Medicine and Health Sciences Commons^™

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling To Promote Health And Longevity, Mahmoud Abdellatif, Tobias Pendl, Sebastian J Hofer, Moydul Islam, Abhinav Diwan, Tobias Eisenberg, Frank Madeo, Et Al

2020-Current year OA Pubs

BACKGROUND: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial.

METHODS: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling. Male mice with human IGF1R overexpression or dominant negative phosphoinositide 3-kinase mutation were examined at different life stages by echocardiography, invasive hemodynamics, and treadmill coupled to indirect calorimetry. In vitro assays included cardiac histology, mitochondrial respiration, ATP synthesis, autophagic …

Effects Of Paternal High-Fat Diet And Maternal Rearing Environment On The Gut Microbiota And Behavior., Austin C Korgan, Christine L Foxx, Heraa Hashmi, Saydie A Sago, Christopher E Stamper, Jared D Heinze, Elizabeth O'Leary, Jillian L King, Tara S Perrot, Christopher A Lowry, Ian C G Weaver

Faculty Research 2022

Exposing a male rat to an obesogenic high-fat diet (HFD) influences attractiveness to potential female mates, the subsequent interaction of female mates with infant offspring, and the development of stress-related behavioral and neural responses in offspring. To examine the stomach and fecal microbiome's potential roles, fecal samples from 44 offspring and stomach samples from offspring and their fathers were collected and bacterial community composition was studied by 16 small subunit ribosomal RNA (16S rRNA) gene sequencing. Paternal diet (control, high-fat), maternal housing conditions (standard or semi-naturalistic housing), and maternal care (quality of nursing and other maternal behaviors) affected the within-subjects …

Gut Dysbiosis And Age-Related Neurological Diseases In Females, Janelle M Korf, Bhanu P Ganesh, Louise D Mccullough

Faculty, Staff and Student Publications

Historically, females have been underrepresented in biological research. With increased interest in the gut microbiome and the gut-brain axis, it is important for researchers to pursue studies that consider sex as a biological variable. The composition of the gut microbiome is influenced by environmental factors, disease, diet, and varies with age and by sex. Detrimental changes in the gut microbiome, referred to as dysbiosis, is believed to influence the development and progression of age-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and stroke. Many are investigating the changes in microbial populations in order or to better understand …

Neoadjuvant Immunotherapy Across Cancers: Meeting Report From The Immunotherapy Bridge-December 1st–2nd, 2021, Elizabeth M Burton, Rodabe N Amaria, Tina Cascone, Myriam Chalabi, Neil D Gross, Elizabeth A Mittendorf, Richard A Scolyer, Padmanee Sharma, Paolo A Ascierto

Faculty, Staff and Student Publications

After the success of immunotherapy in the treatment of advanced metastatic cancer, further evaluation in earlier settings, including high-risk, surgically-resectable disease is underway. Potential benefits of a neoadjuvant immunotherapeutic approach include presurgical tumor shrinkage, reduced surgical morbidity, early eradication of micrometastases and prevention of distant disease, and greater antigen-specific T cell response. For some cancers, pathologic response has been established as a surrogate measure for long-term outcomes, therefore offering the ability for early and objective assessment of treatment efficacy and the potential to inform and personalize adjuvant treatment clinical decision-making. Leveraging the neoadjuvant treatment setting offers the ability to deeply …

Navigation Programs Relevant For African American Men With Prostate Cancer: A Scoping Review Protocol, Nynikka R. Palmer, Ashley Nicole Smith, Brittany A. Campbell, Ghilamichael Andemeskel, Peggy Tahir, Tisha M. Felder Phd, Msw, Barbara Cicerelli

Publications

BACKGROUND:

The excess incidence and mortality due to prostate cancer that impacts African American men constitutes the largest of all cancer disparities. Patient navigation is a patient-centered healthcare system intervention to eliminate barriers to timely, high-quality care across the cancer continuum and improves health outcomes among vulnerable patients. However, little is known regarding the extent to which navigation programs include cultural humility to address prostate cancer disparities among African American men. We present a scoping review protocol of an in-depth examination of navigation programs in prostate cancer care-including navigation activities/procedures, training, and management-with a special focus on cultural context and …

