Digital Commons Network^™

An Overview Of The Effects Of Tenapanor On Visceral Hypersensitivity In The Treatment Of Irritable Bowel Syndrome With Constipation, Prashant Singh, Gregory S Sayuk, David P Rosenbaum, Susan Edelstein, Kenji Kozuka, Lin Chang

2020-Current year OA Pubs

BACKGROUND: Patients with irritable bowel syndrome with constipation (IBS-C) experience persistent abdominal pain, a common symptom leading to greater healthcare utilization and reports of treatment non-response. Clinically significant improvements in abdominal pain were observed in clinical trials of tenapanor, a first-in-class inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), for the treatment of IBS-C in adults.

AIM: This narrative review reports the current knowledge about visceral hypersensitivity as a mechanism for abdominal pain in patients with IBS-C and explores the published evidence for hypothesized mechanisms by which tenapanor may reduce visceral hypersensitivity leading to the observed clinical response of decreased abdominal …

Extensive Reactive Cutaneous Histiocytic Infiltrate Resembling Non-Langerhans Cell Histiocytosis As The Presenting Sign Of Underlying Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic Syndrome, Cynthia X Wang, Christine C Yokoyama, Ilana S Rosman, Amy C Musiek

2020-Current year OA Pubs

No abstract provided.

Targeting Of Oncogenic Aaa-Atpase Trip13 Reduces Progression Of Pancreatic Ductal Adenocarcinoma, Farrukh Afaq, Sumit Agarwal, Prachi Bajpai, Sameer Al Diffalha, Hyung-Gyoon Kim, Shajan Peter, Moh'd Khushman, Subhash C Chauhan, Priyabrata Mukherjee, Sooryanarayana Varambally, Upender Manne

2020-Current year OA Pubs

Thyroid hormone receptor-interacting protein 13 (TRIP13) is involved in cancer progression, but its role in pancreatic ductal adenocarcinoma (PDAC) is unknown. Thus, we assessed the expression, functional role, and mechanism of action of TRIP13 in PDAC. We further examined the efficacy of TRIP13 inhibitor, DCZ0415, alone or in combination with gemcitabine on malignant phenotypes, tumor progression, and immune response. We found that TRIP13 was overexpressed in human PDACs relative to corresponding normal pancreatic tissues. TRIP13 knockdown or treatment of PDAC cells with DCZ0415 reduced proliferation and colony formation, and induced G2/M cell cycle arrest and apoptosis. Additionally, TRIP13 knockdown or …

Neurosteroids Mediate And Modulate The Effects Of Pro-Inflammatory Stimulation And Toll-Like Receptors On Hippocampal Plasticity And Learning, Yukitoshi Izumi, Kazuko A. O'Dell, Anil G. Cashikar, Steven M. Paul, Douglas F. Covey, Steven J. Mennerick, Charles F. Zorumski

2020-Current year OA Pubs

Pro-inflammatory changes contribute to multiple neuropsychiatric illnesses. Understanding how these changes are involved in illnesses and identifying strategies to alter inflammatory responses offer paths to potentially novel treatments. We previously found that acute pro-inflammatory stimulation with high (μg/ml) lipopolysaccharide (LPS) for 10-15 min dampens long-term potentiation (LTP) in the hippocampus and impairs learning. Effects of LPS involved non-canonical inflammasome signaling but were independent of toll-like receptor 4 (TLR4), a known LPS receptor. Low (ng/ml) LPS also inhibits LTP when administered for 2-4 h, and here we report that this LPS exposure requires TLR4. We also found that effects of low …

Control Of Acute Myeloid Leukemia And Generation Of Immune Memory In Vivo Using Amv564, A Bivalent Bispecific Cd33 X Cd3 T Cell Engager, Linda G. Eissenberg, Julie K. Ritchey, Michael P. Rettig, Dilan A. Patel, Kiran Vij, Feng Gao, Victoria Smith, Tae H Han, John F. Dipersio

2020-Current year OA Pubs

Off-the-shelf immunotherapeutics that suppress tumor growth and provide durable protection against relapse could enhance cancer treatment. We report preclinical studies on a CD33 x CD3 bivalent bispecific diabody, AMV564, that not only suppresses tumor growth, but also facilitates memory responses in a mouse model of acute myelogenous leukemia (AML). Mechanistically, a single 5-day treatment with AMV564 seems to reduce tumor burden by redirection of T cells, providing a time window for allogeneic or other T cells that innately recognize tumor antigens to become activated and proliferate. When the concentration of bispecific becomes negligible, the effector: target ratio has also shifted, …

