Evaluation of a Prelicensure Nursing Capstone Preceptorship

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A Review on the Use of Confocal Laser Endomicroscopy in the Bile Duct

Background. Current methods to diagnose malignant biliary strictures are of low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) is a new approach that can be used to evaluate in vivo histopathology of the GI tract. This paper is of studies evidencing pCLE's application in the diagnosis of indeterminate biliary strictures. Methods. This paper examined peer-reviewed studies conducted between January 2000 and November 2011. A PubMed search for relevant articles was performed using the following keywords:“pCLE”, “confocal”, “endomicroscopy”, “probe-based confocal laser endomicroscopy”, “and “bile duct”. Further individual review was done to assess the screened articles' relevance to the topic. Results. After individual review, 6 studies were included; with a cumulative sample size of 165, with 75 subjects identified as having a malignancy. These studies included tertiary care centers in Germany, France, and USA, including one multicenter trial. 3 studies assessed pCLE's specificity (range 67%–88%) ,sensitivity (range 83%–98), and accuracy (range 81%–86%). Conclusion. Confocal endomicroscopy is a novel and promising modality for the biliary tree. Further studies need to be conducted both to establish its usefulness for the diagnosis of indeterminate biliary strictures and to understand the histological meaning of the imaging patterns that are observed

Temperature Response of 129 Xe Depolarization Transfer and Its Application for Ultrasensitive NMR Detection

Trapping xenon in functionalized cryptophane cages makes the sensitivity of hyperpolarized (HP) 129Xe available for specific NMR detection of biomolecules. Here, we study the signal transfer onto a reservoir of unbound HP xenon by gating the residence time of the nuclei in the cage through the temperature-dependant exchange rate. Temperature changes larger than ∼0.6  K are detectable as an altered reservoir signal. The temperature response is adjustable with lower concentrations of caged xenon providing more sensitivity at higher temperatures. Ultrasensitive detection of functionalized cryptophane at 310 K is demonstrated with a concentration of 10 nM, corresponding to a ∼4000−fold sensitivity enhancement compared to conventional detection. This makes HPNMR capable of detecting such constructs in concentrations far below the detection limit of benchtop uv-visible light absorbance

Wee1-Regulated Apoptosis Mediated by the Crk Adaptor Protein in Xenopus Egg Extracts

Many of the biochemical reactions of apoptotic cell death, including mitochondrial cytochrome c release and caspase activation, can be reconstituted in cell-free extracts derived from Xenopus eggs. In addition, because caspase activation does not occur until the egg extract has been incubated for several hours on the bench, upstream signaling processes occurring before full apoptosis are rendered accessible to biochemical manipulation. We reported previously that the adaptor protein Crk is required for apoptotic signaling in egg extracts (Evans, E.K., W. Lu, S.L. Strum, B.J. Mayer, and S. Kornbluth. 1997. EMBO (Eur. Mol. Biol. Organ.) J. 16:230–241). Moreover, we demonstrated that removal of Crk Src homology (SH)2 or SH3 interactors from the extracts prevented apoptosis. We now report the finding that the relevant Crk SH2-interacting protein, important for apoptotic signaling in the extract, is the well-known cell cycle regulator, Wee1. We have demonstrated a specific interaction between tyrosine-phosphorylated Wee1 and the Crk SH2 domain and have shown that recombinant Wee1 can restore apoptosis to an extract depleted of SH2 interactors. Moreover, exogenous Wee1 accelerated apoptosis in egg extracts, and this acceleration was largely dependent on the presence of endogenous Crk protein. As other Cdk inhibitors, such as roscovitine and Myt1, did not act like Wee1 to accelerate apoptosis, we propose that Wee1–Crk complexes signal in a novel apoptotic pathway, which may be unrelated to Wee1's role as a cell cycle regulator

Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial.

Importance: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. Objective: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. Design, Setting, and Participants: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF ( Interventions: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. Main Outcomes and Measures: The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). Results: Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P \u3e .05. Conclusions and Relevance: Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. Trial Registration: clinicaltrials.gov Identifier: NCT02188784

Expert recommendations for implementing change (ERIC): Protocol for a mixed methods study

BACKGROUND: Identifying feasible and effective implementation strategies that are contextually appropriate is a challenge for researchers and implementers, exacerbated by the lack of conceptual clarity surrounding terms and definitions for implementation strategies, as well as a literature that provides imperfect guidance regarding how one might select strategies for a given healthcare quality improvement effort. In this study, we will engage an Expert Panel comprising implementation scientists and mental health clinical managers to: establish consensus on a common nomenclature for implementation strategy terms, definitions and categories; and develop recommendations to enhance the match between implementation strategies selected to facilitate the use of evidence-based programs and the context of certain service settings, in this case the U.S. Department of Veterans Affairs (VA) mental health services. METHODS/DESIGN: This study will use purposive sampling to recruit an Expert Panel comprising implementation science experts and VA mental health clinical managers. A novel, four-stage sequential mixed methods design will be employed. During Stage 1, the Expert Panel will participate in a modified Delphi process in which a published taxonomy of implementation strategies will be used to establish consensus on terms and definitions for implementation strategies. In Stage 2, the panelists will complete a concept mapping task, which will yield conceptually distinct categories of implementation strategies as well as ratings of the feasibility and effectiveness of each strategy. Utilizing the common nomenclature developed in Stages 1 and 2, panelists will complete an innovative menu-based choice task in Stage 3 that involves matching implementation strategies to hypothetical implementation scenarios with varying contexts. This allows for quantitative characterizations of the relative necessity of each implementation strategy for a given scenario. In Stage 4, a live web-based facilitated expert recommendation process will be employed to establish expert recommendations about which implementations strategies are essential for each phase of implementation in each scenario. DISCUSSION: Using a novel method of selecting implementation strategies for use within specific contexts, this study contributes to our understanding of implementation science and practice by sharpening conceptual distinctions among a comprehensive collection of implementation strategies

Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting.

In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure

Asymptomatic SARS Coronavirus Infection among Healthcare Workers, Singapore

We conducted a study among healthcare workers (HCWs) exposed to patients with severe acute respiratory syndrome (SARS) before infection control measures were instituted. Of all exposed HCWs, 7.5% had asymptomatic SARS-positive cases. Asymptomatic SARS was associated with lower SARS antibody titers and higher use of masks when compared to pneumonic SARS