alternative to surgery. Despite this, past studies have largely been focused on either small- to medium-sized atrial septal defects or percutaneous closure in children and young adults.

Purpose: Our study sought to examine if right ventricular function and size improved after percutaneous closure of large atrial septal defects in the adult population.

Methods: Over a 5-year span, 25 patients underwent percutaneous closure of a secundum atrial septal defect with an occluder device. A retrospective examination was conducted for each patient, including both echocardiography and chart review …


Contemporary Usage Of Intra-Arterial Catheter-Directed Thrombolytic (Cdt) Power Pulse Spray With Rheolytic Thrombectomy In Failed Cdt Alone For Acute Limb Ischemia, Hani Hashim, M. Fuad Jan, Maharaj Singh, Suhail Allaqaband, Tanvir Bajwa, Anjan Gupta Nov 2015

Contemporary Usage Of Intra-Arterial Catheter-Directed Thrombolytic (Cdt) Power Pulse Spray With Rheolytic Thrombectomy In Failed Cdt Alone For Acute Limb Ischemia, Hani Hashim, M. Fuad Jan, Maharaj Singh, Suhail Allaqaband, Tanvir Bajwa, Anjan Gupta

Journal of Patient-Centered Research and Reviews

Background: Acute lower limb ischemia (ALI) caused by arterial embolism, thrombosis of native vessels, and/or grafts is a serious condition associated with substantial morbidity and mortality. Peripheral arterial thrombolysis utilizing catheter-directed thrombolytic (CDT) has become established as a useful option in the management of ALI. However, use and outcome of adjunctive power pulse spray with rheolytic thrombectomy (PPSRT) following unsuccessful CDT is underreported in the literature.

Purpose: To evaluate outcome of contemporary use of intra-arterial CDT PPSRT as an adjunct to unsuccessful standard CDT for ALI.

Methods: We reviewed 78 consecutive patients (mean age 69 ± 14.2 years, 48.8% female) …


Complete Genome Sequence Of Staphylococcus Aureus, Strain Ilri_Eymole1/1, Isolated From A Kenyan Dromedary Camel, Saima Zubair, Anne Fischer, Anne Liljander, Jochen Meens, Jan Hegerman, Hadrien Gourlé, Richard P. Bishop, Ina Roebbelen, Mario Younan, Mudassir Imran Mustafa, Mamoona Mushtaq, Erik Bongcam-Rudloff, Joerg Jores Nov 2015

Complete Genome Sequence Of Staphylococcus Aureus, Strain Ilri_Eymole1/1, Isolated From A Kenyan Dromedary Camel, Saima Zubair, Anne Fischer, Anne Liljander, Jochen Meens, Jan Hegerman, Hadrien Gourlé, Richard P. Bishop, Ina Roebbelen, Mario Younan, Mudassir Imran Mustafa, Mamoona Mushtaq, Erik Bongcam-Rudloff, Joerg Jores

All Peer-Reviewed Publications

We report the genome of a Staphylococcus aureus strain (ILRI_Eymole1/1) isolated from a nasal swab of a dromedary camel (Camelus dromedarius) in North Kenya. The complete genome sequence of this strain consists of a circular chromosome of 2,874,302 bp with a GC-content of 32.88 %. In silico annotation predicted 2755 protein-encoding genes and 76 non-coding genes. This isolate belongs to MLST sequence type 30 (ST30). Phylogenetic analysis based on a subset of 283 core genes revealed that it falls within the human clonal complex 30 (CC30) S. aureus isolate cluster but is genetically distinct. About 79 % of the protein …


Microrna Molecular Profiling From Matched Tumor And Bio-Fluids In Bladder Cancer, David A. Armstrong, Benjamin B. Green, John D. Seigne, Alan R. Schned, Carmen Marsit Nov 2015

Microrna Molecular Profiling From Matched Tumor And Bio-Fluids In Bladder Cancer, David A. Armstrong, Benjamin B. Green, John D. Seigne, Alan R. Schned, Carmen Marsit

Dartmouth Scholarship

MicroRNAs have been identified as potential cancer biomarkers due to their presence and stability in many body fluids including urine and plasma, but the relationship of the pattern of expression of these messengers across various biological media has not been addressed and could provide important information in order to translate these biomarkers for epidemiologic or clinical use. We analyzed microRNA of matched FFPE-tumor tissue, plasma, urine exosomes (n = 16) and WBCs (n = 11) from patients with bladder cancer, using Nanostring miRNA assays and droplet digital PCR for validation. Pearson correlations were used to compare expression between …


