Urethral catheters: can we reduce use?

<p>Abstract</p> <p>Background</p> <p>Indwelling urinary catheters are the main cause of healthcare-associated urinary tract infections. It can be expected that reduction of the use of urinary catheters will lead to decreased numbers of urinary tract infection.</p> <p>Methods</p> <p>The efficacy of an intervention programme to improve adherence to recommendations to reduce the use of urethral catheters was studied in a before-after comparison in ten Dutch hospitals. The programme detected barriers and facilitators and each individual facility was supported with developing their own intervention strategy. Outcome was evaluated by the prevalence of catheters, alternatives such as diapers, numbers of urinary tract infections, the percentage of correct indications and the duration of catheterization. The costs of the implementation as well as the catheterization were evaluated.</p> <p>Results</p> <p>Of a population of 16,495 hospitalized patients 3335 patients of whom 2943 were evaluable for the study, had a urethral catheter. The prevalence of urethral catheters decreased insignificantly in neurology (OR 0.93; 95% CI 0.77 - 1.13) and internal medicine wards (OR 0.97; 95% CI 0.83 - 1.13), decreased significantly in surgical wards (OR 0.84; 95% CI 0.75 - 0.96), but increased significantly in intensive care (IC) and coronary care (CC) units (OR 1.48; 95% CI 1.01 - 2.17). The use of alternatives was limited and remained so after the intervention. Duration of catheterization decreased insignificantly in IC/CC units (ratio after/before 0.95; 95% CI 0.78 - 1.16) and neurology (ratio 0.97; 95% CI 0.80 - 1.18) and significantly in internal medicine (ratio 0.81; 95% CI 0.69 - 0.96) and surgery wards (ratio 0.80; 95% CI 0.71 - 0.90). The percentage of correct indications on the day of inclusion increased from 50 to 67% (p < 0.0001). The prevalence of urinary tract infections in catheterized patients did not change. The mean cost saved per 100 patients was € 537.</p> <p>Conclusion</p> <p>Targeted implementation of recommendations from an existing guideline can lead to better adherence and cost savings. Especially, hospitals which use a lot of urethral catheters or where catheterization is prolonged, can expect important improvements.</p

A four phase development model for integrated care services in the Netherlands

Background. Multidisciplinary and interorganizational arrangements for the delivery of coherent integrated care are being developed in a large number of countries. Although there are many integrated care programs worldwide, the process of developing these programs and interorganizational collaboration is described in the literature only to a limited extent. The purpose of this study is to explore how local integrated care services are developed in the Netherlands, and to conceptualize and operationalize a development model of integrated care. Methods. The research is based on an expert panel study followed by a two-part questionnaire, designed to identify the development process of integrated care. Essential elements of integrated care, which were developed in a previous Delphi and Concept Mapping Study, were analyzed in relation to development process of integrated care. Results. Integrated care development can be characterized by four developmental phases: the initiative and design phase; the experimental and execution phase; the expansion and monitoring phase; and the consolidation and transformation phase. Different elements of integrated care have been identified in the various developmental phases. Conclusion. The findings provide a descriptive model of the development process that integrated care services can undergo in the Netherlands. The findings have important implications for integrated care services, which can use the model as an instrument to reflect on their current practices. The model can be used to help to identify improvement areas in practice. The model provides a framework for developing evaluation designs for integrated care arrangements. Further research is recommended to test the developed model in practice and to add international experiences

Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion

The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis

Enhanced Fusion Pore Expansion Mediated by the Trans-Acting Endodomain of the Reovirus FAST Proteins

The reovirus fusion-associated small transmembrane (FAST) proteins are virus-encoded membrane fusion proteins that function as dedicated cell–cell fusogens. The topology of these small, single-pass membrane proteins orients the majority of the protein on the distal side of the membrane (i.e., inside the cell). We now show that ectopic expression of the endodomains of the p10, p14, and p15 FAST proteins enhances syncytiogenesis induced by the full-length FAST proteins, both homotypically and heterotypically. Results further indicate that the 68-residue cytoplasmic endodomain of the p14 FAST protein (1) is endogenously generated from full-length p14 protein expressed in virus-infected or transfected cells; (2) enhances syncytiogenesis subsequent to stable pore formation; (3) increases the syncytiogenic activity of heterologous fusion proteins, including the differentiation-dependent fusion of murine myoblasts; (4) exerts its enhancing activity from the cytosol, independent of direct interactions with either the fusogen or the membranes being fused; and (5) contains several regions with protein–protein interaction motifs that influence enhancing activity. We propose that the unique evolution of the FAST proteins as virus-encoded cellular fusogens has allowed them to generate a trans-acting, soluble endodomain peptide to harness a cellular pathway or process involved in the poorly understood process that facilitates the transition from microfusion pores to macrofusion and syncytiogenesis

Self-authorship and creative industries workers’ career decision-making

Career decision-making is arguably at its most complex within professions where work is precarious and career calling is strong. This article reports from a study that examined the career decision-making of creative industries workers, for whom career decisions can impact psychological well-being and identity just as much as they impact individuals’ work and career. The respondents were 693 creative industries workers who used a largely open-ended survey to create in-depth reflections on formative moments and career decision-making. Analysis involved the theoretical model of self-authorship, which provides a way of understanding how people employ their sense of self to make meaning of their experiences. The self-authorship process emerged as a complex, non-linear and consistent feature of career decision-making. Theoretical contributions include a non-linear view of self-authorship that exposes the authorship of visible and covert multiple selves prompted by both proactive and reactive identity work

