Shiga toxin 1 elicits diverse biologic responses in mesangial cells

Shiga toxin 1 elicits diverse biologic responses in mesangial cells.BackgroundShiga toxin 1 (Stx1) is a causative agent in hemolytic uremic syndrome (HUS). Its receptor, the glycosphingolipid globotriaosylceramide (Gb3), is expressed on cultured human endothelial and mesangial cells. Mesangial cell injury in HUS ranges from mild cellular edema to severe mesangiolysis and eventual glomerulosclerosis. We hypothesized that, in addition to endothelial cells, mesangial cells are targets of Stx1.MethodsHuman mesangial cells were exposed to Stx1. Protein synthesis was measured using [35S]-methionine/cysteine. Cell viability was measured as the lysosomal uptake of Neutral Red. Monocyte chemotactic peptide (MCP-1) mRNA and protein were analyzed by Northern blotting and ELISA.ResultsStx1 (0.25 to 2500ng/ml) resulted in a dose-dependent inhibition of protein synthesis. This effect of Stx1 was potentiated by preincubation of the cells with interleukin-1α (IL-1α; 2ng/ml) or tumor necrosis-α (TNF-α; 500 U/ml). Stx1 had little effect on mesangial cell viability during the first 24hours of exposure to Stx1. However, prolonged incubation with Stx1 for 48 and 72hours resulted in a 68% and 80% decrease in cell-viability, respectively. Stx1 elicited a dose and time dependent increase in the levels of MCP-1 mRNA, an effect that was potentiated by preincubation with IL-1α.ConclusionThese data indicate that mesangial cells are susceptible to the effects of Stx1 in vitro. Stx1 exerts a spectrum of biologic effects on mesangial cells ranging from activation of chemokine genes to a lethal toxic injury. Immunoinflammatory cytokines potentiate the effects of Stx1. Thus, glomerular pathology in HUS may also result from a direct effect of Stx1 on mesangial cells

SDSS IV MaNGA - Rotation Velocity Lags in the Extraplanar Ionized Gas from MaNGA Observations of Edge-on Galaxies

We present a study of the kinematics of the extraplanar ionized gas around several dozen galaxies observed by the Mapping of Nearby Galaxies at the Apache Point Observatory (MaNGA) survey. We considered a sample of 67 edge-on galaxies out of more than 1400 extragalactic targets observed by MaNGA, in which we found 25 galaxies (or 37%) with regular lagging of the rotation curve at large distances from the galactic midplane. We model the observed $H\alpha$ emission velocity fields in the galaxies, taking projection effects and a simple model for the dust extinction into the account. We show that the vertical lag of the rotation curve is necessary in the modeling, and estimate the lag amplitude in the galaxies. We find no correlation between the lag and the star formation rate in the galaxies. At the same time, we report a correlation between the lag and the galactic stellar mass, central stellar velocity dispersion, and axial ratio of the light distribution. These correlations suggest a possible higher ratio of infalling-to-local gas in early-type disk galaxies or a connection between lags and the possible presence of hot gaseous halos, which may be more prevalent in more massive galaxies. These results again demonstrate that observations of extraplanar gas can serve as a potential probe for accretion of gas.Comment: 13 pages, 11 figures, accepted for publication in Ap

Skill competency development strategies by a contractor

Construction skills are one of the vital aspects of construction work which is growing in importance due to skill gaps and skill shortages during different economic cycles. The aim of this study was to investigate competence development strategies by a traditional construction company within its own pool of skill resources and among its supply chain members. The study was carried out via literature review, empirical studies involving a focus study, analysis of documentary evidence supported by unstructured interviews and a report of skill development/supply chain conference. The study demonstrates how long-term skill development can be achieved through: (a) strategic capacity planning which allows high retention, continuous training, and balanced construction demand and contractor’s supply capacity over the long term; (b) updating and upgrading the knowledge base of the supply chain through conferences and training schemes; (c) strategic investment in the workforce through training, vocational and higher degrees; and (d) acquaintance with different sources of finance. This study will assist small traditional firms in building competencies in skill development and improvement. It will assist an international audience who may face similar issue with their construction firm

Empiema necessitans y osteomielitis aguda secundaria a una infección por Staphylo-coccus aureus resistente a meticilina asociado a la comunidad

