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Over-the-counter (OTC) and direct-to-consumer (DTC) tests have been gaining popularity due to their potential to provide accurate and quick diagnostic results without any test order from healthcare professionals, while providing patients the opportunity to actively engage in their own health management. Group A streptococcus is a common transmissible pathogen that leads to acute pharyngitis. Accurate and timely diagnosis of Group A streptococcus pharyngitis is critical to urge patients to seek professional healthcare, to support antibiotic stewardship, to reduce disease transmission, and to prevent rare but potentially life-threatening complications such as acute rheumatic fever, rheumatic heart disease, and poststreptococcal glomerulonephritis. This review provides an overview for OTC and DTC testing in general, discusses the clinical utilization of Group A streptococcus testing, analyzes the limitations and challenges of current Group A streptococcus testing methodologies if developed into OTC or DTC tests. Finally, this review provides an outlook for future developments that would further improve healthcare outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Fat-soluble vitamins are measured to identify deficiencies that may lead to rickets, osteomalacia, night blindness, and reversible motor and sensory neuropathies. We present a rapid liquid chromatography-mass spectrometry (LC-MS/MS) method that simultaneously measures 25-hydroxyvitamin D3 (25[OH]D3), epi-25(OH)D3, 25(OH)D2, vitamin A, α-tocopherol, and γ-tocopherol.Methods: We mixed 100 µL serum with internal standard and extracted it by using supported liquid extraction plates. Reconstituted specimens were analyzed by LC-MS/MS with a 10-minute gradient.Results: The method was linear, covering physiological levels with r2 > 0.99, and the total precision was less than 15% at all quality control levels. The lower limit of the measuring intervals for 25(OH)D3, epi-25(OH)D3, 25(OH)D2, vitamin A, α-tocopherol, and γ-tocopherol were 4 ng/mL, 4 ng/mL, 4 ng/mL, 1 µg/dL, 0.2 µg/mL, and 0.2 µg/mL, respectively, with coefficient of variation of 20% or less. Recoveries were between 92% and 111% for National Institute of Standards and Technology reference materials and 81% and 122% for spike-recovery studies. Comparison studies for vitamin D total, vitamin A, and α-tocopherol demonstrated slopes between 1.04 and 1.11 and r2 between 0.94 and 0.96. Minimal matrix effect was observed for all analytes.Conclusions: We developed and validated a rapid LC-MS/MS method for the simultaneous measurement of 25(OH)D3, epi-25(OH)D3, 25(OH)D2, vitamin A, α-tocopherol, and γ-tocopherol. [ABSTRACT FROM AUTHOR]

Abstract: Background: Tacrolimus, a widely used immunosuppressant, inhibits T-lymphocyte signal transduction and cytokine upregulation. We evaluated and compared the performance of a newly developed tacrolimus immunoassay method to LC–MS/MS. Method: Analytical performance was assessed using quality control materials and whole blood patient samples. Interferences studies were performed using pooled whole-blood samples spiked with each interferent, respectively. Comparison studies were conducted using 145 de-identified whole blood samples collected after routine tacrolimus analysis by LC–MS/MS. Results: CVs were between 3.9 and 8.1% and the method was linear (r 2 =0.99) up to 30.0ng/ml. Calibration was stable ≤12days and LOQ was 0.7ng/ml (14.4% CV). Bilirubin (≤48mg/dl), hemoglobin (≤345mg/dl), and triglycerides (<2800mg/dl) showed no significant interference. Comparison (Passing–Bablok regression) for all samples showed a proportional bias of 17%. Comparisons of liver and kidney transplant patients showed slope biases of 22% and 31%, respectively, whereas other remaining transplant patients (stem cell, heart, lung, and islet) showed a slope bias of 0.98. Conclusions: Overall, the QMS Tacrolimus Immunoassay showed good analytical performance. Comparison studies showed a proportional bias of 17%, which can be attributed to the significant number of liver and kidney transplant patients present in this study (121/145). [Copyright &y& Elsevier]

