Digital Commons Network^™

Precision Neuromodulation: Promises And Challenges Of Spinal Stimulation For Multi-Modal Rehabilitation, Maria F Bandres, Jefferson L Gomes, Gerson N Moreno Romero, Avery R Twyman, Jacob Graves Mcpherson

2020-Current year OA Pubs

Spinal cord injury results in multiple, simultaneous sensorimotor deficits. These include, but are not limited to, full or partial paralysis of muscles below the lesion, muscle spasms, spasticity, and neuropathic pain. Bowel, bladder, and sexual dysfunction are also prevalent. Yet, the majority of emerging spinal stimulation-based therapies focus on a single issue: locomotor rehabilitation. Despite the enormous potential of these translational advances to transform the lives of people living with spinal cord injury, meaningful recovery in other domains deemed critical priorities remains lacking. Here, we highlight the importance of considering the diverse patterns of neural transmission that underlie clinically similar …

The Function Of Histone Methylation And Acetylation Regulators In Gbm Pathophysiology, Colin Mccornack, Timothy Woodiwiss, Angela Hardi, Hiroko Yano, Albert H Kim

2020-Current year OA Pubs

Glioblastoma (GBM) is the most common and lethal primary brain malignancy and is characterized by a high degree of intra and intertumor cellular heterogeneity, a starkly immunosuppressive tumor microenvironment, and nearly universal recurrence. The application of various genomic approaches has allowed us to understand the core molecular signatures, transcriptional states, and DNA methylation patterns that define GBM. Histone posttranslational modifications (PTMs) have been shown to influence oncogenesis in a variety of malignancies, including other forms of glioma, yet comparatively less effort has been placed on understanding the transcriptional impact and regulation of histone PTMs in the context of GBM. In …

Vigorous-Intensity Exercise As A Modulator Of Cardiac Adipose Tissue In Women With Obesity: A Cross-Sectional And Randomized Pilot Study, Sumsen Thapa, Bharath S Selvaraj, Paige N Davis, Bryan Smith, Amy H Givan, Jose A Perez-Rivera, Pamela K Woodard, Jon D Klingensmith, Maria Fernandez-Del-Valle

2020-Current year OA Pubs

Cardiac adipose tissue (CAT) has become an important target for the reduction of disease risk. Supervised exercise programs have shown potential to "significantly" reduce CAT; however, the impact of different exercise modalities is not clear, and the relationships between CAT, physical activity (PA) levels and fitness (PFit) remain unknown. Therefore, the purpose of this study was to analyze the relationships between CAT, PA and PFit, and to explore the effects of different exercise modalities in a group of women with obesity. A total of 26 women (age: 23.41 ± 5.78 years-old) were enrolled in the cross-sectional study. PA, cardiorespiratory fitness, …

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 …

Proteins In Tumor-Derived Plasma Extracellular Vesicles Indicate Tumor Origin, Meltem Barlin, Petra Erdmann-Gilmore, Jacqueline L Mudd, Qiang Zhang, Robert W Seymour, Zhanfang Guo, Julia R Miessner, S Peter Goedegebuure, Ye Bi, Omar A Osorio, Jennifer Alexander-Brett, Shunqiang Li, Cynthia X Ma, Ryan C Fields, R Reid Townsend, Jason M Held

2020-Current year OA Pubs

Cancer-derived extracellular vesicles (EVs) promote tumorigenesis, premetastatic niche formation, and metastasis via their protein cargo. However, the proteins packaged by patient tumors into EVs cannot be determined in vivo because of the presence of EVs derived from other tissues. We therefore developed a cross-species proteomic method to quantify the human tumor-derived proteome of plasma EVs produced by patient-derived xenografts of four cancer types. Proteomic profiling revealed individualized packaging of novel protein cargo, and machine learning accurately classified the type of the underlying tumor.

