Digital Commons Network^™

Venous Thromboembolism Risk In Cancer Patients Receiving First-Line Immune Checkpoint Inhibitor Versus Chemotherapy, Ang Li, Sarah B May, Jennifer La, Kylee L Martens, Christopher I Amos, Christopher R Flowers, Nhan V Do, Mary T Brophy, Vipul Chitalia, Katya Ravid, John Michael Gaziano, Nathanael R Fillmore

Faculty, Staff and Students Publications

It remains unclear if immune checkpoint inhibitor (ICI) therapy is associated with higher rate of venous thromboembolism (VTE) compared with cytotoxic chemotherapy (chemo) in patients with comparable cancer type, staging, and comorbidities. Using the national Veterans Affairs healthcare system database from 2016 to 2021, we performed a propensity score (PS)-weighted retrospective cohort study to compare the incidence of VTE in patients with selected stage III/IV cancer receiving first-line ICI versus chemo. The PS model utilized overlap weights to balance age, sex, race, treatment year, VTE history, paralysis/immobilization, prolonged hospitalization, cancer type, staging, time between diagnosis and treatment, and National Cancer …

Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma: Pathogenesis And Treatment, Josep M Llovet, Catherine E Willoughby, Amit G Singal, Tim F Greten, Mathias Heikenwälder, Hashem B El-Serag, Richard S Finn, Scott L Friedman

Faculty, Staff and Students Publications

Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation, nonalcoholic steatohepatitis (NASH), has a global prevalence of 20-25% and is a major public health problem. Its incidence is increasing in parallel to the rise in obesity, diabetes and metabolic syndrome. Progression from NASH to NASH-related hepatocellular carcinoma (HCC) (~2% of cases per year) is influenced by many factors, including the tissue and immune microenvironment, germline mutations in PNPLA3, and the microbiome. NASH-HCC has unique molecular and immune traits compared with other aetiologies of HCC and is equally prevalent in men and women. Comorbidities associated with NASH, such as obesity …

Effects Of Cathepsin S Inhibition In The Age-Related Dry Eye Phenotype, Jeremias G Galletti, Kaitlin K Scholand, Claudia M Trujillo-Vargas, Wolfgang Haap, Tiago Santos-Ferreira, Christoph Ullmer, Zhiyuan Yu, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss-/-) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease.

METHODS: Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet-Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify …

Health Information Seeking In The Digital Age: A National Survey Of Women With Disabilities, Susan Robinson-Whelen, Rosemary B Hughes, Jeanne L Alhusen, Leanne Beers, Charles G Minard, David Davidson

Faculty, Staff and Students Publications

PURPOSE: Access to high quality and accessible online health information (OHI) is critical for reducing disparities, overcoming barriers, and improving the health of women with disabilities. This study aimed to understand women with physical disabilities' use of the Internet to access OHI, most often searched health topics, perceived usefulness of OHI, and self-reported eHealth literacy and challenges in OHI seeking.

METHODS: We conducted a national online survey with 508 women with physical disabilities who used the Internet.

RESULTS: Respondents utilized a wide variety of OHI resources. They searched a broad array of health and disability-related topics, with bowel/bladder and finding …

Disparities In Antifibrotic Medication Utilization Among Veterans With Idiopathic Pulmonary Fibrosis, Bhavika Kaul, Joyce S Lee, Laura A Petersen, Charles Mcculloch, Ivan O Rosas, Venkata D Bandi, Ning Zhang, Alison M Dedent, Harold R Collard, Mary A Whooley

Faculty, Staff and Students Publications

BACKGROUND: Two antifibrotic medications, pirfenidone and nintedanib, are approved for the treatment of idiopathic pulmonary fibrosis (IPF). Little is known about their real-world adoption.

RESEARCH QUESTION: What are the real-world antifibrotic utilization rates and factors associated with uptake among a national cohort of veterans with IPF?

