Fixed-target serial crystallography at the Structural Biology Center.

Serial synchrotron crystallography enables the study of protein structures under physiological temperature and reduced radiation damage by collection of data from thousands of crystals. The Structural Biology Center at Sector 19 of the Advanced Photon Source has implemented a fixed-target approach with a new 3D-printed mesh-holder optimized for sample handling. The holder immobilizes a crystal suspension or droplet emulsion on a nylon mesh, trapping and sealing a near-monolayer of crystals in its mother liquor between two thin Mylar films. Data can be rapidly collected in scan mode and analyzed in near real-time using piezoelectric linear stages assembled in an XYZ arrangement, controlled with a graphical user interface and analyzed using a high-performance computing pipeline. Here, the system was applied to two ß-lactamases: a class D serine ß-lactamase from Chitinophaga pinensis DSM 2588 and L1 metallo-ß-lactamase from Stenotrophomonas maltophilia K279a.

Care erosion in sedation assessment: A prospective comparison of usual care Richmond Agitation-Sedation Scale assessment with protocolized assessment for medical intensive care unit patients.

OBJECTIVES: To determine concordance between an explicit protocolized assessment of the Richmond Agitation-Sedation Scale and an assessment performed during usual care nursing practice. RESEARCH DESIGN: In an urban, safety-net hospital, intensive care nurses previously trained in sedation assessment recorded a bedside Richmond Agitation-Sedation Scale assessment, while study investigators used an explicit script to perform the assessment at a similar time point. Kappa indices determined concordance of the assessments. Bivariate analyses explored factors associated with discordance and unresponsiveness. RESULTS: Twenty-one subjects with 38 observations were analysed. Bedside nursing assessment was poorly concordant with protocolized assessment (ƙ = 0.21) with the former reporting significantly lighter sedation (median -2 vs. -5, p = .01). Bedside assessment was significantly less likely than protocolized assessment to categorize subjects as unresponsive (29 vs. 50%, p = .02). CONCLUSION: Methods used in usual clinical practice to assess adequacy of sedation frequently led to oversedation. We propose that care erosion, the deterioration of skills over time, may help explain this finding. IMPLICATIONS FOR NURSING MANAGEMENT: Results suggest sedation assessment may be particularly vulnerable to care erosion. Nurse managers should monitor for signs of care erosion and consider utilization of explicit scripts during sedation assessment and/or frequent education to ensure sedation assessment accuracy.

Effect of Interhospital ICU Relocation on Patient Physiology and Clinical Outcomes.

Relocation of large numbers of critically ill patients between hospitals is sometimes necessary and the risks associated with relocation may be high. In the setting of adherence to an interhospital intensive care unit (ICU) relocation protocol, we aimed to determine whether the interhospital relocation of all ICU patients in a single day is associated with changes in vital signs, device removal, and worse clinical outcomes. We conducted a prospective, observational, cohort study of all critically ill adults admitted to a tertiary medical center's ICUs on the day of a planned hospital relocation and exposed to interhospital ICU relocation compared with unexposed critically ill adults. Changes in vital signs were evaluated by the before-and-after interhospital relocation measurement of vital signs, and clinical outcomes were collected for all patients. A total of 699 patients were admitted to the ICU during the observation period, 24 of whom were exposed to interhospital ICU relocation on a single day. The median interhospital transport duration was 28 minutes (interquartile range: 24-35) and 29% of patients were receiving invasive mechanical ventilation. Patients exposed to interhospital ICU relocation had no significant change in any vital sign measurement and no devices were unintentionally removed. Inhospital mortality was similar (8.3%) to patients not exposed to interhospital ICU relocation (9.2%, P > .99). In the setting of adherence to an ICU relocation protocol, the interhospital ICU relocation of all critically ill adults during a single day is not associated with changes in vital signs, device removal, or worse clinical outcomes.

Exercise and Cyclic Light Preconditioning Protect Against Light-Induced Retinal Degeneration and Evoke Similar Gene Expression Patterns.

