Taxonomic status and origin of the shrews (Soricidae) from the Canary islands inferred from a mtDNA comparison with the European Crocidura species.

European island shrews are either relicts of the endemic Pleistocene fauna, e.g.,. Crocidura zimmermanni, or were introduced from continental source populations. In order to clarify the taxonomic status and the origin of the two shrew species from the Canary islands, a 981bp fragment of cytochrome b gene was investigated in all European Crocidura species and compared with the Canary shrew (Crocidura canariensis) and the Osorio shrew (Crocidura osorio). The first shares its karyotype with the Sicilian shrew Crocidura sicula (2N=36), the second with the Greater white-toothed shrew Crocidura russula (2N=42), suggesting possible sister species relationships. Results confirm the monophyly of taxa sharing the same karyotype. Genetic distances between C. sicula and C. canariensis suggest a separation since 5 Myr. The first was probably isolated from the North African ancestor after the Messinian desiccation; the second arrived on the Canary islands by natural jump dispersal. Within the 2N=42 cluster, a first split separated an Eastern line (Tunisia) from a western line (Morocco/Europe) of C. russula. C. osorio clusters together with C. russula from Spain, indicating conspecificy. This suggests a recent introduction from Spain by human.

Epigenetic regulation of histone H3 serine 10 phosphorylation status by HCF-1 proteins in C. elegans and mammalian cells.

BACKGROUND: The human herpes simplex virus (HSV) host cell factor HCF-1 is a transcriptional coregulator that associates with both histone methyl- and acetyltransferases, and a histone deacetylase and regulates cell proliferation and division. In HSV-infected cells, HCF-1 associates with the viral protein VP16 to promote formation of a multiprotein-DNA transcriptional activator complex. The ability of HCF proteins to stabilize this VP16-induced complex has been conserved in diverse animal species including Drosophila melanogaster and Caenorhabditis elegans suggesting that VP16 targets a conserved cellular function of HCF-1. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of HCF proteins in animal development, we have characterized the effects of loss of the HCF-1 homolog in C. elegans, called Ce HCF-1. Two large hcf-1 deletion mutants (pk924 and ok559) are viable but display reduced fertility. Loss of Ce HCF-1 protein at reduced temperatures (e.g., 12 degrees C), however, leads to a high incidence of embryonic lethality and early embryonic mitotic and cytokinetic defects reminiscent of mammalian cell-division defects upon loss of HCF-1 function. Even when viable, however, at normal temperature, mutant embryos display reduced levels of phospho-histone H3 serine 10 (H3S10P), a modification implicated in both transcriptional and mitotic regulation. Mammalian cells with defective HCF-1 also display defects in mitotic H3S10P status. CONCLUSIONS/SIGNIFICANCE: These results suggest that HCF-1 proteins possess conserved roles in the regulation of cell division and mitotic histone phosphorylation.

Recurrence of status epilepticus: Prognostic role and outcome predictors.

OBJECTIVE: Predictors of morbidity and mortality after status epilepticus (SE) have been studied extensively in hospital- and population-based cohorts. However, little attention has been directed toward SE recurrence after an incident episode. We investigated clinical and demographic characteristics of patients presenting SE recurrence and its specific prognostic role. METHODS: In this observational cohort study, we screened our prospective registry of consecutive adults with SE between April 2006 and February 2014. Demographic and clinical data were compared between incident and recurrent SE episodes; risk of SE recurrence was assessed through survival analysis, and the prognostic role of SE recurrence with multivariable logistic regressions. RESULTS: Of the incident cohort (509 patients), 68 (13%) experienced recurrent SE. The cumulative recurrence rate over 4 years was 32%. Recurrence risk was significantly reduced after an acute SE etiology (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.31-0.82; p = 0.005), and was borderline increased in women (HR 1.59, 95% CI 0.97-2.65; p = 0.06). Although recurrent SE episodes showed lower morbidity and mortality, prognosis was independently related to Status Epilepticus Severity Score (STESS) and potentially fatal etiology, but not to SE recurrence. SIGNIFICANCE: This study provides class III evidence that SE recurrence involves a significant proportion of patients, and that recurrence risk is independently associated with chronic etiology and to a lesser extent with female gender. However, contrary to underlying cause and SE severity, SE recurrence per se does not independently correlate with outcome. Early identification of patients at higher risk of SE recurrence may influence their management during follow-up.

MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status.

The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma. Recent studies in anaplastic glioma suggest a prognostic value for MGMT methylation. Investigation of pathogenetic and epigenetic features of this intriguingly distinct behavior requires accurate MGMT classification to assess high throughput molecular databases. Promoter methylation-mediated gene silencing is strongly dependent on the location of the methylated CpGs, complicating classification. Using the HumanMethylation450 (HM-450K) BeadChip interrogating 176 CpGs annotated for the MGMT gene, with 14 located in the promoter, two distinct regions in the CpG island of the promoter were identified with high importance for gene silencing and outcome prediction. A logistic regression model (MGMT-STP27) comprising probes cg1243587 and cg12981137 provided good classification properties and prognostic value (kappa = 0.85; log-rank p < 0.001) using a training-set of 63 glioblastomas from homogenously treated patients, for whom MGMT methylation was previously shown to be predictive for outcome based on classification by methylation-specific PCR. MGMT-STP27 was successfully validated in an independent cohort of chemo-radiotherapy-treated glioblastoma patients (n = 50; kappa = 0.88; outcome, log-rank p < 0.001). Lower prevalence of MGMT methylation among CpG island methylator phenotype (CIMP) positive tumors was found in glioblastomas from The Cancer Genome Atlas than in low grade and anaplastic glioma cohorts, while in CIMP-negative gliomas MGMT was classified as methylated in approximately 50 % regardless of tumor grade. The proposed MGMT-STP27 prediction model allows mining of datasets derived on the HM-450K or HM-27K BeadChip to explore effects of distinct epigenetic context of MGMT methylation suspected to modulate treatment resistance in different tumor types.