Staphylococcus aureus is a well recognized pathogen with global distribution. In recent years community-associated, methicillin-resistant S. aureus has emerged as an increasing cause of severe infections among adults and children. Herein, a case is reported of a previously healthy, 19-month-old male, who presented with empyema necessitans and acute osteomyelitis due to a community-associated, methicillin-resistant, S. aureus strain. This report highlights the evolving epidemiology of S. aureus, as important pathogen in the community as well as the hospital setting, and the importance of establishing appropriate guidelines for diagnosis, management and surveillance of this public health problem.Staphylococcus aureus es uno de los principales patógenos a nivel mundial. Durante los últimos años se ha reportado un incremento en el número de casos de S. aureus resistente a la meticilina adquiridos en la comunidad, tanto en niños como en adultos de los Estados Unidos y de otras partes del mundo.En el presente trabajo reportamos un caso de empiema necessitans y osteomielitis aguda en un niño de 19 meses de edad previamente sano. El presente reporte resalta la cambiante epidemiología de S. aureus tanto en la comunidad como en el medio hospitalario y la importancia de establecer guías apropiadas para el diagnóstico, el tratamiento y la vigilancia de este relevante problema de salud pública

Kinesins relocalize the chromosomal passenger complex to the midzone for spindle disassembly.

Mitotic spindle disassembly after chromosome separation is as important as spindle assembly, yet the molecular mechanisms for spindle disassembly are unclear. In this study, we investigated how the chromosomal passenger complex (CPC), which contains the Aurora B kinase Ipl1, swiftly concentrates at the spindle midzone in late anaphase, and we researched the role of this dramatic relocalization during spindle disassembly. We showed that the kinesins Kip1 and Kip3 are essential for CPC relocalization. In cells lacking Kip1 and Kip3, spindle disassembly is severely delayed until after contraction of the cytokinetic ring. Purified Kip1 and Kip3 interact directly with the CPC and recruit it to microtubules in vitro, and single-molecule experiments showed that the CPC diffuses dynamically on microtubules but that diffusion stops when the CPC encounters a Kip1 molecule. We propose that Kip1 and Kip3 trap the CPC at the spindle midzone in late anaphase to ensure timely spindle disassembly

Follow-up observations at 16 and 33 GHz of extragalactic sources from WMAP 3-year data: I - Spectral properties

We present follow-up observations of 97 point sources from the Wilkinson Microwave Anisotropy Probe (WMAP) 3-year data, contained within the New Extragalactic WMAP Point Source (NEWPS) catalogue between declinations of -4 and +60 degrees; the sources form a flux-density-limited sample complete to 1.1 Jy (approximately 5 sigma) at 33 GHz. Our observations were made at 16 GHz using the Arcminute Microkelvin Imager (AMI) and at 33 GHz with the Very Small Array (VSA). 94 of the sources have reliable, simultaneous -- typically a few minutes apart -- observations with both telescopes. The spectra between 13.9 and 33.75 GHz are very different from those of bright sources at low frequency: 44 per cent have rising spectra (alpha < 0.0), where flux density is proportional to frequency^-alpha, and 93 per cent have spectra with alpha < 0.5; the median spectral index is 0.04. For the brighter sources, the agreement between VSA and WMAP 33-GHz flux densities averaged over sources is very good. However, for the fainter sources, the VSA tends to measure lower values for the flux densities than WMAP. We suggest that the main cause of this effect is Eddington bias arising from variability.Comment: 12 pages, 13 figures, submitted to MNRA

