Digital Commons Network^™

Protein-Altering Germline Mutations Implicate Novel Genes Related To Lung Cancer Development., Xuemei Ji, Semanti Mukherjee, Maria Teresa Landi, Yohan Bosse, Philippe Joubert, Dakai Zhu, Ivan Gorlov, Xiangjun Xiao, Younghun Han, Olga Gorlova, Rayjean J Hung, Yonathan Brhane, Robert Carreras-Torres, David C Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, Chu Chen, Jinyoung Byun, Konstantin H Dragnev, John K Field, Lambertus Fa Kiemeney, Philip Lazarus, Shan Zienolddiny, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Pier A Bertazzi, Angela C Pesatori, Nancy Diao, Li Su, Lei Song, Ruyang Zhang, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H F M Van Der Heijden, Jin Hee Kim, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Erich Wichmann, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Lesley M Butler, Kenneth Offit, Preethi Srinivasan, Chaitanya Bandlamudi, Matthew D Hellmann, David B Solit, Mark E Robson, Charles M Rudin, Zsofia K Stadler, Barry S Taylor, Michael F Berger, Richard Houlston, John Mclaughlin, Victoria Stevens, David C Nickle, Ma'en Obeidat, Wim Timens, María Soler Artigas, Sanjay Shete, Hermann Brenner, Stephen Chanock, Paul Brennan, James D Mckay, Christopher I Amos

Articles, Abstracts, and Reports

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10-15) and replication (adjusted OR = 2.93, P = 2.22 × 10-3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is …

Mentored Training And Its Association With Dissemination And Implementation Research Output: A Quasi-Experimental Evaluation, Rebekah R Jacob, Angeline Gacad, Margaret Padek, Graham A Colditz, Karen M Emmons, Jon F Kerner, David A Chambers, Ross C Brownson

Open Access Publications

BACKGROUND: There is a continued need to evaluate training programs in dissemination and implementation (D&I) research. Scientific products yielded from trainees are an important and objective measure to understand the capacity growth within the D&I field. This study evaluates our mentored training program in terms of scientific productivity among applicants.

METHODS: Post-doctoral and early-career cancer researchers were recruited and applied to the R25 Mentored Training for Dissemination and Implementation Research in Cancer (MT-DIRC) between 2014 and 2017. Using application details and publicly available bibliometric and funding data, we compared selected fellows with unsuccessful applicants (nonfellows). We extracted Scopus citations and …

Can Cities Be Feminist? A Cross-National Analysis Of Factors Affecting Local Female Representation In Latin America, Katie Davis

Honors Theses

Women are underrepresented in mayor’s offices and on city councils across Latin America. In this paper, I examine gender-based differences in individual opinions toward running for office in Argentina and Uruguay, as well as conduct a twenty-six country analysis on factors related to female representation in municipal government. Based on these analyses, I make three main conclusions about female local representation in Latin America. The first conclusion is that women in Latin America are significantly less likely to want to run or feel qualified to run for office. The second conclusion is that cross-national variation in the percentage of female …

The Effects Of Activity-Based Anorexia On The Rewarding Properties Of Methamphetamine And Wheel Running, Rachael M. Langa

Theses and Dissertations

An activity-based anorexia (ABA) paradigm in adolescent female mice was used to explore whether anorexia affects circuits underlying reward. The ABA paradigm significantly enhanced methamphetamine-induced conditioned place preference (CPP), but not wheel-induced CPP. These results indicate that the ABA paradigm enhances the rewarding properties of methamphetamine, but not wheel running.

