Effect of sleep on interictal spikes and distribution of sleep spindles on electrocorticography in children with focal epilepsy.

OBJECTIVE: To determine how sleep with central spindles alters the spatial distribution of interictal spike frequency in children with intractable focal seizures, and whether such children have spindles arising from the medial temporal region in addition to the frontal-central region. METHODS: Seventeen children (age: 7 months-17 years) were studied using extraoperative electrocorticography (ECoG). RESULTS: Overall spike frequency across the subdural electrodes was greater during sleep with central spindles compared to wakefulness. In 13 children showing at least 1 spike/min in an electrode, the spatial distribution of spike frequency was similar during wakefulness and sleep; in addition, the spike frequency was greater in the seizure onset zones compared to the non-onset areas, regardless of wakefulness or sleep. Spindles were identified in the medial temporal region during sleep with central spindles in all 17 children. CONCLUSION: Overall spike frequency may be increased by sleep with spindles, but the spatial distribution of spike frequency appears similar during wakefulness and sleep in children with intractable focal seizures. SIGNIFICANCE: Both awake and sleep ECoG may be useful to predict seizure onset zones in children with intractable focal epilepsy. Medial temporal spindles are present in some children with focal epilepsy.     

Immunological markers contributing to successful aging in Bulgarians

In order to clarify immunogenetic markers contributing to successful aging, HLA and cytokine gene profiles were analyzed in healthy elderly Bulgarians. Family segregation analysis was performed to define combined effect of haplotypes and immunophenotype profiles. The results of this study did not reveal any statistically significant allele and haplotype frequency differences between elderly and control group. In families with two generations longevity members we did not observed HLA alleles and haplotypes associated with autoimmunity. IL-10 genotype -1082G/A, -819 C/C, -592 C/C, related to the intermediate production, was positively associated, while genotype -1082A/A, -819 C/T, -592 C/A, related to the low level of production, was negatively associated with longevity in Bulgarians. This effect was modulated by IL-6 and IFNgamma genotypes associated with the low level of these pro-inflammatory cytokines. Immunophenotypic studies indicated lower relative and absolute numbers of CD3+8+, CD8+28+ and CD8+57+ cells in elderly people. Analysis in families showed that although most pronounced in the elderly group, lower numbers of CD8+ T cells were also found in middle aged and young members of the families compared to the age matched controls. A progressive CD8+28+ cell subsets decline was seen with aging. In addition, we did not observed the 'immune risk phenotype' which is a marker of an increased inflammatory activity. Based on the results of this study, it seems reasonable to suggest that a combination of specific immunogenetic and immunophenotype profiles could contribute to the successful aging and to maintaining healthy status in elderly.     

Selective silencing of DNA-specific B lymphocytes delays lupus activity in MRL/lpr mice

The pathological DNA-specific B lymphocytes in lupus are logical targets for a selected therapeutic intervention. We have hypothesized that it should be possible to suppress selectively the activity of these B cells in lupus mice by administering to them an artificial molecule that cross-links their surface immunoglobulins with the inhibitory FcgammaIIb surface receptors. A hybrid molecule was constructed by coupling the DNA-mimicking DWEYSVWLSN peptide to a monoclonal anti-mouse FcgammaRIIb antibody. This chimeric antibody was added to cultured spleen cells from sick MRL/lpr mice, immunized with diphtheria toxoid, resulting in reduction of the numbers of anti-DNA but not of anti-diphtheria IgG antibody-producing cells. Intravenous infusions with the DNA-peptide antibody chimera to 7-wk-old animals prevented the appearance of IgG anti-DNA antibodies and of albuminuria in the next 2 months. The administration of the DNA-peptide chimeric antibody to 18 wk-old mice with full-blown disease resulted in the maintenance of a flat level of IgG anti-DNA antibodies and in delay of the aggravation of the lupus glomerulonephritis. The use of chimeric antibodies targeting inhibitory B lymphocyte receptors represents a novel approach for the selective suppression of autoreactive disease-associated B cells in autoimmune diseases.     

