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Engineering a simple lateral flow device for animal blood coagulation monitoring
Increasing numbers of animals are diagnosed with thromboembolism, requiring anticoagulation treatment to prevent thrombotic events. Frequent and periodic coagulation monitoring is critical to ensure treatment effectiveness and patient safety by limiting blood coagulation ability within the desired therapeutic range. Point-of-care diagnostics is an ideal candidate for frequent coagulation monitoring due to rapid test results and no need for laboratory setting. This article reports the first utilization of no-reaction lateral flow assay (nrLFA) device for simple and low-cost animal blood coagulation monitoring in resource-limited setting. The nrLFA device consists of sample pad, analytical membrane and wicking pad, without conjugate pad, reagent printing or membrane drying. Citrated and heparinized animal blood were utilized to mimic different blood coagulation abilities in vitro by adding reversal agents CaCl2 and protamine sulfate. The travel distance of red blood cells (RBCs) on the nrLFA after a pre-determined test time serves as endpoint marker. Upon adding 500 mM CaCl2 solution to citrated bovine, canine, rabbit and equine blood, the average travel distance decreases from 10.9 to 9.4 mm, 8.8 to 5.7 mm, 12.6 to 9 mm, and 15.3 to 11.3 mm, respectively. For heparinized bovine and rabbit blood, the average distance decreases from 14.5 to 11.4 mm and from 9.8 to 7.2 mm, respectively, when adding 300 mg/l protamine sulfate solution. The effect of hematocrit on RBC travel distance in the nrLFA was also investigated. The nrLFA device will potentially improve treatment efficiency, patient safety, quality of life, and satisfaction for both animal patients and their owners
High payload nanostructured lipid carriers fabricated with alendronate/polyethyleneimine ion complexes
Oral bioavailability of the anti-osteoporotic drug alendronate (AL) is limited to ≤ 1% due to unfavorable physicochemical properties. To augment absorption across the gastrointestinal mucosa, an ion pair complex between AL and polyethyleneimine (PEI) was formed and incorporated into nanostructured lipid carriers (NLCs) using a modified solvent injection method. When compared to free AL, ion pairing with PEI increased drug encapsulation efficiency in NLCs from 10% to 87%. Drug release from NLCs measured in vitro using fasted state simulated intestinal fluid, pH 6.5 (FaSSIF-V2) was significantly delayed after PEI complexation. Stability of AL/PEI was pH-dependent resulting in 10-fold faster dissociation of AL in FaSSIF-V2 than measured at pH 7.4. Intestinal permeation properties estimated in vitro across Caco-2 cell monolayers revealed a 3-fold greater flux of AL encapsulated as hydrophobic ion complex in NLCs when compared to AL solution (Papp = 8.43 ± 0.14 × 10−6 cm/s and vs. 2.76 ± 0.42 × 10−6 cm/s). Cellular safety of AL/PEI-containing NLCs was demonstrated up to an equivalent AL concentration of 2.5 mM. These results suggest that encapsulation of AL/PEI in NLCs appears a viable drug delivery strategy for augmenting oral bioavailability of this clinically relevant bisphosphonate drug and, simultaneously, increase gastrointestinal safety
Correcting the effect of hematocrit in whole blood coagulation analysis on paper-based lateral flow device
A simple method to correct the effect of hematocrit (Hct) on a paper-based lateral flow assay device that is designed to assess whole blood coagulation is reported. By quantifying the effect of Hct on red blood cell (RBC) transport, a calibration procedure is obtained that compensates for the Hct effect, while maintaining the dependence of blood coagulation on RBC transport
The discharge companion pilot program
“Quality Improvement Success Stories” are published by the American Diabetes Association in collaboration with the American College of Physicians, Inc., and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a pilot project aimed at improving overall quality of care and reducing readmissions for patients discharged from a community hospital in Arizona
Arterial blood sampling in male CD-1 and C57BL/6J mice with 1% isoflurane is similar to awake mice
Isoflurane (ISO) is a commonly used anesthetic that offers rapid recovery for laboratory animal research. Initial studies indicated no difference in arterial PCO 2 (Pa CO2 ) or pH between conscious (NO ISO) and 1% ISO-exposed CD-1 mice. Our laboratory investigated whether arterial blood sampling with 1% ISO is a suitable alternative to NO ISO sampling for monitoring ventilation in a commonly studied mouse strain. We hypothesized similar blood chemistry, breathing patterns, and cardiovascular responses with NO ISO and 1% ISO. C57BL/6J mice underwent unrestrained barometric plethysmography to quantify the pattern of breathing. Mice exposed to hypoxic and hypercapnic gas under 1% ISO displayed blunted responses; with air, there were no breathing differences. Blood pressure and heart rate were not different between NO ISO and 1% ISO-exposed mice breathing air. Oxygen saturation was not different between groups receiving 2% ISO, 1% ISO, or air. Breathing frequency stabilized at ~11 min of 1% ISO following 2% ISO exposure, suggesting that 11 min is the optimal time for a sample in C57BL/6J mice. Blood samples at 1% ISO and NO ISO revealed no differences in blood pH and Pa CO2 in C57BL/6J mice. Overall, this method reveals similar arterial blood sampling values in awake and 1% ISO CD-1 and C57BL/6J mice exposed to air. Although this protocol may be appropriate in other mouse strains when a conscious sample is not feasible, caution is warranted first to identify breathing frequency responses at 1% ISO to tailor the protocol. NEW & NOTEWORTHY Conscious arterial blood sampling is influenced by extraneous factors and is a challenging method due to the small size of mice. Through a series of experiments, we show that arterial blood sampling with 1% isoflurane (ISO) is an alternative to awake sampling in C57BL/6J and CD-1 male mice breathing air. Monitoring breathing frequency during 1% ISO is important to the protocol and should be closely followed to confirm adequate recovery after the catheter implantation