Dna Methylation Signature For Ezh2 Functionally Classifies Sequence Variants In Three Prc2 Complex Genes, Sanaa Choufani, William T. Gibson, Andrei L. Turinsky, Brian H Y Chung, Tianren Wang, Kopal Garg, Alessandro Vitriolo, Ana S A Cohen, Sharri Cyrus, Sarah Goodman, Eric Chater-Diehl, Jack Brzezinski, Michael Brudno, Luk Ho Ming, Susan M. White, Sally Ann Lynch, Carol Clericuzio, I Karen Temple, Frances Flinter, Vivienne Mcconnell, Tom Cushing, Lynne M. Bird, Miranda Splitt, Bronwyn Kerr, Stephen W. Scherer, Jerry Machado, Eri Imagawa, Nobuhiko Okamoto, Naomichi Matsumoto, Guiseppe Testa, Maria Iascone, Romano Tenconi, Oana Caluseriu, Roberto Mendoza-Londono, David Chitayat, Cheryl Cytrynbaum, Katrina Tatton-Brown, Rosanna Weksberg

Pediatrics Research and Scholarship

Weaver syndrome (WS), an overgrowth/intellectual disability syndrome (OGID), is caused by pathogenic variants in the histone methyltransferase EZH2, which encodes a core component of the Polycomb repressive complex-2 (PRC2). Using genome-wide DNA methylation (DNAm) data for 187 individuals with OGID and 969 control subjects, we show that pathogenic variants in EZH2 generate a highly specific and sensitive DNAm signature reflecting the phenotype of WS. This signature can be used to distinguish loss-of-function from gain-of-function missense variants and to detect somatic mosaicism. We also show that the signature can accurately classify sequence variants in EED and SUZ12, which encode two other …

Association Of Multisetting Community Programs And Policies With Child Body Mass Index: The Healthy Communities Study, Vicki L. Collie-Akers, Stephen B. Fawcett, Jerry A. Schultz, Kandace K. Fleming, Rebecca E. Swinburne Romine, Lorrene D. Ritchie, Edward A. Frongillo Jr., S Sonia Arteaga

Faculty Publications

INTRODUCTION:

Expert opinion suggests that efforts to address childhood obesity should seek to transform the environments in which children operate. The objective of this study was to describe the extent to which multisetting programs and policies interact with community and child predictors and are associated with child body mass index (BMI) in the 130 US communities participating in the Healthy Communities Study.

METHODS:

For 2 years beginning in fall 2013, we collected data through key informant interviews on community programs and policies related to healthy weight among children that occurred in the 10 years before the interview. We characterized community …

Switching To Lurasidone Following 12 Months Of Treatment With Risperidone: Results Of A 6-Month, Open-Label Study, Greg W Mattingly, Peter M Haddad, Michael Tocco, Jane Xu, Debra Phillips, Andrei Pikalov, Antony Loebel

Open Access Publications

BACKGROUND: Patients with a diagnosis of schizophrenia are at an increased risk for developing metabolic syndrome, which is associated with greater cardiovascular morbidity and mortality. Treatment with some commonly used antipsychotic medications may increase the risk of developing metabolic syndrome. The aim of the study was to evaluate the safety of lurasidone in patients who continued lurasidone or switched from risperidone to lurasidone. A secondary aim was assessment of the effect of long-term lurasidone on the Positive and Negative Syndrome Scale (PANSS).

METHODS: The treatment sample in the current study consisted of clinically stable patients with schizophrenia (N = 223) …

Nk Cell-Derived Gm-Csf Potentiates Inflammatory Arthritis And Is Negatively Regulated By Cis, Cynthia Louis, Fernando Souza-Fonseca-Guimaraes, Yuyan Yang, Damian D'Silva, Tobias Kratina, Laura Dagley, Soroor Hediyeh-Zadeh, Jai Rautela, Seth Lucian Masters, Melissa J Davis, Jeffrey J Babon, Bogoljub Ciric, Eric Vivier, Warren S Alexander, Nicholas D Huntington, Ian P Wicks