Direct Proteomic Detection And Prioritization Of 19 Onchocerciasis Biomarker Candidates In Humans, Bruce A Rosa, Kurt Curtis, Petra Erdmann Gilmore, John Martin, Qiang Zhang, Robert Sprung, Gary J Weil, R Reid Townsend, Peter U Fischer, Makedonka Mitreva

2020-Current year OA Pubs

Onchocerca volvulus, the causative agent of onchocerciasis, infects over 20 million people and can cause severe dermatitis and ocular conditions including blindness. Current treatments employed in mass drug administration programs do not kill adult female worms, and common diagnostic tests cannot reliably assess viability of adult worms. There is an urgent need for better diagnostic tests to facilitate monitoring the efficacy of new treatments and disease elimination efforts. Here, eight plasma samples collected from individuals infected with O. volvulus and seven from uninfected individuals were analyzed by MS/MS spectrometry to directly identify O. volvulus proteins present in infected but absent …

Down Syndrome And Alzheimer's Disease: A Scoping Review Of Functional Performance And Fall Risk, Selena E Washington, Emily Cler, Cameron Lowery, Susan L Stark

2020-Current year OA Pubs

INTRODUCTION: Alzheimer's disease (AD) occurs in aging adults with Down syndrome (DS) at a higher prevalence and an earlier age than in typical aging adults. As with the general aging adult population, there is an urgent need to understand the preclinical and early phases of AD progression in the adult population with DS. The aim of this scoping review was to synthesize the current state of the evidence and identify gaps in the literature regarding functional activity performance and falls and their significance to disease staging (i.e., mild, moderate, and severe defined staging criteria) in relation to Alzheimer's disease and …

Impact Of Early Pericardial Fluid Chymase Activation After Cardiac Surgery, Brittany Butts, Lee A Goeddel, Jingyi Zheng, Betty Pat, Pamela Powell, James Mobley, Sarfaraz Ahmad, Chad Steele, David Mcgiffin, James E Davies, James F George, Spencer J Melby, Carlos M Ferrario, Louis J Dell'italia

2020-Current year OA Pubs

INTRODUCTION: Chymase is a highly destructive serine protease rapidly neutralized in the circulation by protease inhibitors. Here we test whether pericardial fluid (PCF) chymase activation and other inflammatory biomarkers determine intensive care unit length of stay, and explore mechanisms of chymase delivery by extracellular vesicles to the heart.

METHODS: PCF was collected from adult patients (17 on-pump; 13 off-pump) 4 h after cardiac surgery. Extracellular vesicles (EVs) containing chymase were injected into Sprague-Dawley rats to test for their ability to deliver chymase to the heart.

RESULTS: The mean intensive care unit (ICU) stay and mean total length of stay was …

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 …

Feasibility And Acceptability Of Remote Smartphone Cognitive Testing In Frontotemporal Dementia Research, Jack Carson Taylor, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Remote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp).

METHODS: A diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD = 0 [

RESULTS: It was feasible for participants to complete the ALLFTD-mApp on their own smartphones. Participants reported high smartphone familiarity, completed ∼ 70% of tasks, and considered the time commitment acceptable (98% of respondents). Greater disease severity …

Genotype And Clinical Characteristics Of Patients With Wolfram Syndrome And Wfs1-Related Disorders, Evan M Lee, Megha Verma, Nila Palaniappan, Emiko M Pope, Sammie Lee, Lindsey Blacher, Pooja Neerumalla, William An, Toko Campbell, Cris Brown, Stacy Hurst, Bess Marshall, Tamara Hershey, Fumihiko Urano, Et Al.

2020-Current year OA Pubs

No abstract provided.

