Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Valorisation des coproduits issus des industries d’agrumes : extraction des molécules bioactives par des technologies innovantes

This work consists of the valorization of citrus by-products with innovative technologies. Citrus pressing produces millions of tons of waste per year worldwide. This waste (peels, pulps and seeds) is generally dedicated to animal feed or eliminated by composting or incineration. However its content in bioactive molecules leads to several ways of valorization. Since peels present about half of the citrus waste mass, studies have been focused on the valorization of citrus peels by the extraction of bioactive compounds. Conventional methods generally used for the extraction of bioactive compounds (solid-liquid extraction, hydrodistillation) have several disadvantages such as the use of expensive and toxic solvents, long extraction times and high energy consumption. For this reason, several innovative non-thermal technologies such as Pulsed Electric Fields (PEF), High Voltage Electrical Discharges (HVED) and Ultrasounds (US) and thermal treatments such as microwaves (MO) and infrared (IR) have been tested for the valorization of citrus by-products. Whole citrus fruits (oranges, pomelos, lemons) were PEF treated at an intensity of 3 kV/cm, then citrus juice and polyphenols were extracted by pressing. The study of the PEF-induced cell permeabilization was conducted by several methods and showed that the degree of damage varied according to the type of the treated fruit. The electroporation of the cells induced by the PEF, allowed an increase the juice yields after pressing and improved the liberation of the polyphenols from the citrus peels into the juice. This explains the possibility of obtaining a juice rich in polyphenols by treating the whole fruits with PEF before pressing. Among the solvents tested for the extraction of polyphenols from citrus peels, water is the least effective. The addition of 20% glycerol to water changed the polarity of the medium and improved the extraction of the polyphenols. The use of an enzyme mixture enhanced the release of the polyphenols related to the polysaccharides. Deep eutectic solvents have been as effective as hydroethanolic mixtures. To improve the yields and the kinetics of extractions in the different green solvents and in the enzyme mixture, citrus peels were pretreated with HVED in water. The mechanical effect of HVED, based on the fragmentation of the peels has improved the extraction of polyphenols in the various solvents. The intensification of polyphenols extraction was also conducted by IR and US. The extraction of polyphenols by IR was optimized using the surface response methodology. IR heating did not alter the extracted polyphenols which have significant antifungal and anti-mycotoxinogenic activities. The pretreatment of citrus peels with IR weakened the cell structures, increasing thus the diffusion of polyphenols during US treatment.Ce travail de doctorat consiste à valoriser les coproduits issus des industries d’agrumes par des technologies innovantes. Le pressage des agrumes produit des millions de tonnes de déchets par an dans le monde. Ces déchets (peaux, pulpes et pépins) sont généralement dédiés à l’alimentation animale ou bien éliminés par compostage ou incinération. Cependant leur contenu en molécules bioactives conduit à plusieurs voies de valorisation. Vu que les peaux constituent à peu près la moitié de la masse des déchets d’agrumes, les études ont été faites sur la valorisation des peaux de différents types d’agrumes. Les méthodes conventionnelles généralement utilisées pour l’extraction des molécules d’intérêt (extraction solide-liquide, hydrodistillation) présentent plusieurs désavantages tels que l’utilisation des solvants coûteux et toxiques, les longues durées d’extraction et la consommation élevée en énergie. Pour cette raison plusieurs technologies innovantes non thermiques telles que les Champs Electriques Pulsés (CEP), les Décharges Électriques de Haute Tension (DEHT) et les ultrasons (US) et thermiques comme les microondes (MO) et les infrarouges (IR) ont été testées dans ce travail de thèse, pour la valorisation des coproduits d’agrumes. Les agrumes entiers (oranges, pomelos, citrons) sont traités par les CEP à une intensité de 3 kV/cm et l’extraction du jus d’agrumes et des polyphénols a été réalisée par pressage. L’étude de la perméabilisation cellulaire induite par les CEP a été réalisée par plusieurs méthodes et a montré que les degrés d’endommagement diffèrent selon le type d’agrumes traités. L’électroporation des cellules, induite par les CEP a permis d’augmenter les rendements en jus après pressage et d’améliorer le passage des polyphénols des peaux d’agrumes dans le jus. Ce qui explique la possibilité d’obtention d’un jus riche en polyphénols en traitant les agrumes par les CEP avant leur pressage. Parmi les solvants testés pour l’extraction des polyphénols à partir des peaux d’agrumes, l’eau est le moins efficace. L’ajout de 20% de glycérol dans l’eau a modifié la polarité du milieu et a amélioré l’extraction des polyphénols. L’utilisation d’un mélange enzymatique a favorisé la libération des polyphénols piégés dans les polysaccharides. Les solvants eutectiques profonds préparés, ont été aussi efficaces que les mélanges hydro éthanoliques. Pour améliorer d’avantages l’extraction dans les différents solvants verts ou dans le mélange enzymatique, les peaux d’agrumes ont été prétraitées par les DEHT dans l’eau. L’effet mécanique des DEHT, capable de fragmenter les peaux a permis d’améliorer l’extraction des polyphénols 6 dans les différents solvants. L’intensification de l’extraction des polyphénols a été aussi réalisée par les IR et les US. L’extraction des polyphénols par les IR a été optimisée en ayant recours à la méthodologie de surface de réponse. Le chauffage par les IR n’a pas altéré les polyphénols extraits qui ont gardé des activités antifongiques et anti-mycotoxinogènes importantes. Le prétraitement des peaux d’agrumes par les IR sans solvant a fragilisé les structures cellulaires, ce qui a permis d’augmenter la diffusion des polyphénols durant le traitement avec les US

