Enhanced tonic GABAA inhibition in typical absence epilepsy

The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy.peer-reviewe

Phylogenetic evidence for the invasion of a commercialized European Phasmarhabditis hermaphrodita lineage into North America and New Zealand

Biological control (biocontrol) as a component of pest management strategies reduces reliance on synthetic chemicals, and seemingly offers a natural approach that minimizes environmental impact. However, introducing a new organism to new environments as a classical biocontrol agent can have broad and unanticipated biodiversity effects and conservation consequences. Nematodes are currently used in a variety of commercial biocontrol applications, including the use of Phasmarhabditis hermaphrodita as an agent targeting pest slug and snail species. This species was originally discovered in Germany, and is generally thought to have European origins. P. hermaphrodita is sold under the trade name Nemaslug®, and is available only in European markets. However, this nematode species was discovered in New Zealand and the western United States, though its specific origins remained unclear. In this study, we analyzed 45 nematode strains representing eight different Phasmarhabditis species, collected from nine countries around the world. A segment of nematode mitochondrial DNA (mtDNA) was sequenced and subjected to phylogenetic analyses. Our mtDNA phylogenies were overall consistent with previous analyses based on nuclear ribosomal RNA (rRNA) loci. The recently discovered P. hermaphrodita strains in New Zealand and the United States had mtDNA haplotypes nearly identical to that of Nemaslug®, and these were placed together in an intraspecific monophyletic clade with high support in maximum likelihood and Bayesian analyses. We also examined bacteria that co-cultured with the nematode strains isolated in Oregon, USA, by analyzing 16S rRNA sequences. Eight different bacterial genera were found to associate with these nematodes, though Moraxella osloensis, the bacteria species used in the Nemaslug® formulation, was not detected. This study provided evidence that nematodes deriving from the Nemaslug® biocontrol product have invaded countries where its use is prohibited by regulatory agencies and not commercially available

Systemic lupus erythematosus in Pakistan

Clinical features of systemic lupus erythematosus (SLE) have been described from different geographical regions in the world, with some clinical differences among different racial groups. Although data on the characteristics of SLE in Pakistan is scarce, it is not uncommon in the South East Asian region. The purpose of this study was, therefore, to delineate the clinical pattern and disease course in Pakistani patients with SLE and to compare it with international data on lupus patients. A total of 196 patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatism Association admitted to the hospital between 1986 and 2001 were studied by means of a retrospective review of their records. Demographically, it was seen that SLE is a disease predominantly of females in their third decade, which is consistent with worldwide data. The mean age of presentation was 31 years (range 14-76) and the mean duration of follow up was 34 (4-179) months. Generally, there was less cutaneous (46%), arthritic (38%), serositis (22%) and renal involvement (33%) but more neuropsychiatric symptoms (26%) in our population. Eighty-six percent of patients were ANA positive, whereas anti dsDNA was positive in 74% of patients. Infections, renal involvement, seizures and thrombocytopenia were associated with poor prognosis (P \u3c 0.05). This study is the first of its kind in Pakistan. The clinical and laboratory characteristics of SLE patients in our study place our population in the middle of a spectrum between the Caucasians and other Asian populations. It has shown that the clinical characteristics of SLE patients in this country may be different to those of its neighbors

Networks of Survivorship Care for Young Cancer Patients

Forty-two chapters have been structured according to the toxicities in cancer entities, and the late effects and follow-up proposals have been discussed by European and American authors. Cancer diseases in children, adolescents and young adults are treated within specific treatment protocols and can produce different late effects that will have to be cared for by specific follow-up recommendations. Over the last decades, the therapy which was considered the best was used to save patients’ lives. The pattern of toxicities and late effects have changed over time, depending on the treatment protocols used. Rather than delivering standard and conclusive recommendations for survivorship care in all healthcare systems, this book gives an instantaneous picture of the current and fast developing practices, as well as the work in progress. Its common, yet important aim will be to point out the development of harmonized guidelines for cancer survivors that could be implemented in different health-care systems

Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene.

Calcium has a pivotal role in biological functions, and serum calcium levels have been associated with numerous disorders of bone and mineral metabolism, as well as with cardiovascular mortality. Here we report results from a genome-wide association study of serum calcium, integrating data from four independent cohorts including a total of 12,865 individuals of European and Indian Asian descent. Our meta-analysis shows that serum calcium is associated with SNPs in or near the calcium-sensing receptor (CASR) gene on 3q13. The top hit with a p-value of 6.3 x 10(-37) is rs1801725, a missense variant, explaining 1.26% of the variance in serum calcium. This SNP had the strongest association in individuals of European descent, while for individuals of Indian Asian descent the top hit was rs17251221 (p = 1.1 x 10(-21)), a SNP in strong linkage disequilibrium with rs1801725. The strongest locus in CASR was shown to replicate in an independent Icelandic cohort of 4,126 individuals (p = 1.02 x 10(-4)). This genome-wide meta-analysis shows that common CASR variants modulate serum calcium levels in the adult general population, which confirms previous results in some candidate gene studies of the CASR locus. This study highlights the key role of CASR in calcium regulation