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School of Medicine Faculty Publications

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Full-Text Articles in Medical Sciences

Serum Micrornas Associated With Concussion In Football Players, Dorota Wyczechowska, Paul Harch, Shelly Mullenix, Erin S. Fannin, Brenda B. Chiappinelli, Duane Jeansonne, Adam Lassak, Nicolas G. Bazan, Francesca Peruzzi Apr 2023

Serum Micrornas Associated With Concussion In Football Players, Dorota Wyczechowska, Paul Harch, Shelly Mullenix, Erin S. Fannin, Brenda B. Chiappinelli, Duane Jeansonne, Adam Lassak, Nicolas G. Bazan, Francesca Peruzzi

School of Medicine Faculty Publications

Mild Traumatic Brain Injury (mild TBI)/concussion is a common sports injury, especially common in football players. Repeated concussions are thought to lead to long-term brain damage including chronic traumatic encephalopathy (CTE). With the worldwide growing interest in studying sport-related concussion the search for biomarkers for early diagnosis and progression of neuronal injury has also became priority. MicroRNAs are short, non-coding RNAs that regulate gene expression post-transcriptionally. Due to their high stability in biological fluids, microRNAs can serve as biomarkers in a variety of diseases including pathologies of the nervous system. In this exploratory study, we have evaluated changes in the …

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Biophysical Changes Of Leukocyte Activation (And Netosis) In The Cellular Host Response To Sepsis, Matt G. Sorrells, Yurim Seo, Melia Magnen, Bliss Broussard, Roya Sheybani, Ajay M. Shah, Hollis R. O’Neal, Henry T.K. Tse, Mark R. Looney, Dino Di Carlo Apr 2023

Biophysical Changes Of Leukocyte Activation (And Netosis) In The Cellular Host Response To Sepsis, Matt G. Sorrells, Yurim Seo, Melia Magnen, Bliss Broussard, Roya Sheybani, Ajay M. Shah, Hollis R. O’Neal, Henry T.K. Tse, Mark R. Looney, Dino Di Carlo

School of Medicine Faculty Publications

Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a …

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Upregulation Of Cell Surface Glycoproteins In Correlation With Kshv Lana In The Kaposi Sarcoma Tumor Microenvironment, Sara R. Privatt, Owen Ngalamika, Jianshui Zhang, Qinsheng Li, Charles Wood, John T. West Apr 2023

Upregulation Of Cell Surface Glycoproteins In Correlation With Kshv Lana In The Kaposi Sarcoma Tumor Microenvironment, Sara R. Privatt, Owen Ngalamika, Jianshui Zhang, Qinsheng Li, Charles Wood, John T. West

School of Medicine Faculty Publications

HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein …

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Lkb1 Signaling And Patient Survival Outcomes In Hepatocellular Carcinoma, Khoa Nguyen, Katherine Hebert, Emily Mcconnell, Nicole Cullen, Thomas Cheng, Susanna Awoyode, Elizabeth Martin, Weina Chen, Tong Wu, Suresh K. Alahari, Reza Izadpanah, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow Apr 2023

Lkb1 Signaling And Patient Survival Outcomes In Hepatocellular Carcinoma, Khoa Nguyen, Katherine Hebert, Emily Mcconnell, Nicole Cullen, Thomas Cheng, Susanna Awoyode, Elizabeth Martin, Weina Chen, Tong Wu, Suresh K. Alahari, Reza Izadpanah, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow

School of Medicine Faculty Publications

The liver is a major organ that is involved in essential biological functions such as digestion, nutrient storage, and detoxification. Furthermore, it is one of the most metabolically active organs with active roles in regulating carbohydrate, protein, and lipid metabolism. Hepatocellular carcinoma is a cancer of the liver that is associated in settings of chronic inflammation such as viral hepatitis, repeated toxin exposure, and fatty liver disease. Furthermore, liver cancer is the most common cause of death associated with cirrhosis and is the 3rd leading cause of global cancer deaths. LKB1 signaling has been demonstrated to play a role in …

