1,115 research outputs found

    Does coordinated postpartum care influence costs?

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    Questions under study: To investigate changes to health insurance costs for post-discharge postpartum care after the introduction of a midwife-led coordinated care model. Methods: The study included mothers and their newborns insured by the Helsana health insurance group in Switzerland and who delivered between January 2012 and May 2013 in the canton of Basel Stadt (BS) (intervention canton). We compared monthly post-discharge costs before the launch of a coordinated postpartum care model (control phase, n = 144) to those after its introduction (intervention phase, n = 92). Costs in the intervention canton were also compared to those in five control cantons without a coordinated postpartum care model (cross-sectional control group: n = 7, 767). Results: The average monthly post-discharge costs for mothers remained unchanged in the seven months following the introduction of a coordinated postpartum care model, despite a higher use of midwife services (increasing from 72% to 80%). Likewise, monthly costs did not differ between the intervention canton and five control cantons. In multivariate analyses, the ambulatory costs for mothers were not associated with the post-intervention phase. Cross-sectionally, however, they were positively associated with midwifery use. For children, costs in the post-intervention phase were lower in the first month after hospital discharge compared to the pre-intervention phase (difference of –114 CHF [95%CI –202 CHF to –27 CHF]), yet no differences were seen in the cross-sectional comparison. Conclusions: The introduction of a coordinated postpartum care model was associated with decreased costs for neonates in the first month after hospital discharge. Despite increased midwifery use, costs for mothers remained unchanged

    Effective Partnership in Community-Based Health Promotion: Lessons from the Health Literacy Partnership

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    This paper aims to explore key elements needed to successfully develop healthy partnerships and collaborative working in community-based health promotion. It draws upon the lessons learned from a case study with the Health Literacy Partnership in Stoke-on-Trent, UK in developing the health literacy strategy in the area. The process was underpinned by respect for diverse yet complementary perspectives and skills from the grassroots up. This involved engagement with key stakeholders, development and support for community projects, and sharing of good practice with other national and local organizations. Stakeholders involved in developing the strategy also had a keen interest in health literacy and a strong commitment to promoting health and well-being in the area. Through patience, perseverance, and continuous open communication and learning, the health literacy strategy in Stoke-on-Trent, UK is beginning to have a ripple effect into local practice, and will potentially influence policy in the future. Keywords: health literacy; effective partnerships; community-based health promotion; collaborative workin

    Identification of the protease cleavage sites in a reconstituted Gag polyprotein of an HERV-K(HML-2) element

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    <p>Abstract</p> <p>Background</p> <p>The human genome harbors several largely preserved HERV-K(HML-2) elements. Although this retroviral family comes closest of all known HERVs to producing replication competent virions, mutations acquired during their chromosomal residence have rendered them incapable of expressing infectious particles. This also holds true for the HERV-K113 element that has conserved open reading frames (ORFs) for all its proteins in addition to a functional LTR promoter. Uncertainty concerning the localization and impact of post-insertional mutations has greatly hampered the functional characterization of these ancient retroviruses and their proteins. However, analogous to other betaretroviruses, it is known that HERV-K(HML-2) virions undergo a maturation process during or shortly after release from the host cell. During this process, the subdomains of the Gag polyproteins are released by proteolytic cleavage, although the nature of the mature HERV-K(HML-2) Gag proteins and the exact position of the cleavage sites have until now remained unknown.</p> <p>Results</p> <p>By aligning the amino acid sequences encoded by the <it>gag-pro-pol </it>ORFs of HERV-K113 with the corresponding segments from 10 other well-preserved human specific elements we identified non-synonymous post-insertional mutations that have occurred in this region of the provirus. Reversion of these mutations and a partial codon optimization facilitated the large-scale production of maturation-competent HERV-K113 virus-like particles (VLPs). The Gag subdomains of purified mature VLPs were separated by reversed-phase high-pressure liquid chromatography and initially characterized using specific antibodies. Cleavage sites were identified by mass spectrometry and N-terminal sequencing and confirmed by mutagenesis. Our results indicate that the <it>gag </it>gene product Pr74<sup>Gag </sup>of HERV-K(HML-2) is processed to yield p15-MA (matrix), SP1 (spacer peptide of 14 amino acids), p15, p27-CA (capsid), p10-NC (nucleocapsid) and two C-terminally encoded glutamine- and proline-rich peptides, QP1 and QP2, spanning 23 and 19 amino acids, respectively.</p> <p>Conclusions</p> <p>Expression of reconstituted sequences of original HERV elements is an important tool for studying fundamental aspects of the biology of these ancient viruses. The analysis of HERV-K(HML-2) Gag processing and the nature of the mature Gag proteins presented here will facilitate further studies of the discrete functions of these proteins and of their potential impact on the human host.</p

    Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients

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    Background: A novel gammaretrovirus named xenotropic murine leukemia virus-related virus (XMRV) has been recently identified and found to have a prevalence of 40% in prostate tumor samples from American patients carrying a homozygous R462Q mutation in the RNaseL gene. This mutation impairs the function of the innate antiviral type I interferon pathway and is a known susceptibility factor for prostate cancer. Here, we attempt to measure the prevalence of XMRV in prostate cancer cases in Germany and determine whether an analogous association with the R462Q polymorphism exists. Results: 589 prostate tumor samples were genotyped by real-time PCR with regard to the RNaseL mutation. DNA and RNA samples from these patients were screened for the presence of XMRV-specific gag sequences using a highly sensitive nested PCR and RT-PCR approach. Furthermore, 146 sera samples from prostate tumor patients were tested for XMRV Gag and Env antibodies using a newly developed ELISA assay. In agreement with earlier data, 12.9% (76 samples) were shown to be of the QQ genotype. However, XMRV specific sequences were detected at neither the DNA nor the RNA level. Consistent with this result, none of the sera analyzed from prostate cancer patients contained XMRV-specific antibodies. Conclusion: Our results indicate a much lower prevalence (or even complete absence) of XMRV in prostate tumor patients in Germany. One possible reason for this could be a geographically restricted incidence of XMRV infections

    One-step selection of Vaccinia virus-binding DNA aptamers by MonoLEX

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    <p>Abstract</p> <p>Background</p> <p>As a new class of therapeutic and diagnostic reagents, more than fifteen years ago RNA and DNA aptamers were identified as binding molecules to numerous small compounds, proteins and rarely even to complete pathogen particles. Most aptamers were isolated from complex libraries of synthetic nucleic acids by a process termed SELEX based on several selection and amplification steps. Here we report the application of a new one-step selection method (MonoLEX) to acquire high-affinity DNA aptamers binding Vaccinia virus used as a model organism for complex target structures.</p> <p>Results</p> <p>The selection against complete Vaccinia virus particles resulted in a 64-base DNA aptamer specifically binding to orthopoxviruses as validated by dot blot analysis, Surface Plasmon Resonance, Fluorescence Correlation Spectroscopy and real-time PCR, following an aptamer blotting assay. The same oligonucleotide showed the ability to inhibit <it>in vitro </it>infection of Vaccinia virus and other orthopoxviruses in a concentration-dependent manner.</p> <p>Conclusion</p> <p>The MonoLEX method is a straightforward procedure as demonstrated here for the identification of a high-affinity DNA aptamer binding Vaccinia virus. MonoLEX comprises a single affinity chromatography step, followed by subsequent physical segmentation of the affinity resin and a single final PCR amplification step of bound aptamers. Therefore, this procedure improves the selection of high affinity aptamers by reducing the competition between aptamers of different affinities during the PCR step, indicating an advantage for the single-round MonoLEX method.</p

    Nonuniqueness of the Potentials of Spin-Density-Functional Theory

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    It is shown that, contrary to widely held beliefs, the potentials of spin-density-functional theory (SDFT) are not unique functionals of the spin densities. Explicit examples of distinct sets of potentials with the same ground-state densities are constructed, and general arguments that uniqueness should not occur in SDFT and other generalized density-functional theories are given. As a consequence, various types of applications of SDFT require significant corrections or modifications.Comment: 4 pages, no figure

    The human host response to monkeypox infection: a proteomic case series study

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    The rapid rise of monkeypox (MPX) cases outside previously endemic areas prompts for a better understanding of the disease. We studied the plasma proteome of a group of MPX patients with a similar infection history and clinical manifestation typical for the current outbreak. We report that MPX in this case series is associated with a strong plasma proteomic response among nutritional and acute phase response proteins. Moreover, we report a correlation between plasma proteins and disease severity. Contrasting the MPX host response with that of COVID‐19, we find a range of similarities, but also important differences. For instance, CFHR1 is induced in COVID‐19, but suppressed in MPX, reflecting the different roles of the complement system in the two infectious diseases. Of note, the spatial overlap in response proteins suggested that a COVID‐19 biomarker panel assay could be repurposed for MPX. Applying a targeted protein panel assay provided encouraging results and distinguished MPX cases from healthy controls. Hence, our results provide a first proteomic characterization of the MPX human host response and encourage further research on protein‐panel assays in emerging infectious diseases

    Disease Severity, Fever, Age, and Sex Correlate With SARS-CoV-2 Neutralizing Antibody Responses

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    Clinical trials on the use of COVID-19 convalescent plasma remain inconclusive. While data on safety is increasingly available, evidence for efficacy is still sparse. Subgroup analyses hint to a dose-response relationship between convalescent plasma neutralizing antibody levels and mortality. In particular, patients with primary and secondary antibody deficiency might benefit from this approach. However, testing of neutralizing antibodies is limited to specialized biosafety level 3 laboratories and is a time- and labor-intense procedure. In this single center study of 206 COVID-19 convalescent patients, clinical data, results of commercially available ELISA testing of SARS-CoV-2 spike-IgG and -IgA, and levels of neutralizing antibodies, determined by plaque reduction neutralization testing (PRNT), were analyzed. At a medium time point of 58 days after symptom onset, only 12.6% of potential plasma donors showed high levels of neutralizing antibodies (PRNT50 >= 1:320). Multivariable proportional odds logistic regression analysis revealed need for hospitalization due to COVID-19 (odds ratio 6.87; p-value 0.0004) and fever (odds ratio 3.00; p-value 0.0001) as leading factors affecting levels of SARS-CoV-2 neutralizing antibody titers in convalescent plasma donors. Using penalized estimation, a predictive proportional odds logistic regression model including the most important variables hospitalization, fever, age, sex, and anosmia or dysgeusia was developed. The predictive discrimination for PRNT50 >= 1:320 was reasonably good with AUC: 0.86 (with 95% CI: 0.79-0.92). Combining clinical and ELISA-based pre-screening, assessment of neutralizing antibodies could be spared in 75% of potential donors with a maximal loss of 10% of true positives (PRNT50 >= 1:320)
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