STUDY DESIGN AND METHODS: This study identified veterans with IPF who received care either provided by the Veterans Affairs (VA) Healthcare System or non-VA care paid for by the VA. Patients who had filled at least one antifibrotic prescription through the VA pharmacy or Medicare Part D between October 15, 2014, and December 31, …

Heterogeneity Of The Group B Streptococcal Type Vii Secretion System And Influence On Colonization Of The Female Genital Tract, Brady L Spencer, Alyx M Job, Clare M Robertson, Zainab A Hameed, Camille Serchejian, Caitlin S Wiafe-Kwakye, Jéssica C Mendonça, Morgan A Apolonio, Prescilla E Nagao, Melody N Neely, Natalia Korotkova, Konstantin V Korotkov, Kathryn A Patras, Kelly S Doran

Faculty, Staff and Students Publications

Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-helical proteins and toxins. Recently, we characterized T7SSb in group B Streptococcus (GBS), a leading cause of infection in newborns and immunocompromised adults. GBS T7SS comprises four subtypes based on variation in the C-terminus of EssC and the repertoire of downstream effectors; however, the intraspecies diversity of GBS T7SS and impact on GBS-host interactions remains unknown. Bioinformatic analysis indicates that GBS T7SS loci encode subtype-specific putative effectors, which have low interspecies and inter-subtype homology but contain similar domains/motifs and therefore …

Deconvolution Of Cancer Cell States By The Xdec-Sm Method, Oscar D Murillo, Varduhi Petrosyan, Emily L Laplante, Lacey E Dobrolecki, Michael T Lewis, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

Proper characterization of cancer cell states within the tumor microenvironment is a key to accurately identifying matching experimental models and the development of precision therapies. To reconstruct this information from bulk RNA-seq profiles, we developed the XDec Simplex Mapping (XDec-SM) reference-optional deconvolution method that maps tumors and the states of constituent cells onto a biologically interpretable low-dimensional space. The method identifies gene sets informative for deconvolution from relevant single-cell profiling data when such profiles are available. When applied to breast tumors in The Cancer Genome Atlas (TCGA), XDec-SM infers the identity of constituent cell types and their proportions. XDec-SM also …

Real-World Perspectives And Practices For Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use In Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer, Hope S Rugo, Christine L Crossno, Yaron B Gesthalter, Kristen Kelley, Heather B Moore, Mothaffar F Rimawi, Kelly E Westbrook, Saundra S Buys

Faculty, Staff and Students Publications

Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate with a topoisomerase I payload that targets the human epidermal growth factor receptor 2 (HER2). T-DXd is approved for patients with previously treated HER2-positive or HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/ISH-) metastatic/unresectable breast cancer (BC). In a second-line HER2-positive metastatic BC (mBC) population (DESTINY-Breast03 [ClinicalTrials.gov identifier: NCT03529110]), T-DXd demonstrated significantly improved progression-free survival (PFS) over ado-trastuzumab emtansine (12-month rate: 75.8%

Crat Links Cholesterol Metabolism To Innate Immune Responses In The Heart, Hua Mao, Aude Angelini, Shengyu Li, Guangyu Wang, Luge Li, Cam Patterson, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

Chronic inflammation is associated with increased risk and poor prognosis of heart failure; however, the precise mechanism that provokes sustained inflammation in the failing heart remains elusive. Here we report that depletion of carnitine acetyltransferase (CRAT) promotes cholesterol catabolism through bile acid synthesis pathway in cardiomyocytes. Intracellular accumulation of bile acid or intermediate, 7α-hydroxyl-3-oxo-4-cholestenoic acid, induces mitochondrial DNA stress and triggers cGAS-STING-dependent type I interferon responses. Furthermore, type I interferon responses elicited by CRAT deficiency substantially increase AIM2 expression and AIM2-dependent inflammasome activation. Genetic deletion of cardiomyocyte CRAT in mice of both sexes results in myocardial inflammation and dilated cardiomyopathy, …

Effective Methods For Bulk Rna-Seq Deconvolution Using Scnrna-Seq Transcriptomes, Francisco Avila Cobos, Mohammad Javad Najaf Panah, Jessica Epps, Xiaochen Long, Tsz-Kwong Man, Hua-Sheng Chiu, Elad Chomsky, Evgeny Kiner, Michael J Krueger, Diego Di Bernardo, Luis Voloch, Jan Molenaar, Sander R Van Hooff, Frank Westermann, Selina Jansky, Michele L Redell, Pieter Mestdagh, Pavel Sumazin

