Interprofessional collaboration among first responder students in a simulated disaster exercise.

Introduction: Interprofessional disaster simulation exercises provide an opportunity for first responder students to learn about disaster response and recovery, to practice their roles and to learn to collaborate with other first responders. With the move to virtual education during the COVID-19 pandemic, a table-top disaster exercise is an alternative format to inperson exercises. To date, most disaster simulation exercises for students have focused on the roles of healthcare providers.

A rapid and non-invasive proteomic analysis using DBS and buccal swab for multiplexed second-tier screening of Pompe disease and Mucopolysaccharidosis type I.

Purpose: Current newborn screening programs for Pompe disease (PD) and mucopolysaccharidosis type I (MPS I) suffer from a high false positive rate and long turnaround time for clinical follow up. This study aimed to develop a novel proteomics-based assay for rapid and accurate second-tier screening of PD and MPS I. A fast turnaround assay would enable the identification of severe cases who need immediate clinical follow up and treatment.

A Systematic Review of Motivational Interviewing to Address Substance Use with Justice-Involved Adults.

Motivational Interviewing (MI) is widely used in substance abuse treatment, possibly due to the short sessions and the treatment's cost-effectiveness. Previous research has established the efficacy of MI among a broad range of populations and outcomes. However, there is a lack of a review of the knowledge about if MI works with justice-involved individuals who have substance use issues.

Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease.

Background & Aims: Both existing clinical criteria and genetic testing have significant limitations for the diagnosis of Wilson disease (WD), often creating ambiguities in patient identification and leading to delayed diagnosis and ineffective management. ATP7B protein concentration, indicated by direct measurement of surrogate peptides from patient dried blood spot samples, could provide primary evidence of WD. ATP7B concentrations were measured in patient samples from diverse backgrounds, diagnostic potential is determined, and results are compared with biochemical and genetic results from individual patients.

p.P1379S, a benign variant with reduced ATP7B protein level in Wilson Disease.

Background: Wilson disease (WD) is an autosomal recessive disorder of copper transport caused by inherited defects in the gene and results in toxic accumulation of copper in various organs. We previously reported a family with three consecutive generations affected by WD that carries the variant, p.P1379S, which was classified at the time as likely pathogenic.

Multiplexed Proteomic Analysis for Diagnosis and Screening of Five Primary Immunodeficiency Disorders From Dried Blood Spots.

Early detection of Primary Immunodeficiencies Disorders (PIDDs) is of paramount importance for effective treatment and disease management. Many PIDDs would be strong candidates for newborn screening (NBS) if robust screening methods could identify patients from dried blood spots (DBS) during the neonatal period. As majority of congenital PIDDs result in the reduction or absence of specific proteins, direct quantification of these target proteins represents an attractive potential screening tool.

The co-occurrence of Wilson disease and X-linked agammaglobulinemia in one family highlights the promising diagnostic potential of proteolytic analysis.

Background: We report the first case of a family with co-occurrence of Wilson disease (WD), an autosomal recessive disorder of copper metabolism, and X-linked agammaglobulinemia (XLA), a primary immunodeficiency disorder (PIDD) that features marked reduction in circulating B lymphocytes and serum immunoglobulins.

Methods And Results: Through utilization of a multiplexed biomarker peptide quantification method known as the immuno-SRM assay, we were able to simultaneously and independently identify which family members are affected with WD and which are affected with XLA using dried blood spots (DBS).

Conclusion: Being able to delineate multiple diagnoses using proteolytic analysis from a single DBS provides support for implementation of this methodology for clinical diagnostic use as well as large-scale population screening, such as newborn screening (NBS).

Rapid Multiplexed Proteomic Screening for Primary Immunodeficiency Disorders From Dried Blood Spots.

Primary immunodeficiency disorders (PIDD) comprise a group of life-threatening congenital diseases characterized by absent or impaired immune responses. Despite the fact that effective, curative treatments are available with optimal clinical outcomes when diagnosed early, newborn screening does not exist for the majority of these diseases due to the lack of detectable, specific biomarkers or validated methods for population-based screening. Peptide immunoaffinity enrichment coupled with selected reaction monitoring mass spectrometry (immuno-SRM) is a sensitive proteomic assay, involving antibody-mediated peptide capture, that allows for concurrent quantification of multiple analytes.

Gd:DOTA-Modified 2-Hydroxypropyl-β-Cyclodextrin/4-Sulfobutyl Ether-β-Cyclodextrin-Based Polyrotaxanes as Long Circulating High Relaxivity MRI Contrast Agents.

