Medicine and Health Sciences Commons^™

Stakeholder Engagement In Adoption, Implementation, And Sustainment Of An Evidence-Based Intervention To Increase Mammography Adherence Among Low-Income Women, Jennifer Holcomb, Gayla M Ferguson, Jiali Sun, Gretchen H Walton, Linda Highfield

Faculty, Staff and Student Publications

Multi-level organizational stakeholder engagement plays an important role across the research process in a clinical setting. Stakeholders provide organizational specific adaptions in evidence-based interventions to ensure effective adoption, implementation, and sustainability. Stakeholder engagement strategies involve building mutual trust, providing clear communication, and seeking feedback. Using constructs from the Consolidated Framework for Implementation Research and The International Association for Public Participation spectrum, a conceptual framework was created to guide stakeholder engagement in an evidence-based intervention to increase mammography appointment adherence in underserved and low-income women. A document review was used to explore the alignment of the conceptual framework with intervention activities …

Association Of Puberty Stage And Weight Status With Cardiometabolic Risk In Children And Adolescents Living On The Texas-Mexico Border, Ee Vien Low, Miryoung Lee, Cici Bauer, Susan P Fisher-Hoch, Joseph B Mccormick, Susan Abughosh, Ekere J Essien, Jessica Rodriguez, Hua Chen

Faculty, Staff and Student Publications

Background: This retrospective cohort study aimed to examine the interaction effect between puberty stage and weight status on individual and clustering of cardiometabolic risk factors (CMRFs) among Mexican American children and adolescents. A total of 333 children and adolescents (aged 8-18 years) enrolled in the Cameron County Hispanic Cohort (CCHC) from 2014 to 2020 were included in the study.

Methods: CCHC is a longitudinal, randomly recruited cohort based on the United States Census tracts/blocks of Mexican Americans living on the Texas-Mexico border. Individual CMRFs, including high blood pressure, central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and insulin resistance (IR) were …

Longitudinal Change In Blood Dna Epigenetic Signature After Smoking Cessation, Amena Keshawarz, Roby Joehanes, Weihua Guan, Tianxiao Huan, Dawn L Demeo, Megan L Grove, Myriam Fornage, Daniel Levy, George O'Connor

Faculty, Staff and Student Publications

Cigarette smoking is associated with epigenetic changes that may be reversible following smoking cessation. Whole blood DNA methylation was evaluated in Framingham Heart Study Offspring (n = 169) and Third Generation (n = 30) cohort participants at two study visits 6 years apart and in Atherosclerosis Risk in Communities (ARIC) study (n = 222) participants at two study visits 20 years apart. Changes in DNA methylation (delta β values) at 483,565 cytosine-phosphate-guanine (CpG) sites and differentially methylated regions (DMRs) were compared between participants who were current, former, or never smokers at both visits (current-current, former-former, never-never, respectively), versus those who …

Maternal Occupational Exposure To Chemicals And Child Cognitive Function, Jennifer Ish, Elaine Symanski, David Gimeno Ruiz De Porras, Maribel Casas, George L Delclos, Mònica Guxens, Jesús M Ibarluzea, Carmen Iñiguez, Aitana Lertxundi, Marisa Rebagliato, Michael D Swartz, Kristina W Whitworth

Faculty, Staff and Student Publications

BACKGROUND: Limited data exist regarding child neurodevelopment in relation to maternal occupational exposure to endocrine-disrupting chemicals (EDCs).

METHODS: We included 1058 mother-child pairs from the INfancia y Medio Ambiente (INMA) project (2003-2008). Using a job-exposure matrix, exposure probability scores for ten EDC groups were assigned to each mother based on her longest held job during pregnancy. At the child's 5-year visit, the McCarthy Scales of Children's Abilities was administered, yielding the general cognitive index and scales for specific cognitive domains. We analyzed region-specific associations between EDC exposures and each outcome separately using adjusted linear regression and combined region-specific effect estimates …

Effectiveness And Feasibility Of The Workout On Wheels Internet Intervention (Wowii) For Individuals With Spinal Cord Injury: A Randomized Controlled Trial, Katherine Froehlich-Grobe, Jaehoon Lee, Christa Ochoa, Amber Lopez, Erina Sarker, Simon Driver, Ross Shegog, Suh-Jen Lin

Faculty, Staff and Student Publications

STUDY DESIGN: Randomized-controlled trial (RCT) with immediate intervention (IMM) and wait-list control (WLC) groups; WLC participants received the intervention during delivery to subsequent cohorts.

