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The visual analogue scale (VAS) and ordered categorical scales, i.e. numeric rating scales (NRS), are commonly used in the assessment of pain. However, these scales are bounded by fixed endpoints and thus the range of measurement is limited. The disparity in repeated assessments of perceived pain intensity with the VAS, NRS, and electrical stimulation applied as a matching stimulus was studied in 69 patients (48 women and 21 men, 19-72 years) with chronic nociceptive or neurogenic pain. Responsiveness with transcutaneous electrical nerve stimulation (TENS) using the same measurement procedures was evaluated in the same patients. Comparison of results from the three pain assessments showed that the painmatcher is at least as reliable and responsive as VAS and NRS. None of the three measurements showed evidence for systematic disagreement and had only significant random individual disagreement. They also showed evidence for responsiveness. [ABSTRACT FROM AUTHOR]

A review of the articles "Sensitivity to lysosome-dependent cell death is directly regulated by lysosomal cholesterol content," by H. Appelqvist and colleagues and "Cyclodextrin mediates rapid changes in lipid balance in Npc11 mice without carrying cholesterol through the bloodstream," by A. M. Taylor and colleagues, which appeared in the periodicals "PLoS One" and "Journal of Lipid Research" respectively in 2012, are presented.

Human activities present significant threats to tropical freshwater ecosystems, notably in many global biodiversity hotspots, threats that are further increased by inadequate taxonomic knowledge and the lack of appropriate biomonitoring tools. This study integrates globally validated biomonitoring approaches with DNA-based identification methods to create a macroinvertebrate-based tool for diagnosing ecosystem health and assessing the biodiversity of tropical river ecosystems in Myanmar (Indo-Burma bioregion). To evaluate river site degradation, comprehensive data on water and habitat quality, as well as land use information, were collected. Riverine macroinvertebrates were sampled by kick sampling, and subsequent DNA barcoding analysis was used to establish molecular taxonomic units (MTUs) for key bioindicator groups, including Ephemeroptera, Plecoptera, Trichoptera, Coleoptera, and Odonata (EPTCO) as species-level identification nomenclature was lacking. Tolerance scores for the local fauna were derived along an environmental degradation gradient to enable comparisons with widely adopted global assessment tools relying on macroinvertebrate metrics. In both study areas, the upper parts of the river networks were generally undisturbed by human activities while stressors associated with urban and agricultural land use were evident in the lower parts of the catchments. The highest precision for assessment of river health was found when establishing tolerance scores adjusted to local species composition in each study area separately. Although a family-level-based multimetric approach was significantly related to the main environmental degradation gradient, assessments utilizing cryptic species-level data (MTUs) emerged as the being most precise indicator in both areas. Our study highlights the synergistic benefits of merging traditional biomonitoring with DNA-based methods for species identification for biomonitoring in tropical river ecosystems. To halt biodiversity decline and curb the extent of the escalating nature crisis, such integrated approaches will be highly valuable in understudied and biodiversity-rich aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Freshwater macroinvertebrates are a diverse group and play key ecological roles, including accelerating nutrient cycling, filtering water, controlling primary producers, and providing food for predators. Their differences in tolerances and short generation times manifest in rapid community responses to change. Macroinvertebrate community composition is an indicator of water quality. In Europe, efforts to improve water quality following environmental legislation, primarily starting in the 1980s, may have driven a recovery of macroinvertebrate communities. Towards understanding temporal and spatial variation of these organisms, we compiled the TREAM dataset (Time seRies of European freshwAter Macroinvertebrates), consisting of macroinvertebrate community time series from 1,816 river and stream sites (mean length of 19.2 years and 14.9 sampling years) of 22 European countries sampled between 1968 and 2020. In total, the data include >93 million sampled individuals of 2,648 taxa from 959 genera and 212 families. These data can be used to test questions ranging from identifying drivers of the population dynamics of specific taxa to assessing the success of legislative and management restoration efforts., (© 2024. The Author(s).)

