Medicine and Health Sciences Commons^™

Connective Tissue Presentation In Two Families Expands The Phenotypic Spectrum Of Pyroxd1 Disorders, Frances J Evesson, Gregory Dziaduch, Samantha J Bryen, Francesca Moore, Sara Pittman, Beena Devanapalli, Leigh B Waddell, Monique M Ryan, Manoj P Menezes, Conrad C Weihl, Adviye Ayper Tolun, Craig Zaidman, Helen Young, Lesley C Adès, Sandra T Cooper

2020-Current year OA Pubs

Recessive variants in the oxidoreductase PYROXD1 are reported to cause a myopathy in 22 affected individuals from 15 families. Here, we describe two female probands from unrelated families presenting with features of a congenital connective tissue disorder including osteopenia, blue sclera, soft skin, joint hypermobility and neuromuscular junction dysfunction in addition to known features of PYROXD1 myopathy including respiratory difficulties, weakness, hypotonia and oromotor dysfunction. Proband AII:1 is compound heterozygous for the recurrent PYROXD1 variant Chr12(GRCh38):g.21452130A>G;NM_024854.5:c.464A>G;p.(N155S) and Chr12(GRCh38):g.21462019_21462022del;NM_024854.5:c.892_895del;p.(V298Mfs*4) and proband BII:1 is compound heterozygous for Chr12(GRCh38):g.21468739-21468741del;NM_024854.5:c.1488_1490del;p.(E496del) and Chr12(GRCh38):g.21467619del;NM_024854.5:c.1254+1del. RNA studies demonstrate c.892_895del;p.(V298Mfs*4) is targeted by nonsense mediated decay …

Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, C Charles Gu, Et Al.

2020-Current year OA Pubs

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs …

Igg4 Antibodies To The Recombinant Filarial Antigen Wb-Bhp-1 Decrease Dramatically Following Treatment Of Lymphatic Filariasis, Sarah E. Greene, Yuefang Huang, Kurt C. Curtis, Christopher L. King, Peter U. Fischer, Gary J. Weil

2020-Current year OA Pubs

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease and a major cause of chronic disability. Improved diagnostic tests are needed because of long-term persistence of anti-filarial antibodies or circulating filarial antigenemia after treatments that clear microfilaremia. Here, we assess changes in levels of antibodies to the recombinant filarial antigens Wb-Bhp-1, Wb123, and Bm14 after anti-filarial treatment.

METHODOLOGY/PRINCIPAL FINDINGS: IgG4 antibodies to recombinant filarial antigens were assessed by ELISA. We tested serial plasma samples from a clinical trial in Papua New Guinea. Before treatment, 90%, 71% and 99% of participants had antibodies to Wb-Bhp-1, Wb123, and Bm14, respectively. Antibodies to …

Improvements In Physical Function And Pain Interference And Changes In Mental Health Among Patients Seeking Musculoskeletal Care, Wei Zhang, Som P Singh, Amdiel Clement, Ryan P Calfee, Janine D Bijsterbosch, Abby L Cheng

2020-Current year OA Pubs

IMPORTANCE: Among patients seeking care for musculoskeletal conditions, there is mixed evidence regarding whether traditional, structure-based care is associated with improvement in patients' mental health.

OBJECTIVE: To determine whether improvements in physical function and pain interference are associated with meaningful improvements in anxiety and depression symptoms among patients seeking musculoskeletal care.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included adult patients treated by an orthopedic department of a tertiary care US academic medical center from June 22, 2015, to February 9, 2022. Eligible participants presented between 4 and 6 times during the study period for 1 or more musculoskeletal conditions …

Terrorist Attacks Against Sports Venues: Emerging Trends And Characteristics Spanning 50 Years, Grace R Rahman, Gregory N Jasani, Stephen Y Liang

2020-Current year OA Pubs

INTRODUCTION: Sports venues foster community and support local economies. Due to their capacity to host hundreds to thousands of spectators, sports venues are vulnerable to becoming targets of terrorism. Types of venues targeted, regional trends, and methods of attack employed world-wide have not been well-described.