A family of five water-soluble Gd:1,4,7,10-tetraazacyclododecane-1,4,7-tetraacetic acid-modified polyrotaxane (PR) magnetic resonance contrast agents bearing mixtures of 2-hydroxypropyl-β-cyclodextrin and 4-sulfobutylether-β-cyclodextrin macrocycles threaded onto Pluronic cores were developed as long circulating magnetic resonance contrast agents. Short diethylene glycol diamine spacers were utilized for linking the macrocyclic chelator to the PR scaffold prior to Gd chelation. The PR products were characterized by H NMR, gel permeation chromatography/multiangle light scattering, dynamic light scattering, and analytical ultracentrifugation.

Pluronic based β-cyclodextrin polyrotaxanes for treatment of Niemann-Pick Type C disease.

Niemann-Pick Type C disease (NPC) is a rare metabolic disorder characterized by disruption of normal cholesterol trafficking within the cells of the body. There are no FDA approved treatments available for NPC patients. Recently, the cycloheptaglucoside 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) has shown efficacy as a potential NPC therapeutic by extending lifetime in NPC mice, delaying neurodegeneration, and decreasing visceral and neurological cholesterol burden.

PLGA-PEG nano-delivery system for epigenetic therapy.

Efficient delivery of cytidine analogues such as Azacitidine (AZA) into solid tumors constitutes a primary challenge in epigenetic therapies. We developed a di-block nano-vector based on poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) for stabilization of the conjugated AZA under physiological conditions. With equimolar drug content, our nano-conjugate could elicit a better anti-proliferative effect over free drug in breast cancer both in vitro and in vivo, through reactivation of p21 and BRCA1 to restrict cell proliferation.

Human resource management and unit performance in knowledge-intensive work.

To clarify the potential value of a targeted system of human resource (HR) practices, we explore the unique effects of a relationship-oriented HR system and the more commonly studied high commitment HR system on unit performance in the context of knowledge-intensive work. We develop theoretical arguments suggesting that the high commitment HR system contributes to unit performance through its positive effects on employees' collective organizational commitment, general and firm-specific human capital, and access to knowledge. We argue that the relationship-oriented HR system contributes to unit performance through its positive effects on employees' collective access to knowledge by fostering a social context and interpersonal exchange conditions which support employees' ongoing access to knowledge flows within and outside their unit and broader organization.

Influence of Molecular Structure on the In Vivo Performance of Flexible Rod Polyrotaxanes.

Polyrotaxanes, a family of rod-shaped nanomaterials comprised of noncovalent polymer/macrocycle assemblies, are being used in a growing number of materials and biomedical applications. Their physiochemical properties can vary widely as a function of composition, potentially leading to different in vivo performance outcomes. We sought to characterize the pharmacokinetic profiles, toxicities, and protein corona compositions of 2-hydroxypropyl-β-cyclodextrin polyrotaxanes as a function of variations in macrocycle threading efficiency, molecular weight, and triblock copolymer core structure.

Impact of Mixed β-Cyclodextrin Ratios on Pluronic Rotaxanation Efficiency and Product Solubility.

Water-soluble polyrotaxanes have been prepared under heterogeneous conditions from mixtures of β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), methyl-β-cyclodextrin, or 6-monoazido-β-cyclodextrin with 4-sulfobutyl ether-β-cyclodextrin (SBE-β-CD) and Pluronic L81 copolymer modified with cholesterol end caps. Threading reactions gave polyrotaxane products in modest chemical yield that were reflective of the β-CD feed ratios in the reaction. Polyrotaxanes containing mixtures of HP-β-CD and SBE-β-CD were screened and found to be biologically active in an in vitro model of Niemann-Pick Type C disease where they mobilize aberrantly stored cholesterol similarly to monomeric cyclodextrin controls.

Microfluidic Assembly of Cationic-β-Cyclodextrin:Hyaluronic Acid-Adamantane Host:Guest pDNA Nanoparticles.

Traditionally, transfection complexes are typically formed by bulk mixing, producing particles with high polydispersity and limited control over vector size. Herein, we demonstrate the use of a commercial micro-reactor to assemble pDNA:cationic cyclodextrin:pendant polymer nanoparticles using a layer-by-layer approach. Our studies reveal that the particles formulated via microfluidic assembly have much smaller sizes, lower polydispersity, lower ζ-potentials, and comparable cell viability and transfection profiles in HeLa cells than bulk mixed particles.

