Identification of Srp9 as a febrile seizure susceptibility gene

Objective: Febrile seizures (FS) are the most common seizure type in young children. Complex FS are a risk factor for mesial temporal lobe epilepsy (mTLE). To identify new FS susceptibility genes we used a forward genetic strategy in mice and subsequently analyzed candidate genes in humans. Methods: We mapped a quantitative trait locus (QTL1) for hyperthermia-induced FS on mouse chromosome 1, containing the signal recognition particle 9 (Srp9) gene. Effects of differential Srp9 expression were assessed in vivo and in vitro. Hippocampal SRP9 expression and genetic association were analyzed in FS and mTLE patients. Results: Srp9 was differentially expressed between parental strains C57BL/6J and A/J. Chromosome substitution strain 1 (CSS1) mice exhibited lower FS susceptibility and Srp9 expression than C57BL/6J mice. In vivo knockdown of brain Srp9 reduced FS susceptibility. Mice with reduced Srp9 expression and FS susceptibility, exhibited reduced hippocampal AMPA and NMDA currents. Downregulation of neuronal Srp9 reduced surface expression of AMPA receptor subunit GluA1. mTLE patients with antecedent FS had higher SRP9 expression than patients without. SRP9 promoter SNP rs12403575(G/A) was genetically associated with FS and mTLE. Interpretation: Our findings identify SRP9 as a novel FS susceptibility gene and indicate that SRP9 conveys its effects through endoplasmic reticulum (ER)-dependent synthesis and trafficking of membrane proteins, such as glutamate receptors. Discovery of this new FS gene and mechanism may provide new leads for early diagnosis and treatment of children with complex FS at risk for mTLE

Ureteral Reconstruction after Renal Transplantation: Clinical Outcome and Risk Factors

INTRODUCTION: The incidence of urological complications after renal transplantation ranges from 2.5 to 30%. Often surgical revision is necessary. The risk factors for surgical revision and which surgical techniques to apply are not elucidated. This study investigates the outcome and risk factors for surgical revision of the ureterocystostomy. MATERIALS AND METHODS: Between January 1995 and March 2009, 1,157 consecutive kidney transplantations were performed. All patient charts and surgical reports were reviewed. RESULTS: Urological complications occurred in 142 (12.3%) patients. In 60 patients (5.2%) surgical revision was necessary. Of these 60 patients, 43 (71.7%) received neoureterocystostomy, 10 (16.7%) ureteropyelostomy reconstruction and 7 (11.7%) other techniques. Independent risk factors for surgical revision were donor ureteral reconstruction (odds ratio (OR) 48.66, 95% confidence interval (CI) 5.01-472.97), recipient age <18 years (OR 4.85, 95% CI 1.50-15.72) and delayed graft function (OR 2.70, 95% CI 1.36-5.36). Ureteral stenting was a protective factor for surgical revision (OR 0.30, 95% CI 0.12-0.81). The urological complication rates after neoureterocystostomy, ureteropyelostomy reconstruction and other techniques were 16, 0 and 0%, respectively. The overall surgical success rate was 92%. CONCLUSIONS: Ureteral stenting, recipient age, delayed graft function and perioperative ureteral reconstruction are significant factors associated with surgical revision of the ureterocystostomy. Surgical revision of the ureterocystostomy is a successful therapy with a low recurrence rate

Early use of phonetic information in spoken word recognition: Lexical stress drives eye movements immediately

Contains fulltext : 90217.pdf (publisher's version ) (Closed access)For optimal word recognition listeners should use all relevant acoustic information as soon as it comes available. Using printed-word eye tracking we investigated when during word processing Dutch listeners use suprasegmental lexical stress information to recognize words. Fixations on targets such as “OCtopus” (capitals indicate stress) were more frequent than fixations on segmentally overlapping but differently stressed competitors (“okTOber”) before segmental information could disambiguate the words. Furthermore, prior to segmental disambiguation, initially stressed words were stronger lexical competitors than noninitially stressed words. Listeners recognize words by immediately using all relevant information in the speech signal.12 p

AIS and MCS for Port Community Systems: An empirical analysis from Italy

The purpose of this paper is to analyse the role of Accounting Information Sys-tems (AIS) and Management Control Systems (MCS) in the information management within seaports when an information technology platform has been adopted, such as the Port Commu-nity Systems (PCSs). We conducted a literature review on PCSs and on how AIS and MCS could contribute to the platform in order to support the decision making processes of port users, like forwarder and shipping agents. Starting from previous studies focused on Italian seaports, by using the case study methodology, we collected data through semi-structured interviews to managers of the selected seaport. Indeed, we have outlined the usefulness in adopting AIS and MCS for PCS in the forwarder and shipping agents perspective