Incidence and prevalence of drug-resistant epilepsy : a systematic review and meta-analysis

Objective To evaluate the incidence and prevalence of drug-resistant epilepsy (DRE) as well as its predictors and correlates, we conducted a systematic review and meta-analysis of observational studies. Methods Our protocol was registered with PROSPERO, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology reporting standards were followed. We searched MEDLINE, Embase, and Web of Science. We used a double arcsine transformation and random-effects models to perform our meta-analyses. We performed random-effects meta-regressions using study-level data. Results Our search strategy identified 10,794 abstracts. Of these, 103 articles met our eligibility criteria. There was high interstudy heterogeneity and risk of bias. The cumulative incidence of DRE was 25.0% (95% confidence interval [CI]: 16.8–34.3) in child studies but 14.6% (95% CI: 8.8–21.6) in adult/mixed age studies. The prevalence of DRE was 13.7% (95% CI: 9.2–19.0) in population/community-based populations but 36.3% (95% CI: 30.4–42.4) in clinic-based cohorts. Meta-regression confirmed that the prevalence of DRE was higher in clinic-based populations and in focal epilepsy. Multiple predictors and correlates of DRE were identified. The most reported of these were having a neurologic deficit, an abnormal EEG, and symptomatic epilepsy. The most reported genetic predictors of DRE were polymorphisms of the ABCB1 gene. Conclusions Our observations provide a basis for estimating the incidence and prevalence of DRE, which vary between populations. We identified numerous putative DRE predictors and correlates. These findings are important to plan epilepsy services, including epilepsy surgery, a crucial treatment option for people with disabling seizures and DRE

Hydrosilylation asymétrique de cétones fonctionnalisées avec le PMHS (utilisation de complexes de zinc)

L'hydrosilylation asymétrique est une voies d'accès aux alcools et amines énantiopurs. Bien que très efficace, le coût et la toxicité des réducteurs silanes associés limite son application industrielle. Notre étude a porté sur le développement d'un système catalytique associant le zinc à des diamines et utilisant le PMHS, hydrosilane peu cher, stable et nontoxique. En milieu aprotique, la réduction d'alkylarylcétones s'effectue avec de hautes cbimio- et énantiosélectivités. La synthèse de nouvelles 1,2-diamines a permis d'atteindre 91 % d'excès énantiomérique sur l'acétophénone. Les substrats polyfonctionnels sont cependant difficilement réduits dans le toluène. A l'opposée, ce système est efficace en milieu protique sur une large gamme de substrats (alkylarylcétones, a- et b-cétoesters, cétoamides et imines). La procédure de réduction simple en une étape mène à d'excellentes activités et chimiosélectivités, les énantiosélectivités restant toutefois modestes (15-48 %). Divers précurseurs catalytiques simples et peu chers, tels que Zn(OMe)2ou Zn(OH)2,peuvent être employés. L'étude des mécanismes en milieu aprotique/protique a conduit à la synthèse et à l'étude de la réactivité de nouveaux complexes de zinc, proposés comme intermédiaires réactionnels ) pour expliquer les réactivités inhabituelles en milieu protique.LILLE1-BU (590092102) / SudocSudocFranceF

Aquaporins Mediate Silicon Transport in Humans.

In animals, silicon is an abundant and differentially distributed trace element that is believed to play important biological functions. One would thus expect silicon concentrations in body fluids to be regulated by silicon transporters at the surface of many cell types. Curiously, however, and even though they exist in plants and algae, no such transporters have been identified to date in vertebrates. Here, we show for the first time that the human aquaglyceroporins, i.e., AQP3, AQP7, AQP9 and AQP10 can act as silicon transporters in both Xenopus laevis oocytes and HEK-293 cells. In particular, heterologously expressed AQP7, AQP9 and AQP10 are all able to induce robust, saturable, phloretin-sensitive silicon transport activity in the range that was observed for low silicon rice 1 (lsi1), a silicon transporter in plant. Furthermore, we show that the aquaglyceroporins appear as relevant silicon permeation pathways in both mice and humans based on 1) the kinetics of substrate transport, 2) their presence in tissues where silicon is presumed to play key roles and 3) their transcriptional responses to changes in dietary silicon. Taken together, our data provide new evidence that silicon is a potentially important biological element in animals and that its body distribution is regulated. They should open up original areas of investigations aimed at deciphering the true physiological role of silicon in vertebrates

AQP expression and Si transport in HEK-293 cells.

