Sugars separation in a fermentative broth by simulated moving bed chromatography : SMB

Des sucres tels que les fructo-oligosaccharides (FOS) sont bénéfiques pour leurs hôtes car ils stimulent la croissance de bactéries bénéfiques dans le colon du fait qu’ils ne sont pas digérés par l’organisme. Ces FOS peuvent être produits à grande échelle par un procédé de fermentation du sucrose dont le milieu résultant (FOS + autres sucres + sels) doit être séparé en ses différents constituants afin de respecter les normes agroalimentaires. Parmi les techniques permettant cette séparation, seule la chromatographie liquide est applicable à grande échelle afin d’obtenir les puretés requises. La technique de séparation par lit mobile simulé (Simulated Moving Bed – SMB) permet de rendre le procédé continu et de diminuer la consommation d’éluant tout en augmentant la productivité. L’efficacité des techniques chromatographiques dépendant en grande partie de la nature de l’adsorbant, une étude préliminaire a été réalisée dans le but d’identifier le meilleur adsorbant pour cette séparation. Une résine échangeuse d’ions choisie, différentes techniques d’identification des paramètres de fonctionnement ont été mises en oeuvre afin de tester la séparation en mode SMB. Les résultats obtenus permettent de montrer qu’à partir d’un milieu de fermentation contenant 40% de FOS, il est possible d’obtenir un produit final pur à plus de 80%. Néanmoins, il a été mis en évidence que si la présence de sucrose dans le milieu de fermentation est inévitable, il faut absolument la contrôler au maximum pour éviter la pollution du produit finalFructooligosaccharides (FOS) are non-digestible sugars which affect positively the host by stimulating the growth of specific bacteria in the colon. At large scale, FOS can be produced from sucrose through fermentation. The fermentative broth obtained from this process is a complex mixture. The application of these sugars in the food industry requires their fractionation in order to meet final product specifications. Simulated moving bed chromatography (SMB) appears to be an efficient downstream process for the fractionation of sugars at an industrial scale. Thanks to this technique it is possible to work continuously reducing the solvent consumption and increasing the productivity. The major challenge when designing the separation process is the choice of an efficient adsorbent. A preliminary study was thus realized in order to identify the best adsorbent. An ion exchange resin was chosen and several parametric identification techniques were performed in order to realize the SMB separation. The results display the possibility to increase the FOS purity from 40% to 80%. Nevertheless, it was also displayed that sucrose present in the broth troubles the separation and must be strictly controlled during the fermentation

Operating conditions of a simulated moving bed chromatography unit for the purification of fructooligosaccharides

C. Nobre acknowledges the F.C.T. - Fundacao para a Ciencia e a Tecnologia (Portugal) for the PhD Grant ref. SFRH/BD/32514/2006. A. Severino is funded by Belgian Fund for Scientific Research (F.S.R.- FNRS).This paper presents research results of the Belgian Network DYSCO (Dynamical Systems, Control, and Optimization), funded by the Interuniversity Attraction Poles Programme, initiated by the Belgian Federal Science Policy Office (BELSPO). The scientific responsibility rests with its authors

Acute effect of whole body vibration in the upper limbs strength

O objetivo desse estudo foi verificar o efeito agudo da aplicação de vibração de corpo inteiro (VCI) sobre o impulso e sobre a força máxima de membros superiores. Vinte voluntários do sexo masculino, treinados, com idade: 23,8 ± 3,3 anos, foram submetidos a 3 sessões (uma sessão de familiarização e duas sessões de intervenção). Em cada uma das sessões de intervenção os voluntários realizaram uma contração voluntária máxima (CVM) de flexores do cotovelo sem aplicação de vibração e duas CVM com adição de vibração. Foram utilizadas 4 frequências de VCI (10, 20, 30 e 40Hz) distribuídas de maneira aleatória nas 4 CVM realizadas com vibração nas duas sessões de coleta. Os resultados encontrados mostraram que a força máxima e o impulso gerados na contração sem vibração foram significativamente maiores do que a força máxima e o impulso gerados durante a contração realizada com aplicação de VCI. Para o treinamento de força, a aplicação de VCI, nas frequências testadas na presente investigação, representou um menor estímulo de treinamento para os membros superiores, uma vez que gerou uma redução na força máxima e no impulso dos músculos flexores do cotovelo.The aim of this study was to investigate, from a protocol of maximal isometric contractions of the elbow flexors, the effect of WBV in the maximal force and of impulse in strength-trained individuals. Twenty male volunteers, age: 23.8 ± 3.3 years, performed 3 sessions (one familiarization session and two intervention session). The sessions were composed by 3 MVC of the elbows flexor muscles with 5 minute of rest between them. The first CVM was performed without vibration and the others, applying aleatory WBV with 10, 20, 30, 40Hz, and amplitude of 6mm. The results showed that the maximal force and of impulse obtained during the MVC without vibration was significantly higher than the maximal force and of impulse recorded during the application of WBV. For strength training, the application of WBV, in the adopted frequencies, was not able to generate sufficient stimulus to induce acute adaptations in muscle strength of upper limbs

Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD

Characterisation of age and polarity at onset in bipolar disorder

Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses

Lipid nanoparticles for the posterior eye segment

This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug carriers for pathologies affecting the posterior ocular segment. Eye anatomy and the most relevant diseases affecting the posterior segment will be summarized. Moreover, preparation methods and different types and subtypes of lipid nanoparticles will also be reviewed. Lipid nanoparticles used as carriers to deliver drugs to the posterior eye segment as well as their administration routes, pharmaceutical forms and ocular distribution will be discussed emphasizing the different targeting strategies most recently employed for ocular drug delivery.This research was funded by the Portuguese Science and Technology Foundation (FCT/MCT) and European Funds (PRODER/COMPETE), under the project reference UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

In papillary thyroid carcinoma BRAFV600E is associated with increased expression of the urokinase plasminogen activator and its cognate receptor, but not with disease-free interval

Context It has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAFV600E mutation have a worse prognosis. We showed in PTC that high levels of urokinase plasminogen activator (uPA) and its cognate receptor (uPAR) inversely correlate with disease-free interval (DFI). Objectives To investigate the effects of BRAFV600E on the expression of uPA and uPAR and to evaluate the prognostic relevance of BRAFV600E alone or in combination with uPA and uPAR. Design/Setting/Patients/Intervention The case study included 91 patients with PTC. All patients underwent thyroidectomy and radioiodine therapy. Follow-up was available for 75 patients. Main outcome measures The BRAFV600E mutation was analysed by sequencing and mutant allele-specific PCR amplification; uPA and uPAR expression by quantitative RT-PCR. Results BRAFV600E was found in 44 of the 91 patients and associated with older age, but not with high-risk clinicopathological features. Urokinase PA and uPAR mRNA levels were higher in tumour tissues by 9.51 similar to +/-similar to 1.30 and 4.64 similar to +/-similar to 0.44 fold, respectively, compared to normal matched tissues, being significantly higher in BRAFV600E-positive patients. In vitro induction of BRAFV600E in PCCL3 cells caused a significant increase in both uPA and uPAR mRNAs. Higher levels of uPA and uPAR correlated with lymph node metastases, TNM stage and disease recurrences. KaplanMeier and multivariate analyses demonstrated that uPA and uPAR were associated with shorter DFI, while the BRAFV600E was not. Conclusion In PTC, BRAFV600E induces uPA and uPAR expression. The latter, but not BRAFV600E, associates with advanced stages and shorter DFI. If confirmed in larger case studies, they may represent reliable prognostic markers for more accurate risk stratification and postoperative decision-making in patients with PTC

Interlaboratory study of a supercritical fluid chromatography method for the determination of pharmaceutical impurities: Evaluation of multi-systems reproducibility

Modern supercritical fluid chromatography (SFC) is now a well-established technique, especially in the field of pharmaceutical analysis. We recently demonstrated the transferability and the reproducibility of a SFC-UV method for pharmaceutical impurities by means of an inter-laboratory study. However, as this study involved only one brand of SFC instrumentation (Waters®), the present study extends the purpose to multi-instrumentation evaluation. Specifically, three instrument types, namely Agilent®, Shimadzu®, and Waters®, were included through 21 laboratories (n = 7 for each instrument). First, method transfer was performed to assess the separation quality and to set up the specific instrument parameters of Agilent® and Shimadzu® instruments. Second, the inter-laboratory study was performed following a protocol defined by the sending lab. Analytical results were examined regarding consistencies within- and between-laboratories criteria. Afterwards, the method reproducibility was estimated taking into account variances in replicates, between-days and between-laboratories. Reproducibility variance was larger than that observed during the first study involving only one single type of instrumentation. Indeed, we clearly observed an ‘instrument type’ effect. Moreover, the reproducibility variance was larger when considering all instruments than each type separately which can be attributed to the variability induced by the instrument configuration. Nevertheless, repeatability and reproducibility variances were found to be similar than those described for LC methods; i.e. reproducibility as %RSD was around 15 %. These results highlighted the robustness and the power of modern analytical SFC technologies to deliver accurate results for pharmaceutical quality control analysis.FEDER PHARE - FAKEPHAR