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Association Between Calcaneal Spurs And Plantar Fasciitis: A Study Comparing Heel Plain Radiography And Sonography, Micah Silaba Ominde May 2017

Association Between Calcaneal Spurs And Plantar Fasciitis: A Study Comparing Heel Plain Radiography And Sonography, Micah Silaba Ominde

Master of Medicine in Imaging and Diagnostic Radiology

Background: Heel pain is a common clinical entity that requires appropriate diagnostic evaluation. Multiple clinical conditions are known to cause heel pain but plantar fasciitis is the most common. Calcaneal spurs are thought to be associated with heel pain and plantar fasciitis but conclusive studies to prove this are sparse. Plain radiography is usually the first line imaging modality for imaging patients with heel pain. Magnetic Resonance Imaging is the gold standard for diagnosing plantar fasciitis but studies have shown ultrasound to be comparable in sensitivity and specificity. The aim is to establish whether a relationship exists between calcaneal spurs …


Impact Of Deep Versus Awake Laryngeal Mask Airway Removal On Airway Complications In Spontaneously Breathing Adult Patients Following Isoflurane General Anesthesia., Ronald Ombaka May 2017

Impact Of Deep Versus Awake Laryngeal Mask Airway Removal On Airway Complications In Spontaneously Breathing Adult Patients Following Isoflurane General Anesthesia., Ronald Ombaka

Master of Medicine in Anaesthesiology

Background: The Laryngeal Mask Airway (LMA) is one of several supra-glottic airway management devices used in anaesthesia. The scope of use of the LMA is progressively expanding to areas previously contraindicated, for instance laparoscopy and prone position surgery. Certain aspects of LMA use remain unsettled. Whether to remove the LMA when a patient is “awake” vs “deep” following anaesthesia is one such area. The manufacturer Ambu® recommends that the AuraOnce™ LMA be removed once the patient is fully awake and protective airway reflexes are active. Despite this, several studies have shown benefit in removal of the LMA while a patient …


A Randomized Controlled Trial Comparing The Proportion Of Hypoxia In Sedated Adults Undergoing Upper Gastrointestinal Endoscopy Using Target Controlled Infusion Of Propofol Versus Intermittent Boluses., Catherine Ndosi May 2017

A Randomized Controlled Trial Comparing The Proportion Of Hypoxia In Sedated Adults Undergoing Upper Gastrointestinal Endoscopy Using Target Controlled Infusion Of Propofol Versus Intermittent Boluses., Catherine Ndosi

Master of Medicine in Anaesthesiology

Background: A wide variety of sedation techniques are employed to facilitate various invasive diagnostic and therapeutic procedures. Increasingly, propofol is emerging as the preferred sedative agent. Traditionally, it has been administered as intermittent boluses to achieve deep sedation to facilitate gastrointestinal endoscopy. Propofol target controlled infusion can be employed to provide suitably conducive conditions for this purpose. Objective: The primary objective sought to compare the proportion of hypoxia between the study group receiving intermittent boluses of propofol at 0.25mg/kg as needed, and the other receiving target-controlled infusion of propofol at 2.5mcg/ml during upper gastrointestinal endoscopy. The secondary objectives were to …


Association Between Female Sexual Dysfunction And Fertility Among Women Of Reproductive Age At The Aga Khan University Hospital, Nairobi., Felix Mwembi Oindi May 2017

Association Between Female Sexual Dysfunction And Fertility Among Women Of Reproductive Age At The Aga Khan University Hospital, Nairobi., Felix Mwembi Oindi

Master of Medicine in Obstetrics and Gynecology

Introduction: Sexual function plays an essential role in the bio-psychosocial wellbeing and quality of life of women and disturbances in sexual functioning often result in significant stress. Sexual dysfunction in women is a highly prevalent condition affecting up to 43% of women. Subfertility being a common problem affecting up to 20% of the population, causes significant psychosocial distress which might adversely affect sexual functioning and vice versa. However, despite the high prevalence of both conditions, little has been studied on the effects of subfertility on sexual functioning especially in sub-Saharan Africa. Objectives: This study primarily compared the prevalence of female …


