Off-hours admission and mortality in two pediatric intensive care units without 24-h in-house senior staff attendance

To compare risk-adjusted mortality of children non-electively admitted during off-hours with risk-adjusted mortality of children admitted during office hours to two pediatric intensive care units (PICUs) without 24-h in-house attendance of senior staff. Prospective observational study, performed between January 2003 and December 2007, in two PICUs without 24-h in-house attendance of senior staff, located in tertiary referral children's hospitals in the Netherlands. Standardized mortality rates (SMRs) of patients admitted during off-hours were compared to SMRs of patients admitted during office hours using Pediatric Index of Mortality (PIM1) and Pediatric Risk of Mortality (PRISM2) scores. Office hours were defined as week days between 8:00 a.m. and 6:00 p.m., with in-house attendance of senior staff, and off-hours as week days between 6:00 p.m. and 8:00 a.m., Saturdays, Sundays and public holidays, with one resident covering the PICU and senior staff directly available on-call. Of 3,212 non-elective patients admitted to the PICUs, 2,122 (66%) were admitted during off-hours. SMRs calculated according to PIM1 and PRISM2 did not show a significant difference with those of patients admitted during office hours. There was no significant effect of admission time on mortality in multivariate logistic regression with odds ratios of death in off-hours of 0.95 (PIM1, 95% CI 0.71-1.27, p = 0.73) and 1.03 (PRISM2, 95% CI 0.76-1.39, p = 0.82). Off-hours admission to our PICUs without 24-h in-house attendance of senior staff was not associated with higher SMRs than admission during office hours when senior staff were available in-house

Optimizing diffusion of an online computer tailored lifestyle program: a study protocol

ABSTRACT: Background Although the Internet is a promising medium to offer lifestyle interventions to large amounts of people at relatively low costs and effort, actual exposure rates of these interventions fail to meet the high expectations. Since public health impact of interventions is determined by intervention efficacy and level of exposure to the intervention, it is imperative to put effort in optimal dissemination. The present project attempts to optimize the dissemination process of a new online computer tailored generic lifestyle program by carefully studying the adoption process and developing a strategy to achieve sustained use of the program. Methods/Design A prospective study will be conducted to yield relevant information concerning the adoption process by studying the level of adoption of the program, determinants involved in adoption and characteristics of adopters and non-adopters as well as satisfied and unsatisfied users. Furthermore, a randomized control trial will be conducted to the test the effectiveness of a proactive strategy using periodic e-mail prompts in optimizing sustained use of the new program. Discussion Closely mapping the adoption process will gain insight in characteristics of adopters and non-adopters and satisfied and unsatisfied users. This insight can be used to further optimize the program by making it more suitable for a wider range of users, or to develop adjusted interventions to attract subgroups of users that are not reached or satisfied with the initial intervention. Furthermore, by studying the effect of a proactive strategy using period prompts compared to a reactive strategy to stimulate sustained use of the intervention and, possibly, behaviour change, specific recommendations on the use and the application of prompts in online lifestyle interventions can be developed. Trial registration Dutch Trial Register (NTR1786) and Medical Ethics Committee of Maastricht University and the University Hospital Maastricht (NL2723506809/MEC0903016)

Characterization of a putative NsrR homologue in Streptomyces venezuelae reveals a new member of the Rrf2 superfamily

Members of the Rrf2 superfamily of transcription factors are widespread in bacteria but their functions are largely unexplored. The few that have been characterized in detail sense nitric oxide (NsrR), iron limitation (RirA), cysteine availability (CymR) and the iron sulfur (Fe-S) cluster status of the cell (IscR). In this study we combined ChIP-seq with in vitro biochemistry to characterize a putative NsrR homologue in the model organism Streptomyces venezuelae. ChIP seq analysis revealed that rather than regulating the nitrosative stress response like NsrR, Sven6563 binds to a different, much larger regulon of genes with a diverse range of functions, including a range of regulators, genes required for glutamine synthesis, NADH/NAD(P)H metabolism, as well as general DNA/RNA and amino acid/protein turn over. Our biochemical experiments further show that Sven6563 has a [2Fe-2S] cluster and that the switch between oxidized and reduced cluster controls its DNA binding activity in vitro. To our knowledge, both the sensing domain and the target gene regulon are novel for an Rrf2 protein, suggesting Sven6563 represents a new member of the Rrf2 superfamily. Given the redox sensitivity of its Fe-S cluster we have tentatively named the protein RsrR for Redox sensitive response Regulator

