Quantitative assessment of angiogenesis in murine antigen-induced arthritis by intravital fluorescence microscopy

Inhibition of angiogenesis might be a therapeutic approach to prevent joint destruction caused by the overgrowing synovial tissue during chronic joint inflammation. The aim of this study was to investigate angiogenesis in the knee joint of mice with antigen-induced arthritis (AIA) by means of intravital microscopy. In 14 mice (C57BL6/129Sv) intravital microscopic assessment was performed on day 8 after AIA induction in two groups (controls, AIA). Synovial tissue was investigated by intravital fluorescence microscopy using FITC-dextran (150 kD). Quantitative assessment of vessel density was performed according to the following categories: functional capillary density (FCD, vessels 10 mum) and FVD of vessels with angiogenic criteria (convoluted vessels, abrupt changes of diameter, vessels which are generated by sprouting and progressively pruned and remodelled). Microvessel count was performed using immunohistochemistry. There was no significant difference in FCD between the control group (337 +/- 9 cm/cm(2); mean +/-SEM) and the AIA group (359 +/- 13 cm/cm(2)). The density of vessels larger than 10 gm diameter was significantly increased in animals with AIA (135 +/- 10 vs. 61 +/- 5 cm/cm(2) in control). The density of blood vessels with angiogenic criteria was enhanced in arthritic animals (79 +/- 17 vs. 12 +/- 2 cm/cm(2) in control). There was a significant increase in the microvessel count in arthritic animals (297 +/- 25 vs. 133 +/- 16 mm(-2) in control). These findings demonstrate that angiogenesis in murine AIA can be assessed quantitatively using intravital microscopy. Further studies will address antiangiogenic strategies in AIA

Indications for phosphorus fertilizer-derived uranium mobilization from arable soils to groundwater

Uranium (U) and many trace elements are enriched in phosphorus fertilizers. Concentrations up to 260 mg/kg P2O5 indicate the potential of U contamination of the environment. Two fertilized long-time soil monitoring fields (BDF) in Lower Saxony have higher top soil concentration than comparable unfertilized top soils sampled at the Green-Belt in the vicinity of the BDFs. Extraction experiments could show that fertilizer-derived U is easier mobilized and hence might be leached faster to the groundwater than the geogenic U in soils. Groundwater analyses in an area of intense agricultural production show U in correlation with nitrate, indicating an impact of anthropogenic fertilization on the U concentration in shallow groundwater. The results of soil, soil extract and groundwater analyses are giving indications for fertilizer-derived U leaching to groundwater aquifers and hence show the potential hazard for our drinking water resources

The Counterpart Principle of Analogical Support by Structural Similarity

We propose and investigate an Analogy Principle in the context of Unary Inductive Logic based on a notion of support by structural similarity which is often employed to motivate scientific conjectures

Permeability of anti-fouling PEGylated surfaces probed by fluorescence correlation spectroscopy

The present work reports on in situ observations of the interaction of organic dye probe molecules and dye-labeled protein with different poly(ethylene glycol) (PEG) architectures (linear, dendron, and bottle brush). Fluorescence correlation spectroscopy (FCS) and single molecule event analysis were used to examine the nature and extent of probe朠EG interactions. The data support a sieve-like model in which size-exclusion principles determine the extent of probe朠EG interactions. Small probes are trapped by more dense PEG architectures and large probes interact more with less dense PEG surfaces. These results, and the tunable pore structure of the PEG dendrons employed in this work, suggest the viability of electrochemically-active materials for tunable surfaces

Unified superresolution experiments and stochastic theory provide mechanistic insight into protein ion-exchange adsorptive separations

Chromatographic protein separations, immunoassays, and biosensing all typically involve the adsorption of proteins to surfaces decorated with charged, hydrophobic, or affinity ligands. Despite increasingly widespread use throughout the pharmaceutical industry, mechanistic detail about the interactions of proteins with individual chromatographic adsorbent sites is available only via inference from ensemble measurements such as binding isotherms, calorimetry, and chromatography. In this work, we present the direct superresolution mapping and kinetic characterization of functional sites on ion-exchange ligands based on agarose, a support matrix routinely used in protein chromatography. By quantifying the interactions of single proteins with individual charged ligands, we demonstrate that clusters of charges are necessary to create detectable adsorption sites and that even chemically identical ligands create adsorption sites of varying kinetic properties that depend on steric availability at the interface. Additionally, we relate experimental results to the stochastic theory of chromatography. Simulated elution profiles calculated from the molecular-scale data suggest that, if it were possible to engineer uniform optimal interactions into ion-exchange systems, separation efficiencies could be improved by as much as a factor of five by deliberately exploiting clustered interactions that currently dominate the ion-exchange process only accidentally