Valorization of Low-Cost Substrates for the Production of Odd Chain Fatty Acids by the Oleaginous Yeast Yarrowia lipolytica

Odd-chain fatty acids (OCFAs) have recently gained interest as target compounds in microbial production due to their diverse applications in the medical, pharmaceutical and chemical industries for the production of biofuels. Yarrowia lipolytica is a promising oleaginous yeast that has the ability to accumulate high quantities of fatty acids. However, the use of Y. lipolytica oils is still under research, in order to decrease the production costs related to the fermentation process and improve economic feasibility. In this work, sugar beet molasses (10–50 g/L) and crude glycerol (30 g/L) were used as the main carbon sources to reduce the processing costs of oil production from a genetically engineered Y. lipolytica strain. The effects of medium composition were studied on biomass production, lipid content, and OCFAs profile. Lipid production by yeast growing on molasses (20 g/L sucrose) and crude glycerol reached 4.63 ± 0.95 g/L of culture medium. OCFAs content represented 58% of the total fatty acids in lipids, which corresponds to ≈2.69 ± 0.03 g/L of culture medium. The fermentation was upscaled to 5 L bioreactors and fed-batch co-feeding increased OCFA accumulation in Y. lipolytica by 56% compared to batch cultures

Valorization of byproducts from citrus industries : extraction of bioactive molecules using innovative technologies

