A shadowing program for PAs and APRNs to promote collaborative care.

ABSTRACT: This article describes a shadowing program aimed at promoting collaborative care among PAs and NPs at an academic medical center. The program fostered interprofessional and interdisciplinary experiences to improve collaborative skills. Clinicians who completed the program had a significant improvement in collaborative competencies, as measured by the Interprofessional Collaboration Competency Attainment Survey.

The millennial engagement, resiliency and retention study: What does your millennial advanced practice registered nurse workforce really want?

BACKGROUND: Increasing the use of advanced practice nurses may be one of the most viable options to meeting the burgeoning health care demands of older Americans and impending provider shortage over the next two decades. However, keeping the millennial workforce engaged and retained continues to be a significant challenge for health care administrators. PURPOSE: The purpose of this study was to understand the intergenerational advanced practice registered nurse (APRN) workforce and assess what job satisfaction factors impact APRN intention to stay, and explore how variables such as resiliency style and age affect retention in these young careerists. METHODS: This was a single-center, cross-sectional descriptive study using survey methodology. A total of 405 APRNs from all specialties and practice sites from a large Midwestern Academic Medical Center were eligible to participate. A total of 165 APRNs completed the survey, which was a 41% response rate. RESULTS: There were no significant differences in mean resiliency scores by age cohort (p > .05) or a higher intention to leave in millennial-aged APRNs versus older APRNs (p > .05); however, there were significant mean differences in job satisfaction responses that warrant consideration in millennial versus older "baby boomer" APRNs on items such as professional growth, compensation, monetary bonuses, and expanding procedures and skills within scope of practice. IMPLICATIONS FOR PRACTICE: Understanding generational differences in APRN job satisfaction assists hospital leaders to develop strategies to support, engage, and retain younger careerists, which may help mitigate turnover.

Sialic acid mediated mechanical activation of ß2 adrenergic receptors by bacterial pili.

Meningococcus utilizes ß-arrestin selective activation of endothelial cell ß2 adrenergic receptor (ß2AR) to cause meningitis in humans. Molecular mechanisms of receptor activation by the pathogen and of its species selectivity remained elusive. We report that ß2AR activation requires two asparagine-branched glycan chains with terminally exposed N-acetyl-neuraminic acid (sialic acid, Neu5Ac) residues located at a specific distance in its N-terminus, while being independent of surrounding amino-acid residues. Meningococcus triggers receptor signaling by exerting direct and hemodynamic-promoted traction forces on ß2AR glycans. Similar activation is recapitulated with beads coated with Neu5Ac-binding lectins, submitted to mechanical stimulation. This previously unknown glycan-dependent mode of allosteric mechanical activation of a G protein-coupled receptor contributes to meningococcal species selectivity, since Neu5Ac is only abundant in humans due to the loss of CMAH, the enzyme converting Neu5Ac into N-glycolyl-neuraminic acid in other mammals. It represents an additional mechanism of evolutionary adaptation of a pathogen to its host.

Changes in canine serum N-glycosylation as a result of infection with the heartworm parasite Dirofilaria immitis.

Filariases are diseases caused by infection with filarial nematodes and transmitted by insect vectors. The filarial roundworm Dirofilaria immitis causes heartworm disease in dogs and other carnivores. D. immitis is closely related to Onchocerca volvulus, Wuchereria bancrofti and Brugia malayi, which cause onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis) in humans and are neglected tropical diseases. Serum N-glycosylation is very sensitive to both pathological infections and changes in mammalian biology due to normal aging or lifestyle choices. Here, we report significant changes in the serum N-glycosylation profiles of dogs infected with D. immitis. Our data derive from analysis of serum from dogs with established patent infections and from a longitudinal infection study. Overall, galactosylation and core fucosylation increase, while sialylation decreases in infected dog sera. We also identify individual glycan structures that change significantly in their relative abundance during infection. Notably, the abundance of the most dominant N-glycan in canine serum (biantennary, disialylated A2G2S2) decreases by over 10 percentage points during the first 6 months of infection in each dog analyzed. This is the first longitudinal study linking changes in mammalian serum N-glycome to progression of a parasitic infection.

Glycosylation profiling of dog serum reveals differences compared to human serum.

