Oxidative-nitrosative stress and systemic vascular function in highlanders with and without exaggerated hypoxemia

ABSTRACT BACKGROUND: Acute exposure to high-altitude stimulates free radical formation in lowlanders yet whether this persists during chronic exposure in healthy well-adapted and maladapted highlanders suffering from chronic mountain sickness (CMS) remains to be established. METHODS: Oxidative-nitrosative stress [ascorbate radical (A•-), electron paramagnetic resonance spectroscopy and nitrite (NO2-), ozone-based chemiluminescence] was assessed in venous blood of 25 male highlanders living at 3,600 m with (n = 13, CMS+) and without (n = 12, CMS-) CMS. Twelve age and activity-matched healthy male lowlanders were examined at sea-level and during acute hypoxia. We also measured flow-mediated dilatation (FMD), arterial stiffness (AIx-75) and carotid intima-media thickness (IMT). RESULTS: Compared to normoxic lowlanders, oxidative-nitrosative stress was moderately increased in CMS- (P < 0.05) as indicated by elevated A•- (3,191 ± 457 vs. 2,640 ± 445 arbitrary units (AU)] and lower NO2- (206 ± 55 vs. 420 ± 128 nmol/L) whereas vascular function remained preserved. This was comparable to that observed during acute hypoxia in lowlanders in whom vascular dysfunction is typically observed. In contrast, this response was markedly exaggerated in CMS+ (A•-: 3,765 ± 429 AU and NO2- : 148 ± 50 nmol/L) compared to both CMS- and lowlanders (P < 0.05). This was associated with systemic vascular dysfunction as indicated by lower (P < 0.05 vs. CMS-) FMD (4.2 ± 0.7 vs. 7.6 ± 1.7 %) and increased AIx-75 (23 ± 8 vs. 12 ± 7 %) and carotid IMT (714 ± 127 vs. 588 ± 94 µM). CONCLUSIONS: Healthy highlanders display a moderate sustained elevation in oxidative-nitrosative stress that unlike the equivalent increase evoked by acute hypoxia in healthy lowlanders, failed to affect vascular function. Its more marked elevation in patients with CMS may contribute to systemic vascular dysfunction.Clinical Trials Gov Registration # NCT011827921Neurovascular Research Laboratory, Faculty of Health, Science and Sport, University of Glamorgan, Wales, UK;2Sondes Moléculaires en Biologie et Stress Oxydant, Institut de Chimie Radicalaire, CNRS UMR 7273, Aix-Marseille University, France;3Department of Cardiology, University Hospital of Bern, Bern, Switzerland;4Institute of Clinical Physiology, CNR, Pisa, Italy;5Instituto Bolivano de Biologia de Altura, La Paz, Bolivia;6Centre for Clinical and Population Sciences, Queen's University Belfast, Belfast, Northern Ireland,7Botnar Center for Clinical Research, Hirslanden Group, Lausanne, Switzerland;8Facultad de Ciencias, Departamento de Biología, Universidad de Tarapacá, Arica, Chile and9Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland*Drs Bailey, Rimoldi, Scherrer and Sartori contributed equally to this workCorrespondence: Damian Miles Bailey, Neurovascular Research Laboratory, Faculty of Health, Science and Sport, University of Glamorgan, UK CF37 4AT email: dbailey1@glam.ac.uk.

Use of a lux-marked rhizobacterium as a biosensor to assess changes in rhizosphere C flow due to pollutant stress

The flow of carbon from plant roots into soil supports a range of microbial processes and is therefore critical to ecosystem function and health. Pollution-induced stress, which influences rhizosphere C flow is of considerable potential importance, and therefore needs to be evaluated. This paper reports on a method, based on reporter gene technology, for quantifying pollutant effects on rhizosphere C flow. The method uses the lux-marked rhizobacterium Pseudomonas fluorescens, where bioluminescence output of this biosensor is directly correlated with the metabolic activity and reports on C flow in root exudate. Plantago lanceolata was treated with paraquat (representing a model pollutant stress) in a simple microcosm system. The lux-biosensor response correlated closely with C concentrations in the exudate and demonstrated that the pollutant stress increased the C flow from the plantago roots, 24 h after application of the herbicide. The lux-reporter system therefore potentially offers a technique for use in assessing the impact of pollutant stress on rhizosphere C flow through the soil microbial biomass.

