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BACKGROUND: Hip fracture is a major health concern and the use of an indwelling urinary catheter (IUC) constitutes a significant burden on elderly patients undergoing hip fracture surgery. LOCAL PROBLEM: The institution had a high rate of urinary tract infection (UTI) and IUC reinsertion after hip fracture surgery. METHODS: A pre/post-implementation design was used for this quality improvement initiative. INTERVENTIONS: A nurse-driven process was developed and implemented to improve the successful removal of IUC among patients after hip fracture surgery. RESULTS: There was a significant reduction in post-operative urinary retention (P = .042), UTI rate (P = .047), and IUC reinsertion (P = .042) in the post-implementation group. IUC duration decreased by 1.1 days, however this was not significant (P = .206). Nurse compliance with following the new process was 93.3%. CONCLUSION: The nurse-driven process designed for elderly patients following hip fracture surgery presents a promising approach to reducing IUC reinsertion rates and UTI.
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Osteoporosis is often untreated especially in older people. This study found a low prescribing rate of osteoporosis treatment medication of 22.4% in older people admitted under the hip-fracture pathway. Factors associated with greater odds of being prescribed osteoporosis medications are categorized into patient-related, physician-related and system-related factors. INTRODUCTION: Osteoporosis represents a growing healthcare problem which is often overlooked by healthcare providers and untreated especially in older people. This study aims to assess the rate of osteoporosis treatment initiation and to investigate underlying physician and system-related barriers in geriatric patients admitted for hip fracture. METHODS: A retrospective study was conducted on patients aged 60 years and older, admitted under the hip-fracture pathway from January 2019 to December 2019. Data collected included demographics, co-morbid conditions and laboratory data. Clinical charts were reviewed for whether bone mineral density (BMD) scan has been ordered, plans for bone health were made and reflected in the discharge summary, and if appropriate memos were written. The primary outcome was the prescription of osteoporosis treatment medications. Prescription lists were also reviewed for prescribing patterns of calcium and vitamin D. RESULTS: A total of 375 patients older than 60 years old were identified. 281 patients who fit the inclusion and exclusion criteria with complete data were further analysed. Within 1 year of hip fracture admission, 63 (22.4%) of them were prescribed with osteoporosis treatment. Multivariate logistic regression identified milder stage of CKD (p = 0.038, OR = 0.617, 95% CI 0.392-0.973) and BMD scan performed (p < 0.001, OR = 6.515, 95% CI 3.180-13.348) as independent factors associated with the prescription of osteoporosis treatment within 1 year of hip fracture admission. CONCLUSION: The rate of osteoporosis treatment initiation post-hip fracture is low. Systematic solutions will need to be established to ensure that osteoporosis treatment is addressed prior to discharge.
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Conservadores de la Densidad Ósea , Fracturas de Cadera , Osteoporosis , Fracturas Osteoporóticas , Humanos , Anciano , Persona de Mediana Edad , Conservadores de la Densidad Ósea/uso terapéutico , Calcio/uso terapéutico , Estudios Retrospectivos , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiología , Osteoporosis/complicaciones , Fracturas de Cadera/complicaciones , Vitamina D/uso terapéutico , Fracturas Osteoporóticas/complicacionesRESUMEN
Snake venoms are rich sources of biologically active proteins and polypeptides. Three-finger toxins are non-enzymatic proteins present in elapid (cobras, kraits, mambas and sea snakes) and colubrid venoms. These proteins contain four conserved disulfide bonds in the core to maintain the three-finger folds. Although all three-finger toxins have similar fold, their biological activities are different. A new three-finger toxin (hemachatoxin) was isolated from Hemachatus haemachatus (Ringhals cobra) venom. Its amino acid sequence was elucidated, and crystal structure was determined at 2.43 Å resolution. The overall fold is similar to other three-finger toxins. The structure and sequence analysis revealed that the fold is maintained by four highly conserved disulfide bonds. It exhibited highest similarity to particularly P-type cardiotoxins that are known to associate and perturb the membrane surface with their lipid binding sites. Also, the increased B value of hemachotoxin loop II suggests that loop II is flexible and may remain flexible until its interaction with membrane phospholipids. Based on the analysis, we predict hemachatoxin to be cardiotoxic/cytotoxic and our future experiments will be directed to characterize the activity of hemachatoxin.