Typology systems are frequently used in applied and fundamental ecology and are relevant for environmental monitoring and conservation. They aggregate ecosystems into discrete types based on biotic and abiotic variables, assuming that ecosystems of the same type are more alike than ecosystems of different types with regard to a specific property of interest. We evaluated whether this assumption is met by the Broad River Types (BRT), a recently proposed European river typology system, that classifies river segments based on abiotic variables, when it is used to group biological communities. We compiled data on the community composition of diatoms, fishes, and aquatic macrophytes throughout Europe and evaluated whether the composition is more similar in site groups with the same river type than in site groups of different river types using analysis of similarities, classification strength, typical species analysis, and the area under zeta diversity decline curves. We compared the performance of the BRT with those of four region-based typology systems, namely, Illies Freshwater Ecoregions, the Biogeographic Regions, the Freshwater Ecoregions of the World, and the Environmental Zones, as well as spatial autocorrelation (SA) classifications. All typology systems received low scores from most evaluation methods, relative to predefined thresholds and the SA classifications. The BRT often scored lowest of all typology systems. Within each typology system, community composition overlapped considerably between site groups defined by the types of the systems. The overlap tended to be the lowest for fishes and between Illies Freshwater Ecoregions. In conclusion, we found that existing broad-scale river typology systems fail to delineate site groups with distinct and compositionally homogeneous communities of diatoms, fishes, and macrophytes. A way to improve the fit between typology systems and biological communities might be to combine segment-based and region-based typology systems to simultaneously account for local environmental variation and historical distribution patterns, thus potentially improving the utility of broad-scale typology systems for freshwater biota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: To investigate trends in the haemoglobin (Hb) level in middle-aged Swedish women from 1968 to 2017 and to examine the potential association between Hb and the use of hormonal contraceptives (HCs)., Design: A prospective observational population study of representative 38- and 50-year-old women of Gothenburg, Sweden., Setting: The population study of women in Gothenburg started in 1968-1969 and has continued since then with new examinations every 12 years, including both follow-ups and new recruited cohorts. The study consists of both physical examinations and questionnaires., Subjects: Two thousand four hundred eighty-eight women aged 38 and 50 participated in the study from 1968 to 2017., Statistical Methods: Linear regression model analyses were used to analyse linear and non-linear trends in the level of Hb. Linear and logistic regression models were used to analyse possible associations between HC and Hb and possible associations between the use of HC and anaemia, respectively., Main Outcome Measures and Covariates: Hb was measured in g/L. HC included any ongoing use of HC therapy. Covariates were smoking, body mass index (BMI), alcohol consumption and education., Results: A non-linear U-shaped trend in mean Hb was seen in the two age groups, 38- and 50-years old. After adjusting for covariates, a significantly higher mean Hb was seen in the 2016-2017 examination compared to 1980-1981, 1992-1993 and 2004-2005. In 38-year-olds, using HC was associated with a reduced risk of anaemia (OR 0.35, 95% CI 0.13-0.75). In both age groups, the use of HC was significantly associated with having a higher Hb., Conclusions: Mean levels of Hb in middle-aged women of the general population seem to be increasing again after lower levels in the 1980s and 1990s. The use of HC was associated with having a higher Hb and a lower risk of anaemia in 38-year-old women.

