Effects of the mycotoxin patulin at the level of nuclear receptor transcriptional activity and steroidogenesis in vitro

Patulin (PAT) is a mycotoxin produced by various species of fungi, with Penicillium expansum being the most commonly occurring. Apples and apple products are the main sources of PAT contamination. This mycotoxin has been shown to induce toxic effects in animals, a few of which include reproductive toxicity and interference with the endocrine system. Here the endocrine disrupting potential of PAT has been investigated in vitro to identify disruption at the level of oestrogen, androgen, progestagen and glucocorticoid nuclear receptor transcriptional activity, and to assess interferences in estradiol, testosterone and progesterone steroid hormone production. At the receptor level, 0.5-5000ng/ml (0.0032-32μM) PAT did not appear to induce any specific (ant) agonistic responses in reporter gene assays (RGAs); however, nuclear transcriptional activity was affected. A >6 fold increase in the glucocorticoid receptor transcriptional activity was observed following treatment with 5000ng/ml PAT in the presence of cortisol. At the hormone production level, despite cytotoxicity being observed after treatment with 5000ng/ml PAT, estradiol levels had increased >2 fold. At 500ng/ml PAT treatment, an increase in progesterone and a decrease in testosterone production were observed. The findings of this study could be considered in assessing the health risks following exposure to PAT.

Effects of Undaria pinnatifida, Himanthalia elongata and Porphyra umbilicalis extracts on in vitro α-glucosidase activity and glucose diffusion

Background: Seaweeds are good sources of dietary fibre, which can influence glucose uptake and glycemic control.Objective: To investigate and compare the in vitro inhibitory activity of different extracts from Undaria pinnatifida (Wakame), Himanthalia elongata (Sea spaghetti) and Porphyra umbilicalis (Nori) on α-glucosidase activity and glucose diffusion.Methods: The in vitro effects chloroform-, ethanol- and water-soluble extracts of the three algae were assayed on α- glucosidase activity and glucose diffusion through membrane. Principal Components Analysis (PCA) was applied to identify patterns in the data and to discriminate which extract will show the most proper effect.Results: Only water extracts of Sea spaghetti possessed significant in vitro inhibitory effects on α-glucosidase activity (26.2% less mmol/L glucose production than control, p < 0.05) at 75 min. PCA distinguished Sea spaghetti effects, supporting that soluble fibre and polyphenols were involved. After 6 h, Ethanol-Sea spaghetti and water-Wakame extracts exerted the highest inhibitory effects on glucose diffusion (65.0% and 60.2% vs control, respectively). This extracts displayed the lowest slopes for glucose diffusion-time lineal adjustments (68.2% and 62.8% vs control, respectively).Conclusions: The seaweed hypoglycemic effects appear multi-faceted and not necessarily concatenated. According to present results, ethanol and water extracts of Sea spaghetti, and water extracts of Wakame could be useful for the development of functional foods with specific hypoglycemic properties.

FAD binding overcomes defects in activity and stability displayed by cancer-associated variants of human NQO1

NAD(P)H quinone oxidoreductase 1 is involved in antioxidant defence and protection from cancer, stabilizing the apoptosis regulator p53 towards degradation. Here, we studied the enzymological, biochemical and biophysical properties of two cancer-associated variants (p.R139W and p.P187S). Both variants (especially p.187S) have lower thermal stability and greater susceptibility to proteolysis compared to the wild-type. p.P187S also has reduced activity due to a lower binding affinity for the FAD cofactor as assessed by activity measurements and direct titrations. Native gel electrophoresis and dynamic light scattering also suggest that p.P187S has a higher tendency to populate unfolded states under native conditions. Detailed thermal stability studies showed that all variants irreversibly denature causing dimer dissociation, while addition of FAD restores the stability of the polymorphic forms to wild-type levels. The kinetic destabilization induced by polymorphisms as well as the kinetic protection exerted by FAD was confirmed by measuring denaturation kinetics at temperatures close to physiological. Our data suggest that the main molecular mechanisms associated with these cancer-related variants are their low binding affinity for FAD and/or kinetic instability. Thus, pharmacological chaperones may be useful in the treatment of patients bearing these polymorphisms.

