Commentary: Fish and the thyroid: A Janus Bifrons relationship caused by pollutants and the omega-3 polyunsaturated fatty acids

We read with interest the paper published in the journal by Benvenga S, et al. about the complex interplay between thyroid disorders and the intake of omega-3 polyunsaturated fatty acids (PUFAs), whose main dietary source is represented by fish. In their review, Benvenga et al. put a specific warning on the potential heavy metal content in fish and the risks deriving from its consumption, suggesting that there would be the place for the use of nutraceuticals containing omega-3 PUFAs to prevent or contrast autoimmune thyroiditis, overcoming the risk of contaminants in fish. Although pharmacological supplementation would be sometimes useful, also limiting dietary consumption to fishes containing low levels of pollutants and including fish within the framework of a healthy diet represent a good choice

Tyrosine kinase inhibitors for the therapy of anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC) is often incurable so new therapeutic approaches are needed. Tyrosine kinases inhibitors (such as imanitib, sunitinib or sorafenib) are under evaluation for the treatment of ATC. Other vascular disrupting agents, such as combretastatin A4 phosphate, and antiangiogenic agents, such as aplidin, PTK787/ZK222584 and human VEGF monoclonal antibodies (bevacizumab, cetuximab), have been evaluated. Small-molecule adenosine triphosphate competitive inhibitors directed intracellularly at EGFRs tyrosine kinase, such as erlotinib or gefitinib, are also studied. Furthermore, new molecules have been shown to be active against ATC, such as CLM94 and CLM3. However, more research is needed to finally identify therapies able to control and to cure this disease

The Influence of Food Regimes on Oxidative Stress: A Permutation-Based Approach Using the NPC Test

(1) Background: This paper aims to assess the existence of significant differences between two dietary regimes (omnivorous vs. semi-vegetarian) with reference to some oxidative stress markers (SOD, GPx, TRxR, GR, AGEs, and AOPPs) using non-parametric combination methodology based on a permutation test. (2) Methods: At the endocrinology unit of Messina University Hospital, two hundred subjects were asked to fill out a questionnaire about their dietary habits. None were under any pharmacological treatment. Using the NPC test, all comparisons were performed stratifying patients according to gender, age (≤40 or >40 years), BMI (normal weight vs. overweight), physical activity (sedentary vs. active lifestyle), TSH, FT4 levels in quartiles, and diagnosis of Hashimoto’s thyroiditis. We evaluated differences in oxidative stress parameters in relation to two examined dietary regimes (omnivorous vs. semi-vegetarian). (3) Results: The antioxidant parameters GPx and TRxR were significantly lower in subjects with an omnivorous diet than in semi-vegetarians, particularly in females, both age groups, subjects with normal weight, those not affected by Hashimoto’s thyroiditis, and both the sedentary and active lifestyle groups. Finally, the AGE and AOPP markers were significantly lower in semi-vegetarians. (4) Conclusion: Thanks to the NPC methodology, we can state that dietary patterns exert a significant influence on some oxidative stress parameters

Association of treatment satisfaction and psychopathological sub-syndromes among involuntary patients with psychotic disorders

Publisher's version: http://www.springerlink.com/content/rx24036274667t10

Lack of Support for the Genes by Early Environment Interaction Hypothesis in the Pathogenesis of Schizophrenia

Ursini et al reported recently that the liability of schizophrenia explained by a polygenic risk score (PRS) derived from the variants most associated with schizophrenia was increased 5-fold in individuals who experienced complications during pregnancy or birth. Follow-up gene expression analysis showed that the genes mapping to the most associated genetic variants are highly expressed in placental tissues. If confirmed, these findings will have major implications in our understanding of the joint effect of genes and environment in the pathogenesis of schizophrenia. We examined the interplay between PRS and obstetric complications (OCs) in 5 independent samples (effective N = 2110). OCs were assessed with the full or modified Lewis-Murray scale, or with birth weight < 2.5 kg as a proxy. In a large cohort we tested whether the pathways from placenta-relevant variants in the original report were associated with case-control status. Unlike in the original study, we did not find significant effect of PRS on the presence of OCs in cases, nor a substantial difference in the association of PRS with case-control status in samples stratified by the presence of OCs. Furthermore, none of the PRS by OCs interactions were significant, nor were any of the biological pathways, examined in the Swedish cohort. Our study could not support the hypothesis of a mediating effect of placenta biology in the pathway from genes to schizophrenia. Methodology differences, in particular the different scales measuring OCs, as well as power constraints for interaction analyses in both studies, may explain this discrepancy

Implications of Training in Incremental Theories of Intelligence for Undergraduate Statistics Students

