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Patient-Specific Dendritic Cell Vaccines With Autologous Tumor Antigens In 72 Patients With Metastatic Melanoma., Robert O Dillman, Andrew N Cornforth, Edward F Mcclay, Carol Depriest May 2019

Patient-Specific Dendritic Cell Vaccines With Autologous Tumor Antigens In 72 Patients With Metastatic Melanoma., Robert O Dillman, Andrew N Cornforth, Edward F Mcclay, Carol Depriest

Articles, Abstracts, and Reports

Aim: Metastatic melanoma patients were treated with patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated cells from short-term autologous tumor cell lines.

Patients & methods: A total of 72 patients were enrolled in a single-arm Phase I/II (NCT00948480) trial or a randomized Phase II (NCT00436930).

Results: Toxicity was minimal. Median overall survival (OS) was 49.4 months; 5-year OS 46%. A 5-year OS was 72% for 18 recurrent stage 3 without measurable disease when treated and 53% for 30 stage 4 without measurable disease when treated. A total of 24 patients with measurable stage 4 when treated …


Second-Harmonic Generation Microscopy Analysis Reveals Proteoglycan Decorin Is Necessary For Proper Collagen Organization In Prostate., Kirby R. Campbell, Rajeev Chaudhary, Monica Montano, Renato V. Iozzo, Wade A. Bushman, Paul J. Campagnola May 2019

Second-Harmonic Generation Microscopy Analysis Reveals Proteoglycan Decorin Is Necessary For Proper Collagen Organization In Prostate., Kirby R. Campbell, Rajeev Chaudhary, Monica Montano, Renato V. Iozzo, Wade A. Bushman, Paul J. Campagnola

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Collagen remodeling occurs in many prostate pathologies; however, the underlying structural architecture in both normal and diseased prostatic tissues is largely unexplored. Here, we use second-harmonic generation (SHG) microscopy to specifically probe the role of the proteoglycan decorin (Dcn) on collagen assembly in a wild type (wt) and Dcn null mouse (Dcn  -    /    -  ). Dcn is required for proper organization of collagen fibrils as it regulates size by forming an arch-like structure at the end of the fibril. We have utilized SHG metrics based on emission directionality (forward-backward ratio) and relative conversion efficiency, which are both related to …


The Clinical Rationale For The Sentry Bioconvertible Inferior Vena Cava Filter For The Prevention Of Pulmonary Embolism., Michael D Dake, Gary M Ansel, Matthew S Johnson, Robert Mendes, H Bob Smouse May 2019

The Clinical Rationale For The Sentry Bioconvertible Inferior Vena Cava Filter For The Prevention Of Pulmonary Embolism., Michael D Dake, Gary M Ansel, Matthew S Johnson, Robert Mendes, H Bob Smouse

Heart and Vascular Articles

The Sentry inferior vena cava (IVC) filter is designed to provide temporary protection against pulmonary embolism (PE) during transient high-risk periods and then to bioconvert after 60 days after implantation. At the time of bioconversion, the device's nitinol arms retract from the filtering position into the caval wall. Subsequently, the stable stent-like nitinol frame is endothelialized. The Sentry bioconvertible IVC filter has been evaluated in a multicenter investigational-device-exemption pivotal trial (NCT01975090) of 129 patients with documented deep vein thrombosis (DVT) or PE, or at temporary risk of developing DVT or PE, and with contraindications to anticoagulation. Successful filter conversion was …


Leptin Produced By Obesity-Altered Adipose Stem Cells Promotes Metastasis But Not Tumorigenesis Of Triple-Negative Breast Cancer In Orthotopic Xenograft And Patient-Derived Xenograft Models, Rachel A. Sabol, Annie C. Bowles, Alex Côté, Rachel Wise, Benjamen O'Donnell, Margarite D. Matossian, Fokhrul M. Hossain, Hope E. Burks, Luis Del Valle, Lucio Miele, Bridgette M. Collins-Burow, Matthew E. Burow, Bruce A. Bunnell May 2019

Leptin Produced By Obesity-Altered Adipose Stem Cells Promotes Metastasis But Not Tumorigenesis Of Triple-Negative Breast Cancer In Orthotopic Xenograft And Patient-Derived Xenograft Models, Rachel A. Sabol, Annie C. Bowles, Alex Côté, Rachel Wise, Benjamen O'Donnell, Margarite D. Matossian, Fokhrul M. Hossain, Hope E. Burks, Luis Del Valle, Lucio Miele, Bridgette M. Collins-Burow, Matthew E. Burow, Bruce A. Bunnell

School of Medicine Faculty Publications

BACKGROUND: Breast cancer is the second leading cause of cancer deaths in the USA. Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer with high rates of metastasis, tumor recurrence, and resistance to therapeutics. Obesity, defined by a high body mass index (BMI), is an established risk factor for breast cancer. Women with a high BMI have increased incidence and mortality of breast cancer; however, the mechanisms(s) by which obesity promotes tumor progression are not well understood. METHODS: In this study, obesity-altered adipose stem cells (obASCs) were used to evaluate obesity-mediated effects of TNBC. Both in vitro …


Altered Detrusor Contractility And Voiding Patterns In Mice Lacking The Mechanosensitive Trek-1 Channel., Ricardo H. Pineda, Joseph Hypolite, Sanghee Lee, Alonso Carrasco, Nao Iguchi, Randall B. Meacham, Anna P. Malykhina May 2019

Altered Detrusor Contractility And Voiding Patterns In Mice Lacking The Mechanosensitive Trek-1 Channel., Ricardo H. Pineda, Joseph Hypolite, Sanghee Lee, Alonso Carrasco, Nao Iguchi, Randall B. Meacham, Anna P. Malykhina

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Previously published results from our laboratory identified a mechano-gated two-pore domain potassium channel, TREK-1, as a main mechanosensor in the smooth muscle of the human urinary bladder. One of the limitations of in vitro experiments on isolated human detrusor included inability to evaluate in vivo effects of TREK-1 on voiding function, as the channel is also expressed in the nervous system, and may modulate micturition via neural pathways. Therefore, in the present study, we aimed to assess the role of TREK-1 channel in bladder function and voiding patterns in vivo by using TREK-1 knockout (KO) mice.

METHODS: Adult C57BL/6 …


Monitoring Progression Of Ductal Carcinoma In Situ Using Photoacoustics And Contrast-Enhanced Ultrasound., Ryan Margolis, Corinne Wessner, Maria Stanczak, Ji-Bin Liu, Jingzhi Li, Kibo Nam, Flemming Forsberg, John R. Eisenbrey May 2019

Monitoring Progression Of Ductal Carcinoma In Situ Using Photoacoustics And Contrast-Enhanced Ultrasound., Ryan Margolis, Corinne Wessner, Maria Stanczak, Ji-Bin Liu, Jingzhi Li, Kibo Nam, Flemming Forsberg, John R. Eisenbrey

Department of Radiology Faculty Papers

Breast cancer is the leading form of cancer in women, accounting for approximately 41,400 deaths in 2018. While a variety of risk factors have been identified, physical exercise has been linked to reducing both the risk and aggressiveness of breast cancer. Within breast cancer, ductal carcinoma in situ (DCIS) is a common finding. However, less than 25% of DCIS tumors actually progress into invasive breast cancer, resulting in overtreatment. This overtreatment is due to a lack of predictive precursors to assess aggressiveness and development of DCIS. We hypothesize that tissue oxygenation and perfusion measured by photoacoustic and contrast-enhanced ultrasound imaging, …


A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker May 2019

A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker

Pharmaceutical Sciences Faculty Publications

Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates < 40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.


