Opportunity recognition attitudes of nascent indigenous entrepreneurs

This exploratory research aims to fill a gap in the literature. The current theory of entrepreneurial attitude toward opportunity recognition (EOR) is primarily based upon a non-indigenous entrepreneurship theory. Yet, there are significant differences between non-indigenous and indigenous forms of entrepreneurship. Non-indigenous entrepreneurship tends to emphasise economic objectives whereas indigenous entrepreneurship tends to embrace both economic and non-economic objectives. As such, the current EOR theory needs to be expanded to include both non-indigenous and indigenous similarities and differences. This research uses indigenous culture as a context for examining the relationships between personal values, EOR and expected personal success of nascent indigenous entrepreneurs.

Rapid bioassay-guided screening of toxic substances in vegetable oils that shorten the life of SHRSP rats

It has been consistently reported that vegetable oils including canola oil have a life shortening effect in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) and this toxic effect is not due to the fatty acid composition of the oil. Although it is possible that the phytosterol content or type of phytosterol present in vegetable oils may play some role in the life shortening effect observed in SHRSP rats this is still not completely resolved. Furthermore supercritical CO2 fractionation of canola oil with subsequent testing in SHRSP rats identified safe and toxic fractions however, the compounds responsible for life shortening effect were not characterised. The conventional approach to screen toxic substances in oils using rats takes more than six months and involves large number of animals. In this article we describe how rapid bioassay-guided screening could be used to identify toxic substances derived from vegetable oils and/or processed foods fortified with vegetable oils. The technique incorporates sequential fractionation of oils/processed foods and subsequent treatment of human cell lines that can be used in place of animal studies to determine cytotoxicity of the fractions with structural elucidation of compounds of interest determined via HPLC-MS and GC-MS. The rapid bioassay-guided screening proposed would require two weeks to test multiple fractions from oils, compared with six months if animal experiments were used to screen toxic effects. Fractionation of oil before bio-assay enhances the effectiveness of the detection of active compounds as fractionation increases the relative concentration of minor components.

Targeting Hsp90 with small molecule inhibitors induces the over-expression of the anti-apoptotic molecule, survivin, in human A549, HONE-1 and HT-29 cancer cells

Survivin is a dual functioning protein. It inhibits the apoptosis of cancer cells by inhibiting caspases, and also promotes cancer cell growth by stabilizing microtubules during mitosis. Since the molecular chaperone Hsp90 binds and stabilizes survivin, it is widely believed that down-regulation of survivin is one of the important therapeutic functions of Hsp90 inhibitors such as the phase III clinically trialed compound 17-AAG. However, Hsp90 interferes with a number of molecules that up-regulate the intracellular level of survivin, raising the question that clinical use of Hsp90 inhibitors may indirectly induce survivin expression and subsequently enhance cancer anti-drug responses. The purpose of this study is to determine whether targeting Hsp90 can alter survivin expression differently in different cancer cell lines and to explore possible mechanisms that cause the alteration in survivin expression.

Suppressive actions of eicosapentaenoic acid on lipid droplet formation in 3T3-L1 adipocytes

Background : Lipid droplet (LD) formation and size regulation reflects both lipid influx and efflux, and is central in the regulation of adipocyte metabolism, including adipokine secretion. The length and degree of dietary fatty acid (FA) unsaturation is implicated in LD formation and regulation in adipocytes. The aims of this study were to establish the impact of eicosapentaenoic acid (EPA; C20:5n-3) in comparison to SFA (STA; stearic acid, C18:0) and MUFA (OLA; oleic acid, C18:1n-9) on 3T3-L1 adipocyte LD formation, regulation of genes central to LD function and adipokine responsiveness. Cells were supplemented with 100 μM FA during 7-day differentiation.

Results : EPA markedly reduced LD size and total lipid accumulation, suppressing PPARγ, Cidea and D9D/SCD1 genes, distinct from other treatments. These changes were independent of alterations of lipolytic genes, as both EPA and STA similarly elevated LPL and HSL gene expressions. In response to acute lipopolysaccharide exposure, EPA-differentiated adipocytes had distinct improvement in inflammatory response shown by reduction in monocyte chemoattractant protein-1 and interleukin-6 and elevation in adiponectin and leptin gene expressions.

