A Contemporary Review of the Genomic Associations of Coronary Artery Myocardial Bridging.

Background: Myocardial bridging (MB) is a congenital coronary artery anomaly that has limited molecular disease state characterization. Though a large portion of individuals may be asymptomatic, the myocardial ischemia caused by this anomaly can lead to angina, acute coronary syndrome, coronary artery disease, and sudden cardiac death in patients.

Objective: This study aims to summarize and consolidate the current literature regarding the genomic associations of myocardial bridge development and, in doing so, prompt further investigation into the molecular basis of myocardial bridge development.

Developing a Semantically Based Query Recommendation for an Electronic Medical Record Search Engine: Query Log Analysis and Design Implications.

Background: An effective and scalable information retrieval (IR) system plays a crucial role in enabling clinicians and researchers to harness the valuable information present in electronic health records. In a previous study, we developed a prototype medical IR system, which incorporated a semantically based query recommendation (SBQR) feature. The system was evaluated empirically and demonstrated high perceived performance by end users.

The Efficacy of Health Information Technology in Supporting Health Equity for Black and Hispanic Patients With Chronic Diseases: Systematic Review.

Background: Racial inequity persists for chronic disease outcomes amid the proliferation of health information technology (HIT) designed to support patients in following recommended chronic disease self-management behaviors (ie, medication behavior, physical activity, and dietary behavior and attending follow-up appointments). Numerous interventions that use consumer-oriented HIT to support self-management have been evaluated, and some of the related literature has focused on racial minorities who experience disparate chronic disease outcomes. However, little is known about the efficacy of these interventions.

The selective 5-HT receptor agonist lasmiditan inhibits trigeminal nociceptive processing: Implications for migraine and cluster headache.

Background And Purpose: Lasmiditan is a novel selective 5-HT receptor agonist, recently approved for acute treatment of migraine. 5-HT receptors are widely expressed in the CNS and trigeminovascular system. Here, we have explored the therapeutic effects of 5-HT receptor activation in preclinical models of migraine and cluster headache.

Usability Testing of an Interactive Dashboard for Surgical Quality Improvement in a Large Congenital Heart Center.

Background: Interactive data visualization and dashboards can be an effective way to explore meaningful patterns in large clinical data sets and to inform quality improvement initiatives. However, these interactive dashboards may have usability issues that undermine their effectiveness. These usability issues can be attributed to mismatched mental models between the designers and the users.

Transgene expression and effective gene silencing in vagal afferent neurons in vivo using recombinant adeno-associated virus vectors.

Vagal afferent fibres innervating thoracic structures such as the respiratory tract and oesophagus are diverse, comprising several subtypes of functionally distinct C-fibres and A-fibres. Both morphological and functional studies of these nerve subtypes would be advanced by selective, effective and long-term transduction of vagal afferent neurons with viral vectors. Here we addressed the hypothesis that vagal sensory neurons can be transduced with adeno-associated virus (AAV) vectors in vivo, in a manner that would be useful for morphological assessment of nerve terminals, using enhanced green fluorescent protein (eGFP), as well as for the selective knock-down of specific genes of interest in a tissue-selective manner.

Residual factor VIII-like cofactor activity of thioredoxin and related oxidoreductases.

Background: Factor VIII is the cofactor for Factor X activation by Factor IXa. Activated Factor X, Factor Xa, in turn activates prothrombin in a sequence that leads to fibrin clot formation at the site of vascular injury. Although the biochemistry of the cascade has been well studied, the molecular mechanism underlying the cofactor role of Factor VIII is not understood.

Atypical CTSK transcripts and ARNT transcription read-through into CTSK.

The aryl hydrocarbon receptor nuclear translocator (ARNT) and cathepsin K (CTSK) genes lie in a tandem head-to-tail arrangement on human chromosome 1. The two genes are in extremely close proximity; the usual CTSK transcription start site is less than 1.4 kb downstream of the end of the longest reported ARNT transcript.

