Feasibility of 'parkrun' for people with knee osteoarthritis: A mixed methods pilot study.

Objective: To investigate the feasibility of 'parkrun' for people with knee osteoarthritis (OA) and examine its potential to improve symptoms and increase physical activity. Design: This uncontrolled mixed methods pilot study enrolled people with knee OA not meeting physical activity guidelines. Participants were asked to walk in four consecutive parkrun events supervised by an exercise physiologist/physiotherapist. Feasibility was assessed by recruitment data (numbers screened and time to enrol 15 participants), adherence to the protocol, acceptability (measured by confidence, enjoyment, difficulty ratings and qualitative interviews), and safety (adverse events). Secondary measures were changes in knee pain, function, stiffness, and physical activity levels. Results: Participants (n â€‹= â€‹17) were enrolled over 11 months and recruitment was slower than anticipated. Fourteen participants attended all four parkruns and three of these participants shortened the 5 â€‹km course to ∼3 â€‹km. Across all four parkruns, 75% of participants reported high confidence that they could complete the upcoming parkrun and the majority (87%) enjoyed participating. Most participants rated parkrun either "slightly difficult" (38.5%) or "moderately difficult" (35%) and two mild adverse events were reported. Participants showed improvements in knee pain, function, stiffness, and physical activity levels. Conclusions: This pilot study demonstrates parkrun's feasibility, acceptability, safety and, its potential to improve knee OA symptoms and physical activity levels. Participating in parkrun was acceptable and enjoyable for some, but not all participants. The scalability, accessibility and wide appeal of parkrun supports the development of larger programs of research to evaluate the use of parkrun for people with knee OA.

Anti-oxidative hormetic effects of cellular autophagy induced by nutrient deprivation in a molluscan animal model.

This investigation using a molluscan animal model tested the hypothesis that experimentally induced lysosomal autophagy protects against oxidative cell injury. Induction of augmented lysosomal autophagy has previously been implicated in this protective process. Four treatment groups of blue mussels (Mytilus galloprovincialis) were used: Group 1 (fed - control), Group 2 (fasted), Group 3 (copper + fed) and Group 4 (copper + fasted). Groups 2 and 4 were fasted in order to trigger autophagy; and samples of hepatopancreas (liver analogue or digestive gland) from all 4 groups were taken at 3, 6 and 15 days. Treatment with copper provided a positive reference for oxidative stress: Groups 3 and 4 were treated with copper (10 µg Cu2+/animal/day) for three days only. Oxidative damage and cellular injury in hepatopancreatic digestive cells was found to decrease in Group 2 (fasted) compared to Group 1 (fed - control). Group 3 (fed + copper) showed clear evidence of oxidative stress and cell injury, as well as induction of antioxidant activities. Group 4 (copper + fasted) had a reduced uptake of copper and toxicity of copper was also reduced, compared with Group 3. It was concluded that augmented autophagy had a hormetic cytoprotective anti-oxidant effect.

Oxidative stress, lysosomal damage and dysfunctional autophagy in molluscan hepatopancreas (digestive gland) induced by chemical contaminants.

Autophagy is a highly conserved evolutionary survival or defence process that enables cells and organisms to survive periods of environmental stress by breaking down cellular organelles and macromolecules in autolysosomes to provide a supply of nutrients for cell maintenance. However, autophagy is also a part of normal cellular physiology that facilitates the turnover of cellular constituents under normal conditions: it can be readily augmented by mild environmental stress; but becomes dysfunctional with severe oxidative stress leading to cellular pathology. The molluscan hepatopancreas or digestive gland provides a versatile and environmentally relevant model to investigate lysosomal autophagy and stress-induced dysfunctional autophagy. This latter process has been implicated in many animal and human disease conditions, including degenerative and neurodegenerative diseases, as well as obesity related conditions. Many environmental pollutants have also been found to induce dysfunctional autophagy in molluscan hepatopancreatic digestive cells, and in this study, the marine blue mussel Mytilus galloprovincialis was exposed for 7 days to: 0.1 µM, 1 µM and 10 µM concentrations of fluoranthene and phenanthrene (PAHs); chlorpyrifos and malathion (organophosphorus compounds); atrazine (triazine herbicide); copper (transition metal) and dodecylbenzene sulphonic acid (LAS, surfactant). The marine snail or periwinkle, Littorina littorea, was also exposed to phenanthrene, chlorpyrifos and copper. Indices of oxidative stress, cell injury and dysfunctional autophagy were measured (i.e., lysosomal membrane stability, protein carbonyls, lipofuscin, and lysosomal accumulation of lipid or lipidosis). Evidence of oxidative stress, based on the elevation of lipofuscin and protein carbonyls, was found for all compounds tested; with chlorpyrifos being the most toxic to both species. Dysfunctional autophagy was induced by all of the compounds tested in both species, except for atrazine in mussels. This failure of normal autophagy was consistently associated with oxidative stress. Autophagic dysfunction is an important emerging feature in the aetiology of many disease conditions in animals and humans; and an explanatory conceptual mechanistic model has been developed for dysregulation of autophagy in response to oxidative stress.