Population genetic evaluations within a co-distributed taxonomic group: a multi-species approach to conservation planning
Multi-species approaches provide valuable insight for conservation planning, yet most studies focus on only one species while generalizing across taxa. Here, we employed 5–14 microsatellite DNA loci to evaluate population genetic patterns and future vulnerability for a freshwater turtle assemblage distributed across north-eastern Illinois. Focal species (Emydoidea blandingii, Clemmys guttata, Chrysemys picta and Chelydra serpentina) differ in conservation status as well as in ecological and life-history traits, which modulate gene flow across heterogeneous landscapes. We hypothesized (1) common and more ubiquitous species (C. picta and C. serpentina) would exhibit higher levels of genetic connectivity compared to species more restricted in distributions and with an elevated conservation status (E. blandingii and C. guttata) and (2) endangered species exhibit a greater loss of future genetic diversity. We found that genetic patterns varied considerably among co-distributed species. Endangered species had lower levels of genetic diversity and gene flow, more pronounced genetic structure and a higher risk of genetic drift compared to common species, thus supporting our hypotheses. The observed patterns are potentially attributable to life-history and ecological traits and will affect the long-term viability of the four species within a modified north-eastern Illinois landscape. Our study is an important first step for understanding how landscape features and species-specific traits interact to affect gene flow and population genetic structure within altered landscapes. It also underscores how multi-species approaches can be informative for conservation actions
Lipid-coated superparamagnetic nanoparticles for thermoresponsive cancer treatment
Poor aqueous solubility, chemical instability, and indiscriminate cytotoxicity have limited clinical development of camptothecin (CPT) as potent anticancer therapeutic. This research aimed at fabricating thermoresponsive nanocomposites that enhance solubility and stability of CPT in aqueous milieu and enable stimulus-induced drug release using magnetic hyperthermia. 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and L-α-dipalmitoylphosphatidyl glycerol (DPPG) (1:1, mol/mol) were immobilized on the surface of superparamagnetic Fe3O4 nanoparticles (SPIONs) via high affinity avidin-biotin interactions. Heating behavior was assessed using the MFG-1000 magnetic field generator. Encapsulation efficiency and drug release were quantified by fluorescence spectroscopy. Anticancer efficacy of medicated nanoparticles was measured in vitro using Jurkat cells. The results revealed that drug incorporation did not significantly alter particle size, zeta potential, magnetization, and heating properties of lipid-coated SPIONs. Drug loading efficiency was 93.2 ± 5.1%. Drug release from medicated nanoparticles was significantly faster at temperatures above the lipid transition temperature, reaching 37.8 ± 2.6% of incorporated payload after 12 min under therapeutically relevant hyperthermia (i.e., 42 °C). Medicated SPIONs induced greater cytotoxicity than CPT in solution suggesting synergistic activity of magnetically-induced hyperthermia and drug-induced apoptosis. These results underline the opportunity for thermoresponsive phospholipid-coated SPIONs to enable clinical development of highly lipophilic and chemically unstable drugs such as CPT for stimulus-induced cancer treatment
The effect of plan type and comprehensive medication reviews on high-risk medication use
BACKGROUND: In 2007, the Centers for Medicare & Medicaid Services(CMS) instituted a star rating system using performance outcome measuresto assess Medicare Advantage Prescription Drug (MAPD) andPrescription Drug Plan (PDP) providers.OBJECTIVE: To assess the relationship between 2 performance outcomemeasures for Medicare insurance providers, comprehensive medicationreviews (CMRs), and high-risk medication use.METHODS: This cross-sectional study included Medicare Part C and Part Dperformance data from the 2014 and 2015 calendar years. Performancedata were downloaded per Medicare contract from the CMS. We matchedMedicare insurance provider performance data with the enrollment data ofeach contract. Mann Whitney U and Spearman rho tests and a hierarchicallinear regression model assessed the relationship between provider characteristics,high-risk medication use, and CMR completion rate outcomemeasures.RESULTS: In 2014, an inverse correlation between CMR completion rateand high-risk medication use was identified among MAPD plan providers.This relationship was further strengthened in 2015. No correlation wasdetected between the CMR completion rate and high-risk medication useamong PDP plan providers in either year. A multivariate regression foundan inverse association with high-risk medication use among MAPD planproviders in comparison with PDP plan providers in 2014 (beta = -0.358,P \u3c 0.001) and 2015 (beta = -0.350, P \u3c 0.001), the CMR completion ratein 2015 (beta = -0.221, P \u3c 0.001), and enrollee population size in 2015(beta = -0.203, P = 0.001).CONCLUSIONS: This study found that MAPD plan providers and higher CMRcompletion rates were associated with lower use of high-risk medicationsamong beneficiaries
Radiation Safety Policy and Procedures
This policy is designed to provide Authorized Users, Radiation Workers and other staff of University of Health Sciences and Pharmacy in St. Louis and the affiliated personnel of the Center for Clinical Pharmacology a convenient reference to the compliance requirements of the Radiation Safety Program related to the use of radioactive materials.
Applies to laboratory personnel engaged in research involving use of radioactive materials