Faculty, Staff and Students Publications

Background: RNA profiling technologies at single-cell resolutions, including single-cell and single-nuclei RNA sequencing (scRNA-seq and snRNA-seq, scnRNA-seq for short), can help characterize the composition of tissues and reveal cells that influence key functions in both healthy and disease tissues. However, the use of these technologies is operationally challenging because of high costs and stringent sample-collection requirements. Computational deconvolution methods that infer the composition of bulk-profiled samples using scnRNA-seq-characterized cell types can broaden scnRNA-seq applications, but their effectiveness remains controversial.

Results: We produced the first systematic evaluation of deconvolution methods on datasets with either known or scnRNA-seq-estimated compositions. Our analyses revealed …

Interplay Between Zero Cac, Quantitative Plaque Analysis, And Adverse Events In A Diverse Patient Cohort, Michael Fattouh, Toshiki Kuno, Pamela Pina, John P Skendelas, Daniel Lorenzatti, Javier Arce, Jonathan Daich, Gustavo Duarte, Carol Fernandez-Hazim, Miguel Rodriguez-Guerra, Patrick Neshiwat, Aldo L Schenone, Lili Zhang, Carlos J Rodriguez, Armin Arbab-Zadeh, Piotr J Slomka, Salim S Virani, Michael J Blaha, Daniel S Berman, Damini Dey, Mario J Garcia, Leandro Slipczuk

Faculty, Staff and Students Publications

Background: Coronary artery calcium scoring (CAC) has garnered attention in the diagnostic approach to chest pain patients. However, little is known about the interplay between zero CAC, sex, race, ethnicity, and quantitative coronary plaque analysis.

Methods: We conducted a retrospective analysis from our computed tomography registry of patients with stable angina without prior myocardial infarction or revascularization undergoing coronary computed tomography angiography at Montefiore Healthcare System. Follow-up end points collected included invasive angiography, type-1 myocardial infarction, coronary revascularization, cardiovascular and all-cause death.

Results: A total of 2249 patients were included (66% female). The median follow-up was 5.5 years. The median …

Polymorphisms In The Nonhomologous End-Joining Dna Repair Pathway Are Associated With Hpv Integration In Cervical Dysplasia, Jennifer M Geris, E Susan Amirian, Deborah A Marquez-Do, Martial Guillaud, Laura M Dillon, Michele Follen, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Previous evidence indicates that HPV integration status may be associated with cervical cancer development and progression. However, host genetic variation within genes that may play important roles in the viral integration process is understudied. The aim of this study was to examine the association between HPV16 and HPV18 viral integration status and single nucleotide polymorphisms (SNPs) in non-homologous end-joining (NHEJ) DNA repair pathway genes on cervical dysplasia. Women enrolled in two large trials of optical technologies for cervical cancer detection and positive for HPV16 or HPV18 were selected for HPV integration analysis and genotyping. Associations between SNPs and cytology (normal, …

Cell Surface B2m-Free Human Leukocyte Antigen (Hla) Monomers And Dimers: Are They Neo-Hla Class And Proto-Hla?, Mepur H. Ravindranath, Narendranath M. Ravindranath, Senthamil R. Selvan, Fatiha El Hilali, Carly J. Amato-Menker, Edward J. Filippone

Division of Nephrology Faculty Papers

Cell surface HLA-I molecules (Face-1) consist of a polypeptide heavy chain (HC) with two groove domains (G domain) and one constant domain (C-domain) as well as a light chain, B2-microglobulin (B2m). However, HCs can also independently emerge unfolded on the cell surface without peptides as B2m-free HC monomers (Face-2), B2m-free HC homodimers (Face 3), and B2m-free HC heterodimers (Face-4). The transport of these HLA variants from ER to the cell surface was confirmed by antiviral antibiotics that arrest the release of newly synthesized proteins from the ER. Face-2 occurs at low levels on the normal cell surface of the lung, …