Statistical dynamical model to predict extreme events and anomalous features in shallow water waves with abrupt depth change.

Understanding and predicting extreme events and their anomalous statistics in complex nonlinear systems are a grand challenge in climate, material, and neuroscience as well as for engineering design. Recent laboratory experiments in weakly turbulent shallow water reveal a remarkable transition from Gaussian to anomalous behavior as surface waves cross an abrupt depth change (ADC). Downstream of the ADC, probability density functions of surface displacement exhibit strong positive skewness accompanied by an elevated level of extreme events. Here, we develop a statistical dynamical model to explain and quantitatively predict the above anomalous statistical behavior as experimental control parameters are varied. The first step is to use incoming and outgoing truncated Korteweg-de Vries (TKdV) equations matched in time at the ADC. The TKdV equation is a Hamiltonian system, which induces incoming and outgoing statistical Gibbs invariant measures. The statistical matching of the known nearly Gaussian incoming Gibbs state at the ADC completely determines the predicted anomalous outgoing Gibbs state, which can be calculated by a simple sampling algorithm verified by direct numerical simulations, and successfully captures key features of the experiment. There is even an analytic formula for the anomalous outgoing skewness. The strategy here should be useful for predicting extreme anomalous statistical behavior in other dispersive media.

Emergent synergistic lysosomal toxicity of chemical mixtures in molluscan blood cells (hemocytes).

The problem of effective assessment of risk posed by complex mixtures of toxic chemicals in the environment is a major challenge for government regulators and industry. The biological effect of the individual contaminants, where these are known, can be measured; but the problem lies in relating toxicity to the multiple constituents of contaminant cocktails. The objective of this study was to test the hypothesis that diverse contaminant mixtures may cause a greater toxicity than the sum of their individual parts, due to synergistic interactions between contaminants with different intracellular targets. Lysosomal membrane stability in hemocytes from marine mussels was used for in vitro toxicity tests; and was coupled with analysis using the isobole method and a linear additive statistical model. The findings from both methods have shown significant emergent synergistic interactions between environmentally relevant chemicals (i.e., polycyclic aromatic hydrocarbons, pesticides, biocides and a surfactant) when exposed to isolated hemocytes as a mixture of 3 & 7 constituents. The results support the complexity-based hypothesis that emergent toxicity occurs with increasing contaminant diversity, and raises questions about the validity of estimating toxicity of contaminant mixtures based on the additive toxicity of single components. Further experimentation is required to investigate the potential for interactive effects in mixtures with more constituents (e.g., 50-100) at more environmentally realistic concentrations in order to test other regions of the model, namely, very low concentrations and high diversity. Estimated toxicant diversity coupled with tests for lysosomal damage may provide a potential tool for determining the toxicity of estuarine sediments, dredge spoil or contaminated soil.

Changing views of the interconnections between the oceans and human health in Europe.

