Medicine and Health Sciences Commons^™

Gray Matter Volumes Discriminate Cognitively Impaired And Unimpaired People With Hiv, Mikki Schantell, Brittany K. Taylor, Brandon Lew, Jennifer O'Neill, Pamela E. May, Susan Swindells, Tony W. Wilson

Journal Articles: Infectious Diseases

BACKGROUND: Current diagnostic criteria of HIV-associated neurocognitive disorders (HAND) rely on neuropsychological assessments. The aim of this study was to evaluate if gray matter volumes (GMV) can distinguish people with HAND, neurocognitively unimpaired people with HIV (unimpaired PWH), and uninfected controls using linear discriminant analyses.

METHODS: A total of 231 participants, including 110 PWH and 121 uninfected controls, completed a neuropsychological assessment and an MRI protocol. Among PWH, HAND (n = 48) and unimpaired PWH (n = 62) designations were determined using the widely accepted Frascati criteria. We then assessed the extent to which GMV, corrected for intracranial volume, could …

Prophylactic Corticosteroid Use In Patients Receiving Axicabtagene Ciloleucel For Large B-Cell Lymphoma, Olalekan O. Oluwole, Krimo Bouabdallah, Javier Muñoz, Sophie De Guibert, Julie M. Vose, Nancy L. Bartlett, Yi Lin, Abhinav Deol, Peter A. Mcsweeney, Andre H. Goy, Marie José Kersten, Caron A. Jacobson, Umar Farooq, Monique C. Minnema, Catherine Thieblemont, John M. Timmerman, Patrick Stiff, Irit Avivi, Dimitrios Tzachanis, Jenny J. Kim, Zahid Bashir, Jeff Mcleroy, Yan Zheng, John M. Rossi, Lisa Johnson, Lovely Goyal, Tom Van Meerten

Journal Articles: Internal Medicine

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 10⁶ CAR-T cells/kg (day 0) …

Structural Atrophy Of The Right Superior Frontal Gyrus In Adolescents With Severe Irritability, Ji-Woo Seok, Sahil Bajaj, Brigette S. Vaughan, Arica Lerdahl, William Garvey, Alexandra Bohn, Ryan Edwards, Christopher J. Kratochvil, James Blair, Soonjo Hwang

Journal Articles: Psychiatry

Severe irritability is common in youths with psychiatric disorders and results in significant dysfunction across domains (academic, social, and familial). Prior structural MRI studies in the pediatric population demonstrated that aberrations of cortical thickness (CT) and gray matter volume (GMV) in the fronto-striatal-temporal regions which have been associated with irritability. However, the directions of the correlations between structural alteration and irritability in the individual indices were not consistent. Thus, we aim to address this by implementing comprehensive assessments of CT, GMV, and local gyrification index (LGI) simultaneously in youths with severe levels of irritability by voxel-based morphometry and surface-based morphometry. …

Elevated S-Adenosylhomocysteine Induces Adipocyte Dysfunction To Promote Alcohol-Associated Liver Steatosis, Madan Kumar Arumugam, Srinivas Chava, Karuna Rasineni, Matthew C. Paal, Terrence Donohue, Natalia A. Osna, Kusum K. Kharbanda

Journal Articles: Internal Medicine

It has been previously shown that chronic ethanol administration-induced increase in adipose tissue lipolysis and reduction in the secretion of protective adipokines collectively contribute to alcohol-associated liver disease (ALD) pathogenesis. Further studies have revealed that increased adipose S-adenosylhomocysteine (SAH) levels generate methylation defects that promote lipolysis. Here, we hypothesized that increased intracellular SAH alone causes additional related pathological changes in adipose tissue as seen with alcohol administration. To test this, we used 3-deazaadenosine (DZA), which selectively elevates intracellular SAH levels by blocking its hydrolysis. Fully differentiated 3T3-L1 adipocytes were treated in vitro for 48 h with DZA and analysed for …

Capacity Building For A New Multicenter Network Within The Echo Idea States Pediatric Clinical Trials Network, Robert D. Annett, Scott Bickel, John C. Carlson, Kelly Cowan, Sara Cox, Mark J. Fisher, J. Dean Jarvis, Alberta S. Kong, Jessica S. Kosut, Kurtis R. Kulbeth, Abbot Laptook, Pearl A. Mcelfish, Mary M. Mcnally, Lee M. Pachter, Barbara A. Pahud, Lee A. Pyles, Jennifer Shaw, Kari Simonsen, Jessica Snowden, Christine B. Turley, Andrew M. Atz