Conclusions : This study demonstrates that EPA differentially modulates adipogenesis and lipid accumulation to suppress LD formation and size. This may be due to suppressed gene expression of key proteins closely associated with LD function. Further analysis is required to determine if EPA exerts a similar influence on LD formation and regulation in-vivo.

The effect of short-term canola oil ingestion on oxidative stress in the vasculature of stroke-prone spontaneously hypertensive rats

Background: This study aimed to determine if 25 days of canola oil intake in the absence of excess dietary salt or together with salt loading affects antioxidant and oxidative stress markers in the circulation. A further aim was to determine the mRNA expression of NADPH oxidase subunits and superoxide dismutase (SOD) isoforms in the aorta of stroke-prone spontaneously hypertensive (SHRSP) rats.

Methods: Male SHRSP rats, were fed a defatted control diet containing 10% wt/wt soybean oil or a defatted treatment diet containing 10% wt/wt canola oil, and given tap water or water containing 1% NaCl. Blood was collected at the end of study for analysis of red blood cell (RBC) antioxidant enzymes, RBC and plasma malondialdehyde (MDA), plasma 8-isoprostane and plasma lipids. The aorta was removed and the mRNA expression of NOX2, p22phox, CuZn-SOD, Mn-SOD and EC-SOD were determined.

Results: In the absence of salt, canola oil reduced RBC SOD and glutathione peroxidase, and increased total cholesterol and LDL cholesterol compared with soybean oil. RBC glutathione peroxidase activity was significantly lower in both the salt loaded groups compared to the soybean oil only group. In addition, RBC MDA and plasma HDL cholesterol were significantly higher in both the salt loaded groups compared to the no salt groups. Plasma MDA concentration was higher and LDL cholesterol concentration lower in the canola oil group loaded with salt compared to the canola oil group without salt. The mRNA expression of NADPH oxidase subunits and SOD isoforms were significantly reduced in the canola oil group with salt compared to canola oil group without salt.

Conclusion: In conclusion, these results indicate that canola oil reduces antioxidant status and increases plasma lipids, which are risk factors for cardiovascular disease. However, canola oil in combination with salt intake increased MDA, a marker of lipid peroxidation and decreased NAPDH oxidase subunits and aortic SOD gene expression.

The effect of cocoa supplementation on hepatic steatosis, reactive oxygen species and LFABP in a rat model of NASH

Background: Non alcoholic steatohepatitis is hypothesised to develop via a mechanism involving fat accumulation and oxidative stress. The current study aimed to investigate if an increase in oxidative stress was associated with changes in the expression of liver fatty acid binding protein in a rat model of non alcoholic steatohepatitis and whether cocoa supplementation attenuated those changes.

Methods: Female Sprague Dawley rats were fed a high fat control diet, a high fat methionine choline deficient diet, or one of four 12.5% cocoa supplementation regimes in combination with the high fat methionine choline deficient diet.

Results: Liver fatty acid binding protein mRNA and protein levels were reduced in the liver of animals with fatty liver disease when compared to controls. Increased hepatic fat content was accompanied by higher levels of oxidative stress in animals with fatty liver disease when compared to controls. An inverse association was found between the levels of hepatic liver fatty acid binding protein and the level of hepatic oxidative stress in fatty liver disease. Elevated NADPH oxidase protein levels were detected in the liver of animals with increased severity in inflammation and fibrosis. Cocoa supplementation was associated with partial attenuation of these pathological changes, although the severity of liver disease induced by the methionine choline deficient diet prevented complete reversal of any disease associated changes. Red blood cell glutathione was increased by cocoa supplementation, whereas liver glutathione was reduced by cocoa compared to methionine choline deficient diet fed animals.

Conclusion: These findings suggest a potential role for liver fatty acid binding protein and NADPH oxidase in the development of non alcoholic steatohepatitis. Furthermore, cocoa supplementation may have be of therapeutic benefit in less sever forms of NASH.

Does the choice of neighbourhood supermarket access measure influence associations with individual-level fruit and vegetable consumption? A case study from Glasgow

Background
Previous studies have provided mixed evidence with regards to associations between food store access and dietary outcomes. This study examines the most commonly applied measures of locational access to assess whether associations between supermarket access and fruit and vegetable consumption are affected by the choice of access measure and scale.