Systemic Ablation Of Camkk2 Impairs Metastatic Colonization And Improves Insulin Sensitivity In Tramp Mice: Evidence For Cancer Cell-Extrinsic Camkk2 Functions In Prostate Cancer, Thomas L Pulliam, Dominik Awad, Jenny J Han, Mollianne M Murray, Jeffrey J Ackroyd, Pavithr Goli, Jonathan S Oakhill, John W Scott, Michael M Ittmann, Daniel E Frigo

Faculty, Staff and Students Publications

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2's effects on whole-body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of

Tomatoes, Lycopene, And Prostate Cancer: What Have We Learned From Experimental Models?, Nancy E Moran, Jennifer M Thomas-Ahner, Lei Wan, Krystle E Zuniga, John W Erdman, Steven K Clinton

Children’s Nutrition Research Center Staff Publications

Human epidemiology suggests a protective effect of tomatoes or tomato phytochemicals, such as lycopene, on prostate cancer risk. However, human epidemiology alone cannot reveal causal relations. Laboratory animal models of prostate cancer provide opportunities to investigate hypotheses regarding dietary components in precisely controlled, experimental systems, contributing to our understanding of diet and cancer risk relations. We review the published studies evaluating the impact of tomatoes and/or lycopene in preclinical models of prostate carcinogenesis and tumorigenesis. The feeding of tomatoes or tomato components demonstrates anti-prostate cancer activity in both transplantable xenograft models of tumorigenesis and models of chemically- and genetically-driven carcinogenesis. …

French-Fried Potato Consumption And Energy Balance: A Randomized Controlled Trial, Daniel L Smith, Rebecca L Hanson, Stephanie L Dickinson, Xiwei Chen, Amy M Goss, John B Cleek, W Timothy Garvey, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Epidemiologic observations suggest increased potato consumption correlates with weight gain, adiposity, and diabetes risk, whereas nut consumption is associated with weight control and metabolic health. Randomized controlled trial (RCT) data indicate humans respond to changes in energy intake in single dietary components and compensate for extra energy consumed.

Objectives: We completed an RCT testing whether increased daily potato consumption influences energy balance [specifically, fat mass (FM)] compared with calorie-matched almond consumption.

Methods: A 30-d RCT of 180 adults prescribed calorie-matched (300 kcal/d, n = 60 participants/group) than consumed 1 of the following: 1) almonds (almond group), 2) French fries …

Effect Of Awake Prone Positioning On Endotracheal Intubation In Patients With Covid-19 And Acute Respiratory Failure: A Randomized Clinical Trial, Waleed Alhazzani, Ken Kuljit S Parhar, Jason Weatherald, Zainab Al Duhailib, Mohammed Alshahrani, Abdulrahman Al-Fares, Sarah Buabbas, Sujith V Cherian, Laveena Munshi, Eddy Fan, Fahad Al-Hameed, Jamal Chalabi, Amera A Rahmatullah, Erick Duan, Jennifer L Y Tsang, Kimberley Lewis, François Lauzier, John Centofanti, Bram Rochwerg, Sarah Culgin, Katlynne Nelson, Sheryl Ann Abdukahil, Kirsten M Fiest, Henry T Stelfox, Haytham Tlayjeh, Maureen O Meade, Dan Perri, Kevin Solverson, Daniel J Niven, Rachel Lim, Morten Hylander Møller, Emilie Belley-Cote, Lehana Thabane, Hani Tamim, Deborah J Cook, Yaseen M Arabi, Covi-Prone Trial Investigators And The Saudi Critical Care Trials Group

Faculty, Staff and Student Publications

Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19.

Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19.

Design, setting, and participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021.