Journal Articles: Pediatrics

Introduction: Research capacity building is a critical component of professional development for pediatrician scientists, yet this process has been elusive in the literature. The ECHO IDeA States Pediatric Clinical Trials Network (ISPCTN) seeks to implement pediatric trials across medically underserved and rural populations. A key component of achieving this objective is building pediatric research capacity, including enhancement of infrastructure and faculty development. This article presents findings from a site assessment inventory completed during the initial year of the ISPCTN. Methods: An assessment inventory was developed for surveying ISPCTN sites. The inventory captured site-level activities designed to increase clinical trial research …

Accumulation Of Succinyl Coenzyme A Perturbs The Methicillin-Resistant Staphylococcus Aureus (Mrsa) Succinylome And Is Associated With Increased Susceptibility To Beta-Lactam Antibiotics, Christopher Campbell, Claire Fingleton, Merve S. Zeden, Emilio Bueno, Laura A Gallagher, Dhananjay Shinde, Jong-Sam Ahn, Heather M. Olson, Thomas L. Fillmore, Joshua N. Adkins, Fareha Razvi, Kenneth W. Bayles, Paul D. Fey, Vinai Chittezham Thomas, Felipe Cava, Geremy C. Clair, James P. O'Gara

Journal Articles: Pathology and Microbiology

Penicillin binding protein 2a (PBP2a)-dependent resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) is regulated by the activity of the tricarboxylic acid (TCA) cycle via a poorly understood mechanism. We report that mutations in sucC and sucD, but not other TCA cycle enzymes, negatively impact β-lactam resistance without changing PBP2a expression. Increased intracellular levels of succinyl coenzyme A (succinyl-CoA) in the sucC mutant significantly perturbed lysine succinylation in the MRSA proteome. Suppressor mutations in sucA or sucB, responsible for succinyl-CoA biosynthesis, reversed sucC mutant phenotypes. The major autolysin (Atl) was the most succinylated protein in the proteome, …

The Prospect Of Nanoparticle Systems For Modulating Immune Cell Polarization During Central Nervous System Infection, Lee E. Korshoj, Wen Shi, Bin Duan, Tammy Kielian

Journal Articles: Pathology and Microbiology

The blood-brain barrier (BBB) selectively restricts the entry of molecules from peripheral circulation into the central nervous system (CNS) parenchyma. Despite this protective barrier, bacteria and other pathogens can still invade the CNS, often as a consequence of immune deficiencies or complications following neurosurgical procedures. These infections are difficult to treat since many bacteria, such as Staphylococcus aureus, encode a repertoire of virulence factors, can acquire antibiotic resistance, and form biofilm. Additionally, pathogens can leverage virulence factor production to polarize host immune cells towards an anti-inflammatory phenotype, leading to chronic infection. The difficulty of pathogen clearance is magnified by …

Patient-Reported Outcomes Through 1 Year Of An Hiv-1 Clinical Trial Evaluating Long-Acting Cabotegravir And Rilpivirine Administered Every 4 Or 8 Weeks (Atlas-2m), Vasiliki Chounta, Edgar T. Overton, Anthony Mills, Susan Swindells, Paul D. Benn, Simon Vanveggel, Rodica Van Solingen-Ristea, Yuanyuan Wang, Krischan J. Hudson, Mark S. Shaefer, David A. Margolis, Kimberly Y. Smith, William R. Spreen

Journal Articles: Infectious Diseases

BACKGROUND: Advances in HIV-1 therapeutics have led to the development of a range of daily oral treatment regimens, which share similar high efficacy rates. Consequently, more emphasis is being placed upon the individual's experience of treatment and impact on quality of life. The first long-acting injectable antiretroviral therapy for HIV-1 (long-acting cabotegravir + rilpivirine [CAB + RPV LA]) may address challenges associated with oral treatment for HIV-1, such as stigma, pill burden/fatigue, drug-food interactions, and adherence. Patient-reported outcomes (PROs) collected in an HIV-1 clinical trial (ATLAS-2M; NCT03299049) comparing participants' experience with two dosing regimens (every 4 weeks [Q4W] vs. every …

