Nonverbal cognition in deaf children following cochlear implantation: motor sequencing disturbances mediate language delays

We assessed profoundly deaf children with cochlear implants (CIs) (N = 24) and age-matched normal-hearing children (N = 31) on several nonverbal cognition measures: motor sequencing, tactile discrimination, response inhibition, visual-motor integration, and visual-spatial processing. The results revealed that the children with CIs showed disturbances solely on motor sequencing and that performance on this task was significantly correlated with scores on the Clinical Evaluation of Language Fundamentals, 4th Edition (CELF-4). These findings suggest that a period of auditory deprivation before cochlear implantation affects motor sequencing skills, which in turn may mediate the language delays displayed by some deaf children with CIs.     

Sesquiterpene lactones: antispasmodic principles of the freshwater algae Hydrodictyon reticulatum

Hydrodictyon reticulatum is used in traditional medicine in Mexico to decrease gastrointestinal disorders suggesting that some of its chemical components have properties that relax smooth muscle. The hexane extract showed the most promising biological effects, with IC₅₀ of 49.34?μg/ml in the spontaneous contraction of ileum. A detailed phytochemical analysis of the hexane extract led to the isolation of the known sesquiterpenes: β-Cayophyllene-4,5-α-oxide (1) and two new sesquiterpene lactones, 3α,4α,8α-trihydroxy-10α-methoxy-1α,5α,7α,11βH-guaia,6α,12-olide (2) and 4α,8α-dihydroxy-10α-methoxy-1α,5α,7α,11-βH-guaia,6α,12- olide (3). The identification and characterization of these compounds were determined using 1-D and 2-D-NMR (through interpretation of NMR data). The antispasmodic activity of sesquiterpenes of H. reticulatum was studied on isolated tissue preparations from rabbit and rat intestine. The compounds at 1.79 at 3.44?×?10^?8?M doses reduced acetylcholine (Ach), histamine, and barium chloride-induced contractions on isolated rat ileum. Therefore, possess similar relaxant mechanism of action, in view of the fact that sesquiterpenes inhibit K⁺-induced contraction and act through serotoninic, muscarinic, and histaminic receptors. So these data support that extract may interfere with calcium mobilization from intracellular stores or with calcium interaction with regular proteins or in the other steps in the calcium-signaling pathway.     

A polymorphism in the inducible nitric oxide synthase gene is associated with tuberculosis

iNOS or NOS2 is a molecule that plays a key role in the immunological control of a broad spectrum of infectious agents. Investigation is hampered by difficulty in estimating in vivo production of nitric oxide (NO), but genetic studies provide a potential means of examining the relation between NO production and disease outcome. To better characterize the host genetic factors determining the susceptibility to TB, we evaluated the influence of two polymorphisms in the NOS2A gene on the risk of developing pulmonary TB in a Northwestern Colombian population, which is a moderately-high endemic area. One hundred and fourteen patients with TB and negative for human immunodeficiency virus, plus 304 healthy controls were examined for NOS2A CCTTT and TAAA polymorphisms. A total of 160 healthy controls mentioned before, underwent tuberculin skin test (TST). Analysis disclosed significant differences between patients and controls with NOS2A CCTTT polymorphism (P=0.0001, Pc=0.001, OR=0.4, and 95%CI=0.3-0.7) independent of TST status. When the NOS2A alleles were stratified into short (8-11) and long (12-16) repeats, significant differences with short repeats were observed between TB patients and all controls (P=0.005, OR=0.63, 95%CI=0.46-0.86). No individual association with NOS2A TAAA was detected. These results indicate that a polymorphism in the NOS2A gene influences the susceptibility to TB and suggest a role for NOS2A in the pathogenesis of mycobacterial infection.     

PTPN22 C1858T polymorphism in Colombian patients with autoimmune diseases

A functional single nucleotide polymorphism (SNP) C1858T in the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene encoding an intracellular phosphatase with negative regulatory effects on T-cell activation is associated with some autoimmune diseases in Caucasians. Taking into account firstly, that SNP frequencies may vary across populations and, secondly, that replication studies are important to confirm previous associations, we examined the influence of PTPN22 polymorphism in 621 Colombian patients with four autoimmune diseases. Accordingly, 298 patients with rheumatoid arthritis (RA), 143 with systemic lupus erythematosus (SLE), 70 with primary Sjogren's syndrome (pSS) and 110 with Type 1 diabetes (T1D) were studied. The control group consisted of 308 matched healthy individuals. Genotyping of PTPN22 was performed by the real-time polymerase chain reaction technology, using the Taq Man 5'-allele discrimination assay. The 1858 T allele was found to be a risk factor for pSS (odds ratio (OR)=2.42), SLE (OR=2.56), and T1D (OR=1.83). A lower but nonsignificant trend was observed for RA (OR=1.26). These results confirm the influence of PTPN22 in autoimmunity and indicate that autoimmune phenotypes could represent pleiotropic outcomes of nonspecific disease genes that underlie similar immunogenetic mechanisms.     

The Relationship Between CAG Repeat Length and Age of Onset Differs for Huntington's Disease Patients with Juvenile Onset or Adult Onset

Age of onset for Huntington's disease (HD) varies inversely with the length of the disease-causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R-squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present evidence that a two-segment exponential regression curve provides a significantly better fit than the simple exponential regression. A plot of natural log-transformed age of onset against CAG repeat length reveals this segmental relationship. This two-segment exponential regression on age of onset data increases the adjusted R-squared values by 0.012 in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the amount of additional variance explained by the segmental regression approach is modest, the two slopes of the two-segment regression are significantly different from each other in both the Venezuelan kindreds [F(2, 439) = 11.13, P = 2 × 10⁻⁵] and in the HD MAPS cohort [F(2, 688) = 38.27, P = 2 × 10⁻¹⁶]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult-onset range of CAG repeats than in the juvenile-onset range.