Introducing the operative value index for glioma surgery: an integration of quality-adjusted life years with time-driven activity-based costing.

Background: Although many studies have examined outcomes after glioma surgery, few have explored the factors driving variation in the cost-effectiveness of surgical care. In this study, we integrate granular time-driven activity-based costing (TDABC) methodology with quality-adjusted life years (QALYs) to measure the true "value" (outcomes achieved per dollar spent) of glioma surgery.

Methods: 176 glioma surgeries performed at a single institution were reviewed.

Heat activates the AAA+ HslUV protease by melting an axial autoinhibitory plug.

At low temperatures, protein degradation by the AAA+ HslUV protease is very slow. New crystal structures reveal that residues in the intermediate domain of the HslU unfoldase can plug its axial channel, blocking productive substrate binding and subsequent unfolding, translocation, and degradation by the HslV peptidase. Biochemical experiments with wild-type and mutant enzymes support a model in which heat-induced melting of this autoinhibitory plug activates HslUV proteolysis.

Molecular detection of inflammation in cell models using hyperpolarized C-pyruvate.

The detection and treatment monitoring of inflammatory states remain challenging in part due to the multifactorial mechanisms of immune activation and spectrum of clinical manifestations. Currently, diagnostic strategies tend to be subjective and limited quantitative tools exist to monitor optimal treatment strategies. Pro-inflammatory M1 polarized macrophages exhibit a distinct metabolic glycolytic phenotype compared to the continuum of M2 polarization states.

Detection of Bacteria-Specific Metabolism Using Hyperpolarized [2-C]Pyruvate.

The differentiation of bacterial infection from other causes of inflammation is difficult in clinical practice and is critical where patient outcomes rely heavily on early interventions. In addition to physical exam and laboratory markers, several imaging modalities are frequently employed, but these techniques generally target the host immune response, rather than the living microorganisms themselves. Here, we describe a method to detect bacteria-specific metabolism using hyperpolarized (HP) C magnetic resonance spectroscopy.

Hyperpolarized C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model.

Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) C dehydroascorbate (DHA) and C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI).

NMR detection of intermolecular interaction sites in the dimeric 5'-leader of the HIV-1 genome.

HIV type-1 (HIV-1) contains a pseudodiploid RNA genome that is selected for packaging and maintained in virions as a noncovalently linked dimer. Genome dimerization is mediated by conserved elements within the 5'-leader of the RNA, including a palindromic dimer initiation signal (DIS) that has been proposed to form kissing hairpin and/or extended duplex intermolecular contacts. Here, we have applied a H-edited NMR approach to directly probe for intermolecular interactions in the full-length, dimeric HIV-1 5'-leader (688 nucleotides; 230 kDa).

RNA structure. Structure of the HIV-1 RNA packaging signal.

The 5' leader of the HIV-1 genome contains conserved elements that direct selective packaging of the unspliced, dimeric viral RNA into assembling particles. By using a (2)H-edited nuclear magnetic resonance (NMR) approach, we determined the structure of a 155-nucleotide region of the leader that is independently capable of directing packaging (core encapsidation signal; Ψ(CES)). The RNA adopts an unexpected tandem three-way junction structure, in which residues of the major splice donor and translation initiation sites are sequestered by long-range base pairing and guanosines essential for both packaging and high-affinity binding to the cognate Gag protein are exposed in helical junctions.