Glycosylation is the most common post-translational modification of serum proteins, and changes in the type and abundance of glycans in human serum have been correlated with a growing number of human diseases. While the glycosylation pattern of human serum is well studied, little is known about the profiles of other mammalian species. Here, we report detailed glycosylation profiling of canine serum by hydrophilic interaction chromatography-ultraperformance liquid chromatography (HILIC-UPLC) and mass spectrometry. The domestic dog (Canis familiaris) is a widely used model organism and of considerable interest for a large veterinary community. We found significant differences in the serum N-glycosylation profile of dogs compared to that of humans, such as a lower abundance of galactosylated and sialylated glycans. We also compare the N-glycan profile of canine serum to that of canine IgG - the most abundant serum glycoprotein. Our data will serve as a baseline reference for future studies when performing serum analyses of various health and disease states in dogs.

An engineered high affinity Fbs1 carbohydrate binding protein for selective capture of N-glycans and N-glycopeptides.

A method for selective and comprehensive enrichment of N-linked glycopeptides was developed to facilitate detection of micro-heterogeneity of N-glycosylation. The method takes advantage of the inherent properties of Fbs1, which functions within the ubiquitin-mediated degradation system to recognize the common core pentasaccharide motif (Man3GlcNAc2) of N-linked glycoproteins. We show that Fbs1 is able to bind diverse types of N-linked glycomolecules; however, wild-type Fbs1 preferentially binds high-mannose-containing glycans. We identified Fbs1 variants through mutagenesis and plasmid display selection, which possess higher affinity and improved recovery of complex N-glycomolecules. In particular, we demonstrate that the Fbs1 GYR variant may be employed for substantially unbiased enrichment of N-linked glycopeptides from human serum. Most importantly, this highly efficient N-glycopeptide enrichment method enables the simultaneous determination of N-glycan composition and N-glycosites with a deeper coverage (compared to lectin enrichment) and improves large-scale N-glycoproteomics studies due to greatly reduced sample complexity.

Profiling of core fucosylated N-glycans using a novel bacterial lectin that specifically recognizes α1,6 fucosylated chitobiose.

A novel fucose-binding lectin (SL2-1) from the bacterium Streptomyces rapamycinicus was identified by analysis of metagenomic DNA sequences. SL2-1 belongs to a new group of bacterial fucose-specific lectins that have no similarity to known bacterial fucose-binding proteins, but are related to certain eukaryotic fucose-binding lectins. The 17 kDa protein was expressed recombinantly in E. coli and purified by affinity chromatography. Glycan microarray analysis with fluorescently labeled recombinant SL2-1 demonstrated its ability to bind to core α1-6 fucosylated N-glycans, but not to core α1-3 fucosylated N-glycans, or other α1-2, α1-3 and α1-4 fucosylated oligosaccharides. The minimal high affinity binding epitope of SL2-1 was α1-6 fucosylated di-n-acetylchitobiose. The recombinant lectin was efficient in detection of N-glycan core fucosylation using lectin blotting and lectin ELISA assays. Finally, a workflow using SL2-1 for selective and quantitative profiling of core fucosylated N-glycans using UPLC-HILIC-FLR analysis was established. The approach was validated for selective capture and analysis of core fucosylated N-glycans present in complex glycan mixtures derived from mammalian serum IgG.

Ultrahigh throughput, ultrafiltration-based n-glycomics platform for ultraperformance liquid chromatography (ULTRA(3)).

Accurate, reproducible, and fast quantification of N-glycans is crucial not only for the development and quality control of modern glycosylated biopharmaceuticals, but also in clinical biomarker discovery. Several methods exist for fluorescent labeling of N-glycans and subsequent chromatographic separation and quantification. However, the methods can be complex, lengthy, and expensive. Here we report an automated ultrafiltration-based N-glycoanalytical workflow combined with a glycan labeling strategy that is based on the reaction of glycosylamines with fluorescent carbamate. The entire protocol is quick, simple, and cost-effective and requires less than 1 µg of protein per sample. As many as 768 affinity purified IgG glycoprotein samples can be prepared in a single run with a liquid handling platform.

Formation of luminescent terbium(III) self-assemblies from pyridyl bis-amidothioureas based ligands in MeOH and in water-DMSO solutions and their use in anion sensing application.

