Influence of hyperhomocysteinemia on the cellular redox state - Impact on homocysteine-induced endothelial dysfunction

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteines deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation. The resultant increase in superoxide levels is further amplified by homocysteinedependent alterations in the function of cellular antioxidant enzymes such as cellular glutathione peroxidase or extracellular superoxide dismutase. One direct clinical consequence of elevated vascular superoxide levels is the inactivation of the vasorelaxant messenger nitric oxide, leading to endothelial dysfunction. Scavenging of superoxide anion by either superoxide dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings incubated with homocysteine. Similarly, homocysteineinduced endothelial dysfunction is also reversed by increasing the concentration of the endogenous antioxidant glutathione or overexpressing cellular glutathione peroxidase in animal models of mild hyperhomocysteinemia. Taken together, these findings strongly suggest that the adverse vascular effects of homocysteine are at least partly mediated by oxidative inactivation of nitric oxide

A hysteretic multiscale formulation for validating computational models of heterogeneous structures

A framework for the development of accurate yet computationally efficient numerical models is proposed in this work, within the context of computational model validation. The accelerated computation achieved herein relies on the implementation of a recently derived multiscale finite element formulation, able to alternate between scales of different complexity. In such a scheme, the micro-scale is modelled using a hysteretic finite elements formulation. In the micro-level, nonlinearity is captured via a set of additional hysteretic degrees of freedom compactly described by an appropriate hysteric law, which gravely simplifies the dynamic analysis task. The computational efficiency of the scheme is rooted in the interaction between the micro- and a macro-mesh level, defined through suitable interpolation fields that map the finer mesh displacement field to the coarser mesh displacement field. Furthermore, damage related phenomena that are manifested at the micro-level are accounted for, using a set of additional evolution equations corresponding to the stiffness degradation and strength deterioration of the underlying material. The developed modelling approach is utilized for the purpose of model validation; firstly, in the context of reliability analysis; and secondly, within an inverse problem formulation where the identification of constitutive parameters via availability of acceleration response data is sought

Reconstructing ‘the Alcoholic’: Recovering from Alcohol Addiction and the Stigma this Entails

Public perception of alcohol addiction is frequently negative, whilst an important part of recovery is the construction of a positive sense of self. In order to explore how this might be achieved, we investigated how those who self-identify as in recovery from alcohol problems view themselves and their difficulties with alcohol and how they make sense of others’ responses to their addiction. Semi-structured interviews with six individuals who had been in recovery between 5 and 35 years and in contact with Alcoholics Anonymous were analysed using Interpretative Phenomenological Analysis. The participants were acutely aware of stigmatising images of ‘alcoholics’ and described having struggled with a considerable dilemma in accepting this identity themselves. However, to some extent they were able to resist stigma by conceiving of an ‘aware alcoholic self’ which was divorced from their previously unaware self and formed the basis for a new more knowing and valued identity

Pathways and Management of Phosphorus in urban areas

Due to the finite nature of mineral phosphorus reserves, effective management of anthropogenic phosphorus flows is currently under investigation by the international research community. This article emphasizes the importance of urban phosphorus flows, which are often marginalized due to the greater magnitude of agricultural phosphorus flows. A study on phosphorus flows in Gothenburg, Sweden, points out the potential role of solid waste in nutrient management, as the amounts of phosphorus in solid waste and in wastewater were found to be equal. Importation of food commodities accounts for 50% of the total inflow of phosphorus, and food waste is a major contributor of phosphorus to solid waste. The results suggest that solid waste incineration residues represent a large underestimated sink of phosphorus. Focusing on wastewater as the sole source of recovered phosphorus is not sufficient. The Swedish national goal on phosphorus recycling, which is limited to sewage sludge, targets only a part of the total phosphorus flow that can potentially be recovered. In contrast to previous studies, agricultural flows in Gothenburg were marginal compared to flows related to the urban waste management infrastructure. We emphasize the need for debate on preferable routes for disposal of waste with a high phosphorus content. Both recovery potential and usefulness of the recovered product for agricultural purposes have to be considered. Impacts of five waste management strategies on phosphorus flows were evaluated: incineration of all the waste, comprehensive food waste separation, installation of kitchen grinders, urine diversion, and separation of blackwater and food waste