Is Biventricular Vascular Coupling A Better Indicator Of Ventriculo-Ventricular Interaction In Congenital Heart Disease?, Emily L. Yang, Shelby Kutty, Brian D. Soriano, Sathish Mallenahalli, Mark R. Ferguson, Mark B. Lewin, Sujatha Buddhe

Journal Articles: Pediatrics

BACKGROUND: Ventriculo-ventricular interactions are known to exist, though not well quantified. We hypothesised that the ventricular-vascular coupling ratio assessed by cardiovascular MRI would provide insight into this relationship. We also sought to compare MRI-derived ventricular-vascular coupling ratio to echocardiography and patient outcomes.

METHODS: Children with cardiac disease and biventricular physiology were included. Sanz's and Bullet methods were used to calculate ventricular-vascular coupling ratio by MRI and echocardiography, respectively. Subgroup analysis was performed for right and left heart diseases. Univariate and multivariate regressions were performed to determine associations with outcomes.

RESULTS: A total of 55 patients (age 14.3 ± 2.5 years) …

Natural Recovery By The Liver And Other Organs After Chronic Alcohol Use, Paul G. Thomes, Karuna Rasineni, Viswanathan Saraswathi, Kusum K. Kharbanda, Dahn L. Clemens, Sarah A. Sweeney, Jacy L. Kubik, Terrence M. Donohue, Carol A. Casey

Journal Articles: Internal Medicine

Chronic, heavy alcohol consumption disrupts normal organ function and causes structural damage in virtually every tissue of the body. Current diagnostic terminology states that a person who drinks alcohol excessively has alcohol use disorder. The liver is especially susceptible to alcohol-induced damage. This review summarizes and describes the effects of chronic alcohol use not only on the liver, but also on other selected organs and systems affected by continual heavy drinking-including the gastrointestinal tract, pancreas, heart, and bone. Most significantly, the recovery process after cessation of alcohol consumption (abstinence) is explored. Depending on the organ and whether there is relapse, …

Extracellular Vesicles From Infected Cells Are Released Prior To Virion Release, Yuriy Kim, Gifty A. Mensah, Sarah Al Sharif, Daniel O. Pinto, Heather Branscome, Sowmya V. Yelamanchili, Maria Cowen, James Erickson, Pooja Khatkar, Renaud Mahieux, Fatah Kashanchi

Journal Articles: Anesthesiology

Here, we have attempted to address the timing of EV and virion release from virally infected cells. Uninfected (CEM), HIV-1-infected (J1.1), and human T cell leukemia virus-1 (HTLV-1)-infected (HUT102) cells were synchronized in G₀. Viral latency was reversed by increasing gene expression with the addition of serum-rich media and inducers. Supernatants and cell pellets were collected post-induction at different timepoints and assayed for extracellular vesicle (EV) and autophagy markers; and for viral proteins and RNAs. Tetraspanins and autophagy-related proteins were found to be differentially secreted in HIV-1- and HTLV-1-infected cells when compared with uninfected controls. HIV-1 proteins were …

Properties Of Multivesicular Release From Mouse Rod Photoreceptors Support Transmission Of Single-Photon Responses, Cassandra L. Hays, Asia L. Sladek, Greg D. Field, Wallace B. Thoreson

Journal Articles: Ophthalmology

Vision under starlight requires rod photoreceptors to transduce and transmit single-photon responses to the visual system. Small single-photon voltage changes must therefore cause detectable reductions in glutamate release. We found that rods achieve this by employing mechanisms that enhance release regularity and its sensitivity to small voltage changes. At the resting membrane potential in darkness, mouse rods exhibit coordinated and regularly timed multivesicular release events, each consisting of ~17 vesicles and occurring two to three times more regularly than predicted by Poisson statistics. Hyperpolarizing rods to mimic the voltage change produced by a single photon abruptly reduced the probability of …