Validity of the Global Physical Activity Questionnaire (GPAQ) in assessing levels and change in moderate-vigorous physical activity and sedentary behaviour

Background

Feasible, cost-effective instruments are required for the surveillance of moderate-to-vigorous physical activity (MVPA) and sedentary behaviour (SB) and to assess the effects of interventions. However, the evidence base for the validity and reliability of the World Health Organisation-endorsed Global Physical Activity Questionnaire (GPAQ) is limited. We aimed to assess the validity of the GPAQ, compared to accelerometer data in measuring and assessing change in MVPA and SB.

Participants (n = 101) were selected randomly from an on-going research study, stratified by level of physical activity (low, moderate or highly active, based on the GPAQ) and sex. Participants wore an accelerometer (Actigraph GT3X) for seven days and completed a GPAQ on Day 7. This protocol was repeated for a random sub-sample at a second time point, 3–6 months later. Analysis involved Wilcoxon-signed rank tests for differences in measures, Bland-Altman analysis for the agreement between measures for median MVPA and SB mins/day, and Spearman’s rho coefficient for criterion validity and extent of change.

95 participants completed baseline measurements (44 females, 51 males; mean age 44 years, (SD 14); measurements of change were calculated for 41 (21 females, 20 males; mean age 46 years, (SD 14). There was moderate agreement between GPAQ and accelerometer for MVPA mins/day (r = 0.48) and poor agreement for SB (r = 0.19). The absolute mean difference (self-report minus accelerometer) for MVPA was −0.8 mins/day and 348.7 mins/day for SB; and negative bias was found to exist, with those people who were more physically active over-reporting their level of MVPA: those who were more sedentary were less likely to under-report their level of SB. Results for agreement in change over time showed moderate correlation (r = 0.52, p = 0.12) for MVPA and poor correlation for SB (r = −0.024, p = 0.916).

Levels of agreement with objective measurements indicate the GPAQ is a valid measure of MVPA and change in MVPA but is a less valid measure of current levels and change in SB. Thus, GPAQ appears to be an appropriate measure for assessing the effectiveness of interventions to promote MVPA.

Using postal questionnaires to evaluate physical activity and diet behaviour change: case study exploring implications of valid responder characteristics in interpreting intervention outcomes.

Background: Patient reported outcome measures (PROMs) are used to evaluate lifestyle interventions but littleis known about differences between patients returning valid and invalid responses, or of potential for bias inevaluations. We aimed to examine the characteristics of patients who returned valid responses to lifestylequestionnaires compared to those whose responses were invalid for evaluating lifestyle change. 
Methods: We conducted a secondary data analysis from the SPHERE Study, a trial of an intervention to improveoutcomes for patients with coronary heart disease in primary care. Postal questionnaires were used to assessphysical activity (Godin) and diet (DINE) among study participants at baseline and 18 month follow-up. Three binaryresponse variables were generated for analysis: (1) valid Godin score; (2) valid DINE Fibre score; and (3) validDINE Total Fat score. Multivariate analysis comprised generalised estimating equation regression to examine theassociation of patients’ characteristics with their return of valid responses at both timepoints. 
Results: Overall, 92.1% of participants (832/903) returned questionnaires at both baseline and 18 months. Relativelyfewer valid Godin scores were returned by those who left school aged <15 years (36.5%) than aged 18 and over(50.5%), manual workers (39.5%) than non-manual (49.5%) and those with an elevated cholesterol (>5 mmol)(34.7%) than those with a lower cholesterol (44.4%) but multivariate analysis identified that only school leaving age(p = 0.047) was of statistical significance.Relatively fewer valid DINE scores were returned by manual than non-manual workers (fibre: 80.8% v 86.8%;fat: 71.2% v 80.0%), smokers (fibre: 72.6% v 84.7%; fat: 67.5% v 76.9%), patients with diabetes (fibre: 75.9% v 82.9%;fat: 66.9% v 75.8%) and those with cholesterol >5 mmol (fat: 68.2% v 76.2%) but multivariate analysis showedstatistical significance only for smoking (fibre: p = 0.013; fat: p = 0.045), diabetes (fibre: p = 0.039; fat: p = 0.047), andcholesterol (fat: p = 0.039). 
Conclusions: Our findings illustrate the importance of detailed reporting of research methods, with clearinformation about response rates, respondents and valid outcome data. Outcome measures which are relevant to astudy population should be chosen carefully. The impact of methods of outcome measurement and valid responserates in evaluating healthcare requires further study.