The effect of past use of oral contraceptive on bone mineral density, bone biochemical markers and muscle strength in healthy pre and post menopausal women

<p>Abstract</p> <p>Background</p> <p>during adulthood, most studies have reported that oral contraceptive (OC) pills had neutral, or possibly beneficial effect on bone health. We proposed this study of pre and post menopausal women assessing BMD, bone biochemical markers and physical performance among OC past users and comparable women who have never use Ocs.</p> <p>Methods</p> <p>A cross-sectional study comparing the bone density, bone biochemical markers (osteocalcin, CTX) and three measures to assess physical performance: timed get-up-and-go test "TGUG", five-times-sit-to-stand test "5 TSTS" and 8-feet speed walk "8 FSW" of users and never users OC. We were recruited 210 women who used OC for at least 2 years with that of 200 nonusers was carried out in pre and postmenopausal women (24-86 years).</p> <p>Results</p> <p>when analysing the whole population, BMD and biochemical markers values were similar for Ocs past users and control subjects. However when analysing the subgroup of premenopausal women, there was a statistically significant difference between users and never-users in osteocalcin (15,5 ± 7 ng/ml vs 21,6 ± 9 ng/ml; p = 0,003) and CTX (0,30 ± 0,1 ng/ml vs 0,41 ± 0,2 ng/ml; p = 0,025). This difference persisted after adjustment for age, BMI, age at menarche and number of pregnancies. In contrast, in post menopausal women, there was no difference in bone biochemical markers between OC users and the control. On the other hand OC past users had a significant greater performance than did the never users group. And when analysing the physical performance tests by quartile OC duration we found a significant negative association between the three tests and the use of OC more than 10 years.</p> <p>Conclusion</p> <p>the funding show no evidence of a significant difference in BMD between Ocs users and never user control groups, a decrease in bone turn over in OC pre menopausal users and a greater physical performances in patients who used OC up than 10 years.</p

The "silver" Japanese quail and the MITF gene: causal mutation, associated traits and homology with the "blue" chicken plumage

<p>Abstract</p> <p>Background</p> <p>The <it>MITF </it>(<it>microphthalmia-associated transcription factor</it>) gene has been investigated in mice and various vertebrates but its variations and associated effects have not yet been explored much in birds. The present study describes the causal mutation <it>B </it>at the <it>MITF </it>gene responsible for the "silver" plumage colour in the Japanese quail (<it>Coturnix japonica</it>), and its associated effects on growth and body composition, and tests its allelism with the "blue" plumage colour mutation <it>Bl </it>in <it>Gallus gallus</it>.</p> <p>Results</p> <p>The semi dominant <it>B </it>mutation results from a premature stop codon caused by a 2 bp deletion in exon 11 of <it>MITF</it>. Homozygous "white" (<it>B/B</it>) quail which have a white plumage also show a slightly lower growth, lower body temperature, smaller heart, and lighter <it>pectoralis </it>muscles but more abdominal adipose tissue than the recessive homozygous "wild-type" (<it>+/+</it>) and heterozygous "silver" (<it>B/+</it>) quail. Similar observations on cardiac and body growth were made on mice (<it>Mus musculus</it>) homozygous for mutations at <it>MITF</it>. The production of chicken-quail hybrids with a white plumage obtained by crossing <it>Bl/+ </it>chicken heterozygous for the <it>blue </it>mutation with <it>B/B </it>white quail indicated that the mutations were allelic.</p> <p>Conclusion</p> <p>The "silver" Japanese quail is an interesting model for the comparative study of the effects of <it>MITF </it>in birds and mammals. Further investigation using a chicken family segregating for the "blue" plumage and molecular data will be needed to confirm if the "blue" plumage in chicken results from a mutation in <it>MITF</it>.</p