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Co-Occurrence Of Depression, Anxiety, And Perinatal Posttraumatic Stress In Postpartum Persons, Shelby Howard, Caitlin Witt, Karla Martin, Ateshi Bhatt, Emily Venable, Sarah Buzhardt, Andrew G. Chapple, Elizabeth F. Sutton Apr 2023

Co-Occurrence Of Depression, Anxiety, And Perinatal Posttraumatic Stress In Postpartum Persons, Shelby Howard, Caitlin Witt, Karla Martin, Ateshi Bhatt, Emily Venable, Sarah Buzhardt, Andrew G. Chapple, Elizabeth F. Sutton

School of Medicine Faculty Publications

Background: The study aim was to describe the incidence of depression, anxiety, perinatal-post-traumatic stress disorder (PTSD), and their co-occurrences in the early postpartum period in a low-resource OB/GYN clinic serving majority Medicaid-eligible persons. We hypothesized that postpartum persons screening positive for depression will have an increased risk of a positive screen for anxiety and perinatal PTSD. Methods: A retrospective study of postpartum persons receiving care in Baton Rouge, Louisiana was conducted using responses abstracted from the electronic medical record (EMR) of the Patient Health Questionnaire-9 (PHQ9), Generalized Anxiety Disorder-7 (GAD7), and Perinatal Post Traumatic Stress Disorder Questionnaire-II (PPQII). Categorical distributions …

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Decoupling Body Shape And Mass Distribution In Birds And Their Dinosaurian Ancestors, Sophie Macaulay, Tatjana Hoehfurtner, Samuel R.R. Cross, Ryan D. Marek, John R. Hutchinson, Emma R. Schachner, Alice E. Maher, Karl T. Bates Mar 2023

Decoupling Body Shape And Mass Distribution In Birds And Their Dinosaurian Ancestors, Sophie Macaulay, Tatjana Hoehfurtner, Samuel R.R. Cross, Ryan D. Marek, John R. Hutchinson, Emma R. Schachner, Alice E. Maher, Karl T. Bates

School of Medicine Faculty Publications

It is accepted that non-avian theropod dinosaurs, with their long muscular tails and small forelimbs, had a centre-of-mass close to the hip, while extant birds, with their reduced tails and enlarged wings have their mass centred more cranially. Transition between these states is considered crucial to two key innovations in the avian locomotor system: crouched bipedalism and powered flight. Here we use image-based models to challenge this dichotomy. Rather than a phylogenetic distinction between ‘dinosaurian’ and ‘avian’ conditions, we find terrestrial versus volant taxa occupy distinct regions of centre-of-mass morphospace consistent with the disparate demands of terrestrial bipedalism and flight. …

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Circulating Plasma Exosomal Proteins Of Either Shiv-Infected Rhesus Macaque Or Hiv-Infected Patient Indicates A Link To Neuropathogenesis, Partha K. Chandra, Stephen E. Braun, Sudipa Maity, Jorge A. Castorena-Gonzalez, Hogyoung Kim, Jeffrey G. Shaffer, Sinisa Cikic, Ibolya Rutkai, Jia Fan, Jessie J. Guidry, David K. Worthylake, Chenzhong Li, Asim B. Abdel-Mageed, David W. Busija Mar 2023

Circulating Plasma Exosomal Proteins Of Either Shiv-Infected Rhesus Macaque Or Hiv-Infected Patient Indicates A Link To Neuropathogenesis, Partha K. Chandra, Stephen E. Braun, Sudipa Maity, Jorge A. Castorena-Gonzalez, Hogyoung Kim, Jeffrey G. Shaffer, Sinisa Cikic, Ibolya Rutkai, Jia Fan, Jessie J. Guidry, David K. Worthylake, Chenzhong Li, Asim B. Abdel-Mageed, David W. Busija