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

Financing equitable access to antiretroviral treatment in South Africa

<p>Abstract</p> <p>Background</p> <p>While South Africa spends approximately 7.4% of GDP on healthcare, only 43% of these funds are spent in the public system, which is tasked with the provision of care to the majority of the population including a large proportion of those in need of antiretroviral treatment (ART). South Africa is currently debating the introduction of a National Health Insurance (NHI) system. Because such a universal health system could mean increased public healthcare funding and improved access to human resources, it could improve the sustainability of ART provision. This paper considers the minimum resources that would be required to achieve the proposed universal health system and contrasts these with the costs of scaled up access to ART between 2010 and 2020.</p> <p>Methods</p> <p>The costs of ART and universal coverage (UC) are assessed through multiplying unit costs, utilization and estimates of the population in need during each year of the planning cycle. Costs are from the provider’s perspective reflected in real 2007 prices.</p> <p>Results</p> <p>The annual costs of providing ART increase from US$1 billion in 2010 to US$3.6 billion in 2020. If increases in funding to public healthcare only keep pace with projected real GDP growth, then close to 30% of these resources would be required for ART by 2020. However, an increase in the public healthcare resource envelope from 3.2% to 5%-6% of GDP would be sufficient to finance both ART and other services under a universal system (if based on a largely public sector model) and the annual costs of ART would not exceed 15% of the universal health system budget.</p> <p>Conclusions</p> <p>Responding to the HIV-epidemic is one of the many challenges currently facing South Africa. Whether this response becomes a “resource for democracy” or whether it undermines social cohesiveness within poor communities and between rich and poor communities will be partially determined by the steps that are taken during the next ten years. While the introduction of a universal system will be complex, it could generate a health system responsive to the needs of all South Africans.</p

Early severe morbidity and resource utilization in South African adults on antiretroviral therapy

BACKGROUND:High rates of mortality and morbidity have been described in sub-Saharan African patients within the first few months of starting highly active antiretroviral therapy (HAART). There is limited data on the causes of early morbidity on HAART and the associated resource utilization. METHODS: A cross-sectional study was conducted of medical admissions at a secondary-level hospital in Cape Town, South Africa. Patients on HAART were identified from a register and HIV-infected patients not on HAART were matched by gender, month of admission, and age group to correspond with the first admission of each case. Primary reasons for admission were determined by chart review. Direct health care costs were determined from the provider's perspective. RESULTS: There were 53 in the HAART group with 70 admissions and 53 in the no-HAART group with 60 admissions. The median duration of HAART was 1 month (interquartile range 1-3 months). Median baseline CD4 count in the HAART group was 57 x 106 cells/L (IQR 15-115). The primary reasons for admission in the HAART group were more likely to be due to adverse drug reactions and less likely to be due to AIDS events than the no-HAART group (34% versus 7%; p < 0.001 and 39% versus 63%; p = 0.005 respectively). Immune reconstitution inflammatory syndrome was the primary reason for admission in 10% of the HAART group. Lengths of hospital stay per admission and inpatient survival were not significantly different between the two groups. Five of the 15 deaths in the HAART group were due to IRIS or adverse drug reactions. Median costs per admission of diagnostic and therapeutic services (laboratory investigations, radiology, intravenous fluids and blood, and non-ART medications) were higher in the HAART group compared with the no-HAART group (US$190 versus US$111; p = 0.001), but the more expensive non-curative costs (overhead, capital, and clinical staff) were not significantly different (US$1199 versus US$1128; p = 0.525). CONCLUSIONS: Causes of early morbidity are different and more complex in HIV-infected patients on HAART. This results in greater resource utilization of diagnostic and therapeutic services

Consumer perceptions of safety in hospitals

BACKGROUND: Studies investigating adverse events have traditionally been principally undertaken from a medical perspective. The impact that experience of an adverse event has on consumer confidence in health care is largely unknown. The objectives of the study were to seek public opinion on 1) the rate and severity of adverse events experienced in hospitals; and 2) the perception of safety in hospitals, so that predictors of lack of safety could be identified. METHODS: A multistage, clustered survey of persons residing in South Australia (2001), using household interviews (weighted n = 2,884). RESULTS: A total of 67% of respondents aged over forty years reported having at least one member of their household hospitalised in the past five years; with the average being two hospital admissions in five years. Respondents stated that 7.0% (95%CI: 6.2% to 7.9%) of those hospital admissions were associated with an adverse event; 59.7% of respondents (95% CI: 51.4% to 67.5%) rated the adverse event as really serious and 48.5% (95% CI: 40.4% to 56.8%) stated prolonged hospitalisation was required as a consequence of the adverse event. Perception of safety in hospitals was largely affected by the experience of an adverse event; really serious events were the most significant predictor of lack of safety in those aged 40 years and over (RR 2.38; p<0.001). CONCLUSION: The experience of adverse events negatively impacted on public confidence in hospitals. The consumer-reported adverse event rate in hospitals (7.0%) is similar to that identified using medical record review. Based on estimates from other studies, self-reported claims of adverse events in hospital by consumers appear credible, and should be considered when developing appropriate treatment regimes