OBJECTIVES: Investigate the effectiveness and feasibility of a virtually-delivered exercise intervention.

SETTING: Home and community.

METHODS: A total of 168 middle-aged (49.6 [12.3] years old) men (57%) and women (43%) who lived an average 15.5 (12.3) years with spinal cord injury (SCI) participated. The 16-week program provides users (a) website access with exercise information, resources, and 16 skill-building modules; (b) virtual 60-minute, group-based weekly meetings; and (c) a starter package of exercise equipment. Primary outcomes included …

First-In-Human Study Of An Ox40 (Ivuxolimab) And 4-1bb (Utomilumab) Agonistic Antibody Combination In Patients With Advanced Solid Tumors, Omid Hamid, Alberto A Chiappori, John A Thompson, Toshihiko Doi, Siwen Hu-Lieskovan, Ferry A L M Eskens, Willeke Ros, Adi Diab, Jean-Philippe Spano, Naiyer A Rizvi, Jeffrey S Wasser, Eric Angevin, Patrick A Ott, Alison Forgie, Wenjing Yang, Cen Guo, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

Background: Ivuxolimab (PF-04518600) and utomilumab (PF-05082566) are humanized agonistic IgG2 monoclonal antibodies against OX40 and 4-1BB, respectively. This first-in-human, multicenter, open-label, phase I, dose-escalation/dose-expansion study explored safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ivuxolimab+utomilumab in patients with advanced solid tumors.

Methods: Dose-escalation: patients with advanced bladder, gastric, or cervical cancer, melanoma, head and neck squamous cell carcinoma, or non-small cell lung cancer (NSCLC) who were unresponsive to available therapies, had no standard therapy available or declined standard therapy were enrolled into five dose cohorts: ivuxolimab (0.1-3 mg/kg every 2 weeks (Q2W)) intravenously plus utomilumab (20 or 100 mg every …

Stat3 Inhibits Autocrine Ifn Signaling In Type I Conventional Dendritic Cells, Taylor T Chrisikos, Yifan Zhou, Laura M Kahn, Bhakti Patel, Nina L Denne, Athena Brooks, Li Shen, Jing Wang, Stephanie S Watowich

Faculty, Staff and Student Publications

Type I conventional dendritic cells (cDC1s) are an essential Ag-presenting population required for generating adaptive immunity against intracellular pathogens and tumors. While the transcriptional control of cDC1 development is well understood, the mechanisms by which extracellular stimuli regulate cDC1 function remain unclear. We previously demonstrated that the cytokine-responsive transcriptional regulator STAT3 inhibits polyinosinic:polycytidylic acid [poly(I:C)]-induced cDC1 maturation and cDC1-mediated antitumor immunity in murine breast cancer, indicating an intrinsic, suppressive role for STAT3 in cDC1s. To probe transcriptional mechanisms regulating cDC1 function, we generated novel RNA sequencing datasets representing poly(I:C)-, IL-10-, and STAT3-mediated gene expression responses in murine cDC1s. Bioinformatics analyses …

A Systematic Review And Meta-Analysis Of The Impact Of Radiation-Related Lymphopenia On Outcomes In High-Grade Gliomas, Supriya Mallick, Anjali V R, Prashanth Giridhar, Rituraj Upadhyay, Byung-Kyu Kim, Amrish Sharma, Hagar Elghazawy, Thiraviyam Elumalai, Vinod Solipuram, Cheng En Hsieh, Courtney Hentz, Abhishek A Solanki, Jing Li, Dennis Pai Chan, Emily Ness, Bhanu Prasad Venkatesulu, David R Grosshans

Faculty, Staff and Student Publications

Introduction  Malignant gliomas are the most common primary malignant brain tumors and are typically treated with maximal safe surgical resection followed by chemoradiation. One of the unintended effects of radiation is depletion of circulating lymphocyte pool, which has been correlated with inferior overall survival outcomes.