School of Medicine Faculty Publications

Despite the suppression of human immunodeficiency virus (HIV) replication by combined antiretroviral therapy (cART), 50–60% of HIV-infected patients suffer from HIV-associated neurocognitive disorders (HAND). Studies are uncovering the role of extracellular vesicles (EVs), especially exosomes, in the central nervous system (CNS) due to HIV infection. We investigated links among circulating plasma exosomal (crExo) proteins and neuropathogenesis in simian/human immunodeficiency virus (SHIV)-infected rhesus macaques (RM) and HIV-infected and cART treated patients (Patient-Exo). Isolated EVs from SHIV-infected (SHIV-Exo) and uninfected (CTL-Exo) RM were predominantly exosomes (particle size < 150 nm). Proteomic analysis quantified 5654 proteins, of which 236 proteins (~4%) were significantly, differentially expressed (DE) between SHIV-/CTL-Exo. Interestingly, different CNS cell specific markers were abundantly expressed in crExo. Proteins involved in latent viral reactivation, neuroinflammation, neuropathology-associated interactive as well as signaling molecules were expressed at significantly higher levels in SHIV-Exo than CTL-Exo. However, proteins involved in mitochondrial biogenesis, ATP production, autophagy, endocytosis, exocytosis, and cytoskeleton organization were significantly less expressed in SHIV-Exo than CTL-Exo. Interestingly, proteins involved in oxidative stress, mitochondrial biogenesis, ATP production, and autophagy were significantly downregulated in primary human brain microvascular endothelial cells exposed with HIV+/cART+ Patient-Exo. We showed that Patient-Exo significantly increased blood–brain barrier permeability, possibly due to loss of platelet endothelial cell adhesion molecule-1 protein and actin cytoskeleton structure. Our novel findings suggest that circulating exosomal proteins expressed CNS cell markers—possibly associated with viral reactivation and neuropathogenesis—that may elucidate the etiology of HAND.

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A New Era Of Morphological Investigations: Reviewing Methods For Comparative Anatomical Studies, K. L. Ford, J. S. Albert, A. P. Summers, B. P. Hedrick, E. R. Schachner, A. S. Jones, K. Evans, P. Chakrabarty Mar 2023

A New Era Of Morphological Investigations: Reviewing Methods For Comparative Anatomical Studies, K. L. Ford, J. S. Albert, A. P. Summers, B. P. Hedrick, E. R. Schachner, A. S. Jones, K. Evans, P. Chakrabarty

School of Medicine Faculty Publications

The increased use of imaging technology in biological research has drastically altered morphological studies in recent decades and allowed for the preservation of important collection specimens alongside detailed visualization of bony and soft-tissue structures. Despite the benefits associated with these newer imaging techniques, there remains a need for more "tra- ditional"methods of morphological examination in many comparative studies. In this paper, we describe the costs and benefits of the various methods of visualizing, examining, and comparing morphological structures. There are significant differences not only in the costs associated with these different methods (monetary, time, equipment, and software), but also in …

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Patient Perspectives On Noninvasive Prenatal Testing Among Black Women In The United States: A Scoping Review, Shameka P. Thomas, Madison A. Keller, Tiara Ranson, Rachele E. Willard Mar 2023

Patient Perspectives On Noninvasive Prenatal Testing Among Black Women In The United States: A Scoping Review, Shameka P. Thomas, Madison A. Keller, Tiara Ranson, Rachele E. Willard

School of Medicine Faculty Publications

Advances in reproductive health technologies such as noninvasive prenatal testing (NIPT) are changing the landscape of prenatal care and maternal health. NIPT, made clinically available in the United States (US) in 2011, is a screening test that utilizes cell-free DNA (cfDNA) to detect for aneuploidies and genetic characteristics in fetal DNA. In September 2020, the American College of Obstetricians and Gynecologists (ACOG) recommended NIPT for all pregnant patients regardless of age or risk factors. We examined peer-reviewed, empirical studies published from January 2011 to February 2022, assessing NIPT studies with patient perspectives in the US and what is known about …

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Preclinical Perspectives On The Mechanisms Underlying The Therapeutic Actions Of Psilocybin In Psychiatric Disorders, Andreas B. Wulff, Charles D. Nichols, Scott M. Thompson Mar 2023

Preclinical Perspectives On The Mechanisms Underlying The Therapeutic Actions Of Psilocybin In Psychiatric Disorders, Andreas B. Wulff, Charles D. Nichols, Scott M. Thompson