Taxonomic status of Hylomys parvus and Hylomys suillus (Insectivora: Erinaceidae): biochemical and morphological analyses

The genus Hylomys was thought to be represented by a single widespread species. Biochemical and morphometric analyses of several Southeast Asian populations reveal that Sumatra is inhabited by two distinct species, the dwarf gymnure (H. parvus) and the lesser gymnure (H. suillus). The absence of interbreeding between these two groups along with their relatively ancient common origins are documented by several diagnostic loci and a large Nei's genetic distance (D = 0.353 +/- 0.035). The dwarf gymnure has been reported only from the slopes of the Mt. Kerinci volcano in Sumatra, where the species lives at higher elevations than its potential competitor, the lesser gymnure. Other populations of Hylomys from Java, Borneo, and Malaysia are more closely related to the Sumatran sample of H. suillus, but they exhibit strong interpopulational genetic differentiation (D = 0.165 +/- 0.040) that may be accounted for by their isolated montane habitat. In addition, a principal-components analysis based on 16 measurements of the skull clearly separates adult specimens of both species. There is little overlap in the measurements between H. suillus (which is larger) and H. parvus. On Sumatra where both species may be sympatric, the notched space between premaxillary tips, soft texture of the fur, and more delicate skull and dentition are diagnostic of H. parvus.

Bowel ischemia: a rare complication of thiopental treatment for status epilepticus.

BACKGROUND: Refractory status epilepticus (RSE) treatment is usually performed with coma induction using an appropriate general anesthetic. Most frequent complications are represented by hypotension and infection. Other side-effects may however be encountered. OBSERVATIONS: We describe two patients suffering from acute bowel ischemia after thiopental (THP) treatment for RSE. A 73-year-old man with a complex-patial RSE following an acute stroke received THP (303 mg/kg over 48 h); 36 h after THP discontinuation, he presented abdominal tenderness and lactate elevation. Necrosis of the terminal ileum and colon was seen during surgical exploration; he deceased shortly thereafter. A 21 year-old woman had a cryptogenic de novo generalized-convulsive RSE resistant to 5 attempts of EEG burst-suppression. During the 6th attempt, after THP (840 mg/kg over 150 h) together with mild hypothermia, she developed an ileus with elevated serum lactate; caecum necrosis was observed during surgery. Hypernatremia, acidosis and hyperlactatemia heralded this complication in both patients. CONCLUSION: In these two patients, mechanical vascular ischemia may have resulted from drug-induced paralytic ileus. To our knowledge, this is the first report describing this potential fatal side effect in adults with RSE.

Determinants of methicillin-susceptible Staphylococcus aureus native bone and joint infection treatment failure: a retrospective cohort study.

BACKGROUND: Although methicillin-susceptible Staphylococcus aureus (MSSA) native bone and joint infection (BJI) constitutes the more frequent clinical entity of BJI, prognostic studies mostly focused on methicillin-resistant S. aureus prosthetic joint infection. We aimed to assess the determinants of native MSSA BJI outcomes. METHODS: Retrospective cohort study (2001-2011) of patients admitted in a reference hospital centre for native MSSA BJI. Treatment failure determinants were assessed using Kaplan-Meier curves and binary logistic regression. RESULTS: Sixty-six patients (42 males [63.6%]; median age 61.2 years; interquartile range [IQR] 45.9-71.9) presented an acute (n = 38; 57.6%) or chronic (n = 28; 42.4%) native MSSA arthritis (n = 15; 22.7%), osteomyelitis (n = 19; 28.8%) or spondylodiscitis (n = 32; 48.5%), considered as "difficult-to-treat" in 61 cases (92.4%). All received a prolonged (27.1 weeks; IQR, 16.9-36.1) combined antimicrobial therapy, after surgical management in 37 cases (56.1%). Sixteen treatment failures (24.2%) were observed during a median follow-up period of 63.3 weeks (IQR, 44.7-103.1), including 13 persisting infections, 1 relapse after treatment disruption, and 2 super-infections. Independent determinants of treatment failure were the existence of a sinus tract (odds ratio [OR], 5.300; 95% confidence interval [CI], 1.166-24.103) and a prolonged delay to infectious disease specialist referral (OR, 1.134; 95% CI 1.013-1.271). CONCLUSIONS: The important treatment failure rate pinpointed the difficulty of cure encountered in complicated native MSSA BJI. An early infectious disease specialist referral is essential, especially in debilitated patients or in presence of sinus tract.