Medical Specialties Commons^™

Metabolic Targeting, Immunotherapy And Radiation In Locally Advanced Non-Small Cell Lung Cancer: Where Do We Go From Here?, Annika Dhawan, Phillip M Pifer, Vlad C Sandulache, Heath D Skinner

Faculty, Staff and Students Publications

In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with …

Three-Dimensional (3d) Anatomic Location, Extension, And Timing Of Severe Osteoradionecrosis Of The Mandible, Lucas G Sapienza, Justin J Thomas, Weiyuan Mai, Alexander N Hanania, Sandeep Hunjan, Vlad C Sandulache, Albert C Chen

Faculty, Staff and Students Publications

BACKGROUND: The purpose of this study was to describe the topography, extension (volume), and timing of severe osteoradionecrosis (ORN) that required mandible resection in patients previously treated for head and neck cancer at a high-volume Veterans Affairs Medical Center.

MATERIALS AND METHODS: The records from a reference hyperbaric oxygen clinic were retrospectively analyzed (n = 50, 2018-2021). Inclusion criteria were: I) severe ORN defined as progressive ORN that required resection; II) pathologic confirmation of ORN; and III) availability of pre-operative CT-imaging. Using a radiotherapy (RT) imaging software, we performed a detailed volumetric (3D) analysis of the bone involvement by ORN. …

Integrated Microtia And Aural Atresia Management, Mai Thy Truong, Yi-Chun Carol Liu, Jocelyn Kohn, Sivakumar Chinnadurai, David A Zopf, Melissa Tribble, Paul B Tanner, Kathleen Sie, Kay W Chang

Faculty, Staff and Students Publications

OBJECTIVES: To present recommendations for the coordinated evaluation and management of the hearing and reconstructive needs of patients with microtia and aural atresia.

METHODS: A national working group of 9 experts on microtia and atresia evaluated a working document on the evaluation and treatment of patients. Treatment options for auricular reconstruction and hearing habilitation were reviewed and integrated into a coordinated care timeline.

RESULTS: Recommendations were created for children with microtia and atresia, including diagnostic considerations, surgical and non-surgical options for hearing management and auricular reconstruction, and the treatment timeline for each option. These recommendations are based on the collective …

Extended Effects Of A Wearable Sensory Prosthesis On Gait, Balance Function And Falls After 26 Weeks Of Use In Persons With Peripheral Neuropathy And High Fall Risk–The Walk2wellness Trial, Lars I E Oddsson, Teresa Bisson, Helen S Cohen, Ikechukwu Iloputaife, Laura Jacobs, Doris Kung, Lewis A Lipsitz, Brad Manor, Patricia Mccracken, Yvonne Rumsey, Diane M Wrisley, Sara R Koehler-Mcnicholas

Faculty, Staff and Students Publications

BACKGROUND: We recently reported that individuals with impaired plantar sensation and high fall risk due to sensory peripheral neuropathy (PN) improved gait and balance function following 10 weeks of use of Walkasins

MATERIALS AND METHODS: Participants had clinically diagnosed PN with impaired plantar sensation, high fall risk (Functional Gait Assessment, FGA score < 23) and ability to sense tactile stimuli above the ankle at the location of the device. Additional outcomes included 10 m Gait Speed, Timed Up and Go (TUG), Four-Stage Balance Test, and self-reported outcomes, including Activities-Specific Balance Confidence scale and Vestibular Disorders Activities of Daily Living Scale. Participants tracked falls using a calendar.

RESULTS: We assessed falls and self-reported outcomes from 44 individuals after 26 weeks of device use; 30 of them conducted in-person testing of clinical outcomes. Overall, improvements in clinical outcomes seen at 10 weeks of use remained sustained at 26 weeks with statistically significant increases compared to baseline …

Screening For Balance In Children And Adults In A Community Science Education Setting: Normative Data, Influence Of Age, Sex, And Body Mass Index, And Feasibility, Phyllis Friello, Nathan Silver, Haleh Sangi-Haghpeykar, Helen S Cohen

Faculty, Staff and Students Publications

BACKGROUND: Screening standing and walking balance is useful for people suspected of having vestibular disorders, a variety of neurologic and musculoskeletal disorders, and for screening astronauts returning after exposure to microgravity. Visitors to a community science education center children and adults, aged 4 to 85, were tested on tandem walking with eyes closed and the modified Romberg test on compliant foam. They were then asked about their experience participating in research, many people for the first time.