Early steps in the emergence of the discipline of "Oceans and Human Health" are charted in the USA and discussed in relation to past and present marine environment and human health research activities in Europe. Differences in terminology are considered, as well as differences in circumstances related to the various seas of Europe and the intensity of human coastal activity and impact. Opportunities to progress interdisciplinary research are described, and the value of horizon scanning for the early identification of emerging issues is highlighted. The challenges facing researchers and policymakers addressing oceans and human health issues are outlined and some suggestions offered regarding how further progress in research and training into both the risks and benefits of Oceans and Human Health might be made on both sides of the Atlantic.

Integration of biochemical, histochemical and toxicogenomic indices for the assessment of health status of mussels from the Tamar Estuary, U.K.

The aim of this study was to examine whether a combination of biochemical, histopathological and toxicogenomic data could be used as a valuable tool for the assessment of biological risk associated with pollutants within the Tamar River and Estuary, S.W. England, U.K. Accordingly, biochemical and histopathological biomarkers (protein carbonyls, lipofuscin, neutral lipids, lysosomal stability [N-acetyl-ß-hexosaminidase and neutral red], lysosomal volume, ferric reducing antioxidant power [FRAP] and malonaldehyde [MDA]) and gene expression profiles were assessed in 5 sites from the Tamar River and Estuary (Neal Point, Town Quay, Wilcove, Cremyll Ferry and Whitsand; and a reference site, Trebarwith Strand, N. Cornwall). PAHs were measured in mussel tissue and sediment and metals were measured in mussel tissue only. Data from the biomarkers was integrated into a Mussel Expert System (MES) model to produce a simple assessment of mussel stress. Clear gradients of mussel toxicity were identified by the biomarkers (with the exception of neutral lipids) with the highest impacted animals found furthest up the Tamar, whilst the MES was unable to identify a gradient of effect. Gene expression profiles also indicated a gradient of stress with the greatest number of significantly up- or down- regulated genes found at the uppermost 2 sites. The MES did, however, determine that mussels from all sites, except the reference site, were highly stressed; a conclusion that could not be inferred from the biomarker data alone. It is concluded that the MES is a valuable tool that permits integration and interpretation of complex sets of biomarker data by identifying the biological meaning of biomarker changes.

Development of an expert system for the integration of biomarker responses in mussels into an animal health index.

Biomarkers on sentinel organisms are utilised worldwide in biomonitoring programs. However, the lack of effective interpretational capacity has hampered their uptake for use for assessment of risk in environmental management. The aim of the present study was to develop and test an objective decision-support or expert system capable of integrating biomarker results into a five-level health-status index. The expert system is based on a set of rules derived from available data on responses to natural and contaminant-induced stress of marine mussels. Integration of parameters includes: level of biological organization; biological significance; mutual interrelationship; and qualitative trends in a stress gradient. The system was tested on a set of biomarker data obtained from the field and subsequently validated with data from previous studies. The results demonstrate that the expert system can effectively quantify the biological effects of different levels of pollution. The system represents a simple tool for risk assessment of the harmful impact of contaminants by providing a clear indication of the degree of stress syndrome induced by pollutants in mussels.

Do nanoparticles present ecotoxicological risks for the health of the aquatic environment?

Nanotechnology is a major innovative scientific and economic growth area, which may present a variety of hazards for environmental and human health. The surface properties and very small size of nanoparticles and nanotubes provide surfaces that may bind and transport toxic chemical pollutants, as well as possibly being toxic in their own right by generating reactive radicals. There is a wealth of evidence for the harmful effects of nanoscale combustion-derived particulates (ultrafines), which when inhaled can cause a number of pulmonary pathologies in mammals and humans. However, release of manufactured nanoparticles into the aquatic environment is largely an unknown. This review addresses the possible hazards associated with nanomaterials and harmful effects that may result from exposure of aquatic animals to nanoparticles. Possible nanoparticle association with naturally occurring colloids and particles is considered together with how this could affect their bioavailability and uptake into cells and organisms. Uptake by endocytotic routes are identified as probable major mechanisms of entry into cells; potentially leading to various types of toxic cell injury. The higher level consequences for damage to animal health, ecological risk and possible food chain risks for humans are also considered based on known behaviours and toxicities for inhaled and ingested nanoparticles in the terrestrial environment. It is concluded that a precautionary approach is required with individual evaluation of new nanomaterials for risk to the health of the environment. Although current toxicity testing protocols should be generally applicable to identify harmful effects associated with nanoparticles, research into new methods is required to address the special properties of nanomaterials.

