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Vital Signs, Summer 2017, Boonshoft School Of Medicine

Vital Signs

A forty-four page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes a variety of feature articles, alumni profiles, class notes, and more.

The Rhoj-Bad Signaling Network: An Achilles' Heel For Braf Mutant Melanomas., Rolando Ruiz, Sohail Jahid, Melissa Harris, Diego M Marzese, Francisco Espitia, Priya Vasudeva, Chi-Fen Chen, Sebastien De Feraudy, Jie Wu, Daniel L Gillen, Tatiana B Krasieva, Bruce J Tromberg, William J Pavan, Dave S B Hoon, Anand K Ganesan

Articles, Abstracts, and Reports

Genes and pathways that allow cells to cope with oncogene-induced stress represent selective cancer therapeutic targets that remain largely undiscovered. In this study, we identify a RhoJ signaling pathway that is a selective therapeutic target for BRAF mutant cells. RhoJ deletion in BRAF mutant melanocytes modulates the expression of the pro-apoptotic protein BAD as well as genes involved in cellular metabolism, impairing nevus formation, cellular transformation, and metastasis. Short-term treatment of nascent melanoma tumors with PAK inhibitors that block RhoJ signaling halts the growth of BRAF mutant melanoma tumors in vivo and induces apoptosis in melanoma cells in vitro via …

Association Of Altered Collagen Content And Lysyl Oxidase Expression In Degenerative Mitral Valve Disease, K-Raman Purushothaman, Meerarani Purushothaman, Irene C. Turnbull, David H. Adams, Anelechi Anyanwu, Prakash Krishnan, Annapoorna Kini, Samin K. Sharma, William N. O'Connor, Pedro R. Moreno

Pathology and Laboratory Medicine Faculty Publications

Background—Collagen cross-linking is mediated by lysyl oxidase (LOX) enzyme in the extracellular matrix (ECM) of mitral valve leaflets. Alterations in collagen content and LOX protein expression in the ECM of degenerative mitral valve may enhance leaflet expansion and disease severity.

Methods—Twenty posterior degenerative mitral valve leaflets from patients with severe mitral regurgitation were obtained at surgery. Five normal posterior mitral valve leaflets procured during autopsy served as controls. Valvular interstitial cells (VICs) density was quantified by immunohistochemistry, collagen types I and III by picro-sirius red staining and immunohistochemistry, and proteoglycans by alcian blue staining. Protein expression of LOX …

Tumor-Treating Fields Plus Chemotherapy Versus Chemotherapy Alone For Glioblastoma At First Recurrence: A Post Hoc Analysis Of The Ef-14 Trial., Santosh Kesari, Zvi Ram

Articles, Abstracts, and Reports

BACKGROUND: This post hoc analysis of the EF-14 trial (NCT00916409) of tumor-treating fields (TTFields) plus temozolomide versus temozolomide alone in newly diagnosed glioblastoma compared the efficacy of TTFields plus chemotherapy (physician's choice) versus chemotherapy alone after first recurrence.

METHODS: Patients on TTFields plus temozolomide continued TTFields plus second-line chemotherapy after first recurrence. Some patients on temozolomide alone crossed over after approval of TTFields for recurrent GBM. The primary efficacy outcome was overall survival (OS).

RESULTS: After disease progression, 131 patients received TTFields plus chemotherapy and 73 chemotherapy alone. Thirteen patients in the original temozolomide-alone group crossed over to receive TTFields …

Oncolog, Volume 62, Number 07, July 2017, Joe Munch, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• RAS Mutations and Colorectal Cancer Liver Metastases: Gene mutations may have implications for local therapy for liver metastases from colorectal cancer.
• Active Surveillance for Prostate Cancer: Clinical trial may clarify which patients with prostate cancer will benefit from active surveillance rather than immediate treatment.
• Gut Microbiome May Affect Immunotherapy Response in Melanoma: Metastatic melanoma patients who experience responses to checkpoint inhibitors have a distinct gut bacterial genetic signature.
• HOUSE CALL: Cancer-Related fatigue-Tips for fighting fatigue