Department of Neurology Faculty Papers

Despite increasing recognition of the importance of GM-CSF in autoimmune disease, it remains unclear how GM-CSF is regulated at sites of tissue inflammation. Using GM-CSF fate reporter mice, we show that synovial NK cells produce GM-CSF in autoantibody-mediated inflammatory arthritis. Synovial NK cells promote a neutrophilic inflammatory cell infiltrate, and persistent arthritis, via GM-CSF production, as deletion of NK cells, or specific ablation of GM-CSF production in NK cells, abrogated disease. Synovial NK cell production of GM-CSF is IL-18–dependent. Furthermore, we show that cytokine-inducible SH2-containing protein (CIS) is crucial in limiting GM-CSF signaling not only during inflammatory arthritis but also …

Why Do Graduates Choose To Work In A Less Attractive Specialty? A Cross-Sectional Study On The Role Of Personal Values And Expectations, Van Anh Nguyen, Karen D. Könings, E Pamela Wright Phd, Ms, Med, Rn, Cen, Giang Bao Kim, Hoat Ngoc Luu, Albert J. Scherpbier, Jeroen J. Van Merriënboer

Publications

BACKGROUND: Primary health care (PHC), of which preventive medicine (PM) is a subspecialty, will have to cope with a deficiency of staff in the future, which makes the retention of graduates urgent. This study was conducted in Vietnam, where PM is an undergraduate degree in parallel to medical training. It aims to identify facilitating and hindering factors that impact recruitment and retention of PM graduates in the specialty. METHODS: A cross-sectional study enrolled 167 graduates who qualified as PM doctors from a Vietnamese medical school, between 2012 and 2018. Data were collected via an online questionnaire that asked participants about …

Seizure Freedom Improves Health-Related Quality Of Life After Epilepsy Surgery In Children., Puneet Jain, Mary Lou Smith, Kathy Speechley, Mark Ferro, Mary Connolly, Rajesh Ramachandrannair, Salah Almubarak, Andrea Andrade, Elysa Widjaja

Paediatrics Publications

AIM: To determine whether epilepsy surgery improved health-related quality of life (HRQoL) and whether seizure freedom after surgery mediated the improvement in HRQoL.

METHOD: This multicenter cohort study compared HRQoL after epilepsy surgery to pharmacological management in children with drug-resistant epilepsy (DRE). HRQoL was measured using the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire at baseline and 1-year follow-up. The mediator between treatment type and HRQoL was seizure freedom.

RESULTS: Two hundred and thirty-seven patients were recruited (surgery group: n=147 [92 males, 45 females]; pharmacological group: n=90 [53 males, 37 females]). Mean age at seizure onset was 6 years …

Age At Migration And The Risk Of Psychotic Disorders: A Systematic Review And Meta-Analysis., Kelly K. Anderson, Jordan Edwards

Epidemiology and Biostatistics Publications

OBJECTIVE: To conduct a systematic review and meta-analysis of the existing evidence on the association between age at migration and the risk of psychotic disorders.

METHODS: Observational studies were eligible for inclusion if they presented data on the association between age at migration and the risk of psychotic disorders among first-generation migrant groups. We used two random effects meta-analyses to pool effect estimates for each stratum of age at migration relative to (i) a native-born reference category and (ii) the youngest age stratum (0 to 2 years).

RESULTS: Ten studies met inclusion criteria, and five were included in the meta-analysis. …

Accelerating Care Through Echo: Case Examples From The Field., Mirna Becevic, Emmanuelle Wallach, Lincoln R. Sheets, Hope Misterovich, Susan Norris, Evelyn Aboagye, Jonathan A Dyer, Bruce R Bacon, Karen Edison, Kristin Sohl

Project ECHO Bibliography

In this article, we describe three life-changing patient cases demonstrating high-quality and timely care they received in their communities, thanks to the Show-Me ECHO project. Early autism diagnosis, a potentially deadly tumor manifesting as a benign-looking rash, a recalcitrant case of hepatitis C: rural and underserved Missourians now have access to state-of-the-art care through their local providers receiving interdisciplinary telementoring on evidence based practices.