Validation Of The Iief - 5 Questionnaire In A Clinic Population At Aga Khan University Hospital, Nairobi, Denis Otim May 2017

Validation Of The Iief - 5 Questionnaire In A Clinic Population At Aga Khan University Hospital, Nairobi, Denis Otim

Master of Medicine in General Surgery

Background: Men with lower urinary tract symptoms (LUTS) are at risk of erectile dysfunction (ED) and other co - morbidities. The clinical assessment of ED is unreliable and the International Index of Erectile Function – 5 (IIEF – 5) a widely used tool is not validated in our setting. We aimed to validate the IIEF – 5 as a screening tool for ED in men with LUTS visiting the outpatient services. Methodology: In the study, 99 men above 40 years with LUTS attending the urology clinics were consecutively enrolled, administered with the IIEF – 5 and assigned an ED status. …


Foundational Knowledge And Other Predictors Of Commitment To Trauma-Informed Care, Stephanie Anne Sundborg May 2017

Foundational Knowledge And Other Predictors Of Commitment To Trauma-Informed Care, Stephanie Anne Sundborg

Dissertations and Theses

Trauma-informed care (TIC) is an approach to service delivery based on the understanding of the prevalence of psychological trauma among service users, knowledge about the impact trauma has on engagement to services, and recognition that service settings can be re-traumatizing. For more than a decade, momentum has been building on this topic. Practitioners are pursuing the knowledge and skills needed to implement trauma-informed service delivery, while organizations are building infrastructure and processes aimed at supporting this approach. Disciplines across many human service sectors are eager to incorporate TIC into policy and practice. Despite this enthusiasm, implementation efforts are slow. Acquiring …


Offering Self-Administered Oral Hiv Testing As A Choice To Truck Drivers In Kenya: Predictors Of Uptake And Need For Guidance While Self-Testing, Elizabeth A. Kelvin, Gavin George, Eva Mwai, Eston N. Nyaga, Joanne E. Mantell, Matthew L. Romo, Jacob O. Odhiambo, Kaymarlin Govender May 2017

Offering Self-Administered Oral Hiv Testing As A Choice To Truck Drivers In Kenya: Predictors Of Uptake And Need For Guidance While Self-Testing, Elizabeth A. Kelvin, Gavin George, Eva Mwai, Eston N. Nyaga, Joanne E. Mantell, Matthew L. Romo, Jacob O. Odhiambo, Kaymarlin Govender

Publications and Research

We assessed predictors of choosing self-administered oral HIV testing in the clinic with supervision versus the standard provider-administered blood test when offered the choice among 149 Kenyan truck drivers, described the types of guidance participants needed during self-testing and predictors of needing guidance. Overall, 56.38% of participants chose the self-test, 23.49% the provider-administered test, and 20.13% refused testing. In the adjusted regression models, each additional unit on the fatalism and self-efficacy scales was associated with 0.97 (p = 0.003) and 0.83 (p = 0.008) times lower odds of choosing the self-test, respectively. Overall, 52.38% of self-testers did so correctly without …


Modulation Of Estrogen Related Receptor Alpha Activity By The Kinesin Kif17, Am Pramodh Bandara Seneviratne, Zeynep Turan, Aurelie Hermant, Patrick Lecine, William O. Smith, Jean-Paul Borg, Fanny Jaulin, Geri Kreitzer May 2017

Modulation Of Estrogen Related Receptor Alpha Activity By The Kinesin Kif17, Am Pramodh Bandara Seneviratne, Zeynep Turan, Aurelie Hermant, Patrick Lecine, William O. Smith, Jean-Paul Borg, Fanny Jaulin, Geri Kreitzer

Publications and Research

Estrogen-related receptor alpha (ERR1) is an orphan nuclear receptor that can bind transcriptional co-activators constitutively. ERR1 expression correlates with poor patient outcomes in breast cancer, heightening interest in this nuclear receptor as a therapeutic target. Because ERR1 has no known regulatory ligand, a major challenge in targeting its activity is to find cellular or synthetic modulators of its function. We identified an interaction between ERR1 and KIF17, a kinesin-2 family microtubule motor, in a yeast-2-hybrid screen. We confirmed the interaction using in vitro biochemical assays and determined that binding is mediated by the ERR1 ligand-binding/AF2 domain and the KIF17 C-terminal …


A Mixed Methods Study Of Multiple Health Behaviors Among Individuals With Stroke, Matthew Plow, Shirley M. Moore, Martha Sajatovic May 2017

A Mixed Methods Study Of Multiple Health Behaviors Among Individuals With Stroke, Matthew Plow, Shirley M. Moore, Martha Sajatovic

Faculty Scholarship

Background: Individuals with stroke often have multiple cardiovascular risk factors that necessitate promoting engagement in multiple health behaviors. However, ob-servational studies of individuals with stroke have typically focused on promoting a single health behavior. Thus, there is a poor understanding of linkages between healthy behaviors and the circumstances in which factors, such as stroke impairments, may influence a single or multiple health behaviors. Methods. We conducted a mixed methods convergent parallel study of 25 individuals with stroke to examine the relationships between stroke impairments and physical activity, sleep, and nutrition. Our goal was to gain further insight into possible strategies …


Mindfulness And Law Enforcement: An Effective Approach To Implementing Mindfulness For First Responders, Gina White May 2017

Mindfulness And Law Enforcement: An Effective Approach To Implementing Mindfulness For First Responders, Gina White

Mindfulness Studies Theses

An increasing number of studies show that people employed as first responders in high trauma service jobs tend to experience a high level of stress, at work and after hours. Studies suggest that constant exposure to job related stress leads to both physical and mental dysregulation. This study looks at the effects of implementing mindfulness tools and techniques to those working in law enforcement. Other works on this topic report mindfulness as a successful tool to increase wellbeing to a broad spectrum of populations. The methodology used in this study was designed specifically for first responders. The data findings were …


A Randomized Controlled Trial Of Individual Versus Group-Format Exercise And Self-Management In Individuals With Parkinson's Disease And Comorbid Depression, Martha Sajatovic, Ellen M. Walter, Curtis M. Tatsuoka, Steven A. Gunzler, Christina M. Whitney, Benjamin L. Walter May 2017

A Randomized Controlled Trial Of Individual Versus Group-Format Exercise And Self-Management In Individuals With Parkinson's Disease And Comorbid Depression, Martha Sajatovic, Ellen M. Walter, Curtis M. Tatsuoka, Steven A. Gunzler, Christina M. Whitney, Benjamin L. Walter

Faculty Scholarship

Background: Depression is common in people with Parkinson’s disease (PD), and exercise is known to improve depression and PD. However, lack of motivation and low self-efficacy can make exercise difficult for people with PD and comorbid depression (PD-Dep). A combined group exercise and chronic disease self-management (CDSM) program may improve the likelihood that individuals will engage in exercise and will show a reduction in depression symptoms. The purpose of this study was to compare changes in depression in PD-Dep between individual versus group exercise plus CDSM and to examine participant adherence and perception of the interventions. Methods: Participants (N=30) were …


Bendablesound: An Elastic Multisensory Surface Using Touch-Based Interactions To Assist Children With Severe Autism During Music Therapy, Franceli L. Cibrian, Oscar Peña, Deysi Ortega, Monica Tentori May 2017

Bendablesound: An Elastic Multisensory Surface Using Touch-Based Interactions To Assist Children With Severe Autism During Music Therapy, Franceli L. Cibrian, Oscar Peña, Deysi Ortega, Monica Tentori

Engineering Faculty Articles and Research

Neurological Music Therapy uses live music to improve the sensorimotor regulation of children with severe autism. However, they often lack musical training and their impairments limit their interactions with musical instruments. In this paper, we present our co-design work that led to the BendableSound prototype: an elastic multisensory surface encouraging users to practice coordination movements when touching a fabric to play sounds. We present the results of a formative study conducted with 18 teachers showing BendableSound was perceived as “usable” and “attractive”. Then, we present a deployment study with 24 children with severe autism showing BendableSound is “easy to use” …


Hemodynamic And Metabolic Responses During Self-Paced And Ramp Graded Exercise Testing Treadmill Protocols, Nicholas Mark Beltz May 2017

Hemodynamic And Metabolic Responses During Self-Paced And Ramp Graded Exercise Testing Treadmill Protocols, Nicholas Mark Beltz

Health, Exercise, and Sports Sciences ETDs

Purpose: To investigate: 1) if a self-paced (SP) graded exercise testing protocol elicits similar and reliable maximal oxygen uptake (VO2max) responses compared to a ramp (RAMP) treadmill protocol; 2) the impact of SP on cardiac output (Q), stroke volume (SV), and arteriovenous oxygen difference (a-vO2diff); and 3) the metabolic response during SP through blood lactate (BLa-) accumulation and ventilatory threshold (VT) attainment. Methods: Sixteen recreationally trained men (23.7±3.0 yrs) completed two separate treadmill graded exercise testing protocols. SP consisted of five 2-min stages (10 min total) of increasing speed based on the Borg …


Research Brief: "The National Veteran Sleep Disorder Study: Descriptive Epidemiology And Secular Trends, 2000–2010", Institute For Veterans And Military Families At Syracuse University May 2017

Research Brief: "The National Veteran Sleep Disorder Study: Descriptive Epidemiology And Secular Trends, 2000–2010", Institute For Veterans And Military Families At Syracuse University

Institute for Veterans and Military Families

This brief is about the relation between sleep disorder diagnosis and cardiovascular disease, cancer, and mental health disorders among veterans. In policy and practice, physicians should familiarize themselves with signs of and screenings for sleep disorders and should discuss factors that affect sleep with their veteran patients; the VHA should continue recommending policies that help veterans receive a prompt diagnosis and treatment of their sleep disorders, policymakers should fund early intervention programs to help veterans learn how to cope with reintegration, and the VHA should create a database on sleep disorders in veterans. Suggestions for future research include studying veterans …


The Skin Cancer Health Crisis And Recommended Intervention Methods, Blaire Brooks May 2017

The Skin Cancer Health Crisis And Recommended Intervention Methods, Blaire Brooks

Senior Theses

Despite the increasing research connecting UVR exposures to skin cancer, rates of skin cancer are rising. Skin cancer is now the most common form of cancer and there are significant health care costs associated with treating the cases (Balk et al., 2013). As a result, the United States needs greater initiatives to increase educational programs, physician counseling, and political action regarding ultraviolet exposure and incidence of skin cancer. Evaluation of the types of skin cancer, perceptions of tanning, and current regulations and recommendations are required in order to form the initiatives to combat the growth of skin cancer.


Epigenetic Modifications Of Human Placenta Associated With Preterm Birth, Drissa Toure May 2017

Epigenetic Modifications Of Human Placenta Associated With Preterm Birth, Drissa Toure

Theses & Dissertations

Preterm birth is a complex multifactorial process. Despite the well-known role of the placenta in supporting the fetal development and maternal-fetal tolerance, the placental epigenetic modifications and preterm birth (PTB) remains poorly understood and under investigated. Various maternal and environment factors can influence epigenetic programming during fetal development to affect the functioning and structures of organs, including the placenta, which can lead to adverse pregnancy outcomes, including PTB. The understanding of the placental epigenetic alterations and maternal determinants associated with PTB are apparently indispensable for the development of actual diagnosis and methods of prevention and treatment of premature labor. The …


Optimal Nutrition For Endurance Exercise: A Systematic Review, Sarah E. Andrus Ms, Bruce W. Andrus Md Ms May 2017

Optimal Nutrition For Endurance Exercise: A Systematic Review, Sarah E. Andrus Ms, Bruce W. Andrus Md Ms

Dartmouth Scholarship

Introduction

As fatigue in endurance events correlates with depletion of muscle glycogen, the traditional approach to nutritional support has been carbohydrate loading. However, there has been recent interest in improving athletic endurance performance by novel diets in the days to weeks prior to endurance events, the pre-event meal, and during exercise.

Methods

We searched PubMed and SCOPUS for randomized trials published from 1992-2017 with a primary endpoint of endurance performance. We identified 407 citations which were examined against our inclusion criteria of randomization or crossover allocation to diet and for which a primary outcome was endurance performance.