Tp53 Induced Glycolysis And Apoptosis Regulator And Monocarboxylate Transporter 4 Drive Metabolic Reprogramming With C-Myc And Nfkb Activation In Breast Cancer, Megan E. Roche, Ying-Hui Ko, Marina Domingo-Vidal, Zhao Lin, Diana Whitaker-Menezes, Ruth C. Birbe, Madalina Tuluc, Balázs Győrffy, Jaime Caro, Nancy J. Philp, Ramon Bartrons, Ubaldo Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

Breast cancer is composed of metabolically coupled cellular compartments with upregulation of TP53 Induced Glycolysis and Apoptosis Regulator (TIGAR) in carcinoma cells and loss of caveolin 1 (CAV1) with upregulation of monocarboxylate transporter 4 (MCT4) in fibroblasts. The mechanisms that drive metabolic coupling are poorly characterized. The effects of TIGAR on fibroblast CAV1 and MCT4 expression and breast cancer aggressiveness was studied using coculture and conditioned media systems and in-vivo. Also, the role of cytokines in promoting tumor metabolic coupling via MCT4 on cancer aggressiveness was studied. TIGAR downregulation in breast carcinoma cells reduces tumor growth. TIGAR overexpression in carcinoma …

Prescribing Patterns Of Fall Risk-Increasing Drugs In Older Adults Hospitalized For Heart Failure, Esther Liu, Musarrat Nahid, Mahad Musse, Ligong Chen, Sarah N Hilmer, Andrew Zullo, Min Ji Kwak, Mark Lachs, Emily B Levitan, Monika M Safford, Parag Goyal

Faculty, Staff and Student Publications

BACKGROUND: Older adults hospitalized for heart failure (HF) are at risk for falls after discharge. One modifiable contributor to falls is fall risk-increasing drugs (FRIDs). However, the prevalence of FRIDs among older adults hospitalized for HF is unknown. We describe patterns of FRIDs use and examine predictors of a high FRID burden.

METHODS: We used the national biracial REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective cohort recruited from 2003-2007. We included REGARDS participants aged ≥ 65 years discharged alive after a HF hospitalization from 2003-2017. We determined FRIDs -cardiovascular (CV) and non-cardiovascular (non-CV) medications - …

Telehealth Diagnosis Of Autism Spectrum Disorder Through Clinical Cases, Emmanuela Ojukwu, Eunice Bawafaa, Sara Afsah, Shivangi Singh, Harsimran Grewal, Zainab Raja, Emily Mckay

Faculty, Staff and Student Publications

INTRODUCTION: African, Caribbean and Black (ACB) adolescents are disproportionately affected by teen pregnancy in North America. Teen pregnancy poses risks to the quality of life of adolescent boys and girls, including physical, psychosocial and socioeconomic risks. Our review aims to explore this public health concern for ACB adolescents within North America. We aim to identify and analyse available evidence on the incidence and prevalence of, associated factors of and interventions to curtail teen pregnancy involvement (TPI) among ACB adolescent boys and girls in North America. This review will explore TPI, rather than teen pregnancy, to ensure a review of men' …

Pseudohypercreatininemia After Surgery For Aortic Dissection: A Case Report, Ayako Tasaki, Makoto Fukuda, Yuki Ikeda, Masatora Yamasaki, Ikko Yamaguchi, Shinichi Aishima, Motoaki Miyazono

Children’s Nutrition Research Center Staff Publications

Background: Elevated creatinine concentrations often indicate acute renal injury and renal biopsies are considered in this situation. However,pseudohypercreatininemia is potential cause of elevated creatinine concentrations, and invasive interventions should be avoided.