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 …

T-Cell Redirecting Therapies For B-Cell Non-Hodgkin Lymphoma: Recent Progress And Future Directions, David A Russler-Germain, Armin Ghobadi

2020-Current year OA Pubs

Several key advances in the treatment of B-cell non-Hodgkin lymphoma (B-NHL) over the past two decades have strategically exploited B-cell lineage markers suitable for targeting by immunotherapies. First, the addition of the anti-CD20 monoclonal antibody (mAb) rituximab to a range of standard therapies conferred remarkable outcomes improvements in diverse settings, perhaps most prominently an overall survival advantage in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Subsequently, multiple chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have revolutionized the treatment of relapsed/refractory (rel/ref) DLBCL and are active in other B-NHL subtypes as well. Most recently, the longstanding aspiration to exploit patients' …

Financial Burden Of Men With Localized Prostate Cancer: A Process Paper, Ashley J Housten, Hannah E Rice, Su-Hsin Chang, Allison J L'Hotta, Eric H Kim, Bettina F Drake, Robin Wright-Jones, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Many individuals undergoing cancer treatment experience substantial financial hardship, often referred to as financial toxicity (FT). Those undergoing prostate cancer treatment may experience FT and its impact can exacerbate disparate health outcomes. Localized prostate cancer treatment options include: radiation, surgery, and/or active surveillance. Quality of life tradeoffs and costs differ between treatment options. In this project, our aim was to quantify direct healthcare costs to support patients and clinicians as they discuss prostate cancer treatment options. We provide the transparent steps to estimate healthcare costs associated with treatment for localized prostate cancer among the privately insured population using a …

The Evaluation Of The Delayed Swollen Breast In Patients With A History Of Breast Implants, Grace C Keane, Alexandra M Keane, Ryan Diederich, Kaitlyn Kennard, Eric J Duncavage, Terence M Myckatyn

2020-Current year OA Pubs

Breast implants, whether placed for reconstructive or cosmetic purposes, are rarely lifetime devices. Rupture, resulting from compromised implant shell integrity, and capsular contracture caused by constriction of the specialized scar tissue that normally forms around breast implants, have long been recognized, and remain the leading causes of implant failure. It is apparent, however, that women with breast implants may also experience delayed breast swelling due to a range of etiologic factors. While a majority of delayed seromas associated with breast implants have a benign etiology, this presentation cannot be ignored without an adequate workup as malignancies such as breast implant …

Locus Specific Endogenous Retroviral Expression Associated With Alzheimer's Disease, Tyson Dawson, Uzma Rentia, Jessie Sanford, Carlos Cruchaga, John S K Kauwe, Keith A Crandall

2020-Current year OA Pubs

INTRODUCTION: Human endogenous retroviruses (HERVs) are transcriptionally-active remnants of ancient retroviral infections that may play a role in Alzheimer's disease.

METHODS: We combined two, publicly available RNA-Seq datasets with a third, novel dataset for a total cohort of 103 patients with Alzheimer's disease and 45 healthy controls. We use telescope to perform HERV quantification for these samples and simultaneously perform gene expression analysis.

RESULTS: We identify differentially expressed genes and differentially expressed HERVs in Alzheimer's disease patients. Differentially expressed HERVs are scattered throughout the genome; many of them are members of the HERV-K superfamily. A number of HERVs are correlated …

Functional Trajectories During Innate Spinal Cord Repair, Nicholas O Jensen, Brooke Burris, Lili Zhou, Hunter Yamada, Catrina Reyes, Zachary Pincus, Mayssa H Mokalled

2020-Current year OA Pubs

Adult zebrafish are capable of anatomical and functional recovery following severe spinal cord injury. Axon growth, glial bridging and adult neurogenesis are hallmarks of cellular regeneration during spinal cord repair. However, the correlation between these cellular regenerative processes and functional recovery remains to be elucidated. Whereas the majority of established functional regeneration metrics measure swim capacity, we hypothesize that gait quality is more directly related to neurological health. Here, we performed a longitudinal swim tracking study for 60 individual zebrafish spanning 8 weeks of spinal cord regeneration. Multiple swim parameters as well as axonal and glial bridging were integrated. We …

Cell Wall Composition In Cryptococcus Neoformans Is Media Dependent And Alters Host Response, Inducing Protective Immunity, Rajendra Upadhya, Woei C Lam, Camaron R Hole, Joseph G Vasselli, Jennifer K Lodge

2020-Current year OA Pubs

INTRODUCTION:

OBJECTIVE: The purpose of this study was to determine how different media influenced the amount of chitin and chitosan in the cell wall, which in turn impacted the cell wall architecture and host response.