METHODS: Subjects performed 10 steps of tandem walking with eyes closed, and three trials of the modified Romberg, or Clinical Test of Sensory …

Subjective Versus Objective Tests Of Dizziness And Vestibular Function In Epidemiologic Screening Research, Helen S Cohen, Haleh Sangi-Haghpeykar, Michael W Plankey

Faculty, Staff and Students Publications

BACKGROUND: Many epidemiologic studies of vestibular disorders are based on responses to questionnaires which have not been tested against objective tests of the vestibular system.

OBJECTIVE: The goal was to determine if the dizziness and balance questions used in the National Health Interview Survey (NHIS) are valid and predict performance on objective tests of the vestibular system (VNG).

METHODS: Data from 367 participants recruited from the community, aged 21.4 to 87.6 years, were collected in the Otolaryngology department at a tertiary care center. They were asked the eight NHIS questions twice, at least 30 minutes apart and were tested on …

Crispr/Cas9-Mediated Genome Editing Reveals 12 Testis-Enriched Genes Dispensable For Male Fertility In Mice, Yuki Oyama, Haruhiko Miyata, Keisuke Shimada, Yoshitaka Fujihara, Keizo Tokuhiro, Thomas X Garcia, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Gene expression analyses suggest that more than 1000-2000 genes are expressed predominantly in mouse and human testes. Although functional analyses of hundreds of these genes have been performed, there are still many testis-enriched genes whose functions remain unexplored. Analyzing gene function using knockout (KO) mice is a powerful tool to discern if the gene of interest is essential for sperm formation, function, and male fertility in vivo. In this study, we generated KO mice for 12 testis-enriched genes, 1700057G04Rik, 4921539E11Rik, 4930558C23Rik, Cby2, Ldhal6b, Rasef, Slc25a2, Slc25a41, Smim8, Smim9, Tmem210, and Tomm20l, using the clustered regularly interspaced short palindromic repeats /CRISPR-associated …

Sarscov-2 Serostatus Amongst Vaccinated Employees At A Pediatric Hospital System, Sridevi Devaraj, Izmarie Poventud-Fuentes, Matthew Girotto, Jermaine Monroe, Julie Boom, George Delclos, James Versalovic

Faculty, Staff and Students Publications

To gain insights on the heterogeneity of immune responses to vaccination against SARS-CoV-2 and to identify factors that could make individuals vulnerable to infection due to lack of response to vaccination, our hospital started offering free voluntary post-antibody testing against the spike protein IgG for all fully vaccinated employees.

Post-vaccination response against SARS-CoV-2 was assessed using the FDA-EUA approved VITROS anti-SARS-CoV-2 IgG immunometric assay specific to the spike protein.

Out of a total of 3266 antibody tests performed in fully vaccinated Texas Children’s, 99.4% had a positive antibody response to the spike protein. From the 21 employees (0.6%) that had …

Foxo1 Is Present In Stomach Epithelium And Determines Gastric Cell Distribution, Wendy M Mckimpson, Taiyi Kuo, Takumi Kitamoto, Sei Higuchi, Jason C Mills, Rebecca A Haeusler, Domenico Accili

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.

METHODS: Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.