Case presentation: A 54-year-old woman underwent surgery for descending aortic dissection.Nine days postoperatively, her creatinine concentration increased from 1 mg/dl to 5.78 mg/dl (normal range, 0.47-0.7 mg/dl). Azotemia and hyperkalemia were absent and physical examination findings were unremarkable. Cystatin C concentration was 1.56 mg/l (normal range, 0.56-0.8 mg/l) and pseudohypercreatininemia was suspected. Testing with different reagents showed a creatinine concentration of 0.84 mg/dl. Immunoglobulin (Ig)G was markedly elevated, and …

Abatacept, Cenicriviroc, Or Infliximab For Treatment Of Adults Hospitalized With Covid-19 Pneumonia: A Randomized Clinical Trial, Jane A O'Halloran, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W Mccarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M Lachiewicz, Cynthia Gonzalez, P Brian Smith, Sabina Mendivil-Tuchia De Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M Rauseo, Cameron R Wolfe, Britta Witting, Jennifer P Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M O'Brien, Hussein R Al-Khalidi, Michael A Maldonado, Richard Melsheimer, William G Ferguson, Steven E Mcnulty, Pearl Zakroysky, Susan Halabi, Daniel K Benjamin, Sandra Butler, Jane C Atkinson, Stacey J Adam, Soju Chang, Lisa Lavange, Michael Proschan, Samuel A Bozzette, William G Powderly, Activ-1 Im Study Group Members

Faculty, Staff and Student Publications

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19.

OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and …

Abatacept, Cenicriviroc, Or Infliximab For Treatment Of Adults Hospitalized With Covid-19 Pneumonia: A Randomized Clinical Trial, Jane A O'Halloran, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W Mccarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M Lachiewicz, Cynthia Gonzalez, P Brian Smith, Sabina Mendivil-Tuchia De Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M Rauseo, Cameron R Wolfe, Britta Witting, Jennifer P Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M O'Brien, Hussein R Al-Khalidi, Michael A Maldonado, Richard Melsheimer, William G Ferguson, Steven E Mcnulty, Pearl Zakroysky, Susan Halabi, Daniel K Benjamin, Sandra Butler, Jane C Atkinson, Stacey J Adam, Soju Chang, Lisa Lavange, Michael Proschan, Samuel A Bozzette, William G Powderly

Faculty, Staff and Student Publications

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19.

OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and …

Selection Of Optimal Quantile Protein Biomarkers Based On Cell-Level Immunohistochemistry Data, Misung Yi, Tingting Zhan, Amy R. Peck, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, Hai Hu, Yunguang Sun, Hallgeir Rui, Inna Chervoneva

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: Protein biomarkers of cancer progression and response to therapy are increasingly important for improving personalized medicine. Advanced quantitative pathology platforms enable measurement of protein expression in tissues at the single-cell level. However, this rich quantitative cell-by-cell biomarker information is most often not exploited. Instead, it is reduced to a single mean across the cells of interest or converted into a simple proportion of binary biomarker-positive or -negative cells.

RESULTS: We investigated the utility of retaining all quantitative information at the single-cell level by considering the values of the quantile function (inverse of the cumulative distribution function) estimated from a …

Pragmatic, Randomized, Blinded Trial To Shorten Pharmacologic Treatment Of Newborns With Neonatal Opioid Withdrawal Syndrome (Nows), Adam Czynski, Abbot Laptook, Abhik Das, Brian Smith, Alan Simon, Rachel Greenberg, Robert Annett, Jeannette Lee, Jessica Snowden, Claudia Pedroza, Barry Lester, Barry Eggleston, Drew Bremer, Elisabeth Mcgowan

Faculty, Staff and Student Publications

BACKGROUND: The incidence of maternal opioid use in the USA has increased substantially since 2000. As a consequence of opioid use during pregnancy, the incidence of neonatal opioid withdrawal syndrome (NOWS) has increased fivefold between 2002 and 2012. Pharmacological therapy is indicated when signs of NOWS cannot be controlled, and the objective of pharmacological therapy is to control NOWS signs. Once pharmacologic therapy has started, there is great variability in strategies to wean infants. An important rationale for studying weaning of pharmacological treatment for NOWS is that weaning represents the longest time interval of drug treatment. Stopping medications too early …

China Stroke Surveillance Report 2021, Wen-Jun Tu, Long-De Wang, Special Writing Group Of China Stroke Surveillance Report

Faculty, Staff and Student Publications

Since 2015, stroke has become the leading cause of death and disability in China, posing a significant threat to the health of its citizens as a major chronic non-communicable disease. According to the China Stroke High-risk Population Screening and Intervention Program, an estimated 17.8 million [95% confidence interval (CI) 17.6–18.0 million] adults in China had experienced a stroke in 2020, with 3.4 million (95% CI 3.3–3.5 million) experiencing their first-ever stroke and another 2.3 million (95% CI 2.2–2.4 million) dying as a result. Additionally, approximately 12.5% (95% CI 12.4–12.5%) of stroke survivors were left disabled, as defined by a modified …