Pathological reactions and recovery of hepatopancreatic digestive cells from the marine snail Littorina littorea following exposure to a polycyclic aromatic hydrocarbon.

The aim of this study was to investigate the cellular pathological responses of hepatopancreatic digestive cells from the periwinkle Littorina littorea exposed to the polycyclic aromatic hydrocarbon (PAH) fluoranthene and to ascertain whether any injurious effects were reversible within the experimental time scale. A secondary objective was to establish the relationship of the various reactions to animal health status, using lysosomal stability as an index of well-being. Exposure of snails to a concentration of 335 microgl(-1) (1.7 microM) fluoranthene (seawater renewed and spiked daily with fluoranthene) for 5 days resulted in a reduction in lysosomal stability (neutral red retention) and endocytosis; and an increase in smooth endoplasmic reticulum (ER) and 7-ethoxycoumarin-o-deethylase (ECOD; measured as cyano-ECOD) activity measured in isolated live digestive cells. Exposed snails treated with clean seawater for a further 8 days resulted in a return to control levels of lysosomal stability, ECOD and ER; endocytosis showed only a partial recovery. Multi-variate and uni-variate analysis showed that there were strong correlations between the various cellular biomarker responses. These findings are interpretable within the current framework of molluscan biomarker responses to PAHs. Principal component analysis was used to derive the first principal component for endocytosis, ER and ECOD reactions and these were plotted against lysosomal stability as a measure of cellular well-being. The resulting significant regression represents the mapping of the individual biomarkers within health status space for a gradient of fluoranthene toxicity. From this analysis, we concluded that endocytosis is an indicator of healthy snails while proliferation of ER and to a lesser extent induced ECOD are indicative of dysfunction and reduced health. Finally, the results indicate that stress induced by chronic exposure to a PAH is reversible.

A carbon and nitrogen flux model of mussel digestive gland epithelial cells and their simulated response to pollutants.

The mussel digestive gland epithelial cells provide a key interface between the organism and pollutants such as aromatic hydrocarbons. The simulation of their uptake and export mechanisms as well as an internal protein degradation pathway, and any subsequent disruption to any of them, has been undertaken. A computational model is described, which simulates the flow of carbon and nitrogen through a mussel's digestive cell. The model uses a compartmentalised view of the cell with inviolate 'pipelines' connecting each of the volume-variable partitions. Only the major physiological pathways relevant to the flow of either carbon or nitrogen or volume are modelled. Simulated response to hydrocarbon exposure is examined.

Mercury- and copper-induced lysosomal membrane destabilisation depends on [Ca2+]i dependent phospholipase A2 activation.

Heavy metals are environmental pollutants able to produce different cellular effects, such as an alteration of Ca2+ homeostasis and lysosomal membrane destabilisation. The latter is one of the most used stress indices in biomonitoring programs. Recently, it has been demonstrated that cytosolic calcium increase can modulate lysosomal membrane destabilisation via activation of Ca(2+)-dependent phospholipase A2 (cPLA2). The aim of this work was to investigate the possible involvement of Ca(2+)-activated PLA2 in lysosomal membrane destabilisation induced by heavy metals in mussel haemolymph cells. We have studied the effects of Hg2+ and Cu2+ on free cytosolic calcium using Fura2/AM-loaded cells and lysosomal membrane destabilisation using neutral red (NR) staining. Hg2+ induced a [Ca2+]i rise from 100 to 780 nM in 30 min, and a lysosome destaining of 70% after 60 min that indicates destabilisation of lysosomal membranes. Both effects were reduced in a Ca(2+)-free medium, suggesting a cause-effect relationship. Exposure to Cu2+ produced the same effects, but with an intensity of about 50% respect to Hg2+. Metal-induced lysosomal destabilisation was also reduced in cells pre-exposed to a specific Ca(2+)-dependent cPLA2 inhibitor (AACOCF3). Conversely, haemocyte pretreatment with a Ca(2+)-independent PLA2 inhibitor (bromoenol-lactone (BEL)) did not prevent the destabilizing effect of heavy metals on lysosomes. Exposure to heavy metals also produced an increase in lysosomal volume of 1.8-2-folds, that was prevented by pre-incubation with AACOCF3 but not with BEL. These data indicate an involvement of cPLA2 in lysosomal membrane destabilisation induced by heavy metals.

