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101.
102.
Timothy Abuya Charlotte E. Warren Nora Miller Rebecca Njuki Charity Ndwiga Alice Maranga Faith Mbehero Anne Njeru Ben Bellows 《PloS one》2015,10(4)
Background
Poor quality of care including fear of disrespect and abuse (D&A) perpetuated by health workers influences women’s decisions to seek maternity care. Key manifestations of D&A include: physical abuse, non-consented care, non-confidential care, non-dignified care, discrimination, abandonment, and detention in facilities. This paper describes manifestations of D&A experienced in Kenya and measures their prevalence.Methods
This paper is based on baseline data collected during a before-and-after study designed to measure the effect of a package of interventions to reduce the prevalence of D&A experienced by women during labor and delivery in thirteen Kenyan health facilities. Data were collected through an exit survey of 641 women discharged from postnatal wards. We present percentages of D&A manifestations and odds ratios of its relationship with demographic characteristics using a multivariate fixed effects logistic regression model.Results
Twenty percent of women reported any form of D&A. Manifestations of D&A includes: non-confidential care (8.5%), non-dignified care (18%), neglect or abandonment (14.3%), Non-consensual care (4.3%) physical abuse (4.2%) and, detainment for non-payment of fees (8.1). Women aged 20-29 years were less likely to experience non-confidential care compared to those under 19; OR: [0.6 95% CI (0.36, 0.90); p=0.017]. Clients with no companion during delivery were less likely to experience inappropriate demands for payment; OR: [0.49 (0.26, 0.95); p=0.037]; while women with higher parities were three times more likely to be detained for lack of payment and five times more likely to be bribed compared to those experiencing there first birth.Conclusion
One out of five women experienced feeling humiliated during labor and delivery. Six categories of D&A during childbirth in Kenya were reported. Understanding the prevalence of D&A is critical in developing interventions at national, health facility and community levels to address the factors and drivers that influence D&A in facilities and to encourage clients’ future facility utilization. 相似文献103.
Michelle E. LeBlanc Weiwen Wang Nora B. Caberoy Xiuping Chen Feiye Guo Gabriela Alvarado Chen Shen Feng Wang Hui Wang Rui Chen Zhao-Jun Liu Keith Webster Wei Li 《PloS one》2015,10(5)
Hepatoma-derived growth factor-related protein-3 (Hdgfrp3 or HRP-3) was recently reported as a neurotrophic factor and is upregulated in hepatocellular carcinoma to promote cancer cell survival. Here we identified HRP-3 as a new endothelial ligand and characterized its in vitro and in vivo functional roles and molecular signaling. We combined open reading frame phage display with multi-round in vivo binding selection to enrich retinal endothelial ligands, which were systematically identified by next generation DNA sequencing. One of the identified endothelial ligands was HRP-3. HRP-3 expression in the retina and brain was characterized by Western blot and immunohistochemistry. Cell proliferation assay showed that HRP-3 stimulated the growth of human umbilical vein endothelial cells (HUVECs). HRP-3 induced tube formation of HUVECs in culture. Wound healing assay indicated that HRP-3 promoted endothelial cell migration. HRP-3 was further confirmed for its in vitro angiogenic activity by spheroid sprouting assay. HRP-3 extrinsically activated the extracellular-signal-regulated kinase ½ (ERK1/2) pathway in endothelial cells. The angiogenic activity of HRP-3 was independently verified by mouse cornea pocket assay. Furthermore, in vivo Matrigel plug assay corroborated HRP-3 activity to promote new blood vessel formation. These results demonstrated that HRP-3 is a novel angiogenic factor. 相似文献
104.
Aleksandra Inic-Kanada Marijana Stojanovic Simone Schlacher Elisabeth Stein Sandra Belij-Rammerstorfer Emilija Marinkovic Ivana Lukic Jacqueline Montanaro Nadine Schuerer Nora Bintner Vesna Kovacevic-Jovanovic Ognjen Krnjaja Ulrike Beate Mayr Werner Lubitz Talin Barisani-Asenbauer 《PloS one》2015,10(12)
Trachoma, caused by the intracellular bacterium Chlamydia trachomatis (Ct), remains the world’s leading preventable infectious cause of blindness. Recent attempts to develop effective vaccines rely on modified chlamydial antigen delivery platforms. As the mechanisms engaged in the pathology of the disease are not fully understood, designing a subunit vaccine specific to chlamydial antigens could improve safety for human use. We propose the delivery of chlamydia-specific antigens to the ocular mucosa using particulate carriers, bacterial ghosts (BGs). We therefore characterized humoral and cellular immune responses after conjunctival and subcutaneous immunization with a N-terminal portion (amino acid 1–893) of the chlamydial polymorphic membrane protein C (PmpC) of Ct serovar B, expressed in probiotic Escherichia coli Nissle 1917 bacterial ghosts (EcN BGs) in BALB/c mice. Three immunizations were performed at two-week intervals, and the immune responses were evaluated two weeks after the final immunization in mice. In a guinea pig model of ocular infection animals were immunized in the same manner as the mice, and protection against challenge was assessed two weeks after the last immunization. N-PmpC was successfully expressed within BGs and delivery to the ocular mucosa was well tolerated without signs of inflammation. N-PmpC-specific mucosal IgA levels in tears yielded significantly increased levels in the group immunized via the conjunctiva compared with the subcutaneously immunized mice. Immunization with N-PmpC EcN BGs via both immunization routes prompted the establishment of an N-PmpC-specific IFNγ immune response. Immunization via the conjunctiva resulted in a decrease in intensity of the transitional inflammatory reaction in conjunctiva of challenged guinea pigs compared with subcutaneously and non-immunized animals. The delivery of the chlamydial subunit vaccine to the ocular mucosa using a particulate carrier, such as BGs, induced both humoral and cellular immune responses. Further investigations are needed to improve the immunization scheme and dosage. 相似文献
105.
Background
Time out-of-home has been linked with numerous health outcomes, including cognitive decline, poor physical ability and low emotional state. Comprehensive characterization of this important health metric would potentially enable objective monitoring of key health outcomes. The objective of this study is to determine the relationship between time out-of-home and cognitive status, physical ability and emotional state.Methods and Findings
Participants included 85 independent older adults, age 65–96 years (M = 86.36; SD = 6.79) who lived alone, from the Intelligent Systems for Assessing Aging Changes (ISAAC) and the ORCATECH Life Laboratory cohorts. Factors hypothesized to affect time out-of-home were assessed on three different temporal levels: yearly (cognitive status, loneliness, clinical walking speed), weekly (pain and mood) or daily (time out-of-home, in-home walking speed, weather, and season). Subject characteristics including age, race, and gender were assessed at baseline. Total daily time out-of-home in hours was assessed objectively and unobtrusively for up to one year using an in-home activity sensor platform. A longitudinal tobit mixed effects regression model was used to relate daily time out-of-home to cognitive status, physical ability and emotional state. More hours spend outside the home was associated with better cognitive function as assessed using the Clinical Dementia Rating (CDR) Scale, where higher scores indicate lower cognitive function (β CDR = -1.69, p<0.001). More hours outside the home was also associated with superior physical ability (β Pain = -0.123, p<0.001) and improved emotional state (β Lonely = -0.046, p<0.001; β Low mood = -0.520, p<0.001). Weather, season, and weekday also affected the daily time out-of-home.Conclusions
These results suggest that objective longitudinal monitoring of time out-of-home may enable unobtrusive assessment of cognitive, physical and emotional state. In addition, these results indicate that the factors affecting out-of-home behavior are complex, with factors such as living environment, weather and season significantly affecting time out-of-home. Studies investigating the relationship between time out-of-home and health outcomes may be optimized by taking into account the environment and life factors presented here. 相似文献106.