Cancer risks following diagnostic and therapeutic radiation exposure in children

The growing use of interventional and fluoroscopic imaging in children represents a tremendous benefit for the diagnosis and treatment of benign conditions. Along with the increasing use and complexity of these procedures comes concern about the cancer risk associated with ionizing radiation exposure to children. Children are considerably more sensitive to the carcinogenic effects of ionizing radiation than adults, and children have a longer life expectancy in which to express risk. Numerous epidemiologic cohort studies of childhood exposure to radiation for treatment of benign diseases have demonstrated radiation-related risks of cancer of the thyroid, breast, brain and skin, as well as leukemia. Many fewer studies have evaluated cancer risk following diagnostic radiation exposure in children. Although radiation dose for a single procedure might be low, pediatric patients often receive repeated examinations over time to evaluate their conditions, which could result in relatively high cumulative doses. Several cohort studies of girls and young women subjected to multiple diagnostic radiation exposures have been informative about increased mortality from breast cancer with increasing radiation dose, and case-control studies of childhood leukemia and postnatal diagnostic radiation exposure have suggested increased risks with an increasing number of examinations. Only two long-term follow-up studies of cancer following cardiac catheterization in childhood have been conducted, and neither reported an overall increased risk of cancer. Most cancers can be induced by radiation, and a linear dose-response has been noted for most solid cancers. Risks of radiation-related cancer are greatest for those exposed early in life, and these risks appear to persist throughout life

The gut microbiome in dogs with congestive heart failure: a pilot study

Compromised gut health and dysbiosis in people with heart failure has received a great deal of attention over the last decade. Whether dogs with heart failure have a similar dysbiosis pattern to what is described in people is currently unknown. We hypothesised that dogs with congestive heart failure have quantifiable dysbiosis compared to healthy dogs that are similar in sex and age. A total of 50 dogs (15 healthy dogs and 35 dogs with congestive heart failure) were prospectively recruited, and their faecal gut microbiome was assessed using 16S rRNA sequencing (Illumina MiSeq platform). There was no significant change in the microbial diversity and richness in dogs with congestive heart failure. However, there was an increase in abundance of Proteobacteria in the congestive heart failure group (p = 0.014), particularly due to an increase in the family Enterobacteriaceae (p = 0.002) and Escherichia coli (p = 0.033). We conclude that dogs with congestive heart failure have dysbiosis, and we show additional trends in our data suggesting that dogs may have a similar pattern to that described in people. The results of this study provide useful preliminary information and raise the possibility that dogs represent a clinically relevant animal model of dysbiosis in people with heart failure

A systematic evaluation of expression of HERV-W elements; influence of genomic context, viral structure and orientation

<p>Abstract</p> <p>Background</p> <p>One member of the W family of human endogenous retroviruses (HERV) appears to have been functionally adopted by the human host. Nevertheless, a highly diversified and regulated transcription from a range of HERV-W elements has been observed in human tissues and cells. Aberrant expression of members of this family has also been associated with human disease such as multiple sclerosis (MS) and schizophrenia. It is not known whether this broad expression of HERV-W elements represents transcriptional leakage or specific transcription initiated from the retroviral promoter in the long terminal repeat (LTR) region. Therefore, potential influences of genomic context, structure and orientation on the expression levels of individual HERV-W elements in normal human tissues were systematically investigated.</p> <p>Results</p> <p>Whereas intronic HERV-W elements with a pseudogene structure exhibited a strong anti-sense orientation bias, intronic elements with a proviral structure and solo LTRs did not. Although a highly variable expression across tissues and elements was observed, systematic effects of context, structure and orientation were also observed. Elements located in intronic regions appeared to be expressed at higher levels than elements located in intergenic regions. Intronic elements with proviral structures were expressed at higher levels than those elements bearing hallmarks of processed pseudogenes or solo LTRs. Relative to their corresponding genes, intronic elements integrated on the sense strand appeared to be transcribed at higher levels than those integrated on the anti-sense strand. Moreover, the expression of proviral elements appeared to be independent from that of their corresponding genes.</p> <p>Conclusions</p> <p>Intronic HERV-W provirus integrations on the sense strand appear to have elicited a weaker negative selection than pseudogene integrations of transcripts from such elements. Our current findings suggest that the previously observed diversified and tissue-specific expression of elements in the HERV-W family is the result of both directed transcription (involving both the LTR and internal sequence) and leaky transcription of HERV-W elements in normal human tissues.</p