School of Medicine Faculty Publications

Psychedelic compounds have shown extraordinary potential in treating a wide range of neuropsychiatric disorders. Psilocybin, for example, has now been shown in several clinical trials to induce a rapid (within days) and persistent (3–12 months) improvement in human treatment-resistant depression and other neuropsychiatric conditions. Here we review the preclinical models and experimental approaches that have been used to study the neurobiological actions of psychedelic drugs. We further summarize the insights these studies have provided into the possible mechanisms underlying the induction of their therapeutic actions, including the receptors to which psychedelics bind and the second messenger signaling cascades that they …

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Myo1e Overexpression In Lung Adenocarcinoma Is Associated With Increased Risk Of Mortality, Ignacio Jusue-Torres, Richies Tiv, Julio C. Ricarte-Filho, Apurva Mallisetty, Leglys Contreras-Vargas, Maria Jose Godoy-Calderon, Karam Khaddour, Kathleen Kennedy, Klara Valyi-Nagy, Odile David, Martha Menchaca, Anastasia Kottorou, Angelos Koutras, Foteinos Dimitrakopoulos, Khaled M. Abdelhady, Malek Massad, Israel Rubinstein, Lawrence Feldman, John Stewart, Takeshi Shimamura, Ludmila Danilova, Alicia Hulbert Mar 2023

Myo1e Overexpression In Lung Adenocarcinoma Is Associated With Increased Risk Of Mortality, Ignacio Jusue-Torres, Richies Tiv, Julio C. Ricarte-Filho, Apurva Mallisetty, Leglys Contreras-Vargas, Maria Jose Godoy-Calderon, Karam Khaddour, Kathleen Kennedy, Klara Valyi-Nagy, Odile David, Martha Menchaca, Anastasia Kottorou, Angelos Koutras, Foteinos Dimitrakopoulos, Khaled M. Abdelhady, Malek Massad, Israel Rubinstein, Lawrence Feldman, John Stewart, Takeshi Shimamura, Ludmila Danilova, Alicia Hulbert

School of Medicine Faculty Publications

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. …

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Induction Of Antimicrobial Protein S100a15 Expression By Oral Microbial Pathogens Is Toll-Like Receptors-Dependent Activation Of C-Jun-N-Terminal Kinase (Jnk), P38, And Nf-Κb Pathways, Denis Selimovic, Naji Kharouf, Florence Carrouel, Sofie Yasmin Hassan, Thomas W. Flanagan, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan Mar 2023

Induction Of Antimicrobial Protein S100a15 Expression By Oral Microbial Pathogens Is Toll-Like Receptors-Dependent Activation Of C-Jun-N-Terminal Kinase (Jnk), P38, And Nf-Κb Pathways, Denis Selimovic, Naji Kharouf, Florence Carrouel, Sofie Yasmin Hassan, Thomas W. Flanagan, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

The antimicrobial protein S100A15 belongs to the S100 family, which is differentially expressed in a variety of normal and pathological tissues. Although the function of S100A15 protein has been discussed in several studies, its induction and regulation in oral mucosa, so far, are largely unknown. In this study, we demonstrate that S100A15 is induced by the stimulation of oral mucosa with gram− or gram+ bacterial pathogens, as well as with the purified membrane components, namely lipopolysaccharides (LPS) and lipoteichoic acid (LTA). The stimulation of the human gingival fibroblast (GF) and the human mouth epidermal carcinoma (KB) cell lines with either …

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New Synthetic Opioids: Clinical Considerations And Dangers, Amber Edinoff, David Martinez Garza, Stephen Vining, Megan Vasterling, Eric Jackson, Kevin Murnane, Adam Kaye, Richard Fair, Yair Jose Lopez Torres, Ahmed Badr, Elyse Cornett, Alan Kaye Feb 2023

New Synthetic Opioids: Clinical Considerations And Dangers, Amber Edinoff, David Martinez Garza, Stephen Vining, Megan Vasterling, Eric Jackson, Kevin Murnane, Adam Kaye, Richard Fair, Yair Jose Lopez Torres, Ahmed Badr, Elyse Cornett, Alan Kaye

