Advancing Pharmacist Collaborative Care within Academic Health Systems.

INTRODUCTION:The scope of pharmacy practice has evolved over the last few decades to focus on the optimization of medication therapy. Despite this positive impact, the lack of reimbursement remains a significant barrier to the implementation of innovative pharmacist practice models. SUMMARY:We describe the successful development, implementation and outcomes of three types of pharmacist collaborative care models: (1) a pharmacist with physician oversight, (2) pharmacist-interprofessional teams and (3) physician-pharmacist teams. The outcome measurement of these pharmacist care models varied from the design phase to patient volume measurement and to comprehensive quality dashboards. All of these practice models have been successfully funded by affiliated health systems or grants. CONCLUSIONS:The expansion of pharmacist services delivered by clinical faculty has several benefits to affiliated health systems: (1) significant improvements in patient care quality, (2) access to experts in specialty areas, and (3) the dissemination of outcomes with national and international recognition, increasing the visibility of the health system

The Maunakea Spectroscopic Explorer Book 2018

(Abridged) This is the Maunakea Spectroscopic Explorer 2018 book. It is intended as a concise reference guide to all aspects of the scientific and technical design of MSE, for the international astronomy and engineering communities, and related agencies. The current version is a status report of MSE's science goals and their practical implementation, following the System Conceptual Design Review, held in January 2018. MSE is a planned 10-m class, wide-field, optical and near-infrared facility, designed to enable transformative science, while filling a critical missing gap in the emerging international network of large-scale astronomical facilities. MSE is completely dedicated to multi-object spectroscopy of samples of between thousands and millions of astrophysical objects. It will lead the world in this arena, due to its unique design capabilities: it will boast a large (11.25 m) aperture and wide (1.52 sq. degree) field of view; it will have the capabilities to observe at a wide range of spectral resolutions, from R2500 to R40,000, with massive multiplexing (4332 spectra per exposure, with all spectral resolutions available at all times), and an on-target observing efficiency of more than 80%. MSE will unveil the composition and dynamics of the faint Universe and is designed to excel at precision studies of faint astrophysical phenomena. It will also provide critical follow-up for multi-wavelength imaging surveys, such as those of the Large Synoptic Survey Telescope, Gaia, Euclid, the Wide Field Infrared Survey Telescope, the Square Kilometre Array, and the Next Generation Very Large Array.Comment: 5 chapters, 160 pages, 107 figure

Synthesis of Starch-Functionalized Dibromomaleimide for Peptide Delivery

The application of peptides as pharmaceutical drugs demonstrates many advantages including high specificity, low toxicity, and high biocompatibility and degradability. Although peptide-based therapeutics is an advantageous method of peptide delivery, one of the main challenges with the use of peptides is the enzymatic degradation of peptide-based drugs in the bloodstream. PEGylation has been used to increase the circulation half-life of peptides, but it does so at the cost of accumulating PEG in organs and releasing potentially toxic by-products upon degradation. One alternative is the covalent attachment of saccharides as the transport moieties. Utilization of saccharides is growing in the field of drug delivery because they are abundant, renewable, and low costing with excellent biodegradability and biocompatibility. In particular, starch is one of the most versatile polysaccharides for synthesizing new hybrid biomaterials because its structure can easily be manipulated. Our research group aims to synthesize a novel starch-peptide conjugated macromolecule consisting of peptides, a hetero-functionalized small molecule linker, and starch as a peptide drug carrier system. In previous studies, the macromolecular nature of the starch moiety caused the saturation of NMR signals and obscured the peak readings. Our prospective work includes investigating optimal reaction conditions to perform successful copper click reactions of the linker molecule and starch moiety in order to conjugate peptides to our starch-linker complex. We hope that final molecule will find utility in the development of peptides as drugs and other drug delivery systems

Impact of time to revision total knee arthroplasty on outcomes following aseptic failure

