Antimicrobial lipids such as fatty acids and monoglycerides are promising antibacterial agents that destabilize bacterial cell membranes, causing a wide range of direct and indirect inhibitory ...effects. The goal of this review is to introduce the latest experimental approaches for characterizing how antimicrobial lipids destabilize phospholipid membranes within the broader scope of introducing current knowledge about the biological activities of antimicrobial lipids, testing strategies, and applications for treating bacterial infections. To this end, a general background on antimicrobial lipids, including structural classification, is provided along with a detailed description of their targeting spectrum and currently understood antibacterial mechanisms. Building on this knowledge, different experimental approaches to characterize antimicrobial lipids are presented, including cell-based biological and model membrane-based biophysical measurement techniques. Particular emphasis is placed on drawing out how biological and biophysical approaches complement one another and can yield mechanistic insights into how the physicochemical properties of antimicrobial lipids influence molecular self-assembly and concentration-dependent interactions with model phospholipid and bacterial cell membranes. Examples of possible therapeutic applications are briefly introduced to highlight the potential significance of antimicrobial lipids for human health and medicine, and to motivate the importance of employing orthogonal measurement strategies to characterize the activity profile of antimicrobial lipids.
To evaluate new classification criteria for peripheral spondyloarthritis (SpA) in patients with SpA with peripheral manifestations only.
In this Assessment of SpondyloArthritis international Society ...(ASAS) study, two prespecified sets of criteria were compared against the European Spondylarthropathy Study Group (ESSG) and Amor criteria in newly referred consecutive patients with undiagnosed peripheral arthritis, and/or enthesitis, and/or dactylitis that usually began before 45 years of age. The clinical diagnosis (SpA vs no SpA) made by the ASAS rheumatologist served as reference standard.
In all, 24 ASAS centres included 266 patients, with a final diagnosis of SpA being made in 66.2%. After adjustments a final set of criteria showed the best balance between sensitivity (77.8%) and specificity (82.9%): arthritis and/or enthesitis and/or dactylitis plus (A) one or more of the following parameters: psoriasis, inflammatory bowel disease, preceding infection, human leucocyte antigen B27, uveitis, sacroiliitis on imaging, or (B) two or more other parameters: arthritis, enthesitis, dactylitis, inflammatory back pain in the past, family history of SpA. The new criteria performed better than modified versions of the ESSG (sensitivity 62.5%, specificity 81.1%) and the Amor criteria (sensitivity 39.8%, specificity 97.8%), particularly regarding sensitivity. In the entire ASAS population of 975 patients the combined use of ASAS criteria for axial SpA and ASAS criteria for peripheral SpA also had a better balance (sensitivity 79.5%, specificity 83.3%) than the modified ESSG (sensitivity 79.1%, specificity 68.8%) and Amor criteria (sensitivity 67.5%, specificity 86.7%), respectively.
The new ASAS classification criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis.
To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA).
All Assessment of SpondyloArthritis international Society (ASAS) members were ...invited to include consecutively new patients with chronic (> or =3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%.
Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having "non-radiographic" axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature ("imaging arm") or the presence of HLA-B27 plus at least two SpA features ("clinical arm"). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%).
The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain.
NCT00328068.
The quality of groundwater was evaluated in a rural watershed of northern Portugal (River Sordo basin) where environmental land use conflicts have developed in the course of a progressive invasion of ...forest and pasture lands by agriculture, especially by vineyards. The selected groundwater quality parameters were the concentrations of sodium, calcium, bicarbonate, chloride and nitrates, derived from natural and anthropogenic sources. The environmental land use conflicts were revealed by the coupling of land use and land capability raster maps. The land capability evaluation allocated 70.3% of the basin to the practicing of agriculture, 20% to livestock pasturing and 9.7% to a mosaic of land uses including agriculture, livestock pasturing and forestry. The assessment of land use conflicts allocated 93.9% of the basin to no conflict areas. Minor conflict areas (4.1%) were found concentrated in the western region of the watershed. They correspond to an invasion of farmlands towards sectors of the catchment capable for the practicing of livestock pasturing. Moderate (1.6%) and major (0.4%) conflict areas were found limited to the eastern region, matching steep hillsides capable for the practicing of livestock pasturing or forestry but presently occupied with vineyards. The spatial distributions of ion concentrations were generally justified by common geochemical processes. The dominance of high concentration levels in moderate and major conflict areas was justified within the framework of nutrient dynamics in vineyard environment. Nitrate in groundwater was likewise produced via the nitrification of N-fertilizers. Apparently, this process promoted the weathering of plagioclase by the nitric acid reaction, in concurrence with the weathering by the carbonic acid reaction. The impact of nitrification was found more important in moderate and major conflict areas, relative to no conflict areas.