The self-assembly between the amidothiourea ligands 1 and 2 and Tb(III) gave rise to the formation of 1:1 and 3:1 (ligand-Tb) supramolecular architectures that were shown to be luminescent in both MeOH and in water-DMSO solutions; preliminary investigations in the latter system also showed that their emission was modulated upon interacting with anions such as acetate and phosphate due to host-guest formation.

High-throughput quantitative N-glycan analysis of glycoproteins.

N-linked oligosaccharides are complex non-template-derived structures that are attached to the side chains of asparagine, via the nitrogen atom. Specific changes in the N-glycans of serum glycoproteins have been associated with the pathogenesis of many diseases. The oligosaccharides present on the C(H)2 domain of immunoglobulins are known to modulate the effector functions of the molecule. These glycans provoke various biological effects, necessitating the development of robust high-throughput technology in order to fully characterize the N-glycosylation profile. This chapter describes in detail four methods to release N-glycans from the glycoprotein of interest. Two of these protocols, referred to as the "In-Gel Block" and "1D sodium dodecyl sulfate-polyacrylamide gel electrophoresis" methods, require immobilization of the glycoprotein prior to analysis. An automated method is also described, involving the purification of immunoglobulins directly from fermentation media, and, finally, an "In-solution method" is detailed, which directly releases the N-glycans into solution. HILIC and WAX-HPLC are used to analyze the N-glycan profile. Exoglycosidase enzymes digestion arrays, in combination with computer-assisted data analysis, are used to determine both the sequence and linkage of the N-glycans present.

Recognition and sensing of biologically relevant anions in alcohol and mixed alcohol-aqueous solutions using charge neutral cleft-like glycol-derived pyridyl-amidothiourea receptors.

In this paper, the synthesis and the spectroscopic investigation of new colorimetric receptors for anions 3-6, possessing a glycol chain at the 4-position of the pyridyl ring, and 1 and 2, which lack such a chain, and the X-ray crystal structure of 2 is presented. Structures 3-6 are able to bind to anions in competitive media, such as alcohol or in a mixture of methanol and water, where the anion recognition gives rise to changes in the absorption spectra, which is red-shifted, in 1:1 or 1:2 (sensor/anion) stoichiometry. The anion recognition for 1 and 2 was also investigated in organic solvents and in a 4:1 mixture of DMSO/H(2)O. The binding of 1 to anions such as acetate, phosphate, and fluoride was also evaluated using (1)H NMR in DMSO-d(6).

Colorimetric and fluorescent anion sensors: an overview of recent developments in the use of 1,8-naphthalimide-based chemosensors.

This critical review focuses on the development of anion sensors, being either fluorescent and/or colorimetric, based on the use of the 1,8-naphthalimide structure; a highly versatile building unit that absorbs and emits at long wavelengths. The review commences with a short description of the most commonly used design principles employed in chemosensors, followed by a discussion on the photophysical properties of the 4-amino-1,8-naphthalimide structure which has been most commonly employed in both cation and anion sensing to date. This is followed by a review of the current state of the art in naphthalimide-based anion sensing, where systems using ureas, thioureas and amides as hydrogen-bonding receptors, as well as charged receptors have been used for anion sensing in both organic and aqueous solutions, or within various polymeric networks, such as hydrogels. The review concludes with some current and future perspectives including the use of the naphthalimides for sensing small biomolecules, such as amino acids, as well as probes for incorporation and binding to proteins; and for the recognition/sensing of polyanions such as DNA, and their potential use as novel therapeutic and diagnostic agents (95 references).

Colorimetric sensing of anions in aqueous solution using a charge neutral, cleft-like, amidothiourea receptor: tilting the balance between hydrogen bonding and deprotonation in anion recognition.

The design, synthesis and physical evaluation of 1, a visible colorimetric 'naked eye' pyridyl based bis-amidothiourea sensor for anions, is described. This charge neutral sensor gives rise to significant changes in the absorption spectra upon interactions with several important biological anions such as AMP and ADP in 4:1 DMSO-H(2)O solution, while ATP was not detected. These colorimetric changes are due to the formation, or the combination of hydrogen bonding complexes and/or deprotonation between these anions and 1.