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Venenos Elapídicos/química , Elapidae/metabolismo , Conformación Proteica , Toxinas Biológicas/química , Secuencia de Aminoácidos , Animales , Cromatografía Líquida de Alta Presión , Cromatografía de Fase Inversa , Cristalografía por Rayos X , Modelos Moleculares , Datos de Secuencia Molecular , Análisis de Secuencia de Proteína , Homología de Secuencia de Aminoácido , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
The recently identified type VI secretion system (T6SS) is implicated in the virulence of many gram-negative bacteria. Edwardsiella tarda is an important cause of hemorrhagic septicemia in fish and also gastro- and extra-intestinal infections in humans. The E. tardavirulent protein (EVP) gene cluster encodes a conserved T6SS which contains 16 open reading frames. EvpC is one of the three major EVP secreted proteins and shares high sequence similarity with Hcp1, a key T6SS virulence factor from Pseudomonas aeruginosa. EvpC contributes to the virulence of E. tarda by playing an essential role in functional T6SS. Here, we report the crystal structure of EvpC from E. tarda PPD130/91 at a 2.8 Å resolution, along with functional studies of the protein. EvpC has a ß-barrel domain with extended loops. The ß-barrel consists of 11 anti-parallel ß-strands with an α-helix located on one side. In solution, EvpC exists as a dimer at low concentration and as a hexamer at higher concentration. In the crystal, the symmetry related EvpC molecules form hexameric rings which stack together to form a tube similar to Hcp1. Structure based mutagenesis revealed that N-terminal negatively charged residues, Asp4, Glu15 and Glu26, and C-terminal positively charged residues, Lys161, Lys162 and Lys163, played crucial roles in the secretion of EvpC. Moreover, the localization study indicates the presence of wild type EvpC in cytoplasm, periplasm and secreted fractions, whereas the N-terminal and C-terminal mutants were found mostly in the periplasmic region and was completely absent in the secreted fraction. Results reported here provide insight into the structure, assembly and function of EvpC. Further, these findings can be extended to other EvpC homologs for understanding the mechanism of T6SS and targeting T6SS mediated virulence in gram-negative pathogens.
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Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Edwardsiella tarda/metabolismo , Espacio Extracelular/metabolismo , Factores de Virulencia/química , Factores de Virulencia/metabolismo , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Cristalografía por Rayos X , Edwardsiella tarda/química , Edwardsiella tarda/genética , Edwardsiella tarda/patogenicidad , Espacio Extracelular/genética , Conformación Molecular , Datos de Secuencia Molecular , Estructura Secundaria de Proteína , Transporte de Proteínas , Alineación de Secuencia , Factores de Virulencia/genéticaRESUMEN
We report the crystal structures of three noncovalent retrobinding inhibitors in complex with mature cathepsin L up to resolutions of 2.5, 1.8, and 2.5 A, respectively. These inhibitors were Bpa-(Nepsilon-Bpa)Lys-DArg-Tyr-Npe, Bpa-(Nepsilon-Bpa)Lys-DArg-Phe-Npe, and Bpa-MCys-DArg-Phe-Npe, where Bpa = biphenylacetyl and Pea = N-phenylethyl. These were selected to clarify the binding mode of the biphenyl groups in the S' subsites because the addition of a second biphenyl does not improve potency. Examination of the symmetry-related monomers in the crystal structures revealed inhibitor-inhibitor crystal packing interactions. Molecular dynamics simulations were then used to explore the structure and dynamical behavior of the isolated protein-ligand complexes in solution. In the simulations, the backbone biphenyl groups for all three inhibitors ended up in the same location despite having started out in different orientations in the initial crystal structure conformations. The lack of improved potency of the larger inhibitors over the smaller one is attributed to a correspondingly greater entropic cost of binding.
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Catepsina L/antagonistas & inhibidores , Catepsina L/química , Modelos Moleculares , Oligopéptidos/química , Oligopéptidos/farmacología , Inhibidores de Proteasas/química , Inhibidores de Proteasas/farmacología , Secuencia de Aminoácidos , Catepsina L/metabolismo , Cristalografía por Rayos X , Dimerización , Humanos , Conformación Molecular , Oligopéptidos/metabolismo , Inhibidores de Proteasas/metabolismoRESUMEN
We report a series of noncovalent, reversible inhibitors of cathepsin L that have been designed to explore additional binding interactions with the S' subsites. The design was based on our previously reported crystal structure that suggested the possibility of engineering increased interactions with the S' subsites ( Chowdhury et al. J. Med. Chem. 2002, 45, 5321-5329 ). A representative of these new inhibitors has been co-crystallized with mature cathepsin L, and the structure has been solved and refined at 2.2 A. The inhibitors described in this work extend farther into the S' subsites of cathepsins than any inhibitors reported in the literature thus far. These interactions appear to make use of a S3' subsite that can potentially be exploited for enhanced specificity and/or affinity.