Ce travail de doctorat consiste à valoriser les coproduits issus des industries d’agrumes par des technologies innovantes. Le pressage des agrumes produit des millions de tonnes de déchets par an dans le monde. Ces déchets (peaux, pulpes et pépins) sont généralement dédiés à l’alimentation animale ou bien éliminés par compostage ou incinération. Cependant leur contenu en molécules bioactives conduit à plusieurs voies de valorisation. Vu que les peaux constituent à peu près la moitié de la masse des déchets d’agrumes, les études ont été faites sur la valorisation des peaux de différents types d’agrumes. Les méthodes conventionnelles généralement utilisées pour l’extraction des molécules d’intérêt (extraction solide-liquide, hydrodistillation) présentent plusieurs désavantages tels que l’utilisation des solvants coûteux et toxiques, les longues durées d’extraction et la consommation élevée en énergie. Pour cette raison plusieurs technologies innovantes non thermiques telles que les Champs Electriques Pulsés (CEP), les Décharges Électriques de Haute Tension (DEHT) et les ultrasons (US) et thermiques comme les microondes (MO) et les infrarouges (IR) ont été testées dans ce travail de thèse, pour la valorisation des coproduits d’agrumes. Les agrumes entiers (oranges, pomelos, citrons) sont traités par les CEP à une intensité de 3 kV/cm et l’extraction du jus d’agrumes et des polyphénols a été réalisée par pressage. L’étude de la perméabilisation cellulaire induite par les CEP a été réalisée par plusieurs méthodes et a montré que les degrés d’endommagement diffèrent selon le type d’agrumes traités. L’électroporation des cellules, induite par les CEP a permis d’augmenter les rendements en jus après pressage et d’améliorer le passage des polyphénols des peaux d’agrumes dans le jus. Ce qui explique la possibilité d’obtention d’un jus riche en polyphénols en traitant les agrumes par les CEP avant leur pressage. Parmi les solvants testés pour l’extraction des polyphénols à partir des peaux d’agrumes, l’eau est le moins efficace. L’ajout de 20% de glycérol dans l’eau a modifié la polarité du milieu et a amélioré l’extraction des polyphénols. L’utilisation d’un mélange enzymatique a favorisé la libération des polyphénols piégés dans les polysaccharides. Les solvants eutectiques profonds préparés, ont été aussi efficaces que les mélanges hydro éthanoliques. Pour améliorer d’avantages l’extraction dans les différents solvants verts ou dans le mélange enzymatique, les peaux d’agrumes ont été prétraitées par les DEHT dans l’eau. L’effet mécanique des DEHT, capable de fragmenter les peaux a permis d’améliorer l’extraction des polyphénols 6 dans les différents solvants. L’intensification de l’extraction des polyphénols a été aussi réalisée par les IR et les US. L’extraction des polyphénols par les IR a été optimisée en ayant recours à la méthodologie de surface de réponse. Le chauffage par les IR n’a pas altéré les polyphénols extraits qui ont gardé des activités antifongiques et anti-mycotoxinogènes importantes. Le prétraitement des peaux d’agrumes par les IR sans solvant a fragilisé les structures cellulaires, ce qui a permis d’augmenter la diffusion des polyphénols durant le traitement avec les US.This work consists of the valorization of citrus by-products with innovative technologies. Citrus pressing produces millions of tons of waste per year worldwide. This waste (peels, pulps and seeds) is generally dedicated to animal feed or eliminated by composting or incineration. However its content in bioactive molecules leads to several ways of valorization. Since peels present about half of the citrus waste mass, studies have been focused on the valorization of citrus peels by the extraction of bioactive compounds. Conventional methods generally used for the extraction of bioactive compounds (solid-liquid extraction, hydrodistillation) have several disadvantages such as the use of expensive and toxic solvents, long extraction times and high energy consumption. For this reason, several innovative non-thermal technologies such as Pulsed Electric Fields (PEF), High Voltage Electrical Discharges (HVED) and Ultrasounds (US) and thermal treatments such as microwaves (MO) and infrared (IR) have been tested for the valorization of citrus by-products. Whole citrus fruits (oranges, pomelos, lemons) were PEF treated at an intensity of 3 kV/cm, then citrus juice and polyphenols were extracted by pressing. The study of the PEF-induced cell permeabilization was conducted by several methods and showed that the degree of damage varied according to the type of the treated fruit. The electroporation of the cells induced by the PEF, allowed an increase the juice yields after pressing and improved the liberation of the polyphenols from the citrus peels into the juice. This explains the possibility of obtaining a juice rich in polyphenols by treating the whole fruits with PEF before pressing. Among the solvents tested for the extraction of polyphenols from citrus peels, water is the least effective. The addition of 20% glycerol to water changed the polarity of the medium and improved the extraction of the polyphenols. The use of an enzyme mixture enhanced the release of the polyphenols related to the polysaccharides. Deep eutectic solvents have been as effective as hydroethanolic mixtures. To improve the yields and the kinetics of extractions in the different green solvents and in the enzyme mixture, citrus peels were pretreated with HVED in water. The mechanical effect of HVED, based on the fragmentation of the peels has improved the extraction of polyphenols in the various solvents. The intensification of polyphenols extraction was also conducted by IR and US. The extraction of polyphenols by IR was optimized using the surface response methodology. IR heating did not alter the extracted polyphenols which have significant antifungal and anti-mycotoxinogenic activities. The pretreatment of citrus peels with IR weakened the cell structures, increasing thus the diffusion of polyphenols during US treatment