•Conceive environmental land use conflicts (LUC) in rural watersheds•Investigate groundwater quality in watersheds with LUC•Investigate environmental implications of LUC
•Management of organic solid waste in Rio de Janeiro was investigated through LCA.•An attributional approach was compared to a consequential.•Two approaches for identification of electricity marginal ...were compared.•The chosen approach can affect hierarchy between compared treatment alternatives.
The environmental impacts from three management alternatives for organic fraction of municipal solid waste were compared using lifecycle assessment methodology. The alternatives (sanitary landfill, selective collection of organic waste for anaerobic digestion and anaerobic digestion after post-separation of organic waste) were modelled applying an attributional as well as consequential approach, in parallel with the aim of identifying if and how these approaches can affect results and conclusions. The marginal processes identified in the consequential modelling were in general associated with higher environmental impacts than average processes modelled with an attributional approach. As all investigated waste management alternatives result in net-substitution of energy and in some cases also materials, the consequential modelling resulted in lower absolute environmental impacts in five of the seven environmental impact categories assessed in the study. In three of these, the chosen modelling approach can alter the hierarchy between compared waste management alternatives. This indicates a risk of underestimating potential benefits from efficient energy recovery from waste when applying attributional modelling in contexts in which electricity provision historically has been dominated by technologies presenting rather low environmental impacts, but where projections point at increasing impacts from electricity provision in coming years. Thus, in the present case study, the chosen approach affects both absolute and relative results from the comparison. However, results were largely related to the processes identified as affected by investigated changes, and not merely the chosen modelling approach. The processes actually affected by future choices between different waste management alternatives are intrinsically uncertain. The study demonstrates the benefits of applying different assumptions regarding the processes affected by investigated choices – both for provision of energy and materials substituted by waste management processes in consequential LCA modelling, in order to present outcomes that are relevant as decision support within the waste management sector.
To analyze the diagnostic sensitivity and specificity of various brain-derived proteins (14-3-3, Tau, neuron specific enolase NSE, and S100b) in the CSF of patients with Creutzfeldt-Jakob disease ...(CJD) and to analyze biologic factors that modify these parameters.
CSF was tested for 14-3-3, Tau, NSE, and S100b in 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD, and in 1,117 controls.
The highest sensitivity was achieved for 14-3-3 and Tau in sporadic CJD (85% and 86%), and a combined determination of 14-3-3 and Tau, S100b, or NSE increased the sensitivity to over 93%. A multivariate analysis showed that the sensitivity of all tests was highest in patients with the shortest disease duration, age at onset >40 years, and homozygosity at codon 129 of the prion protein gene. In a group of patients with repeated lumbar punctures, a second test also increased the diagnostic sensitivity.
The detection of elevated levels of brain-derived proteins in the CSF in patients with suspected Creutzfeldt-Jakob disease is a valuable diagnostic test. A second lumbar puncture may be of value in patients with atypical clinical course in whom the first test was negative.
Fatty acids and monoglycerides are single-chain lipid amphiphiles that interact with phospholipid membranes as part of various biological activities. For example, they can exhibit membrane-disruptive ...behavior against microbial pathogens on the human skin surface. Supported lipid bilayers (SLBs) provide a useful experimental platform to characterize these membrane-disruptive behaviors, although related studies have been limited to neutral pH conditions. Herein, we investigated how lauric acid (LA) and glycerol monolaurate (GML) interact with SLBs and cause membrane morphological changes under acidic pH conditions that are representative of the human skin surface. Although LA induces tubule formation under neutral pH conditions, we discovered that LA causes membrane phase separation under acidic pH conditions. By contrast, GML induced membrane budding in both pH environments, although there was more extensive membrane remodeling under acidic pH conditions. We discuss these findings in the context of how solution pH affects the ionization states and micellar aggregation properties of LA and GML as well as its effect on the bending stiffness of lipid bilayers. Collectively, the findings demonstrate that solution pH plays an important role in modulating the interaction of fatty acids and monoglycerides with phospholipid membranes, and hence influences the scope and potency of their membrane-disruptive activities.
Background and purpose
Several diagnostic biomarkers are currently available for clinical use in early‐onset cognitive impairment. The decision on which biomarker is used in each patient depends on ...several factors such as its predictive value or tolerability.
Methods
There were a total of 40 subjects with early‐onset cognitive complaints (<65 years of age): 26 with Alzheimer's disease (AD), five with frontotemporal dementia and nine with diagnostic suspicion of non‐neurodegenerative disorder. Clinical and neuropsychological evaluation, lumbar puncture for cerebrospinal fluid (CSF) AD core biochemical marker determination, medial temporal atrophy evaluation on magnetic resonance imaging, amyloid‐positron emission tomography (PET) and 18F‐fluorodeoxyglucose‐PET were performed. Neurologists provided pre‐ and post‐biomarker diagnosis, together with diagnostic confidence and clinical/therapeutic management. Patients scored the tolerability of each procedure.
Results
Cerebrospinal fluid biomarkers and amyloid‐PET increased diagnostic confidence in AD (77.4%–86.2% after CSF, 92.4% after amyloid‐PET, P < 0.01) and non‐neurodegenerative conditions (53.6%–75% after CSF, 95% after amyloid‐PET, P < 0.05). Biomarker results led to diagnostic (32.5%) and treatment (32.5%) changes. All tests were well tolerated.
Conclusions
Biomarker procedures are well tolerated and have an important diagnostic/therapeutic impact on early‐onset cognitive impairment.
Differences during the last 15years in materials' composition in Municipal Solid Waste Incineration (MSWI) regarding bottom ash (BA) were assessed as a function of particle size (>16, 8–16, 4–8, 2–4, ...1–2 and 0–1mm). After sieving, fractions >2mm were carefully washed in order to separate fine particles adhering to bigger particles. The characterization took into account five types of materials: glass (primary and secondary), ceramics (natural and synthetic), non-ferrous metals, ferrous metals and unburned organic matter. The evaluation was performed through a visual (>2mm) and chemical (0–2mm) classification. Results showed that total weight of glass in the particles over 16mm has decreased with respect to 1999. Moreover, the content of glass (primary and secondary) in BA was estimated to be 60.8wt%, with 26.4wt% corresponding to primary glass in >2mm size fractions. Unlike 1999, in which glass was the predominant material, ceramics are currently the major phase in bottom ash (BA) coarse fractions. As for the metals, respect to 1999, results showed a slight increase in all size fractions. The greatest content (>22wt%) of ferromagnetic was observed for the 2–4mm size fraction while the non-ferrous type was almost non-existent in particles over 16mm, remaining below 10wt% for the rest fractions. In the finest fractions (<2mm), about 60 to 95% of non-ferrous metals corresponded to metallic aluminium. The results from the chemical characterization also indicated that the finest fractions contributed significantly to the total heavy metals content, especially for Pb, Zn, Cu, Mn and Ti.
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•The content of glass in particles >16mm has decreased in weathered bottom ash (WBA).•Entire glass bottles have been easily recycled and extensively substituted by plastic.•There's still a significant amount of glass that's left unrecycled: 60.8%.•Ceramics are currently the major phase in WBA coarse fractions.•The finest fractions are the major contributors to the heavy metals content.
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