Tetraspanin Cd82 Drives Acute Myeloid Leukemia Chemoresistance By Modulating Protein Kinase C Alpha And Β1 Integrin Activation, Muskan Floren, Sebastian Restrepo Cruz, Christina M. Termini, Kristopher D. Marjon, Keith A. Lidke, Jennifer M. Gillette

Pathology Research and Scholarship

A principal challenge in treating acute myeloid leukemia (AML) is chemotherapy refractory disease. As such, there remains a critical need to identify key regulators of chemotherapy resistance in AML. In this study, we demonstrate that the membrane scaffold, CD82, contributes to the chemoresistant phenotype of AML. Using an RNA-seq approach, we identified the increased expression of the tetraspanin family member, CD82, in response to the chemotherapeutic, daunorubicin. Analysis of the TARGET and BEAT AML databases identifies a correlation between CD82 expression and overall survival of AML patients. Moreover, using a combination of cell lines and patient samples, we find that …

Effect Of Pembrolizumab Plus Neoadjuvant Chemotherapy On Pathologic Complete Response In Women With Early-Stage Breast Cancer: An Analysis Of The Ongoing Phase 2 Adaptively Randomized I-Spy2 Trial., Rita Nanda, Minetta C Liu, Christina Yau, Rebecca Shatsky, Lajos Pusztai, Anne Wallace, A Jo Chien, Andres Forero-Torres, Erin D Ellis, Heather Han, Amy Clark, Kathy Albain, Judy C Boughey, Nora T Jaskowiak, Anthony Elias, Claudine Isaacs, Kathleen Kemmer, Teresa Helsten, Melanie Majure, Erica Stringer-Reasor, Catherine Parker, Marie C Lee, Tufia Haddad, Ronald N Cohen, Smita Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Katherine Steeg, Adam Asare, Jeffrey B Matthews, Scott Berry, Ashish Sanil, Richard Schwab, W Fraser Symmans, Laura Van 'T Veer, Douglas Yee, Angela Demichele, Nola M Hylton, Michelle Melisko, Jane Perlmutter, Hope S Rugo, Donald A Berry, Laura J Esserman

Articles, Abstracts, and Reports

Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed.

Objective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial.

Design, Setting, and Participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with …

Randomized Phase Ii Study Of Stereotactic Body Radiotherapy And Interleukin-2 Versus Interleukin-2 In Patients With Metastatic Melanoma., Brendan Curti, Marka R Crittenden, Steven K Seung, Christopher B Fountain, Roxanne Payne, Shuching Chang, Jessica Fleser, Kimberly Phillips, Ian Malkasian, Lyn B Dobrunick, Walter Urba

Articles, Abstracts, and Reports

BACKGROUND: A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma.

METHODS: Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) …

Network Meta-Analysis To Compare Venaseal With Other Superficial Venous Therapies For Chronic Venous Insufficiency., Raghu Kolluri, Janice Chung, Sue Kim, Nibir Nath, Bhoomika Bajaj Bhalla, Tarun Jain, Joseph Zygmunt, Alun Davies

Heart and Vascular Articles

OBJECTIVE: Several randomized controlled trials (RCTs) have compared different interventions for chronic venous insufficiency (CVI) management, but mixed comparison of these interventions is lacking. The aim of this network meta-analysis was to compare VenaSeal closure system (Medtronic, Minneapolis, Minn) with endovenous laser ablation (EVLA), radiofrequency ablation (RFA), mechanochemical ablation, sclerotherapy, and surgery for management of CVI to achieve anatomic success (complete closure of treated vein within 6 months after intervention) as the primary outcome and health-related quality of life (HRQoL; EuroQol-5 Dimension, Aberdeen Varicose Vein Questionnaire), Venous Clinical Severity Score (VCSS), pain scores, and adverse events as secondary outcomes.