Owing to a long history of anthropogenic pressures, freshwater ecosystems are among the most vulnerable to biodiversity loss 1 . Mitigation measures, including wastewater treatment and hydromorphological restoration, have aimed to improve environmental quality and foster the recovery of freshwater biodiversity 2 . Here, using 1,816 time series of freshwater invertebrate communities collected across 22 European countries between 1968 and 2020, we quantified temporal trends in taxonomic and functional diversity and their responses to environmental pressures and gradients. We observed overall increases in taxon richness (0.73% per year), functional richness (2.4% per year) and abundance (1.17% per year). However, these increases primarily occurred before the 2010s, and have since plateaued. Freshwater communities downstream of dams, urban areas and cropland were less likely to experience recovery. Communities at sites with faster rates of warming had fewer gains in taxon richness, functional richness and abundance. Although biodiversity gains in the 1990s and 2000s probably reflect the effectiveness of water-quality improvements and restoration projects, the decelerating trajectory in the 2010s suggests that the current measures offer diminishing returns. Given new and persistent pressures on freshwater ecosystems, including emerging pollutants, climate change and the spread of invasive species, we call for additional mitigation to revive the recovery of freshwater biodiversity., (© 2023. The Author(s).)

The genome of the soil Bacteroidota Chitinophaga pinensis encodes a large number of glycoside hydrolases (GHs) with noteworthy features and potentially novel functions. Several are predicted to be active on polysaccharide components of fungal and oomycete cell walls, such as chitin, β-1,3-glucan and β-1,6-glucan. While several fungal β-1,6-glucanase enzymes are known, relatively few bacterial examples have been characterised to date. We have previously demonstrated that C. pinensis shows strong growth using β-1,6-glucan as the sole carbon source, with the efficient release of oligosaccharides from the polymer. We here characterise the capacity of the C. pinensis secretome to hydrolyse the β-1,6-glucan pustulan and describe three distinct enzymes encoded by its genome, all of which show different levels of β-1,6-glucanase activity and which are classified into different GH families. Our data show that C. pinensis has multiple tools to deconstruct pustulan, allowing the species' broad utility of this substrate, with potential implications for bacterial biocontrol of pathogens via cell wall disruption. Oligosaccharides derived from fungal β-1,6-glucans are valuable in biomedical research and drug synthesis, and these enzymes could be useful tools for releasing such molecules from microbial biomass, an underexploited source of complex carbohydrates., (© 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Humans have severely altered freshwater ecosystems globally, causing a loss of biodiversity. Regulatory frameworks, like the Water Framework Directive, have been developed to support actions that halt and reverse this loss. These frameworks use typology systems that summarize freshwater ecosystems into environmentally delineated types. Within types, ecosystems that are minimally impacted by human activities, i.e., in reference conditions, are expected to be similar concerning physical, chemical, and biological characteristics. This assumption is critical when water quality assessments rely on comparisons to type-specific reference conditions. Lyche Solheim et al. (2019) developed a pan-European river typology system, the Broad River Types, that unifies the national Water Framework Directive typology systems and is gaining traction within the research community. However, it is unknown how similar biological communities are within these individual Broad River Types. We used analysis of similarities and classification strength analysis to examine if the Broad River Types delineate distinct macroinvertebrate communities across Europe and whether they outperform two ecoregional approaches: the European Biogeographical Regions and Illies' Freshwater Ecoregions. We determined indicator and typical taxa for the types of all three typology systems and evaluated their distinctiveness. All three typology systems captured more variation in macroinvertebrate communities than random combinations of sites. The results were similar among typology systems, but the Broad River Types always performed worse than either the Biogeographic Regions or Illies' Freshwater Ecoregions. Despite reaching statistical significance, the statistics of analysis of similarity and classification strength were low in all tests indicating substantial overlap among the macroinvertebrate communities of different types. We conclude that the Broad River Types do not represent an improvement upon existing freshwater typologies when used to delineate macroinvertebrate communities and we propose future avenues for advancement: regionally constrained types, better recognition of intermittent rivers, and consideration of biotic communities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Regional-scale ecological processes, such as the spatial flows of material, energy, and organisms, are fundamental for maintaining biodiversity and ecosystem functioning in river networks. Yet these processes remain largely overlooked in most river management practices and underlying policies. Here, we propose adoption of a meta-system approach, where regional processes acting at different levels of ecological organization - populations, communities, and ecosystems - are integrated into conventional river conservation, restoration, and biomonitoring. We also describe a series of measurements and indicators that could be assimilated into the implementation of relevant biodiversity and environmental policies. Finally, we highlight the need for alternative management strategies that can guide practitioners toward applying recent advances in ecology to preserve and restore river ecosystems and the ecosystem services they provide, in the context of increasing alteration of river network connectivity worldwide., (© 2021 The Authors. Frontiers in Ecology and the Environment published by Wiley Periodicals LLC on behalf of the Ecological Society of America.)