Intervention: Patients were …

Synchronized Diaphragmatic Stimulation: A Case Report Of A Novel Extra-Cardiac Intervention For Chronic Heart Failure., Lee R Goldberg, Ana Jorbenadze, Tamaz Shaburishvilli, Michael Mirro Md, Marat Fudim, Michel Zuber, Simon F Stämpfli, Felix C Tanner, Paul Erne, John G Cleland

Parkview Heart Institute

Synchronized diaphragmatic stimulation (SDS) is a novel extra-cardiac device-based therapy for symptomatic heart failure with reduced ejection fraction. SDS provides imperceptible chronic stimulation of the diaphragm through a laparoscopically implanted system consisting of an implantable pulse generator and two sensing/stimulating leads affixed to the inferior surface of the diaphragm delivering imperceptible R-wave gaited pulses that alter intrathoracic pressure improving ventricular filling and cardiac output. We describe, in a man with a history of myocardial infarctions resulting in heart failure and persistent New York Heart Association Class III symptoms despite standard therapies, the successful implantation of SDS resulting in improved quality …

Circadian Disruption Of Hippocampus In An Early Senescence Male Mouse Model, Jennifer A Davis, Jodi R Paul, Mugdha V Mokashi, Stefani A Yates, Daniel J Mount, Hira A Munir, Lacy K Goode, Martin E Young, David B Allison, Karen L Gamble

Children’s Nutrition Research Center Staff Publications

Age-related cognitive decline and disruptions in circadian rhythms are growing problems as the average human life span increases. Multiple strains of the senescence-accelerated mouse (SAM) show reduced life span, and the SAMP8 strain in particular has been well documented to show cognitive deficits in behavior as well as a bimodal pattern of circadian locomotor activity. However, little is known about circadian regulation within the hippocampus of these strains of mice. Here we test the hypothesis that in this early senescence model, disruption of the molecular circadian clock in SAMP8 animals drives disrupted behavior and physiology. We found normal rhythms in …

Association Of Alcohol Use And Physical Activity With Body Mass Index In Mexican-Origin Adults, Natalia I Heredia, Qiong Dong, Shine Chang, Lorna H Mcneill

Faculty, Staff and Student Publications

BACKGROUND: Studies across racial/ethnic groups indicate that physical activity (PA) and alcohol consumption are positively associated, and that alcohol consumption is negatively associated with body mass index (BMI), but this relationship is less often evaluated in Hispanics. The purpose of this study was to assess the relationships between alcohol consumption, PA, and BMI in Hispanic adults.

METHODS: In this secondary data analysis of a Mexican-American cohort, we collected self-reported PA, alcohol consumption, and demographics, and measured height and weight. Linear regression assessed the association between PA and alcohol consumption with BMI, controlling for covariates. Total sample for analyses was n …

Integrative Analysis Of Clinical And Epigenetic Biomarkers Of Mortality, Tianxiao Huan, Steve Nguyen, Elena Colicino, Carolina Ochoa-Rosales, W David Hill, Jennifer A Brody, Mette Soerensen, Yan Zhang, Antoine Baldassari, Mohamed Ahmed Elhadad, Tanaka Toshiko, Yinan Zheng, Arce Domingo-Relloso, Dong Heon Lee, Jiantao Ma, Chen Yao, Chunyu Liu, Shih-Jen Hwang, Roby Joehanes, Myriam Fornage, Jan Bressler, Joyce B J Van Meurs, Birgit Debrabant, Jonas Mengel-From, Jacob Hjelmborg, Kaare Christensen, Pantel Vokonas, Joel Schwartz, Sina A Gahrib, Nona Sotoodehnia, Colleen M Sitlani, Sonja Kunze, Christian Gieger, Annette Peters, Melanie Waldenberger, Ian J Deary, Luigi Ferrucci, Yishu Qu, Philip Greenland, Donald M Lloyd-Jones, Lifang Hou, Stefania Bandinelli, Trudy Voortman, Brenner Hermann, Andrea Baccarelli, Eric Whitsel, James S Pankow, Daniel Levy

Faculty, Staff and Student Publications

DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10

Assessment Of Oral And Overall Health Parameters Using The Sillha Oral Wellness System, Shawn S Adibi, Ryan Hanson, David F Fray, Tania Abedi, Brianna Neil, Danielle Maher, Gena Tribble, Ben F Warner, Mary C Farach-Carson

Faculty, Staff and Student Publications

OBJECTIVE: The study evaluated use of a multipoint saliva analyzer to assess patient wellness in a contemporary dental practice setting.

