Medicine and Health Sciences Commons^™

Lecanemab In Early Alzheimer's Disease, Christopher H Van Dyck, Randall J Bateman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer's disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, is being tested in persons with early Alzheimer's disease.

METHODS: We conducted an 18-month, multicenter, double-blind, phase 3 trial involving persons 50 to 90 years of age with early Alzheimer's disease (mild cognitive impairment or mild dementia due to Alzheimer's disease) with evidence of amyloid on positron-emission tomography (PET) or by cerebrospinal fluid testing. Participants were randomly assigned in a 1:1 ratio to receive intravenous lecanemab …

Olutasidenib (Ft-2102) In Patients With Relapsed Or Refractory Idh1-Mutant Glioma: A Multicenter, Open-Label, Phase Ib/Ii Trial, Macarena I De La Fuente, Brian A Van Tine, Et Al.

2020-Current year OA Pubs

BACKGROUND: Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation.

METHODS: This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1R132X-mutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety …

Alcohol Consumption And Epigenetic Age Acceleration In Young Adults, Drew R Nannini, Lei Liu, Et Al.

2020-Current year OA Pubs

Alcohol is a widely consumed substance in the United States, however its effect on aging remains understudied. In this study of young adults, we examined whether cumulative alcohol consumption, i.e., alcohol years of beer, liquor, wine, and total alcohol, and recent binge drinking, were associated with four measures of age-related epigenetic changes via blood DNA methylation. A random subset of study participants in the Coronary Artery Risk Development in Young Adults Study underwent DNA methylation profiling using the Illumina MethylationEPIC Beadchip. Participants with alcohol consumption and methylation data at examination years 15 (

Preclinical Studies In Krabbe Disease: A Model For The Investigation Of Novel Combination Therapies For Lysosomal Storage Diseases, Gregory Heller, Allison M Bradbury, Mark S Sands, Ernesto R Bongarzone

2020-Current year OA Pubs

Krabbe disease (KD) is a lysosomal storage disease (LSD) caused by mutations in the galc gene. There are over 50 monogenetic LSDs, which largely impede the normal development of children and often lead to premature death. At present, there are no cures for LSDs and the available treatments are generally insufficient, short acting, and not without co-morbidities or long-term side effects. The last 30 years have seen significant advances in our understanding of LSD pathology as well as treatment options. Two gene therapy-based clinical trials, NCT04693598 and NCT04771416, for KD were recently started based on those advances. This review will …

Individual Differences In Naturalistic Learning Link Negative Emotionality To The Development Of Anxiety, William J Villano, Noah I Kraus, Travis R Reneau, Brittany A Jaso, A Ross Otto, Aaron S Heller

2020-Current year OA Pubs

Organisms learn from prediction errors (PEs) to predict the future. Laboratory studies using small financial outcomes find that humans use PEs to update expectations and link individual differences in PE-based learning to internalizing disorders. Because of the low-stakes outcomes in most tasks, it is unclear whether PE learning emerges in naturalistic, high-stakes contexts and whether individual differences in PE learning predict psychopathology risk. Using experience sampling to assess 625 college students' expected exam grades, we found evidence of PE-based learning and a general tendency to discount negative PEs, an "optimism bias." However, individuals with elevated negative emotionality, a personality trait …

Provider Beliefs In Effectiveness And Recommendations For Primary Hpv Testing In 3 Health-Care Systems, Gina R Kruse, Jacquelyn M Lykken, Eric J Kim, Jennifer S Haas, Robin T Higashi, Steven J Atlas, Anne Marie Mccarthy, Jasmin A Tiro, Michelle I Silver, Celette S Skinner, Aruna Kamineni