Methods  A comprehensive and systematic searches of the PubMed, Cochrane Central, and Embase databases were done to assess the studies that have reported radiation-related lymphopenia in high-grade gliomas. Hazard ratios (HRs), odds ratios (OR), and mean differences were represented with Forest plots comparing patients with severe lymphopenia and no severe lymphopenia. Review Manager Version 5.3 …

Comprehensive Multiplexed Immune Profiling Of The Ductal Carcinoma In Situ Immune Microenvironment Regarding Subsequent Ipsilateral Invasive Breast Cancer Risk, Mathilde M Almekinders, Tycho Bismeijer, Tapsi Kumar, Fei Yang, Bram Thijssen, Rianne Van Der Linden, Charlotte Van Rooijen, Shiva Vonk, Baohua Sun, Edwin R Parra Cuentas, Ignacio I Wistuba, Savitri Krishnamurthy, Lindy L Visser, Iris M Seignette, Ingrid Hofland, Joyce Sanders, Annegien Broeks, Jason K Love, Brian Menegaz, Lodewyk Wessels, Alastair M Thompson, Karin E De Visser, Erik Hooijberg, Esther Lips, Andrew Futreal, Jelle Wesseling

Faculty, Staff and Student Publications

Background: Ductal carcinoma in situ (DCIS) is treated to prevent subsequent ipsilateral invasive breast cancer (iIBC). However, many DCIS lesions will never become invasive. To prevent overtreatment, we need to distinguish harmless from potentially hazardous DCIS. We investigated whether the immune microenvironment (IME) in DCIS correlates with transition to iIBC.

Methods: Patients were derived from a Dutch population-based cohort of 10,090 women with pure DCIS with a median follow-up time of 12 years. Density, composition and proximity to the closest DCIS cell of CD20+ B-cells, CD3+CD8+ T-cells, CD3+CD8- T-cells, CD3+FOXP3+ regulatory T-cells, CD68+ cells, and CD8+Ki67+ T-cells was assessed with …

Wide-Necked Middle Cerebral Artery Aneurysm Clipping Following Failed Occlusion After Woven Endobridge Placement: 2-Dimensional Operative Video, Stephen Capone, Anil Roy, Matthew Kole, Spiros L Blackburn

Faculty, Staff and Student Publications

No abstract provided.

Metabolic, Physiological And Anatomical Responses Of Soybean Plants Under Water Deficit And High Temperature Condition, Roberto Gomes Vital, Caroline Müller, Francisco Bruno Silva Freire, Fábia Barbosa Silva, Priscila Ferreira Batista, David Fuentes, Arthur Almeida Rodrigues, Luciana Minervina Freitas Moura, Danilo Menezes Daloso, Adinan Alves Silva, Andrew Merchant, Alan Carlos Costa

Faculty, Staff and Student Publications

Water deficit (WD) combined with high temperature (HT) is the major factor limiting agriculture worldwide, and it is predicted to become worse according to the current climate change scenario. It is thus important to understand how current cultivated crops respond to these stress conditions. Here we investigated how four soybean cultivars respond to WD and HT isolated or in combination at metabolic, physiological, and anatomical levels. The WD + HT increased the level of stress in soybean plants when compared to plants under well-watered (WW), WD, or HT conditions. WD + HT exacerbates the increases in ascorbate peroxidase activity, which …

Preconditioning By Voluntary Wheel Running Attenuates Later Neuropathic Pain Via Nuclear Factor E2-Related Factor 2 Antioxidant Signaling In Rats, Suzanne M Green-Fulgham, Michael E Harland, Jayson B Ball, Jiahe Li, Michael J Lacagnina, Heather D'Angelo, Renee A Dreher, Kendal F Willcox, Sabina A Lorca, Andrew J Kwilasz, Steven F Maier, Linda R Watkins, Peter M Grace

Faculty, Staff and Student Publications

Animal and human studies have shown that exercise prior to nerve injury prevents later chronic pain, but the mechanisms of such preconditioning remain elusive. Given that exercise acutely increases the formation of free radicals, triggering antioxidant compensation, we hypothesized that voluntary running preconditioning would attenuate neuropathic pain by supporting redox homeostasis after sciatic nerve injury in male and female rats. We show that 6 weeks of voluntary wheel running suppresses neuropathic pain development induced by chronic constriction injury across both sexes. This attenuation was associated with reduced nitrotyrosine immunoreactivity-a marker for peroxynitrite-at the sciatic nerve injury site. Our data suggest …

Anchor Arthropathy Caused By Cartilage Penetration: An Approach To Revision Hip Arthroscopy With Removal Of Problematic Anchors, Payam W Sabetian, Olivia A Paraschos, W Taylor Harris, Paulo P Padilla, David R Maldonado, Benjamin G Domb