The prevailing opinion is that prefibrillar β-amyloid (Aβ) species, rather than end-stage amyloid fibrils, cause neuronal dysfunction in Alzheimer's disease, although the mechanisms behind Aβ neurotoxicity remain to be elucidated. Luminescent conjugated oligothiophenes (LCOs) exhibit spectral properties upon binding to amyloid proteins and have previously been reported to change the toxicity of Aβ 1-42 and prion protein. In a previous study, we showed that an LCO, pentamer formyl thiophene acetic acid (p-FTAA), changed the toxicity of Aβ 1-42 . Here we investigated whether an LCO, heptamer formyl thiophene acetic acid (h-FTAA), could change the toxicity of Aβ 1-42 by comparing its behavior with that of p-FTAA. Moreover, we investigated the effects on toxicity when Aβ with the Arctic mutation (Aβ Arc ) was aggregated with both LCOs. Cell viability assays on SH-SY5Y neuroblastoma cells demonstrated that h-FTAA has a stronger impact on Aβ 1-42 toxicity than does p-FTAA. Interestingly, h-FTAA, but not p-FTAA, rescued the Aβ Arc -mediated toxicity. Aggregation kinetics and binding assay experiments with Aβ 1-42 and Aβ Arc when aggregated with both LCOs showed that h-FTAA and p-FTAA either interact with different species or affect the aggregation in different ways. In conclusion, h-FTAA protects against Aβ 1-42 and Aβ Arc toxicity, thus showing h-FTAA to be a useful tool for improving our understanding of the process of Aβ aggregation linked to cytotoxicity.

Legislations and commitments regulate Baltic Sea status assessments and monitoring. These assessments suffer from monitoring gaps that need prioritization. We used three sources of information; scientific articles, project reports and a stakeholder survey to identify gaps in relation to requirements set by the HELCOM's Baltic Sea Action Plan, the Marine Strategy Framework Directive and the Water Framework Directive. The most frequently mentioned gap was that key requirements are not sufficiently monitored in space and time. Biodiversity monitoring was the category containing most gaps. However, whereas more than half of the gaps in reports related to biodiversity, scientific articles pointed out many gaps in the monitoring of pollution and water quality. An important finding was that the three sources differed notably with respect to which gaps were mentioned most often. Thus, conclusions about gap prioritization for management should be drawn after carefully considering the different viewpoints of scientists and stakeholders., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this study was to examine if the previously found trend of increasing menopausal age is continuing, taking into consideration hormonal use and surgical menopause in both 38- and 50-year-old women of today., Methods: Cohort comparisons of five generations of population-based samples of 38- and 50-year-old women from the Prospective Population Study of Women in Gothenburg with start in 1968/1969, and with follow-ups in 1980/1981, 1992/1993, 2004/2005, and 2016/2017. Across the time periods newly recruited women as well as earlier participants were included. Use of hormonal contraceptives, estrogen plus progestogen therapy (EPT), and time for menopause was registered. Changes between different generations of 38- and 50-year-old women from 1968/1969 until today were studied. The overall sample size across the time periods was 1,873 individuals., Results: The prevalence of oral contraceptives in 38-year-old women was about 10% in 1968/1969, increasing from 16% in 2004/2005 to almost 22% in 2016/2017. From 2004/2005 the use of hormonal intrauterine contraceptive method (the Levonorgestrel-releasing intrauterine system [LNG-IUS]) increased from about 11% to 14% in 2016/2017. The same pattern was found in 50-year-old women using LNG-IUS, increasing from 6% to 15.5% between 2004/2005 and 2016/2017. The total hormonal use, including LNG-IUS, oral contraceptives, and EPT, was 28% in 50-year-old women in 2016/2017. The total proportion of hormone use in 50-year-old women increased over the years and together with surgical menopause it reached over 37% in the 2016/2017 survey., Conclusions: This study has shown an increase in the hormonal use, in both 38- and 50-year-old women, making it difficult to determine when the actual menopause occurs. Thus, the previously found increasing secular trend in menopausal age will be more complicated to assess in female generations of today and tomorrow.