RESULTS: FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, …

Severe Inflammatory Colitis Related To Encorafenib And Binimetinib Following Immune Checkpoint Inhibitor Therapy, Aaron G Issac, David Szafron, Dongguang Wei, Jennifer L Mcquade, Yinghong Wang

Faculty, Staff and Students Publications

Encorafenib, a BRAF kinase inhibitor, in combination with binimetinib, a selective MEK inhibitor have known gastrointestinal adverse events; however, adverse colitis events have not been well studied. We report a case series of 4 patients with melanoma who developed inflammatory colitis after BRAF and MEK inhibition with encorafenib and binimetinib, respectively. In the setting of immune checkpoint inhibitor use, BRAF and MEK inhibitors can cause significant inflammatory colitis with endoscopic patterns of predominant right colon ulcerations. It can lead to significant morbidity and frequent interruption of cancer treatment. Early recognition and prompt intervention are critical to improving patient outcomes.

Cytomegalovirus Infection Among Patients With Cancer Receiving Immune Checkpoint Inhibitors, Kavea Panneerselvam, David Szafron, Rajan N Amin, Dongguang Wei, Dongfeng Tan, Mehmet Altan, Pablo C Okhuysen, Malek Shatila, Gottumukkala Subba Raju, Anusha S Thomas, Yinghong Wang

Faculty, Staff and Students Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs), used for the treatment of solid and hematologic malignancies, come with the risk of immune-related adverse events (irAEs). Opportunistic infections (e.g., cytomegalovirus [CMV]) mimic irAE symptoms and are understudied in this population. We aimed to describe the incidence, characteristics, treatment and outcomes of CMV infection in ICI-treated patients.

METHODS: We conducted a single-center retrospective review of all adult patients who were CMV-positive after ICI therapy between 06/2011 and 05/2020. A CMV-positive non-ICI cohort was matched to the ICI group based on age, sex and cancer type. Variables of interest were collected through electronic medical records. …

Glucocentric Drugs In Cardiovascular Disease Protection And Heart Failure, Khawaja M Talha, Gregg C Fonarow, Salim S Virani, Javed Butler

Faculty, Staff and Students Publications

Evidence for cardiovascular outcomes with older-generation antihyperglycemic drugs in the management of type 2 diabetes is based on aggregated data from prior randomized controlled trials and observational studies that were not focused on prespecified cardiovascular end points. Newer antihyperglycemic medications have undergone a rigorous evaluation of cardiovascular outcomes through randomized controlled trials since the US Food and Drug Administration imposed a mandatory requirement for all glucose-lowering drugs in 2008. The three classes of drugs that have been most extensively studied are dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, the latter two reporting significant …

Dual Orexin Receptor Antagonists For Treatment Of Insomnia: A Systematic Review And Meta-Analysis On Randomized, Double-Blind, Placebo-Controlled Trials Of Suvorexant And Lemborexant, Habibolah Khazaie, Masoud Sadeghi, Sepideh Khazaie, Max Hirshkowitz, Amir Sharafkhaneh

Faculty, Staff and Students Publications

Study objectives: Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials.

Methods: We conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval …

Obesity And Asthma: A Focused Review, Rubabin Tooba, Tianshi David Wu

Faculty, Staff and Students Publications

No abstract provided.

Spatial Transcriptomics Of The Lacrimal Gland Features Macrophage Activity And Epithelium Metabolism As Key Alterations During Chronic Inflammation, Olivier Mauduit, Vanessa Delcroix, Takeshi Umazume, Cintia S De Paiva, Darlene A Dartt, Helen P Makarenkova

Faculty, Staff and Students Publications

The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren’s syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, a mouse model of SS, utilizing bulk RNAseq and Visium spatial gene expression. With Seurat we performed unsupervised clustering and analyzed the spatial cell distribution and gene expression changes in all cell clusters within the LG sections. Moreover, for the …

Convalescent Plasma In Hospitalized Pediatric And Obstetric Coronavirus Disease 2019 (Covid-19) Patients, Saki Ikeda, Eduardo Benzi, Lisa A Hensch, Sridevi Devaraj, Shiu-Ki Rocky Hui, Manisha Gandhi, Karin A Fox, Jun Teruya, Flor M Munoz

Faculty, Staff and Students Publications

BACKGROUND: Published data on coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) use in children and obstetric patients are limited. We describe a single-center experience of hospitalized patients who received CCP for acute COVID-19.

