SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally control the expression of their target genes via RNA interference. There is increasing evidence that expression of miRNAs is dysregulated in neuronal disorders, including epilepsy, a chronic neurological disorder characterized by spontaneous recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is a common type of focal epilepsy in which disease-induced abnormalities of hippocampal neurogenesis in the subgranular zone as well as gliosis and neuronal cell loss in the cornu ammonis area are reported. We hypothesized that in MTLE altered miRNA-mediated regulation of target genes could be involved in hippocampal cell remodeling. A miRNA screen was performed in hippocampal focal and non-focal brain tissue samples obtained from the temporal neocortex (both n=8) of MTLE patients. Out of 215 detected miRNAs, two were differentially expressed (hsa-miR-34c-5p: mean increase of 5.7 fold (p=0.014), hsa-miR-212-3p: mean decrease of 76.9% (p=0.0014)). After in-silico target gene analysis and filtering, reporter gene assays confirmed RNA interference for hsa-miR-34c-5p with 3'-UTR sequences of GABRA3, GRM7 and GABBR2 and for hsa-miR-212-3p with 3'-UTR sequences of SOX11, MECP2, ADCY1 and ABCG2. Reporter gene assays with mutated 3'-UTR sequences of the transcription factor SOX11 identified two different binding sites for hsa-miR-212-3p and its primary transcript partner hsa-miR-132-3p. Additionally, there was an inverse time-dependent expression of Sox11 and miR-212-3p as well as miR-132-3p in rat neonatal cortical neurons. Transfection of neurons with anti-miRs for miR-212-3p and miR-132-3p suggest that both miRNAs work synergistically to control Sox11 expression. Taken together, these results suggest that differential miRNA expression in neurons could contribute to an altered function of the transcription factor SOX11 and other genes in the setting of epilepsy, resulting not only in impaired neural differentiation, but also in imbalanced neuronal excitability and accelerated drug export.

AHRQ's hospital survey on patient safety culture: psychometric analyses.

OBJECTIVE: This project analyzed the psychometric properties of the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture (HSOPSC) including factor structure, interitem reliability and intraclass correlations, usefulness for assessment, predictive validity, and sensitivity. METHODS: The survey was administered to 454 health care staff in 3 hospitals before and after a series of multidisciplinary interventions designed to improve safety culture. Respondents (before, 434; after, 368) included nurses, physicians, pharmacists, and other hospital staff members. RESULTS: Factor analysis partially confirmed the validity of the HSOPSC subscales. Interitem consistency reliability was above 0.7 for 5 subscales; the staffing subscale had the lowest reliability coefficients. The intraclass correlation coefficients, agreement among the members of each unit, were within recommended ranges. The pattern of high and low scores across the subscales of the HSOPSC in the study hospitals were similar to the sample of Pacific region hospitals reported by the Agency for Healthcare Research and Quality and corresponded to the proportion of items in each subscale that are worded negatively (reverse scored). Most of the unit and hospital dimensions were correlated with the Safety Grade outcome measure in the tool. CONCLUSION: Overall, the tool was shown to have moderate-to-strong validity and reliability, with the exception of the staffing subscale. The usefulness in assessing areas of strength and weakness for hospitals or units among the culture subscales is questionable. The culture subscales were shown to correlate with the perceived outcomes, but further study is needed to determine true predictive validity.

Clinical features of status epilepticus in patients with HIV infection.

The authors reviewed the records of 42 patients with HIV infection and status epilepticus (SE). Brain tumor and infection were the most common etiologies. The median duration of SE was 2.0 +/- 10 hours. Most patients (37 [88%]) responded to IV benzodiazepine or phenytoin treatment. Nevertheless, 12 (29%) patients died and 15 (36%) developed new neurologic deficits. In patients with HIV infection, aggressive management of seizures may limit the risk of SE.