Results

Twenty full …


Effect Of Activity Trackers And Text Messaging On Exercise, Fitness, And Physical Activity Self-Efficacy Of Middle School Students, Alison F. Pittman May 2017

Effect Of Activity Trackers And Text Messaging On Exercise, Fitness, And Physical Activity Self-Efficacy Of Middle School Students, Alison F. Pittman

Nursing Theses and Dissertations

A decrease in physical activity as children age is a contributing factor to the U.S. obesity epidemic. Middle school children are particularly vulnerable to sedentary activities. Activity trackers show promise as a means to motivate children and adults to increase physical activity (PA). This study examined the effect of a text messaging intervention and use of activity trackers with a companion social website on the body mass index (BMI), body fat percentage, physical fitness, and PA self-efficacy of middle school children. Children aged 11-14 (n=102) were randomly assigned to one of three groups for a 10-week intervention: activity tracker group; …


Diagnostic Effectiveness Of High-Sensitivity Troponins, Sean R. Bodin, Jacqueline Ramirez May 2017

Diagnostic Effectiveness Of High-Sensitivity Troponins, Sean R. Bodin, Jacqueline Ramirez

Physician Assistant Capstones, 2016 to 2019

Background: Acute myocardial infarctions (AMI) are a leading cause of death in the United States. The key to increasing survivability is early recognition to expedite the proper treatment modalities. In conjunction with the clinical presentation and electrocardiograms, the use of cardiac biomarkers is exponentially important in not only recognizing a cardiac event but also determining the extent of injury. Advancement in laboratory technology has led to the development of high-sensitive troponin (hs-troponin) assays which can detect smaller cardiac troponin serum levels compared to conventional troponin assays. This implies that the use of hs-troponin assays is more effective in the …


Early Versus Delayed Rehabilitation After Arthroscopic Rotator Cuff Repair, Abigail Chang, Jessica Dennis May 2017

Early Versus Delayed Rehabilitation After Arthroscopic Rotator Cuff Repair, Abigail Chang, Jessica Dennis

Physician Assistant Capstones, 2016 to 2019

Objective: To determine how the timing of rehabilitation, early versus delayed, affects clinical results and tendon healing rates after arthroscopic rotator cuff repair. Design: Systematic literature review. Methods: Searches were done in PubMed, utilizing the terms arthroscopic rotator cuff repair, rehabilitation, early, and delayed. In PubMed the following filters and terms were used: published in the last 10 years, humans, randomized controlled trial, free full-text articles, and English. Results: The Keener et al study was included because it evaluated clinical results and tendon healing rates after arthroscopic repair using two distinct rehabilitation protocols, early versus delayed …


Effects Of Glucosamine Versus Chondroitin Sulfate In Reducing Joint Space Narrowing In Knee Osteoarthritis, Caroline Horton, Ashani Andrews May 2017

Effects Of Glucosamine Versus Chondroitin Sulfate In Reducing Joint Space Narrowing In Knee Osteoarthritis, Caroline Horton, Ashani Andrews

Physician Assistant Capstones, 2016 to 2019

Objective: To determine if over the counter supplements, chondroitin sulfate and glucosamine, in combination or alone, are effective in the treatment of joint space narrowing (JSN) in knee osteoarthritis.

Design: Systematic Literature Review

Methods: Database search of PubMed and MEDLINE using the search terms “glucosamine”, “chondroitin sulfate”, “osteoarthritis”, and joint space narrowing. Filters were implemented to include articles that only dealt with human subjects, that were published in 2000 or later, and were full-text. Articles were excluded if they were cohort studies, reviews, non-English papers, or had pain as the only outcome.

Results: Sawitzke et al.primary outcomes revealed no …


Application Of D-Dimer To Aid In Diagnosis Of Acute Aortic Dissection, Hannah Scarboro, Julia Starkey May 2017

Application Of D-Dimer To Aid In Diagnosis Of Acute Aortic Dissection, Hannah Scarboro, Julia Starkey

Physician Assistant Capstones, 2016 to 2019

Introduction: Acute aortic dissection (AAD) is an emergent, relatively uncommon condition that typically presents with sudden onset severe chest or back pain.1 Advanced imaging, such as computerized tomography, is currently the gold standard to diagnose AAD; this can be expensive and unavailable at all health care centers. D-dimer is a blood test that has been shown in recent studies to be elevated in acute aortic dissection. This may be a more cost-effective way to help the clinician “rule-out” an acute aortic dissection.1

Objective: The purpose of this research was to determine if there is significant data regarding the sensitivity and …


Bupivacaine Vs. Ropivacaine: Looking At The Chondrotoxic Effects Of Intraarticular Anesthetics In Osteoarthritic Joints, Sarah Burke, Lauren Price May 2017

Bupivacaine Vs. Ropivacaine: Looking At The Chondrotoxic Effects Of Intraarticular Anesthetics In Osteoarthritic Joints, Sarah Burke, Lauren Price

Physician Assistant Capstones, 2016 to 2019

Objectives: Intraarticular injections of corticosteroids used in combination with local anesthetics are commonly used in orthopedic practice for osteoarthritic pain relief. Many orthopedists question whether these anesthetics have chondrotoxic effects on human articular cartilage. The purpose of this meta- analysis is to examine the chondrotoxic effects of local anesthetics on osteoarthritic human articular cartilage and to determine whether ropivacaine has fewer chondrotoxic effects than bupivacaine.

Methods: Studies were found using PubMed with the search terms, “Ropivacaine,” “Bupivacaine,” and “Chondrocytes.” Initially 20 studies were found. Several studies were eliminated using the following excluding factors: human studies, published in last 10 years, …


Implementation Of A Standardized Handoff During Transition Of Care From The Emergency Department To The Intensive Care Unit, Melinda Abbring May 2017

Implementation Of A Standardized Handoff During Transition Of Care From The Emergency Department To The Intensive Care Unit, Melinda Abbring

Evidence-Based Practice Project Reports

Patient safety and nursing communication are crucial to the nursing handoff during transition of care from the emergency department (ED) to the intensive care unit (ICU). The Institute of Medicine published To Err is Human: Building a Safer Health System (1999) and Crossing the Quality Chasm (2001) highlighting ED handoffs as a safety measure. In 2006, the Joint Commission recognized handoffs with the National Patient Safety Goal 2E. The purpose of this evidence-based practice project was to determine if implementation of a standardized handoff would improve nursing communication and patient safety during transition of care from the ED to the …


Hydration And Hot Yoga: Encouragement, Behaviors, And Outcomes, Casey Mace-Firebaugh, Brandon Eggleston May 2017

Hydration And Hot Yoga: Encouragement, Behaviors, And Outcomes, Casey Mace-Firebaugh, Brandon Eggleston

All Faculty Scholarship for the College of Education and Professional Studies

Context: Currently, the literature on hot yoga is lacking, and there is still much to understand regarding the safety of these practices. However, one point of safety often emphasized is hydration during the practice of hot yoga. Aim: The aim of this study was to examine hydration encouragement by hot yoga instructors and hydration behaviors and related outcomes by hot yoga participants. Methods: A cross-sectional study (n = 700) collected self-report data on demographics, types and frequency of yoga practiced, hydration behaviors, and self-report measures of adverse outcomes experienced by participants during hot yoga. Associations between hydration encouragement, protective …


Decreasing Cost In The Gi Endoscopy Suite By Utilizing Best Sedation Practices, Casey Brianne Mancini May 2017

Decreasing Cost In The Gi Endoscopy Suite By Utilizing Best Sedation Practices, Casey Brianne Mancini

Doctoral Projects

Colorectal cancer is a leading cause of cancer death in the United States (Mandel, Tanner, Lichtenstein, Metz, Katzka, Ginsberg, & Kochman, 2008; Siegel, DeSantis, & Jemal, 2014). Because this lethal disease claims lives of many people every year, more patients are undergoing screening colonoscopies, which have greatly aided in decreasing the number of colorectal cancer deaths (Siegel et al., 2014). The most common form of sedation for colonoscopies is moderate sedation with a benzodiazepine and an opioid (Cohen, Hightower, Wood, Miller, & Aisenberg, 2004; Lera dos Santos, et. al., 2013). However, sedation by anesthesia providers using propofol is becoming more …