Faculty, Staff and Student Publications

Hip arthroscopy has been proven to effectively treat labral tears in the setting of femoroacetabular impingement. Anchors used for this treatment have constantly evolved and improved to ensure safety and minimal invasion. However, acetabular drilling and anchor placement are technically challenging due to the concavity of the acetabular articular surface, limited angles for anchor insertion, and finite bone availability in the anterior and posterior column. Inadequate technique can result in protruding anchors, which may lead to full-thickness articular cartilage damage, manifesting in pain, mechanical symptoms, and impaired function. This Technical Note demonstrates arthroscopic removal of protruding anchors and management of …

Aerosol Production With Surgical Instrumentation: Implications For Head And Neck Surgery In The Covid-19 Era, Garren M I Low, Bailey Leconte, Arturo A Eguia, Ashley Kim, Ron J Karni, Amber U Luong, Kunal S Jain

Faculty, Staff and Student Publications

Evaluating the aerosolization of droplets from surgical instruments to assess the implications of surgery in SARS-CoV-2 transmission for both patients and providers. Cadaver study. Outpatient surgery center. Aerosolized particles between 0.3 and 25 microns were measured. Instruments tested included monopolar cautery with and without suction, bipolar cautery, a bipolar vessel sealing device, and tissue scissors. Each trial was compared to a background reading. Monopolar cautery without suction, Ligasure used continuously and Bipolar cautery produced the most aerosols. Monopolar cautery with simultaneous suction produced no detectable aerosols. Ligasure used for a single cycle produced notably fewer aerosols than during continuous use. …

A Hydrogen-Sulfide Derivative Of Mesalamine Reduces The Severity Of Intestinal And Lung Injury In Necrotizing Enterocolitis Through Endothelial Nitric Oxide Synthase, Brian D Hosfield, Chelsea E Hunter, Hongge Li, Natalie A Drucker, Anthony R Pecoraro, Krishna Manohar, W Christopher Shelley, Troy A Markel

Faculty, Staff and Student Publications

Necrotizing enterocolitis (NEC) remains a devastating disease that affects preterm infants. Hydrogen sulfide (H2S) donors have been shown to reduce the severity of NEC, but the optimal compound has yet to be identified. We hypothesized that oral H2S-Mesalamine (ATB-429) would improve outcomes in experimental NEC, and its benefits would be dependent on endothelial nitric oxide synthase (eNOS) pathways. NEC was induced in 5-day-old wild-type (WT) and eNOS knockout (eNOSKO) pups by formula feeding and stress. Four groups were studied in both WT and eNOSKO mice: 1) breastfed controls, 2) NEC, 3) NEC + 50 mg/kg mesalamine, and …

Comparison Of Brain Nicotine Uptake From Electronic Cigarettes And Combustible Cigarettes, Yantao Zuo, Alexey G Mukhin, Hannah Berg, Janiece D Morgan, Akiva Mintz, Jed E Rose, Kiran Kumar Solingapuram Sai

Faculty, Staff and Student Publications

Brain accumulation rate and magnitude are critical for the acute reinforcing effects of nicotine. Despite electronic cigarettes’ (E-cigs) appeal as substitutes for traditional combustible cigarettes (C-cigs), brain nicotine accumulation (BNA) from E-cigs has not been compared with that from C-cigs using a within-subjects design. BNA was directly assessed with 16 adult dual users (10 females) of E-cigs (e-liquid pH 9.4) and C-cigs, using 11C-nicotine and positron emission tomography (PET). Participants went through two 15-min head scanning sessions during which they inhaled a single puff of E-cig vapor or C-cig smoke containing 11C-nicotine in a randomized order. A full-body scan was …

Aging After Stroke: How To Define Post-Stroke Sarcopenia And What Are Its Risk Factors?, Sheng Li, Javier Gonzalez-Buonomo, Jaskiran Ghuman, Xinran Huang, Aila Malik, Nuray Yozbatiran, Elaine Magat, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia, generally described as "aging-related loss of skeletal muscle mass and function", can occur secondary to a systemic disease.

AIM: This project aimed to study the prevalence of sarcopenia in chronic ambulatory stroke survivors and its associated risk factors using the two most recent diagnostic criteria.

DESIGN: A cross-sectional observational study.