Synthesis, characterization, and evaluation of pluronic-based β-cyclodextrin polyrotaxanes for mobilization of accumulated cholesterol from Niemann-Pick type C fibroblasts.

Several lines of evidence suggest that β-cyclodextrin (β-CD) derivatives initiate the efflux of accumulated, unesterified cholesterol from the late endosomal/lysosomal compartment in Niemann Pick C (NPC) disease models. Unfortunately, repeated injections or continuous infusions of current β-CD therapies are required to sustain suppression of symptoms and prolong life. In an effort to make CD treatment a more viable option by boosting efficacy and improving pharmacokinetics, a library of Pluronic surfactant-based β-CD polyrotaxanes has been developed using biocompatible poly(ethylene glycol) (PEG)-polypropylene glycol (PPG)-PEG triblock copolymers.

Association of Inhalation Toxicologists (AIT) working party recommendation for standard delivered dose calculation and expression in non-clinical aerosol inhalation toxicology studies with pharmaceuticals.

There are many ways in which the dose can be expressed in inhalation toxicology studies. This can lead to confusion when comparing results from studies performed in different laboratories. A working party of the Association of Inhalation Toxicologists has reviewed this subject in detail and has collected data from 10 inhalation laboratories and used these data to determine a new algorithm for the calculation of Respiratory Minute Volume (RMV), one of the most important factors in the calculation of delivered dose.

Functional molecular wires.

The properties of self-assembled molecules may be tuned by sequentially coupling components on a gold surface, the molecular electronics toolbox of chemically reactive building blocks yielding molecular wires with diode-like current-voltage (I-V) characteristics. The bias for rectification in each case is dependent upon the sequence of electron-donating and electron-accepting moieties and similar behaviour has been achieved for four different contacting techniques.

Solvent and temperature effects on the reduction and amination reactions of electrophiles by lithium dialkylaminoborohydrides.

The influence of temperature and solvent effects on the reduction and amination mechanisms of iodomethane by lithium N,N-diisopropylaminoborohydride (iPr-LAB) was examined in varying concentrations of THF and dioxane. The reactions of benzyl chloride and trimethylsilyl chloride with iPr-LAB in THF were also studied. The amination of iodomethane is favored over reduction at low and room temperatures in pure THF and with increasing the amount of dioxane in THF.

The interactive effects of recruitment practices and product awareness on job seekers' employer knowledge and application behaviors.

In this article, the author draws on research from the literature on marketing and recruitment to identify how recruitment practices and company product awareness are related to job seekers' application behaviors through 3 aspects of job seekers' employer knowledge. Based on results from a within-subject design with data from 123 recruiting companies and 456 student job seekers, the author's findings suggest that the relationships between recruitment strategies and application intentions and decisions are moderated by product awareness. Specifically, low-information recruitment practices are significantly and positively related to application behaviors through employer familiarity and employer reputation when product awareness is low.

Isotopically labeled crosslinking reagents: resolution of mass degeneracy in the identification of crosslinked peptides.

Mass spectrometry in three dimensions (MS3D) is a newly developed method for the determination of protein structures involving intramolecular chemical crosslinking of proteins, proteolytic digestion of the resulting adducts, identification of crosslinks by mass spectrometry (MS), peak assignment using theoretical mass lists, and computational reduction of crosslinks to a structure by distance geometry methods. To facilitate the unambiguous identification of crosslinked peptides from proteolytic digestion mixtures of crosslinked proteins by MS, we introduced double 18O isotopic labels into the crosslinking reagent to provide the crosslinked peptides with a characteristic isotope pattern. The presence of doublets separated by 4 Da in the mass spectra of these materials allowed ready discrimination between crosslinked and modified peptides, and uncrosslinked peptides using automated intelligent data acquisition (IDA) of MS/MS data.

The relationship between early recruitment-related activities and the application decisions of new labor-market entrants: a brand equity approach to recruitment.

Theory and research from the marketing literature on customer-based brand equity were used to predict how positive exposure to 4 early recruitment-related activities-publicity, sponsorships, word-of-mouth endorsements, and advertising-may affect the application decisions of engineering students. Similar to prior marketing findings, the results suggested that early recruitment-related activities were indirectly related to intentions and decisions through 2 dimensions of employer brand image: general attitudes toward the company and perceived job attributes. The relationships between word-of-mouth endorsements and the 2 dimensions of brand image were particularly strong.