METHODS: …

Pre-Exercise Hydration Status Changes In Females Throughout The Menstrual Cycle, Kristen A. Splaine

Honors Scholar Theses

In the field of athletics, research including females is limited. Oftentimes, research that only included male subjects is generalized and is later used to incorporate guidelines for both male and female athletes. This study focused on how the menstrual cycle, a female exclusive bodily process, could change hydration status. Participants within the study were between the ages of 18 and 35 and only data from females was analyzed. The study was designed as a crossover subject trial over the span of two months. Subjects participated in a total of four trials that were divided into phase-hydration groups. Two trials were …

The Β3-Adrenergic Receptor Agonist Mirabegron Improves Glucose Homeostasis In Obese Humans, Brian S. Finlin, Hasiyet Memetimin, Beibei Zhu, Amy L. Confides, Hemendra J. Vekaria, Riham H. El Khouli, Zachary R. Johnson, Philip M. Westgate, Jianzhong Chen, Andrew J. Morris, Patrick G. Sullivan, Esther E. Dupont-Versteegden, Philip A. Kern

Internal Medicine Faculty Publications

BACKGROUND. Beige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.

METHODS. Before and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and …

Exploration Of The Intersection Of Social Identities Of Female Leaders In Postsecondary Education: A Phenomenological Approach, Sara Shaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study was to explore the lived experiences of female leaders currently in leadership roles in postsecondary education. This hermeneutic phenomenological study was conducted to explore intersecting identities and how the identities affected female leaders’ leadership experiences and decision-making processes. Through the theoretical framework of intersectionality, I explored the relationships among females, leadership, career decision-making, and other categorical social identities. Data gathered from semi-structured one-on-one interviews and demographic surveys with 11 female postsecondary leaders sought to understand how gender and selected social identities affect career decision-making of women in postsecondary leadership positions. The researcher identified seven themes: …

Hypoglycaemia Is Reduced With Use Of Inhaled Technosphere ® Insulin Relative To Insulin Aspart In Type 1 Diabetes Mellitus, E R Seaquist, L Blonde, J B Mcgill, S R Heller, D M Kendall, J B Bumpass, F M Pompilio, M L Grant

2020-Current year OA Pubs

AIM: To evaluate the effect of final HbA

METHODS: In the randomized, phase 3, multicentre AFFINITY-1 study, adults (N = 375) who had type 1 diabetes for ≥ 12 months and an HbA

RESULTS: Participants treated with Technosphere Insulin experienced statistically significantly fewer level 1 and 2 hypoglycaemic events and a lower incidence of level 3 hypoglycaemia than participants treated with insulin aspart. The lower rate of hypoglycaemia with Technosphere Insulin was observed across the range of end-of-treatment HbA

CONCLUSIONS: Participants using Technosphere Insulin experienced clinically non-inferior glycaemic control and lower hypoglycaemia rates across a range of HbA

Three-Dimensional Facial Morphology In Cantú Syndrome, Helen I Roessler, Kathleen Shields, Dorothy K Grange, Nine V A M Knoers, Gijs Van Haaften, Peter Hammond, Mieke M Van Haelst

2020-Current year OA Pubs

Cantú syndrome (CS) was first described in 1982, and is caused by pathogenic variants in ABCC9 and KCNJ8 encoding regulatory and pore forming subunits of ATP-sensitive potassium (K

No Difference In Strength And Clinical Outcome Between Early And Late Repair After Achilles Tendon Rupture, Michael R Carmont, Jennifer A Zellers, Annelie Brorsson, Karin Grävare Silbernagel, Jón Karlsson, Katarina Nilsson-Helander

2020-Current year OA Pubs

PURPOSE: This retrospective study aimed to determine the patient-reported and functional outcome of patients with delayed presentation, who had received no treatment until 14 days following injury of Achilles tendon rupture repaired with minimally invasive surgery and were compared with a group of sex- and age-matched patients presenting acutely. Based on the outcomes following delayed presentation reported in the literature, it was hypothesized that outcomes would be inferior for self-reported outcome, tendon elongation, heel-rise performance, ability to return to play, and complication rates than for acutely managed patients.