Activity and coke formation of nickel and nickel carbide in dry reforming: A deactivation scheme from density functional theory

Dry reforming is a promising reaction to utilise the greenhouse gases CO2 and CH4. Nickel-based catalysts are the most popular catalysts for the reaction, and the coke formation on the catalysts is the main obstacle to the commercialisation of dry reforming. In this study, the whole reaction network of dry reformation on both flat and stepped nickel catalysts (Ni(111) and Ni(211)) as well as nickel carbide (flat: Ni3C(001); stepped: Ni3C(111)) is investigated using density functional theory calculations. The overall reaction energy profiles in the free energy landscape are obtained, and kinetic analyses are utilised to evaluate the activity of the four surfaces. By careful examination of our results, we find the following regarding the activity: (i) flat surfaces are more active than stepped surfaces for the dry reforming and (ii) metallic nickel catalysts are more active than those of nickel carbide, and therefore, the phase transformation from nickel to nickel carbide will reduce the activity. With respect to the coke formation, the following is found: (i) the coke formation probability can be measured by the rate ratio of CH oxidation pathway to C oxidation pathway (r(CH)/r(C)) and the barrier of CO dissociation, (ii) on Ni(111), the coke is unlikely to form, and (iii) the coke formations on the stepped surfaces of both nickel and nickel carbide can readily occur. A deactivation scheme, using which experimental results can be rationalised, is proposed. 

The nitric oxide ISO photocatalytic reactor system: Measurement of NOx removal activity and capacity

Although the NO removal-based air-purification ISO method ISO 22197-1:2007 is well established, its preconditioning requirements mean that only the initial activity of the photocatalyst under test is measured owing to the often-reported, gradual alteration of the surface kinetics for NO oxidation by air through the accumulation of surface HNO3. Herein, we compare the photocatalytic NO removal abilities of a number of different, common TiO2 materials, surface-saturated with photogenerated HNO3, with their behaviours observed during the typical 5 h-long ISO standard test. It is found that all the TiO2 materials studied eventually become largely NO to NO2 converters after sufficient exposure to NO under irradiation (>5 h) due to the accumulation of surface HNO3. The UV exposure time, t*, necessary to reach this HNO3 saturated condition is different for each different catalyst. As a consequence, an alternative preconditioning process for the ISO method is proposed which can be used to provide a more realistic measure of the photocatalytic activity of the underlying material and provide a measure of the NOx removing capacity of the photocatalytic material under test.

Physical activity and sport participation for people with long-term illness

Purpose:Physical activity is recommended for optimal prevention of cardiovascular disease(CVD) and participation in sport is associated with improved well-being. However, people with long-standing illness/disability are less likely to participate in sport than others. Evidence of factors associated with their participation is limited and the best approach to encourage participation is unknown. This study aimed to identify sport participation levels and their correlates, among adults with long standing illness/disability in Northern Ireland, where CVD prevalence is high. Method:Using routinely collected data in annual surveys of population samples from 2007 to 2011, descriptive statistics were derived. Chi-squared tests were used to compare characteristics of those with a long-term illness/disability and those without long-term health problems. Uni-variate binary regression analysis for the whole sample and those with a long-standing illness/disability, using sport participation as the dependent variable, was performed and variables with a p-value of 0.1 or less were taken into a multi-variate analysis. Results:The sample included 13,683 adults; 3550(26%) reported having long-term illness/disability. Fewer of those with, than without, long-term illness/disability reported sport participation in the previous year (868/3550(24.5%) v 5615/10133(55.6%)). Multi-variate analysis showed that, for those with long-standing illness/disability, being single and less socio-economically deprived correlated positively with sport participation. For both those with long-standing illness/disability and the full sample, sport participation correlated positively with being male, aged <56 years, access to a household car/van, sports club membership, health ‘fairly good’ or ‘good’ in the previous year, doing paid/unpaid work, and living in an urban location. For the full sample but not those with long-standing illness/disability, sport participation correlated positively with being a non-smoker, higher educational status and personal internet access. Of note, personal internet access was less for those with, than without, long-term illness/disability (41% v 70%). Conclusions:Efforts to promote physical activity in sport for those with long-standing illness/disability should target older people, married females, those who live rurally, and those who are socio-economically deprived and report their health as ‘not good’. Implementation of initiatives should not rely on the internet, to which these people may not have ready access, to help support their sport participation and physical activity in optimal CVD prevention.

Importance of surface carbide formation on the activity and selectivity of Pd surfaces in the selective hydrogenation of acetylene

A recent experimental investigation (Kim et al. J. Catal. 306 (2013) 146-154) on the selective hydrogenation of acetylene over Pd nanoparticles with different shapes concluded that Pd(100) showed higher activity and selectivity than Pd(111) for acetylene hydrogenation. However, our recent density functional calculations (Yang et al. J. Catal. 305 (2013) 264-276) observed that the clean Pd(111) surface should result in higher activity and ethylene selectivity compared with the clean Pd(100) surface for acetylene hydrogenation. In the current work, using density functional theory calculations, we find that Pd(100) in the carbide form gives rise to higher activity and selectivity than Pd(111) carbide. These results indicate that the catalyst surface is most likely in the carbide form under the experimental reaction conditions. Furthermore, the adsorption energies of hydrogen atoms as a function of the hydrogen coverage at the surface and subsurface sites over Pd(100) are compared with those over Pd(111), and it is found that the adsorption of hydrogen atoms is always less favoured on Pd(100) over the whole coverage range. This suggests that the Pd(100) hydride surface will be less stable than the Pd(111) hydride surface, which is also in accordance with the experimental results reported.

The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models

Colorectal cancer is the second most common cause of cancer-related death in the United States. Recent studies showed that interleukin-8 (IL-8) and its receptors (CXCR1 and CXCR2) are significantly upregulated in both the tumor and its microenvironment, and act as key regulators of proliferation, angiogenesis, and metastasis. Our previous study showed that IL-8 overexpression in colorectal cancer cells triggers the upregulation of the CXCR2-mediated proliferative pathway. The aim of this study was to investigate whether the CXCR2 antagonist, SCH-527123, inhibits colorectal cancer proliferation and if it can sensitize colorectal cancer cells to oxaliplatin both in vitro and in vivo. SCH-527123 showed concentration-dependent antiproliferative effects in HCT116, Caco2, and their respective IL-8-overexpressing variants colorectal cancer cell lines. Moreover, SCH-527123 was able to suppress CXCR2-mediated signal transduction as shown through decreased phosphorylation of the NF-κB/mitogen-activated protein kinase (MAPK)/AKT pathway. These findings corresponded with decreased cell migration and invasion, while increased apoptosis in colorectal cancer cell lines. In vivo results verified that SCH-527123 treatment decreased tumor growth and microvessel density when compared with vehicle-treated tumors. Importantly, these preclinical studies showed that the combination of SCH-527123 and oxaliplatin resulted in a greater decrease in cell proliferation, tumor growth, apoptosis, and angiogenesis that was superior to single-agent treatment. Taken together, these findings suggest that targeting CXCR2 may block tumor proliferation, migration, invasion, and angiogenesis. In addition, CXCR2 blockade may further sensitize colorectal cancer to oxaliplatin treatment.