STUDY DESIGN: Unstimulated saliva from a diverse 104 patient cohort was analyzed using the SillHa Oral Wellness System. The device measures the following 7 analytes present in the patient's oral rinse: cariogenic bacteria, acidity, buffer capacity, blood, leukocytes, protein, and ammonia. Data obtained were compared with validated clinical assessment data independently provided by credentialed dental professionals.

RESULTS: Measured leukocyte and protein levels were higher in patients with periodontal disease and/or deep gingival pockets. Patients with a history of cancer and/or …

Anal Cytology Screening In Men Who Have Sex With Men With Hiv At A University Hospital In Bogotá, Colombia, I Tatiana Ordoñez-Blanco, Samuel Martínez-Vernaza, Kevin J Blair, Camilo Quiroga, Ellen Lowenstein, Luis J Lombana Amaya, Jesse Clark, Jordan E Lake, Sandra Liliana Valderrama-Beltrán

Faculty, Staff and Student Publications

Background: Risk of anal squamous cell carcinoma (anal cancer) is greater among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). We describe the frequency of and factors associated with abnormal anal cytology results in Colombian MSM living with HIV.

Methods: This retrospective observational cohort study included MSM ≥18 years old living with HIV screened with anal cytology at Hospital Universitario San Ignacio in Bogotá, Colombia between January 2019 and February 2020. A multivariable log-binomial regression model estimated associations with abnormal anal cytology.

Results: A total of 211 patients were included. Mean age was 35.6 years. …

Nexmif Pathogenic Variants In Individuals Of Korean, Vietnamese, And Mexican Descent, Elizabeth Langley, Laura S Farach, Mary K Koenig, Hope Northrup, David F Rodriguez-Buritica, Kate Mowrey

Faculty, Staff and Student Publications

NEXMIF pathogenic variants have been known to produce a wide spectrum of X-linked intellectual disability (ID) in both males and females. Thus far, few individuals from diverse populations have been described with NEXMIF-related disorders. Herein, we report three individuals with NEXMIF pathogenic variants, the first two are the only males of Korean and Vietnamese descent described with this disorder to our knowledge. The last patient is a Hispanic female who harbors the same pathogenic variant as a previously described Caucasian individual, but with differing clinical presentation. These patients present with many classic symptoms of NEXMIF-related disorders including ID, epilepsy, developmental …

Impact Of Covid19 On Maxillofacial Fractures In The Province Of L’Aquila, Abruzzo, Italy Review Of 296 Patients Treated With Statistical Comparison Of The Two-Year Pre-Covid19 And Covid19, Filippo Giovannetti, Ettore Lupi, Danilo Di Giorgio, Secondo Scarsella, Antonio Oliva, Desiderio Di Fabio, Paolo Prata, Giada Petricca, Valentino Valentini

Faculty, Staff and Student Publications

The aim of this study was to understand the impact of the COVID-19 pandemic on the epidemiology of maxillofacial trauma in a regional trauma center in L'Aquila, Abruzzo, Italy, during the first wave of the pandemic and comparted it to an equivalent period from 2015 to 2018. The authorshave retrospectively analyzed personal data, site of trauma, etiology, and mechanism of injury. Statistical analysis has been carried out utilizing IBM SPSS Statistics software (IBM Corp., Armonk, NY) and significance was accepted for P values of 0.05) as opposed to the etiology in which the road traffic accidents decreased in favor of …

Long-Term Outcomes Among Adolescent And Young Adult Survivors Of Acute Leukemia: A Surveillance, Epidemiology, And End Results Analysis, Amy M Berkman, Clark R Andersen, Branko Cuglievan, David C Mccall, Philip J Lupo, Susan K Parsons, Courtney D Dinardo, Nicholas J Short, Nitin Jain, Tapan M Kadia, J A Livingston, Michael E Roth

Faculty, Staff and Student Publications

Background: There is a growing population of adolescent and young adult (AYA, age 15-39 years) acute leukemia survivors in whom long-term mortality outcomes are largely unknown.

