U.S. adults increasingly report using cannabis to manage chronic pain and rural areas have inadequate comprehensive pain management.
View Article and Find Full Text PDFPurpose: To assess the association between travel distance to an academic health system and overall survival for patients with human papillomavirus (HPV)-associated cancers.
Methods: Using hospital-based cancer registry data from 2005-2019, we calculated unidirectional travel distance from each patient's geocoded address to our academic health center through network analysis. We categorized distance as (<25 miles), (25-74.
Background: Data on the population-based incidence of cancer-associated venous thromboembolism (VTE) from racially diverse populations are limited.
Objective: To evaluate the incidence and burden of cancer-associated VTE, including demographic and racial subgroups in the general population of Oklahoma County-which closely mirrors the United States.
Design: A population-based prospective study.
The 6-minute walk distance (6MWD) carries prognostic value in patients with heart failure with reduced ejection fraction (HFrEF). We performed this systematic review and meta-analysis to evaluate the effect of heart failure therapies on improvement in 6MWD. A systematic search of MEDLINE and Embase was conducted for randomized controlled trials measuring 6MWD at baseline and at follow-up in at least 50 patients with HFrEF across both arms.
View Article and Find Full Text PDFIntroduction: The purpose of this study was to examine low-dose computed tomography (LDCT) for lung cancer screening (LCS) eligibility, utilization, and factors associated with self-reported participation among eligible individuals.
Methods: Data from the 2017 and 2018 Oklahoma Behavioral Risk Factor Surveillance System (BRFSS) were used and analysis was restricted to data from individuals eligible for screening based on the US Preventive Services Task Force (USPSTF) guidelines. Analyses using recursive partitioning and weighted logistic regression were conducted from November 2019 to March 2020.
Objective: The purpose of the present study is to investigate the existence and/or prevalence of clinical practice variation in management of aneurysmal subarachnoid hemorrhage (aSAH) and to determine the need for long-term follow-up.
Methods: A single-center study was carried out of patients with aSAH over a 5-year period divided into 2 halves (2.5 years each) before and after addition of a dually trained cerebrovascular neurosurgeon.
Purpose: Post-hemorrhage period after aneurysmal subarachnoid hemorrhage (aSAH) has several systemic manifestations including prothrombotic and pro-inflammatory states. Inter-relationship between these states using established/routine laboratory biomarkers and its long-term effect on clinical outcome is not well-defined.
Materials And Methods: Retrospective analysis of prospective cohort of 44 aSAH patients.
Acute phase after aneurysmal subarachnoid hemorrhage (aSAH) is associated with several metabolic derangements including stress-induced hyperglycemia (SIH). The present study is designed to identify objective radiological determinants for SIH to better understand its contributory role in clinical outcomes after aSAH. A computer-aided detection tool was used to segment admission computed tomography (CT) images of aSAH patients to estimate intracranial blood and cerebrospinal fluid volumes.
View Article and Find Full Text PDFBackground: Delayed cerebral ischemia (DCI) is a major cause of disability after aneurysmal subarachnoid hemorrhage (aSAH). Activated platelets are surrogate markers for DCI occurrence and are reliably represented by mean platelet volume (MPV) to platelet count (PLT) ratio. If validated as a predictor of DCI, the ratio will allow clinicians to use it as a readily available tool in patient management.
View Article and Find Full Text PDFAneurysmal subarachnoid hemorrhage (aSAH) is associated with high socio-economic burden. Prothrombotic states of early brain injury (EBI) and delayed cerebral ischemia (DCI) after aSAH determine morbidity and mortality. To understand how activated platelets might contribute to such prothrombotic states, we studied trends in coated-platelets during EBI and DCI periods.
View Article and Find Full Text PDFDelivering polynucleotides into animals has been a major challenge facing their success as therapeutic agents. Given the matured understanding of antibody-mediated delivery techniques, it is possible to rationally design delivery vehicles that circulate in the blood stream and are specifically delivered into target organs. If the targeting moiety is designed to contain the cargo of an RNAi mediator without impacting its paratope, directed delivery can be achieved.
View Article and Find Full Text PDFIt is very clear that RNA interference (RNAi) is a potent and versatile tool for gene silencing. One of the hurdles to making siRNA/miRNA a human therapeutic includes effective in vivo delivery and being able to deliver drugs to target cells only. The commercial success of in vivo applications of RNAi hinges on the development of new delivery methods.
View Article and Find Full Text PDFKnockdown of cellular RNA using short interfering RNA has enabled researchers to perform loss-of-function (LOF) experiments in a wide variety of cell types and model systems. RNA interference techniques and reagents have made possible experiments that test everything from the analysis of function of single genes to screening for genes that are involved in critical biological pathways on a genome-wide scale. Although siRNA experiments are generally common practice in research laboratories, it is still important to keep in mind that many factors can influence efficacy of knockdown.
View Article and Find Full Text PDFMethods Mol Biol
May 2008
Although the majority of gene function studies center themselves around protein-encoding RNAs, the study of non-protein-encoding RNAs is becoming more widespread because of the discovery of hundreds of small RNA termed micro (mi) RNA that have regulator functions within cells. Currently, over 470 human miRNA genes are predicted to exist and are annotated within the "miRBase" public miRNA database ( http://microrna.sanger.
View Article and Find Full Text PDFMicroRNAs have been increasingly implicated in human cancer and interest has grown about the potential to use microRNAs to combat cancer. Lung cancer is the most prevalent form of cancer worldwide and lacks effective therapies. Here we have used both in vitro and in vivo approaches to show that the let-7 microRNA directly represses cancer growth in the lung.
View Article and Find Full Text PDFExpert Opin Ther Targets
January 2008
Small interfering RNAs (siRNA) and microRNAs (miRNA) are gaining considerable attention in the pharmaceutical and biotechnology industries, as research has revealed their likely clinical and agricultural applications. The capacity of siRNAs to dramatically and specifically reduce the expression of targeted genes has spawned multiple clinical trials to establish the therapeutic potential of small RNAs targeting viral, cancer and other disease-related genes. The successful application of siRNAs will enable the development of therapeutic applications based on miRNAs that have been observed to contribute to a variety of human diseases.
View Article and Find Full Text PDFBirth Defects Res C Embryo Today
June 2006
Mature microRNAs (miRNAs) are single-stranded RNA molecules of 17-24 nucleotides (nt) in length that are encoded in the genomes of plants and animals. The seminal discoveries of miRNA made in C. elegans have led the way to the rampant discoveries being made today in this field.
View Article and Find Full Text PDFKu protein is a heterodimer (Ku70 and Ku86) known to play an important role in V(D)J recombination, apoptosis, telomere fusion, and double-strand break repair. Its role in double-strand breaks is relevant to cancer therapy because lack of Ku86 causes one of the most radiation-responsive phenotypes (hamster cells, XRS5). Although it is known that the heterodimer is necessary for the various functions of this protein, the impact of targeting Ku in human cancer cells has not been shown due to lack of appropriate approaches.
View Article and Find Full Text PDFOf the over 200 identified mammalian microRNAs (miRNAs), only a few have known biological activity. To gain a better understanding of the role that miRNAs play in specific cellular pathways, we utilized antisense molecules to inhibit miRNA activity. We used miRNA inhibitors targeting miR-23, 21, 15a, 16 and 19a to test efficacy of antisense molecules in reducing miRNA activity on reporter genes bearing miRNA-binding sites.
View Article and Find Full Text PDFIn a BCR/ABL-expressing myeloid precursor cell line, p53 levels were markedly downmodulated. Expression of MDM2, the negative regulator of p53, was upregulated in a tyrosine kinase-dependent manner in growth factor-independent BCR/ABL-expressing cells, and in accelerated phase and blast crisis CML samples. Increased MDM2 expression was associated with enhanced mdm2 mRNA translation, which required the interaction of the La antigen with mdm2 5' UTR.
View Article and Find Full Text PDFTelomere length maintenance, an activity essential for chromosome stability and genome integrity, is regulated by telomerase- and telomere-associated factors. The DNA repair protein Ku (a heterodimer of Ku70 and Ku80 subunits) associates with mammalian telomeres and contributes to telomere maintenance. Here, we analyzed the physical association of Ku with human telomerase both in vivo and in vitro.
View Article and Find Full Text PDFUsing immortalized human pancreatic endocrine cell lines, we have shown previously that differentiation into hormone-expressing cells requires cell-cell contact acting in synergy with the homeodomain transcription factor pancreatic duodenal homeobox-1 (PDX-1). Although differentiation is associated with a decrease in cell proliferation, the mechanisms behind this relationship are not known. Using TRM-6, a delta cell line, and betalox5, a beta-cell line, we show here that cell-cell contact and subsequent endocrine differentiation lead to a down-regulation of the c-myc protooncogene.
View Article and Find Full Text PDFThe heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large family of nucleic acid binding proteins that are often found in, but not restricted to, the 40S-ribonucleoprotein particle. Subsets of hnRNPs are strictly nuclear while others shuttle between the nucleus and cytoplasm. Members of the hnRNP family have been implicated to have roles in many aspects of mRNA maturation/turnover and in telomere and telomerase regulation.
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