Method
Supermarket location data from Glasgow, UK (n = 119), and fruit and vegetable intake data from the 'Health and Well-Being' Survey (n = 1041) were used to compare various measures of locational access. These exposure variables included proximity estimates (with different points-of-origin used to vary levels of aggregation) and density measures using three approaches (Euclidean and road network buffers and Kernel density estimation) at distances ranging from 0.4 km to 5 km. Further analysis was conducted to assess the impact of using smaller buffer sizes for individuals who did not own a car. Associations between these multiple access measures and fruit and vegetable consumption were estimated using linear regression models.

Results
Levels of spatial aggregation did not impact on the proximity estimates. Counts of supermarkets within Euclidean buffers were associated with fruit and vegetable consumption at 1 km, 2 km and 3 km, and for our road network buffers at 2 km, 3 km, and 4 km. Kernel density estimates provided the strongest associations and were significant at a distance of 2 km, 3 km, 4 km and 5 km. Presence of a supermarket within 0.4 km of road network distance from where people lived was positively associated with fruit consumption amongst those without a car (coef. 0.657; s.e. 0.247; p0.008).

Conclusions
The associations between locational access to supermarkets and individual-level dietary behaviour are sensitive to the method by which the food environment variable is captured. Care needs to be taken to ensure robust and conceptually appropriate measures of access are used and these should be grounded in a clear a priori reasoning.

Arginase II inhibition prevents nitrate tolerance

BACKGROUND AND PURPOSE Nitrate tolerance, the loss of vascular responsiveness with continued use of nitrates, remains incompletely understood and is a limitation of these therapeutic agents. Vascular superoxide, generated by uncoupled endothelial NOS (eNOS), may play a role. As arginase competes with eNOS for L-arginine and may exacerbate the production of reactive oxygen species (ROS), we hypothesized that arginase inhibition might reduce nitrate tolerance.

EXPERIMENTAL APPROACH Vasodilator responses were measured in aorta from C57Bl/6 and arginase II knockout (argII –/–) mice using myography. Uncoupling of eNOS, determined as eNOS monomer : dimer ratio, was assessed using low-temperature SDS-PAGE and ROS levels were measured using L-012 and lucigenin-enhanced chemiluminescence.

KEY RESULTS Repeated application of glyceryl trinitrate (GTN) on aorta isolated from C57Bl/6 mice produced a 32-fold rightward shift of the concentration–response curve. However this rightward shift (or resultant tolerance) was not observed in the presence of the arginase inhibitor (s)-(2-boronethyl)-L-cysteine HCl (BEC; 100 µM) nor in aorta isolated from argII –/– mice. Similar findings were obtained after inducing nitrate tolerance in vivo. Repeated administration of GTN in human umbilical vein endothelial cells induced uncoupling of eNOS from its dimeric state and increased ROS levels, which were reduced with arginase inhibition and exogenous L-arginine. Aortae from GTN tolerant C57Bl/6 mice exhibited increased arginase activity and ROS production, whereas vessels from argII –/– mice did not.

CONCLUSION AND IMPLICATIONS Arginase II removal prevents nitrate tolerance. This may be due to decreased uncoupling of eNOS and consequent ROS production.

Reperfusion-induced myocardial dysfunction is prevented by endogenous annexin-A1 and its N-terminal-derived peptide Ac-ANX-A12-26

BACKGROUND AND PURPOSE : Annexin-A1 (ANX-A1) is an endogenous, glucocorticoid-regulated anti-inflammatory protein. The N-terminal-derived peptide Ac-ANX-A12–26 preserves cardiomyocyte viability, but the impact of ANX-A1-peptides on cardiac contractility is unknown. We now test the hypothesis that ANX-A1 preserves post-ischaemic recovery of left ventricular (LV) function.

EXPERIMENTAL APPROACH : Ac-ANX-A12–26 was administered on reperfusion, to adult rat cardiomyocytes as well as hearts isolated from rats, wild-type mice and mice deficient in endogenous ANX-A1 (ANX-A1–/–). Myocardial viability and recovery of LV function were determined.