This chapter documents the effects of training in incremental theories of intelligence on students in introductory statistics courses at a liberal arts university in the US. Incremental theories of intelligence examine the beliefs individuals hold of knowledge and how it is attained. An individual with an incremental theory of intelligence believes that intelligence can be developed. The research examined differences by gender in mastery of statistics and attitudes toward statistics for students who received growth mind-set training. A pre-test, post-test design utilised the Students’ Attitudes Toward Statistics© instrument and the Comprehensive Assessment of Outcomes in a first Statistics course. An ANCOVA revealed that females gained more than males on their value of statistics (F(1, 63) 9.40, MSE 3.79, p .003, η2 P 0.134) and decreased less for effort expended to learn statistics (F(1, 63) 4.41, MSE 4.07, p .040, η2 P 0.067). Females also gained mastery of statistical concepts at a greater rate (F(1, 63) 5.30, MSE 0.06, p .025, η2 P 0.080) indicating a possible path to alleviate the under-representation of females in STEM

Consequences Of On-Track Competition In Railways By Use Of Simulations

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Cleavage of von Willebrand Factor by Granzyme M Destroys Its Factor VIII Binding Capacity

Von Willebrand factor (VWF) is a pro-hemostatic multimeric plasma protein that promotes platelet aggregation and stabilizes coagulation factor VIII (FVIII) in plasma. The metalloproteinase ADAMTS13 regulates the platelet aggregation function of VWF via proteolysis. Severe deficiency of ADAMTS13 is associated with thrombotic thrombocytopenic purpura, but does not always correlate with its clinical course. Therefore, other proteases could also be important in regulating VWF activity. In the present study, we demonstrate that VWF is cleaved by the cytotoxic lymphocyte granule component granzyme M (GrM). GrM cleaved both denaturated and soluble plasma-derived VWF after Leu at position 276 in the D3 domain. GrM is unique in that it did not affect the multimeric size and pro-hemostatic platelet aggregation ability of VWF, but instead destroyed the binding of VWF to FVIII in vitro. In meningococcal sepsis patients, we found increased plasma GrM levels that positively correlated with an increased plasma VWF/FVIII ratio in vivo. We conclude that, next to its intracellular role in triggering apoptosis, GrM also exists extracellularly in plasma where it could play a physiological role in controlling blood coagulation by determining plasma FVIII levels via proteolytic processing of its carrier VWF

Granular Assembly of α-Synuclein Leading to the Accelerated Amyloid Fibril Formation with Shear Stress

α-Synuclein participates in the Lewy body formation of Parkinson's disease. Elucidation of the underlying molecular mechanism of the amyloid fibril formation is crucial not only to develop a controlling strategy toward the disease, but also to apply the protein fibrils for future biotechnology. Discernable homogeneous granules of α-synuclein composed of approximately 11 monomers in average were isolated in the middle of a lag phase during the in vitro fibrillation process. They were demonstrated to experience almost instantaneous fibrillation during a single 12-min centrifugal membrane-filtration at 14,000×g. The granular assembly leading to the drastically accelerated fibril formation was demonstrated to be a result of the physical influence of shear force imposed on the preformed granular structures by either centrifugal filtration or rheometer. Structural rearrangement of the preformed oligomomeric structures is attributable for the suprastructure formation in which the granules act as a growing unit for the fibril formation. To parallel the prevailing notion of nucleation-dependent amyloidosis, we propose a double-concerted fibrillation model as one of the mechanisms to explain the in vitro fibrillation of α-synuclein, in which two consecutive concerted associations of monomers and subsequent oligomeric granular species are responsible for the eventual amyloid fibril formation

Challenges to undertaking randomised trials with looked after children in social care settings.

BACKGROUND: Randomised controlled trials (RCTs) are widely viewed as the gold standard for assessing effectiveness in health research; however many researchers and practitioners believe that RCTs are inappropriate and un-doable in social care settings, particularly in relation to looked after children. The aim of this article is to describe the challenges faced in conducting a pilot study and phase II RCT of a peer mentoring intervention to reduce teenage pregnancy in looked after children in a social care setting. METHODS: Interviews were undertaken with social care professionals and looked after children, and a survey conducted with looked after children, to establish the feasibility and acceptability of the intervention and research design. RESULTS: Barriers to recruitment and in managing the intervention were identified, including social workers acting as informal gatekeepers; social workers concerns and misconceptions about the recruitment criteria and the need for and purpose of randomisation; resource limitations, which made it difficult to prioritise research over other demands on their time and difficulties in engaging and retaining looked after children in the study. CONCLUSIONS: The relative absence of a research infrastructure and culture in social care and the lack of research support funding available for social care agencies, compared to health organisations, has implications for increasing evidence-based practice in social care settings, particularly in this very vulnerable group of young people