To compare patterns of gene expression following preconditioning cyclic light rearing versus preconditioning aerobic exercise. BALB/C mice were preconditioned either by rearing in 800 lx 12:12 h cyclic light for 8 days or by running on treadmills for 9 days, exposed to toxic levels of light to cause light-induced retinal degeneration (LIRD), then sacrificed and retinal tissue harvested. Subsets of mice were maintained for an additional 2 weeks and for assessment of retinal function by electroretinogram (ERG). Both preconditioning protocols partially but significantly preserved retinal function and morphology and induced similar leukemia inhibitory factor (LIF) gene expression pattern. The data demonstrate that exercise preconditioning and cyclic light preconditioning protect photoreceptors against LIRD and evoke a similar pattern of retinal LIF gene expression. It may be that similar stress response pathways mediate the protection provided by the two preconditioning modalities.

The pharmacist's role in reducing infusion-related phlebitis.

PURPOSE: Pharmacists oversee parenteral drug preparation and administration in hospitals, clinics, infusion centers, and home infusion settings. Infusion-related phlebitis (IRP), the most common complication of intravenous infusion therapy, significantly impacts therapeutic outcomes, patient satisfaction, cost of care, and provider workload. Here we review the major etiologies of IRP and describe potential pharmacological and nonpharmacological interventions for preventing and managing the condition as well as for improving vascular access health in multiple-drug administration settings. SUMMARY: Many parenterally administered drugs cause phlebitis due to mechanical, chemical, or infectious etiologies. Pharmacists can recommend nonpharmacological strategies to mitigate phlebitis, including -judicious device selection and placement; adjustment of the drug concentration, flow rate, or formulation; infusion site rotation; and use of inline filters to minimize contaminant particulates. Pharmacological treatments for phlebitis include topical, local, and systemic anti-inflammatory and analgesic agents that can reduce symptom severity and prevent further treatment complications or delays. CONCLUSION: Pharmacists can contribute a unique perspective to interprofessional teams tasked with making policy and formulary decisions that minimize the negative impacts of IRP on drug delivery and patient outcomes.

Preparing Pharmacy Educators as Expedition Guides to Support Professional Identity Formation in Pharmacy Education.

Objective. To provide an educator-friendly travel guide for supporting pharmacy students' lifelong journey to professional identity formation.Findings. In contrast to professionalism, which has emphasized externally visible behaviors, professional identity focuses on the internalization of the attitudes, standards, and behavioral norms of a profession, such that one "thinks, acts, and feels" like a member of that profession. Identity, whether personal or professional, is continuously developed in part during interactions with others and in response to internal and external feedback on those interactions. Educators play a critical role in helping students navigate the "provocative moments" (eg, transitions, dissonance) that accompany identity formation. To help educators travel with purpose, several identity formation theories suggest means of creating learning experiences and supporting the development of a professional identity. Additionally, guidebooks for the trip (ie, published literature) provide examples of didactic and experiential teaching approaches that can be used to promote professional identity formation. While further exploration and research are necessary, traveling this journey with colleagues can help members of the Academy succeed in sustainably and effectively infusing intentional professional identity formation within pharmacy education and training.Summary. There are myriad ways for educators to develop and support professional identity formation, which can present a challenge when defining the role that educators play in this complex, dynamic process. Educators must understand the reasoning behind various approaches and the common dialogue used to engage and support learners as their expedition guides on the lifelong journey to professional identity formation.

More than Our Enemy: Making Space for the Microbiome in Pharmacy Education.