Evaluation of the mGlu8 receptor as a putative therapeutic target in schizophrenia.

Aberrant glutamatergic neurotransmission may underlie the pathogenesis of schizophrenia and metabotropic glutamate receptors (mGluRs) have been implicated in the disease. We have established the localization of the group III mGluR subtype, mGluR8, in the human body and investigated the biological effects of the selective mGluR8 agonist (S)-3,4-dicarboxyphenylglycine ((S)-3,4-DCPG) in schizophrenia-related animal models. The mGlu8 receptor has a widespread CNS distribution with expression observed in key brain regions associated with schizophrenia pathogenesis including the hippocampus.

Human islet isolation outcomes from pancreata preserved with Histidine-Tryptophan Ketoglutarate versus University of Wisconsin solution.

This study was designed to compare Histadine-Tryptophan-Ketogluterate (HTK) with University of Wisconsin (UW) solution. Pancreata from extended criteria donors were flushed and transported with HTK (n=41) or UW (n=45). Isolation outcomes were determined by islet yields, viability and in vitro and in vivo function.

TRPM2 is elevated in the tMCAO stroke model, transcriptionally regulated, and functionally expressed in C13 microglia.

We report the detailed expression profile of TRPM2 mRNA within the human central nervous system (CNS) and demonstrate increased TRPM2 mRNA expression at 1 and 4 weeks following ischemic injury in the rat transient middle cerebral artery occlusion (tMCAO) stroke model. Microglial cells play a key role in pathology produced following ischemic injury in the CNS and possess TRPM2, which may contribute to stroke-related pathological responses. We show that TRPM2 mRNA is present in the human C13 microglial cell line and is reduced by antisense treatment.

Tissue distribution profiles of the human TRPM cation channel family.

Eight members of the TRP-melastatin (TRPM) subfamily have been identified, whose physiological functions and distribution are poorly characterized. Although tissue expression and distribution patterns have been reported for individual TRPM channels, comparisons between individual studies are not possible because of variations in analysis techniques and tissue selection. We report here a comparative analysis of the expression patterns of all of the human TRPM channels in selected peripheral tissues and the central nervous system (CNS) using two distinct but complimentary approaches: TaqMan and SYBR Green real-time quantitative reverse transcription polymerase chain reaction (RT-PCR).

Cytochrome P450 gene induction in rats ex vivo assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (TaqMan).

Drug-induced changes in expression of cytochrome P450 (P450) genes are a significant issue in the preclinical development of pharmaceuticals. For example, preclinically, P450 induction can affect safety studies by reducing the systemic exposure of a compound undergoing toxicological evaluation, thus limiting the exposure that can be safely investigated in patients. Therefore, the induction potential of candidate drugs has been studied as part of the drug development process, typically using protein and/or catalytic end points.

Comparison of histidine-tryptophan ketoglutarate solution and University of Wisconsin solution in prolonged cold preservation of kidney allografts.

Although University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation, Histidine-Tryptophan Ketogluatarate (HTK) solution has been increasingly used. This study compared HTK or UW for cold static storage of kidney allografts. In all, 149 renal transplants were performed with cold ischemic times (CI) greater than 16 hr (UW 87, HTK 62) and a subset analysis was performed with CI over 24 hr (HTK 31, UW 38).

Comparison of histidine-tryptophan-ketoglutarate solution (HTK) and University of Wisconsin solution (UW) in adult liver transplantation.

Histidine-tryptophan-ketoglutarate solution (HTK) and University of Wisconsin solution (UW) have been shown to have similar outcomes in cadaveric kidney, pancreas, and liver transplantation. Our institution changed from UW to HTK as the primary preservation solution for liver, kidney and pancreas transplantation. This study compares the perioperative and first year outcomes of liver transplantation using UW or HTK.

Follow-up experience using histidine-tryptophan ketoglutarate solution in clinical pancreas transplantation.