METHODS: A retrospective review of children 0-18-years-old and pregnant patients hospitalized with laboratory-confirmed acute COVID-19 who received CCP from March 1, 2020 to March 1, 2021 was performed. Clinical and laboratory data were collected to assess the safety of CCP administration. Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were measured in the CCP products and in patients before transfusion and at various time points post-transfusion. …

Esophageal Perforation Successfully Treated With Evt, Kavea Panneerselvam, Ronald Samuel, Robert J Sealock

Faculty, Staff and Students Publications

Esophageal perforation is rare and carries high morbidity and mortality. A high degree of suspicion is needed for timely diagnosis and treatment. A 54-year-old man presented with fever and confusion. Imaging revealed air in the hepatic inferior vena cava and concern for a fistula between the distal esophagus and the inferior vena cava. An upper endoscopic evaluation revealed a dental floss pick penetrating the distal esophagus. The foreign body was removed, and endoluminal vacuum therapy was used to close the perforation. Endoluminal vacuum therapy is an emerging therapy to treat full-thickness gastrointestinal injuries.

Management Of A Novel Autoimmune Disease, Copa Syndrome, In Pregnancy, Archana Ayyar, Rachel D Seaman, Kalpalatha Guntupalli, Mary C Tolcher

Faculty, Staff and Students Publications

BACKGROUND: COPA syndrome is a rare autoimmune disease, demonstrating an autosomal dominant inheritance pattern with variable penetration that occurs more frequently in females than males. This disease manifests in childhood as pulmonary hemorrhage, arthritis, and renal disease.

CASE: We present a case of obstetric management of a 20-year-old nulligravida patient with a diagnosis of COPA syndrome. Her case was further complicated by multiple antepartum admissions for hypoxemia and a complex psychosocial history of substance use. On her first antepartum admission, rheumatology recommended management with hydroxychloroquine, inhaled corticosteroids (budesonide), and bronchodilators (albuterol inhaler) as needed. On admission for induction of labor, …

In Alzheimer-Prone Brain Regions, Metabolism And Risk-Gene Expression Are Strongly Correlated, Fengdan Ye, Quentin Funk, Elijah Rockers, Joshua M Shulman, Joseph C Masdeu, Belen Pascual

Duncan NRI Faculty and Staff Publications

Neuroimaging in the preclinical phase of Alzheimer’s disease provides information crucial to early intervention, particularly in people with a high genetic risk. Metabolic network modularity, recently applied to the study of dementia, is increased in Alzheimer’s disease patients compared with controls, but network modularity in cognitively unimpaired elderly with various risks of developing Alzheimer’s disease needs to be determined. Based on their 5-year cognitive progression, we stratified 117 cognitively normal participants (78.3 ± 4.0 years of age, 52 women) into three age-matched groups, each with a different level of risk for Alzheimer’s disease. From their fluorodeoxyglucose PET we constructed metabolic …

Interleukin-1Β Secretion Induced By Mucosa-Associated Gut Commensal Bacteria Promotes Intestinal Barrier Repair, Wan-Jung H Wu, Myunghoo Kim, Lin-Chun Chang, Adrien Assie, Fatima B Saldana-Morales, Daniel F Zegarra-Ruiz, Kendra Norwood, Buck S Samuel, Gretchen E Diehl

Faculty, Staff and Students Publications

The gut microbiota is essential for maintenance and repair of the intestinal epithelial barrier. As shifts in both intestinal epithelial barrier function and microbiota composition are found in inflammatory bowel disease patients, it is critical to understand the role of distinct bacteria in regulating barrier repair. We identified a mouse commensal E. coli isolate, GDAR2-2, that protects mice from Citrobacter rodentium infection and dextran sulfate sodium-induced colitis. Colonization with GDAR2-2 in mice resulted in expansion of CX3CR1+ mononuclear phagocytes, including CX3CR1+ macrophages/dendritic cells and monocytes, along with IL-22-secreting type 3 innate lymphoid cells and improved epithelial barrier function. In vitro …