A comparison of stress intensity factors through crack closure integral and other approaches using eXtended element-free Galerkin method

In this paper, a new approach for extracting stress intensity factors (SIFs) by the extended element-free Galerkin method, through a crack closure integral (CCI) scheme, is proposed. The CCI calculation is used in conjunction with a local smoothing technique to improve the accuracy of the computed SIFs in a number of case studies of linear elastic fracture mechanics. The cases involve problems of mixed-mode, curved crack and thermo-mechanical loading. The SIFs by CCI, displacement and stress methods are compared with those based on the M-integral technique reported in the literature. The proposed CCI method involves very simple relations, and still gives good accuracy. The convergence of the results is also examined.

Income, deprivation and economic stress in the enlarged European Union

At risk of poverty indicators based on relative income measures suggest that within the enlarged EU societies located at quite different points on a continuum of affluence have similar levels of poverty. Substantial differences in levels of income between societies do not in themselves invalidate this approach. However, the relative income approach fails to capture the fact that, if countries are grouped in terms of level of GDP, between economic cluster differences in life-style deprivation are sharper at lower income levels. Support for the argument relating to restricted reference groups is found in relation to the contrast between the twelve most affluent EU countries and all others. The limitations of relative income poverty lines have little to do with the process of enlargement as such. Instead the major problem involves the weak association between income and deprivation in the more affluent countries. However, as a consequence of such difficulties, such indicators do not provide entirely meaningful comparisons of levels of disadvantage across economic clusters. The current analysis, rather than supporting the alternative of a focus on absolute income or an EU wide poverty line, suggests that we should take the argument for adopting a multidimensional approach to the measurement of poverty more seriously.

A Kinetic-Based Model of Radiation-Induced Intercellular Signalling

It is now widely accepted that intercellular communication can cause significant variations in cellular responses to genotoxic stress. The radiation-induced bystander effect is a prime example of this effect, where cells shielded from radiation exposure see a significant reduction in survival when cultured with irradiated cells. However, there is a lack of robust, quantitative models of this effect which are widely applicable. In this work, we present a novel mathematical model of radiation-induced intercellular signalling which incorporates signal production and response kinetics together with the effects of direct irradiation, and test it against published data sets, including modulated field exposures. This model suggests that these so-called "bystander" effects play a significant role in determining cellular survival, even in directly irradiated populations, meaning that the inclusion of intercellular communication may be essential to produce robust models of radio-biological outcomes in clinically relevant in vivo situations.

The stress process in palliative cancer care:A qualitative study on informal caregiving and its implication for the delivery of care

Objective: The primary objective of this study was to examine how the comprehensive nature of the Stress Process Model could elucidate on the stressors associated with caring for a palliative cancer patient. Method: A qualitative research strategy involving home-based face-to-face interviews with 12 bereaved family caregivers was used to examine the caregiving experience. Results: The primary stressors associated with caring for the palliative cancer care patients stemmed from care recipient symptoms and personal care needs. The absence of adequate support from the formal health care delivery system was a consistent message from all participants. There was evidence of financial stress primarily associated with the purchase of private home care to supplement formal care. In contrast, the resources that family caregivers relied on to moderate the stressful effects of caregiving included extended family, friends, and neighbors. While the stress of direct caregiving was high, the study revealed that formal care was also a significant source of stress for family caregivers. Conclusion: It was concluded that an appropriately financed, integrated system of care that followed a person-centered philosophy of care would best meet the needs of the patient and his or her family. © The Author(s) 2010.