Multi-Level Considerations For Optimal Implementation Of Long-Acting Injectable Antiretroviral Therapy To Treat People Living With Hiv: Perspectives Of Health Care Providers Participating In Phase 3 Trials, Andrea Mantsios, Miranda Murray, Tahilin S. Karver, Wendy Davis, Noya Galai, Princy Kumar, Susan Swindells, U. Fritz Bredeek, Rafael Rubio García, Antonio Antela, Santiago Cenoz Gomis, Miguel Pascual Bernáldez, Maggie Czarnogorski, Krischan Hudson, Nicki Walters, Deanna Kerrigan

Journal Articles: Infectious Diseases

BACKGROUND: Long-acting injectable antiretroviral therapy (LA ART) has been shown to be non-inferior to daily oral ART, with high patient satisfaction and preference to oral standard of care in research to date, and has recently been approved for use in the United States and Europe. This study examined the perspectives of health care providers participating in LA ART clinical trials on potential barriers and solutions to LA ART roll-out into real world settings.

METHODS: This analysis draws on two data sources: (1) open-ended questions embedded in a structured online survey of 329 health care providers participating in the ATLAS-2 M …

Integrative Network Analyses Of Transcriptomics Data Reveal Potential Drug Targets For Acute Radiation Syndrome, Robert Moore, Bhanwar Lal Puniya, Robert Powers, Chittibabu Guda, Kenneth W. Bayles, David B. Berkowitz, Tomáš Helikar

Journal Articles: Pathology and Microbiology

Recent political unrest has highlighted the importance of understanding the short- and long-term effects of gamma-radiation exposure on human health and survivability. In this regard, effective treatment for acute radiation syndrome (ARS) is a necessity in cases of nuclear disasters. Here, we propose 20 therapeutic targets for ARS identified using a systematic approach that integrates gene coexpression networks obtained under radiation treatment in humans and mice, drug databases, disease-gene association, radiation-induced differential gene expression, and literature mining. By selecting gene targets with existing drugs, we identified potential candidates for drug repurposing. Eight of these genes (BRD4, NFKBIA, CDKN1A, TFPI, MMP9, …

Drug Susceptibility Patterns Of Mycobacterium Tuberculosis From Adults With Multidrug-Resistant Tuberculosis And Implications For A Household Contact Preventive Therapy Trial, Anne-Marie Demers, Soyeon Kim, Sara Mccallum, Kathleen Eisenach, Michael Hughes, Linda Naini, Alberto Mendoza-Ticona, Neeta Pradhan, Kim Narunsky, Selvamuthu Poongulali, Sharlaa Badal-Faesen, Caryn Upton, Elizabeth Smith, N Sarita Shah, Gavin Churchyard, Amita Gupta, Anneke Hesseling, Susan Swindells, Actg A5300/Impaact I2003 Phoenix Feasibility Study Team

Journal Articles: Internal Medicine

BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs).

METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations …

Lipid Droplet Membrane Proteome Remodeling Parallels Ethanol-Induced Hepatic Steatosis And Its Resolution, Carol A. Casey, Terrence Donohue, Jacy L. Kubik, Vikas Kumar, Michael J. Naldrett, Nicholas T. Woods, Cole P. Frisbie, Mark A. Mcniven, Paul G. Thomes

Journal Articles: Internal Medicine

Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains poorly understood. We hypothesized that chronic ethanol consumption, subsequent abstinence from ethanol, or fasting differentially affects the LD membrane proteome content and that these changes influence how LDs interact with other intracellular organelles. Here, male Wistar rats were pair-fed liquid control or ethanol diets for 6 weeks, and then, randomly chosen animals from both groups were either refed …

Echocardiographic Screening Of Anomalous Origin Of Coronary Arteries In Athletes With A Focus On High Take-Off, Massimiliano Cantinotti, Raffaele Giordano, Nadia Assanta, Martin Koestenberger, Eliana Franchi, Pietro Marchese, Alberto Clemente, Shelby Kutty, Flavio D'Ascenzi

Journal Articles: Pediatrics

Anomalous aortic origin of coronary arteries (AAOCA) represents a rare congenital heart disease. However, this disease is the second most common cause of sudden cardiac death in apparently healthy athletes. The aim of this systematic review is to analyze the feasibility and the detection rate of AAOCA by echocardiography in children and adults. A literature search was performed within the National Library of Medicine using the following keywords: coronary artery origin anomalies and echocardiography; then, the search was redefined by adding the keywords: athletes, children, and high take-off. Nine echocardiographic studies investigating AAOCA and a total of 33,592 children and …