Adrenomedullin And Its Receptors Are Expressed In Mouse Pancreatic Β-Cells And Suppresses Insulin Synthesis And Secretion, Yuanlin Dong, Simone Hernandez Ruano, Akansha Mishra, Kathleen A Pennington, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, …

Single-Port Laparoscopic Sacrospinous Ligament Suspension Via The Natural Vaginal Cavity (Svnotes) For Pelvic Prolapse: The First Feasibility Study, Yuanyuan Lyu, Huafeng Ding, Jin Ding, Yonghong Luo, Xiaoming Guan, Guantai Ni

Faculty, Staff and Students Publications

Objective

This study aims to investigate the feasibility and short-term efficacy of single-port laparoscopic-assisted transvaginal natural cavity endoscopic sacrospinous ligament suspensions (SvNOTES).

Methods

A total of 30 patients diagnosed with anterior or/and middle pelvic organ prolapse Stages III and IV underwent natural vaginal cavity (SvNOTES), and 30 patients who underwent conventional sacrospinous ligament (SSLF) were used as a control group. The operation time, blood loss, postoperative POP-Q score, length of hospital stay, and complications were compared between the two groups.

Results

The operation time for SvNOTE was (60 ± 13) min, which was longer than (30 ± 15) min for …

Pathologic Inflammation In Malnutrition Is Driven By Proinflammatory Intestinal Microbiota, Large Intestine Barrier Dysfunction, And Translocation Of Bacterial Lipopolysaccharide, Grace T Patterson, Elvia Y Osorio, Alex Peniche, Sara M Dann, Erika Cordova, Geoffrey A Preidis, Ji Ho Suh, Ichiaki Ito, Omar A Saldarriaga, Michael Loeffelholz, Nadim J Ajami, Bruno L Travi, Peter C Melby

Faculty, Staff and Students Publications

Acute malnutrition, or wasting, is implicated in over half of all deaths in children under five and increases risk of infectious disease. Studies in humans and preclinical models have demonstrated that malnutrition is linked to an immature intestinal microbiota characterized by increased prevalence of Enterobacteriaceae. Observational studies in children with moderate acute malnutrition (MAM) have also observed heightened systemic inflammation and increased circulating bacterial lipopolysaccharides (LPS; endotoxin). However, the mechanisms that underpin the systemic inflammatory state and endotoxemia, and their pathophysiological consequences, remain uncertain. Understanding these pathophysiological mechanisms is necessary to design targeted treatments that will improve the unacceptable rate …

A Precision Medicine Agenda In Traumatic Brain Injury, Jovany Cruz Navarro, Lucido L Ponce Mejia, Claudia Robertson

Faculty, Staff and Students Publications

Traumatic brain injury remains a leading cause of death and disability across the globe. Substantial uncertainty in outcome prediction continues to be the rule notwithstanding the existing prediction models. Additionally, despite very promising preclinical data, randomized clinical trials (RCTs) of neuroprotective strategies in moderate and severe TBI have failed to demonstrate significant treatment effects. Better predictive models are needed, as the existing validated ones are more useful in prognosticating poor outcome and do not include biomarkers, genomics, proteonomics, metabolomics, etc. Invasive neuromonitoring long believed to be a "game changer" in the care of TBI patients have shown mixed results, and …

Diagnosis And Interpretation Of Testing For Cat Scratch Disease, Nasim Khalfe, Doris Lin

Faculty, Staff and Students Publications

Cat scratch disease (CSD) is an infectious disease caused by Bartonella henselae that presents as regional lymphadenopathy which can appear within weeks after a cat scratch. There is no gold standard for diagnosis. Rather, clinicians rely on an amalgam of criteria to make a definitive diagnosis. We describe a case of a 44-year-old woman with six cats who presented with a painful left inguinal mass, had splenic lesions on imaging, and had positive serology but a negative polymerase chain reaction test for B. henselae.