An overview of animal prion diseases

Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy of primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, animal prion diseases have basically occurred via the acquisition of infection from contaminated feed or via the exposure to contaminated environment. Scrapie and chronic wasting disease are naturally sustaining epidemics. The transmission of BSE to human has caused more than 200 cases of variant Cruetzfeldt-Jacob disease and has raised serious public health concerns. The present review discusses the epidemiology, clinical neuropathology, transmissibility and genetics of animal prion diseases

Prion protein-specific antibodies that detect multiple TSE agents with high sensitivity

This paper describes the generation, characterisation and potential applications of a panel of novel anti-prion protein monoclonal antibodies (mAbs). The mAbs were generated by immunising PRNP null mice, using a variety of regimes, with a truncated form of recombinant ovine prion protein spanning residues 94–233. Epitopes of specific antibodies were mapped using solid-phase Pepscan analysis and clustered to four distinct regions within the PrP molecule. We have demonstrated the utility of these antibodies by use of Western blotting and immunohistochemistry in tissues from a range of different species affected by transmissible spongiform encephalopathy (TSE). In comparative tests against extensively-used and widely-published, commercially available antibodies, similar or improved results can be obtained using these new mAbs, specifically in terms of sensitivity of detection. Since many of these antibodies recognise native PrPC, they could also be applied to a broad range of immunoassays such as flow cytometry, DELFIA analysis or immunoprecipitation. We are using these reagents to increase our understanding of TSE pathogenesis and for use in potential diagnostic screening assays

Functional Redundancy of Two Pax-Like Proteins in Transcriptional Activation of Cyst Wall Protein Genes in Giardia lamblia

The protozoan Giardia lamblia differentiates from a pathogenic trophozoite into an infectious cyst to survive outside of the host. During encystation, genes encoding cyst wall proteins (CWPs) are coordinately induced. Pax family transcription factors are involved in a variety of developmental processes in animals. Nine Pax proteins have been found to play an important role in tissue and organ development in humans. To understand the progression from primitive to more complex eukaryotic cells, we tried to identify putative pax genes in the G. lamblia genome and found two genes, pax1 and pax2, with limited similarity. We found that Pax1 may transactivate the encystation-induced cwp genes and interact with AT-rich initiatior elements that are essential for promoter activity and transcription start site selection. In this study, we further characterized Pax2 and found that, like Pax1, Pax2 was present in Giardia nuclei and it may specifically bind to the AT-rich initiator elements of the encystation-induced cwp1-3 and myb2 genes. Interestingly, overexpression of Pax2 increased the cwp1-3 and myb2 gene expression and cyst formation. Deletion of the C-terminal paired domain or mutation of the basic amino acids of the paired domain resulted in a decrease of nuclear localization, DNA-binding activity, and transactivation activity of Pax2. These results are similar to those found in the previous Pax1 study. In addition, the profiles of gene expression in the Pax2 and Pax1 overexpressing cells significantly overlap in the same direction and ERK1 associated complexes may phosphorylate Pax2 and Pax1, suggesting that Pax2 and Pax1 may be downstream components of a MAPK/ERK1 signaling pathway. Our results reveal functional redundancy between Pax2 and Pax1 in up-regulation of the key encystation-induced genes. These results illustrate functional redundancy of a gene family can occur in order to increase maintenance of important gene function in the protozoan organism G. lamblia

Four types of scrapie in goats differentiated from each other and bovine spongiform encephalopathy by biochemical methods

Scrapie in goats has been known since 1942, the archetype of prion diseases in which only prion protein (PrP) in misfolded state (PrPSc) acts as infectious agent with fatal consequence. Emergence of bovine spongiform encephalopathy (BSE) with its zoonotic behaviour and detection in goats enhanced fears that its source was located in small ruminants. However, in goats knowledge on prion strain typing is limited. A European-wide study is presented concerning the biochemical phenotypes of the protease resistant fraction of PrPSc (PrPres) in over thirty brain isolates from transmissible spongiform encephalopathy (TSE) affected goats collected in seven countries. Three different scrapie forms were found: classical scrapie (CS), Nor98/atypical scrapie and one case of CH1641 scrapie. In addition, CS was found in two variants—CS-1 and CS-2 (mainly Italy)—which differed in proteolytic resistance of the PrPres N-terminus. Suitable PrPres markers for discriminating CH1641 from BSE (C-type) appeared to be glycoprofile pattern, presence of two triplets instead of one, and structural (in)stability of its core amino acid region. None of the samples exhibited BSE like features. BSE and these four scrapie types, of which CS-2 is new, can be recognized in goats with combinations of a set of nine biochemical parameters

Decision support tools for site-specific fertilizer recommendations and agricultural planning in selected countries in sub-Sahara Africa

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