Molecular and biochemical study of glutaric aciduria type 1 in 49 Russian families: nine novel mutations in the GCDH gene

Metabolic Brain Disease - Glutaric aciduria type 1 (GA1, deficiency of glutaryl CoA dehydrogenase, glutaric acidemia type 1) (ICD-10 code: E72.3; MIM 231670) is an autosomal recessive disease...     

Review of statistical methods for analysing healthcare resources and costs

We review statistical methods for analysing healthcare resource use and costs, their ability to address skewness, excess zeros, multimodality and heavy right tails, and their ease for general use. We aim to provide guidance on analysing resource use and costs focusing on randomised trials, although methods often have wider applicability. Twelve broad categories of methods were identified: (I) methods based on the normal distribution, (II) methods following transformation of data, (III) single‐distribution generalized linear models (GLMs), (IV) parametric models based on skewed distributions outside the GLM family, (V) models based on mixtures of parametric distributions, (VI) two (or multi)‐part and Tobit models, (VII) survival methods, (VIII) non‐parametric methods, (IX) methods based on truncation or trimming of data, (X) data components models, (XI) methods based on averaging across models, and (XII) Markov chain methods. Based on this review, our recommendations are that, first, simple methods are preferred in large samples where the near‐normality of sample means is assured. Second, in somewhat smaller samples, relatively simple methods, able to deal with one or two of above data characteristics, may be preferable but checking sensitivity to assumptions is necessary. Finally, some more complex methods hold promise, but are relatively untried; their implementation requires substantial expertise and they are not currently recommended for wider applied work. Copyright © 2010 John Wiley & Sons, Ltd.     

Humanized SCID mice models of SLE

The pathological DNA-specific B cells in Systemic lupus erythematosus are a logical target for a selected therapeutic intervention. It has been recently shown that complement receptor type 1 on human B and T-lymphocytes has suppressive activity. The co-crosslinking of this receptor with the B-cell receptor (BCR) inhibits B cell activation and proliferation and it could be an attractive new target for negative signal delivery. Experimental therapy in humans is limited by many restrictions. Severe combined immunodeficiency (SCID) mice, which lack both T and B lymphocytes and accept xenogenic cells have been used for human cell transfer for evaluating the pathogenesis of human SLE. We hypothesize that it may be possible to re-establish tolerance to native DNA in humanized SCID mice with cells transferred from SLE patients by administering to them a chimeric molecule, containing a monoclonal antibody against human inhibitory complement receptor type 1 coupled to a decapeptide DWEYSVWLSN that mimics DNA antigenically. These protein-engineered molecules are able to co-crosslink selectively the antigen receptors of B-cells possessing anti-native DNA specificity with the inhibitory surface receptors, thus delivering a strong suppressive signal.     

Circulating miR-618 Has Prognostic Significance in Patients with Metastatic Colon Cancer

The present study evaluated the prognostic role of circulating miRNA-618 in patients with metastatic colon cancer (mCC) and whether miR-618 gene rs2682818 single nucleotide polymorphisms (SNP) are associated with colon cancer susceptibility and expression levels of mature miR-618. In total, 104 patients with mCC before starting the chemotherapy were investigated. The expression status of circulating miR-618 in mCC was evaluated by quantitative PCR. TaqMan PCR assay was used for rs2682818 SNP genotyping. miR-618 was overexpressed in serum of mCC patients. Patients with high and intermediate expression of miR-618 had a significantly longer mean overall survival (OS) of 21 months than patients with low expression—16 months. In addition, multivariate Cox regression analysis confirmed the association between high/intermediate levels of miRNA-618 and longer OS, HR = 0.51, 95% CI: 0.30–0.86, p = 0.012. miR-618 rs2682818 SNP significantly decreased the risk of colon cancer susceptibility in both heterozygous codominant (AC vs. CC, OR = 0.39, 95% CI: 0.17–0.88, p = 0.024) and overdominant (AC vs. CC + AA, OR = 0.37, 95% CI: 0.16–0.85, p = 0.018) genetic models. Our data suggest that circulating miRNA-618 could be useful as a prognostic biomarker in mCC. Patients harboring AC rs2682818 genotype have a decreased risk for colon cancer in comparison with patients with CC and AA genotypes.