Targeting EGFR Induced Oxidative Stress by PARP1 Inhibition in Glioblastoma Therapy

Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis [1,2], EGFR targeted therapies have achieved limited clinical efficacy [3]. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction [4,5]. A directed RNAi screen revealed that glioblastoma cells overexpressing EGFRvIII [6], an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER) genes required for the repair of Reactive Oxygen Species (ROS)-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1). Subsequent studies revealed that EGFRvIII overexpression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyperactivation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

Fatigue Life Assessment and Static Testing of Structural GFRP Tubes Based on Coupon Tests

Fiber-reinforced polymer (FRP) hollow tubes are used in structural applications, such as utility poles and pipelines. Concrete-filled FRP tubes (CFFTs) are also used as piles and bridge piers. Applications such as poles and marine piles are typically governed by cyclic bending. In this paper, the fatigue behavior of glass-FRP filament-wound tubes is studied using coupons cut from the tubes. Several coupon configurations were first examined in 24 tension and five compression monotonic loading tests. Fatigue tests were then conducted on 81 coupons to examine several parameters; namely, loading frequency as well as maximum-to-ultimate (max ult) and minimum-to-maximum (min max) stress ratios, including tension tension and tension compression, to simulate reversed bending. The study demonstrated the sensitivity of test results and failure mode to coupon configuration. The presence of compression loads reduced fatigue life, while increasing load frequency increased fatigue life. Stiffness degradation behavior was also established. To achieve at least one million cycles, it is recommended to limit (max ult) to 0.25. Models were used to simulate stiffness degradation and fatigue life curve of the tube. Fatigue life predictions of large CFFT beams showed good correlation with experimental results. © 2008 ASCE.

The effects of the Omagh bomb on adolescent mental health: a school-based study

Background: The main objective of this study was to assess psychiatric morbidity among adolescentsfollowing the Omagh car bombing in Northern Ireland in 1998.

Methods: Data was collected within schools from adolescents aged between 14 and 18 years via a selfcompletionbooklet comprised of established predictors of PTSD; type of exposure, initialemotional response, long-term adverse physical problems, predictors derived from Ehlers andClark’s (2000) cognitive model, a PTSD symptoms measure (PDS) and the General HealthQuestionnaire (GHQ).

Results:Those with more direct physical exposure were significantly more likely to meet caseness onthe GHQ and the PDS. The combined pre and peri trauma risk factors highlighted in previousmeta-analyses accounted for 20% of the variance in PDS scores but the amount of varianceaccounted for increased to 56% when the variables highlighted in Ehlers and Clark’scognitive model for PTSD were added.

Conclusions: High rates of chronic PTSD were observed in adolescents exposed to the bombing. Whilstincreased exposure was associated with increased psychiatric morbidity, the best predictors ofPTSD were specific aspects of the trauma (‘seeing someone you think is dying’), what youare thinking during the event (‘think you are going to die’) and the cognitive mechanismsemployed after the trauma. As these variables are in principle amenable to treatment theresults have implications for teams planning treatment interventions after future traumas.

Strawberry as a functional food:an evidence-based review

Emerging research provides substantial evidence to classify strawberries as a functional food with several preventive and therapeutic health benefits. Strawberries, a rich source of phytochemicals (ellagic acid, anthocyanins, quercetin, and catechin) and vitamins (ascorbic acid and folic acid), have been highly ranked among dietary sources of polyphenols and antioxidant capacity. It should however be noted that these bioactive factors can be significantly affected by differences in strawberry cultivars, agricultural practices, storage, and processing methods: freezing versus dry heat has been associated with maximum retention of strawberry bioactives in several studies. Nutritional epidemiology shows inverse association between strawberry consumption and incidence of hypertension or serum C-reactive protein; controlled feeding studies have identified the ability of strawberries to attenuate high-fat diet induced postprandial oxidative stress and inflammation, or postprandial hyperglycemia, or hyperlipidemia in subjects with cardiovascular risk factors. Mechanistic studies have elucidated specific biochemical pathways that might confer these protective effects of strawberries: upregulation of endothelial nitric oxide synthase (eNOS) activity, downregulation of NF-kB activity and subsequent inflammation, or inhibitions of carbohydrate digestive enzymes. These health effects may be attributed to the synergistic effects of nutrients and phytochemicals in strawberries. Further studies are needed to define the optimal dose and duration of strawberry intake in affecting levels of biomarkers or pathways related to chronic diseases.