2020-Current year OA Pubs

In 2018, the US Preventive Services Task Force endorsed primary human papillomavirus testing (pHPV) for cervical cancer screening. We aimed to describe providers' beliefs about pHPV testing effectiveness and which screening approach they regularly recommend. We invited providers who performed 10 or more cervical cancer screens in 2019 in 3 healthcare systems that had not adopted pHPV testing: Kaiser Permanente Washington, Mass General Brigham, and Parkland Health; 53.7% (501/933) completed the survey between October and December 2020. Response distributions varied across modalities (P < .001), with cytology alone or cotesting being more often viewed as somewhat or very effective for 30- to 65-year-olds compared with pHPV (cytology alone 94.1%, cotesting 96.1%, pHPV 66.0%). In 21- to 29-year-olds, the pattern was similar (cytology alone 92.2%, 64.7% cotesting, 50.8% pHPV). Most providers were either incorrect or unsure of the guideline-recommended screening interval for pHPV. Educational efforts are needed about the relative effectiveness and recommended use of pHPV to promote guideline-concordant care.

Large Variations In The Prices Of Urologic Procedures At Academic Medical Centers 1 Year After Implementation Of The Price Transparency Final Rule, Zeynep G Gul, Danielle R Sharbaugh, Cailey J Guercio, Daniel L Pelzman, Cameron A Jones, Emily C Hacker, Vivian I Anyaeche, Levi Bowers, Ashti M Shah, Michael G Stencel, Jonathan G Yabes, Bruce L Jacobs, Benjamin J Davies

2020-Current year OA Pubs

IMPORTANCE: Patients with urologic diseases often experience financial toxicity, defined as high levels of financial burden and concern, after receiving care. The Price Transparency Final Rule, which requires hospitals to disclose both the commercial and cash prices for at least 300 services, was implemented to facilitate price shopping, decrease price dispersion, and lower health care costs.

OBJECTIVE: To evaluate compliance with the Price Transparency Final Rule and to quantify variations in the price of urologic procedures among academic hospitals and by insurance class.

DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study that determined the prices of 5 common urologic …

Effect Of A Muc5ac Antibody (Npc-1c) Administered With Second-Line Gemcitabine And Nab-Paclitaxel On The Survival Of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial, Brandon M Huffman, Andrea Wang-Gillam, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel.

OBJECTIVE: To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis …

Arginine Methylation Of The Pgc-1Α C-Terminus Is Temperature-Dependent, Meryl Mendoza, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia I. Zurita-Lopez

2020-Current year OA Pubs

We set out to determine whether the C-terminus (amino acids 481-798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed

Association Of State Insurance Mandates For Fertility Treatment With Multiple Embryo Transfer After Preimplantation Genetic Testing For Aneuploidy, Bronwyn S Bedrick, Katelin B Nickel, Joan K Riley, Tarun Jain, Emily S Jungheim

2020-Current year OA Pubs

IMPORTANCE: Multiple gestation is one of the biggest risks after in vitro fertilization (IVF), largely due to multiple embryo transfer (MET). Single embryo transfer (SET) uptake has increased over time and has been attributed to various factors, such as mandated insurance coverage for IVF and preimplantation genetic testing for aneuploidy (PGT-A).

OBJECTIVE: To investigate whether mandates for IVF insurance coverage are associated with decreased use of MET after PGT-A.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using data on embryo transfers reported to the Society for Assisted Reproductive Technology between 2014 and 2016. Data were analyzed from January …

Magnify Is A Universal Molecular Anchoring Strategy For Expansion Microscopy, Aleksandra Klimas, Brendan R Gallagher, Piyumi Wijesekara, Sinda Fekir, Emma F Dibernardo, Zhangyu Cheng, Donna B Stolz, Franca Cambi, Simon C Watkins, Steven L Brody, Amjad Horani, Alison L Barth, Christopher I Moore, Xi Ren, Yongxin Zhao

2020-Current year OA Pubs

Expansion microscopy enables nanoimaging with conventional microscopes by physically and isotropically magnifying preserved biological specimens embedded in a crosslinked water-swellable hydrogel. Current expansion microscopy protocols require prior treatment with reactive anchoring chemicals to link specific labels and biomolecule classes to the gel. We describe a strategy called Magnify, which uses a mechanically sturdy gel that retains nucleic acids, proteins and lipids without the need for a separate anchoring step. Magnify expands biological specimens up to 11 times and facilitates imaging of cells and tissues with effectively around 25-nm resolution using a diffraction-limited objective lens of about 280 nm on conventional …

