Digital Commons Network^™

St-Producing E. Coli Oppose Carcinogen-Induced Colorectal Tumorigenesis In Mice., Peng Li, Jieru E. Lin, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may …

Procalcitonin: The Pros And Cons In Pediatrics, Kris Rooney Md

Department of Pediatrics

No abstract provided.

A Global Staphylococcus Aureus Proteome Resource Applied To The In Vivo Characterization Of Host-Pathogen Interactions., Stephan Michalik, Maren Depke, Annette Murr, Manuela Gesell Salazar, Ulrike Kusebauch, Zhi Sun, Tanja C Meyer, Kristin Surmann, Henrike Pförtner, Petra Hildebrandt, Stefan Weiss, Laura Marcela Palma Medina, Melanie Gutjahr, Elke Hammer, Dörte Becher, Thomas Pribyl, Sven Hammerschmidt, Eric W Deutsch, Samuel L Bader, Michael Hecker, Robert L Moritz, Ulrike Mäder, Uwe Völker, Frank Schmidt

Articles, Abstracts, and Reports

Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation …

Long-Term Impact Of Changing Childhood Malnutrition On Rotavirus Diarrhoea: Two Decades Of Adjusted Association With Climate And Socio-Demographic Factors From Urban Bangladesh, Sumon Kumar Das, Mohammod Jobayer Chisti, Mohammad Habibur Rahman Sarker, Jui Das, Shawnawaz Ahmed, K. M. Shahunja, Shamsun Nahar, Nora Gibbons, Tahmeed Ahmed, Abu Syed Golam Faruque, Mustafizur Rahman, George J. Fuchs Iii, Abdullah Al Mamun, Peter John Baker

Pediatrics Faculty Publications

Background

There is strong association between childhood rotavirus, diarrhoea, climate factors and malnutrition. Conversely, a significant nutritional transition (reduced under-nutrition) with a concurrent increasing trend of rotavirus infection in last decade was also observed among under 5 children, especially in developing countries including Bangladesh. Considering the pathophysiology of rotavirus, there might be an interaction of this nutrition transition which plays a pivotal role in increasing rotavirus infection in addition to climate and other man-made factors in urban areas such as Dhaka, Bangladesh.

Methods

Relevant monthly data from 1993–2012 were extracted from the archive of the Diarrhoeal Disease Surveillance System of …

Cortical Activation During Action Observation, Action Execution, And Interpersonal Synchrony In Adults: A Functional Near-Infrared Spectroscopy (Fnirs) Study, Anjana Bhat, Michael Hoffman, Susanna Trost, Mckenzie Culotta, Jeffrey Eilbott, Daisuke Tsuzuki, Kevin A. Pelphrey

Psychiatry and Behavioral Sciences Faculty Publications

Introduction: Humans engage in Interpersonal Synchrony (IPS) as they synchronize their own actions with that of a social partner over time. When humans engage in imitation/IPS behaviors, multiple regions in the frontal, temporal, and parietal cortices are activated including the putative Mirror Neuron Systems (Iacoboni, 2005; Buxbaum et al., 2014). In the present study, we compared fNIRS-based cortical activation patterns across three conditions of action observation (“Watch” partner), action execution (“Do” on your own), and IPS (move “Together”).

Methods: Fifteen typically developing adults completed a reach and cleanup task with the right arm while cortical activation was …

Amlexanox Enhances Premature Termination Codon Read-Through In Col7a1 And Expression Of Full Length Type Vii Collagen: Potential Therapy For Recessive Dystrophic Epidermolysis Bullosa., Velina S. Atanasova, Qiujie Jiang, Marco Prisco, Christina Gruber, Josefina Piñón Hofbauer, Mei Chen, Cristina Has, Leena Bruckner-Tuderman, John A. Mcgrath, Jouni Uitto, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder caused by the lack of functional type VII collagen, leading to skin fragility and subsequent trauma-induced separation of the epidermis from the underlying dermis. A total of 46% of patients with RDEB harbor at least one premature termination codon (PTC) mutation in COL7A1, and previous studies have shown that aminoglycosides are able to overcome RDEB PTC mutations by inducing "read-through" and incorporation of an amino acid at the PTC site. However, aminoglycoside toxicity will likely prevent widespread clinical application. Here the FDA-approved drug amlexanox was tested for its ability …

Probing The Metabolic Phenotype Of Breast Cancer Cells By Multiple Tracer Stable Isotope Resolved Metabolomics, Andrew N. Lane, Julie Tan, Yali Wang, Jun Yan, Richard M. Higashi, Teresa W. -M. Fan

Center for Environmental and Systems Biochemistry Faculty Publications

Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using ¹³C₆-glucose, ¹³C-1+2-glucose, ¹³C₅,¹⁵N₂-Gln, ¹³C₃-glycerol, and ¹³C₈-octanoate as tracers. These tracers were designed to probe the central energy producing …

Effects Of Bomb Blast Injury On The Ears: The Aga Khan University Hospital Experience, Talha Ahmed Qureshi,, Mohammad Sohail Awan, Nabeel Hamayun Hassan, Agha Hussain Aftab, Syed Adnan Ali

Section of Otolaryngology, Head & Neck Surgery

Abstract Objective: To evaluate the frequency and effects of blast-related otologic injuries. Methods: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised charts of patients who were victims of bomb explosions between January 2011 and July 2013. Frequency and percentages were reported using cross tabulation with size of bomb, distance of person from blast and the presence of victim in open or closed space. Association of associated variables were also analysed. Results: Of the 100 patients, 81(81%) were men and 19(19%) were women. Besides, 68(68%) patients were aged <30 years. Also, 78(78%) subjects were exposed to < 80kg of explosives and 68(68%) were at a distance of>10m. Furthermore, 61(61%) patients were exposed to …

Knowledge And Utilisation Of Emergency Contraception Pills Among Female Undergraduate Students At The University Of Nairobi, Kenya, Mwaniki Grace Nyambura, James N. Kiarie, Elkanah Omenge, Okubatsion Tekeste Okube

Obstetrics and Gynaecology, East Africa

Background: Emergency Contraception (EC) is used after unprotected sexual intercourse, following sexual abuse, misuse of regular contraception or non-use of contraception. Seventeen percent of pregnancies in Kenya are unintended, potentially leading to unsafe abortion that contributes to the high maternal mortality rate in Country. According to 2016 Kenya Demographic and Health Survey (KDHS), the maternal mortality ratio was 362 maternal deaths per 100,000 live births. Female students in University or College are vulnerable to unplanned pregnancies and illegal abortions resulting in mortality, morbidity and psychosocial problems. Knowledge on EC is very important for students as they are not in stable …

National Football League Skilled And Unskilled Positions Vary In Opportunity And Yield In Return To Play After An Anterior Cruciate Ligament Injury., Jaewon Yang, Jonathan D. Hodax, Jason T. Machan, Eric S. Secrist, Wesley M. Durand, Brett D. Owens, Adam E.M. Eltorai, Christopher C. Dodson

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Anterior cruciate ligament (ACL) injuries pose a significant risk to the careers of players in the National Football League (NFL). The relationships between draft round and position on return to play (RTP) among NFL players are not well understood, and the ability to return to preinjury performance levels remains unknown for most positions.

PURPOSE: To test for differences in RTP rates and changes in performance after an ACL injury by position and draft round. We hypothesized that skilled positions would return at a lower rate compared to unskilled positions. We further hypothesized that early draft-round status would relate to …

Tailoring A Nicu-Based Tobacco Treatment Program For Mothers Who Are Dependent On Opioids, Amanda Fallin-Bennett, Kristin Ashford

Nursing Faculty Publications

Objective—To collect formative information to design a tailored tobacco treatment intervention for women with newborns treated or evaluated for neonatal abstinence syndrome and to explore current tobacco use behaviors and facilitators and barriers to smoking cessation.

Design—Qualitative descriptive study.

Setting—An academic medical center in the southern United States.

