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Cannabidiol (CBD) is a non-psychoactive cannabinoid purported to reduce symptoms of discomfort. Individuals are now using CBD to treat symptoms of multiple sclerosis, seizures, and chronic pain. Animal models indicate that CBD may be effective at reducing inflammation post fatiguing exercise. However, little evidence is available to evaluate these findings in humans. Therefore, the purpose of this investigation was to evaluate the impact of two doses of CBD oil on inflammation (IL-6), performance, and pain after an eccentric loading protocol. Participants (n = 4) participated in three conditions (placebo, low dose, and high dose), in this randomized, counterbalanced design. Each condition took 72 hours to complete, with a 1-week washout period between conditions. At the beginning of each week, participants were subjected to a loading protocol of six sets of ten eccentric only repetitions in the single-arm bicep curl. Participants consumed capsules of either a placebo, low dose (2mg/kg) or high dose (10mg/kg) of CBD oil immediately following the session and continued every twelve hours for 48 hours. Venipunctures were taken before exercise and repeated at 24, 48, and 72 hours post exercise. Blood samples were centrifuged for 15 minutes in gel and lithium heparin vacutainers. Plasma was separated from cells and stored at −80° until analysis. Samples were analyzed using an immunometric assay for IL-6 (ELISA). Data were analyzed using a three (condition) by four (time) repeated measure ANOVA. There were no differences in inflammation between conditions (F(2,6) = 0.726, p = 0.522, n(p)(2) = 0.195) or across time (F(3,9) = 0.752, p = 0.548, n(p)(2) = 0.200), handgrip strength between conditions (F(2,6) = 0.542, p = 0.607, n(p)(2) = .153) or across time (F(3,9) = 2.235, p = .153, n(p)(2) = .427), or bicep curl strength between conditions (F(2,6) = 0.675, p = 0.554, n(p)(2) = .184) or across time (F(3,9) = 3.513, p = .150, n(p)(2) = .539). There were no differences in pain between conditions (F(2,6) = 0.495, p = 0.633, n(p)(2) = .142), but there was a difference across time (F(3,9) = 7.028, p = .010, n(p)(2) = .701). There were no significant interactions to note. Although there was no statistical significance between conditions (likely due to the low sample size), there was a visible increase in IL-6 48 (4.88 ± 6.53) and 72 hours (3.12 ± 4.26) post exercise in the placebo condition which was not observed in the low (48: 0.35 ± 2.22; 72: 1.34 ± 5.6) and high dose condition (48: 1.34 ± 1.34; 72: −0.79 ± 5.34). Future investigations should consider implementing eccentric resistance training across a larger portion of the body to improve ecological validity of the exercise. A larger sample would reduce risk of researchers committing a type II statistical error and give strength to detecting differences between conditions.

In this article, the solution to the elasticity boundary-value problem for an infinitesimally thin dilatational disk (ITDD) embedded in an elastically isotropic half-space is presented. The plane of the disk is parallel to the free surface. To solve the boundary value problem, the method of virtual defects is used. The image (mirror) ITDD and radial Somigliana dislocation loops (RSDLs), distributed continuously over the free surface coaxially with the ITDD, are chosen as virtual defects. The ITDD displacements, strains, and stresses are represented in the form of the sums of the Lipschitz - Hankel integrals. It is shown that the elastic field of the ITDD disk is distorted near the free surface and possesses nonzero dilatation and hydrostatic stress. Numerical estimates of dilatation are given and its influence on some characteristics of semiconductors is briefly discussed.

The original version of this Article omitted a declaration from the competing interests statement, which should have included the following: ‘One of the authors, Y.L., is an editor on the staff of Nature Communications, but was not in any way involved in the journal review process. The other authors declare no competing interests’. This has now been corrected in both the PDF and HTML versions of the Article.

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Item does not contain fulltext Glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of noxious agents. Genes encoding for GSTA1, GSTP1, GSTT1, and GSTM1 proteins are polymorphic in humans, which can result in (partial) loss of enzyme activity. Previous epidemiologic studies have associated dysfunction of these GST genes with a higher risk of cancer, but this is still controversial. The aim of this study was to investigate the susceptibility to gastric cancer in relation to the above-mentioned GST polymorphisms. Patients visiting the Can Tho General Hospital in Vietnam between January 2004 and August 2004 for upper gastrointestinal endoscopy, who were diagnosed with gastric cancer, were compared with a control group of endoscoped dyspepsia patients with no history of malignancy. Genotypes of the GSTs mentioned above were assessed by multiplex PCR. Fifty-nine patients with gastric cancer (mean age: 63 years, 80% males), and 109 dyspeptic controls (mean age: 46 years, 69% males) were included in this study. The frequencies of the combined heterozygote and homozygote mutant GSTA1 and GSTP1 genotypes were 10% and 48% in patients with gastric cancer versus 28% and 40% in dyspeptic controls, respectively. GSTT1 and GSTM1 were deleted in 42% and 73% of patients with gastric cancer and in 35% and 69% of the controls, respectively. The GSTA1 homozygous wild-type genotype was significantly more often present in patients with gastric cancer compared with controls (odds ratio 4.3, 95% CI 1.2-17), which was even more apparent after adjustment for age, gender, current smoking, current alcohol consumption, and polymorphisms in GSTP1, GSTT1, or GSTM1 (odds ratio 5.0, 95% CI 1.2-25). The present work shows that the homozygous wild-type GSTA1 genotype is associated with gastric cancer in a Vietnamese population, whereas there was no relationship with polymorphisms in GSTP1, GSTT1, or GSTM1.

Over 30% of ER? breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ER? binding. Here we demonstrate that PBX1 plays a central role in regulating the ER? transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ER? genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ER?-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ER?-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ER?-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ER?-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ER?-positive breast cancer.

The use of efficient early warning bioindication systems represents a powerful approach for assessing and interpreting the impact of natural or anthropogenic perturbations in soil ecosystems preventing environmental alteration and human disease. Living organisms provide information on the cumulative effects of environmental stressors and as such bioindication is complementary to direct physical and chemical measurements (Heger et al., 2012). Trifolium repens is a pollutant-sensitive plant, suitable for biomonitoring campaigns. Specifically, its environmental exposition followed by a DNA analysis with molecular markers allows the detection of sublethal levels of genotoxic compounds in the environment (Piraino et al., 2006). However, given the limited information available on the joint genotoxic-effect of chemicals, the interpretation of biomonitoring results is often difficult. There is then a clear need to improve the knowledge about the combined effects of stressors on bioindicators. Starting from these considerations, the objective of the first part of my PhD research was to study the combined toxic and genotoxic effects of soil Cd and As, two of the most dangerous compounds for both environment and human health, whose joint action is still unknown. The results that I obtained showed that individual and joint toxicity and genotoxicity were related to the concentration of Cd and As measured in plant organs and that As concentration was the most relevant variable. Joint effects on plant growth were additive or synergistic, whereas joint genotoxic effects were additive or antagonistic. The interaction between Cd and As occurred at both soil and plant level. in soil the presence of As limited the bioavailability of Cd, whereas the presence of Cd increased the bioavailability of As. Nevertheless only the As biovailability was linearly correlated with the amount of As absorbed by plants. These results revealed that the simultaneous presence in soil of Cd and As, although producing an additive or synergistic toxic effect on Trifolium repens L. growth, generates a lower DNA damage. I have supposed that growth reduction was due to both toxic effects of Cd and As and to plant response to the high DNA damage, which led to a temporary arrest of cell cycle providing a longer time for DNA repair and for free radical scavenger production. This would be consistent with the antagonistic genotoxic effect that I observed in most of the combined treatments. Nevertheless I am also aware that the antagonistic interaction of Cd and As that I observed can be also associated to the similar genotoxic mechanisms own of the two metal(loid)s. In the second part of my PhD, I used the information and the techniques that I learned during the first period to assess the genotoxicity of soils in Lombardy Region (Italy). I analyzed a total of 67 samples of surface soil (0-30 cm in depth) which were collected in 7 different agricultural areas of concern, within Lombardy region. Results showed that in general soils did not affect the survival of the test plants, excepted for the soils CR3 and CR6 (from the area of Treviglio) and O1 (from the Origgio area). Furthermore, no statistically significant change was observed in the growth of seedlings (measured in terms of dry weight), except for some soils from the Treviglio area (CR2, CR3, CR6 and CR14) and for IT5 soil from the Broni area (PV). The other soils from this last area, although induced a reduction of root growth, were considered not potentially toxic as the shoot growth of the text plants was not affected and the soil characteristics were not appropriate for white clover development. Regarding the soil genotoxicity, all soils except those from Broni area were found to contain genotoxic bioavailable compounds and were classified as "moderately genotoxic”.

This study was undertaken to investigate combined toxic and genotoxic effects of cadmium (Cd) and arsenic (As) on white clover, a pollutant sensitive plant frequently used as environmental bioindicator. Plants were exposed to soil spiked with increasing concentrations of cadmium sulfate (20, 40 and 60 mg Kg 21 ) or sodium arsenite (5, 10 and 20 mg Kg 21 ) as well as with their combinations. Metal(loid) bioavailability was assessed after soil contamination, whereas plant growth, metal(loid) concentration in plant organs and DNA damage were measured at the end of plant exposition. Results showed that individual and joint toxicity and genotoxicity were related to the concentration of Cd and As measured in plant organs, and that As concentration was the most relevant variable. Joint effects on plant growth were additive or synergistic, whereas joint genotoxic effects were additive or antagonistic. The interaction between Cd and As occurred at both soil and plant level. In soil the presence of As limited the bioavailability of Cd, whereas the presence of Cd increased the bioavailability of As. Nevertheless only As biovailability determined the amount of As absorbed by plants. The amount of Cd absorbed by plant was not linearly correlated with the fraction of bioavailable Cd in soil suggesting the involvement of additional factors, such as plant uptake mechanisms. These results reveal that the simultaneous presence in soil of Cd and As, although producing an additive or synergistic toxic effect on Trifolium repens L. growth, generates a lower DNA damage.