SETTING: A scientific laboratory.

POPULATION: Chronic stroke.

METHODS: Twenty-eight ambulatory chronic stroke survivors (12 females; mean age=57.8±11.8 years; time after stroke=76±45 months), hand-grip strength, gait speed, and appendicular skeletal muscle mass (ASM) were measured to define sarcopenia. Risk factors, including motor impairment and spasticity, were identified using regression …

Aging After Stroke: How To Define Post-Stroke Sarcopenia And What Are Its Risk Factors?, Sheng Li, Javier Gonzalez-Buonomo, Jaskiran Ghuman, Xinran Huang, Aila Malik, Nuray Yozbatiran, Elaine Magat, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia, generally described as "aging-related loss of skeletal muscle mass and function", can occur secondary to a systemic disease.

AIM: This project aimed to study the prevalence of sarcopenia in chronic ambulatory stroke survivors and its associated risk factors using the two most recent diagnostic criteria.

DESIGN: A cross-sectional observational study.

SETTING: A scientific laboratory.

POPULATION: Chronic stroke.

METHODS: Twenty-eight ambulatory chronic stroke survivors (12 females; mean age=57.8±11.8 years; time after stroke=76±45 months), hand-grip strength, gait speed, and appendicular skeletal muscle mass (ASM) were measured to define sarcopenia. Risk factors, including motor impairment and spasticity, were identified using regression …

Development Of The International Spinal Cord Injury Basic Data Set For Informal Caregivers, Carol Haywood, Rebecca Martin, Kathryn Dent, M J Mulcahey

Faculty, Staff and Student Publications

STUDY DESIGN: Mixed-methods, including expert consensus for initial development and a multi-center repeated measures design for field testing.

OBJECTIVES: To develop an International Spinal Cord Injury Basic Data Set for caregivers of individuals with spinal cord injury/disorder (SCI/D) for use in research and clinical care settings.

SETTING: International, multi-disciplinary working group with field testing in five North American pediatric rehabilitation hospitals.

METHODS: The data set was developed iteratively through meetings and online surveys with a working group of experts in pediatric and adult SCI/D rehabilitation and caregivers of individuals with SCI/D. Initial reliability was examined through repeat administration of a …

Rumination As A Mediator Of The Association Between Racial Discrimination And Depression Among Black Youth, Donte L Bernard, Colleen A Halliday, Funlola Are, Devin E Banks, Carla Kmett Danielson

Faculty, Staff and Student Publications

BACKGROUND: Racial discrimination constitutes a significant risk factor for depressive symptoms among Black youth. Rumination, a maladaptive self-regulatory stress response, is a notable pathway by which racial discrimination contributes to depressive symptoms among racial/ethnic minority adults. Yet, examinations of the mechanistic nature of rumination in the context of racial discrimination among racial/ethnic minority youth remain limited. The present study investigated rumination as a mediator of the association between racial discrimination and depressive symptoms among Black youth.

METHODS: Data for the current study were drawn from baseline questionnaire responses of community recruited Black pre-and-early adolescents (N = 158, 53% female, M …

Genetics And Epigenetics Of Self-Injurious Thoughts And Behaviors: Systematic Review Of The Suicide Literature And Methodological Considerations, Salahudeen Mirza, Anna R Docherty, Amanda Bakian, Hilary Coon, Jair C Soares, Consuelo Walss-Bass, Gabriel R Fries

Faculty, Staff and Student Publications

Suicide is a multifaceted and poorly understood clinical outcome, and there is an urgent need to advance research on its phenomenology and etiology. Epidemiological studies have demonstrated that suicidal behavior is heritable, suggesting that genetic and epigenetic information may serve as biomarkers for suicide risk. Here we systematically review the literature on genetic and epigenetic alterations observed in phenotypes across the full range of self-injurious thoughts and behaviors (SITB). We included 577 studies focused on genome-wide and epigenome-wide associations, candidate genes (SNP and methylation), noncoding RNAs, and histones. Convergence of specific genes is limited across units of analysis, although pathway-based …

Ocrelizumab Reduces Thalamic Volume Loss In Patients With Rms And Ppms, Douglas L Arnold, Till Sprenger, Amit Bar-Or, Jerry S Wolinsky, Ludwig Kappos, Shannon Kolind, Ulrike Bonati, Stefano Magon, Johan Van Beek, Harold Koendgen, Oscar Bortolami, Corrado Bernasconi, Laura Gaetano, Anthony Traboulsee

Faculty, Staff and Student Publications

Background: In multiple sclerosis (MS), thalamic integrity is affected directly by demyelination and neuronal loss, and indirectly by gray/white matter lesions outside the thalamus, altering thalamic neuronal projections.