Botulinum toxin as treatment for a unique case of subcutaneous emphysema.

A developmentally delayed 11-year-old male developed extensive spontaneous subcutaneous emphysema 6 weeks after a laryngotracheal separation. Computed tomography demonstrated a small amount of air at the distal end of the laryngeal stump and significant esophageal air. Aerophagia was diagnosed with air presumed diverted through the laryngeal stump due to cricopharyngeal hypertension. Cricopharyngeal botulinum toxin injection was coordinated with a minimal neck dissection to drain the subcutaneous emphysema. The subcutaneous emphysema gradually improved and the patient was discharged home. His subcutaneous emphysema has not returned after four total botulinum toxin injections every 3 months.

Perioperative management of sickle cell disease children undergoing adenotonsillectomy.

OBJECTIVE: To determine if outpatient tailored perioperative management has the same complication rate as that previously published for sickle cell disease (SCD) children who undergo adenotonsillectomy. STUDY DESIGN AND SETTING: Retrospective chart review of SCD children who underwent tonsillectomy with outcome measures of perioperative management and postsurgical complications. RESULTS: Of 41 patients, 61% were monitored for <24 hours with the average length of stay being 2 days (range, 1 to 10). Postoperative complications were noted in 9 (22%) patients, including 8 (20%) with hypoxia, 4 (10%) fever, 3 (8%) acute chest syndrome, and 1 (2.4%) airway fire, which are similar to the published literature. CONCLUSIONS: Current literature supports extensive perioperative management with hospital stays averaging 3 to 5 days. These data demonstrate that the majority of these patients can be managed with <24-hour hospitalization stays with similar complication rates as previously described in the literature. SIGNIFICANCE: This study establishes a new paradigm for perioperative management of SCD children who undergo adenotonsillectomy. EBM RATING: C-4.

Dental status and quality of life in long-term head and neck cancer survivors.

OBJECTIVES: To analyze how the dental status of long-term head and neck cancer survivors affects their subjective quality of life. STUDY DESIGN: Observational case series. METHODS: A convenience sample of 5-year head and neck cancer survivors underwent the following battery of tests: 1) targeted head and neck examination, 2) updated medical history, 3) dental evaluation, 4) standardized quality of life questionnaires. RESULTS: Eighty-six survivors were included in the study. The following associations were identified: 1) those who became edentulous secondary to cancer treatment and those without occlusion at time of the study demonstrated worse Pain, Activity, Recreation/Entertainment, Chewing, Swallowing, Speech, Eating in Public, Normalcy of Diet, Physical Well-Being, Social/Family Well-Being, Functional Well-Being, and Additional Concerns scores; 2) higher Decayed/Missing/Filled scores were associated with worse Pain, Disfigurement, Activity, Recreation/Entertainment, Employment, Chewing, Swallowing, Speech, Eating in Public, Understandability of Speech, Normalcy of Diet, Physical Well-Being, Additional Concerns scores, and weight loss; 3) decreased oral opening measurements were associated with worse Chewing, Swallowing, Eating in Public, Normalcy of Diet, Additional Concerns scores, and weight loss; 4) edentulous survivors who did not use dentures had worse Pain, Activity, Recreation/Entertainment, Understandability of Speech, and Eating in Public scores. CONCLUSIONS: Although previous studies have shown that many of the effects of cancer treatment disappear between 1 and 3 years, this study shows that the dental status has a persistent impact on subjective quality of life.

The relationship between parental factors at infancy and parent-reported control over children's eating at age 7.

The objective of this study was to determine predictors of parental control over children's eating. Data were obtained from 135 children and their parents from the Stanford Infant Growth Study. Assessments were obtained from parents at their child's birth and age 7. Parental body dissatisfaction at their child's birth predicted pressure to eat for both sons and daughters. In addition, minority status, parent being born outside of the United States, and a mother's early return to work predicted parental pressure to eat for sons. For daughters, an early maternal pushy feeding style also predicted parental pressure to eat. Parental hunger, a parental history of eating disorders and parent being born outside of the United States predicted food restriction for daughters. There were no predictors of food restriction for sons. We concluded that parental control appears not always to be simply a reaction to a child's lack of self-control or overweight, but may be present before such issues arise, particularly with the presence of certain cultural factors.