Participants—Mothers of newborns who were treated or evaluated for neonatal abstinence syndrome at birth within the preceding three months. Women were recruited who were older than 18 and reported opioid dependence and smoking during pregnancy.

Methods—Participants took part in semi-structured individual interviews that lasted approximately one hour. …

A Multi-Institutional Consensus On How To Perform Endoscopic Ultrasound-Guided Peri-Pancreatic Fluid Collection Drainage And Endoscopic Necrosectomy., Jintao Guo, Adrian Saftoiu, Peter Vilmann, Pietro Fusaroli, Marc Giovannini, Girish Mishra, Surinder S. Rana, Sammy Ho, Jan-Werner Poley, Tiing Leong Ang, Evangelos Kalaitzakis, Ali A. Siddiqui, Jose G. De La Mora-Levy, Sundeep Lakhtakia, Manoop S. Bhutani, Malay Sharma, Shuntaro Mukai, Pramod Kumar Garg, Linda S. Lee, Juan J. Vila, Everson Artifon, Douglas G. Adler, Siyu Sun

Division of Gastroenterology and Hepatology Faculty Papers

There is a lack of consensus on how endoscopic ultrasound (EUS)-guided pseudocyst drainage and endoscopic necrosectomy should be performed. This survey was carried out amongst members of the EUS Journal Editorial Board to describe their practices in performing this procedure. This was a worldwide multi-institutional survey amongst members of the EUS Journal Editorial Board in May 2017. The responses to a 22-question survey with respect to the practice of EUS-guided pseudocyst drainage and endoscopic necrosectomy were obtained. Twenty-two endoscopists responded to the questionnaire as follows: 72.7% (16/22) were of the opinion that lumen-apposing metal stents (LAMS) should be the standard …

Readiness For Antimicrobial Resistance (Amr) Surveillance In Pakistan; A Model For Laboratory Strengthening, Dania Khalid Saeed, Rumina Hasan, Mahwish Naim, Afia Zafar, Erum Khan, Kauser Jabeen, Seema Irfan, Imran Ahmed Haq, Mohammad Zeeshan, Zabin Wajidali, Joveria Farooqi, Sadia Shakoor, Abdul Chagla, Jason Rao

Department of Pathology and Laboratory Medicine

Background: Limited capacity of laboratories for antimicrobial susceptibility testing (AST) presents a critical diagnostic bottleneck in resource limited countries. This paper aims to identify such gaps and to explore whether laboratory networks could contribute towards improving AST in low resource settings.
Methods: A self-assessment tool to assess antimicrobial susceptibility testing capacity was administered as a pre-workshop activity to participants from 30 microbiology laboratories in 3 cities in Pakistan. Data from public and private laboratories was analyzed and capacity of each scored in percentage terms. Laboratories from Karachi were invited to join a support network. A cohort of five laboratories that …

Readiness For Antimicrobial Resistance (Amr) Surveillance In Pakistan; A Model For Laboratory Strengthening, Dania Khalid Saeed, Rumina Hasan, Mahwish Naim, Afia Zafar, Erum Khan, Kauser Jabeen, Seema Irfan, Imran Ahmed Haq, Mohammad Zeeshan, Zabin Wajidali, Joveria Farooqi, Sadia Shakoor, Abdul Chagla, Jason Rao

Department of Pathology and Laboratory Medicine

Background: Limited capacity of laboratories for antimicrobial susceptibility testing (AST) presents a critical diagnostic bottleneck in resource limited countries. This paper aims to identify such gaps and to explore whether laboratory networks could contribute towards improving AST in low resource settings.
Methods: A self-assessment tool to assess antimicrobial susceptibility testing capacity was administered as a pre-workshop activity to participants from 30 microbiology laboratories in 3 cities in Pakistan. Data from public and private laboratories was analyzed and capacity of each scored in percentage terms. Laboratories from Karachi were invited to join a support network. A cohort of five laboratories that …

Carotid Intima Media Thickness Percentiles For Pakistani Population, Waseem Mirza, Mubashir Aslam Arain, Arif Ali, Vaqar Bari, Mirza Kazim Ali, Kainat Fatima