Βii-Spectrin Is Required For Synaptic Positioning During Retinal Development, Debalina Goswami-Sewell, Caitlin Bagnetto, Cesiah C Gomez, Joseph T Anderson, Akash Maheshwari, Elizabeth Zuniga-Sanchez

Faculty, Staff and Students Publications

Neural circuit assembly is a multistep process where synaptic partners are often born at distinct developmental stages, and yet they must find each other and form precise synaptic connections with one another. This developmental process often relies on late-born neurons extending their processes to the appropriate layer to find and make synaptic connections to their early-born targets. The molecular mechanism responsible for the integration of late-born neurons into an emerging neural circuit remains unclear. Here, we uncovered a new role for the cytoskeletal protein βII-spectrin in properly positioning presynaptic and postsynaptic neurons to the developing synaptic layer. Loss of βII-spectrin …

Women With Large Vessel Occlusion Acute Ischemic Stroke Are Less Likely To Be Routed To Comprehensive Stroke Centers, Muhammad Bilal Tariq, Iman Ali, Sergio Salazar-Marioni, Ananya S Iyyangar, Hussain M Azeem, Swapnil Khose, Victor Lopez, Rania Abdelkhaleq, Louise D Mccullough, Sunil A Sheth, Youngran Kim

Faculty, Staff and Student Publications

Background Prehospital routing of patients with large vessel occlusion (LVO) acute ischemic stroke (AIS) to centers capable of performing endovascular therapy may improve clinical outcomes. Here, we explore whether distance to comprehensive stroke centers (CSCs), stroke severity, and sex are associated with direct-to-CSC prehospital routing in patients with LVO AIS. Methods and Results In this cross-sectional study, we identified consecutive patients with LVO AIS from a prospectively collected multihospital registry throughout the greater Houston area from January 2019 to June 2020. Primary outcome was prehospital routing to CSC and was compared between men and women using modified Poisson regression including …

Psychosocial Impacts Of The Covid-19 Pandemic On Women With Spinal Cord Injury, Heather B Taylor, Rosemary B Hughes, Diana Gonzalez, Muna Bhattarai, Susan Robinson-Whelen

Faculty, Staff and Student Publications

This study represents the first known research addressing the impact of the COVID-19 pandemic on women with spinal cord injury (SCI) in the United States. Women in this population face unique barriers that put them at elevated risk for compromised quality of life, risk that was magnified by physical and social restrictions imposed during the pandemic. This qualitative study examined the perceptions of women with SCI and the effect of the pandemic on their lives. The predominantly White and relatively well-educated sample of 105 women with traumatic SCI was diverse in age, injury characteristics, and geographic representation. Recruited across the …

Efficacy And Safety Of Elamipretide In Individuals With Primary Mitochondrial Myopathy: The Mmpower-3 Randomized Clinical Trial, Amel Karaa, Enrico Bertini, Valerio Carelli, Bruce H Cohen, Gregory M Enns, Marni J Falk, Amy Goldstein, Gráinne Siobhan Gorman, Richard Haas, Michio Hirano, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Costanza Lamperti, Anna Lehman, Nicola Longo, Maria Judit Molnar, Sumit Parikh, Han Phan, Robert D S Pitceathly, Russell Saneto, Fernando Scaglia, Serenella Servidei, Mark Tarnopolsky, Antonio Toscano, Johan L K Van Hove, John Vissing, Jerry Vockley, Jeffrey S Finman, David A Brown, James A Shiffer, Michelango Mancuso, Mmpower-3 Trial Investigators

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Primary mitochondrial myopathies (PMMs) encompass a group of genetic disorders that impair mitochondrial oxidative phosphorylation, adversely affecting physical function, exercise capacity, and quality of life (QoL). Current PMM standards of care address symptoms, with limited clinical impact, constituting a significant therapeutic unmet need. We present data from MMPOWER-3, a pivotal, phase-3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of elamipretide in participants with genetically confirmed PMM.