A Correlation Between Host Star Activity and Planet Mass for Close-in Extrasolar Planets?

The activity levels of stars are influenced by several stellar properties, such as stellar rotation, spectral type, and the presence of stellar companions. Analogous to binaries, planetary companions are also thought to be able to cause higher activity levels in their host stars, although at lower levels. Especially in X-rays, such influences are hard to detect because coronae of cool stars exhibit a considerable amount of intrinsic variability. Recently, a correlation between the mass of close-in exoplanets and their host star's X-ray luminosity has been detected, based on archival X-ray data from the ROSAT All-Sky Survey. This finding has been interpreted as evidence for star-planet interactions. We show in our analysis that this correlation is caused by selection effects due to the flux limit of the X-ray data used and due to the intrinsic planet detectability of the radial velocity method, and thus does not trace possible planet-induced effects. We also show that the correlation is not present in a corresponding complete sample derived from combined XMM-Newton and ROSAT data.

Associations between near work, outdoor activity, and myopia among adolescent students in rural China: the Xichang Pediatric Refractive Error Study report no. 2.

OBJECTIVE:

To study the associations between near work, outdoor activity, and myopia among children attending secondary school in rural China.

METHODS:

Among a random cluster sample of 1892 children in Xichang, China, subjects with an uncorrected acuity of 6/12 or less in either eye (n = 984) and a 25% sample of children with normal vision (n = 248) underwent measurement of refractive error. Subjects were administered a questionnaire on parental education, time spent outdoors, and weekly time spent engaged in and preferred working distance for a variety of near-work activities.

RESULTS:

Among 1232 children with refraction data, 998 (81.0%) completed the near-work survey. Their mean age was 14.6 years (SD, 0.8 years), 55.6% were girls, and 83.1% had myopia of -0.5 diopters or less (more myopia) in both eyes. Time and diopter-hours spent on near activities did not differ between children with and without myopia. In regression models, time spent on near activities and time outdoors were unassociated with myopia, adjusting for age, sex, and parental education.

CONCLUSIONS:

These and other recent results raise some doubts about the association between near work and myopia. Additional efforts to identify other environmental factors associated with myopia risk and that may be amenable to intervention are warranted.

Intentions Toward Physical Activity and Resting Behavior in Pregnant Women: Using the Theory of Planned Behavior Framework in a Cross-Sectional Study

BACKGROUND: Pregnant women are recommended to 1) perform daily moderate-intensity physical activity and 2) limit the amount of sedentary time. Many women do not meet these recommendations. Reduced physical activity and increased sedentary behavior may result from women actively intending to rest during pregnancy. The Theory of Planned Behavior (TPB) has been used to assess attitudes (e.g., positive/negative beliefs), subjective norms (e.g., perception of others' views), perceived behavioral control (PBC) (e.g., self-efficacy), and intention toward exercising while pregnant but has not been applied to aspects pertaining to resting during pregnancy.

METHODS: Pregnant women (n = 345) completed a cross-sectional questionnaire that included two TPB Questionnaires where the target behaviors were 1) being physically active and 2) resting. Bootstrapped paired t tests, ANOVA, and linear hierarchal regression analyses were performed to identify predictors of intentions and whether intentions toward the two behaviors varied at different stages of pregnancy.

RESULTS: As women progressed in their pregnancy, their attitude, PBC, and intention toward being physically active all significantly declined. A positive attitude, subjective norms, and intention toward resting all significantly increased with the advancing trimester. Self-reported health conditions predicted lower intention for physical activity but not for resting.

DISCUSSION: The significantly inverse relationship between physical activity and resting across time suggests that women feel they should focus on one behavior at the expense of the other. Finding that women generally do not perceive these behaviors as mutually compatible has implications in strategizing as to how to encourage women to be active during pregnancy.