Exploring Interventions to Improve the Oral Health and Related Health Behaviours of Adults Experiencing Severe and Multiple Disadvantage: Protocol for a Qualitative Study with Stakeholders

The number of individuals in England experiencing homelessness, substance use, and involvement with the criminal justice system is increasing. These issues, referred to as severe and multiple disadvantage (SMD), are often interlinked and co-occur. Health inequalities, particularly poor oral health, persist for those facing these inter-related issues and are closely linked with high levels of substance use, smoking, and poor diet. However, evidence for interventions that can improve these health outcomes for those experiencing these issues is limited. This paper outlines the design of a qualitative study which aims to explore the perspectives of stakeholders to understand what interventions can help to support SMD groups with their oral health and related health behaviours (i.e., substance use, smoking, diet). Interviews and focus groups will be undertaken with stakeholders comprising two groups: (1) individuals with experience of SMD, and (2) service providers (staff and volunteers), policy makers, and commissioners who support such individuals. Public involvement and engagement is central to the project. For example, stakeholders and research partners in policy and practice and people with lived experience of SMD will provide input at all stages of this study. Findings from the study will inform an ‘evidence for practice’ briefing outlining recommendations for policy. Dissemination will occur through presentations to a range of practice, policy and academic beneficiaries, and through peer-reviewed publications

Investigating the effectiveness and acceptability of oral health and related health behaviour interventions in adults with severe and multiple disadvantage: Protocol for a mixed-methods systematic review

Increasing numbers of people in England experience homelessness, substance use, and repeated offending (known as ‘severe and multiple disadvantage’; SMD). Populations experiencing SMD often have extremely poor oral health, which is closely inter-linked with high levels of substance use, smoking, and poor diet. This study aims to undertake an evidence synthesis to identify the effectiveness, resource requirements, and factors influencing the implementation and acceptability of oral health and related health behaviour interventions in adults experiencing SMD. Two systematic reviews will be conducted using mixed-methods. Review 1 will investigate the effectiveness and resource implications of oral health and related health behaviours (substance use, smoking, diet) interventions; Review 2 will investigate factors influencing the implementation of such interventions. The population includes adults (≥18 years) experiencing SMD. Standard review methods in terms of searches, screening, data extraction, and quality appraisal will be conducted. Narrative syntheses will be conducted. If feasible, a meta-analysis will be conducted for Review 1 and a thematic synthesis for Review 2. Evidence from the two reviews will then be synthesised together. Input from people with experience of SMD will be sought throughout to inform the reviews. An initial logic model will be iteratively refined during the review

Factors influencing implementation and sustainability of interventions to improve oral health and related health behaviours in adults experiencing severe and multiple disadvantage: a mixed-methods systematic review

OBJECTIVES: Among people experiencing severe and multiple disadvantage (SMD), poor oral health is common and linked to smoking, substance use and high sugar intake. Studies have explored interventions addressing oral health and related behaviours; however, factors related to the implementation of these interventions remain unclear. This mixed-methods systematic review aimed to synthesise evidence on the implementation and sustainability of interventions to improve oral health and related health behaviours among adults experiencing SMD. METHODS: Bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, EBSCO, Scopus) and grey literature were searched from inception to February 2023. Studies meeting the inclusion criteria were screened and extracted independently by two researchers. Quality appraisal was undertaken, and results were synthesised using narrative and thematic analyses. RESULTS: Seventeen papers were included (published between 1995 and 2022). Studies were mostly of moderate quality and included views from SMD groups and service providers. From the qualitative synthesis, most findings were related to aspects such as trust, resources and motivation levels of SMD groups and service providers. None of the studies reported on diet and none included repeated offending (one of the aspects of SMD). From the quantitative synthesis, no difference was observed in programme attendance between the interventions and usual care, although there was some indication of sustained improvements in participation in the intervention group. CONCLUSION: This review provides some evidence that trust, adequate resources and motivation levels are potentially important in implementing interventions to improve oral health and substance use among SMD groups. Further research is needed from high quality studies and focusing on diet in this population. PROSPERO REGISTRATION NUMBER: CRD42020202416