Phytoconstituents of leaf extracts of Ziziphus jujuba Mill. plants harvested in Tunisia

The present study aimed to determine the phytoconstituent compositions of the leaves of four Ziziphus jujuba ecotypes (Choutrana, Mahdia, Mahres and Sfax). The chromatographic peaks of 18 compounds, including nine major fatty acids, five sterols, two triterpene alcohols and two methysterols, were quantified by the capillary gaseous chromatography method. The major fatty acids identified were linolenic (42.04%) and palmitic (23.04%). Unsaturated fatty acids ranged between 53% and 60%. The predominant sterols (mg/100g) were β-sitosterol (40.36) and stigmasterol (24.18). Cycloartenol (68.55mg/100g) and citrostadienol (12.27mg/100g) were the major metylsterols. Methylene cycloartanol ranged between 1.2mg/100g (Sfax) and 1.5mg/100g (Mahdia). Total phenolic content measured by Folin-ciocalteux ranged from 3.97mg GAE/g to 6.04mg GAE/g. The predominant flavonoids identified by HPLC were apigenin (6.1mg/g) and rutin (1.91mg/g). The fatty acids and flavonoids in the Z. jujuba leaves were responsible for their therapeutic and pharmaceutical effects. This could explain why Tunisian people traditionally use it as medicine to treat several pathologies

Comparative static curing versus dynamic curing on tablet coating structures

International audienceCuring is generally required to stabilize film coating from aqueous polymer dispersion. This post-coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the coating equipment stands for an attractive industrial application. Recently, the use of various advanced physico-chemical characterization techniques i.e., X-ray micro-computed tomography, vibrational spectroscopies (near infrared and Raman) and X-ray microdiffraction, allowed new insights into the film-coating structures of dynamically cured tablets. Dynamic curing end-point was efficiently determined after 4 h. The aim of the present work was to elucidate the influence of curing conditions on film-coating structures. Results demonstrated that 24 h of static curing and 4 h of dynamic curing, both performed at 60 degrees C and ambient relative humidity, led to similar coating layers in terms of drug release properties, porosity, water content, structural rearrangement of polymer chains and crystalline distribution. Furthermore, X-ray microdiffraction measurements pointed out different crystalline coating compositions depending on sample storage time. An aging mechanism might have occur during storage, resulting in the crystallization and the upward migration of cetyl alcohol, coupled to the downward migration of crystalline sodium lauryl sulfate within the coating layer. Interestingly, this new study clearly provided further knowledge into film-coating structures after a curing step and confirmed that curing operation could be performed in dynamic conditions

Comprehensive study of dynamic curing effect on tablet coating structure

International audienceThe dissolution method is still widely used to determine curing end-points to ensure long-term stability of film coatings. Nevertheless, the process of curing has not yet been fully investigated. For the first time, joint techniques were used to elucidate the mechanisms of dynamic curing over time from ethylcellulose (Aquacoat (R))-based coated tablets. X-ray micro-computed tomography (X mu CT), Near Infrared (NIR), and Raman spectroscopies as well as X-ray microdiffraction were employed as non-destructive techniques to perform direct measurements on tablets. All techniques indicated that after a dynamic curing period of 4 h, reproducible drug release can be achieved and no changes in the microstructure of the coating were any longer detected. X mu CT analysis highlighted the reduced internal porosity, while both NIR and Raman measurements showed that spectral information remained unaltered after further curing. X-ray microdiffraction revealed densification of the coating layer with a decrease in the overall coating thickness of about 10 pm as a result of curing. In addition, coating heterogeneity attributed to cetyl alcohol was observed from microscopic images and Raman analysis. This observation was confirmed by X-ray microdiffraction that showed that crystalline cetyl alcohol melted and spread over the coating surface with curing. Prior to curing, X-ray microdiffraction also revealed the existence of two coating zones differing in crystalline cetyl alcohol and sodium lauryl sulfate concentrations which could be explained by migration of these constituents within the coating layer. Therefore, the use of non-destructive techniques allowed new insights into tablet coating structures and provided precise determination of the curing end-point compared to traditional dissolution testing. This thorough study may open up new possibilities for process and formulation control

