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No-Pass Zone: Multidisciplinary Approach to Responding to Patient Needs. - Journal of nursing care quality
A nurse's need to juggle multiple priorities often leads to delays in responses to patient call lights, which may result in the patient's needs not being met quickly. Low patient satisfaction scores related to hospital staff responding to patient needs created urgency for this system to implement the No-Pass Zone, a multidisciplinary team approach to responding to call lights. A successful implementation of this intervention resulted in patients' needs being met more quickly as indicated by improved Hospital Consumer Assessment of Health Care Providers and Systems performance postimplementation.
Rapid Detection of KPC, NDM, and OXA-48-Like Carbapenemases by Real-Time PCR from Rectal Swab Surveillance Samples. - Journal of clinical microbiology
We describe a multiplex real-time PCR assay for use on the ABI 7500 Fast TaqMan platform to detect all currently described Klebsiella pneumoniae carbapenemases (KPC), New Delhi metallo-Î²-lactamases (NDM), and the OXA-48-like family of carbapenemases from bacterial culture lysates or sample enrichment broth lysates.Copyright Â© 2015, American Society for Microbiology. All Rights Reserved.
Fosmidomycin decreases membrane hopanoids and potentiates the effects of colistin on Burkholderia multivorans clinical isolates. - Antimicrobial agents and chemotherapy
Burkholderia cepacia complex (Bcc) pulmonary infections in people living with cystic fibrosis (CF) are difficult to treat because of the extreme intrinsic resistance of most isolates to a broad range of antimicrobials. Fosmidomycin is an antibacterial and antiparasitic agent that disrupts the isoprenoid biosynthesis pathway, a precursor to hopanoid biosynthesis. Hopanoids are involved in membrane stability and contribute to polymyxin resistance in Bcc bacteria. Checkerboard MIC assays determined that although isolates of the Bcc species B. multivorans were highly resistant to treatment with fosmidomycin or colistin (polymyxin E), antimicrobial synergy was observed in certain isolates when the antimicrobials were used in combination. Treatment with fosmidomycin decreased the MIC of colistin for isolates as much as 64-fold to as low as 8 Î¼g/ml, a concentration achievable with colistin inhalation therapy. A liquid chromatography-tandem mass spectrometry technique was developed for the accurate quantitative determination of underivatized hopanoids in total lipid extracts, and bacteriohopanetetrol cyclitol ether (BHT-CE) was found to be the dominant hopanoid made by B. multivorans. The amount of BHT-CE made was significantly reduced upon fosmidomycin treatment of the bacteria. Uptake assays with 1-N-phenylnaphthylamine were used to determine that dual treatment with fosmidomycin and colistin increases membrane permeability, while binding assays with boron-dipyrromethene-conjugated polymyxin B illustrated that the addition of fosmidomycin had no impact on polymyxin binding. This work indicates that pharmacological suppression of membrane hopanoids with fosmidomycin treatment can increase the susceptibility of certain clinical B. multivorans isolates to colistin, an agent currently in use to treat pulmonary infections in CF patients.Copyright Â© 2014, American Society for Microbiology. All Rights Reserved.
The glypican 3 hepatocellular carcinoma marker regulates human hepatic stellate cells via Hedgehog signaling. - The Journal of surgical research
Hepatocellular carcinoma (HCC) frequently represents two diseases as it often arises in the setting of cirrhosis caused by the proliferation and activation of hepatic stellate cells (HSCs). Previously, we identified that Hedgehog (Hh) signaling regulates HSC viability and fibrinogenesis, as well as HCC tumorigenesis. Although it is increasingly recognized that HSCs and HCCs communicate via paracrine signaling, Hh's role in this process is just emerging. We hypothesized that a secreted HCC tumor marker and Hh mediator, glypican 3 (GPC3), may regulate HSC.Using three human HCC lines (Hep3B, PLC/PRF/5 and SK-Hep-1) and one Hh-responsive human HSC line (LX-2), we developed two inÂ vitro models of HCC-to-HSC paracrine signaling using a Transwell coculture system and HCC-conditioned media. We then evaluated the effects of these models, as well as GPC3, on HSC viability and gene expression.Using our coculture and conditioned media models, we demonstrate that the three HCC lines decrease HSC viability. Furthermore, we demonstrate that recombinant GPC3 dose-dependently decreases the LX-2 viability while inhibiting the expression of Hh target genes that regulate HSC viability. Finally, GPC3's inhibitory effects on cell viability and Hh target gene expression are partially abrogated by heparin, a competitor for GPC3 binding.For the first time, we show that GPC3, an HCC biomarker and Hh mediator, regulates human HSC viability by regulating Hh signaling. This expands on existing data suggesting a role for tumor-stroma interactions in the liver and suggests that GPC3 plays a role in this process.Copyright Â© 2014 Elsevier Inc. All rights reserved.