Chronic Trem2 Activation Exacerbates Aβ-Associated Tau Seeding And Spreading, Nimansha Jain, Caroline A Lewis, Jason D Ulrich, David M Holtzman

2020-Current year OA Pubs

Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene are associated with increased risk for late-onset AD. Genetic loss of or decreased TREM2 function impairs the microglial response to amyloid-β (Aβ) plaques, resulting in more diffuse Aβ plaques and increased peri-plaque neuritic dystrophy and AD-tau seeding. Thus, microglia and TREM2 are at a critical intersection of Aβ and tau pathologies in AD. Since genetically decreasing TREM2 function increases Aβ-induced tau seeding, we hypothesized that chronically increasing TREM2 signaling would decrease amyloid-induced tau-seeding and spreading. Using a mouse model of amyloidosis in which AD-tau is injected into the …

Baricitinib With Cyclosporine Eliminates Acute Graft Rejection In Fully Mismatched Skin And Heart Transplant Models, Ramzi Abboud, Sena Kim, Karl Staser, Reyka G Jayasinghe, Sora Lim, Parmeshwar Amatya, C Corbin Frye, Benjamin Kopecky, Julie Ritchey, Feng Gao, Kory Lavine, Daniel Kreisel, John F Dipersio, Jaebok Choi

2020-Current year OA Pubs

Solid organ transplant represents a potentially lifesaving procedure for patients suffering from end-stage heart, lung, liver, and kidney failure. However, rejection remains a significant source of morbidity and immunosuppressive medications have significant toxicities. Janus kinase (JAK) inhibitors are effective immunosuppressants in autoimmune diseases and graft versus host disease after allogeneic hematopoietic cell transplantation. Here we examine the role of JAK inhibition in preclinical fully major histocompatibility mismatched skin and heart allograft models. Baricitinib combined with cyclosporine A (CsA) preserved fully major histocompatibility mismatched skin grafts for the entirety of a 111-day experimental period. In baricitinib plus CsA treated mice, circulating …

Gene-Educational Attainment Interactions In A Multi-Population Genome-Wide Meta-Analysis Identify Novel Lipid Loci, Lisa De Las Fuentes, Karen L. Schwander, Yun Ju Sung, Mary F. Feitosa, Ahn Do, C. Charles Gu, Treva K. Rice, Mary K. Wojczynski, Michael M. Province, Dabeeru C. Rao, Et Al.

2020-Current year OA Pubs

No abstract provided.

Necrotic Cardiac Myocytes Skew Macrophage Polarization Towards A Classically Activated Phenotype, Wenlong Jiang, Luigi Adamo, Kenji Lim, Scot J Matkovich, Sarah Evans, Cibele Rocha-Resende, Douglas L. Mann

2020-Current year OA Pubs

Necrotic and dying cells release damage-associated molecular patterns (DAMPs) that can initiate sterile inflammatory responses in the heart. Although macrophages are essential for myocardial repair and regeneration, the effect of DAMPs on macrophage activation remains unclear. To address this gap in knowledge we studied the effect of necrotic cardiac myocyte extracts on primary peritoneal macrophage (PPM) cultures in vitro. We first performed unbiased transcriptomic profiling with RNA-sequencing of PPMs cultured for up to 72 hours in the presence and absence of: 1) necrotic cell extracts (NCEs) from necrotic cardiac myocytes in order to mimic the release of DAMPs; 2) lipopolysaccharide …

Leveraging Health Infrastructure To Optimize Hpv Vaccination For Adolescents In Zambia: Protocol For An Implementation Study, Sam Miti, Thembekile Shato, Comfort Asante, Ana Baumann, Gershom Chongwe, Patricia M. Bobo, Michelle I. Silver, Jean M. Hunleth