Phenotypes Of Adults With Congenital Heart Disease Around The Globe: A Cluster Analysis, Edward Callus, Silvana Pagliuca, Sara Boveri, Federico Ambrogi, Koen Luyckx, Adrienne H. Kovacs, Silke Apers, Werner Budts, Junko Enomoto, Maayke A. Sluman, Jou-Kou Wang, Jamie L. Jackson, Paul Khairy, Stephen C. Cook, Shanthi Chidambarathanu, Luis Alday, Katrine Eriksen, Mikael Dellborg, Malin Berghammer, Bengt Johansson, Andrew S. Mackie, Samuel Menahem, Maryanne Caruana, Gruschen Veldtman, Alexandra Soufi, Susan M. Fernandes, Kamila White, Shelby Kutty, Philip Moons, Approach-Is Consortium And The International Society For Adult Congenital Heart Disease (Isachd)

Journal Articles: Pediatrics

OBJECTIVE: To derive cluster analysis-based groupings for adults with congenital heart disease (ACHD) when it comes to perceived health, psychological functioning, health behaviours and quality of life (QoL).

METHODS: This study was part of a larger worldwide multicentre study called APPROACH-IS; a cross sectional study which recruited 4028 patients (2013-2015) from 15 participating countries. A hierarchical cluster analysis was performed using Ward's method in order to group patients with similar psychological characteristics, which were defined by taking into consideration the scores of the following tests: Sense Of Coherence, Health Behavior Scale (physical exercise score), Hospital Anxiety Depression Scale, Illness Perception …

Intrauterine Transfer Of Polyunsaturated Fatty Acids In Mother–Infant Dyads As Analyzed At Time Of Delivery, Vanessa Woodward, Melissa K. Thoene, Matthew Van Ormer, Maranda Thompson, Corrine K. Hanson, Sathish Kumar Natarajan, Maheswari Mukherjee, Ana G. Yuil-Valdes, Tara M. Nordgren, Arzu Ulu, Kristina Harris Jackson, Ann Anderson-Berry

Journal Articles: Pediatrics

Polyunsaturated fatty acids (PUFAs) are essential for fetal development, and intrauterine transfer is the only supply of PUFAs to the fetus. The prevailing theory of gestational nutrient transfer is that certain nutrients (including PUFAs) may have prioritized transport across the placenta. Numerous studies have identified correlations between maternal and infant fatty acid concentrations; however, little is known about what role maternal PUFA status may play in differential intrauterine nutrient transfer. Twenty mother–infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood, and placental tissue samples. Plasma concentrations of PUFAs were assessed using gas chromatography (GC-FID). Intrauterine …

Integrated Systems Analysis Of Mixed Neuroglial Cultures Proteome Post Oxycodone Exposure, Rahul Guda, Katherine E. Odegaard, Chengxi Tan, Victoria L. Schaal, Sowmya V. Yelamanchili, Gurudutt Pendyala

Journal Articles: Anesthesiology

Opioid abuse has become a major public health crisis that affects millions of individuals across the globe. This widespread abuse of prescription opioids and dramatic increase in the availability of illicit opioids have created what is known as the opioid epidemic. Pregnant women are a particularly vulnerable group since they are prescribed for opioids such as morphine, buprenorphine, and methadone, all of which have been shown to cross the placenta and potentially impact the developing fetus. Limited information exists regarding the effect of oxycodone (oxy) on synaptic alterations. To fill this knowledge gap, we employed an integrated system approach to …

Child Health And The Implementation Of Community And District-Management Empowerment For Scale-Up (Codes) In Uganda: A Randomised Controlled Trial, Peter Waiswa, Flavia Mpanga, Danstan Bagenda, Rornald Muhumuza Kananura, Thomas O'Connell, Dorcus Kiwanuka Henriksson, Theresa Diaz, Florence Ayebare, Anne Ruhweza Katahoire, Eric Ssegujja, Anthony Mbonye, Stefan Swartling Peterson

Journal Articles: Anesthesiology

INTRODUCTION: Uganda's district-level administrative units buttress the public healthcare system. In many districts, however, local capacity is incommensurate with that required to plan and implement quality health interventions. This study investigates how a district management strategy informed by local data and community dialogue influences health services.

