Microglia are the primary immune cells of the brain whose phenotype largely depends on their surrounding micro-environment. Microglia respond to a multitude of soluble molecules produced by a variety ...of brain cells. Macrophage colony-stimulating factor (M-CSF) is a cytokine found in the brain whose receptor is expressed by microglia. Previous studies suggest a critical role for M-CSF in brain development and normal functioning as well as in several disease processes involving neuroinflammation.
Using biopsy tissue from patients with intractable temporal epilepsy and autopsy tissue, we cultured primary adult human microglia to investigate their response to M-CSF. Mixed glial cultures were treated with 25 ng/ml M-CSF for 96 hours. Proliferation and phagocytosis assays, and high through-put immunocytochemistry, microscopy and image analysis were performed to investigate microglial phenotype and function.
We found that the phenotype of primary adult human microglia was markedly changed following exposure to M-CSF. A greater number of microglia were present in the M-CSF- treated cultures as the percentage of proliferating (BrdU and Ki67-positive) microglia was greatly increased. A number of changes in protein expression occurred following M-CSF treatment, including increased transcription factors PU.1 and C/EBPβ, increased DAP12 adaptor protein, increased M-CSF receptor (CSF-1R) and IGF-1 receptor, and reduced HLA-DP, DQ, DR antigen presentation protein. Furthermore, a distinct morphological change was observed with elongation of microglial processes. These changes in phenotype were accompanied by a functional increase in phagocytosis of Aβ1-42 peptide.
We show here that the cytokine M-CSF dramatically influences the phenotype of adult human microglia. These results pave the way for future investigation of M-CSF-related targets for human therapeutic benefit.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Developing the next generation of scanning helium microscopes requires the fabrication of optical elements with complex internal geometries. We show that resin stereolithography (SLA) 3D ...printing produces low-cost components with the requisite convoluted structures whilst achieving the required vacuum properties, even without
in situ
baking. As a case study, a redesigned pinhole plate optical element of an existing scanning helium microscope was fabricated using SLA 3D printing. In comparison to the original machined component, the new optical element minimised the key sources of background signal, in particular multiple scattering and the secondary effusive beam.
Scanning helium microscopy is an emerging form of microscopy using thermal energy neutral helium atoms as the probe particle. The very low energy combined with lack of charge gives the technique ...great potential for studying delicate systems, and the possibility of several new forms of contrast. To date, neutral helium images have been dominated by topographic contrast, relating to the height and angle of the surface. Here we present data showing contrast resulting from specular reflection and diffraction of helium atoms from an atomic lattice of lithium fluoride. The signature for diffraction is evident by varying the scattering angle and observing sharp features in the scattered distribution. The data indicates the viability of the approach for imaging with diffraction contrast and suggests application to a wide variety of other locally crystalline materials.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Gas and particle-phase organic carbon compounds soluble in water (e.g., WSOC) were measured simultaneously in Atlanta throughout the summer of 2007 to investigate gas/particle partitioning of ambient ...secondary organic aerosol (SOA). Previous studies have established that, in the absence of biomass burning, particulate WSOC (WSOCp) is mainly from secondary organic aerosol (SOA) production. Comparisons between WSOCp, organic carbon (OC) and elemental carbon (EC) indicate that WSOCp was a nearly comprehensive measure of SOA in the Atlanta summertime. WSOCp and gas-phase WSOC (WSOCg) concentrations both exhibited afternoon maxima, indicating that photochemistry was a major route for SOA formation. An additional nighttime maximum in the WSOCg concentration indicated a dark source for oxidized organic gases, but this was not accompanied by detectable increases in WSOCp. To study SOA formation mechanisms, WSOC gas/particle partitioning was investigated as a function of temperature, RH, NOx, O3, and organic aerosol mass concentration. No clear relationship was observed between temperature and partitioning, possibly due to a simultaneous effect from other temperature-dependent processes. For example, positive temperature effects on emissions of biogenic SOA precursors and photochemical SOA formation may have accounted for the observed similar proportional increases of WSOCp and WSOCg with temperature. Relative humidity data indicated a linear dependence between partitioning and predicted fine particle liquid water. Lower NOx concentrations were associated with greater partitioning to particles, but WSOC partitioning had no visible relation to O3 or fine particle OC mass concentration. There was, however, a relationship between WSOC partitioning and the WSOCp concentration, suggesting a compositional dependence between partitioning semi-volatile gases and the absorbing organic aerosol. Combined, the overall results suggest two dominant SOA formation processes in urban Atlanta during summer. One was the photochemical production of SOA from presumably biogenic precursors that increased with the onset of sunrise and peaked in the afternoon. The other, which showed no apparent diurnal pattern, involved the partitioning of semi-volatile gases to liquid water, followed by heterogeneous reactions. The co-emission of water vapor and biogenic VOCs from vegetation may link these processes.
•Optimal design of a scanning helium microscope obtained through a constrained optimisation.•Model for the intensity includes both the source and atom optics.•Zone plate performance calculated with a ...diffraction model.•Lagrange multipliers are used to perform the constrained optimisation for realistic parameters.•The zone plate setup is shown to be advantageous if the beam standard deviation is below about 300 nm.