<p>(A) Effect of anti-AQP3, AQP7, AQP9 and AQP10 siRNAs on AQPG expression and Si efflux. HEK-293 cells incubated for ~48 h in R medium (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136149#pone.0136149.t002" target="_blank">Table 2</a>) + 2 mM H₄SiO₄ ± 5 different siRNAs and for 5 additional min in R medium alone were assayed for AQP expression by qPCR and for Si content. Data are expressed as % changes between conditions “scrambled siRNAs” and “anti-AQP siRNAs” and are presented as means ± S.E. of 2–8 measurements among 3 experiments. All of the changes are significantly different from 0. Note that threshold cycles in the absence of siRNAs were of ~30 for all the AQGPs. (B) Effect of anti-AQP7 siRNAs on AQPG expression. Protocols used and data expression are as described for panel A. Except for AQP10, all of the changes are significantly different from 0. (C) Total Si and ⁶⁸Ge influx. AQGP-transfected HEK-293 cells incubated for 5 min in R medium + 2 mM H₄GeO₄ with 1 μCi/mL H₄⁶⁸GeO₄ or in R medium + 2 mM H₄SiO₄ were assayed for both ⁶⁸Ge or Si content, respectively. Data are expressed as mean influx values ± S.E. of 4–8 measurements among 3–5 experiments. Compared to the controls, all of the values are significantly different. (D) Background-subtracted ⁶⁸Ge and Si influx. Influx values measured in pCDNA-transfected HEK-293 cells were subtracted from the influx values measured in AQGP-transfected HEK-293 cells. All values are significantly different from 0.</p

Characteristics of Si transport by AQP-expressing <i>Xenopus laevis</i> oocytes.

<p>(A) Dependence of Si influx on [H₄SiO₄]. Oocytes incubated for 30 min (AQP9), 60 min (AQP10) or 90 min (AQP7 and lsi1) in B1 medium (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136149#pone.0136149.t002" target="_blank">Table 2</a>) + 0 to 2 mM H₄SiO₄ were assayed for Si content. Data are expressed as background-subtracted influx values and are presented as means ± S.E. of 3 measurements among 3–5 experiments. (B) Dependence of Si influx on intracellular pH and on extracellular pH, [Na⁺], [K⁺], and [Cl⁻]. Oocytes incubated for 90 min in a modified B1 medium (called medium B3a, B3b, B3c, B3d or B3e) + 2 mM H₄SiO₄ were assayed for Si content. Data are expressed as <i>n</i>-fold differences and presented as means ± S.E. of 3 measurements among 6 experiments. None of the data are significantly different from 1. (C) Effect of phloretin on Si influx and water transport. Left scale: Oocytes incubated for 30 min in B2a medium + 2 mM H₄SiO₄ ± 0.1 mM phloretin were assayed for Si content. Data are expressed as background-subtracted influx values and presented as means ± S.E. of 3 measurements among 6 experiments. Right scale: Oocytes were assayed for cell volume during a 20-s incubation in ~10 mM sucrose ± 0.1 mM phloretin. Data are expressed as <i>n</i>-fold increases in cell volumes (V) relative to initial cell volumes (V₀) and presented as means ± S.E. of 5 oocytes among 4 experiments. * indicates that the values are significantly different between − P and + P. Abbreviations: i, intracellular; o, extracellular; + P, phloretin.</p