Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics.

Background/objectivesA common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues.Subjects/methodsTC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60-93 years) from the Sacramento Area Latino Study on Aging (SALSA).ResultsThe distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (P=0.04). Significant interactions of TC genotype with total B12 (P=0.04) and with holoTC (P< or =0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 micromol/l) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (<156 pmol/l) or holoTC (<35 pmol/l) were low.ConclusionsThis population of older Latinos has a lower prevalence of the TC 776GG variant than reported for Caucasian populations. The association between vitamin B12 and homocysteine concentrations is modified by TC 776 genotype. It remains to be determined whether the TC C776G polymorphism has a significant effect on the hematological and neurological manifestations of B12 deficiency or on vascular and other morbidities associated with hyperhomocysteinemia

A Novel Method for Epileptic Seizure Detection Using Coupled Hidden Markov Models

We propose a novel Coupled Hidden Markov Model to detect epileptic seizures in multichannel electroencephalography (EEG) data. Our model defines a network of seizure propagation paths to capture both the temporal and spatial evolution of epileptic activity. To address the intractability introduced by the coupled interactions, we derive a variational inference procedure to efficiently infer the seizure evolution from spectral patterns in the EEG data. We validate our model on EEG aquired under clinical conditions in the Epilepsy Monitoring Unit of the Johns Hopkins Hospital. Using 5-fold cross validation, we demonstrate that our model outperforms three baseline approaches which rely on a classical detection framework. Our model also demonstrates the potential to localize seizure onset zones in focal epilepsy.Comment: To appear in MICCAI 2018 Proceeding

Changes in life-style after liver transplantation

Sixty-five pediatric patients who received liver transplants between May 1981 and May 1984 were observed for as many as 5 years and examined for changes in life-style. Children were less frequently hospitalized, spent less time hospitalized, required fewer medications, and generally had excellent liver and renal function after hepatic transplantation as compared with their pretransplantation status. Most children were in age-appropriate and standard school classes or were only 1 year behind. Cognitive abilities remained unchanged. Children improved in gross motor function and patients' behavior significantly improved according to parents' perceptions. Enuresis was more prevalent, however, than in the population of children who had not received liver transplants. Parental divorce rates were no greater than those reported for other families with chronically ill children. Overall, objective changes in life-style as well as parents' perceptions of behavior of children appear to be improved after liver transplantation

VEGF(164)-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF(164) increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF(164)-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF(164)-deficient (VEGF(120/188)) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF(+/+)) controls. In contrast, administration of a VEGFk-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte-mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF(164) selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined

Proof Relevant Corecursive Resolution

Resolution lies at the foundation of both logic programming and type class context reduction in functional languages. Terminating derivations by resolution have well-defined inductive meaning, whereas some non-terminating derivations can be understood coinductively. Cycle detection is a popular method to capture a small subset of such derivations. We show that in fact cycle detection is a restricted form of coinductive proof, in which the atomic formula forming the cycle plays the role of coinductive hypothesis. This paper introduces a heuristic method for obtaining richer coinductive hypotheses in the form of Horn formulas. Our approach subsumes cycle detection and gives coinductive meaning to a larger class of derivations. For this purpose we extend resolution with Horn formula resolvents and corecursive evidence generation. We illustrate our method on non-terminating type class resolution problems.Comment: 23 pages, with appendices in FLOPS 201

Second Primary Neoplasms in Patients With Uveal Melanoma: A SEER Database Analysis

PURPOSE: To determine the risk of second primary neoplasms (SPNs) in subjects previously diagnosed with uveal melanoma (UM), including an analysis on whether radiotherapy is a risk factor to develop these SPNs. DESIGN: Retrospective cohort study. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) 9 database, we identified patients diagnosed with UM as their first malignancy between 1973 and 2011 (n = 3976). We obtained standardized incidence ratios (SIR) and excess absolute risks of SPNs on patients with UM compared to a reference population. Multivariate Cox regression models were used to evaluate the effect of radiotherapy in SPN risk. RESULTS: Sixteen percent (n = 641) of the patients developed SPNs during a median follow-up of 83 months (range, 1-463 months). This represented an 11% excess risk compared to the reference population, mainly owing to a significantly increased risk of skin melanomas (SIR = 2.93, 95% CI: 2.23-3.78) and kidney tumors (SIR = 1.91, 95% CI: 1.27-2.76), primarily in those diagnosed between 30 and 59 years of age. The occurrence of second UM was also increased (SIR = 16.90, 95% CI: 9.00-28.90), which likely includes recurrences misclassified as a second cancer. Radiotherapy was performed in 39% (n = 1538) of the patients. Multivariate analysis revealed that this treatment was not an independent risk factor for SPNs (hazard ratio = 1.06, 95% CI: 0.88-1.26, P = .54). CONCLUSIONS: Patients with UM presented an 11% higher risk of SPNs compared to the reference population. Radiotherapy does not seem to be a risk factor. SPNs should be considered in the surveillance of UM.info:eu-repo/semantics/publishedVersio