METHODS: After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously. Primary efficacy endpoints …

Comparison Of Left Bundle Branch Area Pacing And Biventricular Pacing In Candidates For Resynchronization Therapy, Pugazhendhi Vijayaraman, Parikshit S Sharma, Óscar Cano, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Francesco Zanon, Marek Jastrzebski, Jiangang Zou, Mihail G Chelu, Kevin Vernooy, Zachary I Whinnett, Girish M Nair, Manuel Molina-Lerma, Karol Curila, Dipen Zalavadia, Abdul Haseeb, Cicely Dye, Sharath C Vipparthy, Ryan Brunetti, Pawel Moskal, Alexandra Ross, Antonius Van Stipdonk, Jerin George, Yusuf K Qadeer, Mishal Mumtaz, Jeffrey Kolominsky, Syeda A Zahra, Mehrdad Golian, Lina Marcantoni, Faiz A Subzposh, Kenneth A Ellenbogen

Faculty, Staff and Students Publications

Background: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS or expected frequent ventricular pacing. Left bundle branch area pacing (LBBAP) has recently been shown to be a safe alternative to BVP.

Objectives: The aim of this study was to compare the clinical outcomes between BVP and LBBAP among patients undergoing CRT.

Methods: This observational study included patients with LVEF ≤35% who underwent BVP or LBBAP for the first time for Class I or II indications for CRT from January 2018 to …

Nerve Transfer For Restoration Of Lower Motor Neuron-Lesioned Bladder, Urethral, And Anal Sphincter Function In A Dog Model. Part 3. Nicotinic Receptor Characterization, Nagat Frara, Mary F. Barbe, Dania Giaddui, Danielle S. Porreca, Alan S. Braverman, Ekta Tiwari, Attia Ahmad, Justin M. Brown, Benjamin R. Johnston, Stanley F. Bazarek, Michael R. Ruggieri

Department of Neurology Faculty Papers

Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: control (9 female and 11 male normal controls, 5 sham operated), Decentralized (9 females, decentralized 6–21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9–13 mo, then reinnervated with 8–12 mo recovery). Muscle strips were collected, mucosa-denuded, and mounted in muscle baths before incubation with neurotransmitter antagonists, and contractions to the nicotinic receptor agonist epibatidine were determined. Strip response …

Temporal Trends And Geographic Variations In Mortality Rates From Tobacco And Firearms In The United States, Sarah A Palumbo, Robert S Levine, Janet D Robishaw, Charles H Hennekens

Faculty, Staff and Students Publications

We explored temporal trends and geographic variations in United States of America (US) mortality rates from smoking and firearms from 1999 to 2019. To do so, we used the publicly available Centers for Disease Control and Prevention (CDC) Wide Ranging Online Data for Epidemiologic Research (WONDER) with Multiple Cause of Death files from 1999 to 2019. Using age-specific rates and ArcGIS Pro Advanced software for Optimized Hot Spot Analyses from Esri, we generated maps of statistically significant spatial clusters with 90-99% confidence intervals with the Getis-Ord Gi* statistic for mortality from smoking-related causes and firearms. These data show temporal trends …

Isokinetic Strength In Female Soccer Players By Player Position, Carlos Sepúlveda, Vicente Fernández, Rony Silvestre, Felipe Giancáspero, Esteban Aedo-Muñoz, Alejandro Bustamante-Garrido, Carlos Burgos-Jara, Hugo Cerda-Kohler

ISBS Proceedings Archive

This study aimed to establish reference values and compare isokinetic performance in female soccer players according to player position. Eighty-seven female soccer players from the Chilean first-division soccer clubs were evaluated in isokinetic strength. The player position was grouped as goalkeeper (GK), central defender (CD), lateral defender (LD), midfielder (MF), and forward (FW). Concentric knee extension and flexion muscle strength measurements were conducted using a standardized test protocol with an angular velocity of 60º/sec. There were no differences in peak torque of knee extension and flexion between player positions in both the dominant leg (DL) and the nondominant leg (NDL). …