Intermuscular Coherence As An Early Biomarker For Amyotrophic Lateral Sclerosis: The Protocol For A Prospective, Multicenter Study, Naoum P Issa, Serdar Aydin, Eric Polley, Nathan Carberry, Mark A. Garret, Sean Smith, Ali A. Habib, Nicholas W. Baumgartner, Betty Soliven, Kourosh Rezania

2020-Current year OA Pubs

OBJECTIVE: To describe the protocol of a prospective study to test the validity of intermuscular coherence (IMC) as a diagnostic tool and biomarker of upper motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

METHODS: This is a multicenter, prospective study. IMC of muscle pairs in the upper and lower limbs is gathered in ∼650 subjects across three groups using surface electrodes and conventional electromyography (EMG) machines. The following subjects will be tested: 1) neurotypical controls; 2) patients with symptomatology suggestive for early ALS but not meeting probable or definite ALS by Awaji Criteria; 3) patients with a known ALS mimic. …

Adherence To Practice Parameters In Medicare Beneficiaries With Amyotrophic Lateral Sclerosis, Osvaldo J. Laurido-Soto, Irene M. Faust, Susan Searles Nielsen, Brad A. Racette

2020-Current year OA Pubs

OBJECTIVE: Physician adherence to evidence-based clinical practice parameters impacts outcomes of amyotrophic lateral sclerosis (ALS) patients. We sought to investigate compliance with the 2009 practice parameters for treatment of ALS patients in the United States, and sociodemographic and provider characteristics associated with adherence.

METHODS: In this population-based, retrospective cohort study of incident ALS patients in 2009-2014, we included all Medicare beneficiaries age ≥20 with ≥1 International Classification of Diseases, Ninth Revision, Clinical Modification ALS code (335.20) in 2009 and no prior years (N = 8,575). Variables of interest included race/ethnicity, sex, age, urban residence, Area Deprivation Index (ADI), and provider …

Sillyputty: Improved Clustering By Optimizing The Silhouette Width, Polina Bombina, Dwayne Tally, Zachary B. Abrams, Kevin R. Coombes

2020-Current year OA Pubs

Clustering is an important task in biomedical science, and it is widely believed that different data sets are best clustered using different algorithms. When choosing between clustering algorithms on the same data set, reseachers typically rely on global measures of quality, such as the mean silhouette width, and overlook the fine details of clustering. However, the silhouette width actually computes scores that describe how well each individual element is clustered. Inspired by this observation, we developed a novel clustering method, called SillyPutty. Unlike existing methods, SillyPutty uses the silhouette width for individual elements as a tool to optimize the mean …

Buffered Lugol's Iodine Preserves Dna Fragment Lengths, P M Gignac, D Valdez, A C Morhardt, L M Lynch

2020-Current year OA Pubs

Museum collections play a pivotal role in the advancement of biological science by preserving phenotypic and genotypic history and variation. Recently, contrast-enhanced X-ray computed tomography (CT) has aided these advances by allowing improved visualization of internal soft tissues. However, vouchered specimens could be at risk if staining techniques are destructive. For instance, the pH of unbuffered Lugol's iodine (I

Thirty-Day Hospital Readmission In Females With Acute Heart Failure And Breast Cancer: A Retrospective Cohort Study From National Readmission Database, Soumya Kambalapalli, Nischit Baral, Timir K. Paul, Prakash Upreti, Fahimeh Talaei, Sarah Ayad, Mahmoud Ibrahim, Vikas Aggarwal, Gautam Kumar, Chadi Alraies, Joshua Mitchell

2020-Current year OA Pubs

BACKGROUND: Breast Cancer and cardiovascular diseases are amongst the two leading causes of mortality in the United States, and the two conditions are connected in part because of recognized cardiotoxicity of cancer treatments. The aim of this study is to investigate the predictors risk factors for thirty-day readmission in female breast cancer survivors presenting with acute heart failure.

METHODS: This is a retrospective cohort study of acute heart failure (AHF) hospitalization in female patients with breast cancer in 2019 using the National Readmission Database (NRD), which is the largest publicly available all-payer inpatient readmission database in the United States. Our …