A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System

<p>Abstract</p> <p>Background</p> <p>Hendra virus (HeV) and Nipah virus (NiV) are newly emerged zoonotic paramyxoviruses discovered during outbreaks in Queensland, Australia in 1994 and peninsular Malaysia in 1998/9 respectively and classified within the new <it>Henipavirus </it>genus. Both viruses can infect a broad range of mammalian species causing severe and often-lethal disease in humans and animals, and repeated outbreaks continue to occur. Extensive laboratory studies on the host cell infection stage of HeV and NiV and the roles of their envelope glycoproteins have been hampered by their highly pathogenic nature and restriction to biosafety level-4 (BSL-4) containment. To circumvent this problem, we have developed a henipavirus envelope glycoprotein pseudotyped lentivirus assay system using either a luciferase gene or green fluorescent protein (GFP) gene encoding human immunodeficiency virus type-1 (HIV-1) genome in conjunction with the HeV and NiV fusion (F) and attachment (G) glycoproteins.</p> <p>Results</p> <p>Functional retrovirus particles pseudotyped with henipavirus F and G glycoproteins displayed proper target cell tropism and entry and infection was dependent on the presence of the HeV and NiV receptors ephrinB2 or B3 on target cells. The functional specificity of the assay was confirmed by the lack of reporter-gene signals when particles bearing either only the F or only G glycoprotein were prepared and assayed. Virus entry could be specifically blocked when infection was carried out in the presence of a fusion inhibiting C-terminal heptad (HR-2) peptide, a well-characterized, cross-reactive, neutralizing human mAb specific for the henipavirus G glycoprotein, and soluble ephrinB2 and B3 receptors. In addition, the utility of the assay was also demonstrated by an examination of the influence of the cytoplasmic tail of F in its fusion activity and incorporation into pseudotyped virus particles by generating and testing a panel of truncation mutants of NiV and HeV F.</p> <p>Conclusions</p> <p>Together, these results demonstrate that a specific henipavirus entry assay has been developed using NiV or HeV F and G glycoprotein pseudotyped reporter-gene encoding retrovirus particles. This assay can be conducted safely under BSL-2 conditions and will be a useful tool for measuring henipavirus entry and studying F and G glycoprotein function in the context of virus entry, as well as in assaying and characterizing neutralizing antibodies and virus entry inhibitors.</p

The EFF-1A Cytoplasmic Domain Influences Hypodermal Cell Fusions in C. elegans But Is Not Dependent on 14-3-3 Proteins.

BACKGROUND: Regulatory and biophysical mechanisms of cell-cell fusion are largely unknown despite the fundamental requirement for fused cells in eukaryotic development. Only two cellular fusogens that are not of clear recent viral origin have been identified to date, both in nematodes. One of these, EFF-1, is necessary for most cell fusions in Caenorhabditis elegans. Unregulated EFF-1 expression causes lethality due to ectopic fusion between cells not developmentally programmed to fuse, highlighting the necessity of tight fusogen regulation for proper development. Identifying factors that regulate EFF-1 and its paralog AFF-1 could lead to discovery of molecular mechanisms that control cell fusion upstream of the action of a membrane fusogen. Bioinformatic analysis of the EFF-1A isoform\u27s predicted cytoplasmic domain (endodomain) previously revealed two motifs that have high probabilities of interacting with 14-3-3 proteins when phosphorylated. Mutation of predicted phosphorylation sites within these motifs caused measurable loss of eff-1 gene function in cell fusion in vivo. Moreover, a human 14-3-3 isoform bound to EFF-1::GFP in vitro. We hypothesized that the two 14-3-3 proteins in C. elegans, PAR-5 and FTT-2, may regulate either localization or fusion-inducing activity of EFF-1. METHODOLOGY/PRINCIPAL FINDINGS: Timing of fusion events was slightly but significantly delayed in animals unable to produce full-length EFF-1A. Yet, mutagenesis and live imaging showed that phosphoserines in putative 14-3-3 binding sites are not essential for EFF-1::GFP accumulation at the membrane contact between fusion partner cells. Moreover, although the EFF-1A endodomain was required for normal rates of eff-1-dependent epidermal cell fusions, reduced levels of FTT-2 and PAR-5 did not visibly affect the function of wild-type EFF-1 in the hypodermis. CONCLUSIONS/SIGNIFICANCE: Deletion of the EFF-1A endodomain noticeably affects the timing of hypodermal cell fusions in vivo. However, prohibiting phosphorylation of candidate 14-3-3-binding sites does not impact localization of the fusogen. Hypodermal membrane fusion activity persists when 14-3-3 expression levels are reduced

The Nature of Knowledge in Composition and Literary Understanding: The Question of Specificity

↵PETER SMAGORINSKY is Assistant Professor, College of Education, University of Oklahoma, 820 Van Vleet Oval, Norman, OK 73019-0. He specializes in classroom literacy.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances