Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B12 in kidney transplant recipients

Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B12 in kidney transplant recipients.BackgroundCurrently, no evidence is available on the putative associations between a novel single nucleotide polymorphism of the 5,10-methylenetetrahydrofolate reductase gene MTHFR 1793G>A and plasma levels of vitamin B12, folate, or total homocysteine (tHcy).MethodsIn a cross-sectional study of 730 kidney allograft recipients, patients were categorized by MTHFR 1793G>A genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B12, folate, and tHcy plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of MTHFR 1793G>A and these three dependent variables. As hypothesized in previous work, we specifically evaluated possible effect modification between the MTHFR 1793G>A and 1298A>C mutations on these outcomes.ResultsThe allele frequency for MTHFR 1793G>A was 0.052. Heterozygosity (N = 72) or homozygosity (N = 2) for MTHFR 1793G>A was not independently associated with plasma levels of vitamin B12 (P = 0.33) or tHcy (P = 0.70), but a borderline association with higher folate concentrations was detected (Δfolate = 1.91 nmol/L) (95% CI -0.03 to 3.86 nmol/L) (P = 0.05). Further, we found strong and significant positive interactions between the MTHFR 1793G>A and 1298A>C mutations on vitamin B12 concentrations.ConclusionHigher folate concentrations in kidney transplant recipients with MTHFR 1793GA or 1793AA and markedly higher concentrations of vitamin B12 in patients with combined MTHFR 1793G>A and 1298A>C mutations may contribute to the survival advantage that has been postulated for such patients showing these genotypes

Self-control in decision-making involves modulation of the vmPFC valuation system

Every day, individuals make dozens of choices between an alternative with higher overall value and a more tempting but ultimately inferior option. Optimal decision-making requires self-control. We propose two hypotheses about the neurobiology of self-control: (i) Goal-directed decisions have their basis in a common value signal encoded in ventromedial prefrontal cortex (vmPFC), and (ii) exercising self-control involves the modulation of this value signal by dorsolateral prefrontal cortex (DLPFC). We used functional magnetic resonance imaging to monitor brain activity while dieters engaged in real decisions about food consumption. Activity in vmPFC was correlated with goal values regardless of the amount of self-control. It incorporated both taste and health in self-controllers but only taste in non–self-controllers. Activity in DLPFC increased when subjects exercised self-control and correlated with activity in vmPFC

A Toy Model for Testing Finite Element Methods to Simulate Extreme-Mass-Ratio Binary Systems

Extreme mass ratio binary systems, binaries involving stellar mass objects orbiting massive black holes, are considered to be a primary source of gravitational radiation to be detected by the space-based interferometer LISA. The numerical modelling of these binary systems is extremely challenging because the scales involved expand over several orders of magnitude. One needs to handle large wavelength scales comparable to the size of the massive black hole and, at the same time, to resolve the scales in the vicinity of the small companion where radiation reaction effects play a crucial role. Adaptive finite element methods, in which quantitative control of errors is achieved automatically by finite element mesh adaptivity based on posteriori error estimation, are a natural choice that has great potential for achieving the high level of adaptivity required in these simulations. To demonstrate this, we present the results of simulations of a toy model, consisting of a point-like source orbiting a black hole under the action of a scalar gravitational field.Comment: 29 pages, 37 figures. RevTeX 4.0. Minor changes to match the published versio

Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy

Introduction: We reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells. / Methods: This study was a double-blind, randomized, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomized to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors. The primary end point was reduction of proteinuria. Secondary end points included change from baseline in estimated glomerular filtration rate (eGFR) and kidney histology. / Results: Although we could not detect significant reduction in proteinuria with fostamatinib overall, in a predetermined subgroup analysis, there was a trend for dose-dependent reduction in median proteinuria (from baseline to 24 weeks by 14%, 27%, and 36% in the placebo, fostamatinib 100 mg, and 150 mg groups, respectively) in patients with baseline urinary protein-to-creatinine ratios (UPCR) more than 1000 mg/g. Kidney function (eGFR) remained stable in all groups. Fostamatinib was well-tolerated. Side effects included diarrhea, hypertension, and increased liver enzymes. Thirty-nine patients underwent repeat biopsy showing reductions in SYK staining associated with therapy at low dose (−1.5 vs. 1.7 SYK+ cells/glomerulus in the placebo group, P < 0.05). / Conclusions: There was a trend toward reduction in proteinuria with fostamatinib in a predefined analysis of high risk patients with IgAN despite maximal care, as defined by baseline UPCR greater than 1000 mg/g. Further study may be warranted

Effects of common haplotypes of the ileal sodium dependent bile acid transporter gene on the development of sporadic and familial colorectal cancer: A case control study

<p>Abstract</p> <p>Background</p> <p>The genetics of sporadic and non-syndromic familial colorectal cancer (CRC) is not well defined. However, genetic factors that promote the development of precursor lesions, i.e. adenomas, might also predispose to CRC. Recently, an association of colorectal adenoma with two variants (c.507C>T;p.L169L and c.511G>T;p.A171S) of the ileal sodium dependent bile acid transporter gene (<it>SLC10A2</it>) has been reported. Here, we reconstructed haplotypes of the <it>SLC10A2 </it>gene locus and tested for association with non-syndromic familial and sporadic CRC compared to 'hyper-normal' controls who displayed no colorectal polyps on screening colonoscopy.</p> <p>Methods</p> <p>We included 150 patients with sporadic CRC, 93 patients with familial CRC but exclusion of familial adenomatous polyposis and Lynch's syndrome, and 204 'hyper-normal' controls. Haplotype-tagging <it>SLC10A2 </it>gene variants were identified in the Hapmap database and genotyped using PCR-based 5' exonuclease assays with fluorescent dye-labelled probes. Haplotypes were reconstructed using the PHASE algorithm. Association testing was performed with both SNPs and reconstructed haplotypes.</p> <p>Results</p> <p>Minor allele frequencies of all <it>SLC10A2 </it>polymorphisms are within previously reported ranges, and no deviations from Hardy-Weinberg equilibrium are observed. However, we found no association with any of the <it>SLC10A2 </it>haplotypes with sporadic or familial CRC in our samples (all P values > 0.05).</p> <p>Conclusion</p> <p>Common variants of the <it>SLC10A2 </it>gene are not associated with sporadic or familial CRC. Hence, albeit this gene might be associated with early stages of colorectal neoplasia, it appears not to represent a major risk factor for progression to CRC.</p

Health and Pleasure in Consumers' Dietary Food Choices: Individual Differences in the Brain's Value System

Taking into account how people value the healthiness and tastiness of food at both the behavioral and brain levels may help to better understand and address overweight and obesity-related issues. Here, we investigate whether brain activity in those areas involved in self-control may increase significantly when individuals with a high body-mass index (BMI) focus their attention on the taste rather than on the health benefits related to healthy food choices. Under such conditions, BMI is positively correlated with both the neural responses to healthy food choices in those brain areas associated with gustation (insula), reward value (orbitofrontal cortex), and self-control (inferior frontal gyrus), and with the percent of healthy food choices. By contrast, when attention is directed towards health benefits, BMI is negatively correlated with neural activity in gustatory and reward-related brain areas (insula, inferior frontal operculum). Taken together, these findings suggest that those individuals with a high BMI do not necessarily have reduced capacities for self-control but that they may be facilitated by external cues that direct their attention toward the tastiness of healthy food. Thus, promoting the taste of healthy food in communication campaigns and/or food packaging may lead to more successful self-control and healthy food behaviors for consumers with a higher BMI, an issue which needs to be further researched

Increased Migration of Monocytes in Essential Hypertension Is Associated with Increased Transient Receptor Potential Channel Canonical Type 3 Channels

Increased transient receptor potential canonical type 3 (TRPC3) channels have been observed in patients with essential hypertension. In the present study we tested the hypothesis that increased monocyte migration is associated with increased TRPC3 expression. Monocyte migration assay was performed in a microchemotaxis chamber using chemoattractants formylated peptide Met-Leu-Phe (fMLP) and tumor necrosis factor-α (TNF-α). Proteins were identified by immunoblotting and quantitative in-cell Western assay. The effects of TRP channel-inhibitor 2–aminoethoxydiphenylborane (2-APB) and small interfering RNA knockdown of TRPC3 were investigated. We observed an increased fMLP-induced migration of monocytes from hypertensive patients compared with normotensive control subjects (246±14% vs 151±10%). The TNF-α-induced migration of monocytes in patients with essential hypertension was also significantly increased compared to normotensive control subjects (221±20% vs 138±18%). In the presence of 2-APB or after siRNA knockdown of TRPC3 the fMLP-induced monocyte migration was significantly blocked. The fMLP-induced changes of cytosolic calcium were significantly increased in monocytes from hypertensive patients compared to normotensive control subjects. The fMLP-induced monocyte migration was significantly reduced in the presence of inhibitors of tyrosine kinase and phosphoinositide 3-kinase. We conclude that increased monocyte migration in patients with essential hypertension is associated with increased TRPC3 channels

Neuromarketing and consumer neuroscience:contributions to neurology

Background: 'Neuromarketing' is a term that has often been used in the media in recent years. These public discussions have generally centered around potential ethical aspects and the public fear of negative consequences for society in general, and consumers in particular. However, positive contributions to the scientific discourse from developing a biological model that tries to explain context-situated human behavior such as consumption have often been neglected. We argue for a differentiated terminology, naming commercial applications of neuroscientific methods 'neuromarketing' and scientific ones 'consumer neuroscience'. While marketing scholars have eagerly integrated neuroscientific evidence into their theoretical framework, neurology has only recently started to draw its attention to the results of consumer neuroscience.Discussion: In this paper we address key research topics of consumer neuroscience that we think are of interest for neurologists; namely the reward system, trust and ethical issues. We argue that there are overlapping research topics in neurology and consumer neuroscience where both sides can profit from collaboration. Further, neurologists joining the public discussion of ethical issues surrounding neuromarketing and consumer neuroscience could contribute standards and experience gained in clinical research.Summary: We identify the following areas where consumer neuroscience could contribute to the field of neurology:. First, studies using game paradigms could help to gain further insights into the underlying pathophysiology of pathological gambling in Parkinson's disease, frontotemporal dementia, epilepsy, and Huntington's disease.Second, we identify compulsive buying as a common interest in neurology and consumer neuroscience. Paradigms commonly used in consumer neuroscience could be applied to patients suffering from Parkinson's disease and frontotemporal dementia to advance knowledge of this important behavioral symptom.Third, trust research in the medical context lacks empirical behavioral and neuroscientific evidence. Neurologists entering this field of research could profit from the extensive knowledge of the biological foundation of trust that scientists in economically-orientated neurosciences have gained.Fourth, neurologists could contribute significantly to the ethical debate about invasive methods in neuromarketing and consumer neuroscience. Further, neurologists should investigate biological and behavioral reactions of neurological patients to marketing and advertising measures, as they could show special consumer vulnerability and be subject to target marketing

Led into Temptation? Rewarding Brand Logos Bias the Neural Encoding of Incidental Economic Decisions

Human decision-making is driven by subjective values assigned to alternative choice options. These valuations are based on reward cues. It is unknown, however, whether complex reward cues, such as brand logos, may bias the neural encoding of subjective value in unrelated decisions. In this functional magnetic resonance imaging (fMRI) study, we subliminally presented brand logos preceding intertemporal choices. We demonstrated that priming biased participants' preferences towards more immediate rewards in the subsequent temporal discounting task. This was associated with modulations of the neural encoding of subjective values of choice options in a network of brain regions, including but not restricted to medial prefrontal cortex. Our findings demonstrate the general susceptibility of the human decision making system to apparently incidental contextual information. We conclude that the brain incorporates seemingly unrelated value information that modifies decision making outside the decision-maker's awareness