Methods: The current study utilized the Surveillance, Epidemiology, and End Results (SEER) registry to assess long-term outcomes of AYA acute leukemia 5-year survivors. The impact of diagnosis age, sex, race/ethnicity, socioeconomic status, and decade of diagnosis on long-term survival were assessed utilizing an accelerated failure time model.

Results: A total of 1,938 AYA acute lymphoblastic leukemia (ALL) and 2,350 AYA acute myeloid leukemia (AML) survivors diagnosed between 1980 and 2009 were included with a …

Success And Outcomes Following A Second Salvage Attempt For Free Flap Compromise In Patients Undergoing Head And Neck Reconstruction, Allison A Slijepcevic, Gavin Young, Justin Shinn, Steven B Cannady, Matthew Hanasono, Matthew Old, Jeewanjot S Grewal, Tamer Ghanem, Yadranko Ducic, Joseph M Curry, Mark K Wax

Faculty, Staff and Student Publications

Importance: Incidence of perioperative free flap compromise is low, with successful salvage in up to 70%. When the flap is compromised a second time, the value of intervening is unknown.

Objective: To assess the outcomes of a second revascularization attempt for compromised free flaps.

Design, setting, and participants: This multicenter retrospective medical record review included patients undergoing head and neck reconstruction with free flaps at 6 US medical centers from January 1, 2000, through December 30, 2020. Patients were 18 years or older with a history of head and neck defects from cancer, osteoradionecrosis, or other wounds. Of 3510 flaps …

Androgen Receptor Blockade Promotes Response To Braf/Mek-Targeted Therapy, Christopher P Vellano, Michael G White, Miles C Andrews, Manoj Chelvanambi, Russell G Witt, Joseph R Daniele, Mark Titus, Jennifer L Mcquade, Fabio Conforti, Elizabeth M Burton, Matthew J Lastrapes, Gabriel Ologun, Alexandria P Cogdill, Golnaz Morad, Peter Prieto, Alexander J Lazar, Yanshuo Chu, Guangchun Han, M A Wadud Khan, Beth Helmink, Michael A Davies, Rodabe N Amaria, Jeffrey J Kovacs, Scott E Woodman, Sapna Patel, Patrick Hwu, Michael Peoples, Jeffrey E Lee, Zachary A Cooper, Haifeng Zhu, Guang Gao, Hiya Banerjee, Mike Lau, Jeffrey E Gershenwald, Anthony Lucci, Emily Z Keung, Merrick I Ross, Laura Pala, Eleonora Pagan, Rossana Lazcano Segura, Qian Liu, Mikayla S Borthwick, Eric Lau, Melinda S Yates, Shannon N Westin, Khalida Wani, Michael T Tetzlaff, Lauren E Haydu, Mikhila Mahendra, Xiaoyan Ma, Christopher Logothetis, Zachary Kulstad, Sarah Johnson, Courtney W Hudgens, Ningping Feng, Lorenzo Federico, Georgina V Long, P Andrew Futreal, Swathi Arur, Hussein A Tawbi, Amy E Moran, Linghua Wang, Timothy P Heffernan, Joseph R Marszalek, Jennifer A Wargo

Faculty, Staff and Student Publications

Treatment with BRAF/MEK-targeted therapy has revolutionized care in melanoma and other cancers, however therapeutic resistance is common and innovative treatment strategies are needed1,2. We studied a group of melanoma patients treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n=51), and observed significantly higher rates of major pathologic response (MPR= <10% viable tumor at resection) and improved recurrence-free survival (RFS) in females versus males (MPR-66% versus 14%, p=0.001; RFS-64% versus 32% at 2 years, p=0.021). Findings were validated in a several additional cohorts2–4 patients with unresectable metastatic melanoma treated with BRAF and/or MEK-targeted therapy (n=664 patients in total), demonstrating improved progression-free survival (PFS) and overall survival (OS) in females versus males in several of these studies. Studies in pre-clinical models demonstrated significantly impaired anti-tumor activity in male …

