University of Tennessee Health Science Center

About: University of Tennessee Health Science Center is a education organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 15716 authors who have published 26884 publications receiving 1176697 citations.

PG4KDS: A model for the clinical implementation of pre-emptive pharmacogenetics

Abstract: Pharmacogenetics is frequently cited as an area for initial focus of the clinical implementation of genomics Through the PG4KDS protocol, St Jude Children's Research Hospital pre-emptively genotypes patients for 230 genes using the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array supplemented with a CYP2D6 copy number assay The PG4KDS protocol provides a rational, stepwise process for implementing gene/drug pairs, organizing data, and obtaining consent from patients and families Through August 2013, 1,559 patients have been enrolled, and four gene tests have been released into the electronic health record (EHR) for clinical implementation: TPMT, CYP2D6, SLCO1B1, and CYP2C19 These genes are coupled to 12 high-risk drugs Of the 1,016 patients with genotype test results available, 78% of them had at least one high-risk (ie, actionable) genotype result placed in their EHR Each diplotype result released to the EHR is coupled with an interpretive consult that is created in a concise, standardized format To support-gene based prescribing at the point of care, 55 interruptive clinical decision support (CDS) alerts were developed Patients are informed of their genotyping result and its relevance to their medication use through a letter Key elements necessary for our successful implementation have included strong institutional support, a knowledgeable clinical laboratory, a process to manage any incidental findings, a strategy to educate clinicians and patients, a process to return results, and extensive use of informatics, especially CDS Our approach to pre-emptive clinical pharmacogenetics has proven feasible, clinically useful, and scalable

Differential morphology of pyramidal tract-type and intratelencephalically projecting-type corticostriatal neurons and their intrastriatal terminals in rats

Abstract: Two types of corticostriatal projection neurons have been identified: 1) one whose intrastriatal arborization arises as a collateral of a projection to the ipsilateral brainstem via the pyramidal tract (PT-type); and 2) one that projects intratelencephalically to the cortex and striatum, in many cases bilaterally, but not extratelencephalically (IT-type). To assess possible functional differences between these two neuron types, we characterized their laminar location in the cortex, their perikaryal size, and the morphology of their intrastriatal terminals. IT-type neurons were retrogradely labeled by tetramethylrhodamine-dextran amine (RDA)3k injection into the contralateral striatum, whereas their intrastriatal terminals were labeled anterogradely by biotinylated dextran amine (BDA)10k injection into the contralateral motor or primary somatosensory cortex. To label PT-type neurons and their ipsilateral intrastriatal terminals retrogradely, BDA3k was injected into the pontine pyramidal tract. We found that IT-type neuronal perikarya are medium-sized (12-13 microm) and located in layer III and upper layer V, whereas PT-type perikarya are larger (18-19 microm) and most commonly located in lower layer V. At the electron microscopic level, the intrastriatal terminals of both corticostriatal neuron types made asymmetric synaptic contact with spine heads and less frequently with dendrites. IT-type axospinous terminals were characteristically small (0.4-0.5 microm) and regular in shape, whereas PT-type terminals were typically large (0.8-0.9 microm) and often irregular in shape. Perforated postsynaptic densities were common for PT-type terminals, but not IT-type. The clear differences between these two corticostriatal neuron types in perikaryal size and laminar location in the cortex, and in the size and shape of their intrastriatal terminals, suggest that they may differ in the nature of their influence on the striatum.

New fronts emerge in the influenza cytokine storm

Abstract: Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described as a "cytokine storm," associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33-amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here, we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.