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is the leading cause of cancer death in Zambia, where HIV prevalence is also high (11.3%). HIV heightens the risk of developing and dying from cervical cancer. The human papillomavirus (HPV) vaccine can prevent 90% of cervical cancers, and in Zambia is recommended for adolescent girls ages 14-15 years, including those with HIV. Currently they mainly deliver HPV vaccination via school-based campaigns, which may exclude the most vulnerable adolescents-those out-of-school or who irregularly attend. Adolescents living with HIV (ALHIV) are more likely to have these vulnerabilities. Further, school-based campaigns are not tailored to the WHO-recommended HPV vaccination …

Adherence To And Experiences Of K-12 Students In Modified And Standard Home Quarantine During The Sars-Cov-2 Pandemic In Missouri, Mary Claire Worrell, Sara Malone, Patrick Dawson, Stephanie A. Fritz, Ebony Thomas, Bre Peeler, Catherine Rains, Sarah C. Tinker, John C. Neatherlin, Lisa Barrios, Jon Mooney, Katie Towns, Jason Newland, Johanna S. Salzer

2020-Current year OA Pubs

BACKGROUND: In November 2020, during the SARS-CoV-2 pandemic, Missouri allowed local public health jurisdictions the option to implement a modified quarantine policy allowing kindergarten through 12 (K-12) students with low-risk exposures to continue in-person learning. We assessed adherence to quarantine among participants in modified quarantine and standard home quarantine and the psychosocial impacts of quarantine on students and families.

METHODS: In January-March 2021, as part of an investigation of in-school transmission of SARS-CoV-2, parents of 586 participating K-12 students identified as a close contact with a person with SARS-CoV-2 were sent a survey to assess their activities and psychosocial impacts …

Glioblastoma Induces Whole-Brain Spectral Change In Resting State Fmri: Associations With Clinical Comorbidities And Overall Survival, Ki Yun Park, Abraham Z Snyder, Michael Olufawo, Gabriel Trevino, Patrick H Luckett, Bidhan Lamichhane, Tao Xie, John J Lee, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

Glioblastoma, a highly aggressive form of brain tumor, is a brain-wide disease. We evaluated the impact of tumor burden on whole brain resting-state functional magnetic resonance imaging (rs-fMRI) activity. Specifically, we analyzed rs-fMRI signals in the temporal frequency domain in terms of the power-law exponent and fractional amplitude of low-frequency fluctuations (fALFF). We contrasted 189 patients with newly-diagnosed glioblastoma versus 189 age-matched healthy reference participants from an external dataset. The patient and reference datasets were matched for age and head motion. The principal finding was markedly flatter spectra and reduced grey matter fALFF in the patients as compared to the …

Nonalcoholic Fatty Liver Disease Is A Risk Factor For Thiopurine Hepatotoxicity In Crohn's Disease, Alvin T George, Matthew Glover, Quazim Alayo, Maria Zulfiqar, Daniel R Ludwig, Matthew A Ciorba, Scott Mchenry, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Patients with Crohn's disease (CD) are predisposed to nonalcoholic fatty liver disease (NAFLD). CD management often includes thiopurines which can promote hepatotoxicity. We aimed to identify the role of NAFLD on the risk of developing liver injury from thiopurines in CD.

METHODS: In this prospective cohort analysis, CD patients at a single center were recruited 6/2017-5/2018. Patients with alternative liver diseases were excluded. The primary outcome was time to elevation of liver enzymes. Patients underwent MRI with assessment of proton density fat fraction (PDFF) on enrollment, where NAFLD was defined as PDFF >5.5%. Statistical analysis was performed using a …

Structural And Biophysical Characterization Of The Secreted, Β-Helical Adhesin Etpa Of Enterotoxigenic Escherichia Coli, Clifford Manyo Ntui, James M. Fleckenstein, Wolf-Dieter Schubert

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) is a diarrhoeal pathogen associated with high morbidity and mortality especially among young children in developing countries. At present, there is no vaccine for ETEC. One candidate vaccine antigen, EtpA, is a conserved secreted adhesin that binds to the tips of flagellae to bridge ETEC to host intestinal glycans. EtpA is exported through a Gram-negative, two-partner secretion system (TPSS, type Vb) comprised of the secreted EtpA passenger (TpsA) protein and EtpB (TpsB) transporter that is integrated into the outer bacterial membrane. TpsA proteins share a conserved, N-terminal TPS domain followed by an extensive C-terminal domain with …