Simultaneous cloning and selection of hybridomas and transfected cell lines in semisolid media. - Methods in molecular biology (Clifton, N.J.)
Selection and cloning are essential but often laborious and time-consuming steps during the generation of hybridomas and genetically modified cell lines that produce monoclonal antibodies or other proteins with desired properties. Methods for the simultaneous selection and cloning of hybridomas and transfected cell lines (e.g., CHO-S cells) in semisolid methylcellulose-based media have been developed. By using semisolid selection media, the cells that survive the selection process proliferate and form colonies of cells that remain physically separated from other colonies. Each colony thus originates from a single hybridoma or transfected cell and can be isolated and characterized separately. This approach avoids the isolation of multiple identical clones and the loss of useful clones due to overgrowth by other faster-growing, but possibly nonproducing clones, which are major problems of conventional procedures in liquid media. In this chapter, protocols are described for the generation of mouse hybridomas by fusion of spleen cells from immunized mice with myeloma cells and the subsequent selection and cloning of hybridomas in semisolid selection media. Protocol are also described for selection and cloning of transfected cell lines using semisolid antibiotic-containing selection media, as well as strategies to optimize selection and cloning in serum-containing, serum-free, and chemically defined selection media.
EB1 is required for spindle symmetry in mammalian mitosis. - PloS one
Most information about the roles of the adenomatous polyposis coli protein (APC) and its binding partner EB1 in mitotic cells has come from siRNA studies. These suggest functions in chromosomal segregation and spindle positioning whose loss might contribute to tumourigenesis in cancers initiated by APC mutation. However, siRNA-based approaches have drawbacks associated with the time taken to achieve significant expression knockdown and the pleiotropic effects of EB1 and APC gene knockdown. Here we describe the effects of microinjecting APC- or EB1- specific monoclonal antibodies and a dominant-negative EB1 protein fragment into mammalian mitotic cells. The phenotypes observed were consistent with the roles proposed for EB1 and APC in chromosomal segregation in previous work. However, EB1 antibody injection also revealed two novel mitotic phenotypes, anaphase-specific cortical blebbing and asymmetric spindle pole movement. The daughters of microinjected cells displayed inequalities in microtubule content, with the greatest differences seen in the products of mitoses that showed the severest asymmetry in spindle pole movement. Daughters that inherited the least mobile pole contained the fewest microtubules, consistent with a role for EB1 in processes that promote equality of astral microtubule function at both poles in a spindle. We propose that these novel phenotypes represent APC-independent roles for EB1 in spindle pole function and the regulation of cortical contractility in the later stages of mitosis. Our work confirms that EB1 and APC have important mitotic roles, the loss of which could contribute to CIN in colorectal tumour cells.Â© 2011 Bruning-Richardson et al.
Identification of hopanoid biosynthesis genes involved in polymyxin resistance in Burkholderia multivorans. - Antimicrobial agents and chemotherapy
A major challenge to clinical therapy of Burkholderia cepacia complex (Bcc) pulmonary infections is their innate resistance to a broad range of antimicrobials, including polycationic agents such as aminoglycosides, polymyxins, and cationic peptides. To identify genetic loci associated with this phenotype, a transposon mutant library was constructed in B. multivorans ATCC 17616 and screened for increased susceptibility to polymyxin B. Compared to the parent strain, mutant 26D7 exhibited 8- and 16-fold increases in susceptibility to polymyxin B and colistin, respectively. Genetic analysis of mutant 26D7 indicated that the transposon inserted into open reading frame (ORF) Bmul_2133, part of a putative hopanoid biosynthesis gene cluster. A strain with a mutation in another ORF in this cluster, Bmul_2134, was constructed and named RMI19. Mutant RMI19 also had increased polymyxin susceptibility. Hopanoids are analogues of eukaryotic sterols involved in membrane stability and barrier function. Strains with mutations in Bmul_2133 and Bmul_2134 showed increased permeability to 1-N-phenylnaphthylamine in the presence of increasing concentrations of polymyxin, suggesting that the putative hopanoid biosynthesis genes are involved in stabilizing outer membrane permeability, contributing to polymyxin resistance. Results from a dansyl-polymyxin binding assay demonstrated that polymyxin B does not bind well to the parent or mutant strains, suggesting that Bmul_2133 and Bmul_2134 contribute to polymyxin B resistance by a mechanism that is independent of lipopolysaccharide (LPS) binding. Through this work, we propose a role for hopanoid biosynthesis as part of the multiple antimicrobial resistance phenotype in Bcc bacteria.
