A Cross-Sectional, Mixed-Methods Analysis to Identify the Relative Importance of Factors Students and Providers Evaluate When Making a Job Choice.

Little is known about the relative importance of factors that contribute to job choices among health care providers. A convenience sample of 173 health care providers (N=134) and physician assistant students (N=39) completed a cross-sectional survey. Participants rated the importance of sixteen job- (e.g., work environment), community- (e.g., recreational opportunities), and personal-related factors (e.g., children) and one open-ended item. The highest rated item, on average, was an opportunity to make a difference in patient quality of life (mean (M)=4.57, standard deviation (SD)=0.63) while the lowest rated item was wealth/prestige of living in a certain area (M=2.43, SD=1.05). The average importance rating was similar across types of providers and between providers and students. While personal interest to positively affect patients' quality of life was rated as the most important factor, almost all the studied items were rated as important or very important by the majority of participants.

Job attributes valued by physicians, PAs, and NPs: A cross-sectional survey.

OBJECTIVE: This study evaluated the relative importance of job-, community-, and individual-related factors that contribute to job choice among physicians, physician assistants (PAs), and NPs, to inform policy options to recruit clinicians to rural areas. METHODS: A cross-sectional online survey of PA preceptors from three institutions in two states. Participants were asked to rate the importance of 16 job-, community-, and individual-related factors when choosing a job. RESULTS: We received responses from 45 physicians, 74 PAs, and 15 NPs (24.2% response rate), who rated most job-, community-, and individual-related factors as important; ratings were similar across clinicians. PAs rated loan repayment programs and work hours higher than physicians, though the magnitude of the difference was small. CONCLUSIONS: Clinicians similarly rated many factors as important. A better understanding of the tradeoffs clinicians are willing to make between these factors when making a job choice is critical to increase the attractiveness of rural positions.

NP and PA Privileging in Acute Care Settings: Do Scope of Practice Laws Matter?

As hospitals' interest in nurse practitioners (NPs) and physician assistants (PAs) grows, their leadership is eager to know how their medical staffing privileging policies for these professionals compare to peer hospitals. This study assesses the extent of variation of these policies in four clinical areas and examines whether the differences are associated with state scope of practice laws for NPs and PAs. We also examine the relationship of NP and PA privileging policies to each other. Our analysis finds no evidence that hospital privileging is associated with state scope of practice, and indeed within-state variation is more significant than cross-state variation. We also find a strong correlation between NP and PA privileging in all four clinical areas. These results suggest the need for additional research to understand the institutional-level variables and human dynamics at the level of medical staffing committees that may explain the dramatic variation in privileging policies and, ultimately, the effects of different privileging levels on costs and quality.

Adult-onset Leigh syndrome linked to the novel stop codon mutation m.6579G>A in MT-CO1.

Adult-onset Leigh syndrome is a rare but important manifestation of mitochondrial disease. We report a 17 year old female who presented with subacute encephalopathy, brainstem and extrapyramidal signs, raised CSF lactate, and symmetrical hyperintensities in the basal ganglia on T2-weighted cerebral MRI. The presence of cytochrome c oxidase deficient fibres in muscle tissue prompted sequencing of the entire mitochondrial genome which revealed the novel stop codon mutation m.6579G>A; p.Gly226X in MT-CO1. Here we present the case and review the clinicopathological and molecular spectrum of previously reported MT-CO1 truncating mutations.

The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian α-linked glycosylceramides.

Glycosylceramides in mammalian species are thought to be present in the form of ß-anomers. This conclusion was reinforced by the identification of only one glucosylceramide and one galactosylceramide synthase, both ß-transferases, in mammalian genomes. Thus, the possibility that small amounts of α-anomers could be produced by an alternative enzymatic pathway, by an unfaithful enzyme, or spontaneously in unusual cellular compartments has not been examined in detail. We approached the question by taking advantage of the exquisite specificity of T and B lymphocytes and combined it with the specificity of catabolic enzymes of the sphingolipid pathway. Here, we demonstrate that mammalian immune cells produce constitutively very small quantities of α-glycosylceramides, which are the major endogenous ligands of natural killer T cells. Catabolic enzymes of the ceramide and glycolipid pathway tightly control the amount of these α-glycosylceramides. The exploitation of this pathway to manipulate the immune response will create new therapeutic opportunities.

Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure.

OBJECTIVE: Titin gene (TTN) mutations have been described in eight families with hereditary myopathy with early respiratory failure (HMERF). Some of the original patients had features resembling myofibrillar myopathy (MFM), arguing that TTN mutations could be a much more common cause of inherited muscle disease, especially in presence of early respiratory involvement. METHODS: We studied 127 undiagnosed patients with clinical presentation compatible with MFM. Sanger sequencing for the two previously described TTN mutations in HMERF (p.C30071R in the 119th fibronectin-3 (FN3) domain, and p.R32450W in the kinase domain) was performed in all patients. Patients with mutations had detailed review of their clinical records, muscle MRI findings and muscle pathology. RESULTS: We identified five new families with the p.C30071R mutation who were clinically similar to previously reported cases, and muscle pathology demonstrated diagnostic features of MFM. Two further families had novel variants in the 119th FN3 domain (p.P30091L and p.N30145K). No patients were identified with mutations at position p.32450. CONCLUSIONS: Mutations in TTN are a cause of MFM, and titinopathy is more common than previously thought. The finding of the p.C30071R mutation in 3.9% of our study population is likely due to a British founder effect. The occurrence of novel FN3 domain variants, although still of uncertain pathogenicity, suggests that other mutations in this domain may cause MFM, and that the disease is likely to be globally distributed. We suggest that HMERF due to mutations in the TTN gene be nosologically classified as MFM-titinopathy.

Heparin antagonism by polyvalent display of cationic motifs on virus-like particles.

Particles to the rescue! The construction of cationic amino acid motifs on the surface of bacteriophage Qbeta by genetic engineering or chemical conjugation gives particles that are potent inhibitors of the anticoagulant action of heparin, which is a common anticlotting agent subject to clinical overdose.Polyvalent interactions allow biological structures to exploit low-affinity ligand-receptor binding events to affect physiological responses. We describe here the use of bacteriophage Qbeta as a multivalent platform for the display of polycationic motifs that act as heparin antagonists. Point mutations to the coat protein allowed us to generate capsids bearing the K16M, T18R, N10R, or D14R mutations; because 180 coat proteins form the capsid, the mutants provide a spectrum of particles differing in surface charge by as much as +540 units (K16M vs. D14R). Whereas larger poly-Arg insertions (for example, C-terminal Arg(8)) did not yield intact virions, it was possible to append chemically synthesized oligo-Arg peptides to stable wild-type (WT) and K16M platforms. Heparin antagonism by the particles was evaluated by using the activated partial thrombin time (aPTT) clotting assay; this revealed that T18R, D14R, and WT-(R(8)G(2))(95) were the most effective at disrupting heparin-mediated anticoagulation (>95 % inhibition). This activity agreed with measurements of zeta potential (ZP) and retention time on cation exchange chromatography for the genetic constructs, which distribute their added positive charge over the capsid surface (+180 and +360 for T18R and D14R relative to WT). The potent activity of WT-(R(8)G(2))(95), despite its relatively diminished overall surface charge is likely a consequence of the particle's presentation of locally concentrated regions with high positive charge density that interact with heparin's extensively sulfated domains. The engineered cationic capsids retained their ability to inhibit heparin at high concentrations and showed no anticlotting activity of the kind that limits the utility of antiheparin polycationic agents that are currently in clinical use.