Objective: To assess the efficacy of ocrelizumab compared with interferon beta-1a (IFNβ1a)/placebo on thalamic volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II; NCT01247324/NCT01412333) and in primary progressive MS (PPMS, ORATORIO; NCT01194570).

Methods: Thalamic volume change was computed using paired Jacobian integration and analyzed using an adjusted mixed-effects repeated measurement model.

Results: Over the double-blind period, …

Aging After Stroke: How To Define Post-Stroke Sarcopenia And What Are Its Risk Factors?, Sheng Li, Javier Gonzalez-Buonomo, Jaskiran Ghuman, Xinran Huang, Aila Malik, Nuray Yozbatiran, Elaine Magat, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

Background: Sarcopenia, generally described as "aging-related loss of skeletal muscle mass and function", can occur secondary to a systemic disease.

Aim: This project aimed to study the prevalence of sarcopenia in chronic ambulatory stroke survivors and its associated risk factors using the two most recent diagnostic criteria.

Design: A cross-sectional observational study.

Setting: A scientific laboratory.

Population: Chronic stroke.

Methods: Twenty-eight ambulatory chronic stroke survivors (12 females; mean age=57.8±11.8 years; time after stroke=76±45 months), hand-grip strength, gait speed, and appendicular skeletal muscle mass (ASM) were measured to define sarcopenia. Risk factors, including motor impairment and spasticity, were identified using regression …

The Impact Of Covid-19 Pandemic Upon Non-Elective Admissions And Surgery At A Safety-Net Hospital: A Retrospective Cohort Study, Artem Boyev, Srinivas Sanjeevi, Martha M Estrada, Tien C Ko, Curtis J Wray

Faculty, Staff and Student Publications

Introduction: In response to the COVID-19 pandemic, hospitals reported decreased admissions for acute surgical diagnoses, but scant data was available to quantify the decrease and its consequences. The objective of this study was to examine the incidence of acute care surgery encounters before and during the COVID-19 pandemic.

Materials and methods: A retrospective cohort study was performed at a single, urban, United States safety-net hospital. Emergency room encounters, admissions, non-elective surgical procedures, patient acuity, and surgical complications were compared before and after the start of the COVID-19 pandemic. The primary outcome of the study was the incidence rate (IR) and …

Engineering Antibody And Protein Therapeutics To Cross The Blood-Brain Barrier, Peng Zhao, Ningyan Zhang, Zhiqiang An

Faculty, Staff and Student Publications

Diseases in the central nervous system (CNS) are often difficult to treat. Antibody- and protein-based therapeutics hold huge promises in CNS disease treatment. However, proteins are restricted from entering the CNS by the blood-brain barrier (BBB). To achieve enhanced BBB crossing, antibody-based carriers have been developed by utilizing the endogenous macromolecule transportation pathway, known as receptor-mediated transcytosis. In this report, we first provided an overall review on key CNS diseases and the most promising antibody- or protein-based therapeutics approved or in clinical trials. We then reviewed the platforms that are being explored to increase the macromolecule brain entry to combat …

A Population-Based Meta-Analysis Of Circulating Gfap For Cognition And Dementia Risk, Mitzi M Gonzales, Crystal Wiedner, Chen-Pin Wang, Qianqian Liu, Joshua C Bis, Zhiguang Li, Jayandra J Himali, Saptaparni Ghosh, Emy A Thomas, Danielle M Parent, Tiffany F Kautz, Matthew P Pase, Hugo J Aparicio, Luc Djoussé, Kenneth J Mukamal, Bruce M Psaty, William T Longstreth, Thomas H Mosley, Vilmundur Gudnason, Djass Mbangdadji, Oscar L Lopez, Kristine Yaffe, Stephen Sidney, R Nick Bryan, Ilya M Nasrallah, Charles S Decarli, Alexa S Beiser, Lenore J Launer, Myriam Fornage, Russell P Tracy, Sudha Seshadri, Claudia L Satizabal

Faculty, Staff and Student Publications

Objective: Expression of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis, colocalizes with neuropathology in the brain. Blood levels of GFAP have been associated with cognitive decline and dementia status. However, further examinations at a population-based level are necessary to broaden generalizability to community settings.