The Androgen Receptor Is A Therapeutic Target In Desmoplastic Small Round Cell Sarcoma, Salah-Eddine Lamhamedi-Cherradi, Mayinuer Maitituoheti, Brian A Menegaz, Sandhya Krishnan, Amelia M Vetter, Pamela Camacho, Chia-Chin Wu, Hannah C Beird, Robert W Porter, Davis R Ingram, Vandhana Ramamoorthy, Sana Mohiuddin, David Mccall, Danh D Truong, Branko Cuglievan, P Andrew Futreal, Alejandra Ruiz Velasco, Nazanin Esmaeili Anvar, Budi Utama, Mark Titus, Alexander J Lazar, Wei-Lien Wang, Cristian Rodriguez-Aguayo, Ravin Ratan, J Andrew Livingston, Kunal Rai, A Robert Macleod, Najat C Daw, Andrea Hayes-Jordan, Joseph A Ludwig

Faculty, Staff and Student Publications

Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that enzalutamide and AR-directed antisense oligonucleotides (AR-ASO) block 5α-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduce xenograft tumor burden. Gene expression analysis and chromatin immunoprecipitation sequencing (ChIP-seq) were performed to elucidate how AR signaling regulates cellular epigenetic programs. Remarkably, ChIP-seq revealed novel DSRCT-specific AR DNA binding sites adjacent to key oncogenic regulators, including WT1 (the …

Accuracy Of Chest Computed Tomography In Distinguishing Cystic Pleuropulmonary Blastoma From Benign Congenital Lung Malformations In Children, Abigail J Engwall-Gill, Jacqueline M Saito, Rebecca L Hulett Bowling, Et Al.

2020-Current year OA Pubs

Importance: The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear.

Objective: To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children.

Design, Setting, and Participants: This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed …

Association Of State Medicaid Expansion Status With Rates Of Suicide Among Us Adults, Hetal Patel, Justin Barnes, Nosayaba Osazuwa-Peters, Laura Jean Bierut

2020-Current year OA Pubs

Importance: In the US, suicide is the 10th leading cause of death and a serious mental health emergency. National programs that address suicide list access to mental health care as key in prevention, and more large-scale policies are needed to improve access to mental health care and address this crisis. The Patient Protection and Affordable Care Act (ACA) Medicaid Expansion Program was implemented in several states with the goal of increasing access to the health care system.

Objective: To compare changes in suicide rates in states that expanded Medicaid under the ACA vs states that did not.

Design, Setting, and …

Genetic, Epigenetic, And Environmental Mechanisms Govern Allele-Specific Gene Expression, Celine L St Pierre, Juan F Macias-Velasco, Jessica P Wayhart, Li Yin, Clay F Semenkovich, Heather A Lawson

2020-Current year OA Pubs

Allele-specific expression (ASE) is a phenomenon in which one allele is preferentially expressed over the other. Genetic and epigenetic factors cause ASE by altering the final composition of a gene's product, leading to expression imbalances that can have functional consequences on phenotypes. Environmental signals also impact allele-specific expression, but how they contribute to this cross talk remains understudied. Here, we explored how genotype, parent-of-origin, tissue, sex, and dietary fat simultaneously influence ASE biases. Male and female mice from a F

Prognosticators Of Visual Acuity After Indirect Traumatic Optic Neuropathy, Alex J Wright, Joanna H Queen, Emilio P Supsupin, Alice Z Chuang, John J Chen, Rod Foroozan, Ore-Ofe O Adesina

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study is to determine whether there are radiographic and systemic clinical characteristics that can predict final visual outcomes in patients with indirect traumatic optic neuropathy (iTON).

METHODS: This study is a retrospective, multicenter case series of adult patients with iTON treated initially at large, urban, and/or academic trauma centers with follow-up at an affiliated ophthalmology clinic. In addition to detailed cranial computed tomography characteristics, demographics, systemic comorbidities, coinjuries, blood products administered, and intracranial pressure, along with other factors, were gathered. LogMAR visual acuity (VA) at the initial presentation to the hospital and up to 12 …