Pioglitazone Treatment Following Spinal Cord Injury Maintains Acute Mitochondrial Integrity And Increases Chronic Tissue Sparing And Functional Recovery, Samir P. Patel, David H. Cox, Jenna L. Gollihue, William M. Bailey, Werner J. Geldenhuys, John C. Gensel, Patrick G. Sullivan, Alexander G. Rabchevsky

Spinal Cord and Brain Injury Research Center Faculty Publications

Pioglitazone is an FDA-approved PPAR-γ agonist drug used to for treat diabetes, and it has demonstrated neuroprotective effects in multiple models of central nervous system (CNS) injury. Acute treatment after spinal cord injury (SCI) in rats is reported to suppress neuroinflammation, rescue injured tissues, and improve locomotor recovery. In the current study, we additionally assessed the protective efficacy of pioglitazone treatment on acute mitochondrial respiration, as well as functional and anatomical recovery after contusion SCI in adult male C57BL/6 mice. Mice received either vehicle or pioglitazone (10 mg/kg) at either 15 min or 3 hr after injury (75 kDyn at …

Temperature As A Circadian Marker In Older Human Subjects: Relationship To Metabolic Syndrome And Diabetes, Brianna D. Harfmann, Elizabeth A. Schroder, Jonathan H. England, Natalie J. Senn, Philip M. Westgate, Karyn A. Esser, Philip A. Kern

Internal Medicine Faculty Publications

Background: Circadian rhythms are characterized by approximate 24-hour oscillations in physiological and behavioral processes. Disruptions in these endogenous rhythms, most commonly associated with shift work and/or lifestyle, are recognized to be detrimental to health. Several studies have demonstrated a high correlation between disrupted circadian rhythms and metabolic disease. The aim of this study was to determine which metabolic parameters correlate with physiological measures of circadian temperature amplitude (TempAmp) and stability (TempStab).

Methods: Wrist skin temperature was measured in 34 subjects (ages 50 to 70, including lean, obese, and diabetic subjects) every 10 minutes for 7 consecutive days. Anthropometric measures and …

The Write Stuff - Summer 2017 (Vol. 14, No. 3), Research Medical Library

Write Stuff 2017

• Grant Writers' seminars return in October
• Increase INTEREST in your grant proposals
• Academic search engine optimization: Help readers find your research
• Plagiarism policies of journals preferred by MD Anderson authors
• Tips for writing Introduction sections for NIH “resubmission” grant applications
• Unusual terms used in scientific writing and publishing: Journalology

Biochemical Effects Of Exercise On A Fasciocutaneous Flap In A Rat Model., Edita Aksamitiene, Adam L. Baker, Sudeep Roy, Salini Hota, Li-Hui Zhang, Julianna Rodin, Kealan Hobelmann, Jan B. Hoek, Edmund A. Pribitkin

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Importance: An overwhelming amount of data suggest that cardiovascular exercise has a positive effect on the mind and body, although the precise mechanism is not always clear.

Objective: To assess the clinical and biochemical effects of voluntary cardiovascular exercise on pedicled flaps in a rodent model.

Design, Setting, and Participants: Eighteen adult Sprague-Dawley male rats were randomized into a resting animal group (RAG) (n=9) and an exercise animal group (EAG) (n=9) for 14 days (July 23, 2013, through July 30, 2013). A pedicled transposition flap was performed on the ventral surface of the rat, and biopsy specimens were taken from …

Divergence Of Camp Signalling Pathways Mediating Augmented Nucleotide Excision Repair And Pigment Induction In Melanocytes, Erin M. Wolf Horrell, Stuart G. Jarrett, Katharine M. Carter, John A. D'Orazio

