Stuttering: effects of genes and early treatment

As stuttering by most persons resolves after a time, an initial wait-and-see policy has been maintained up to now. Two recent important developments in the area of stuttering have occurred: the discovery of gene mutations that appear to be of relevance to the developmental-neurological abnormality and growing evidence that early intervention helps recovery. The mutated genes found are GNPTAB, GNPTG and NAGPA. They are involved in lysosomal decomposition. Published study results show that early treatment using either the Demands and Capacities Model (indirect treatment aimed at the child's surroundings) or the Lidcome Programme (behavioural therapy based on operant conditioning) results in recovery from stuttering in most children. It is now being recommended that 6-12 months are allowed to pass under supervision to see whether the child is leaning toward natural recovery or, if that does not occur, to initiate specific therapy.     

Improved preoperative evaluation of cerebral cavernomas by high-field, high-resolution susceptibility-weighted magnetic resonance imaging at 3 Tesla: comparison with standard (1.5 T) magnetic resonance imaging and correlation with histopathological findings--preliminary results

OBJECTIVES: To compare high-field, high-resolution, susceptibility-weighted magnetic resonance imaging (3 Tesla [T] HR-SW-MRI) and standard (1.5 Tesla [T]) MRI for the detection of cerebral cavernomas. To evaluate the ability of 3 T HR-SW-MRI to visualize intralesional structures compared with standard (1.5 T) MRI, in correlation with histopathologic findings. MATERIALS AND METHODS: Seventeen patients with cerebral cavernomas underwent both standard (1.5 T) MRI (T1-SE, T2-TSE, T2*-GRE) and 3 T HR-SW-MRI (TR/TE 43.3/9.1 millisecond; 512 x 384 x 48 matrix; FOV 250 mm; SI 72 mm) at our institution. All MR images were evaluated by 3 radiologists in consensus for detectability, size (1 cm), and conspicuity (good, acceptable, poor) of the lesions at both field strengths, and for the presence of hypointense intralesional tubular structures. In 7 patients, MR findings were correlated with histopathologic findings. RESULTS: Both 3 T HR-SW-MRI and standard (1.5 T) MRI detected 22 lesions in 17 patients; 3 T HR-SW-MRI detected an additional 7 lesions in 6 patients. On average, 3 T HR-SW-MRI detected 1.706 +/- 0.92 (median = 1) lesions per patient, whereas standard (1.5 T) MRI detected 1.235 +/- 0.664 lesions per patient (P = 0.016). Lesion conspicuity was good in all 3 T HR-SW-MR images and good in 68.2% and acceptable in 31.8% of standard (1.5 T) MR images (P = 0.016). In 22 lesions detected at both field strengths, 3 T HR-SW-MRI demonstrated intralesional tubular structures in 72.7% and standard (1.5 T) MRI demonstrated these structures in 31.8% (P = 0.001). Intralesional tubular structure correlated to conglomerates of cavernous vessel, as verified by histopathology. CONCLUSION: Compared with standard (1.5 T) MRI, 3 T HR-SW-MRI allows superior detection and characterization of cerebral cavernomas. Despite increased susceptibility effects, ie, signal loss at higher magnetic field strengths, the visualization of intralesional tubular structures is feasible. This may be helpful in the diagnosis, presurgical planning, and noninvasive follow-up after gamma-knife radiosurgery.     

Rapid and preferential distribution of blood-borne alphaCD3epsilonAb to the liver is followed by local stimulation of T cells and natural killer T cells

Dissemination of soluble molecules or antigens via the blood stream is considered to lead to a uniform distribution in the various organs of the body, but organ-specific microarchitecture and vascularization may influence this. Following intravenous injection of alphaCD3epsilon antibody (alphaCD3epsilonAb) we observed clear differences in antibody binding to Fcgamma receptor (FcgammaR)(+) antigen-presenting cells (APCs) or T lymphocytes in different organs. Significant binding of blood-borne alphaCD3epsilonAb was only detected in the spleen and liver and not in the thymus or lymph node. In the spleen, only 10% of dendritic cells/macrophages and 40% of T-cell receptor (TCR)-beta(+) cells were positive for alphaCD3epsilonAb, and, dependent on FcgammaR-mediated cross-linking of alphaCD3epsilonAb, a similar percentage of splenic TCR-beta(+) cells were stimulated and became CD69(+). Stimulation of TCR-beta(+) cells in the liver was at least as efficient as in the spleen, but almost all T cells and all scavenger liver sinusoidal endothelial cells bound alphaCD3epsilonAb. In contrast to CD69 up-regulation, only CD4(+) natural killer T (NKT) cells and CD11a(high) CD8(+) T cells were activated by alphaCD3epsilonAb and expressed interferon (IFN)-gamma. Again, IFN-gamma release from NKT/T cells was at least as efficient in the liver as in the spleen. Taken together, our results support the notion that the combination of extensive hepatic vascularization and very high scavenger activity allows the liver to fulfill its metabolic tasks and to promote stimulation of the large but widely distributed hepatic population of NKT/T cells.     

Stress perception and commuting

This paper analyzes the determinants of the perceived stress level of workers with a special focus on the effects of commuting, while controlling for personal and work-related characteristics. Using ordered logistic regression we find that several dimensions of the commuting situation, such as impedance, control and predictability of commuting, significantly influence the perceived stress level. Therefore, stress and stress-related health problems should be taken into consideration when analyzing the economic costs of commuting.     

Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels

The genetic determinants of variation in iron status are actively sought, but remain incompletely understood. Meta-analysis of two genome-wide association (GWA) studies and replication in three independent cohorts was performed to identify genetic loci associated in the general population with serum levels of iron and markers of iron status, including transferrin, ferritin, soluble transferrin receptor (sTfR) and sTfR-ferritin index. We identified and replicated a novel association of a common variant in the type-2 transferrin receptor (TFR2) gene with iron levels, with effect sizes highly consistent across samples. In addition, we identified and replicated an association between the HFE locus and ferritin and confirmed previously reported associations with the TF, TMPRSS6 and HFE genes. The five replicated variants were tested for association with expression levels of the corresponding genes in a publicly available data set of human liver samples, and nominally statistically significant expression differences by genotype were observed for all genes, although only rs3811647 in the TF gene survived the Bonferroni correction for multiple testing. In addition, we measured for the first time the effects of the common variant in TMPRSS6, rs4820268, on hepcidin mRNA in peripheral blood (n = 83 individuals) and on hepcidin levels in urine (n = 529) and observed an association in the same direction, though only borderline significant. These functional findings require confirmation in further studies with larger sample sizes, but they suggest that common variants in TMPRSS6 could modify the hepcidin-iron feedback loop in clinically unaffected individuals, thus making them more susceptible to imbalances of iron homeostasis.