Prune1 C933g>A Synonymous Variant Induces Exon 7 Skipping, Disrupts The Dhha2 Domain, And Leads To An Atypical Nmihba Syndrome Presentation: Case Report And Review Of The Literature, Christina L Magyar, David R Murdock, Lindsay C Burrage, Hongzheng Dai, Seema R Lalani, Richard A Lewis, Yuezhen Lin, Marcela F Astudillo, Jill A Rosenfeld, Alyssa A Tran, James B Gibson, Undiagnosed Diseases Network, Carlos A Bacino, Brendan H Lee, Hsiao-Tuan Chao

Faculty, Staff and Students Publications

Prune exopolyphosphatase-1 (PRUNE1) encodes a member of the aspartic acid-histidine-histidine (DHH) phosphodiesterase superfamily that regulates cell migration and proliferation during brain development. In 2015, biallelic PRUNE1 loss-of-function variants were identified to cause the neurodevelopmental disorder with microcephaly, hypotonia, and variable brain abnormalities (NMIHBA, OMIM#617481). NMIHBA is characterized by the namesake features and structural brain anomalies including thinning of the corpus callosum, cerebral and cerebellar atrophy, and delayed myelination. To date, 47 individuals have been reported in the literature, but the phenotypic spectrum of PRUNE1-related disorders and their causative variants remains to be characterized fully. Here, we report a novel homozygous …

An Examination Of The Sex-Specific Nature Of Nutrition Assessment Within The Nutrition Care Process: Considerations For Nutrition And Dietetics Practitioners Working With Transgender And Gender Diverse Clients, Whitney Linsenmeyer, Sarah Garwood, Jennifer Waters

2020-Current year OA Pubs

No abstract provided.

Joint Eanm, Snmmi And Iaea Enabling Guide: How To Set Up A Theranostics Centre, Ken Herrmann, Richard L Wahl, Et Al.

2020-Current year OA Pubs

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumours and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumour such as prostate cancer requires the expansion of …

Assessing Researchers' Capabilities, Opportunities, And Motivation To Conduct Equity-Oriented Dissemination And Implementation Research, An Exploratory Cross-Sectional Study, Ana A Baumann, Eva N Woodward, Rajinder Sonia Singh, Prajakta Adsul, Rachel C Shelton

2020-Current year OA Pubs

BACKGROUND: A recent paradigm shift has led to an explicit focus on enhancing health equity through equity-oriented dissemination and implementation (D&I) research. However, the integration and bidirectional learning across these two fields is still in its infancy and siloed. This exploratory study aimed to examine participants' perceived capabilities, opportunities, and motivations to conduct equity-oriented D&I research.

METHODS: We conducted an exploratory cross-sectional survey distributed online from December 2020 to April 2021. Participants were recruited at either D&I or health disparities-oriented conferences, meetings, through social media, or personal outreach via emails. Informed by the Capability, Opportunity, and Motivation Model (COM-B), the …

Discovery Of Potent Bet Bromodomain 1 Stereoselective Inhibitors Using Dna-Encoded Chemical Library Selections, Ram K Modukuri, Zhifeng Yu, Zhi Tan, Hai Minh Ta, Melek Nihan Ucisik, Zhuang Jin, Justin L Anglin, Kiran L Sharma, Pranavanand Nyshadham, Feng Li, Kevin Riehle, John C Faver, Kevin Duong, Sureshbabu Nagarajan, Nicholas Simmons, Stephen S Palmer, Mingxing Teng, Damian W Young, Joanna S Yi, Choel Kim, Martin M Matzuk

Duncan NRI Faculty and Staff Publications

BRDT, BRD2, BRD3, and BRD4 comprise the bromodomain and extraterminal (BET) subfamily which contain two similar tandem bromodomains (BD1 and BD2). Selective BD1 inhibition phenocopies effects of tandem BET BD inhibition both in cancer models and, as we and others have reported of BRDT, in the testes. To find novel BET BD1 binders, we screened >4.5 billion molecules from our DNA-encoded chemical libraries with BRDT-BD1 or BRDT-BD2 proteins in parallel. A compound series enriched only by BRDT-BD1 was resynthesized off-DNA, uncovering a potent chiral compound, CDD-724, with >2,000-fold selectivity for inhibiting BRDT-BD1 over BRDT-BD2. CDD-724 stereoisomers exhibited remarkable differences in …