METHODS: Repair was performed through an incision large enough to permit mobilisation …

Harvest: Poems, Brittney Allen

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Louise Glück wrote, “the actual making of art is a revenge on circumstance.” The risk, she goes on, is in the possibility of shame. Writing poetry then becomes an act of courage, purchased with sacrifice or loss. “Courage, in this usage, alludes to a capacity for facing down the dark forces.”

In Harvest, a poetry chapbook, the speaker takes revenge on the circumstances of her life by being blunt, bare, and brave on the page. She contends with a male-dominated society and abusive childhood as she moves into adulthood and the supposed saving grace of a marriage. The speaker confesses …

Perceptions Of Risk For Stress Fractures: A Qualitative Study Of Female Runners With And Without Stress Fracture Histories., Therese E Johnston, Jeremy Close, Phil Jamora, Susan F Wainwright

Department of Physical Therapy Faculty Papers

OBJECTIVES: To gain insight into perceived factors related to bone health and stress fracture (SF) prevention for female runners and to understand their experiences within the medical community.

DESIGN: Cohort qualitative study.

SETTING: University health system.

PARTICIPANTS: Forty female runners, 20 who had SF histories and 20 age-and-running-distance matched women without SF.

MAIN OUTCOME MEASURES: Women participated in audiotaped qualitative semi-structured interviews. For women with a SF history, questions sought their perspectives on factors that they felt contributed to SF, experiences with the medical community, and changes made post SF. For women without a SF history, questions sought perspectives on …

Estrogen Receptor-Α Expressing Neurons In The Ventrolateral Vmh Regulate Glucose Balance, Yanlin He, Pingwen Xu, Chunmei Wang, Yan Xia, Meng Yu, Yongjie Yang, Kaifan Yu, Xing Cai, Na Qu, Kenji Saito, Julia Wang, Ilirjana Hyseni, Matthew Robertson, Badrajee Piyarathna, Min Gao, Sohaib A Khan, Feng Liu, Rui Chen, Cristian Coarfa, Zhongming Zhao, Qingchun Tong, Zheng Sun, Yong Xu

Children’s Nutrition Research Center Staff Publications

Brain glucose-sensing neurons detect glucose fluctuations and prevent severe hypoglycemia, but mechanisms mediating functions of these glucose-sensing neurons are unclear. Here we report that estrogen receptor-α (ERα)-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) can sense glucose fluctuations, being glucose-inhibited neurons (GI-ERαvlVMH) or glucose-excited neurons (GE-ERαvlVMH). Hypoglycemia activates GI-ERαvlVMH neurons via the anoctamin 4 channel, and inhibits GE-ERαvlVMH neurons through opening the ATP-sensitive potassium channel. Further, we show that GI-ERαvlVMH neurons preferentially project to the medioposterior arcuate nucleus of the hypothalamus (mpARH) and GE-ERαvlVMH neurons preferentially project to the dorsal Raphe nuclei (DRN). Activation of ERαvlVMH …

Characterization Of Adnexal Masses Using Contrast-Enhanced Subharmonic Imaging: A Pilot Study., Lauren J. Delaney, Priscilla Machado, Mehnoosh Torkzaban, Andrej Lyshchik, Corinne Wessner, Christine H. Kim, Md, Norman G Rosenblum, Scott D. Richard, Kirk Wallace, Flemming Forsberg

Department of Radiology Faculty Papers

OBJECTIVES: This pilot study evaluated whether contrast-enhanced subharmonic imaging (SHI) could be used to characterize adnexal masses before surgical intervention.