A systematic review of midwife led interventions to address post traumatic stress syndrome

Objective
to systematically identify interventions that midwives could introduce to address post-traumatic stress in women following childbirth.

Methods
a search strategy was developed and relevant papers were identified from databases including Cinahl, Cochrane Library, EMBASE, Maternity and Infant Care, MEDLINE, PsycINFO, and Web of Science. Key search terms used were post-traumatic stress, post partum, intervention, controlled trial and review. Papers eligible for inclusion were primary studies and reviews of research published from 2002–2012, focusing on interventions which could be implemented by midwives for the prevention and/or management of PTSD. For primary studies, RCTs, controlled clinical trials, and cohort studies with a control group were eligible. Eligible reviews were those with a specified search strategy and inclusion/exclusion criteria. Methodological quality was assessed using recognised frameworks.

Findings
six primary studies and eight reviews were eligible for inclusion. The majority of included studies or reviews focused on debriefing and/or counselling interventions; however the results were not consistent due to significant variation in methodological quality and use of dissimilar interventions. Two of the reviews considered the general management of post partum PTSD and one broadly covered anxiety during pregnancy and the post partum, incorporating a section on PTSD. The majority of women reported that the opportunity to discuss their childbirth experience was subjectively beneficial.

Conclusions and implications for practice
no evidence-based midwifery interventions were identified from this systematic review that can be recommended for introduction into practice to address PTSD. It is recommended that future research in this area should incorporate standardised interventions with similar outcome measures to facilitate synthesis of results. Further research on interventions used in non-maternity populations is needed in order to confirm their usefulness in addressing post partum PTSD.

Determining optimal duration of seed translocation periods for benthic mussel (Mytilus edulis) cultivation using physiological and behavioural measures of stress

During the benthic cultivation process of Mytilus edulis (blue mussels), wild mussel seed is often transplanted from naturally occurring subtidal beds to sheltered in-shore waters to be grown to a commercial size. The survival of these relaid mussels is ultimately a function of their quality and physiological condition upon relaying and it has been recognised that mussels can suffer from a loss in condition following transportation. We investigated whether the process of being transported to ongrowing plots had a negative effect on the physiological health and resultant behaviour of mussels by simulating transportation conditions in a controlled experiment. Mussels were kept, out of water, in plastic piping to recreate translocation conditions and further, we tested if depth held in a ship hold (0, 1.5 and 3 m) and length of time emersed (12, 24 and 48 h) affected mussel condition and behaviour. Physiological condition was assessed by quantifying mussel tissue pH and whole tissue glucose, glycogen, succinate and propionate concentrations. The rate of byssogenesis was also quantified to estimate recovery following a period of re-immersion. The depth at which mussels were held did not affect any of the physiological indicators of mussel stress but short-term byssus production was affected. Mussels held at 3 m produced fewer byssus threads during the first 72 h following re-immersion compared with mussels at 0 m (i.e. not buried) suggesting that depth held can impede recovery following transportation. Duration of emersion affected all stress indicators. Specifically, mussels held out of water for 48 h had a reduced physiological condition compared with those emersed for just 12 h. This work has practical implications for the benthic cultivation industry and based on these results we recommend that mussels are held out of water for less than 24 h prior to relaying to ensure physiological health and resultant condition is preserved.