Department of Radiology

Carotid artery intima media thickness estimation is a well-established way of cardio vascular disease evaluation. The purpose of this cross-sectional study was to develop normal carotid intima media thickness percentile values for a Pakistani cohort. Data was collected at the Departments of Radiology and Family Medicine, The Aga Khan University Hospital, Karachi, from April 2014 to August 2015. High frequency ultrasound of carotid was done in 257 patients [97 male (38%), 160 female (62%)] without any known carotid artery disease. Reference ranges (90% range between 5th and 95th centiles) were constructed for each common carotid and internal carotid artery measurement …

Use Of Smokeless Tobacco Among Young Patients With Acute Ischemic Stroke, Saba Zaidi

Pakistan Journal of Neurological Sciences (PJNS)

This cross sectional study was conducted from April to September 2015at emergency department of Aga khan university.A total of 135 patients presented with signs and symptoms of acute ischemic stroke were included in this research. Participants were selected throughNon probability consecutive samplingtechnique. SPSS 20 was used for data analysis.A predesigned proforma was filled. It has three parts including SocioDemographics, Factors for stroke like hypertension, diabetes Mellitus, dyslipidemia, cigarrete smoking and History of smokeless tobacco use.Young stroke was defined as patients between 20-49 years of age having symptoms of acute ischemic stroke. Smokeless Tobacco users: An individual taking greater than and …

Factors Affecting Compliances With Physiotherapy Among Stroke Patients: Physiotherapist's Perspective: A Study From Peshawar Pakistan., Rabia Basri, Maryam Naseen, Aatika Naz

Pakistan Journal of Neurological Sciences (PJNS)

Non-compliances to physiotherapy are common. Outside the Western nations, little is known to the factors responsible for non-compliances with physiotherapy. This study aimed to evaluate the factors affecting non-compliances with physiotherapy among stroke patients, in Peshawar, Pakistan. METHOD: Seven in practice physiotherapists from Peshawar, Pakistan, were invited to focus group discussion to discuss their opinions about factors affecting stroke patient's non-compliances and the strategies to manage with these factors. The dialogues were transcribed and analyzed. Significant words and statements describing noncompliances were identified. The cluster of meanings developed and used to write a combined description presenting the real meaning of …

Effect Of Extracellular Survivin And Lymphoma Exosomes On Natural Killer Cells, Heather R. Ferguson Bennit

Loma Linda University Electronic Theses, Dissertations & Projects

Tumors alter their microenvironment to promote survival using methods such as angiogenesis promotion, growth signals, and immune suppression. The immune system becomes unresponsive to transformed neoplastic cells through a variety of methods including T cell suppression, increased myeloid-derived suppressor cells (MDSCs), and reduced natural killer (NK) cell activity. NK cells have inherent killing capabilities and thus are among the first responders in recognizing and destroying abnormal cells. However, many types of cancers inhibit the surveillance and cytotoxic abilities of NK cells by releasing exosomes, vesicles that can modulate the tumor microenvironment (TME) and intercellular communication for the purpose of enhancing …

Pattern Of Pigmentation Disorder In Cosmetic Dermatology Clinic H. Adam Malik General Hospital, Medan, 2012 - 2015, Nelva Karmila Jusuf

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Abnormalities of pigmentation is a cosmetic problem which affects the overall appearance of an individual. Pigmentation disorder are caused by the increase (hypermelanosis) or the decrease (hypomelanosis) amount of melanin.

Objective: To determine the pattern of pigmentation disorder in Cosmetic Dermatology Clinic H. Adam Malik General Hospital Medan in 2012-2015.

Methods: A retrospective study using subject's medical records from the Cosmetic Dermatology Clinic H. Adam Malik General Hospital Medan in 2012 - 2015, presented descriptively.