METHODS: A search of the Global Terrorism Database (GTD) was conducted from 1970 through the end of 2019. Pre-coded variables for target type "business" and target subtype "entertainment/cultural/stadium/casino" were used to identify attacks involving venues where sports events might be viewed by spectators as part of an audience. Sports venues were specifically identified using the …

Genomic Approaches To Cancer And Minimal Residual Disease Detection Using Circulating Tumor Dna, Nicholas P. Semenkovich, Jeffrey J. Szymanski, Noah Earland, Pradeep S. Chauhan, Bruna Pellini, Aadel A. Chaudhuri

2020-Current year OA Pubs

Liquid biopsies using cell-free circulating tumor DNA (ctDNA) are being used frequently in both research and clinical settings. ctDNA can be used to identify actionable mutations to personalize systemic therapy, detect post-treatment minimal residual disease (MRD), and predict responses to immunotherapy. ctDNA can also be isolated from a range of different biofluids, with the possibility of detecting locoregional MRD with increased sensitivity if sampling more proximally than blood plasma. However, ctDNA detection remains challenging in early-stage and post-treatment MRD settings where ctDNA levels are minuscule giving a high risk for false negative results, which is balanced with the risk of …

Cat Lca-Crx Model, Homozygous For An Antimorphic Mutation Has A Unique Phenotype, Laurence M Occelli, Nicholas M Tran, Shiming Chen, Simon M Petersen-Jones

2020-Current year OA Pubs

PURPOSE: Mutations in the CRX transcription factor are associated with dominant retinopathies often with more severe macular changes. The CRX-mutant cat (Rdy-A182d2) is the only animal model with the equivalent of the critical retinal region for high-acuity vision, the macula. Heterozygous cats (CRXRdy/+) have a severe phenotype modeling Leber congenital amaurosis. This study reports the distinct ocular phenotype of homozygous cats (CRXRdy/Rdy).

METHODS: Gene expression changes were assessed at both mRNA and protein levels. Changes in globe morphology and retinal structure were analyzed.

RESULTS: CRXRdy/Rdy cats had high levels of mutant CRX mRNA and protein. The expression of photoreceptor target …

A Pentasaccharide For Monitoring Pharmacodynamic Response To Gene Therapy In Gm1 Gangliosidosis, Pamela Kell, Rohini Sidhu, Mingxing Qian, Sonali Mishra, Dennis J Dietzen, Jingqin Luo, Jean E Schaffer, Daniel S Ory, Xuntian Jiang, Et Al.

2020-Current year OA Pubs

BACKGROUND: GM1 gangliosidosis is a rare, fatal, neurodegenerative disease caused by mutations in the GLB1 gene and deficiency in β-galactosidase. Delay of symptom onset and increase in lifespan in a GM1 gangliosidosis cat model after adeno-associated viral (AAV) gene therapy treatment provide the basis for AAV gene therapy trials. The availability of validated biomarkers would greatly improve assessment of therapeutic efficacy.

METHODS: The liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to screen oligosaccharides as potential biomarkers for GM1 gangliosidosis. The structures of pentasaccharide biomarkers were determined with mass spectrometry, as well as chemical and enzymatic degradations. Comparison of LC-MS/MS data …

The Sphingolipids Ceramide And Inositol Phosphorylceramide Protect The Leishmania Major Membrane From Sterol-Specific Toxins, Chaitanya S Haram, Samrat Moitra, Rilee Keane, F Matthew Kuhlmann, Cheryl Frankfater, Fong-Fu Hsu, Stephen M Beverley, Kai Zhang, Peter A Keyel

2020-Current year OA Pubs

The accessibility of sterols in mammalian cells to exogenous sterol-binding agents has been well-described previously, but sterol accessibility in distantly related protozoa is unclear. The human pathogen Leishmania major uses sterols and sphingolipids distinct from those used in mammals. Sterols in mammalian cells can be sheltered from sterol-binding agents by membrane components, including sphingolipids, but the surface exposure of ergosterol in Leishmania remains unknown. Here, we used flow cytometry to test the ability of the L. major sphingolipids inositol phosphorylceramide (IPC) and ceramide to shelter ergosterol by preventing binding of the sterol-specific toxins streptolysin O and perfringolysin O and subsequent …

Transcription Regulation By Card In Mycobacteria Is Guided By Basal Promoter Kinetics, Dennis X Zhu, Christina L Stallings