Methods: Circulating GFAP levels were assayed using a Simoa HD-1 analyzer in 4338 adults without prevalent dementia from four longitudinal community-based cohort studies. The associations between GFAP levels with general cognition, total brain volume, and hippocampal volume were evaluated with separate linear regression models in each cohort with adjustment for age, sex, education, …

Concerns About The Use Of Polygenic Embryo Screening For Psychiatric And Cognitive Traits, Todd Lencz, Maya Sabatello, Anna Docherty, Roseann E Peterson, Takahiro Soda, Jehannine Austin, Laura Bierut, David Crepaz-Keay, David Curtis, Franziska Degenhardt, Laura Huckins, Gabriel Lazaro-Munoz, Manuel Mattheisen, Bettina Meiser, Holly Peay, Marcella Rietschel, Consuelo Walss-Bass, Lea K Davis

Faculty, Staff and Student Publications

Private companies have begun offering services to allow parents undergoing in-vitro fertilisation to screen embryos for genetic risk of complex diseases, including psychiatric disorders. This procedure, called polygenic embryo screening, raises several difficult scientific and ethical issues, as discussed in this Personal View. Polygenic embryo screening depends on the statistical properties of polygenic risk scores, which are complex and not well studied in the context of this proposed clinical application. The clinical, social, and ethical implications of polygenic embryo screening have barely been discussed among relevant stakeholders. To our knowledge, the International Society of Psychiatric Genetics is the first professional …

Role Of Sam68 In Sunitinib Induced Renal Cell Carcinoma Apoptosis, Zeshen Wu, Yulu Peng, Longbin Xiong, Jun Wang, Zhen Li, Kang Ning, Minhua Deng, Ning Wang, Wensu Wei, Zhiyong Li, Pei Dong, Chunping Yu, Fangjian Zhou, Zhiling Zhang

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Sunitinib is one of the first-line targeted drugs for metastatic renal cell carcinoma (RCC) with dual effects of antiangiogensis and proapoptosis. Sam68 (Src-associated in mitosis, 68 KDa), is found being involved in cell apoptosis. This article reveals that Sam68 impacts the sensitivity to sunitinib by mediating the apoptosis of RCC cells. Immunohistochemical staining indicated that the Sam68 expression levels in sunitinib sensitive tumor tissues were markedly higher than those in sunitinib resistant tumor tissues. Sunitinib induced RCC cell apoptosis in a concentration-dependent manner and inhibited the expression of total and phosphorylated Sam68 (p-Sam68). Downregulation of Sam68 expression inhibited RCC cell …

Selective Iga Deficiency In Spontaneously Hypertensive Rats With Gut Dysbiosis, Piu Saha, Blair Mell, Rachel M Golonka, Venugopal R Bovilla, Ahmed A Abokor, Xue Mei, Beng San Yeoh, Peter A Doris, Andrew T Gewirtz, Bina Joe, Matam Vijay-Kumar

Faculty, Staff and Student Publications

BACKGROUND: The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR.

METHODS: IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue, and milk from SHR and Wistar Kyoto rats. IgA regulatory factors like IgM, IgG, and

RESULTS: Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liver

CONCLUSIONS: …

Response To Brentuximab Vedotin By Cd30 Expression In Non-Hodgkin Lymphoma, Deepa Jagadeesh, Steve Horwitz, Nancy L Bartlett, Youn Kim, Eric Jacobsen, Madeleine Duvic, Meredith Little, William Trepicchio, Keenan Fenton, Matthew Onsum, Julie Lisano, Ranjana Advani

Faculty, Staff and Student Publications

BACKGROUND: The safety and efficacy of brentuximab vedotin (BV), an antibody-drug conjugate directed to the CD30 antigen, has been assessed in several trials in patients with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell non-Hodgkin lymphoma (NHL). The objective of this research was to examine the relationship between CD30 expression level and clinical response to BV.

PATIENTS AND METHODS: We analyzed response in patients treated with BV monotherapy in 5 prospective clinical studies in relapsed or refractory PTCL, CTCL, or B-cell NHL. CD30 expression was assessed by immunohistochemistry (IHC) using the Ber H2 antibody for 275 patients.

RESULTS: …