Results: In 2012 - 2015 the number of patients who visited the Cosmetic Dermatology Clinic were respectively 210, 228, 211, 142. …

Post-Traumatic Stress Disorder And Its Predictors In Emergency Medical Service Personnel: A Cross-Sectional Study From Karachi, Pakistan, Salima Kerai, Uzma R. Khan, Muhammad Islam, Nargis Asad, Junaid Razzak, Omrana Pasha

Department of Paediatrics and Child Health

Background: Emergency medical service (EMS) personnel who work to provide emergency medical care at the scene and during transportation are exposed to various kinds of stressors and are particularly susceptible to developing stress-reactions. This study assesses symptoms of post-traumatic stress disorder and its predictors among the personnel of a selected EMS in Karachi, Pakistan.
Methods: Data were gathered from 518 personnel working in an EMS setting from February to May 2014. Participants were screened for post-traumatic stress symptoms using the Impact of Event Scale-Revised (IES-R). Demographic and work-related characteristics, coping styles and the social support systems of the participants were …

The Farnesoid X Receptor Negatively Regulates Osteoclastogenesis In Bone Remodeling And Pathological Bone Loss, Ting Zheng, Ju-Hee Kang, Jung-Sun Sim, Jung-Woo Kim, Jeong-Tae Koh, Chan Soo Shin, Hyungsik Lim, Mijung Yim

Publications and Research

Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Since the role of FXR in osteoclast differentiation remains ill-defined, we investigated the biological function of FXR on osteoclastogenesis, using FXR-deficient mice. We demonstrated that FXR deficiency increases osteoclast formation in vitro and in vivo. First, FXR deficiency was found to accelerate osteoclast formation via down-regulation of c-Jun N-terminal kinase (JNK) 1/2 expression. Increased expression of peroxisome proliferator-activated receptor (PPAR)γ and peroxisome proliferator-activated receptor gamma coactivator 1 (PGC- 1)β seems to mediate the pro-osteoclastogenic effect of FXR deficiency via the JNK pathway. In …

Oxidative Stress-Induced Jnk/Ap-1 Signaling Is A Major Pathway Involved In Selective Apoptosis Of Myelodysplastic Syndrome Cells By Withaferin-A, Karine Z. Oben, Sara S. Alhakeem, Mary Kathryn Mckenna, Jason A. Brandon, Rajeswaran Mani, Sunil K. Noothi, Jinpeng Liu, Shailaja Akunuru, Sanjit Kumar Dhar, Inder P. Singh, Ying Liang, Chi Wang, Ahmed Abdel-Latif, Harold F. Stills Jr., Daret K. St Clair, Hartmut Geiger, Natarajan Muthusamy, Kaoru Tohyama, Ramesh C. Gupta, Subbarao Bondada

Markey Cancer Center Faculty Publications

Myelodysplastic syndromes (MDS) are a diverse group of malignant clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplastic cell morphology in one or more hematopoietic lineages, and a risk of progression to acute myeloid leukemia (AML). Approximately 50% of MDS patients respond to current FDA-approved drug therapies but a majority of responders relapse within 2-3 years. There is therefore a compelling need to identify potential new therapies for MDS treatment. We utilized the MDS-L cell line to investigate the anticancer potential and mechanisms of action of a plant-derived compound, Withaferin A (WFA), in MDS. WFA was potently cytotoxic to …

Tia1 Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia Promote Phase Separation And Alter Stress Granule Dynamics., Ian R. Mackenzie, Alexandra M. Nicholson, Mohona Sarkar, James Messing, Maria D. Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B. Perkerson, Aishe Kurti, Billie J. Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R. Hsiung, Charles Krieger, Melissa E. Murray, Masato Kato, John D. Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A. Zivkovic, Veronica Hirsch-Reinshagen, Raymond P. Roos, Stephan Züchner, Neill R. Graff-Radford, Ronald C. Petersen, Richard J. Caselli, Zbigniew K. Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W. Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B. Boylan, J. Paul Taylor, Rosa Rademakers

Department of Neurology Faculty Papers

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10

Posttranscriptional Upregulation Of Idh1 By Hur Establishes A Powerful Survival Phenotype In Pancreatic Cancer Cells., Mahsa Zarei, Shruti Lal, Seth J. Parker, Avinoam Nevler, Ali Vaziri-Gohar, Katerina Dukleska, Nicole C. Mambelli-Lisboa, Cynthia Moffat, Fernando F Blanco, Saswati N. Chand, Masaya Jimbo, Joseph A. Cozzitorto, Wei Jiang, Charles J. Yeo, Eric R. Londin, Erin L. Seifert, Christian M. Metallo, Jonathan R. Brody, Jordan M. Winter

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C > 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal …

Integrative Analysis Identifies Four Molecular And Clinical Subsets In Uveal Melanoma., A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman

Articles, Abstracts, and Reports

Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.