The ribosome catalyzes two fundamental biological reactions: peptidyl transfer, the formation of a peptide bond during protein synthesis, and peptidyl hydrolysis, the release of the complete protein from the peptidyl tRNA upon completion of translation. The ribosome is able to utilize and distinguish the two different nucleophiles for each reaction, the αα-amine of the incoming aminoacyl tRNA versus the water molecule. The correct binding of substrates induces structural rearrangements of ribosomal active-site residues and the substrates themselves, resulting in an orientation suitable for catalysis. In addition, active-site residues appear to provide further assistance by ordering active-site water molecules and providing an electrostatic environment via a hydrogen network that stabilizes the reaction intermediates and possibly shuttles protons. Major questions remain concerning the timing, components, and mechanism of the proton transfer steps. This review summarizes the recent progress in structural, biochemical, and computational advances and presents the current mechanistic models for these two reactions. [ABSTRACT FROM AUTHOR]

Objectives Critical hyperbilirubinemia in preterm neonates, a condition requiring greater attention, is treated with phototherapy or exchange transfusion when bilirubin results exceed gestational age and age-specific medical decision levels (MDLs) to prevent bilirubin-induced neurologic damage. Conventional evaluation involves multiple manual steps and is poised to inconsistencies and delays. Methods We designed and implemented an electronic clinical decision support (CDS) tool to identify and alert neonatal intensive care unit clinicians of critical hyperbilirubinemia with a SmartZone alert. We evaluated the performance of our manual evaluation workflow, the accuracy of the electronic CDS tool, and the outcome of the electronic CDS tool to reduce the time to place orders for interventions. Results Among the 22 patients who met the criteria to have phototherapy ordered before implementing the electronic CDS tool, 20 (90%) had phototherapy ordered. Fourteen (70%) phototherapy orders were placed less than 24 hours, 4 phototherapy orders were placed 24 to 72 hours, and 2 orders were placed more than 72 hours after bilirubin results exceeded the corresponding MDLs. Among the 15 patients who met the criteria to have phototherapy ordered after implementing the electronic CDS tool, all (100%) received phototherapy orders, with 14 (93%) placed less than 24 hours and 1 order placed less than 48 hours. The electronic CDS tool identified all eligible patients correctly. The proportion of phototherapy ordered less than 24 hours increased from 70% to 93% after the implementation of the electronic CDS tool. Conclusions The electronic CDS tool promoted more appropriate and timely intervention orders to manage critical hyperbilirubinemia in preterm neonates. [ABSTRACT FROM AUTHOR]

Objectives: Analysis of platelet functional responses to stimuli is presently quite limited with respect to measurement of dense granule secretion. We sought to develop a nonradioactive assay of stimulated serotonin release using liquid chromatography tandem mass spectrometry (LC-MS/MS).Methods: Citrated whole blood (200 μL) was incubated with deuterated serotonin (d45-HT). Following uptake by platelets, blood was diluted 10-fold and aliquots were incubated with platelet stimuli. Following stimulation, blood was further diluted, centrifuged, and supernatant was assayed for released d45-HT by micro-LC-MS/MS.Results: This study demonstrated a broad linear range of 50 to 2,000 pg/mL d45-HT, with a total precision of less than 15.0% coefficient of variation at all quality control levels and a limit of quantitation of 50 pg/mL.Conclusions: Quantification of d45-HT by micro-LC-MS/MS assay offers a highly sensitive, nonradioactive methodology for quantitating platelet serotonin uptake and dense granule secretion, requiring only small volumes of patient blood. [ABSTRACT FROM AUTHOR]

Abstract: Ammonia concentration increases in red cell units (RBCs) during storage. We measured absolute amounts of ammonia (AA) per unit serially in stored RBCs and before and after removal of the supernatant by volume reduction (VR) or washing. Ammonia increased 6.4-fold in untreated units over 31days. VR decreased AA 3.7-fold, whereas washing decreased it 38-fold (p <0.0001). At least for certain patients, e.g., infants receiving large volume transfusions and patients in liver failure, it may be advisable to use RBCs as fresh as possible and to limit infusion (by VR or washing) of ammonia in the supernatant. [Copyright &y& Elsevier]