Markey Cancer Center Faculty Publications

Loss‐of‐function melanocortin 1 receptor (MC1R) polymorphisms are common in UV‐sensitive fair‐skinned individuals and are associated with blunted cAMP second messenger signalling and higher lifetime risk of melanoma because of diminished ability of melanocytes to cope with UV damage. cAMP signalling positions melanocytes to resist UV injury by upregulating synthesis of UV‐blocking eumelanin pigment and by enhancing the repair of UV‐induced DNA damage. cAMP enhances melanocyte nucleotide excision repair (NER), the genome maintenance pathway responsible for the removal of mutagenic UV photolesions, through cAMP‐activated protein kinase (protein kinase A)‐mediated phosphorylation of the ataxia telangiectasia‐mutated and Rad3‐related (ATR) protein on the S435 …

Experience With The Quantitative Lyta Gene Real-Time Polymerase Chain Reaction For The Detection Of Streptococcus Pneumoniae From Pediatric Whole Blood In Pakistan, Furqan Kabir, Sahrish Muneer, Adil Kalam, Ana Sami, Shahida Qureshi, Aneeta Hotwani, Atif Riaz, Syed Mohiuddin, Mohammad Tahir Yousafzai, Sara Hussain, Syed Asad Ali, Sadia Shakoor

Department of Paediatrics and Child Health

Background: We present our experience with optimization and diagnostic use of quantitative real-time polymerase chain reaction (PCR) targeting the lytA gene of Streptococcus pneumoniae for the detection of S. pneumoniae in whole blood of children ≥5 CFU/10 μl or 1 copy of DNA/2 μl of blood.
Methods: This assay was applied on 1912 whole blood specimens collected from children pneumonia, of which 35 specimens were lytA positive. The bacterial loads were determined through categorization of load into five different categories, i.e., very high load, high load, moderate load, low load, and very low load.
Results: Of the 35 lytA-positive …

Age And Sex Normalization Of Intestinal Permeability Measures For The Improved Assessment Of Enteropathy In Infancy And Early Childhood: Results From The Mal-Ed Study, Margaret N. Kosek, Gwenyth O. Lee, Richard L. Guerrant, Rashidul Haque, Gagandeep Kang, Tahmeed Ahmed, Pascal Bessong, Syed Asad Ali, Shahida Qureshi, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Objectives: The aim of the study was to describe changes in intestinal permeability in early childhood in diverse epidemiologic settings.
Methods: In a birth cohort study, the lactulose:mannitol (L:M) test was administered to 1980 children at 4 time points in the first 24 months of life in 8 countries. Data from the Brazil site with an incidence of diarrhea similar to that seen in the United States and no growth faltering was used as an internal study reference to derive age- and sex-specific z scores for mannitol and lactulose recoveries and the L:M ratio.
Results: A total of 6602 tests …

The Development And Psychometric Analysis Of The Mu- Fertility Knowledge Assessment Scale, Qiyan Mu

Dissertations (1934 -)

Young women between the ages of 18 to 24 experience disproportionally high rates of negative sexual and reproductive health outcomes. Inadequate and inaccurate fertility knowledge can hinder a young woman’s self-care abilities in managing her sexual and reproductive health. There is no validated instrument to assess young women’s fertility knowledge. The primary purpose of this study is to develop and evaluate the psychometric properties of the MU-fertility knowledge assessment scale (MU-FKAS) for young women. The secondary purpose is to explore the relationships among young women’s individual and contextual factors, self-perceived fertility knowledge, actual fertility knowledge, and fertility health risks. A …

Neuropsychiatric Aspects Of Infectious Diseases: An Update, Sahil Munjal, Stephen J. Ferrando, Zachary Freyberg

NYMC Faculty Publications

Among the critically ill, infectious diseases can play a significant role in the etiology of neuropsychiatric disturbances. All critical care physicians are familiar with delirium as a secondary complication of systemic infection. This article focuses on key infectious diseases that commonly and directly produce neuropsychiatric symptoms, including direct infection of the central nervous system, human immunodeficiency virus infection, and AIDS.

Brain Injury With Systemic Inflammation In Newborns With Congenital Heart Disease Undergoing Heart Surgery, R Pironkova, Joseph Giamelli, H Seiden, V Parnell, D Gruber, C Sison, K Ojamaa

NYMC Faculty Publications

The potential role of systemic inflammation on brain injury in newborns with congenital heart disease (CHD) was assessed by measuring levels of central nervous system (CNS)-derived proteins in serum prior to and following cardiac surgery. A total of 23 newborns (gestational age, 39±1 weeks) with a diagnosis of CHD that required cardiac surgery with cardiopulmonary bypass (CPB) were enrolled in the current study. Serum samples were collected immediately prior to surgery and 2, 24 and 48 h following CPB, and serum levels of phosphorylated neurofilament-heavy subunit (pNF-H), neuron-specific enolase (NSE) and S100B were analyzed. Systemic inflammation was assessed by measuring …

The Path Report Volume 1 Issue 1, Pathology Department, New York Medical College

The Path Report

No abstract provided.

Connecting The Brain To Itself Through An Emulation., Mijail D. Serruya

Department of Neurology Faculty Papers

Pilot clinical trials of human patients implanted with devices that can chronically record and stimulate ensembles of hundreds to thousands of individual neurons offer the possibility of expanding the substrate of cognition. Parallel trains of firing rate activity can be delivered in real-time to an array of intermediate external modules that in turn can trigger parallel trains of stimulation back into the brain. These modules may be built in software, VLSI firmware, or biological tissue as in vitro culture preparations or in vivo ectopic construct organoids. Arrays of modules can be constructed as early stage whole brain emulators, following canonical …

Mammographic Density And Ageing: A Collaborative Pooled Analysis Of Cross-Sectional Data From 22 Countries Worldwide, Anya Burton, Gertraud Maskarinec, Beatriz Perez-Gomez, Celine Vachon, Hui Miao, Martín Lajous, Ruy López-Ridaura, Megan Rice, Ana Pereira, Maria Luisa Garmendia, Rulla M. Tamimi, Kimberly Bertrand, Ava Kwong, Giske Ursin, Sudhir Vinayak, Rose Ndumia, Shivaani Mariapun

Imaging & Diagnostic Radiology, East Africa

Background:Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known.

Methods and findings: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35–85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of …

A Phase Ii Randomized Trial Of Observation Versus Stereotactic Ablative Radiation For Oligometastatic Prostate Cancer (Oriole)., Noura Radwan, Ryan Phillips, Ashley Ross, Steven P. Rowe, Michael A. Gorin, Emmanuel S. Antonarakis, Curtiland Deville, Stephen Greco, Samuel Denmeade, Channing Paller, Daniel Y. Song, Maximilian Diehn, Hao Wang, Michael Carducci, Kenneth J. Pienta, Martin G. Pomper, Theodore L. Deweese, Adam Dicker, Mario Eisenberger, Phuoc T. Tran

Department of Radiation Oncology Faculty Papers

BACKGROUND: We describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints will include local control at 6 months post-SABR, toxicity and quality of life, and androgen deprivation therapy …

The Effects Of C5-Substituted 2,4-Diaminoquinazolines On Selected Transcript Expression In Spinal Muscular Atrophy Cells., Cinsley Gentillon, Andrew J Connell, Ryan W Kirk, Matthew E R Butchbach

Department of Pediatrics Faculty Papers

C5-substituted 2,4-diaminoquinazolines (2,4-DAQs) ameliorate disease severity in SMA mice. It is uncertain, however, that these compounds increase SMN protein levels in vivo even though they were identified as activators of the SMN2 promoter. These compounds also regulate the expression of other transcripts in neuroblastoma cells. In this study, we investigate the mechanism by which the 2,4-DAQs regulate the expression of SMN2 as well as other targets. D156844, D158872, D157161 and D157495 (RG3039) increased SMN2 promoter-driven reporter gene activity by at least 3-fold in NSC-34 cells. These compounds, however, did not significantly increase SMN2 mRNA levels in type II SMA fibroblasts …

Pain And Physical Function In A Socioeconomically Diverse Sample Of Black And White Adults, Angela Sardina

USF Tampa Graduate Theses and Dissertations

Musculoskeletal pain alters physiological function and these changes may be evidenced as early as middle age. Previous research has concluded that middle-aged adults are a high-risk group for chronic pain and report functional limitations similar to older adults. However, few studies have explored the unique individual factors (e.g., sociodemographic, health, and psychosocial characteristics) that may drive the pain experience; and more research is needed that examines the relationships between musculoskeletal pain and physical function, using objective performance measures, in a sample of racially and socioeconomically diverse adults.