Abstract Introduction Prior studies have demonstrated an association between time to revision total knee arthroplasty (rTKA) and indication; however, the impact of early versus late revision on post-operative outcomes has not been reported. Materials and methods A retrospective, observational study examined patients who underwent unilateral, aseptic rTKA at an academic orthopedic hospital between 6/2011 and 4/2020 with > 1-year of follow-up. Patients were early revisions if they were revised within 2 years of primary TKA (pTKA) or late revisions if revised after greater than 2 years. Patient demographics, surgical factors, and post-operative outcomes were compared. Results 470 rTKA were included (199 early, 271 late). Early rTKA patients were younger by 2.5 years (p = 0.002). The predominant indications for early rTKA were instability (28.6%) and arthrofibrosis/stiffness (26.6%), and the predominant indications for late rTKA were aseptic loosening (45.8%) and instability (26.2%; p < 0.001). Late rTKA had longer operative times (119.20 ± 51.94 vs. 103.93 ± 44.66 min; p < 0.001). There were no differences in rTKA type, disposition, hospital length of stay, all-cause 90-day emergency department visits and readmissions, reoperations, and number of re-revisions. Conclusions Aseptic rTKA performed before 2 years had different indications but demonstrated similar outcomes to those performed later. Early revisions had shorter surgical times, which could be attributed to differences in rTKA indication. Level of evidence III, retrospective observational analysis

Myosin Light Chain Kinase Knockout Improves Gut Barrier Function and Confers a Survival Advantage in Polymicrobial Sepsis

Abstract Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the perijunctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK−/− and wild-type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK−/− mice (95% versus 24%, p < 0.0001). Intestinal permeability increased in septic WT mice compared with unmanipulated mice. In contrast, permeability in septic MLCK−/− mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK−/− mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8 and 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion, as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK−/− mice; however, survival was similar between septic MLCK−/− mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins

Advancing Pharmacist Collaborative Care within Academic Health Systems.

The scope of pharmacy practice has evolved over the last few decades to focus on the optimization of medication therapy. Despite this positive impact, the lack of reimbursement remains a significant barrier to the implementation of innovative pharmacist practice models. We describe the successful development, implementation and outcomes of three types of pharmacist collaborative care models: (1) a pharmacist with physician oversight, (2) pharmacist-interprofessional teams and (3) physician-pharmacist teams. The outcome measurement of these pharmacist care models varied from the design phase to patient volume measurement and to comprehensive quality dashboards. All of these practice models have been successfully funded by affiliated health systems or grants. The expansion of pharmacist services delivered by clinical faculty has several benefits to affiliated health systems: (1) significant improvements in patient care quality, (2) access to experts in specialty areas, and (3) the dissemination of outcomes with national and international recognition, increasing the visibility of the health system

Dimerisation of a chromo shadow domain and distinction from the chromodomain as revealed by structural analysis

AbstractBackground: Proteins such as HP1, found in fruit flies and mammals, and Swi6, its fission yeast homologue, carry a chromodomain (CD) and a chromo shadow domain (CSD). These proteins are required to form functional transcriptionally silent centromeric chromatin, and their mutation leads to chromosome segregation defects. CSDs have only been found in tandem in proteins containing the related CD. Most HP1-interacting proteins have been found to associate through the CSD and many of these ligands contain a conserved pentapeptide motif.Results: The 1.9 Å crystal structure of the Swi6 CSD is presented here. This reveals a novel dimeric structure that is distinct from the previously reported monomeric nuclear magnetic resonance (NMR) structure of the CD from the mouse modifier 1 protein (MoMOD1, also known as HP1β or M31). A prominent pit with a non-polar base is generated at the dimer interface, and is commensurate with binding an extended pentapeptide motif. Sequence alignments based on this structure highlight differences between CDs and CSDs that are superimposed on a common structural core. The analyses also revealed a previously unrecognised circumferential hydrophobic sash around the surface of the CD structure.Conclusions: Dimerisation through the CSD of HP1-like proteins results in the simultaneous formation of a putative protein–protein interaction pit, providing a potential means of targeting CSD-containing proteins to particular chromatin sites