In May 2003, at Indiana University, the standard cold preservation solution University of Wisconsin (UW) solution was replaced by histidine-tryptophan ketogluatarate (HTK) solution. Earlier, we presented our initial experience with HTK in pancreas preservation with an analysis of the first 10 pancreas transplants. Here we report updated results with HTK in pancreas transplantation over the past 18 months.

Correlation of protein and gene expression profiles of inflammatory proteins after endotoxin challenge in human subjects.

Administration of endotoxin (LPS) in humans results in profound physiological responses, including activation of peripheral blood mononuclear cells and the release of inflammatory factors. The time course of the response of selected inflammatory proteins was examined in healthy subjects (n = 6) administered a single intravenous dose of the purified derivative of endotoxin (3.0 ng/kg).

Comparison of histidine-tryptophan ketoglutarate and University of Wisconsin solutions as primary preservation in renal allografts undergoing pulsatile perfusion.

Introduction: University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation. Histidine-tryptophan ketogluatarate (HTK) solution has been used increasingly for kidney, pancreas, and liver transplantation. This study compared HTK and UW used during kidney procurement with subsequent pulsatile perfusion.

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction.

Apolipoprotein (apo) E4 is a risk factor for Alzheimer's disease (AD) and other neurodegenerative diseases, compared to wild-type apoE3. The mechanism(s) is unknown. One possibility, demonstrated in peripheral tissue cell lines, is that apoE stimulates nitric oxide synthase (NOS) via a receptor-dependent signalling pathway and that apoE4 generates inappropriate amounts of nitric oxide (NO) compared to apoE3.

Conducting population behavioral health surveillance by using automated diagnostic and pharmacy data systems.

Introduction: The Walter Reed Army Institute of Research used the Electronic Surveillance System for the Early Notification of Community-Based Epidemics (ESSENCE) to conduct population-based behavioral health surveillance among military-health-system beneficiaries. The study analyzed the effectiveness of using prescribing patterns of psychotropic medications to monitor changes in a community's behavioral health status.

Objectives: The objectives of this study were to 1) determine the feasibility of tracking psychiatric illnesses by monitoring prescriptions for psychiatric medications; 2) assess how often psychiatric medications are prescribed for patients with no record of psychiatric illness; 3) determine at what types of clinics these medications are prescribed most often and what other diagnoses are attributed to these patients; and 4) analyze data for potential changes in the population's mental health after high-stress events.

C20orf9-003 (ACI-1), a gene localized on chromosome 20q13.12 encoding for a 49 kD cytoplasmic protein with a putative nucleotide binding site.

Murine NGD5 is a gene identified from NG108-15 cells which is postulated to be involved in opioid receptor function. Here we report the cloning and characterization of a cDNA C20orf9-003 (ACI-1) encoding the human orthologue of the mouse NGD5. Analysis of the genomic structure revealed that C20orf9-003 (ACI-1) contains 13 exons and 12 introns, spanning 52.

Characterization of the human HCN1 channel and its inhibition by capsazepine.

The human hyperpolarization-activated cyclic nucleotide-gated 1 (hHCN1) subunit was heterologously expressed in mammalian cell lines (CV-1 and CHO) and its properties investigated using whole-cell patch-clamp recordings. Activation of this recombinant channel, by membrane hyperpolarization, generated a slowly activating, noninactivating inward current. The pharmacological properties of hHCN1-mediated currents resembled those of native hyperpolarization-activated currents (I(h)), that is, blockade by Cs(+) (99% at 5 mm), ZD 7288 (98% at 100 microm) and zatebradine (92% at 10 microm).

Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats.

Rationale: Neuromedin-U (NmU) is an agonist at NMU1R and NMU2R. The brain distribution of NmU and its receptors, in particular NMU2R, suggests widespread central roles for NmU. In agreement, centrally administered NmU affects feeding behaviour, energy expenditure and pituitary output.