School of Medicine Faculty Publications

Since the early 2010s, synthetic opioids have significantly contributed to overall opioid-related overdose mortalities. For point of reference, of the 68,630 opioid-related deaths recorded in 2020, 56,516 involved synthetic opioids. During much of this period, fentanyl has been the most commonly used synthetic opioid. This time when fentanyl was the most popular opioid has been called the “third wave” of the opioid crisis, partly because it led to a sharp rise in deaths from overdoses. Other synthetic opioids, such as carfentanil, protonitazene, and isotonitazene, have also become more widely diverted for nonmedical used. Carfentanil is an even more potent fentanyl …

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H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam Feb 2023

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

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Conditioned Place Avoidance Is Associated With A Distinct Hippocampal Phenotype, Partly Preserved Pattern Separation, And Reduced Reactive Oxygen Species Production After Stress, D. Parker Kelley, Lucas Albrechet-Souza, Shealan Cruise, Rajani Maiya, Aspasia Destouni, Siva S.V.P. Sakamuri, Alexander Duplooy, Meghan Hibicke, Charles Nichols, Prasad V.G. Katakam, Nicholas W. Gilpin, Joseph Francis Feb 2023

Conditioned Place Avoidance Is Associated With A Distinct Hippocampal Phenotype, Partly Preserved Pattern Separation, And Reduced Reactive Oxygen Species Production After Stress, D. Parker Kelley, Lucas Albrechet-Souza, Shealan Cruise, Rajani Maiya, Aspasia Destouni, Siva S.V.P. Sakamuri, Alexander Duplooy, Meghan Hibicke, Charles Nichols, Prasad V.G. Katakam, Nicholas W. Gilpin, Joseph Francis

School of Medicine Faculty Publications

Stress is associated with contextual memory deficits, which may mediate avoidance of trauma-associated contexts in posttraumatic stress disorder. These deficits may emerge from impaired pattern separation, the independent representation of similar experiences by the dentate gyrus-Cornu Ammonis 3 (DG-CA3) circuit of the dorsal hippocampus, which allows for appropriate behavioral responses to specific environmental stimuli. Neurogenesis in the DG is controlled by mitochondrial reactive oxygen species (ROS) production, and may contribute to pattern separation. In Experiment 1, we performed RNA sequencing of the dorsal hippocampus 16 days after stress in rats that either develop conditioned place avoidance to a predator urine-associated …

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Riluzole And Novel Naphthalenyl Substituted Aminothiazole Derivatives Prevent Acute Neural Excitotoxic Injury In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Vikrant Singh, Heesung Shim, Singh Latika, Hai M. Nguyen, Yi Je Chen, Ellen Terry, Heike Wulff, Jeffrey D. Erickson Feb 2023

Riluzole And Novel Naphthalenyl Substituted Aminothiazole Derivatives Prevent Acute Neural Excitotoxic Injury In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Vikrant Singh, Heesung Shim, Singh Latika, Hai M. Nguyen, Yi Je Chen, Ellen Terry, Heike Wulff, Jeffrey D. Erickson

School of Medicine Faculty Publications

Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vitro that is inhibited by riluzole (IC50 = 1 μM), an anti-convulsant benzothiazole agent. We screened a library of riluzole derivatives and identified SKA-41 followed by a second screen and synthesized several novel chlorinated aminothiazoles (SKA-377, SKA-378, SKA-379) that are also potent MeAIB transport inhibitors in vitro, and brain penetrant following systemic administration. When …

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Evaluation Of Genetic Alterations In Hereditary Cancer Susceptibility Genes In The Ashkenazi Jewish Women Community Of Mexico, Clara Estela Díaz-Velásquez, Rina Gitler, Adriana Antoniano, Ronny Kershenovich Sefchovich, Aldo Hugo De La Cruz-Montoya, Héctor Martínez-Gregorio, Ernesto Arturo Rojas-Jiménez, Ricardo Cortez Cardoso Penha, Luis Ignacio Terrazas, Talia Wegman-Ostrosky, Ephrat Levi-Lahad, Jovanny Zabaleta, Sandra Perdomo, Felipe Vaca-Paniagua Feb 2023

Evaluation Of Genetic Alterations In Hereditary Cancer Susceptibility Genes In The Ashkenazi Jewish Women Community Of Mexico, Clara Estela Díaz-Velásquez, Rina Gitler, Adriana Antoniano, Ronny Kershenovich Sefchovich, Aldo Hugo De La Cruz-Montoya, Héctor Martínez-Gregorio, Ernesto Arturo Rojas-Jiménez, Ricardo Cortez Cardoso Penha, Luis Ignacio Terrazas, Talia Wegman-Ostrosky, Ephrat Levi-Lahad, Jovanny Zabaleta, Sandra Perdomo, Felipe Vaca-Paniagua

School of Medicine Faculty Publications

Background: Individuals of Ashkenazi Jewish ancestry have been identified as having higher prevalence of specific pathogenic variants associated with susceptibility to specific rare and chronic diseases. In Mexico, the prevalence and composition of rare cancer predisposing germline variants in Ashkenazi Jewish individuals has not been evaluated. Aim and methods: We aimed to evaluate the prevalence of pathogenic variants by massive parallel sequencing in a panel of 143 cancer-predisposing genes in 341 women from the Ashkenazi Jewish community of Mexico, who were contacted and invited to participate in the study through the ALMA Foundation for Cancer Reconstruction. Pre- and posttest genetic …

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Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer Feb 2023

Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer

School of Medicine Faculty Publications

BACKGROUND: Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2-hit” murine model. METHODS AND RESULTS: Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat …

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Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue Feb 2023

Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue

School of Medicine Faculty Publications

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue …

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Chimeric Antigen Receptor T-Cell Therapy And Hematopoiesis, Bryanna Reinhardt, Patrick Lee, Joshua P. Sasine Feb 2023

Chimeric Antigen Receptor T-Cell Therapy And Hematopoiesis, Bryanna Reinhardt, Patrick Lee, Joshua P. Sasine

School of Medicine Faculty Publications

Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment option for patients suffering from B-cell- and plasma cell-derived hematologic malignancies and is being adapted for the treatment of solid cancers. However, CAR T is associated with frequently severe toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), macrophage activation syndrome (MAS), and prolonged cytopenias—a reduction in the number of mature blood cells of one or more lineage. Although we understand some drivers of these toxicities, their mechanisms remain under investigation. Since the CAR T regimen is a complex, multi-step process with frequent adverse events, ways …

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Immunotherapeutic Targets In Non-Small Cell Lung Cancer, Habib Sadeghirad, Tayyeb Bahrami, Sepideh M. Layeghi, Hassan Yousefi, Meysam Rezaei, Seyed R. Hosseini-Fard, Payar Radfar, Majid E. Warkiani, Ken O'Byrne, Arutha Kulasinghe Feb 2023

Immunotherapeutic Targets In Non-Small Cell Lung Cancer, Habib Sadeghirad, Tayyeb Bahrami, Sepideh M. Layeghi, Hassan Yousefi, Meysam Rezaei, Seyed R. Hosseini-Fard, Payar Radfar, Majid E. Warkiani, Ken O'Byrne, Arutha Kulasinghe

School of Medicine Faculty Publications

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5-year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in-depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or …

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Yoga And Mindfulness For Social-Emotional Development And Resilience In 3–5 Year-Old Children: Non-Randomized, Controlled Intervention, Alessandra N. Bazzano, Yaoyao Sun, Yuanhao Zu, Julia M. Fleckman, Emma A. Blackson, Tejal Patel, Angie Shorty-Belisle, Keith H. Liederman, Cody Roi Jan 2023

Yoga And Mindfulness For Social-Emotional Development And Resilience In 3–5 Year-Old Children: Non-Randomized, Controlled Intervention, Alessandra N. Bazzano, Yaoyao Sun, Yuanhao Zu, Julia M. Fleckman, Emma A. Blackson, Tejal Patel, Angie Shorty-Belisle, Keith H. Liederman, Cody Roi