METHODS: Yeast extract, peptone, and dextrose (YPD) and yeast nitrogen base (YNB) are two commonly used media for growing Cryptococcus before use in in vitro or in vivo experiments. As a result,

RESULTS: We observed that the growth of wild-type

CONCLUSION: These findings emphasize the importance of culture media and pH during growth in shaping the content and organization of the

Changes In Patient-Reported Pain Interference After Surgical Treatment Of Painful Lower Extremity Neuromas, Adam Liebendorfer, Esther Ochoa, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: Painful neuromas commonly cause neuropathic pain, in up to 1 in 20 cases of traumatic or iatrogenic nerve injury. Despite the multiple surgical treatment types that reduce pain, no type has been universally accepted.

METHODS: We performed a retrospective cohort study by administering follow-up surveys to all surgical patients treated in our department for lower-extremity neuroma from September 1, 2015, to October 22, 2021, that could be contacted, excluding those with Morton neuroma. In addition to the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) questionnaire, survey questions covered the time to pain reduction, use of physical or …

A Universal Neocortical Mask For Centiloid Quantification, Pierrick Bourgeat, Vincent Doré, Christopher C Rowe, Tammie Benzinger, Duygu Tosun, Manu S Goyal, Pamela Lamontagne, Liang Jin, Michael W Weiner, Colin L Masters, Jurgen Fripp, Victor L Villemagne, Alzheimer's Disease Neuroimaging Initiative; Oasis3, Aibl Research Group

2020-Current year OA Pubs

INTRODUCTION: The Centiloid (CL) project was developed to harmonize the quantification of amyloid beta (Aβ) positron emission tomography (PET) scans to a unified scale. The CL neocortical mask was defined using

METHODS: Using data from the Alzheimer's Dementia Onset and Progression in International Cohorts (ADOPIC) study (Australian Imaging Biomarkers and Lifestyle + Alzheimer's Disease Neuroimaging Initiative + Open Access Series of Imaging Studies), age-matched pairs of mild Alzheimer's disease (AD) and healthy controls (HC) were selected:

RESULTS: In the GAAIN dataset, the universal mask led to a small reduction in the variance of the YC, and a small increase in …

Toward A Computational Theory Of Manifold Untangling: From Global Embedding To Local Flattening, Xin Li, Shuo Wang

2020-Current year OA Pubs

It has been hypothesized that the ventral stream processing for object recognition is based on a mechanism called cortically local subspace untangling. A mathematical abstraction of object recognition by the visual cortex is how to untangle the manifolds associated with different object categories. Such a manifold untangling problem is closely related to the celebrated kernel trick in metric space. In this paper, we conjecture that there is a more general solution to manifold untangling in the topological space without artificially defining any distance metric. Geometrically, we can either

Conditional Protein Degradation In Yarrowia Lipolytica Using The Auxin-Inducible Degron, Zhenlin Han, Jessica Maruwan, Yinjie Tang, Wei Wen Su

2020-Current year OA Pubs

Conditional protein degradation is a powerful tool for controlled protein knockdown. The auxin-inducible degron (AID) technology uses a plant auxin to induce depletion of degron-tagged proteins, and it has been shown to be functional in several non-plant eukaryotes. In this study, we demonstrated AID-based protein knockdown in an industrially important oleaginous yeast

A New Measure For Multi-Professional Medical Team Communication: Design And Methodology For Multilingual Measurement Development, Sara Malone, Kim Prewitt, Lara Counts, Douglas A Luke, Et Al.