2020-Current year OA Pubs

Bacterial pathogens like Mycobacterium tuberculosis (Mtb) employ transcription factors to adapt their physiology to the diverse environments within their host. CarD is a conserved bacterial transcription factor that is essential for viability in Mtb. Unlike classical transcription factors that recognize promoters by binding to specific DNA sequence motifs, CarD binds directly to the RNA polymerase to stabilize the open complex intermediate (RP

Molecular Imaging Of Bone Metastasis, Eliana Khojasteh, Farrokh Dehdashti, Monica Shokeen

2020-Current year OA Pubs

Recent advances in molecularly targeted modular designs for in vivo imaging applications has thrusted open possibilities of investigating deep molecular interactions non-invasively and dynamically. The shifting landscape of biomarker concentration and cellular interactions throughout pathological progression requires quick adaptation of imaging agents and detection modalities for accurate readouts. The synergy of state of art instrumentation with molecularly targeted molecules is resulting in more precise, accurate and reproducible data sets, which is facilitating investigation of several novel questions. Small molecules, peptides, antibodies and nanoparticles are some of the commonly used molecular targeting vectors that can be applied for imaging as well …

Language Exposure During Infancy Is Negatively Associated With White Matter Microstructure In The Arcuate Fasciculus, Katiana A Estrada, Sharnya Govindaraj, Hervé Abdi, Luke E Moraglia, Jason J Wolff, Shoba Sreenath Meera, Stephen R Dager, Robert C Mckinstry, Martin A Styner, Lonnie Zwaigenbaum, Joseph Piven, Meghan R Swanson, Ibis Network

2020-Current year OA Pubs

Decades of research have established that the home language environment, especially quality of caregiver speech, supports language acquisition during infancy. However, the neural mechanisms behind this phenomenon remain under studied. In the current study, we examined associations between the home language environment and structural coherence of white matter tracts in 52 typically developing infants from English speaking homes in a western society. Infants participated in at least one MRI brain scan when they were 3, 6, 12, and/or 24 months old. Home language recordings were collected when infants were 9 and/or 15 months old. General linear regression models indicated that …

Characterization Of Cell-Type Specific Circular Rnas Associated With Colorectal Cancer Metastasis, Sidi Zhao, Amy Ly, Jacqueline L Mudd, Emily B Rozycki, Jace Webster, Emily Coonrod, Ghofran Othoum, Jingqin Luo, Ha X Dang, Ryan C Fields, Christopher A Maher

2020-Current year OA Pubs

Colorectal cancer (CRC) is the most common gastrointestinal malignancy and a leading cause of cancer deaths in the United States. More than half of CRC patients develop metastatic disease (mCRC) with an average 5-year survival rate of 13%. Circular RNAs (circRNAs) have recently emerged as important tumorigenesis regulators; however, their role in mCRC progression remains poorly characterized. Further, little is known about their cell-type specificity to elucidate their functions in the tumor microenvironment (TME). To address this, we performed total RNA sequencing (RNA-seq) on 30 matched normal, primary and metastatic samples from 14 mCRC patients. Additionally, five CRC cell lines …

Pet-Determined Prevalence Of Coronary Microvascular Dysfunction And Different Types In A Cardio-Metabolic Risk Population, Anita R Bhandiwad, Ines Valenta, Sudhir Jain, Thomas H Schindler

2020-Current year OA Pubs

BACKGROUND:

METHODS: We prospectively enrolled 239 symptomatic patients with normal pharmacologically-stress and rest myocardial perfusion on

RESULTS: In the whole study population, CMD was present in 54% (130/239). The classical type was more prevalent than the endogen type of CMD (65% vs 35%, p ≤ 0.008). The classical type of CMD was paralleled by a high prevalence of diabetes mellitus, metabolic syndrome, and obesity, while the endogen type of CMD was accompanied by a higher prevalence of arterial hypertension, obesity, and/or morbid obesity. Further, the classical type of nCMF was more frequently observed that the endogen type (74% vs. 26%, …

Involucrin Modulates Vitamin D Receptor Activity In The Epidermis, Alina D Schmidt, Charlene Miciano, Qi Zheng, Mary Elizabeth Mathyer, Elizabeth A Grice, Cristina De Guzman Strong

2020-Current year OA Pubs

Terminally differentiated keratinocytes are critical for epidermal function and are surrounded by involucrin (IVL). Increased IVL expression is associated with a near-selective sweep in European populations compared with those in Africa. This positive selection for increased IVL in the epidermis identifies human adaptation outside of Africa. The functional significance is unclear. We hypothesize that IVL modulates the environmentally sensitive vitamin D receptor (VDR) in the epidermis. We investigated VDR activity in Ivl

Cochlear Implantation And Audiological Findings In A Child With Zellweger Spectrum Disorder, Amit Walia, Amy Lynn Birath, Craig A. Buchman

2020-Current year OA Pubs

No abstract provided.

Tarlatamab, A First-In-Class Dll3-Targeted Bispecific T-Cell Engager, In Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study, Luis Paz-Ares, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

PURPOSE: Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC.

PATIENTS AND METHODS: This study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary end point was safety. Secondary end points included antitumor activity by modified RECIST 1.1, overall survival, and pharmacokinetics.

RESULTS: By July 19, 2022, 107 patients received tarlatamab in dose exploration (0.003 to 100 mg; …

Associations Between Socioeconomic Status, Obesity, Cognition, And White Matter Microstructure In Children, Zhaolong Adrian Li, Yuqi Cai, Rita L Taylor, Sarah A Eisenstein, Deanna M Barch, Scott Marek, Tamara Hershey

2020-Current year OA Pubs

IMPORTANCE: Lower neighborhood and household socioeconomic status (SES) are associated with negative health outcomes and altered brain structure in children. It is unclear whether such findings extend to white matter and via what mechanisms.

OBJECTIVE: To assess whether and how neighborhood and household SES are independently associated with children's white matter microstructure and examine whether obesity and cognitive performance (reflecting environmental cognitive and sensory stimulation) are plausible mediators.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from participants in the Adolescent Brain Cognitive Development (ABCD) study. Data were collected at 21 US sites, and school-based recruitment was used …

Patients With Stricturing Or Penetrating Crohn's Disease Phenotypes Report High Disease Burden And Treatment Needs, Yanni Fan, Ling Zhang, Negar Omidakhsh, Rhonda L Bohn, Jennifer S Thompson, Kimberly G Brodovicz, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Crohn's disease (CD) is a chronic autoimmune disease in which inflammation can progress to complications of stricturing and/or penetrating disease. Real-world data on burden of complicated CD phenotypes are limited.

METHODS: We analyzed cross-sectional data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry from 2016 to 2020. Four mutually exclusive phenotype cohorts were created: inflammatory CD (CD-I), complicated CD (stricturing CD, penetrating CD, and stricturing and penetrating CD [CD-SP]). Statistical analyses were performed using CD-I as the reference.

RESULTS: A total of 1557 patients were identified: CD-I (n = 674, 43.3%), …

Central Carbon Flux Controls Growth/Damage Balance For Streptococcus Pyogenes, Joseph A. Merriman, Wei Xu, Michael G. Caparon

2020-Current year OA Pubs

Microbial pathogens balance growth against tissue damage to achieve maximum fitness. Central carbon metabolism is connected to growth, but how it influences growth/damage balance is largely unknown. Here we examined how carbon flux through the exclusively fermentative metabolism of the pathogenic lactic acid bacterium Streptococcus pyogenes impacts patterns of growth and tissue damage. Using a murine model of soft tissue infection, we systematically examined single and pair-wise mutants that constrained carbon flux through the three major pathways that S. pyogenes employs for reduction of the glycolytic intermediate pyruvate, revealing distinct disease outcomes. Its canonical lactic acid pathway (via lactate dehydrogenase) …

Mri Findings Associated With Anterior Cruciate Ligament Tears In National Football League Athletes, Robert H. Brophy, Jon C. Baker, Jana M. Crain, Mackenzie M. Herzog, Ben Stollberg, Edward M. Wojtys, Christina D. Mack

2020-Current year OA Pubs

BACKGROUND: Anterior cruciate ligament (ACL) tears are a high-frequency injury requiring a lengthy recovery in professional American football players. Concomitant pathology associated with ACL tears as identified on magnetic resonance imaging (MRI) is not well understood in these athletes.