An Evidence-Based, Structured, Expert Approach To Selecting Essential Indicators Of Primary Care Quality, Sylvia J Hysong, Kelley Arredondo, Ashley M Hughes, Houston F Lester, Frederick L Oswald, Laura A Petersen, Lechauncy Woodard, Edward Post, Shelly Deperalta, Daniel R Murphy, Jason Mcknight, Karin Nelson, Paul Haidet

Faculty, Staff and Students Publications

BACKGROUND: The purpose of this article is to illustrate the application of an evidence-based, structured performance measurement methodology to identify, prioritize, and (when appropriate) generate new measures of health care quality, using primary care as a case example. Primary health care is central to the health care system and health of the American public; thus, ensuring high quality is essential. Due to its complexity, ensuring high-quality primary care requires measurement frameworks that can assess the quality of the infrastructure, workforce configurations, and processes available. This paper describes the use of the Productivity Measurement and Enhancement System (ProMES) to compile a …

Growth In Achondroplasia Including Stature, Weight, Weight-For-Height And Head Circumference From Clarity: Achondroplasia Natural History Study-A Multi-Center Retrospective Cohort Study Of Achondroplasia In The Us, Julie E Hoover-Fong, Kerry J Schulze, Adekemi Y Alade, Michael B Bober, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria E Serna, Cory Smid, Chengxin Liu, John Mcgready

Faculty, Staff and Student Publications

BACKGROUND: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments …

Recurrent High-Impact Mutations At Cognate Structural Positions In Class A G Protein-Coupled Receptors Expressed In Tumors, Eunna Huh, Jonathan Gallion, Melina A Agosto, Sara J Wright, Theodore G Wensel, Olivier Lichtarge

Faculty, Staff and Students Publications

G protein-coupled receptors (GPCRs) are the largest family of human proteins. They have a common structure and, signaling through a much smaller set of G proteins, arrestins, and effectors, activate downstream pathways that often modulate hallmark mechanisms of cancer. Because there are many more GPCRs than effectors, mutations in different receptors could perturb signaling similarly so as to favor a tumor. We hypothesized that somatic mutations in tumor samples may not be enriched within a single gene but rather that cognate mutations with similar effects on GPCR function are distributed across many receptors. To test this possibility, we systematically aggregated …

Measuring The Quality Of Postgraduate Physician Assistant Fellowship/Residency Programs With A Surgical Focus, Lesley Davies, Jacqueline Guarino, Caitlin Justus, Cassandra Mueller Pa-C, Ryan Krasnosky, Jordan Rodriguez, Angelo P. Giardino

Journal of Nursing & Interprofessional Leadership in Quality & Safety

Introduction

Postgraduate programs for PAs provide formal postgraduate training for clinical specialty areas. These programs are intended to provide intense specialty training in various fields, as well as to standardize education beyond the entry level. The purpose of this descriptive study was to determine if there are consistent trends or clear differences in program length, approach to training, validation of learning, and accreditation through the Accreditation Review Commission on Education for the Physician Assistant (ARC-PA) for postgraduate programs with a surgical focus in the United States.

Methods

This study is a non-experimental and descriptive research design. Program directors were mailed …

Steroid Receptor-Coregulator Transcriptional Complexes: New Insights From Cryoem, Ping Yi, Xinzhe Yu, Zhao Wang, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptors activate gene transcription through recruitment of a number of coregulators to facilitate histone modification, chromatin remodeling, and general transcription machinery stabilization. Understanding the structures of full-length steroid receptor and coregulatory complexes has been difficult due to their large molecular sizes and dynamic structural conformations. Recent developments in cryo-electron microscopy (cryoEM) technology and proteomics have advanced the structural studies of steroid receptor complexes. Here, we will review the insights we learned from cryoEM studies of the estrogen and androgen receptor transcriptional complexes. Despite similar domain organizations, the two receptors have different coregulator interaction modes. The cryoEM structures now have …