The RAS/MAPK pathway is a major driver of oncogenesis and is dysregulated in approximately 30% of human cancers, primarily by mutations in the BRAF or RAS genes. The extracellular-signal-regulated kinases (ERK1 and ERK2) serve as central nodes within this pathway. The feasibility of targeting the RAS/MAPK pathway has been demonstrated by the clinical responses observed through the use of BRAF and MEK inhibitors in BRAF V600E/K metastatic melanoma; however, resistance frequently develops. Importantly, ERK1/2 inhibition may have clinical utility in overcoming acquired resistance to RAF and MEK inhibitors, where RAS/MAPK pathway reactivation has occurred, such as relapsed BRAF V600E/K melanoma. We describe our structure-based design approach leading to the discovery of AZD0364, a potent and selective inhibitor of ERK1 and ERK2. AZD0364 exhibits high cellular potency (IC 50 = 6 nM) as well as excellent physicochemical and absorption, distribution, metabolism, and excretion (ADME) properties and has demonstrated encouraging antitumor activity in preclinical models.

Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer's disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Aβ 1-42 or AβPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Aβ 1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ 1-42 in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Aβ 1-42 and caused a beneficial effect by binding of lysozyme to toxic species of Aβ 1-42 , which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD., (© 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The aggregation of the amyloid-β (Aβ) peptide into fibrillar deposits has long been considered the key neuropathological hallmark of Alzheimer's disease (AD). Aβ peptides are generated from proteolytic processing of the transmembrane Aβ precursor protein (AβPP) via sequential proteolysis through the β-secretase activity of β-site AβPP-cleaving enzyme (BACE1) and by the intramembranous enzyme γ-secretase. For over a decade, Drosophila melanogaster has been used as a model organism to study AD, and two different approaches have been developed to investigate the toxicity caused by AD-associated gene products in vivo In one model, the Aβ peptide is directly over-expressed fused to a signal peptide, allowing secretion of the peptide into the extracellular space. In the other model, human AβPP is co-expressed with human BACE1, resulting in production of the Aβ peptide through the processing of AβPP by BACE1 and by endogenous fly γ-secretase. Here, we performed a parallel study of flies that expressed the Aβ1-42 peptide alone or that co-expressed AβPP and BACE1. Toxic effects (assessed by eye phenotype, longevity and locomotor assays) and levels of the Aβ1-42, Aβ1-40 and Aβ1-38 peptides were examined. Our data reveal that the toxic effect per amount of detected Aβ1-42 peptide was higher in the flies co-expressing AβPP and BACE1 than in the Aβ1-42-expressing flies, and that the co-existence of Aβ1-42 and Aβ1-40 in the flies co-expressing AβPP and BACE1 could be of significant importance to the neurotoxic effect detected in these flies. Thus, the toxicity detected in these two fly models seems to have different modes of action and is highly dependent on how and where the peptide is generated rather than on the actual level of the Aβ1-42 peptide in the flies. This is important knowledge that needs to be taken into consideration when using Drosophila models to investigate disease mechanisms or therapeutic strategies in AD research., Competing Interests: The authors declare no competing or financial interests., (© 2016. Published by The Company of Biologists Ltd.)