Training In Eight Low-And Middle-Income Countries: Lessons Learned From A Pilot Study Using The Who-Tdr Dissemination And Implementation Massive Open Online Course, Ashlin Rakhra, Victor Davila-Roman, Ana A Baumann, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Non-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle- income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, …

Nrg/Rtog 0837: Randomized, Phase Ii, Double-Blind, Placebo-Controlled Trial Of Chemoradiation With Or Without Cediranib In Newly Diagnosed Glioblastoma, Tracy T Batchelor, Clifford G Robinson, Et Al.

2020-Current year OA Pubs

BACKGROUND: A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma.

METHODS: Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided …

Sleep Deprivation, Sleep Fragmentation, And Social Jet Lag Increase Temperature Preference In Drosophila, S Tanner Roach, Melanie C Ford, Vikram Simhambhatla, Vasilios Loutrianakis, Hamza Farah, Zhaoyi Li, Erica M Periandri, Dina Abdalla, Irene Huang, Arjan Kalra, Paul J Shaw

2020-Current year OA Pubs

Despite the fact that sleep deprivation substantially affects the way animals regulate their body temperature, the specific mechanisms behind this phenomenon are not well understood. In both mammals and flies, neural circuits regulating sleep and thermoregulation overlap, suggesting an interdependence that may be relevant for sleep function. To investigate this relationship further, we exposed flies to 12 h of sleep deprivation, or 48 h of sleep fragmentation and evaluated temperature preference in a thermal gradient. Flies exposed to 12 h of sleep deprivation chose warmer temperatures after sleep deprivation. Importantly, sleep fragmentation, which prevents flies from entering deeper stages of …

Clinical Characteristics And Outcomes Of Infection With Human T-Lymphotropic Virus In A Non-Endemic Area: A Single Institution Study, Margery Gang, Feng Gao, Sneha Poondru, Theodore Thomas, Lee Ratner

2020-Current year OA Pubs

INTRODUCTION: Understanding of human T-lymphotropic virus (HTLV) remains largely based on epidemiologic and clinical data from endemic areas. Globalization has resulted in migration of persons living with HTLV (PLHTLV) from endemic to non-endemic areas, and a rise of HTLV infection in the United States. Yet, due to the historical rarity of this disease, affected patients are often under- and mis-diagnosed. Thus, we sought to characterize the epidemiology, clinical features, comorbidities, and survival of HTLV-1- or HTLV-2-positive individuals identified in a non-endemic area.

METHODS: Our study was a single institution, retrospective case-control analysis of HTLV-1 or HTLV-2 patients between 1998 and …

Adapting A Mobile App To Support Patients With Anorexia Nervosa Following Post-Acute Care: Perspectives From Eating Disorder Treatment Center Stakeholders, Anneliese Haas, Agatha A Laboe, Claire G Mcginnis, Marie-Laure Firebaugh, Jillian Shah, Anna M Bardone-Cone, Kathleen M Pike, C Barr Taylor, Denise E Wilfley, Ellen E Fitzsimmons-Craft

2020-Current year OA Pubs

INTRODUCTION: Anorexia nervosa (AN) is a harmful, life-threatening illness. Patients with severe AN often receive acute treatment but, upon discharge, experience high relapse rates. Evidence-based, outpatient treatment following acute care is critical to preventing relapse; however, numerous barriers (e.g., location, financial limitations, low availability of providers) preclude individuals from accessing treatment. mHealth technologies may help to address these barriers, but research on such digital approaches for those with AN is limited. Further, such technologies should be developed with all relevant stakeholder input considered from the outset. As such, the present study aimed to garner feedback from eating disorder (ED) treatment …