The microbiome is the collection of commensal microorganisms along with their genomes inhabiting the human body. Despite the many known beneficial effects of these microbes on human health, the 2016 ACPE Standards for Doctor of Pharmacy curricula describe Medical Microbiology in Appendix 1 with a pathogen-centered focus. Over the last twenty years, evolving biotechnology has enabled a deeper understanding of the microbiome in the context of both wellness and disease. Retail stores are allocating increasing shelf space to commercial probiotic products, while the approach to PharmD training on the selection and use of these natural care products remains static, creating a disproportionate footprint between PharmD curricula and consumer markets. Looking to the future of patient care, we brief pharmacy educators on the current evidence and invite discussion around a proposed revision to the 2025 ACPE Standards that would add language recognizing the beneficial role of the commensal microbiota and expanding therapeutic applications of microbiome supplementation. We suggest a variety of opportunities within Doctor of Pharmacy curricula as leverage points for including relevant aspects of the microbiome in the training of future pharmacists.

Creating Crosswalks for Knee Outcomes After ACL Reconstruction Between the KOOS and the IKDC-SKF.

BACKGROUND: Anterior cruciate ligament (ACL) registries do not all use the same patient-reported outcome measures, limiting comparisons and preventing pooling of data for meta-analysis. Our objective was to create a statistical crosswalk to convert cohort and registry mean Knee Injury and Osteoarthritis Outcome Scores (KOOS) to International Knee Documentation Committee-Subjective Knee Form (IKDC-SKF) scores and vice versa to allow these comparisons. METHODS: Data from 3 ACL registries were pooled (n = 14,412) and were separated into a training data set (70% of the sample) or a validation data set (30% of the sample). The KOOS and the IKDC-SKF scores were available prior to the operation and at 1, 2, and 5 or 6 years postoperatively. We used equipercentile equating methods to create crosswalks in the training data set and examined accuracy in the validation data set as well as bootstrapping analyses to assess the impact of sample size on accuracy. RESULTS: Preliminary analyses suggested that crosswalks could be attempted: large correlations between scores on the 2 measures (r = 0.84 to 0.94), unidimensionality of scores, and subpopulation invariance were deemed sufficient. When comparing actual scores with crosswalked scores in the validation data set, negligible bias was observed at the group level; however, individual score deviations were variable. The crosswalks are successful for the group level only. CONCLUSIONS: Our crosswalks successfully convert between the KOOS and the IKDC-SKF scores to allow for a group-level comparison of registry and other cohort data. CLINICAL RELEVANCE: These crosswalks allow comparisons among different national ligament registries as well as other research cohorts and studies; they also allow data from different patient-reported outcome measures to be pooled for meta-analysis. These crosswalks have great potential to improve our understanding of recovery after ACL reconstruction and aid in our ongoing efforts to improve outcomes and patient satisfaction, as well as to allow the continued analysis of historical data.

Data collection from crystals grown in microfluidic droplets.

Protein crystals grown in microfluidic droplets have been shown to be an effective and robust platform for storage, transport and serial crystallography data collection with a minimal impact on diffraction quality. Single macromolecular microcrystals grown in nanolitre-sized droplets allow the very efficient use of protein samples and can produce large quantities of high-quality samples for data collection. However, there are challenges not only in growing crystals in microfluidic droplets, but also in delivering the droplets into X-ray beams, including the physical arrangement, beamline and timing constraints and ease of use. Here, the crystallization of two human gut microbial hydrolases in microfluidic droplets is described: a sample-transport and data-collection approach that is inexpensive, is convenient, requires small amounts of protein and is forgiving. It is shown that crystals can be grown in 50-500 pl droplets when the crystallization conditions are compatible with the droplet environment. Local and remote data-collection methods are described and it is shown that crystals grown in microfluidics droplets and housed as an emulsion in an Eppendorf tube can be shipped from the US to the UK using a FedEx envelope, and data can be collected successfully. Details of how crystals were delivered to the X-ray beam by depositing an emulsion of droplets onto a silicon fixed-target serial device are provided. After three months of storage at 4°C, the crystals endured and diffracted well, showing only a slight decrease in diffracting power, demonstrating a suitable way to grow crystals, and to store and collect the droplets with crystals for data collection. This sample-delivery and data-collection strategy allows crystal droplets to be shipped and set aside until beamtime is available.