CD1 Gene Polymorphisms and Phenotypic Variability in X-Linked Adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is characterized by marked phenotypic variation ranging from adrenomyeloneuropathy (AMN) to childhood cerebral ALD (CCALD). X-ALD is caused by mutations in the ABCD1 gene, but no genotype-phenotype correlation has been established so far and modifier gene variants are suspected to modulate phenotypes. Specific classes of lipids, enriched in very long-chain fatty acids that accumulate in plasma and tissues from X-ALD patients are suspected to be involved in the neuroinflammatory process of CCALD. CD1 proteins are lipid- antigen presenting molecules encoded by five CD1 genes in human (CD1A-E). Association studies with 23 tag SNPs covering the CD1 locus was performed in 52 patients with AMN and 87 patients with CCALD. The minor allele of rs973742 located 4-kb downstream from CD1D was significantly more frequent in AMN patients (χ2 = 7.6; P = 0.006). However, this association was no longer significant after Bonferroni correction for multiple testing. The other polymorphisms of the CD1 locus did not reveal significant association. Further analysis of other CD1D polymorphisms did not detect stronger association with X-ALD phenotypes. Although the association with rs973742 warrants further investigations, these results indicate that the genetic variants of CD1 genes do not contribute markedly to the phenotypic variance of X-ALD

Site-specific conjugation for fully controlled glycoconjugate vaccine preparation

Glycoconjugate vaccines are formed by covalently link a carbohydrate antigen to a carrier protein whose role is to achieve a long lasting immune response directed against the carbohydrate antigen. The nature of the sugar antigen, its length, its ratio per carrier protein and the conjugation chemistry impact on both structure and the immune response of a glycoconjugate vaccine. In addition it has long been assumed that the sites at which the carbohydrate antigen is attached can also have an impact. These important issue can now be addressed owing to the development of novel chemoselective ligation reactions as well as techniques such as site-selective mutagenesis, glycoengineering, or extension of the genetic code. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. A synthetic tetrasaccharide representative of the serotype 14 capsular polysaccharide of Streptococcus pneumoniae has been linked using the thiol/maleimide coupling chemistry to four different Pneumococcal surface adhesin A (PsaA) mutants, each harboring a single cysteine mutation at a defined position. Humoral response of these 1 to 1 carbohydrate antigen/PsaA conjugates have been assessed in mice. Our results showed that the carbohydrate antigen-PsaA connectivity impacts the anti-carrier response and raise questions about the design of glycoconjugate vaccine whereby the protein plays the dual role of immunogen and carrier.S

Psychological Balance in High Level Athletes: Gender-Based Differences and Sport-Specific Patterns

OBJECTIVES: Few epidemiological studies have focused on the psychological health of high level athletes. This study aimed to identify the principal psychological problems encountered within French high level athletes, and the variations in their prevalence based on sex and the sport practiced. METHODS: Multivariate analyses were conducted on nationwide data obtained from the athletes' yearly psychological evaluations. RESULTS: A representative sample of 13% of the French athlete population was obtained. 17% of athletes have at least one ongoing or recent disorder, generalized anxiety disorder (GAD) being the most prevalent (6%), followed by non-specific eating disorders (4.2%). Overall, 20.2% of women had at least one psychopathology, against 15.1% in men. This female predominance applied to anxiety and eating disorders, depression, sleep problems and self-harming behaviors. The highest rates of GAD appeared in aesthetic sports (16.7% vs. 6.8% in other sports for men and 38.9% vs. 10.3% for women); the lowest prevalence was found in high risk sports athletes (3.0% vs. 3.5%). Eating disorders are most common among women in racing sports (14% vs. 9%), but for men were found mostly in combat sports (7% vs. 4.8%). DISCUSSION: This study highlights important differences in psychopathology between male and female athletes, demonstrating that the many sex-based differences reported in the general population apply to elite athletes. While the prevalence of psychological problems is no higher than in the general population, the variations in psychopathology in different sports suggest that specific constraints could influence the development of some disorders