Hiroko H. Dodge Jian Zhu Nora C. Mattek Daniel Austin Judith Kornfeld Jeffrey A. Kaye 《PloS one》2015,10(9)
Background
Trials in Alzheimer’s disease are increasingly focusing on prevention in asymptomatic individuals. This poses a challenge in examining treatment effects since currently available approaches are often unable to detect cognitive and functional changes among asymptomatic individuals. Resultant small effect sizes require large sample sizes using biomarkers or secondary measures for randomized controlled trials (RCTs). Better assessment approaches and outcomes capable of capturing subtle changes during asymptomatic disease stages are needed.Objective
We aimed to develop a new approach to track changes in functional outcomes by using individual-specific distributions (as opposed to group-norms) of unobtrusive continuously monitored in-home data. Our objective was to compare sample sizes required to achieve sufficient power to detect prevention trial effects in trajectories of outcomes in two scenarios: (1) annually assessed neuropsychological test scores (a conventional approach), and (2) the likelihood of having subject-specific low performance thresholds, both modeled as a function of time.Methods
One hundred nineteen cognitively intact subjects were enrolled and followed over 3 years in the Intelligent Systems for Assessing Aging Change (ISAAC) study. Using the difference in empirically identified time slopes between those who remained cognitively intact during follow-up (normal control, NC) and those who transitioned to mild cognitive impairment (MCI), we estimated comparative sample sizes required to achieve up to 80% statistical power over a range of effect sizes for detecting reductions in the difference in time slopes between NC and MCI incidence before transition.Results
Sample size estimates indicated approximately 2000 subjects with a follow-up duration of 4 years would be needed to achieve a 30% effect size when the outcome is an annually assessed memory test score. When the outcome is likelihood of low walking speed defined using the individual-specific distributions of walking speed collected at baseline, 262 subjects are required. Similarly for computer use, 26 subjects are required.Conclusions
Individual-specific thresholds of low functional performance based on high-frequency in-home monitoring data distinguish trajectories of MCI from NC and could substantially reduce sample sizes needed in dementia prevention RCTs. 相似文献107.
108.
Nora Wender Jan Hegermann Bettina Brunner Brigitte Nuscher Tim Bartels Armin Giese Klaus Beyer Stefan Eimer Konstanze F Winklhofer Christian Haass 《The EMBO journal》2010,29(20):3571-3589
Aggregation of α‐synuclein (αS) is involved in the pathogenesis of Parkinson's disease (PD) and a variety of related neurodegenerative disorders. The physiological function of αS is largely unknown. We demonstrate with in vitro vesicle fusion experiments that αS has an inhibitory function on membrane fusion. Upon increased expression in cultured cells and in Caenorhabditis elegans, αS binds to mitochondria and leads to mitochondrial fragmentation. In C. elegans age‐dependent fragmentation of mitochondria is enhanced and shifted to an earlier time point upon expression of exogenous αS. In contrast, siRNA‐mediated downregulation of αS results in elongated mitochondria in cell culture. αS can act independently of mitochondrial fusion and fission proteins in shifting the dynamic morphologic equilibrium of mitochondria towards reduced fusion. Upon cellular fusion, αS prevents fusion of differently labelled mitochondrial populations. Thus, αS inhibits fusion due to its unique membrane interaction. Finally, mitochondrial fragmentation induced by expression of αS is rescued by coexpression of PINK1, parkin or DJ‐1 but not the PD‐associated mutations PINK1 G309D and parkin Δ1–79 or by DJ‐1 C106A. 相似文献
109.
Christoph Rademacher Jens Landström Nora Sindhuwinata Monica M. Palcic Göran Widmalm Thomas Peters 《Glycoconjugate journal》2010,27(3):349-358
A substantial body of work has been devoted to the design and synthesis of glycosyltransferase inhibitors. A major obstacle
has always been the demanding chemistry. Therefore, only few potent and selective inhibitors are known to date. Glycosyltransferases
possess two distinct binding sites, one for the donor substrate, and one for the acceptor substrate. In many cases binding
to the donor site is well defined but data for acceptor binding is sparse. In particular, acceptor binding sites are often
shallow, and in many cases the dimensions of the binding pocket are not well defined. One approach to glycosyltransferase
inhibitors is to chemically link donor site and acceptor site ligands to generate high affinity binders. Here, we describe
a novel approach to identify acceptor site ligands from a fragment library. We have chosen human blood group B galactosyltransferase
(GTB) as a biologically important model target. The approach utilizes a combination of STD NMR, spin-lock filtered NMR experiments
and surface plasmon resonance measurements. Following this route we have identified molecular fragments from a fragment library
that bind to the acceptor site of GTB with affinities of the order of a natural acceptor substrate. Unlike natural substrates
these fragments allow for straightforward chemical modifications and, therefore will serve as scaffolds for potent GTB inhibitors.
In general, the approach described is applicable to any glycosyltransferase and may assist in the development of novel glycosyltransferase
inhibitors. 相似文献
110.