We describe a method for obtaining the optimal design of a normal incidence Scanning Helium Microscope (SHeM). Scanning helium microscopy is a recently developed technique that uses low energy neutral helium atoms as a probe to image the surface of a sample without causing damage. After estimating the variation of source brightness with nozzle size and pressure, we perform a constrained optimisation to determine the optimal geometry of the instrument (i.e. the geometry that maximises intensity) for a given target resolution. For an instrument using a pinhole to form the helium microprobe, the source and atom optics are separable and Lagrange multipliers are used to obtain an analytic expression for the optimal parameters. For an instrument using a zone plate as the focal element, the whole optical system must be considered and a numerical approach has been applied. Unlike previous numerical methods for optimisation, our approach provides insight into the effect and significance of each instrumental parameter, enabling an intuitive understanding of effect of the SHeM geometry. We show that for an instrument with a working distance of 1 mm, a zone plate with a minimum feature size of 25 nm becomes the advantageous focussing element if the desired beam standard deviation is below about 300 nm.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Foot ulceration affects 15 to 20% of people with diabetes. It is a major precursor to amputation in this patient group, and early and appropriate treatment provides the greatest ...opportunity for healing. The use of silver for its antimicrobial properties has re‐emerged, and modern wound dressings that release a sustained amount of free silver ions, are now widely used in wound management.
Objectives
To evaluate the effects of silver‐containing dressings and topical agents on infection rates and healing of diabetes related foot ulcers.
Search methods
We searched the Cochrane Wounds Group Specialised Register (Searched 8/2/10); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010 Issue 1); Ovid MEDLINE ‐ 2007 to January Week 3 2010; Ovid MEDLINE ‐ In‐Process & Other Non‐Indexed Citations (Searched 4/2/10); Ovid EMBASE ‐ 2007 to 2010 Week 04; EBSCO CINAHL ‐ 2007 to 8 February 2010.
Selection criteria
Randomised controlled trials and non‐randomised controlled clinical trials were considered for inclusion. Studies were included if they involved participants with Type 1 or Type 2 diabetes and related foot ulcers, met the requirements for randomisation, allocation and concealment where appropriate, and compared the intervention with a placebo or a sham dressing, an alternative non silver based dressing or no dressing, and reported outcomes that represent healing rate or infection.
Data collection and analysis
Two authors independently evaluated the papers identified by the search strategy against the inclusion criteria but identified no trials eligible for inclusion in the review. It was not possible to perform planned subgroup and sensitivity analysis in the absence of data. In future, if eligible trials become available, a random effects model will be applied for meta‐analysis in the presence of statistical heterogeneity (estimated using the I2 statistic). Dichotomous outcomes will be reported as risk ratios with 95% confidence intervals (CI), and continuous outcomes as weighted mean differences (WMD) with 95% CI. Statistical significance will be set at P value < 0.05 for all outcomes and the magnitude of the effect will be estimated by calculating the number needed to treat (NNT) with 95% CI.
Main results
No studies were identified that met with the inclusion criteria
Authors' conclusions
Despite the widespread use of dressings and topical agents containing silver for the treatment of diabetic foot ulcers, no randomised trials or controlled clinical trials exist that evaluate their clinical effectiveness. Trials are needed to determine clinical and cost‐effectiveness and long term outcomes including adverse events.
Resolution is a key parameter for microscopy, but methods for standardizing its definition are often poorly defined. For a developing technique such as scanning helium microscopy, it is critical that ...a consensus-based protocol for determining instrument resolution is prepared as a written standard to allow both comparable quantitative measurements of surface topography and direct comparisons between different instruments. In this paper we assess a range of quantitative methods for determining instrument resolution and determine their relative merits when applied to the specific case of the scanning helium microscope (SHeM). Consequently, we present a preliminary protocol for measuring the resolution in scanning helium microscopy based upon utilizing appropriate test samples with sets of slits of well-defined dimensions to establish the quantitative resolution of any similar instrument.
•Resolution is a key parameter for microscopy, but is often poorly defined.•No agreed definition for resolution in scanning helium microscopy.•We assess a range of quantitative methods for determining instrument resolution.•Experimentally test Fourier based and real space methods for measuring resolution.•Present a protocol to determine resolution using sets of well-defined slits.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The 2008 financial crisis exacerbated an already mounting workforce challenge faced by most health services in the western world, namely the recruitment and retention of qualified nurses.
...Aim
This paper examines two additional challenges of relevance to workforce planning in health care, an ageing nursing workforce and reliance upon migrant nurses to solve short‐term workforce issues.
Methods
Using Ireland as a case exemplar of these issues, this paper argues that policy makers and service providers should seek not only to address the challenge of retaining trained newly qualified and younger nurses but also focus on supporting older nurses and migrant nurses to remain within the workforce.
Findings
The findings of this paper highlight the need for workforce planners, policy makers and service providers to take account of an ageing nursing workforce and reliance on foreign‐trained nurses as a solution to short‐term planning difficulties.
Conclusion
Failure to address this need is likely to lead to significant workforce difficulties for health services into the future and undermine current efforts to increase the number and long‐term retention of qualified nursing staff.
Implications for Nursing Policy
Policy makers and service providers should focus on the retention of trained older nurses as an important element of workforce planning.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
PDF