Understanding The Blogging Practices Of Women Undergoing In Vitro Fertilization (Ivf): A Discourse Analysis Of Women’S Ivf Blogs, Elizabeth Orr, Susan M. Jack, Wendy Sword, Sandra Ireland, Lois Ostolosky

The Qualitative Report

Infertility and its associated treatments, including in vitro fertilization (IVF), can have a profound impact on the emotional health and well-being of women desiring to become mothers. Researchers have measured the impact of infertility and described the experience of infertility and its treatment, leaving the rich descriptions of the IVF experience as captured in women’s blogs to be explored. This discourse analysis describes the blogging practices of women undergoing IVF, exploring both the content and function of the IVF blog discourse. Data were collected from the text of seven women’s blogs (n=1,149 blog posts) and resulted in four main functions …

Stress Increases Peripheral Axon Growth And Regeneration Through Glucocorticoid Receptor-Dependent Transcriptional Programs, Jessica K. Lerch, Jessica K. Alexander, Kathryn M. Madalena, Dario Motti, Tam Quach, Akhil Dhamija, Alicia Zha, John C. Gensel, Jeanette Webster Marketon, Vance P. Lemmon, John L. Bixby, Phillip G. Popovich

Physiology Faculty Publications

Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain, but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal GC receptor (Nr3c1, also known as GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (M. musculus). In response to stress or GCs, adult …

Abl Kinase Regulation By Braf/Erk And Cooperation With Akt In Melanoma, Aditi Jain, Rakshamani Tripathi, Courtney P. Turpin, Chi Wang, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

The melanoma incidence continues to increase, and the disease remains incurable for many due to its metastatic nature and high rate of therapeutic resistance. In particular, melanomas harboring BRAF^V600E and PTEN mutations often are resistant to current therapies, including BRAF inhibitors (BRAFi) and immune checkpoint inhibitors. Abl kinases (Abl/Arg) are activated in melanomas and drive progression; however, their mechanism of activation has not been established. Here we elucidate a novel link between BRAF^V600E/ERK signaling and Abl kinases. We demonstrate that BRAF^V600E/ERK play a critical role in binding, phosphorylating and regulating Abl localization and Abl/Arg activation …

Maternal Intuition Of Fetal Gender, Michael Mcfadzen, David P. Dielentheis, Ronda Kasten, Maharaj Singh, Joe Grundle

Journal of Patient-Centered Research and Reviews

Purpose: Fetal gender speculation is a preoccupation of many expecting parents, and pregnant women commonly profess to intuitively know the gender of their unborn babies. This study objectively compared pregnant mothers’ perceptions of fetal gender to sonographically proven gender determinations. Also, success rates from previously published studies, noninvasive prenatal testing and a myriad of gender determination methods were observed and reported for context.

Methods: All pregnant women presenting for second-trimester screening ultrasound (at 17–23 weeks gestation) in the obstetrics department of a single health center were asked to participate. A medical sonographer described the ultrasound examination, obtained appropriate consent and …

Targeting Hepatic Heparin-Binding Egf-Like Growth Factor (Hb-Egf) Induces Anti-Hyperlipidemia Leading To Reduction Of Angiotensin Ii-Induced Aneurysm Development, Seonwook Kim, Lihua Yang, Seongu Kim, Richard G. Lee, Mark J. Graham, Judith A. Berliner, Aldons J. Lusis, Lei Cai, Ryan E. Temel, Debra L. Rateri, Sangderk Lee

Saha Cardiovascular Research Center Faculty Publications

Objective

The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model.

Approach and results

Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin …