Time course of clinical response to venlafaxine: relevance of plasma level and chirality

Objective: Early clinical response to antidepressant treatment is an important therapeutic goal, considering the psychological, social and economic consequences of depression. The aim of the present study was to investigate the relationship between the time course of response and the concentration of venlafaxine (V), its active metabolite O-desmethylvenlafaxine (ODV) and enantiomeric ratios V(+)/V(−) and ODV(+)/ODV(−). Methods: Depressed inpatients (n=35) received V orally at a fixed 300mg daily dose. Accepted comedication included clorazepate (maximum 60mg/day), zopiclone (maximum 15mg/day) and low-dose trazodone (maximum 200mg/day). Severity of depression was assessed on days0, 4, 7, 11, 14, 21 and 28 (Montgomery and Åsberg Depression Rating Scale). Blood samples were taken on day14 and day28 and submitted to stereoselective determination. All measurements reflected trough steady-state values. First, pattern analysis was used to provide a categorical perspective of clinical response (50% improvement from baseline depression score). Patients displaying non-response, transient response, early persistent response and delayed persistent response were compared with respect to racemic concentrations and enantiomeric ratios. Second, in a dimensional perspective, mixed-effects modelling was used to analyse severity of depression versus time curves with respect to the possible influence of concentrations and enantiomeric ratios. Results: Comparison of patients with and without persistent response did not reveal any significant difference for V, ODV, V+ODV plasma levels or enantiomeric ratios. Persistent response was significantly associated with less frequent pre-study antidepressant medication and less frequent comedication with zopiclone (day14) and clorazepate (day28) during the study. Focus on patients with persistent response (n=19, 54.3%) indicated that early response, first observed before day14, was associated with significantly higher V+ODV concentration than delayed response (median 725ng/ml versus 554ng/ml, P=0.023). No difference was found for pre-study medication or comedication during the study. Shorter time to onset of response was significantly associated with lower V(+)/V(−) enantiomeric ratio (rs=0.48, P<0.05). Mixed-effects modelling of depression severity versus time curves in patients with persistent response confirmed that either higher V+ODV plasma level or lower V(+)/V(−) ratio were significantly associated with more rapid decrease of depression score (likelihood ratio tests, P=0.012 and P=0.046, respectively). Conclusion: Considering its modest sample size, naturalistic design and limited observation period, the present study provided preliminary indication that earlier clinical response may occur with higher V+ODV plasma level, extending previous dose-response studies. The hypothesis was also raised that exposure to a more potent noradrenergic therapeutic moiety, as reflected by a lower V(+)/V(−) ratio, may be relevant to early improvement of depressio

Carnet du 16 au 27 février 1874

Dans l’ensemble proprement océanique du legs fondateur de Victor Hugo à la Bibliothèque nationale, on trouve non seulement les œuvres, publiées ou non, copiées et traitées avec le plus grand soin, mais aussi les dessins, la masse des brouillons non employés, vers et prose mêlés, et enfin une quarantaine de petits carnets remplis de notes quotidiennes. Si ces derniers sont connus du grand public, c’est avant tout pour des raisons éditoriales. Encouragés par le « Testament littéraire » laissé p..

DOGAĐAJ ZA RODITELJE UČENIKA NIŽIH STRUKOVNIH OBRAZOVANJA

Uspjesi, neuspjesi i obrazovni problemi, odnosno njihovo rješavanje, temelje se na obiteljskom odgoju, naravno u vezi sa školskim obrazovanjem i sredinom u kojoj učenik živi i radi.Redovita suradnja roditelja i škole doprinosi pravovremenom informiranju o učenikovom školskom radu i uspjehu, a time i pravodobnom i učinkovitom djelovanju.Komunikacija roditelja i stručnih djelatnika škole odvija se na roditeljskim sastancima, zajedničkim i individualnim razgovorima, individualnim razgovorima u okviru školske savjetodavne službe, sjednicama vijeća roditelja te uz sudjelovanje roditelja na danima otvorenih vrata, danima aktivnosti i priredbama. [1]. Učitelji i roditelji imaju zajednički cilj. Težimo zadovoljstvu, sreći, samostalnosti i uspjehu djece. Stoga je suradnja škole i roditelja iznimno važna. Jedan od oblika suradnje su i priredbe za roditelje koje pripremaju učenici pod mentorstvom nastavnika. Učenici pokazuju barem djelić znanja i kreativnosti koje su stekli tijekom školovanja. Stvaraju se nove veze između učitelja, učenika i roditelja, a ujedno je to i prilika za međupredmetno povezivanje. Ovakva događanja iznimno su važna za učenike koji pohađaju program nižeg strukovnog obrazovanja

UČENJE O ODRŽIVOSTI KROZ PROJEKTE ZAŠTITE OKOLIŠA

U današnje vrijeme poučavanje o globalnim problemima i održivosti više nije dovoljno samo po sebi. Mladi ljudi, donositelji odluka budućnosti, trebaju praktične vještine koje će im omogućiti nastavak učenja i nakon završenog obrazovanja. Obrazovanje je ključno za razvoj i postizanje održivih ciljeva društva. Održivost nije nešto što naučite, to je nešto što živite.Održivost učenja kroz projekte omogućuje nastavnicima planiranje i ciljno usmjeren rad, a učenicima razvijaju samostalnost, inovativnost i kreativnost. Kroz projektni rad učenici dolaze do vlastitih zaključaka i razvijaju svijest o očuvanju okoliša. U članku ću sažeti neke od najistaknutijih aktivnosti koje provodimo u učenju za održivi razvoj

Sex-chrom, a database on plant sex chromosomes

This work has been supported by the Dirección General de Investigación Científica y Técnica (Spanish Government: CGL2016-75694-P AEI/FEDER, UE; CGL2017-84297-R), by the Generalitat de Catalunya (‘Ajuts a grups de recerca consolidats’ 2017SGR01116’), by the Czech Science Foundation (grants 16-08698S, 18-06147S and 19-03442S) and by CIJA PRESERVATION, SL. SG benefitted from a Ramón y Cajal contract (RYC-2014-16608) from the government of Spain, and SB and NS received Erasmus + grants from the European Union.Introduction Types of plant sex chromosomes, sex determination systems and their diversity Model systems in sex chromosome research Materials and Methods Information sources Data mining Database web environment and construction Results and Discussion Future directions Acknowledgements Author contribution

Measurement of the velocity distribution of sputtered Na atoms from NaCl by Doppler shift laser fluorescence

The velocity distribution of sputtered Na atoms from NaCI during 15 keV, Ar+ bombardment was measured by a Doppler shift laser fluorescence technique. Contrary to other measurements, the sputtered Na atoms were found to have a velocity distribution identical to that of a three-dimensional Maxwell-Boltzmann gas.Peer reviewedElectrical and Computer Engineerin

Optical pulse compression based on enhanced frequency chirping

Through numerical simulations, we show that, under relatively general conditions, passage of an intense picosecond pulse through a single-mode optical fiber can cause the pulse to become strongly frequency broadened with a positive chirp (linear frequency sweep) describing essentially all of the energy of the output pulse. Also, because the optical fiber supports only a single transverse mode, the entire output beam profile has the same frequency modulation. These two features allow for unprecedented optical pulse compression.Peer reviewedElectrical and Computer Engineerin