METHODS: A 3-year randomised controlled trial (RCT) comprised of 16 Ugandan districts tested a management approach, Community and District-management Empowerment for Scale-up (CODES). Eight districts were randomly selected for each of the intervention and comparison areas. The approach relies on a customised set of data-driven diagnostic tools to identify and resolve health system bottlenecks. …

A Holistic Systems Approach To Characterize The Impact Of Pre- And Post-Natal Oxycodone Exposure On Neurodevelopment And Behavior, Katherine E. Odegaard, Victoria L. Schaal, Alexander R. Clark, Sneh Koul, Jagadesan Sankarasubramanian, Zhiqiu Xia, Melissa Mellon, Mariano Uberti, Yutong Liu, Andrew Stothert, Matthew J. Van Hook, Han-Jun Wang, Chittibabu Guda, Steven J. Lisco, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Background: Increased risk of oxycodone (oxy) dependency during pregnancy has been associated with altered behaviors and cognitive deficits in exposed offspring. However, a significant knowledge gap remains regarding the effect of in utero and postnatal exposure on neurodevelopment and subsequent behavioral outcomes. Methods: Using a preclinical rodent model that mimics oxy exposure in utero (IUO) and postnatally (PNO), we employed an integrative holistic systems biology approach encompassing proton magnetic resonance spectroscopy (¹H-MRS), electrophysiology, RNA-sequencing, and Von Frey pain testing to elucidate molecular and behavioral changes in the exposed offspring during early neurodevelopment as well as adulthood. Results: ^{1 …}

A Comprehensive Study To Delineate The Role Of An Extracellular Vesicle-Associated Microrna-29a In Chronic Methamphetamine Use Disorder, Subhash Chand, Austin Gowen, Mason Savine, Dalia Moore, Alexander Clark, Wendy Huynh, Niming Wu, Katherine Odegaard, Lucas Weyrich, Rick A. Bevins, Howard S. Fox, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Extracellular vesicles (EVs), which express a repertoire of cargo molecules (cf. proteins, microRNA, lipids, etc.), have been garnering a prominent role in the modulation of several cellular processes. Here, using both non-human primate and rodent model systems, we provide evidence that brain-derived EV (BDE) miRNA, miR-29a-3p (mir-29a), is significantly increased during chronic methamphetamine (MA) exposure. Further, miR-29a levels show significant increase both with drug-seeking and reinstatement in a rat MA self-administration model. We also show that EV-associated miR-29a is enriched in EV pool comprising of small EVs and exomeres and further plays a critical role in MA-induced inflammation and synaptodendritic …

Neural Responses To Fluoxetine In Youths With Disruptive Behavior And Trauma Exposure: A Pilot Study, Soonjo Hwang, Unsun Chung, Yongmin Chang, Eunji Kim, Ji-Woo Suk, Harma Meffert, Christopher J. Kratochvil, Ellen Leibenluft, James Blair

Journal Articles: Psychiatry

Objective: A preliminary investigation of the impact of a serotonergic agent (fluoxetine) on symptom profile and neural response in youths with disruptive behavior disorders (DBDs) and a history of trauma exposure. Methods: There were three participant groups: (i) Youths with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 11); (ii) A matched group of youths with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 10); and (iii) Typically developing youths (n = 18). All participants conducted an expression processing functional magnetic resonance imaging task twice, …

The Promise Of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are The Data?, Kimberly Scarsi, Susan Swindells

Journal Articles: Infectious Diseases

As with other chronic conditions, adherence to daily medications remains a challenge for many individuals living with HIV due to structural, behavioral, and social barriers. Unfortunately, high levels of adherence to antiretroviral therapy are required to maintain virologic suppression. Alternative approaches are being explored to decrease the burden of daily pill administration, including long-acting injectable, oral, and implantable products. Phase 3 data support the efficacy of nanoformulated injectable cabotegravir and rilpivirine for HIV treatment in patients with undetectable viremia, but we have yet to learn how this strategy may benefit those with medication adherence challenges. Despite this, the affected community …

A Midwestern Academic Hiv Clinic Operation During The Covid-19 Pandemic: Implementation Strategy And Preliminary Outcomes, Nada Fadul, Nichole Regan, Layan Kaddoura, Susan Swindells