2020-Current year OA Pubs

BACKGROUND: As implementation science in global health continues to evolve, there is a need for valid and reliable measures that consider diverse linguistic and cultural contexts. A standardized, reproducible process for multilingual measure development may improve accessibility and validity by participants in global health settings. To address this need, we propose a rigorous methodology for multilingual measurement development. We use the example of a novel measure of multi-professional team communication quality, a determinant of implementation efforts.

METHODS: The development and translation of this novel bilingual measure is comprised of seven steps. In this paper, we describe a measure developed in …

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 …

Carotid Atherosclerotic Plaque Segmentation In Multi-Weighted Mri Using A Two-Stage Neural Network: Advantages Of Training With High-Resolution Imaging And Histology, Ran Li, Jie Zheng, Mohamed A Zayed, Jeffrey E Saffitz, Pamela K Woodard, Abhinav K Jha

2020-Current year OA Pubs

INTRODUCTION: A reliable and automated method to segment and classify carotid artery atherosclerotic plaque components is needed to efficiently analyze multi-weighted magnetic resonance (MR) images to allow their integration into patient risk assessment for ischemic stroke. Certain plaque components such as lipid-rich necrotic core (LRNC) with hemorrhage suggest a greater likelihood of plaque rupture and stroke event. Assessment for presence and extent of LRNC could assist in directing treatment with impact upon patient outcomes.

METHODS: To address the need to accurately determine the presence and extent of plaque components on carotid plaque MRI, we proposed a two-staged deep-learning-based approach that …

Ehealth Technology In Cardiac Exercise Therapeutics For Pediatric Patients With Congenital And Acquired Heart Conditions: A Summary Of Evidence And Future Directions, David A White, Aimee M Layton, Tracy Curran, Naomi Gauthier, William B Orr, Kendra Ward, Meg Vernon, Matthew N Martinez, Malloree C Rice, Katherine Hansen, Megan Prusi, Jesse E Hansen

2020-Current year OA Pubs

Many children and adolescents with congenital and acquired heart disease (CHD) are physically inactive and participate in an insufficient amount of moderate-to-vigorous intensity exercise. Although physical activity (PA) and exercise interventions are effective at improving short- and long-term physiological and psychosocial outcomes in youth with CHD, several barriers including resource limitations, financial costs, and knowledge inhibit widespread implementation and dissemination of these beneficial programs. New and developing eHealth, mHealth, and remote monitoring technologies offer a potentially transformative and cost-effective solution to increase access to PA and exercise programs for youth with CHD, yet little has been written on this topic. …

Implementation Strategies For Occupational Therapists To Advance Goal Setting And Goal Management, Eunyoung Kang, Julie Chen, Erin R Foster

2020-Current year OA Pubs

BACKGROUND: There is a need for an effective evidence-based system to support high-quality goal setting and goal management implementation. We developed a new system for community-based rehabilitation, MyGoals, along with implementation strategies to support occupational therapists (OTs) in its administration. This study evaluates the acceptability, appropriateness, and feasibility of the implementation strategies,

METHODS: This mixed-methods case series study evaluated the MyGoals implementation strategies developed using Implementation Mapping (IM), specifically IM Task 5 - Implementation Outcome Evaluation. Seven OTs and 13 adults with chronic conditions participated in this study. OTs participated in two

RESULTS: Seven OTs participated in this study (mean …

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 …

Ube2c Expression Is Elevated In Hepatoblastoma And Correlates With Inferior Patient Survival, Ruth Nousiainen, Katja Eloranta, Noora Isoaho, Stefano Cairo, David B Wilson, Markku Heikinheimo, Marjut Pihlajoki

2020-Current year OA Pubs

Hepatoblastoma (HB) is the most common malignant liver tumor among children. To gain insight into the pathobiology of HB, we performed RNA sequence analysis on 5 patient-derived xenograft lines (HB-243, HB-279, HB-282, HB-284, HB-295) and 1 immortalized cell line (HUH6). Using cultured hepatocytes as a control, we found 2,868 genes that were differentially expressed in all of the HB lines on mRNA level. The most upregulated genes were

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 …