Presurgical Language Fmri: Mapping Of Six Critical Regions, Christopher Benjamin, Patricia Walshaw, Kayleigh Hale, William D. Gaillard, +Several Additional Authors May 2017

Presurgical Language Fmri: Mapping Of Six Critical Regions, Christopher Benjamin, Patricia Walshaw, Kayleigh Hale, William D. Gaillard, +Several Additional Authors

Neurology Faculty Publications

Language mapping is a key goal in neurosurgical planning. fMRI mapping typically proceeds with a focus on Broca's and Wernicke's areas, although multiple other language-critical areas are now well-known. We evaluated whether clinicians could use a novel approach, including clinician-driven individualized thresholding, to reliably identify six language regions, including Broca's Area, Wernicke's Area (inferior, superior), Exner's Area, Supplementary Speech Area, Angular Gyrus, and Basal Temporal Language Area. We studied 22 epilepsy and tumor patients who received Wada and fMRI (age 36.4[12.5]; Wada language left/right/mixed in 18/3/1). fMRI tasks (two × three tasks) were analyzed by two clinical neuropsychologists who flexibly …


Fibulin-4 Is Essential For Maintaining Arterial Wall Integrity In Conduit But Not Muscular Arteries., Carmen M. Halabi, Thomas J. Broekelmann, Michelle Lin, Vivian S. Lee, Mon-Li Chu, Robert P. Mecham May 2017

Fibulin-4 Is Essential For Maintaining Arterial Wall Integrity In Conduit But Not Muscular Arteries., Carmen M. Halabi, Thomas J. Broekelmann, Michelle Lin, Vivian S. Lee, Mon-Li Chu, Robert P. Mecham

Department of Dermatology and Cutaneous Biology Faculty Papers

Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder characterized by significant cardiovascular abnormalities, including abnormal elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B. Fbln4E57K/E57K mice were hypertensive and developed arterial elongation, tortuosity, and ascending aortic aneurysms. Smooth muscle cell organization within the arterial wall of large conducting vessels was abnormal, and elastic fibers were fragmented and had a moth-eaten appearance. …


Sigma1 Targeting To Suppress Aberrant Androgen Receptor Signaling In Prostate Cancer., Jeffrey D. Thomas, Charles G. Longen, Halley M. Oyer, Nan Chen, Christina M. Maher, Joseph M. Salvino, Blase Kania, Kelsey N. Anderson, William F. Ostrander, Karen E. Knudsen, Felix J. Kim May 2017

Sigma1 Targeting To Suppress Aberrant Androgen Receptor Signaling In Prostate Cancer., Jeffrey D. Thomas, Charles G. Longen, Halley M. Oyer, Nan Chen, Christina M. Maher, Joseph M. Salvino, Blase Kania, Kelsey N. Anderson, William F. Ostrander, Karen E. Knudsen, Felix J. Kim

Department of Cancer Biology Faculty Papers

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that …


Dysregulated Gpcr Signaling And Therapeutic Options In Uveal Melanoma., Vivian Chua, Dominic Lapadula, Clinita Randolph, Jeffrey L. Benovic, Philip B. Wedegaertner, Andrew E. Aplin May 2017

Dysregulated Gpcr Signaling And Therapeutic Options In Uveal Melanoma., Vivian Chua, Dominic Lapadula, Clinita Randolph, Jeffrey L. Benovic, Philip B. Wedegaertner, Andrew E. Aplin

Department of Biochemistry and Molecular Biology Faculty Papers

Uveal melanoma is the most common primary intraocular malignant tumor in adults and arises from the transformation of melanocytes in the uveal tract. Even after treatment of the primary tumor, up to 50% of patients succumb to metastatic disease. The liver is the predominant organ of metastasis. There is an important need to provide effective treatment options for advanced stage uveal melanoma. To provide the preclinical basis for new treatments, it is important to understand the molecular underpinnings of the disease. Recent genomic studies have shown that mutations within components of G protein-coupled receptor (GPCR) signaling are early events associated …