Journal Articles: Infectious Diseases

During the COVID-19 pandemic, HIV clinics had to transform care delivery for people with HIV (PWH). We developed a multifaceted telehealth implementation strategy and monitored number of out of care patients (OOC), medical visit frequency (MVF), gap in care (GiC) and viral suppression (VS), and compared measures to baseline data. Between April and October 2020, 1559 visits were scheduled; 328 (21%) were missed, and 63 (4%) were new to care. Of the remaining 1168 follow-up visits, 412 (35%) were telehealth visits. As of October 2020, there were 53 patients OOC, MVF was 55% and GiC was 24% compared to 34, …

Intraventricular Septation In The Context Of Dilated Cardiomyopathy Associated With Ttn Mutation, Karl R. Khandalavala, Jean A. Ballweg, Stanley J. Radio, Jeffrey A. Robinson

Journal Articles: Pediatrics

A 6-month-old infant boy presented with symptomatic heart failure. Dilated cardiomyopathy was found in association with a mutation in TTN. Structural heart disease included novel septation of the left ventricle with a fenestrated membrane resulting from aberrant congenital mitral valve apparatus formation. (Level of Difficulty: Advanced.).

High-Throughput Analysis Of Lung Immune Cells In A Combined Murine Model Of Agriculture Dust-Triggered Airway Inflammation With Rheumatoid Arthritis, Rohit Gaurav, Ted R. Mikuls, Geoffrey M. Thiele, Amy J. Nelson, Meng Niu, Chittibabu Guda, James D. Eudy, Austin E. Barry, Todd A. Wyatt, Debra J. Romberger, Michael J. Duryee, Bryant R. England, Jill A. Poole

Journal Articles: Internal Medicine

Rheumatoid arthritis (RA)-associated lung disease is a leading cause of mortality in RA, yet the mechanisms linking lung disease and RA remain unknown. Using an established murine model of RA-associated lung disease combining collagen-induced arthritis (CIA) with organic dust extract (ODE)-induced airway inflammation, differences among lung immune cell populations were analyzed by single cell RNA-sequencing. Additionally, four lung myeloid-derived immune cell populations including macrophages, monocytes/macrophages, monocytes, and neutrophils were isolated by fluorescence cell sorting and gene expression was determined by NanoString analysis. Unsupervised clustering revealed 14 discrete clusters among Sham, CIA, ODE, and CIA+ODE treatment groups: 3 neutrophils (inflammatory, resident/transitional, …

Alcohol-Induced Lysosomal Damage And Suppression Of Lysosome Biogenesis Contribute To Hepatotoxicity In Hiv-Exposed Liver Cells, Moses New-Aaron, Paul G. Thomes, Murali Ganesan, Raghubendra Singh Dagur, Terrence Donohue, Kusum K. Kharbanda, Larisa Y. Poluektova, Natalia A. Osna

Journal Articles: Internal Medicine

Although the causes of hepatotoxicity among alcohol-abusing HIV patients are multifactorial, alcohol remains the least explored “second hit” for HIV-related hepatotoxicity. Here, we investigated whether metabolically derived acetaldehyde impairs lysosomes to enhance HIV-induced hepatotoxicity. We exposed Cytochrome P450 2E1 (CYP2E1)-expressing Huh 7.5 (also known as RLW) cells to an acetaldehyde-generating system (AGS) for 24 h. We then infected (or not) the cells with HIV-1_ADA then exposed them again to AGS for another 48 h. Lysosome damage was assessed by galectin 3/LAMP1 co-localization and cathepsin leakage. Expression of lysosome biogenesis–transcription factor, TFEB, was measured by its protein levels and by …

Collagen Fiber Regulation In Human Pediatric Aortic Valve Development And Disease, Cassandra L. Clift, Yan Ru Su, David Bichell, Heather Jensen Smith, Jennifer R. Bethard, Kim Norris-Caneda, Susana Comte-Walters, Lauren E. Ball, Michael A. Hollingsworth, Anand S. Mehta, Richard R. Drake, Peggi M. Angel

Journal Articles: Eppley Institute

Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics to investigate collagen fiber production with collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of high-density collagen in pCAVS. Proteomic analysis reported specific collagen peptides are modified by hydroxylated prolines (HYP), …