Family Medicine Clerkship Students’ Experiences With Team-Based Care

Interprofessional team-based care has the potential to improve patient outcomes, improve access to care, decrease costs, and improve team satisfaction. In recent years, efforts to implement team-based care have grown with the adoption of the Patient-Centered Medical Home (PCMH) and an increasing focus on value-based payment models. To better prepare our learners for this future, we introduced a formal team-based care curriculum in our three family medicine residency programs and one pediatric program. In addition to curricula for residents, we developed a team-based care didactic for family medicine clerkship students, presented by an interprofessional team of faculty. This session will describe our curricular efforts, team-based didactic for students, and outcomes related to students’ experiences with and knowledge of team-based care

Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis

Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. Methods: We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Results: Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. Conclusions: DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis.This work was sponsored by grants from Acción Estratégica en Salud (PI13/00297 and PI11/00581), the Neurosciences and Aging Foundation, the Francisco Soria Melguizo Foundation, Octopharma, and Parkinson Madrid (PI2012/0032).S

The Impact of Small Molecule Binding on the Energy Landscape of the Intrinsically Disordered Protein C-Myc

Intrinsically disordered proteins are attractive therapeutic targets owing to their prevalence in several diseases. Yet their lack of well-defined structure renders ligand discovery a challenging task. An intriguing example is provided by the oncoprotein c-Myc, a transcription factor that is over expressed in a broad range of cancers. Transcriptional activity of c-Myc is dependent on heterodimerization with partner protein Max. This protein-protein interaction is disrupted by the small molecule 10058-F4 (1), that binds to monomeric and disordered c-Myc. To rationalize the mechanism of inhibition, structural ensembles for the segment of the c-Myc domain that binds to 1 were computed in the absence and presence of the ligand using classical force fields and explicit solvent metadynamics molecular simulations. The accuracy of the computed structural ensembles was assessed by comparison of predicted and measured NMR chemical shifts. The small molecule 1 was found to perturb the composition of the apo equilibrium ensemble and to bind weakly to multiple distinct c-Myc conformations. Comparison of the apo and holo equilibrium ensembles reveals that the c-Myc conformations binding 1 are already partially formed in the apo ensemble, suggesting that 1 binds to c-Myc through an extended conformational selection mechanism. The present results have important implications for rational ligand design efforts targeting intrinsically disordered proteins

VERIFICATION OF THE DEFENSE WASTE PROCESSING FACILITY'S (DWPF) PROCESS DIGESTION METHOD FOR THE SLUDGE BATCH 7A QUALIFICATION SAMPLE

For each sludge batch that is processed in the Defense Waste Processing Facility (DWPF), the Savannah River National Laboratory (SRNL) performs confirmation of the applicability of the digestion method to be used by the DWPF lab for elemental analysis of Sludge Receipt and Adjustment Tank (SRAT) receipt samples and SRAT product process control samples. DWPF SRAT samples are typically dissolved using a room temperature HF-HNO{sub 3} acid dissolution (i.e., DWPF Cold Chem Method, see DWPF Procedure SW4-15.201) and then analyzed by inductively coupled plasma - atomic emission spectroscopy (ICP-AES). This report contains the results and comparison of data generated from performing the Aqua Regia (AR), Sodium peroxide/Hydroxide Fusion (PF) and DWPF Cold Chem (CC) method digestions of Sludge Batch 7a (SB7a) SRAT Receipt and SB7a SRAT Product samples. The SB7a SRAT Receipt and SB7a SRAT Product samples were prepared in the SRNL Shielded Cells, and the SRAT Receipt material is representative of the sludge that constituates the SB7a Batch or qualification composition. This is the sludge in Tank 51 that is to be transferred into Tank 40, which will contain the heel of Sludge Batch 6 (SB6), to form the Sb7a Blend composition

Development Of Ion Chromatography Methods To Support Testing Of The Glycolic Acid Reductant Flowsheet In The Defense Waste Processing Facility

Ion Chromatography (IC) is the principal analytical method used to support studies of Sludge Reciept and Adjustment Tank (SRAT) chemistry at DWPF. A series of prior analytical ''Round Robin'' (RR) studies included both supernate and sludge samples from SRAT simulant, previously reported as memos, are tabulated in this report.2,3 From these studies it was determined to standardize IC column size to 4 mm diameter, eliminating the capillary column from use. As a follow on test, the DWPF laboratory, the PSAL laboratory, and the AD laboratory participated in the current analytical RR to determine a suite of anions in SRAT simulant by IC, results also are tabulated in this report. The particular goal was to confirm the laboratories ability to measure and quantitate glycolate ion. The target was + or - 20% inter-lab agreement of the analyte averages for the RR. Each of the three laboratories analyzed a batch of 12 samples. For each laboratory, the percent relative standard deviation (%RSD) of the averages on nitrate, glycolate, and oxalate, was 10% or less. The three laboratories all met the goal of 20% relative agreement for nitrate and glycolate. For oxalate, the PSAL laboratory reported an average value that was 20% higher than the average values reported by the DWPF laboratory and the AD laboratory. Because of this wider window of agreement, it was concluded to continue the practice of an additional acid digestion for total oxalate measurement. It should also be noted that large amounts of glycolate in the SRAT samples will have an impact on detection limits of near eluting peaks, namely Fluoride and Formate. A suite of scoping experiments are presented in the report to identify and isolate other potential interlaboratory disceprancies. Specific ion chromatography inter-laboratory method conditions and differences are tabulated. Most differences were minor but there are some temperature control equipment differences that are significant leading to a recommendation of a heated jacket for analytical columns that are remoted for use in radiohoods. A suggested method improvement would be to implement column temperture control at a temperature slightly above ambient to avoid peak shifting due to temperature fluctuations. Temperature control in this manner would improve short and longer term peak retention time stability. An unknown peak was observed during the analysis of glycolic acid and SRAT simulant. The unknown peak was determined to best match diglycolic acid. The development of a method for acetate is summaraized, and no significant amount of acetate was observed in the SRAT products tested. In addition, an alternative Gas Chromatograph (GC) method for glycolate is summarized

Unusual Cause of Heart Failure in a Patient with Marfan Syndrome: A Late Complication of Bioprosthetic Valved Graft Replacement

A high-velocity gradient across the left ventricular outflow tract is most often caused by aortic valve stenosis. We describe the unusual case of a high-velocity gradient caused by a kinked ascending aortic graft in a 69-year-old man who had Marfan syndrome. The patient had a history of ascending aortic aneurysm and had previously undergone replacement of the aortic root and ascending aorta with use of a bioprosthetic valved graft. The kinking was caused by dilation of the native aortic arch. The patient underwent successful hemi-arch replacement and repair of the kinked graft. Late complications and reoperation after proximal aortic surgery in patients with Marfan syndrome are rare, and a high-velocity left ventricular outflow tract gradient caused by the kinking of the aorta is unusual