METHODS: Ten women (with 12 lesions) scheduled for surgery of an ovarian mass underwent an SHI examination of their adnexal region using a modified LOGIQ E9 scanner (GE Healthcare, Waukesha, WI) with an endocavitary transducer, in which digital clips were acquired by pulse destruction-replenishment SHI across the lesions. Time-intensity curves were created offline to quantitatively evaluate SHI parameters (fractional tumor perfusion, peak contrast intensity, time to peak contrast enhancement, and area under the time-intensity curve), which were compared to pathologic …

Delineation Of Phenotypes And Genotypes Related To Cohesin Structural Protein Rad21, Lianne C Krab, Marwan Shinawi, Et Al

Open Access Publications

RAD21 encodes a key component of the cohesin complex, and variants in RAD21 have been associated with Cornelia de Lange Syndrome (CdLS). Limited information on phenotypes attributable to RAD21 variants and genotype-phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with RAD21 alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases. We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. Full clinical information was available for 29 individuals. Their phenotype is an attenuated CdLS phenotype compared to that caused by variants in …

Human Monoclonal Antibodies Against Ross River Virus Target Epitopes Within The E2 Protein And Protect Against Disease, Laura A Powell, Julie M. Fox, Nurgun Kose, Arthur S. Kim, Mahsa Majedi, Robin Bombardi, Robert H. Carnahan, James C. Slaughter, Thomas E. Morrison, Michael S. Diamond, James E. Crowe

Open Access Publications

Ross River fever is a mosquito-transmitted viral disease that is endemic to Australia and the surrounding Pacific Islands. Ross River virus (RRV) belongs to the arthritogenic group of alphaviruses, which largely cause disease characterized by debilitating polyarthritis, rash, and fever. There is no specific treatment or licensed vaccine available, and the mechanisms of protective humoral immunity in humans are poorly understood. Here, we describe naturally occurring human mAbs specific to RRV, isolated from subjects with a prior natural infection. These mAbs potently neutralize RRV infectivity in cell culture and block infection through multiple mechanisms, including prevention of viral attachment, entry, …

Results Of The Adhere Upper Airway Stimulation Registry And Predictors Of Therapy Efficacy., Erica Thaler, Richard Schwab, Joachim Maurer, Ryan Soose, Christopher Larsen, Suzanne Stevens, Damien Stevens, Maurits Boon, Colin Huntley, Karl Doghramji, Tina Waters, Alan Kominsky, Armin Steffen, Eric Kezirian, Benedikt Hofauer, Ulrich Sommer, Kirk Withrow, Kingman Strohl, Clemens Heiser

Department of Psychiatry and Human Behavior Faculty Papers

OBJECTIVE/HYPOTHESIS: The ADHERE Registry is a multicenter prospective observational study following outcomes of upper airway stimulation (UAS) therapy in patients who have failed continuous positive airway pressure therapy for obstructive sleep apnea (OSA). The aim of this registry and purpose of this article were to examine the outcomes of patients receiving UAS for treatment of OSA.

STUDY DESIGN: Cohort Study.

METHODS: Demographic and sleep study data collection occurred at baseline, implantation visit, post-titration (6 months), and final visit (12 months). Patient and physician reported outcomes were also collected. Post hoc univariate and multivariate analysis was used to identify predictors of …

Vasopressor Treatment And Mortality Following Nontraumatic Subarachnoid Hemorrhage: A Nationwide Electronic Health Record Analysis, George Williams, Vahed Maroufy, Laila Rasmy, Derek Brown, Duo Yu, Hai Zhu, Yashar Talebi, Xueying Wang, Emy Thomas, Gen Zhu, Ashraf Yaseen, Hongyu Miao, Luis Leon Novelo, Degui Zhi, Stacia M Desantis, Hongjian Zhu, Jose-Miguel Yamal, David Aguilar, Hulin Wu

Faculty, Staff and Student Publications

OBJECTIVE: Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular condition, not only due to the effect of initial hemorrhage, but also due to the complication of delayed cerebral ischemia (DCI). While hypertension facilitated by vasopressors is often initiated to prevent DCI, which vasopressor is most effective in improving outcomes is not known. The objective of this study was to determine associations between initial vasopressor choice and mortality in patients with nontraumatic SAH.

METHODS: The authors conducted a retrospective cohort study using a large, national electronic medical record data set from 2000-2014 to identify patients with a new diagnosis of nontraumatic SAH …