Impact of the Sea Empress oil spill on lysosomal stability in mussel blood cells.

Coastal zones are among the most productive and vulnerable areas on the planet. An example of impact on these fragile environments was shown in the case of the "Sea Empress" oil tanker, which ran aground in the Bristol Channel in 1996, spilling 72,000 tons of "Forties" crude oil. The objective was to investigate the sub-lethal cellular pathology and tissue hydrocarbon contamination in marine mussel populations, 4 months after the initial spill, using the neutral red retention (NRR) assay for lysosomal stability in blood cells. NRR was reduced in mussels, and indicative of cell injury, from the two sites closest to the spill in comparison with more distant and reference sites. Lysosomal stability was inversely correlated with polycyclic aromatic hydrocarbon concentrations in mussel tissues. Reduced lysosomal stability has previously been shown to contribute to impaired immunocompetence and to autophagic loss of body tissues. The use of this type of technique is discussed in the context of cost-effective, ecotoxicological tools for Integrated Coastal Zone Management.

Characterization of the egg vesicular components in the seaweed, Fucus serratus L. (Fucales, Phaeophyta), using enzyme histochemistry and vital staining: the search for a lysosome-like body.

Fucus serratus eggs were examined for evidence of the existence of a lysosome-like body using enzyme histochemical and vital staining techniques. Simultaneous coupling azo-dye techniques for lysosomal acid phosphatase proved inappropriate owing to endogenous phenolic binding artefacts. The large number of alginate polysaccharide and polyphenolic egg vesicles interfered with vital staining techniques for lysosomes. Lysosomal esterase activity was detected in the abundant egg lipid bodies. The role of the egg lipid body as an equivalent lysosome-like body of higher plants, the spherosome, is discussed in relation to egg fertilization and early zygote development.

Histologic changes and wound healing response following 10-pulse noncontact holmium:YAG laser thermal keratoplasty.

BACKGROUND: Noncontact holmium:YAG laser thermal keratoplasty (Ho:YAG LTK) is a promising new technology for correction of hyperopia and astigmatism. We studied the acute histologic changes and wound healing response following Ho:YAG LTK performed with treatment parameters encompassing those used in clinical studies. METHODS: We performed 10-pulse noncontact Ho:YAG LTK on three human corneas 1 day before their removal at penetrating keratoplasty and on six New Zealand white rabbit corneas followed for up to 3 months. Tissues were studied with light and transmission electron microscopy and immunohistochemistry. RESULTS: The amount of acute tissue injury increased according to the pulse radiant energy. In human corneas, changes in the irradiated zones included epithelial cell injury and death, loss of fine filamentous structure in Bowman's layer, disruption of stromal lamellae, and keratocyte injury and death. In the rabbit corneas, similar acute changes were noted. By 3 weeks, epithelial hyperplasia and stromal contraction were present. Wound healing in the rabbits included repair of the epithelial attachment complex, keratocyte activation, synthesis of type I collagen, partial restoration of stromal keratan sulfate and type VI collagen, and retrocorneal membrane formation. CONCLUSIONS: Noncontact Ho:YAG LTK produces acute epithelial and stromal tissue changes and in rabbit corneas stimulates a brisk wound healing response.

Production of reactive oxygen species by hemocytes from the marine mussel, Mytilus edulis: lysosomal localization and effect of xenobiotics.