School of Medicine Faculty Publications

Background: Early childhood is the key life course period for development of social-emotional skills, providing the foundation for school readiness and resilience in later life. Age-appropriate yoga and mindfulness programs may contribute to the development of critical skills in children. Young children from minoritized communities that face structural racism and health disparities may benefit from programs that support social-emotional development and contribute to future academic success. Systematic reviews of yoga interventions for young children have indicated the potential for effectiveness in supporting social-emotional development, executive function, and physical activity. However, studies of yoga and mindfulness with non-White children are sparse …

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Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava Jan 2023

Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …

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Hereditary Angioedema: Diagnosis, Clinical Implications, And Pathophysiology, Evan S. Sinnathamby, Peter P. Issa, Logan Roberts, Haley Norwood, Kevin Malone, Harshitha Vemulapalli, Shahab Ahmadzadeh, Elyse M. Cornett, Sahar Shekoohi, Alan D. Kaye Jan 2023

Hereditary Angioedema: Diagnosis, Clinical Implications, And Pathophysiology, Evan S. Sinnathamby, Peter P. Issa, Logan Roberts, Haley Norwood, Kevin Malone, Harshitha Vemulapalli, Shahab Ahmadzadeh, Elyse M. Cornett, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a mutation in the C1 esterase inhibitor gene. HAE affects 1/50,000 people worldwide. Three main types of HAE exist: type I, type II, and type III. Type I is characterized by a deficiency in C1-INH. C1-INH is important in the coagulation complement, contact systems, and fibrinolysis. Most HAE cases are type I. Type I and II HAE result from a mutation in the SERPING1 gene, which encodes C1-INH. Formally known as type III HAE is typically an estrogen-dependent or hereditary angioedema with normal C1-INH activity. Current guidelines now recommend subdividing …

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Histoplasma Tympanomastoiditis: Case Report And Literature Review, Terrence Park, Gordon Love, Victoria Burke Jan 2023

Histoplasma Tympanomastoiditis: Case Report And Literature Review, Terrence Park, Gordon Love, Victoria Burke

School of Medicine Faculty Publications

Histoplasma is a dimorphic fungus capable of producing a diverse array of clinical pathology in humans dependent upon the host immune status. Acute symptomatic infection typically presents as an isolated pulmonary or nodal disease in immunocompetent patients with extra-thoracic manifestations rarely seen in this population. In this report, we describe a novel case of Histoplasma capsulatum tympanomastoiditis in an immunocompetent patient who presented with progressively worsening purulent otorrhea, vertigo, and facial nerve palsy. He was successfully managed with surgical debridement and a prolonged antifungal course.

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Educator Perspectives On Non-Technical, Discipline-Independent Skill Acquisition: An International, Qualitative Study, Jessica N. Byram, Sonya E. Van Nuland, Kelly M. Harrell, Jason C. Mussell, Jon Cornwall Jan 2023

Educator Perspectives On Non-Technical, Discipline-Independent Skill Acquisition: An International, Qualitative Study, Jessica N. Byram, Sonya E. Van Nuland, Kelly M. Harrell, Jason C. Mussell, Jon Cornwall

School of Medicine Faculty Publications

Gross anatomy education utilizing body donors and human specimens assists the acquisition of non-traditional, discipline-independent skills (NTDIS) such as teamwork, communication, and leadership. Alterations to anatomy curricula, such as those resulting from the COVID-19 pandemic, likely impact NTDIS acquisition, yet how this manifests is unclear. This study, therefore, explored anatomy educator perspectives on NTDIS acquisition as a response to changes in teaching delivery. Gross anatomy educators across different countries were recruited and took part in one-on-one, semi-structured interviews that were audio recorded and transcribed. Data were analyzed using the framework method. Basic statistical analyses were performed on demographic and categorical …

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Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura Dec 2022

Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura

School of Medicine Faculty Publications

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was …

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A Systematic Review And Meta-Analysis: Assessment Of Hospital Walking Programs Among Older Patients, Christine Loyd, Yue Zhang, Tara Weisberg, James Boyett, Elizabeth R. Huckaby, Jeri Grundhoefer, Steve Otero, Lisa Roberts, Samantha Giordano-Mooga, Carmen Capo-Lugo, Catherine H. Smith, Richard E. Kennedy, Barbara J. King, Cynthia J. Brown Nov 2022