Breast carcinoma detection in ex vivo fresh human breast surgical specimens using a fast slide-free confocal microscopy scanner: HIBISCUSS project

Background: New generation ultra-fast fluorescence confocal microscopy allows the ex vivo intraoperative analysis of fresh tissue. The High resolution Imaging for Breast carcInoma detection in ex vivo Specimens after breast Conserving sUrgery by hiStolog Scanner (HIBISCUSS) project aimed to develop an online learning program to recognize the main breast tissue features on ultra-fast fluorescence confocal microscopy images and to evaluate the performance of surgeons and pathologists in diagnosing cancerous and non-cancerous breast tissue in ultra-fast fluorescence confocal microscopy images. Methods: Patients who underwent conservative surgery or mastectomy for breast carcinoma (invasive or in situ lesions) were included. The fresh specimens were stained with a fluorescent dye and imaged using a large field-of-view (20 cm2) ultra-fast fluorescence confocal microscope. Results: One hundred and eighty-one patients were included. The images from 55 patients were annotated to generate learning sheets and images from 126 patients were blindly interpreted by seven surgeons and two pathologists. The time for tissue processing and ultra-fast fluorescence confocal microscopy imaging was between 8 and 10 min. The training program was composed of 110 images divided into nine learning sessions. The final database for blind performance assessment comprised 300 images. The mean duration for one training session and one performance round was 17 and 27 min respectively. The performance of pathologists was almost perfect with 99.6 per cent (standard deviation (s.d.) 5.4 per cent) accuracy. Surgeons' accuracy significantly increased (P = 0.001) from 83 per cent (s.d. 8.4 per cent) in round 1 to 98 per cent (s.d. 4.1 per cent) in round 7 as well as the sensitivity (P = 0.004). Specificity increased without significance from 84 per cent (s.d. 16.7 per cent) in round 1 to 87 per cent (s.d. 16.4 per cent) in round 7 (P = 0.060). Conclusion: Pathologists and surgeons showed a short learning curve in differentiating breast cancer from non-cancerous tissue in ultra-fast fluorescence confocal microscopy images. Performance assessment for both specialties supports ultra-fast fluorescence confocal microscopy evaluation for intraoperative management. Registration number: NCT04976556 (http://www.clinicaltrials.gov)

Paradigms of Lung Microbiota Functions in Health and Disease, Particularly, in Asthma

Improvements in our knowledge of the gut microbiota have broadened our vision of the microbes associated with the intestine. These microbes are essential actors and protectors of digestive and extra-digestive health and, by extension, crucial for human physiology. Similar reconsiderations are currently underway concerning the endogenous microbes of the lungs, with a shift in focus away from their involvement in infections toward a role in physiology. The discovery of the lung microbiota was delayed by the long-held view that the lungs of healthy individuals were sterile and by sampling difficulties. The lung microbiota has a low density, and the maintenance of small numbers of bacteria seems to be a critical determinant of good health. This review aims to highlight how knowledge about the lung microbiota can change our conception of lung physiology and respiratory health. We provide support for this point of view with knowledge acquired about the gut microbiota and intestinal physiology. We describe the main characteristics of the lung microbiota and its functional impact on lung physiology, particularly in healthy individuals, after birth, but also in asthma. We describe some of the physiological features of the respiratory tract potentially favoring the installation of a dysbiotic microbiota. The gut microbiota feeds and matures the intestinal epithelium and is involved in immunity, when the principal role of the lung microbiota seems to be the orientation and balance of aspects of immune and epithelial responsiveness. This implies that the local and remote effects of bacterial communities are likely to be determinant in many respiratory diseases caused by viruses, allergens or genetic deficiency. Finally, we discuss the reciprocal connections between the gut and lungs that render these two compartments inseparable