KEY RESULTS: Ischaemia–reperfusion markedly impaired both cardiomyocyte viability and recovery of LV function by 60%. Treatment with exogenous Ac-ANX-A12–26 at the onset of reperfusion prevented cardiomyocyte injury and significantly improved recovery of LV function, in both intact rat and wild-type mouse hearts. Ac-ANX-A12–26 cardioprotection was abolished by either formyl peptide receptor (FPR)-nonselective or FPR1-selective antagonists, Boc2 and cyclosporin H, but was relatively insensitive to the FPR2-selective antagonist QuinC7. ANX-A1-induced cardioprotection was associated with increased phosphorylation of the cell survival kinase Akt. ANX-A1−/− exaggerated impairment of post-ischaemic recovery of LV function, in addition to selective LV FPR1 down-regulation.

CONCLUSIONS AND IMPLICATIONS : These data represent the first evidence that ANX-A1 affects myocardial function. Our findings suggest ANX-A1 is an endogenous regulator of post-ischaemic recovery of LV function. Furthermore, the ANX-A1-derived peptide Ac-ANX-A12–26 on reperfusion rescues LV function, probably via activation of FPR1. ANX-A1-based therapies may thus represent a novel clinical approach for the prevention and treatment of myocardial reperfusion injury.

Toxic marine microalgae and shellfish poisoning in the British isles : history, review of epidemiology, and future implications

The relationship between toxic marine microalgae species and climate change has become a high profile and well discussed topic in recent years, with research focusing on the possible future impacts of changing hydrological conditions on Harmful Algal Bloom (HAB) species around the world. However, there is very little literature concerning the epidemiology of these species on marine organisms and human health. Here, we examine the current state of toxic microalgae species around the UK, in two ways: first we describe the key toxic syndromes and gather together the disparate reported data on their epidemiology from UK records and monitoring procedures. Secondly, using NHS hospital admissions and GP records from Wales, we attempt to quantify the incidence of shellfish poisoning from an independent source. We show that within the UK, outbreaks of shellfish poisoning are rare but occurring on a yearly basis in different regions and affecting a diverse range of molluscan shellfish and other marine organisms. We also show that the abundance of a species does not necessarily correlate to the rate of toxic events. Based on routine hospital records, the numbers of shellfish poisonings in the UK are very low, but the identification of the toxin involved, or even a confirmation of a poisoning event is extremely difficult to diagnose. An effective shellfish monitoring system, which shuts down aquaculture sites when toxins exceed regularity limits, has clearly prevented serious impact to human health, and remains the only viable means of monitoring the potential threat to human health. However, the closure of these sites has an adverse economic impact, and the monitoring system does not include all toxic plankton. The possible geographic spreading of toxic microalgae species is therefore a concern, as warmer waters in the Atlantic could suit several species with southern biogeographical affinities enabling them to occupy the coastal regions of the UK, but which are not yet monitored or considered to be detrimental.

A hazardous substance exposure prevention rating method for intervention needs assessment and effectiveness evaluation: the small business exposure index

Aims This paper describes the refinement and adaptation to small business of a previously developed method for systematically prioritizing needs for intervention on hazardous substance exposures in manufacturing worksites, and evaluating intervention effectiveness. Methods We developed a checklist containing six unique sets of yes/no variables organized in a 2 × 3 matrix of exposure potential versus exposure protection at three levels corresponding to a simplified hierarchy of controls: materials, processes, and human interface. Each of the six sets of indicator variables was reduced to a high/moderate/low rating. Ratings from the matrix were then combined to generate an exposure prevention 'Small Business Exposure Index' (SBEI) Summary score for each area. Reflecting the hierarchy of controls, material factors were weighted highest, followed by process, and then human interface. The checklist administered by an industrial hygienist during walk-through inspection (N = 149 manufacturing processes/areas in 25 small to medium-sized manufacturing worksites). One area or process per manufacturing department was assessed and rated. A second hygienist independently assessed 36 areas to evaluate inter-rater reliability. Results The SBEI Summary scores indicated that exposures were well controlled in the majority of areas assessed (58% with rating of 1 or 2 on a 6-point scale), that there was some room for improvement in roughly one-third of areas (31% of areas rated 3 or 4), and that roughly 10% of the areas assessed were urgently in need of intervention (rated as 5 or 6). Inter-rater reliability of EP ratings was good to excellent (e.g., for SBEI Summary scores, weighted kappa = 0.73, 95% CI 0.52–0.93). Conclusion The SBEI exposure prevention rating method is suitable for use in small/medium enterprises, has good discriminatory power and reliability, offers an inexpensive method for intervention needs assessment and effectiveness evaluation, and complements quantitative exposure assessment with an upstream prevention focus.

Reproducibility of aortic intima-media thickness in infants using edge-detection software and manual caliper measurements

Background: Aortic intima-media thickness measured by transabdominal ultrasound (aIMT) is an intermediate phenotype of cardiovascular risk. We aimed to (1) investigate the reproducibility of aIMT in a population-derived cohort of infants; (2) establish the distribution of aIMT in early infancy; (3) compare measurement by edge-detection software to that by manual sonographic calipers; and (4) assess the effect of individual and environmental variables on image quality. Methods. Participants were term infants recruited to a population-derived birth cohort study. Transabdominal ultrasound was performed at six weeks of age by one of two trained operators. Thirty participants had ultrasounds performed by both operators on the same day. Data were collected on environmental (infant sleeping, presence of a sibling, use of sucrose, timing during study visit) and individual (post-conception age, weight, gender) variables. Two readers assessed image quality and measured aIMT by edge-detection software and a subset by manual sonographic calipers. Measurements were repeated by the same reader and between readers to obtain intra-observer and inter-observer reliability. Results: Aortic IMT was measured successfully using edge-detection in 814 infants, and 290 of these infants also had aIMT measured using manual sonographic calipers. The intra-reader intra-class correlation (ICC) (n = 20) was 0.90 (95% CI 0.76, 0.96), mean difference 1.5 μm (95% LOA -39, 59). The between reader ICC using edge-detection (n = 20) was 0.92 (95% CI 0.82, 0.97) mean difference 2 μm (95% LOA -45.0, 49.0) and with manual caliper measurement (n = 290) the ICC was 0.84 (95% CI 0.80, 0.87) mean difference 5 μm (95% LOA -51.8, 61.8). Edge-detection measurements were greater than those from manual sonographic calipers (mean aIMT 618 μm (50) versus mean aIMT 563 μm (49) respectively; p < 0.001, mean difference 44 μm, 95% LOA -54, 142). With the exception of infant crying (p = 0.001), no associations were observed between individual and environmental variables and image quality. Conclusion: In a population-derived cohort of term infants, aIMT measurement has a high level of intra and inter-reader reproducibility. Measurement of aIMT using edge-detection software gives higher inter-reader ICC than manual sonographic calipers. Image quality is not substantially affected by individual and environmental factors. © 2014 McCloskey et al.; licensee BioMed Central Ltd.

Randomised controlled trials in child health in developing countries: trends and lessons over 11 years.

Using a uniform systematic approach annually, we reviewed 1553 publications from randomised controlled trials in child health in developing countries published between July 2002 and June 2013. There were annual increases in such publications, from 38 in the 12 months to July 2003 to over 200 in each of 2012 and 2013. These trials involved children in 76 developing countries. Studies of nutrition (366 publications, 23.6%) and malaria (336 publications, 21%) predominated. 79% of nutrition trials have been of micronutrients (288 publications), with comparatively few publications related to macronutrient interventions or complimentary feeding (48 publications) or measures to improve breast feeding (20 publications). Trials of malaria have involved a comprehensive range of treatment and preventive strategies and have heralded the implementation of new interventions as routine health strategies, and reductions in malaria in each affected country in the world in the last decade. There have been a relatively small number of trials of interventions for treatment or prevention of acute respiratory infection (98 publications, 6.3%), neonatal health (64 publications, 4.1%) and tuberculosis in children (26 publications, 1.7%). In the last 5 years there has been increasing focus on non-communicable diseases such as asthma and allergy, obesity, diabetes and cardiac disease, and behavioural-developmental disorders. Mental health conditions have received little attention (21 publications, 1.4% of publications). There is increasing research activity and capacity in child health in developing countries. Some areas have been the subject of a large amount of research, and have led to the design and implementation of effective public health interventions and reduced disease burdens, while in other areas comprehensive approaches and the systematic application of research findings have been lacking.