Data from the Healthy Aging in Neighborhoods of Diversity across the Life Span …

Dach1 Suppresses Breast Cancer As A Negative Regulator Of Cd44., Hanxiao Xu, Shengnan Yu, Xun Yuan, Jing Xiong, Dong Kuang, Richard Pestell, Kongming Wu

Department of Cancer Biology Faculty Papers

Dachshund homolog 1 (DACH1), a key cell fate determination factor, contributes to tumorigenesis, invasion, metastasis of human breast neoplasm. However, the exact molecular mechanisms for the anti-tumor roles of DACH1 in breast carcinoma are still lack of extensive understanding. Herein, we utilized immunohistochemistry (IHC) staining and public microarray data analysis showing that DACH1 was higher in normal breast, low-grade and luminal-type cancer in comparison with breast carcinoma, high-grade and basal-like tumors respectively. Additionally, both correlation analysis of public databases of human breast carcinoma and IHC analysis of mice xenograft tumors demonstrated that DACH1 inversely related to cancer stem cells (CSCs) …

Pathologists' Diagnosis Of Invasive Melanoma And Melanocytic Proliferations: Observer Accuracy And Reproducibility Study., Joann G Elmore, Raymond L Barnhill, David E Elder, Gary M Longton, Margaret S Pepe, Lisa M Reisch, Patricia A Carney, Linda J Titus, Heidi D Nelson, Tracy Onega, Anna N A Tosteson, Martin A Weinstock, Stevan R Knezevich, Michael W Piepkorn

Articles, Abstracts, and Reports

No abstract provided.

Abnormal Dendritic Maturation Of Developing Cortical Neurons Exposed To Corticotropin Releasing Hormone (Crh): Insights Into Effects Of Prenatal Adversity?, Megan M. Curran, Curt A. Sandman, Elysia Poggi Davis, Laura M. Glynn, Tallie Z. Baram

Psychology: Faculty Scholarship

Corticotropin releasing hormone (CRH) produced by the hypothalamus initiates the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the body’s stress response. CRH levels typically are undetectable in human plasma, but during pregnancy the primate placenta synthesizes and releases large amounts of CRH into both maternal and fetal circulations. Notably, placental CRH synthesis increases in response to maternal stress signals. There is evidence that human fetal exposure to high concentrations of placental CRH is associated with behavioral consequences during infancy and into childhood, however the direct effects on of the peptide on the human brain are unknown. In this study, we used a …

Fatal Rituximab-Induced Nonspecific Interstitial Pneumonia: Case Report And Review Of The Literature, Rino Sato, Md, Jeremy Molligan, Md, Sameh Gaballa, Md

The Medicine Forum

Introduction:

Rituximab is a chimeric anti-CD20 monoclonal antibody that is used to treat some hematological malignancies such as B-cell lymphomas, and various autoimmune diseases including immune thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. The most common side effects include fever, chills, and rigors. Respiratory complications such as cough, bronchospasm, sinusitis, and rhinitis have also been reported in 30% of patients in clinical trials.1 Rituximab-induced lung injury is a very rare but potentially fatal complication. We report a case of fatal single agent rituximab-induced nonspecific interstitial pneumonia to increase awareness about this serious side effect and review …

Case Report: Cytarabine-Induced Pericarditis And Pericardial Effusion, Rino Sato, Md, Robert Park, Md

The Medicine Forum

Introduction:

Cytarabine (cytosine arabinoside, Ara-C) is an antimetabolite analogue of cytidine that is used as a chemotherapeutic agent for the treatment of acute myelogenous leukemia and lymphocytic leukemias1 . The most common side effects of this therapy include myelosuppression, pancytopenia, hepatotoxicity, gastrointestinal ulceration with bleeding, and pulmonary infiltrates2. Cardio-pulmonary complications of cytarabine therapy are uncommon, but include supraventricular and ventricular arrhythmias, sinus bradycardia, and recurrent heart failure2, 3. Occasionally, patients may develop pericarditis leading to pericardial tamponade, which can be fatal. We report a case of cytarabine-induced pericarditis and pericardial effusion to increase awareness about this serious side effect of …

Discoidin Domain Receptor 1 Modulates Insulin Receptor Signaling And Biological Responses In Breast Cancer Cells., Veronica Vella, Roberta Malaguarnera, Maria Luisa Nicolosi, Chiara Palladino, Cristina Spoleti, Michele Massimino, Paolo Vigneri, Michele Purrello, Marco Ragusa, Andrea Morrione, Antonino Belfiore

Department of Urology Faculty Papers

The fetal isoform A of the insulin receptor (IR-A) is frequently overexpressed in a variety of malignancies including breast cancer. IR overexpression has a recognized role in cancer progression and resistance to anticancer therapies. In particular, IR-A has a peculiar mitogenic potential and is activated not only by insulin but also by IGF-2. Previously, we identified discoidin domain receptor 1 (DDR1) as a new IR-A interacting protein. DDR1, a non-integrin collagen tyrosine kinase receptor, is overexpressed in several malignancies and plays a role in cancer progression and metastasis.We now evaluated whether DDR1 is able to exert a role in breast …

Cytotoxicity Of Platinum Anticancer Drugs In Mammalian Cell Lines Of Metastatic Cancer, Hosannah Evie

Mahurin Honors College Capstone Experience/Thesis Projects

With the invention of advanced technology, focus has been put on understanding and looking for potential cures for many diseases, one of which is cancer. The difference in the leaving and non-leaving ligands of the FDA approved cancer drugs contributes to the differential cell specific cytotoxic effects. These drugs such as oxaliplatin approved for colorectal cancer, cisplatin approved for testicular cancer, and their analogs were used to treat different cancer cell lines in an MTT assay. This project aims to determine how changing the molecular shape of these compounds affects their uptake and toxicity into different cell lines. The assay …

Investigating The Synergistic Effects Of Cisplatin And Two Curcuminoid Compounds On Cancer, Denis Hodzic

Mahurin Honors College Capstone Experience/Thesis Projects

Cisplatin is an anti-cancer drug effective against several cancers which can produce the serious side-effect of hearing loss. Curcumin, a natural plant compound, can increase the activity of cisplatin against cancer and counteract cisplatin’s effect against hearing. Because curcumin exhibits poor bioavailability, there is considerable interest in developing synthetic curcumin analogs (curcuminoids) that are more soluble and which retain anti-cancer activity and otoprotective function. This study investigated whether two curcuminoids, EF-24 and CLEFMA, increase the cytotoxic and ototoxic effects of cisplatin against the lung cancer cell line, A549, and the colorectal cancer cell line, Caco2. Cytotoxicity was measured by using …

My Crown And Glory: Community, Identity, Culture, And Black Women’S Concerns Of Hair Product-Related Breast Cancer Risk, Dede K. Teteh, Susanne B. Montgomery, Sabine Monice, Laura Stiel, Phyllis Y. Clark, Eudora Mitchell

Health Sciences and Kinesiology Faculty Articles

Breast cancer (BC) incidence rates for Black and non-Hispanic White women have recently converged; however, Black women continue to die at higher rates from the disease. Black women also use hair products containing hormonally active chemicals at higher rates than other races and ethnic groups. Studies now link chemical components in hair and personal care products to breast cancer risk. Using a community-based participatory research approach, this qualitative study explored community concerns about the role of hair products on breast cancer risk. Focus groups and key informant interviews using triangulation to assure relevant perspectives (women with and without breast cancer …