Improved Orthopaedic Repairs Through Mechanically Optimized, Adhesive Biomaterials, Stephen Wheeler Linderman May 2019

Improved Orthopaedic Repairs Through Mechanically Optimized, Adhesive Biomaterials, Stephen Wheeler Linderman

McKelvey School of Engineering Graduate Student Theses & Dissertations

Despite countless surgical advances over the last several decades refining surgical approaches, repair techniques, and tools to treat tendon and tendon-to-bone injuries, we are still left with repair solutions that rely on fairly crude underlying mechanical principles. Musculoskeletal soft tissues have evolved to transfer high loads by optimizing stress distribution profiles across the tissue at each length scale. However, instead of mimicking these natural load transfer mechanisms, conventional suture approaches are limited by high load transfer across only a small number of anchor points within tissue. This leads to stress concentrations at anchor points that often cause repair failure as …


Effect Of Intravenous Phenobarbital On Left Ventricular Myocardial Contractility Determined By Echocardiography In Children., Arpan R. Doshi, Monesha Gupta Malhotra, Duraisamy Balaguru, Devendra Amre, Christian Erikson May 2019

Effect Of Intravenous Phenobarbital On Left Ventricular Myocardial Contractility Determined By Echocardiography In Children., Arpan R. Doshi, Monesha Gupta Malhotra, Duraisamy Balaguru, Devendra Amre, Christian Erikson

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Animal studies and rare human studies have suggested a negative effect of barbiturates on cardiac function. Although intravenous (IV) phenobarbital is used routinely in children in the clinical setting, studies in children are lacking. We performed a study to evaluate effect of IV phenobarbital loading on myocardial systolic function of children.

Methods: In a prospective pilot study in children without congenital heart defects, the effect of IV phenobarbital was evaluated on the left ventricular systolic function measured by ejection fraction (EF) by Simpson's method via an echocardiogram. Any child less than 18 years of age who received IV loading …


Secreted Tumor-Associated Cytochrome As A Blood-Based Biomarker For Cancer, Rolf Joseph Craven May 2019

Secreted Tumor-Associated Cytochrome As A Blood-Based Biomarker For Cancer, Rolf Joseph Craven

Pharmacology and Nutritional Sciences Faculty Patents

Disclosed herein are methods for detecting Pgrmc 1 in bodily fluids, e.g., blood, plasma and serum, wherein detection of Pgrmcl is a biomarker for the presence of cancer, e.g., lung cancer or head or neck cancer. Pgrmc 1 levels in bodily fluids may be used to predict patient prognosis, e.g., survival and response to therapy.


Initial Experience Of A Community Gastroenterology Practice With Ultraslim Colonoscopy., Rajesh Essrani, Patrick Hickey Do, Hiral N. Shah Md May 2019

Initial Experience Of A Community Gastroenterology Practice With Ultraslim Colonoscopy., Rajesh Essrani, Patrick Hickey Do, Hiral N. Shah Md

Department of Medicine

Colonoscopies are performed for cancer screening as well as for other diagnostic and therapeutic reasons. It is considered successful if cecal intubation is achieved and adequate mucosa is visualized. It is not always possible to achieve cecal intubation due to multiple reasons such as sharp angulation or fixed segments of the colon and stricture. A pediatric colonoscope (PDC) and an ultrathin colonoscope (UTC) are used as a tool to negotiate sharp angulation and the fixed segments of the colon because their small diameter allows easy movement. An ultrathin colonoscope is used at many practices as a rescue in situations where …


Dietary Polyphenols, Resveratrol And Pterostilbene Exhibit Antitumor Activity On An Hpv E6-Positive Cervical Cancer Model: An In Vitro And In Vivo Analysis, Kaushiki Chatterjee, Sumit Mukherjee, Jonathan Vanmanen, Probal Banerjee, Jimmie E. Fata May 2019

Dietary Polyphenols, Resveratrol And Pterostilbene Exhibit Antitumor Activity On An Hpv E6-Positive Cervical Cancer Model: An In Vitro And In Vivo Analysis, Kaushiki Chatterjee, Sumit Mukherjee, Jonathan Vanmanen, Probal Banerjee, Jimmie E. Fata

Publications and Research

Human papilloma virus (HPV)-induced cervical cancer is one of themost frequent cancers in women residing in underdeveloped countries. Natural compounds like polyphenols continue to be of scientific interest as non-toxic effective alternative treatments. Our previous work showed the efficacy of two polyphenols, resveratrol, and pterostilbene on human HeLa cells. Here we explored the in vitro anti-cancer activity and in vivo anti-tumor potential of these two structurally similar compounds on HPV oncogene E6 and E7 positive murine TC1 cells. In vitro analysis confirmed the cytotoxic potential of both resveratrol and pterostilbene compounds with each having a low IC50 value and each …


Loss Of Nrf2 Results In Decreased Neuronal Arborization And Synaptic Density And Causes Exacerbated Age-Related Cognitive Impairment., Mikah Brandes, Nora Gray, Maya Caruso, Jonathan Zweig, Amala Soumyanath, Joseph F. Quinn May 2019

Loss Of Nrf2 Results In Decreased Neuronal Arborization And Synaptic Density And Causes Exacerbated Age-Related Cognitive Impairment., Mikah Brandes, Nora Gray, Maya Caruso, Jonathan Zweig, Amala Soumyanath, Joseph F. Quinn

Student Research Symposium

Background: As the brain ages, free radicals accumulate and cause damage to cellular macromolecules. This increased oxidative damage is thought to contribute to the cognitive decline observed in aging. Activation of the antioxidant regulatory transcription factor NRF2 (Nuclear factor erythroid-derived 2) has been shown to improve neuronal health in aging and neurodegenerative diseases. Yet exactly how NRF2 participates in maintaining synaptic and cognitive function has not been fully elucidated. This study investigates how loss of NRF2 affects synaptic density and cognitive performance in aged mice.

Methods: Dendritic arborization and synaptic was evaluated in hippocampal neurons isolated from mice lacking NRF2 …


Extracellular Vesicle Encapsulated Micrornas In Patients With Type 2 Diabetes Are Affected By Metformin Treatment., Vikas Ghai, Taek-Kyun Kim, Alton Etheridge, Trine Nielsen, Torben Hansen, Oluf Pedersen, David Galas, Kai Wang May 2019

Extracellular Vesicle Encapsulated Micrornas In Patients With Type 2 Diabetes Are Affected By Metformin Treatment., Vikas Ghai, Taek-Kyun Kim, Alton Etheridge, Trine Nielsen, Torben Hansen, Oluf Pedersen, David Galas, Kai Wang

Articles, Abstracts, and Reports

Recently, microRNAs (miRNAs) in circulating extracellular vesicles (EVs), have emerged as a source of potential biomarkers for various pathophysiological conditions, including metabolic disorders such as diabetes. Type 2 diabetes mellitus (T2DM), is the most prevalent form of diabetes in the USA, with 30 million diagnosed patients. Identifying miRNA biomarkers that can be used to assess response to glucose lowering treatments would be useful. Using patient plasma samples from a subset of the Danish Metagenomics of the Human Intestinal Tract (MetaHIT) cohort, we characterized miRNAs from whole plasma, plasma-derived EVs, and EV-depleted plasma by small RNA-sequencing to identify T2DM associated miRNAs. …


The Relationship Between Psychological States And Health Perception In Individuals At Risk For Cardiovascular Disease, Kyoung Suk Lee, Frances J. Feltner, Alison L. Bailey, Terry A. Lennie, Misook L. Chung, Brittany L. Smalls, Donna L. Schuman, Debra K. Moser May 2019

The Relationship Between Psychological States And Health Perception In Individuals At Risk For Cardiovascular Disease, Kyoung Suk Lee, Frances J. Feltner, Alison L. Bailey, Terry A. Lennie, Misook L. Chung, Brittany L. Smalls, Donna L. Schuman, Debra K. Moser

Family and Community Medicine Faculty Publications

Backgrounds: Perceptions of health are important to motivate people to change behaviors. Non-adherence to healthy behaviors that prevent cardiovascular disease may result from inadequate health perceptions. However, there are few studies investigating relationships between health perceptions and psychological states.

Objective: To determine whether psychological states (ie, depressive symptoms and anxiety) are associated with the congruency between health perception and estimated risk for cardiovascular disease in adults with 2 or more cardiovascular disease risk factors.

Methods: Community dwellers at risk for cardiovascular disease were asked to complete the Patient Health Questionnaire-9 and the anxiety subscale of the Brief Symptom Inventory to …


Measurement Of Bystander Actions In Violence Intervention Evaluation: Opportunities And Challenges, Heather M. Bush, Samuel C. Bell, Ann L. Coker May 2019

Measurement Of Bystander Actions In Violence Intervention Evaluation: Opportunities And Challenges, Heather M. Bush, Samuel C. Bell, Ann L. Coker

Biostatistics Faculty Publications

Purpose of Review

This review discusses design and methodological challenges specific to measuring bystander actions in the evaluation of bystander-based violence prevention programming. “Bystanders” are defined as people who are present immediately before, during and/or after a violent event, but are not a perpetrator nor the intended victim. Bystander-based violence prevention programs seek to prevent or mitigate violent events by empowering bystanders to intervene on acts of violence and social norms that promulgate violence.

Recent Findings

Effective bystander-based violence prevention programs demonstrate increased bystander intentions, actions, and attitudes [Bringing in the Bystander: Banyard et al. J Community Psychol. 2007;35:463-481; iSCREAM: …


Relationship Between Binge Eating Disorder And Circadian Chronotype, Leon B. Jons May 2019

Relationship Between Binge Eating Disorder And Circadian Chronotype, Leon B. Jons

Theses & Dissertations

Binge eating disorder (BED) is a common condition in the general population and is more common in individuals with obesity. The later timing of food intake has been associated with an increase incidence of obesity. The purpose of this study was to evaluate the relationship between circadian chronotype and BED in a population of individuals with obesity. The sample consists of a retrospective review of 170 subjects presenting to an obesity medicine clinic who had been clinically evaluated for BED and chronotype.

No significant correlation was found between BED and a late chronotype in this population. In a secondary analysis …


Human Immunodeficiency Virus Theranostics, Christopher J. Woldstad May 2019

Human Immunodeficiency Virus Theranostics, Christopher J. Woldstad

Theses & Dissertations

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. However, maintenance of sustained plasma drug levels, for weeks or months, after a single high-level dosing, could improve regimen adherence but, at the same time, affect systemic toxicities. Of these, the most troubling are those that affect the central nervous system (CNS) In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal …


Evaluation Of The Role Of Microvascular Pathology On Peripheral Artery Disease, Constance Mietus May 2019

Evaluation Of The Role Of Microvascular Pathology On Peripheral Artery Disease, Constance Mietus

Theses & Dissertations

Background: Peripheral Artery Disease (PAD) begins with atherosclerotic narrowing of arteries, including those that supply the legs. Individuals with PAD experience pain during walking, which becomes increasingly limiting. Studies from our group and others have shown that a myopathy is present in the skeletal muscle of PAD patients, and is characterized by myofiber degeneration, fibrosis, and remodeling of vessels ranging from 50 – 150 mm in diameter. However, microvascular pathology, particularly of the smallest microvessels (5 – 15 mm in diameter) remains poorly characterized. Furthermore, little is known about the relationships between microvascular architecture, microperfusion, and patient walking performance. We …


Visual And Verbal Serial List Learning In Patients With Statistically-Determined Mild Cognitive Impairment., Victor Wasserman, Sheina Emrani, Emily F Matusz, David Miller, Kelly Davis Garrett, Katherine A Gifford, Timothy J Hohman, Angela L Jefferson, Rhoda Au, Rod Swenson, David J Libon, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda). May 2019

Visual And Verbal Serial List Learning In Patients With Statistically-Determined Mild Cognitive Impairment., Victor Wasserman, Sheina Emrani, Emily F Matusz, David Miller, Kelly Davis Garrett, Katherine A Gifford, Timothy J Hohman, Angela L Jefferson, Rhoda Au, Rod Swenson, David J Libon, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda).

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background and Objective: Prior research with patients with mild cognitive impairment (MCI) suggests that visual versus verbal episodic memory test performance may be more sensitive to emergent illness. However, little research has examined visual versus verbal episodic memory performance as related to MCI subtypes.

Research Design and Methods: Patients were diagnosed with non-MCI, amnestic MCI (aMCI), and combined mixed/dysexecutive MCI (mixed/dys MCI). Visual and verbal episodic memory were assessed with the Brief Visuospatial Memory Test-Revised (BVMT-R) and the 12-word Philadelphia (repeatable) Verbal Learning Test (P[r]VLT), respectively.

Results: BVMT-R and P(r)VLT scores yielded similar between-group patterns of performance. Non-MCI patients scored …


One Amino Acid Change Of Angiotensin Ii Diminishes Its Effects On Abdominal Aortic Aneurysm, Ya Wang, Yinchuan Xu, Congqing Wu, Hongguang Xia, Yingchao Wang, Jinliang Nan, Jinghai Chen, Hong Yu, Wei Zhu, Peng Shi, Alan Daugherty, Hong S. Lu, Jian'an Wang May 2019

One Amino Acid Change Of Angiotensin Ii Diminishes Its Effects On Abdominal Aortic Aneurysm, Ya Wang, Yinchuan Xu, Congqing Wu, Hongguang Xia, Yingchao Wang, Jinliang Nan, Jinghai Chen, Hong Yu, Wei Zhu, Peng Shi, Alan Daugherty, Hong S. Lu, Jian'an Wang

Saha Cardiovascular Research Center Faculty Publications

Angiotensin (Ang) A is formed by the decarboxylation of the N terminal residue of AngII. The present study determined whether this one amino acid change impacted effects of AngII on abdominal aortic aneurysm (AAA) formation in mice. Computational analyses implicated that AngA had comparable binding affinity to both AngII type 1 and 2 receptors as AngII. To compare effects of these two octapeptides in vivo, male low-density lipoprotein receptor (Ldlr) or apolipoprotein E (Apoe) deficient mice were infused with either AngII or AngA (1 μg/kg/min) for 4 weeks. While AngII infusion induced AAA consistently in …


Effects Of The Kcnq Channel Opener Ezogabine On Functional Connectivity Of The Ventral Striatum And Clinical Symptoms In Patients With Major Depressive Disorder, Aaron Tan, Sara Costi, Laurel S. Morris, Nicholas T. Van Dam, Marin Kautz, Alexis E. Whitton, Allyson K. Friedman, Katherine A. Collins, Gabriella Ahle, Nisha Chadha, Brian Do, Diego A. Pizzagalli, Dan V. Iosifescu, Eric J. Nestler, Ming-Hu Han, James W. Murrough May 2019

Effects Of The Kcnq Channel Opener Ezogabine On Functional Connectivity Of The Ventral Striatum And Clinical Symptoms In Patients With Major Depressive Disorder, Aaron Tan, Sara Costi, Laurel S. Morris, Nicholas T. Van Dam, Marin Kautz, Alexis E. Whitton, Allyson K. Friedman, Katherine A. Collins, Gabriella Ahle, Nisha Chadha, Brian Do, Diego A. Pizzagalli, Dan V. Iosifescu, Eric J. Nestler, Ming-Hu Han, James W. Murrough

Publications and Research

Major depressive disorder (MDD) is a leading cause of disability worldwide, yet current treatment strategies remain limited in their mechanistic diversity. Recent evidence has highlighted a promising novel pharmaceutical target—the KCNQ-type potassium channel—for the treatment of depressive disorders, which may exert a therapeutic effect via functional changes within the brain reward system, including the ventral striatum. The current study assessed the effects of the KCNQ channel opener ezogabine (also known as retigabine) on reward circuitry and clinical symptoms in patients with MDD. Eighteen medication-free individuals with MDD currently in a major depressive episode were enrolled in an open-label study and …


Repetitive Mild Traumatic Brain Injury Impairs Performance In A Rodent Assay Of Cognitive Flexibility, Christopher P. Knapp, Doug P. Fox, Ramesh Raghupathi, Laura L. Giacometti, Stan B. Floresco, Barry D. Waterhouse, Rachel L. Navarra May 2019

Repetitive Mild Traumatic Brain Injury Impairs Performance In A Rodent Assay Of Cognitive Flexibility, Christopher P. Knapp, Doug P. Fox, Ramesh Raghupathi, Laura L. Giacometti, Stan B. Floresco, Barry D. Waterhouse, Rachel L. Navarra

Rowan-Virtua Research Day

Mild traumatic brain injury (mTBI) occurs in almost 80% of the 3 million reported cases of TBI-related emergency department visits each year in the United States. The majority of mTBIs, sometimes classified as concussions, are due to sports-related activities and typically occur repeatedly over the course of an athlete’s career. mTBI symptoms are generally classified as either somatic or neuropsychiatric/cognitive in nature and include impairments in prefrontal cortex mediated functions, including attention, memory, processing speed, reaction times, problem solving, and cognitive flexibility. To date, there remains a major gap in our understanding of the behavioral manifestations, underlying neurobiology, and treatment …


The Effects Of Tracheal Occlusion On Wnt Signaling In A Rabbit Model Of Congenital Diaphragmatic Hernia, Martina Mudri, Shane A. Smith, Christina Vanderboor, Jacob Davidson, Timothy R.H. Regnault, Andreana Bütter May 2019

The Effects Of Tracheal Occlusion On Wnt Signaling In A Rabbit Model Of Congenital Diaphragmatic Hernia, Martina Mudri, Shane A. Smith, Christina Vanderboor, Jacob Davidson, Timothy R.H. Regnault, Andreana Bütter

Paediatrics Publications

Purpose: Tracheal occlusion (TO)reverses pulmonary hypoplasia (PH)in congenital diaphragmatic hernia (CDH), but its mechanism of action remains poorly understood. Wnt signaling plays a critical role in lung development, but few studies exist. The purpose of our study was to a)confirm that our CDH rabbit model produced PH which was reversed by TO and b)determine the effects of CDH +/− TO on Wnt signaling. Methods: CDH was created in fetal rabbits at 23 days, TO at 28 days, and lung collection at 31 days. Lung body weight ratio (LBWR)and mean terminal bronchiole density (MTBD)were determined. mRNA and miRNA expression was determined …


The Practice Of Dermatology Ain't What It Used To Be: The Preauthorization Catastrophe., Lawrence Charles Parish, Jennifer L. Parish, W. Clark Lambert, Carmela Ciferni May 2019

The Practice Of Dermatology Ain't What It Used To Be: The Preauthorization Catastrophe., Lawrence Charles Parish, Jennifer L. Parish, W. Clark Lambert, Carmela Ciferni

Department of Dermatology and Cutaneous Biology Faculty Papers

Many of us remember when a dermatology practice was cash only, and $5 cash was considered appropriate for a specialist. The general practitioner received $2 for an office visit and $4 for a home call. If you recall those days, “dearie you are much older than I.” 1

Not so long ago, the practitioner was confronted with obtaining a referral from the Health Maintenance Organization (HMO) in order to see the patient. Some plans permitted only four such referrals for specialists, annually, so the patient, who might have had a visit or two for gastritis and a similar number of …


Complementary Feeding Practices And Their Determinants In Infants And Young Children On Follow Up At A Private Tertiary Hospital In Nairobi, Catherine Muthoni May 2019

Complementary Feeding Practices And Their Determinants In Infants And Young Children On Follow Up At A Private Tertiary Hospital In Nairobi, Catherine Muthoni

Master of Medicine in Paediatrics and Child Health

Background: More than a third of all deaths in children under five years of age worldwide, are linked to maternal and child under-nutrition. Appropriate complementary feeding is one of the interventions with the greatest potential for reduction of nutrition-related diseases and mortalities, yet uptake of the recommended World Health Organisation (WHO) infant and young child feeding practices in Kenya remains low. Despite provision of nutrition education at Aga Khan University Hospital- Nairobi (AKUH-N), both growth faltering and over-weight trends have been observed, pointing to both under- and over-nutrition. Objectives: This study investigated caregivers' knowledge , attitude and practice (KAP) of …


Silencing The Guca2a-Gucy2c Tumor Suppressor Axis In Cin, Serrated, And Msi Colorectal Neoplasia., Babar Bashir, Dante J. Merlino, Jeff A. Rappaport, Esteban Gnass, Juan P. Palazzo, Ying Feng, Eric R R. Fearon, Adam E. Snook, Scott A. Waldman May 2019

Silencing The Guca2a-Gucy2c Tumor Suppressor Axis In Cin, Serrated, And Msi Colorectal Neoplasia., Babar Bashir, Dante J. Merlino, Jeff A. Rappaport, Esteban Gnass, Juan P. Palazzo, Ying Feng, Eric R R. Fearon, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Colorectal cancers (CRCs) initiate through distinct mutations, including in APC pathway components leading to tubular adenomas (TAs); in BRAF, with epigenetic silencing of CDX2, leading to serrated adenomas (SAs); and in the DNA mismatch repair machinery driving microsatellite instability (MSI). Transformation through the APC pathway involves loss of the hormone GUCA2A that silences the tumor-suppressing receptor GUCY2C. Indeed, oral hormone replacement is an emerging strategy to reactivate GUCY2C and prevent CRC initiation and progression. Moreover, retained expression by tumors arising from TAs has established GUCY2C as a diagnostic and therapeutic target to prevent and treat metastatic CRC. Here, we defined …


The In Vivo Effects Of Alcohol In Lung And Liver Are At Least Partially Mediated Through The Alpha 4 Nicotinic Acetylcholine Receptor, J. Ritzenthaler, E. Torres-Gonzalez, G. E. Arteel, J. Roman May 2019

The In Vivo Effects Of Alcohol In Lung And Liver Are At Least Partially Mediated Through The Alpha 4 Nicotinic Acetylcholine Receptor, J. Ritzenthaler, E. Torres-Gonzalez, G. E. Arteel, J. Roman

Division of Pulmonary, Allergy, and Critical Care Medicine Posters

Rational: Chronic alcohol abuse is a major risk factor for the development of acute lung injury, with 40% of annual cases in the U.S. linked to this disorder. Alcohol is not only associated with increased incidence of acute lung injury in at-risk individuals, but also increased mortality. The exact mechanisms by which alcohol abuse renders the host susceptible to acute lung injury remain poorly defined. We have reported that α4 nicotinic acetylcholine receptors (α4 nAChRs) may serve as potential sensors for alcohol in lung fibroblasts; however, we have not tested their role in vivo.

Methods: To test the role of …


Is There An Association Between Placental Inflammatory Lesions And Vaginal Microbiota In Preterm Labour? A Case Control Study, David Ogechi Atandi May 2019

Is There An Association Between Placental Inflammatory Lesions And Vaginal Microbiota In Preterm Labour? A Case Control Study, David Ogechi Atandi

Master of Medicine in Anatomic Pathology

Background: Preterm birth continues to be a significant contributor to neonatal mortality and morbidity despite diverse unique interventional strategies. There is need for better understanding of differences and influences of the now characterized vaginal microbiome on terminal inflammatory effects in the uterine microenvironment in term and preterm labour to improve on current strategies. How the existence of a postulated placenta microbiome also affects this understanding should be considered. Objectives: The aim of this study was to explore the association between the maternal vaginal microbiota and placental inflammatory lesions in preterm labour and to determine the presence of a placenta microbiome …


Aortic Valve Opening And Closure: The Clover Dynamics., Emmanuel Lansac, Hou-Sen Lim, Yu Shomura, Khee Hiang Lim, Nolan T Rice, Isabelle Di Centa, Pouya Youssefi, Wolfgang Goetz, Carlos M G Duran May 2019

Aortic Valve Opening And Closure: The Clover Dynamics., Emmanuel Lansac, Hou-Sen Lim, Yu Shomura, Khee Hiang Lim, Nolan T Rice, Isabelle Di Centa, Pouya Youssefi, Wolfgang Goetz, Carlos M G Duran

Articles, Abstracts, and Reports

Background: Systolic aortic root expansion is reported to facilitate valve opening, but the precise dynamics remain unknown. A sonometric study with a high data sampling rate (200 to 800 Hz) was conducted in an acute ovine model to better understand the timing, mechanisms, and shape of aortic valve opening and closure.

Methods: Eighteen piezoelectric crystals were implanted in 8 sheep at each annular base, commissures, sinus of Valsalva, sinotubular junction, nodulus of Arantius, and ascending aorta (AA). Geometric changes were time related to pressures and flows.

Results: The aortic root was hemodynamically divided into left ventricular (LV) and aortic compartments …