Hemolymph of M. Edulis is rich in phagocytic hemocytes. Hemocytes contain numerous lysosomes which, in turn, contain various hydrolytic enzymes. Phagocytic activity of M. edulis hemocytes is thought to be associated with NAD(P)H-oxidase activity of the plasma membrane. The laser dye, dihydrorhodamine 123 (DHR), was used for cytochemical and biochemical detection of the generation of reactive oxygen species (ROS) by isolated M. edulis hemocytes. Hemocytes readily take up DHR from the suspension medium and selectively concentrate it in the lysosomes, wherein DHR is oxidized to fluorescent rhodamine 123. Concomitant uptake of DHR with superoxide dismutase or the spin-trap, tert-phenylbutyl nitrone, but not catalase markedly reduced fluorescence in the lysosomes implicating superoxide anion (O2-) but not hydrogen peroxide (H2O2) in DHR oxidation. Uptake of the anthraquinone, purpurin, and FeEDTA with DHR greatly amplified fluorescence within the lysosomes. These data are consistent with uptake of xenobiotics by hemocytes and their concentration in lysosomes wherein, ROS are generated in response to their accumulation. The rate of DHR oxidation by hemocytes was not stimulated by zymosan, a known stimulator of the oxidative burst. In vitro studies using the xanthine oxidase/hypoxanthine reaction to generate O2- and selective inhibitors of ROS production indicated that DHR is oxidized by O2- and H2O2 but not by .OH and that iron can participate in the reaction. Incubating isolated hemocytes promoted low-level, SOD-sensitive, FeEDTA-stimulated production of ethylene from alpha-keto-gamma-methiolbutyric acid, indicating the in situ formation of .OH via production of O2-. The above suggest that enhanced production of ROS in M. edulis hemocytes by xenobiotic accumulation within the lysosomal compartment should be considered in the toxic sequelae of exposure of marine molluscs to chemical pollutants.

Global gladiators: a model for international nursing education.

Vietnam is a beautiful country with many needs related to the achievement of optimal healthcare and the role of nurses in the country. The authors describe a U.S. Agency for International Development funded project sponsored by Health Volunteers Overseas. Nursing educators involved in the project share their experiences to help readers gain insight into the coordination necessary to make an international nursing education project successful.

Epithelial-stromal interactions in human keratotomy wound healing.

OBJECTIVE: To evaluate epithelial-stromal interactions in the healing of stromal wounds and the relationship of such interactions to regional variations in healing throughout keratotomy wounds. METHODS: Ten radial keratotomy autopsy specimens were studied by using light and transmission electron microscopy. RESULTS: Underneath epithelial plugs, the epithelial-stromal interface was characterized by three adjacent morphological zones: a duplicated basement membrane complex, a zone that resembled Bowman's layer, and a third zone with collagenous fiber orientation parallel to the plugs. Scar tissue orientation was transverse at the base of the plug, and sagittal in deeper wound regions. CONCLUSIONS: Basement membrane duplication and a Bowman's layer-like region underneath a plug may result from complicated epithelial-stromal interaction. Asymmetrical organization of the scar, with subepithelial transverse and sagittal deeper scar tissue orientation, may characterize radial keratotomy wound healing, and may relate to variations in final refractive effect.

Scar tissue orientation in unsutured and sutured corneal wound healing.

AIMS: This study aimed to evaluate stromal wound healing morphology in short term unsutured compared with sutured corneal wounds, to define regional variation in healing within radial keratotomy wounds. METHODS: Stromal scar tissue orientation (fibroblast and collagen fibre orientation) was analysed in unsutured and adjacent sutured keratotomy wounds in monkeys, 2 to 9 weeks after surgery, using light and transmission electron microscopy. RESULTS: At 2 to 4 weeks, scar tissue orientation was transverse to the wound edge in unsutured wounds, but sagittal in sutured wounds. At 5 to 9 weeks, a reorientation of scar tissue sagittal to the wound was seen in the unsutured wounds, proceeding from the posterior to anterior wound regions. In sutured wounds, a scar tissue reorientation transverse to the wound was seen, proceeding from the anterior wound region in a posterior direction. CONCLUSIONS: Within the same cornea, sutured and unsutured wounds showed opposite patterns of healing. Sutured wounds initially healed more slowly, but obtained pseudolamellar continuity over time. In contrast, healing of unsutured wounds was characterised by an early approximation towards lamellar repair that was followed by an ineffective reorganisation of the scar. This latter pattern of healing, that may be associated with a variable weakening of the wound, may relate to the clinical findings of unpredictability and/or progression of refractive effect following radial keratotomy.