PURPOSE: To describe the MRI findings of concomitant injuries associated with ACL tears among athletes in the National Football League (NFL).

STUDY DESIGN: Cross-sectional study; Level of evidence, 3.

METHODS: Of 314 ACL injuries in NFL athletes from 2015 through 2019, 191 complete MRI scans from the time of primary ACL injury were identified and reviewed by 2 fellowship-trained musculoskeletal radiologists. …

Autophagy Prevents Early Proinflammatory Responses And Neutrophil Recruitment During Mycobacterium Tuberculosis Infection Without Affecting Pathogen Burden In Macrophages, Rachel L. Kinsella, Jacqueline M. Kimmey, Asya Smirnov, Reilly Woodson, Margaret R. Gaggioli, Sthefany M. Chavez, Darren Kreamalmeyer, Christina L. Stallings

2020-Current year OA Pubs

The immune response to Mycobacterium tuberculosis infection determines tuberculosis disease outcomes, yet we have an incomplete understanding of what immune factors contribute to a protective immune response. Neutrophilic inflammation has been associated with poor disease prognosis in humans and in animal models during M. tuberculosis infection and, therefore, must be tightly regulated. ATG5 is an essential autophagy protein that is required in innate immune cells to control neutrophil-dominated inflammation and promote survival during M. tuberculosis infection; however, the mechanistic basis for how ATG5 regulates neutrophil recruitment is unknown. To interrogate what innate immune cells require ATG5 to control neutrophil recruitment …

Biological Rhythms In Covid-19 Vaccine Effectiveness In An Observational Cohort Study Of 1.5 Million Patients, Guy Hazan, Or A. Duek, Hillel Alapi, Huram Mok, Alex Ganninger, Elaine Ostendorf, Carrie Gierasch, Gabriel Chodick, David Greenberg, Jeffrey A. Haspel

2020-Current year OA Pubs

BACKGROUNDCircadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness.METHODSWe retrospectively analyzed a large Israeli cohort with timestamped COVID-19 vaccinations (n = 1,515,754 patients over 12 years old, 99.2% receiving BNT162b2). Endpoints included COVID-19 breakthrough infection and COVID-19-associated emergency department visits and hospitalizations. Our main comparison was among patients vaccinated during morning (800-1159 hours), afternoon (1200-1559 hours), or evening hours (1600-1959 hours). We employed Cox regression to adjust for differences in age, sex, and comorbidities.RESULTSBreakthrough infections differed based on …

American Academy Of Orthopaedic Surgeons Clinical Practice Guideline Summary: Management Of Anterior Cruciate Ligament Injuries, Robert H. Brophy, Kent Jason Lowry

2020-Current year OA Pubs

Management of Anterior Cruciate Ligament Injuries : Evidence-based Clinical Practice Guideline is based on a systematic review of published studies for the treatment of anterior cruciate ligament injurie in both skeletally mature and immature patients. This guideline contains eight recommendations and seven options to assist orthopaedic surgeons and all qualified physicians managing patients with ACL injuries based on the best current available evidence. It is also intended to serve as an information resource for professional healthcare practitioners and developers of practice guidelines and recommendations. In addition to providing pragmatic practice recommendations, this guideline also highlights gaps in the literature and …

"Brain Age" Predicts Disability Accumulation In Multiple Sclerosis, Matthew R Brier, Zhuocheng Li, Maria Ly, Helmet T Karim, Leda Liang, Weixin Du, John E Mccarthy, Anne H Cross, Tammie L S Benzinger, Robert T Naismith, Salim Chahin

2020-Current year OA Pubs

OBJECTIVE: Neurodegenerative conditions often manifest radiologically with the appearance of premature aging. Multiple sclerosis (MS) biomarkers related to lesion burden are well developed, but measures of neurodegeneration are less well-developed. The appearance of premature aging quantified by machine learning applied to structural MRI assesses neurodegenerative pathology. We assess the explanatory and predictive power of "brain age" analysis on disability in MS using a large, real-world dataset.