A predictive maintenance system for integral type faults based on support vector machines:An application to ion implantation

In semiconductor fabrication processes, effective management of maintenance operations is fundamental to decrease costs associated with failures and downtime. Predictive Maintenance (PdM) approaches, based on statistical methods and historical data, are becoming popular for their predictive capabilities and low (potentially zero) added costs. We present here a PdM module based on Support Vector Machines for prediction of integral type faults, that is, the kind of failures that happen due to machine usage and stress of equipment parts. The proposed module may also be employed as a health factor indicator. The module has been applied to a frequent maintenance problem in semiconductor manufacturing industry, namely the breaking of the filament in the ion-source of ion-implantation tools. The PdM has been tested on a real production dataset. © 2013 IEEE.

Effect of Nanosilica on Rheology, Fresh Properties, and Strength of Cement-Based Grouts

The effect of colloidal nanosilica on the fresh and rheological parameters, plastic shrinkage, heat of hydration, and compressive strength of cement-based grouts is investigated in this paper. The fresh and rheological properties were evaluated by the minislump flow, Marsh cone flow time, Lombardi plate cohesion meter, yield value, and plastic viscosity. The key parameters investigated were the dosages of nanosilica and superplasticizer and temperature of mixing water. Statistical models and isoresponse curves were developed to capture the significant trends. The dosage of nanosilica had a significant effect on the results. The increase in the dosage of nanosilica led to increasing the values of flow time, plate cohesion meter, yield stress, plastic viscosity, heat of hydration at 1 day and 3 days, and compressive strength at 1 day, while reducing the minislump, plastic shrinkage up 24 h, and compressive strength at 3, 7, and 28 days. Conversely, the increase in the dosage of superplasticizer led to decreasing the values of flow time, plate cohesion meter, yield stress, plastic viscosity, heat of hydration at 1 day and 3 days, and compressive strength at 1 day, while increasing the minislump, plastic shrinkage, and compressive strength at 3 and 7 days. Increasing the temperature of mixing water led to a notable increase in the results of minislump, flow time, plastic viscosity, heat of hydration at 3 days, and compressive strength at 1 day, while it reduced the plate cohesion, compressive strength at 3, 7, and 28 days. The statistical models developed in this study can facilitate optimizing the mixture proportions of grouts for target performance by reducing the number of trial batches needed.

Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity

New Findings

What is the central question of this study?Exercise performance is limited during hypoxia by a critical reduction in cerebral and skeletal tissue oxygenation. To what extent an elevation in systemic free radical accumulation contributes to microvascular deoxygenation and the corresponding reduction in maximal aerobic capacity remains unknown.What is the main finding and its importance?We show that altered free radical metabolism is not a limiting factor for exercise performance in hypoxia, providing important insight into the fundamental mechanisms involved in the control of vascular oxygen transport.

Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine  in both normoxia (21% O_{2) and hypoxia (12% O2) separated by a week. Continuous-wave near-infrared spectroscopy was employed to monitor concentration changes in oxy- and deoxyhaemoglobin in the left vastus lateralis muscle and frontal cerebral cortex. Antecubital venous blood samples were obtained at rest and at  to determine oxidative (ascorbate radical by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozone-based chemiluminescence and 3-nitrotyrosine by enzyme-linked immunosorbent assay) and inflammatory stress biomarkers (soluble intercellular/vascular cell adhesion 1 molecules by enzyme-linked immunosorbent assay). Hypoxia was associated with increased cerebral and muscle tissue deoxygenation and lower  (P < 0.05 versus normoxia). Despite an exercise-induced increase in oxidative–nitrosative–inflammatory stress, hypoxia per se did not have an additive effect (P > 0.05 versus normoxia). Consequently, we failed to observe correlations between any metabolic, haemodynamic and cardiorespiratory parameters (P > 0.05). Collectively, these findings suggest that altered free radical metabolism cannot explain the elevated microvascular deoxygenation and corresponding lower  in hypoxia. Further research is required to determine whether free radicals when present in excess do indeed contribute to the premature termination of exercise in hypoxia.}