Structure-function studies of an engineered scaffold protein derived from Stefin A. II: Development and applications of the SQT variant. - Protein engineering, design & selection : PEDS
Constrained binding peptides (peptide aptamers) may serve as tools to explore protein conformations and disrupt protein-protein interactions. The quality of the protein scaffold, by which the binding peptide is constrained and presented, is of crucial importance. SQT (Stefin A Quadruple Mutant-Tracy) is our most recent development in the Stefin A-derived scaffold series. Stefin A naturally uses three surfaces to interact with its targets. SQT tolerates peptide insertions at all three positions. Peptide aptamers in the SQT scaffold can be expressed in bacterial, yeast and human cells, and displayed as a fusion to truncated pIII on phage. Peptides that bind to CDK2 can show improved binding in protein microarrays when presented by the SQT scaffold. Yeast two-hybrid libraries have been screened for binders to the POZ domain of BCL-6 and to a peptide derived from PBP2', specific to methicillin-resistant Staphylococcus aureus. Presentation of the Noxa BH3 helix by SQT allows specific interaction with Mcl-1 in human cells. Together, our results show that Stefin A-derived scaffolds, including SQT, can be used for a variety of applications in cellular and molecular biology. We will henceforth refer to Stefin A-derived engineered proteins as Scannins.
Management of primary rectal cancer by surgeons in Atlantic Canada: results of a regional survey. - Canadian journal of surgery. Journal canadien de chirurgie
We sought to determine the current practice patterns of general surgeons in Atlantic Canada in the management of primary rectal cancer in relation to surgeon-specific variables.We sent mail-out surveys to all practising general surgeons (n = 183) in Atlantic Canada to determine screening preferences, preoperative assessment, the use of neoadjuvant and adjuvant therapy, surgical therapy for rectal cancer and surgeon demographics. We analyzed the responses using Ï‡(2) tests.The response rate was 98 (54%) after 2 mail-outs; there were 82 (49%) eligible responses. Surgeons in practice for 21 years or more were more likely than those with fewer than 21 years of practice to order preoperative ultrasonography of the liver and were less likely to order preoperative computed tomography. Endorectal ultrasonography was ordered routinely by 23% of surgeons, whereas 71% of surgeons would order it if time and resources were available. Surgeons who were not certified by the Royal College of Physicians and Surgeons of Canada were significantly more likely than those who were certified to use neoadjuvant therapy in all patients with rectal cancer (43% v. 12%; p = 0.031). Surgeons who performed more than 10 rectal cancer surgeries per year were significantly more likely than those who performed 10 or fewer surgeries per year to use neoadjuvant treatment for T3 tumours (94% v. 61%; p = 0.007). Surgeons with medical or radiation oncology services in their communities were significantly more likely than those without such services to recommend neoadjuvant treatment in T3 rectal tumours and rectal tumours with pathologic lymph nodes.We found significant variation in the management of rectal cancer depending on surgeon-specific variables. The implications of these differences on the outcomes of patients with rectal cancer are unknown.
Does the "eyes lead the hand" principle apply to reach-to-grasp movements evoked by unexpected balance perturbations? - Human movement science
A fundamental principle that has emerged from studies of natural gaze behavior is that goal-directed arm movements are typically guided by a saccade to the target. In this study, we evaluated a hypothesis that this principle does not apply to rapid reach-to-grasp movements evoked by sudden unexpected balance perturbations. These perturbations involved forward translation of a large (2 Ã— 6 m) motion platform configured to simulate a "real-life" environment. Subjects performed a common "daily-life" visuo-cognitive task (find a telephone and make a call) that required walking to the end of the platform, which was triggered to move as they approached a handrail mounted alongside the travel path. A deception was used to ensure that the perturbation was truly unexpected. Eleven of 18 healthy young-adult subjects (age 22-30) reached to grasp or touch the rail in response to the balance perturbation. In support of the hypothesis, none of these arm reactions was guided by concurrent visual fixation of the handrail. Seven of the 11 looked at the rail upon first entering the environment, and hence may have used "stored" central-field information about the handrail location to guide the subsequent arm reaction. However, the other four subjects never looked directly at the rail, indicating a complete reliance on peripheral vision. These findings add to previous evidence of distinctions in the CNS control of volitional and perturbation-evoked arm movements. Future studies will determine whether similar visuo-motor behavior occurs when the available handhold is smaller or when subjects are not engaged in a concurrent visuo-cognitive task.Copyright Â© 2010 Elsevier B.V. All rights reserved.
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