METHODS: Brain age analysis is predicated on the over-estimation of predicted brain age in patients with more advanced pathology. We compared the performance of three brain age algorithms in a large, longitudinal dataset ( …

Protein Kinetics Of Superoxide Dismutase-1 In Familial And Sporadic Amyotrophic Lateral Sclerosis, Cindy V Ly, Margaret D Ireland, Wade K Self, James Bollinger, Jennifer Jockel-Balsarotti, Hillary Herzog, Peggy Allred, Leah Miller, Michael Doyle, Isabel Anez-Bruzual, Bhavesh Trikamji, Ted Hyman, Tyler Kung, Katherine Nicholson, Robert C Bucelli, Bruce W Patterson, Randall J Bateman, Timothy M Miller

2020-Current year OA Pubs

OBJECTIVE: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts.

METHODS: We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured.

RESULTS: In …

Cortical Adaptation Of The Night Monkey To A Nocturnal Niche Environment: A Comparative Non-Invasive T1w/T2w Myelin Study, Takuro Ikeda, Joonas A Autio, Akihiro Kawasaki, Chiho Takeda, Takayuki Ose, Masahiko Takada, David C Van Essen, Matthew F Glasser, Takuya Hayashi

2020-Current year OA Pubs

Night monkeys (Aotus) are the only genus of monkeys within the Simian lineage that successfully occupy a nocturnal environmental niche. Their behavior is supported by their sensory organs' distinctive morphological features; however, little is known about their evolutionary adaptations in sensory regions of the cerebral cortex. Here, we investigate this question by exploring the cortical organization of night monkeys using high-resolution in-vivo brain MRI and comparative cortical-surface T1w/T2w myeloarchitectonic mapping. Our results show that the night monkey cerebral cortex has a qualitatively similar but quantitatively different pattern of cortical myelin compared to the diurnal macaque and marmoset monkeys. T1w/T2w myelin …

Assessment And Management Of Older Adults Undergoing Pci, Part 1: A Jacc: Advances Expert Panel, Michael G Nanna, Michael W Rich, Et Al.

2020-Current year OA Pubs

As the population ages, older adults represent an increasing proportion of patients referred to the cardiac catheterization laboratory. Older adults are the highest-risk group for morbidity and mortality, particularly after complex, high-risk percutaneous coronary interventions. Structured risk assessment plays a key role in differentiating patients who are likely to derive net benefit vs those who have disproportionate risks for harm. Conventional risk assessment tools from national cardiovascular societies typically rely on 3 pillars: 1) cardiovascular risk; 2) physiologic and hemodynamic risk; and 3) anatomic and procedural risks. We propose adding a fourth pillar: geriatric syndromes, as geriatric domains can supersede …

Interleukin-18 Signaling Promotes Activation Of Hepatic Stellate Cells In Mouse Liver Fibrosis, Jana Knorr, Joel D. Schilling, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Nucleotide-binding oligomerization domain-like receptor-family pyrin domain-containing 3 (NLRP3) inflammasome activation has been shown to result in liver fibrosis. Mechanisms and downstream signaling remain incompletely understood. Here, we studied the role of IL-18 in hepatic stellate cells (HSCs), and its impact on liver fibrosis.

APPROACH AND RESULTS: We observed significantly increased serum levels of IL-18 (128.4 pg/ml vs. 74.9 pg/ml) and IL-18 binding protein (BP; 46.50 ng/ml vs. 15.35 ng/ml) in patients with liver cirrhosis compared with healthy controls. Single cell RNA sequencing data showed that an immunoregulatory subset of murine HSCs highly expresses Il18 and Il18r1 . …

Clinical Programs For Cardiometabolic Health For South Asian Patients In The United States: A Review Of Key Program Components, Reeti K Gulati, Mustafa Husaini, Rajesh Dash, Jaideep Patel, Nilay S Shah

2020-Current year OA Pubs

Medical literature shows that South Asians have approximately a 2-fold higher risk of atherosclerotic cardiovascular disease (CVD) compared with other populations. Given this high prevalence, clinical programs to promote cardiovascular health have emerged in the United States that are dedicated to clinical care for South Asian individuals. In this review, we have summarized the key characteristics of clinical programs in the U.S. dedicated to preventing and managing CVD in South Asian American patients. These clinical centers have many unique components in common that are catered to South Asian patient populations including ethnicity concordance of clinical providers, intensive cardiovascular screening protocols …