Higher Intensity Walking Improves Global Cognition During Inpatient Rehabilitation: A Secondary Analysis Of A Randomized Control Trial, Sue Peters, Keith R Lohse, Tara D Klassen, Teresa Liu-Ambrose, Sean P Dukelow, Mark T Bayley, Michael D Hill, Sepideh Pooyania, Jennifer Yao, Janice J Eng

2020-Current year OA Pubs

Cognitive deficits are common poststroke. Cognitive rehabilitation is typically used to improve cognitive deficits. It is unknown whether higher doses of exercise to promote motor recovery influence cognitive outcomes. Our recent trial, Determining Optimal Post-Stroke Exercise (DOSE), shows more than double the steps and aerobic minutes can be achieved during inpatient rehabilitation versus usual care, and translates to improved long-term walking outcomes. Thus, the secondary analysis aim was to determine the effect of the DOSE protocol on cognitive outcomes over 1-year poststroke. The DOSE protocol progressively increased step number and aerobic minutes during inpatient stroke rehabilitation over 20 sessions. The …

A Novel Dual Nlrp1 And Nlrp3 Inflammasome Inhibitor For The Treatment Of Inflammatory Diseases, Callum Ah Docherty, Anuruddika J Fernando, Sarah Rosli, Maggie Lam, Roland E Dolle, Manuel A Navia, Ronald Farquhar, Danny La France, Michelle D Tate, Christopher K Murphy, Adriano G Rossi, Ashley Mansell

2020-Current year OA Pubs

OBJECTIVES: Inflammasomes induce maturation of the inflammatory cytokines IL-1β and IL-18, whose activity is associated with the pathophysiology of a wide range of infectious and inflammatory diseases. As validated therapeutic targets for the treatment of acute and chronic inflammatory diseases, there has been intense interest in developing small-molecule inhibitors to target inflammasome activity and reduce disease-associated inflammatory burden.

METHODS: We examined the therapeutic potential of a novel small-molecule inhibitor, and associated derivatives, termed ADS032 to target and reduce inflammasome-mediated inflammation

RESULTS: We describe ADS032 as the first dual NLRP1 and NLRP3 inhibitor. ADS032 is a rapid, reversible and stable inflammasome …

Clinical Applications Of Electrical Stimulation For Peripheral Nerve Injury: A Systematic Review, Meredith C Costello, Emily L Errante, Taylor Smartz, Wilson Z Ray, Allan D Levi, Stephen Shelby Burks

2020-Current year OA Pubs

INTRODUCTION: Peripheral nerve injuries are common neurologic injuries that are challenging to treat with current therapies. Electrical stimulation has been shown to accelerate reinnervation and enhance functional recovery. This study aims to review the literature on clinical application of electrical stimulation for peripheral nerve injury.

METHODS: PubMed and Embase were sourced from 1995 to August 2022. Selection was based on predetermined inclusion/exclusion criteria. Eight hundred and thirty-five articles were screened with seven being included in this review.

RESULTS: Two hundred and twenty-nine patients with peripheral nerve injuries were represented. Six of the studies were randomized controlled trials. A variety of …

Defining Solute Carrier Transporter Signatures Of Murine Immune Cell Subsets, Tania Løve Aaes, Javier Burgoa Cardás, Kodi S Ravichandran

2020-Current year OA Pubs

Solute carrier (SLC) transporters are membrane-bound proteins that facilitate nutrient transport, and the movement across cellular membranes of various substrates ranging from ions to amino acids, metabolites and drugs. Recently, SLCs have gained increased attention due to their functional linkage to innate immunological processes such as the clearance of dead cells and anti-microbial defense. Further, the druggable nature of these transporters provides unique opportunities for improving outcomes in different immunological diseases. Although the SLCs represent the largest group of transporters and are often identified as significant hits in omics data sets, their role in immunology has been insufficiently explored. This …

Safety And Efficacy Of Mca‐M2 Thrombectomy In Delayed Time Window: A Propensity Score Analysis From The Star Registry, Kaustubh Limaye, Joshua Osbun, Et Al.

2020-Current year OA Pubs

No abstract provided.