A Systematic Review And Meta-Analysis: Assessment Of Hospital Walking Programs Among Older Patients, Christine Loyd, Yue Zhang, Tara Weisberg, James Boyett, Elizabeth R. Huckaby, Jeri Grundhoefer, Steve Otero, Lisa Roberts, Samantha Giordano-Mooga, Carmen Capo-Lugo, Catherine H. Smith, Richard E. Kennedy, Barbara J. King, Cynthia J. Brown

School of Medicine Faculty Publications

Aim: The aim of this study is to assess effect of hospital walking programs on outcomes for older inpatients and to characterize hospital walking dose reported across studies. Design: A systematic review and meta-analysis examining impact of hospital walking and/or reported walking dose among medical-surgical inpatients. For inclusion, studies were observational or experimental, published in English, enrolled inpatients aged ≥ 65 yrs hospitalized for medical or surgical reasons. Methods: Searches of PubMed, CINAHL, Embase, Scopus, NICHSR, OneSearch, ClinicalTrials.gov, and PsycINFO were completed in December 2020. Two reviewers screened sources, extracted data, and performed quality bias appraisal. Results: Hospital walking dose …

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Effects Of Substance Use Disorder On Oxidative And Antioxidative Stress Markers: A Systematic Review And Meta-Analysis, Thiago Wendt Viola, Rodrigo Orso, Luisa Fossati Florian, Miguel Gomes Garcia, Marco Giovanni Signor Gomes, Eduarda Mascarenhas Mardini, João Paulo Ottolia Niederauer, Aline Zaparte, Rodrigo Grassi-Oliveira Nov 2022

Effects Of Substance Use Disorder On Oxidative And Antioxidative Stress Markers: A Systematic Review And Meta-Analysis, Thiago Wendt Viola, Rodrigo Orso, Luisa Fossati Florian, Miguel Gomes Garcia, Marco Giovanni Signor Gomes, Eduarda Mascarenhas Mardini, João Paulo Ottolia Niederauer, Aline Zaparte, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

Recently, it has been suggested that central and peripheral toxicities identified in persons with substance use disorder (SUD) could be partially associated with an imbalance in reactive oxygen species and antioxidant defenses. We conducted a systematic review and meta-analysis to investigate whether SUD is associated with oxidative stress and to identify biomarkers possibly more affected by this condition. We have included studies that analysed oxidant and antioxidant markers in individuals with SUD caused by stimulants, alcohol, nicotine, opioids, and others (cannabis, inhalants, and polysubstance use). Our analysis showed that persons with SUD show higher oxidant markers and lower antioxidant markers …

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Impact Of Alcohol On Bone Health In People Living With Hiv: Integrating Clinical Data From Serum Bone Markers With Morphometric Analysis In A Non-Human Primate Model, Alexandra Denys, Allison Norman, Daniel S. Perrien, Larry J. Suva, Liz Simon, Lee S. Mcdaniel, Tekeda Ferguson, Kim Pedersen, David Welsh, Patricia E. Molina, Martin J.J. Ronis Nov 2022

Impact Of Alcohol On Bone Health In People Living With Hiv: Integrating Clinical Data From Serum Bone Markers With Morphometric Analysis In A Non-Human Primate Model, Alexandra Denys, Allison Norman, Daniel S. Perrien, Larry J. Suva, Liz Simon, Lee S. Mcdaniel, Tekeda Ferguson, Kim Pedersen, David Welsh, Patricia E. Molina, Martin J.J. Ronis

School of Medicine Faculty Publications

People living with HIV (PLWH) represent a vulnerable population to adverse musculoskeletal outcomes due to HIV infection, antiretroviral therapy (ART), and at-risk alcohol use. Developing measures to prevent skeletal degeneration in this group requires a grasp of the relationship between alcohol use and low bone mass in both the PLWH population and its constituents as defined by sex, age, and race. We examined the association of alcohol use with serum biochemical markers of bone health in a diverse cohort of PLWH enrolled in the New Orleans Alcohol Use in HIV (NOAH) study. To explore the effects of alcohol on bone …

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