Complement is activated in progressive multiple sclerosis cortical grey matter lesions

The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain and spinal cord. Inflammation is tightly linked with neurodegeneration, and it is the accumulation of neurodegeneration that underlies increasing neurological disability in progressive MS. Determining pathological mechanisms at play in MS grey matter is therefore a key to our understanding of disease progression

N-(4-Hydroxy­phen­yl)-2-(1,1,3-trioxo-2,3-di­hydro-1,2-benzothia­zol-2-yl)­acet­amide

In the title compound, C15H12N2O5S, the benzisothia­zole group is approximately planar (r.m.s. deviation excluding H atoms and the two O atoms bonded to S = 0.023 Å). The dihedral angle between the benzisothia­zole ring and the terminal phenol ring is 84.9 (1)°. In the crystal, mol­ecules are joined by N—H⋯O and O—H⋯O hydrogen bonds, and π-stacking inter­actions are observed between alternating phenol and benzisothia­zole rings [centroid–centroid distances = 3.929 (3) and 3.943 (3) Å]

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Caveolae-dependent and -independent uptake of albumin in cultured rodent pulmonary endothelial cells

Although a critical role for caveolae-mediated albumin transcytosis in pulmonary endothelium is well established, considerably less is known about caveolae-independent pathways. In this current study, we confirmed that cultured rat pulmonary microvascular (RPMEC) and pulmonary artery (RPAEC) endothelium endocytosed Alexa488-labeled albumin in a saturable, temperature-sensitive mode and internalization resulted in co-localization by fluorescence microscopy with cholera B toxin and caveolin-1. Although siRNA to caveolin-1 (cav-1) in RPAEC significantly inhibited albumin uptake, a remnant portion of albumin uptake was cav-1-independent, suggesting alternative pathways for albumin uptake. Thus, we isolated and cultured mouse lung endothelial cells (MLEC) from wild type and cav-1-/- mice and noted that ∼ 65% of albumin uptake, as determined by confocal imaging or live cell total internal reflectance fluorescence microscopy (TIRF), persisted in total absence of cav-1. Uptake of colloidal gold labeled albumin was evaluated by electron microscopy and demonstrated that albumin uptake in MLEC from cav-1-/- mice was through caveolae-independent pathway(s) including clathrin-coated pits that resulted in endosomal accumulation of albumin. Finally, we noted that albumin uptake in RPMEC was in part sensitive to pharmacological agents (amiloride [sodium transport inhibitor], Gö6976 [protein kinase C inhibitor], and cytochalasin D [inhibitor of actin polymerization]) consistent with a macropinocytosis-like process. The amiloride sensitivity accounting for macropinocytosis also exists in albumin uptake by both wild type and cav-1 -/- MLEC. We conclude from these studies that in addition to the well described caveolar-dependent pulmonary endothelial cell endocytosis of albumin, a portion of overall uptake in pulmonary endothelial cells is cav-1 insensitive and appears to involve clathrin-mediated endocytosis and macropinocytosis-like process. © 2013 Li et al

Complement in the pathogenesis of Alzheimer's disease

The emergence of complement as an important player in normal brain development and pathological remodelling has come as a major surprise to most scientists working in neuroscience and almost all those working in complement. That a system, evolved to protect the host against infection, should have these unanticipated roles has forced a rethink about what complement might be doing in the brain in health and disease, where it is coming from, and whether we can, or indeed should, manipulate complement in the brain to improve function or restore homeostasis. Complement has been implicated in diverse neurological and neuropsychiatric diseases well reviewed elsewhere, from depression through epilepsy to demyelination and dementia, in most complement drives inflammation to exacerbate the disease. Here, I will focus on just one disease, the most common cause of dementia, Alzheimer’s disease. I will briefly review the current understanding of what complement does in the normal brain, noting, in particular, the many gaps in understanding, then describe how complement may influence the genesis and progression of pathology in Alzheimer’s disease. Finally, I will discuss the problems and pitfalls of therapeutic inhibition of complement in the Alzheimer brain

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

Impaired work functioning due to common mental disorders in nurses and allied health professionals: the Nurses Work Functioning Questionnaire

Common mental disorders (CMD) negatively affect work functioning. In the health service sector not only the prevalence of CMDs is high, but work functioning problems are associated with a risk of serious consequences for patients and healthcare providers. If work functioning problems due to CMDs are detected early, timely help can be provided. Therefore, the aim of this study is to develop a detection questionnaire for impaired work functioning due to CMDs in nurses and allied health professionals working in hospitals. First, an item pool was developed by a systematic literature study and five focus group interviews with employees and experts. To evaluate the content validity, additional interviews were held. Second, a cross-sectional assessment of the item pool in 314 nurses and allied health professionals was used for item selection and for identification and corroboration of subscales by explorative and confirmatory factor analysis. The study results in the Nurses Work Functioning Questionnaire (NWFQ), a 50-item self-report questionnaire consisting of seven subscales: cognitive aspects of task execution, impaired decision making, causing incidents at work, avoidance behavior, conflicts and irritations with colleagues, impaired contact with patients and their family, and lack of energy and motivation. The questionnaire has a proven high content validity. All subscales have good or acceptable internal consistency. The Nurses Work Functioning Questionnaire gives insight into precise and concrete aspects of impaired work functioning of nurses and allied health professionals. The scores can be used as a starting point for purposeful intervention

Post-glacial hunter-gatherer subsistence patterns in Britain:Dietary reconstruction using FRUITS

The diets of 85 individuals from 21 sites were modelled using FRUITS based on their bulk bone collagen C- and N-stable isotope ratio signatures. The sites, which occur in a range of environments, group into three distinct periods corresponding to the British ‘Late Upper Palaeolithic’, ‘Early Mesolithic’ and ‘Late Mesolithic’, respectively.The FRUITS models for three LUP sites dated to the Bølling-Allerød Interstadial suggest an emphasis on terrestrial (animal and plant) resources. The FRUITS predictions for the Early and Late Mesolithic suggest there was significant variability in diet between sites and occasionally between individuals from the same site. The Late Mesolithic coastal site of Cnoc Coig in western Scotland shows the expected emphasis on marine resources. In contrast, Early and Late Mesolithic coastal sites in South Wales show greater reliance on terrestrial food sources. In several cases, our model predictions differ from the interpretations of previous authors. A surprising outcome is the lack of evidence for the consumption of freshwater resources at sites near large rivers.We add the caveat that our model predictions are likely influenced by inadequate baseline δ13C and δ15N data for wild terrestrial plant and aquatic resources, in particular