Knowledge, Attitudes And Practices (Kap) On Rift Valley Fever Among Pastoralist Communities Of Ijara District, North Eastern Kenya, Ismail H. Abdi, Hippolyte D. Affognon, Anthony K. Wanjoya, Washington Onyango-Ouma, Rosemary Sang Nov 2015

Knowledge, Attitudes And Practices (Kap) On Rift Valley Fever Among Pastoralist Communities Of Ijara District, North Eastern Kenya, Ismail H. Abdi, Hippolyte D. Affognon, Anthony K. Wanjoya, Washington Onyango-Ouma, Rosemary Sang

All Peer-Reviewed Publications

Outbreaks of Rift Valley fever (RVF), a mosquito-borne viral zoonosis, have previously been associated with unusually heavy rainfall and extensive flooding. The disease is a serious public health problem in Africa and the Middle East, and is a potential global health threat. In Kenya, outbreaks of the disease have disproportionately affected impoverished pastoralist communities. This study sought to assess the knowledge, attitudes and practices (KAP) regarding RVF among the pastoralists of North Eastern Kenya, and to establish the determinants of KAP on RVF. A cross-sectional study involving 392 pastoralists living in Ijara district (Masalani and Ijara wards) was carried out …


Effect Of Genetic Background On The Dystrophic Phenotype In Mdx Mice., William D Coley, Laurent Bogdanik, Maria Candida Vila, Qing Yu, Terence A Partridge, Kanneboyina Nagaraju, +12 Additional Authors Nov 2015

Effect Of Genetic Background On The Dystrophic Phenotype In Mdx Mice., William D Coley, Laurent Bogdanik, Maria Candida Vila, Qing Yu, Terence A Partridge, Kanneboyina Nagaraju, +12 Additional Authors

Genomics and Precision Medicine Faculty Publications

Genetic background significantly affects phenotype in multiple mouse models of human diseases, including muscular dystrophy. This phenotypic variability is partly attributed to genetic modifiers that regulate the disease process. Studies have demonstrated that introduction of the γ-sarcoglycan null allele onto the DBA/2J background confers a more severe muscular dystrophy phenotype than the original strain, demonstrating the presence of genetic modifier loci in the DBA/2J background. To characterize the phenotype of dystrophin deficiency on the DBA/2J background, we created and phenotyped DBA/2J-congenic Dmdmdx mice (D2-mdx) and compared them to the original, C57BL/10ScSn-Dmdmdx (B10-mdx) model. These strains were compared to their respective …


Perceptions Of Medical Students Of The Role Of The Speech-Language Pathologist In Hiv/Aids Intervention, Kendal Klein, Emily Wagner, Kristi Moore, Tanvi Amin, Brenda Louw Nov 2015

Perceptions Of Medical Students Of The Role Of The Speech-Language Pathologist In Hiv/Aids Intervention, Kendal Klein, Emily Wagner, Kristi Moore, Tanvi Amin, Brenda Louw

ETSU Faculty Works

Survey research was utilized to explore Medical students’ perceptions of Speech-Language Pathologists’(SLP) and Medical Practitioner’s roles in meeting the healthcare needs of people living with HIV/AIDS(PLWHA). Results identified participants’ knowledge and perceptions. Recommendations suggest interprofessional education and training for both professions, at the pre-professional and professional levels.


Academic Preparation In Cleft Palate For Speech-Language Pathologists: Is The Icf-Cy (Who, 2007) Alive And Well?, Mary B. Graham, Jackie Palmer, Brenda Louw Nov 2015

Academic Preparation In Cleft Palate For Speech-Language Pathologists: Is The Icf-Cy (Who, 2007) Alive And Well?, Mary B. Graham, Jackie Palmer, Brenda Louw

ETSU Faculty Works

The purpose of this project is to determine inclusion of the ICF-CY in CLP training curricula for SLPs. Survey research was conducted with course instructors across the nation. Results describe the application of the ICF-CY in CLP courses at the graduate level. Recommendations for including the ICF-CY framework are made.


Mice Null For The Deubiquitinase Usp18 Spontaneously Develop Leiomyosarcomas, Fadzai Chinyengetere, David J. Sekula, Yun Lu, Andrew J. Giustini, Aarti Sanglikar, Masanori Kawakami, Tian Ma Nov 2015

Mice Null For The Deubiquitinase Usp18 Spontaneously Develop Leiomyosarcomas, Fadzai Chinyengetere, David J. Sekula, Yun Lu, Andrew J. Giustini, Aarti Sanglikar, Masanori Kawakami, Tian Ma

Dartmouth Scholarship

USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease.


Linalool Oxide: Generalist Plant Based Lure For Mosquito Disease Vectors, Vincent O. Nyasembe, David P. Tchouassi, Charles M. Mbogo, Catherine L. Sole, Christian Pirk, Baldwyn Torto Nov 2015

Linalool Oxide: Generalist Plant Based Lure For Mosquito Disease Vectors, Vincent O. Nyasembe, David P. Tchouassi, Charles M. Mbogo, Catherine L. Sole, Christian Pirk, Baldwyn Torto

All Peer-Reviewed Publications

Background: Lack of effective vaccines and therapeutics for important arboviral diseases such as Rift Valley fever (RVF) and dengue, necessitates continuous monitoring of vector populations for infections in them. Plant-based lures as surveillance tools has the potential of targeting mosquitoes of both sexes and females of varied physiological states; yet such lures are lacking for vectors of these diseases. Here, we present evidence of the effectiveness of linalool oxide (LO), a single plant-based lure previously developed for malaria vectors in trapping RVF vectors, Aedes mcintoshi and Aedes ochraceus, and dengue vector, Aedes aegypti. Methods: For RVF vectors, we used CDC …


Antioncogenic And Oncogenic Properties Of Nrf2 In Arsenic-Induced Carcinogenesis, Young-Ok Son, Poyil Pratheeshkumar, Ram Vinod Roy, Andrew Hitron, Lei Wang, Sasidharan Padmaja Divya, Mei Xu, Jia Luo, Gang Chen, Zhuo Zhang, Xianglin Shi Nov 2015

Antioncogenic And Oncogenic Properties Of Nrf2 In Arsenic-Induced Carcinogenesis, Young-Ok Son, Poyil Pratheeshkumar, Ram Vinod Roy, Andrew Hitron, Lei Wang, Sasidharan Padmaja Divya, Mei Xu, Jia Luo, Gang Chen, Zhuo Zhang, Xianglin Shi

Center for Research on Environmental Disease Faculty Publications

Arsenic (As3+) is a carcinogen with considerable environmental and occupational relevancy. The present study shows that As3+-transformed human lung bronchial epithelial BEAS-2B cells (AsT cells) exhibit the property of apoptosis resistance. The level of basal reactive oxygen species (ROS) is very low in AsT cells in correlation with elevated expressions of both antioxidant enzymes and antiapoptotic proteins. Nuclear factor erythroid 2-related factor (Nrf2) and p62 are constitutively expressed. These two proteins up-regulate antioxidant enzymes and antiapoptotic proteins. The knockdown of Nrf2 or p62 by small interfering RNA (siRNA) enhanced both ROS levels and As3+-induced …


Active Yap Promotes Pancreatic Cancer Cell Motility, Invasion And Tumorigenesis In A Mitotic Phosphorylation-Dependent Manner Through Lpar3., Shuping Yang, Lin Zhang, Vinee Purohit, Surendra K. Shukla, Xingcheng Chen, Fang Yu, Kai Fu, Yuanhong Chen, Joyce C. Solheim, Surendra K. Shukla, Wei Song, Jixin Dong Nov 2015

Active Yap Promotes Pancreatic Cancer Cell Motility, Invasion And Tumorigenesis In A Mitotic Phosphorylation-Dependent Manner Through Lpar3., Shuping Yang, Lin Zhang, Vinee Purohit, Surendra K. Shukla, Xingcheng Chen, Fang Yu, Kai Fu, Yuanhong Chen, Joyce C. Solheim, Surendra K. Shukla, Wei Song, Jixin Dong

Journal Articles: Eppley Institute

The transcriptional co-activator Yes-associated protein, YAP, is a main effector in the Hippo tumor suppressor pathway. We recently defined a mechanism for positive regulation of YAP through CDK1-mediated mitotic phosphorylation. Here, we show that active YAP promotes pancreatic cancer cell migration, invasion and anchorage-independent growth in a mitotic phosphorylation-dependent manner. Mitotic phosphorylation is essential for YAP-driven tumorigenesis in animals. YAP reduction significantly impairs cell migration and invasion. Immunohistochemistry shows significant upregulation and nuclear localization of YAP in metastases when compared with primary tumors and normal tissue in human. Mitotic phosphorylation of YAP controls a unique transcriptional program in pancreatic cells. …


Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi Nov 2015

Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi

School of Medicine Faculty Publications

The HIV-1 transactivator protein Tat is implicated in the neuronal damage that contributes to neurocognitive impairment affecting people living with HIV/AIDS. Aberrant splicing of TAU exon 10 results in tauopathies characterized by alterations in the proportion of TAU isoforms containing three (3R) or four (4R) microtubule-binding repeats. The splicing factor SC35/SRSF2 binds to nuclear RNA and facilitates the incorporation of exon 10 in the TAU molecule. Here, we utilized clinical samples, an animal model, and neuronal cell cultures and found that Tat promotes TAU 3R up-regulation through increased levels of phosphorylated SC35, which is retained in nuclear speckles. This mechanism …


Viral Infection Causes A Shift In The Self Peptide Repertoire Presented By Human Mhc Class I Molecules, Charles T. Spencer, Jelena S. Bezbradica, Mireya G. Ramos, Chenoa D. Arico, Stephanie B. Conant, Pavlo Gilchuk, Jennifer J. Gray, Mu Zheng, Xinnan Niu, William Hildebrand, Andrew J. Link, Sebastian Joyce Nov 2015

Viral Infection Causes A Shift In The Self Peptide Repertoire Presented By Human Mhc Class I Molecules, Charles T. Spencer, Jelena S. Bezbradica, Mireya G. Ramos, Chenoa D. Arico, Stephanie B. Conant, Pavlo Gilchuk, Jennifer J. Gray, Mu Zheng, Xinnan Niu, William Hildebrand, Andrew J. Link, Sebastian Joyce

Chemistry Faculty Research

Purpose

MHC class I presentation of peptides allows T cells to survey the cytoplasmic protein milieu of host cells. During infection, presentation of self peptides is, in part, replaced by presentation of microbial peptides. However, little is known about the self peptides presented during infection, despite the fact that microbial infections alter host cell gene expression patterns and protein metabolism.

Experimental design

The self peptide repertoire presented by HLA-A*01;01, HLA-A*02;01, HLA-B*07;02, HLA-B*35;01, and HLA-B*45;01 (where HLA is human leukocyte antigen) was determined by tandem MS before and after vaccinia virus infection.

Results

We observed a profound alteration in the self …


‘The Thing Is Not Knowing’: Patients' Perspectives On Surveillance Of An Indeterminate Pulmonary Nodule, Renda Soylemez Wiener, Michael K. Gould, Steven Woloshin, Lisa M. Schwartz, Jack Clark Nov 2015

‘The Thing Is Not Knowing’: Patients' Perspectives On Surveillance Of An Indeterminate Pulmonary Nodule, Renda Soylemez Wiener, Michael K. Gould, Steven Woloshin, Lisa M. Schwartz, Jack Clark

Dartmouth Scholarship

Background: The hundreds of thousands of patients found to have a potentially malignant pulmonary nodule each year are faced with tremendous uncertainty regarding what the nodule is and how it should be evaluated.

Objective: To explore patients' responses to the detection and evaluation of a pulmonary nodule.


Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes To Adopt A Tumorigenic Phenotype, Sujittra Chaidayet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm Jones, Paul J. Brindley, Jeffrey M. Bethony, +9 Additional Authors Nov 2015

Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes To Adopt A Tumorigenic Phenotype, Sujittra Chaidayet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm Jones, Paul J. Brindley, Jeffrey M. Bethony, +9 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Throughout Asia there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes including chronic inflammation and secretion of parasite proteins into the biliary epithelium drive infection towards cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown.

Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterised the EV proteome and associated changes in cholangiocytes after EV uptake, and detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and …


Might I Finally Take Part In A Huntington’S Disease Clinical Trials? An Update On The Latest Research, Kenneth P. Serbin Nov 2015

Might I Finally Take Part In A Huntington’S Disease Clinical Trials? An Update On The Latest Research, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.


“Inhumanly Beautiful”: The Aesthetics Of The Nineteenth-Century Deathbed Scene, Margo Masur Nov 2015

“Inhumanly Beautiful”: The Aesthetics Of The Nineteenth-Century Deathbed Scene, Margo Masur

English Theses

Death today is hidden from our everyday lives so it cannot intermingle with the general public. So when a family member dies, their body becomes an object in need of disposal; no longer can they be recognized as the familiar person they once were. To witness death is to force individuals to confront the truths of human existence, and for most of us seeing such a sight would fill us with an emotion of disgust. Yet during the nineteenth century, the burden of care towards the sick or dying was shared by a community of family, neighbors, and friends; the …


The Physiology And Psychology Of Exercise And Parkinson's Disease, Jess Gibson Nov 2015

The Physiology And Psychology Of Exercise And Parkinson's Disease, Jess Gibson

Senior Honors Theses

Parkinson’s disease is one of the most common degenerative neurological disorders and is currently lacking a cure. While physicians have long debated over the best treatment for Parkinson’s symptoms, treatments such as oral medication and deep brain stimulation have not yet shown to be a permanent solution to the disease. Recently, exercise has emerged as a contender in the fight against Parkinson’s and physicians and physiotherapists have been investigating the benefits of prescribing exercise programs to patients in an effort to slow progression of Parkinson’s symptoms. The following presents an analysis of the effects of exercise on Parkinson’s symptoms and …