Publications by authors named "Darnell J"

Background: The use of technology in health care, often referred to as digital health, has expanded rapidly because of the need to provide remote care during the COVID-19 pandemic. In light of this rapid boom, it is clear that health care professionals need to be trained in these technologies in order to provide high-level care. Despite the growing number of technologies used across health care, digital health is not a commonly taught topic in health care curricula.

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Background: Excessive noradrenergic signaling contributes to aversive symptoms of alcohol withdrawal that interfere with abstinence or reductions in harmful use.

Methods: To address this aspect of alcohol use disorder, 102 active-duty soldiers participating in command-mandated Army outpatient alcohol treatment were randomized to also receive the brain-penetrant alpha-1 adrenergic receptor antagonist prazosin or placebo for 13 weeks. Primary outcomes were scores on the Penn Alcohol Craving Scale (PACS), standard drink units (SDUs) per day averaged over each week, % days of any drinking per week, and % days of heavy drinking per week.

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Biomarkers of exposure (BoE) can help evaluate exposure to combustion-related, tobacco-specific toxicants after smokers switch from cigarettes to potentially less-harmful products like electronic nicotine delivery systems (ENDS). This paper reports data for one (Vuse Solo Original) of three products evaluated in a randomized, controlled, confinement study of BoE in smokers switched to ENDS. Subjects smoked their usual brand cigarette ad libitum for two days, then were randomized to one of three ENDS for a 7-day ad libitum use period, or to smoking abstinence.

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Article Synopsis
  • * This pathway drives quick gene expression triggered by various extracellular signals like cytokines and interleukins.
  • * Research on the JAK-STAT pathway has led to treatments for several conditions, including autoimmune diseases and COVID-19, but there are still significant challenges in understanding and leveraging this pathway.
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Purpose: Free and charitable clinics (FCCs), nonprofits that utilize volunteer licensed health care professionals to provide health services at no cost or a small fee to low-income uninsured patients who are disproportionately from underrepresented communities, have been part of the safety net for over a century. Approximately 1400 known FCCs serve two million patients annually. Despite their longevity and sizable number, evidence regarding the quality of care in FCCs is lacking.

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  • Dysregulated protein synthesis is a key issue in Fragile X Syndrome (FX), with the mGluR Theory suggesting that too much translation of certain mRNAs leads to problematic synaptic changes.
  • Researchers used TRAP-seq and proteomics to discover that mGlu stimulation in FX mice causes increased translation of ribosomal proteins while decreasing the translation of longer mRNAs for synaptic proteins.
  • Inhibiting the translation of ribosomal proteins hinders mGluR-induced synaptic changes, pointing to a problematic shift in the type of mRNAs being translated as a core issue in FX pathology.
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Little is known about how nonprofit volunteer-led free and charitable clinics, which deliver free or low-cost health services to approximately two million uninsured annually, have fared following the Affordable Care Act's (ACA's) Medicaid coverage expansions. In late 2014 we surveyed 156 clinics that are partners of Americares, a key stakeholder, about the impact of the ACA. We used clinics' responses to create outcome measures reflecting 1) how well clinics fared in terms of fundraising, staffing levels, volunteer hours, scope of services, and trends in patients and visits; and 2) their tendency to modify clinic operations, such as integrating new technology, changing the clinic flow, adding new services, or billing patients.

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Evaluate the impact of switching to an anti-retroviral regimen containing tenofovir alafenamide (TAF) on weight and the development of metabolic complications compared to remaining on a non-TAF containing regimen.Single-center retrospective case-control study.We evaluated people living with human immunodeficiency virus (PLWH) who were on an anti-retroviral regimen not containing TAF and were switched to a regimen containing TAF between January 1, 2016 and September 30, 2018.

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Loss of the RNA binding protein FMRP causes Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability, yet it is unknown how FMRP function varies across brain regions and cell types and how this contributes to disease pathophysiology. Here we use conditional tagging of FMRP and CLIP (FMRP cTag CLIP) to examine FMRP mRNA targets in hippocampal CA1 pyramidal neurons, a critical cell type for learning and memory relevant to FXS phenotypes. Integrating these data with analysis of ribosome-bound transcripts in these neurons revealed CA1-enriched binding of autism-relevant mRNAs, and CA1-specific regulation of transcripts encoding circadian proteins.

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RNA "CLIP" (cross-linking immunoprecipitation), the method by which RNA-protein complexes are covalently cross-linked and purified and the RNA sequenced, has attracted attention as a powerful means of developing genome-wide maps of direct, functional RNA-protein interaction sites. These maps have been used to identify points of regulation, and they hold promise for understanding the dynamics of RNA regulation in normal cell function and its dysregulation in disease.

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This protocol describes purification of RNA cross-linking immunoprecipitation (CLIP) tags by proteinase K digestion of the cross-linked protein, addition of a 5' linker to the RNA tags, and amplification of the product by transcription-polymerase chain reaction (RT-PCR). Use of this protocol adds another important purification step: sizing of the PCR products to enrich for those derived from RNA originally cross-linked to the desired RNABP. Finally, sequencing of the PCR products is described.

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This protocol describes the purification by denaturing polyacrylamide gel electrophoresis of RNA linkers for cross-linking immunoprecipitation (CLIP). Purification is necessary because if the 3' linker loses the puromycin blocking group, concatemerization of the 3' linker will occur during the 3' linker ligation reaction. In addition, truncated linkers make bioinformatic processing of the sequencing results more difficult than it need be.

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This first part of this protocol is designed to optimize purification of the RNABP by immunoprecipitation for cross-linking immunoprecipitation (CLIP) experiments. The key variables to assess are the quality and quantity of antibody needed to immunoprecipitate most but not quite all of the RNABP (the titration will decrease nonspecific binding), and the tolerance of the antibody:antigen interaction to stringent wash conditions. The results of these experiments can be checked first by western blot, and subsequently using the pilot CLIP protocol described in the second half of this protocol.

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One of the great advantages of RNA CLIP (cross-linking immunoprecipitation) is that RNA-protein complexes can be "frozen" in situ in live cells by ultraviolet (UV) irradiation. This protocol describes UV cross-linking of mammalian tissue culture cells or whole tissues. For the latter, the tissue is typically triturated to allow UV penetration.

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Background: Alternative RNA processing plays an essential role in shaping cell identity and connectivity in the central nervous system. This is believed to involve differential regulation of RNA processing in various cell types. However, in vivo study of cell type-specific post-transcriptional regulation has been a challenge.

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. Patient navigation is a practice strategy to address barriers to timely diagnosis and treatment of cancer. The aim of this study was to examine the effectiveness of varying intensities of patient navigation and timely diagnostic resolution after abnormal mammography.

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By using a cell fraction technique that separates chromatin-associated nascent RNA, newly completed nucleoplasmic mRNA and cytoplasmic mRNA, we have shown in a previous study that residues in exons are methylated (mA) in nascent pre-mRNA and remain methylated in the same exonic residues in nucleoplasmic and cytoplasmic mRNA. Thus, there is no evidence of a substantial degree of demethylation in mRNA exons that would correspond to so-called "epigenetic" demethylation. The turnover rate of mRNA molecules is faster, depending on mA content in HeLa cell mRNA, suggesting that specification of mRNA stability may be the major role of mA exon modification.

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Background: Past efforts to assess patient navigation on cancer screening utilization have focused on one-time uptake, which may not be sufficient in the long term. This is partially due to limited resources for in-person, longitudinal patient navigation. We examine the effectiveness of a low-intensity phone- and mail-based navigation on multiple screening episodes with a focus on screening uptake after receiving noncancerous results during a previous screening episode.

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Objective: To assess the feasibility of clinical pharmacist-led CYP2C19 genotype-guided P2Y inhibitor antiplatelet drug therapy recommendations to cardiologists in an outpatient cardiology practice.

Methods: This was a prospective, open-labeled, single-arm study conducted in an integrated healthcare delivery system between March 1, 2013 and January 23, 2014. Patients requiring non-emergent cardiac catheterization were included.

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Understanding the biologic role of -methyladenosine (mA) RNA modifications in mRNA requires an understanding of when and where in the life of a pre-mRNA transcript the modifications are made. We found that HeLa cell chromatin-associated nascent pre-mRNA (CA-RNA) contains many unspliced introns and mA in exons but very rarely in introns. The mA methylation is essentially completed upon the release of mRNA into the nucleoplasm.

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Background: The Patient Navigation in Medically Underserved Areas study objectives are to assess if navigation improves: 1) care uptake and time to diagnosis; and 2) outcomes depending on patients' residential medically underserved area (MUA) status. Secondary objectives include the efficacy of navigation across 1) different points of the care continuum among patients diagnosed with breast cancer; and 2) multiple regular screening episodes among patients who did not obtain breast cancer diagnoses.

Design/methods: Our randomized controlled trial was implemented in three community hospitals in South Chicago.

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Objective: Alcohol use disorders (AUDs) are prevalent in the military and are a major public health concern. Although efficacious AUD interventions exist, few service members seek treatment. Army-specific barriers to AUD treatment include treatment being recorded on health records, command being notified of participation, and perceptions that seeking treatment would interfere with promotion or retention in the military.

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Patient navigation is emerging as a standard in breast cancer care delivery, yet multi-site data on the impact of navigation at reducing delays along the continuum of care are lacking. The purpose of this study was to determine the effect of navigation on reaching diagnostic resolution at specific time points after an abnormal breast cancer screening test among a national sample. A prospective meta-analysis estimated the adjusted odds of achieving timely diagnostic resolution at 60, 180, and 365 days.

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