Pulsed electric field treatment for the stimulation of microorganisms: Applications in food production

International audienceThe pulsed electric field (PEF) technology is a non-thermal processing technique usually used for microbial inactivation in food industries. The application of this technology at sub-lethal levels prior to or during the fermentation processes enhances the mass transfer and cell permeability. It could also cause changes in the genetic, metabolic, and physiological responses of microbial strains leading to an improvement in the fermentation process. Several studies reported the benefits of PEF on microorganisms including growth stimulation, an increase in the fermentation rates and product yields, and improvement in the metabolite extraction. All of these modifications could improve the organoleptic and nutritional properties of fermented food products. The purpose of this review is to summarise and discuss the main findings reported in the literature to date about the effect of PEFs applied at sub-lethal levels on microorganisms in the context of food processing

Valorization of Low-Cost Substrates for the Production of Odd Chain Fatty Acids by the Oleaginous Yeast <i>Yarrowia lipolytica</i>

Odd-chain fatty acids (OCFAs) have recently gained interest as target compounds in microbial production due to their diverse applications in the medical, pharmaceutical and chemical industries for the production of biofuels. Yarrowia lipolytica is a promising oleaginous yeast that has the ability to accumulate high quantities of fatty acids. However, the use of Y. lipolytica oils is still under research, in order to decrease the production costs related to the fermentation process and improve economic feasibility. In this work, sugar beet molasses (10–50 g/L) and crude glycerol (30 g/L) were used as the main carbon sources to reduce the processing costs of oil production from a genetically engineered Y. lipolytica strain. The effects of medium composition were studied on biomass production, lipid content, and OCFAs profile. Lipid production by yeast growing on molasses (20 g/L sucrose) and crude glycerol reached 4.63 ± 0.95 g/L of culture medium. OCFAs content represented 58% of the total fatty acids in lipids, which corresponds to ≈2.69 ± 0.03 g/L of culture medium. The fermentation was upscaled to 5 L bioreactors and fed-batch co-feeding increased OCFA accumulation in Y. lipolytica by 56% compared to batch cultures

Strategies for increasing lipid accumulation and recovery from

Microbial-based biodiesel is produced by transesterification of lipids extracted from microbial cells, and is considered as a potential replacement of fossil fuel due to its advantages in reducing greenhouse gas emissions. Yarrowia lipolytica is one of the most studied oleaginous yeasts able to produce lipids under some fermentation conditions and is considered as a potential industrial host for biodiesel production. Several approaches have been evaluated to increase the economical attraction of biodiesel production from Y. lipolytica lipids. In this review, we highlighted the different strategies reported in the literature, allowing this yeast to achieve high lipid accumulation. These include metabolic engineering strategies, the use of low-cost effective substrates, and the optimization of the cultivation conditions for higher lipid productivity and less operating cost. We also summarized the most effective cell disruption technologies that improve the extraction efficiencies of lipids from Y. lipolytica

Determination of heavy metals contamination in thyme products by inductively coupled plasma mass spectrometry

Thyme herbs constitute a major part of the Mediterranean diet and are gaining worldwide popularity. However, their chemical contamination with toxic metals may put consumers at a health risk. The objective of this study was to assess the incidence of Arsenic (As), Cadmium (Cd), Lead (Pb) and Mercury (Hg) in thyme-containing products. Composite samples were collected twice at six-month interval. Samples were digested by microwave digestion oven and analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). 11%, 22%, and 86% of samples had unacceptable levels of As, Hg and Pb respectively according to the international standards set by Codex Alimentarius and all the samples had acceptable limits of Cd. This study highlighted the importance of monitoring and enforcing regulatory actions related to the contamination of the food chain with heavy metals.This work was funded by Qatar National Library

Synthesis of lanthanide tag and experimental studies on paramagnetically induced residual dipolar couplings

Abstract Nuclear Magnetic Resonance (NMR) spectroscopy is an indispensable technique for the structure elucidation of molecules and determination of their characteristic interactions. Residual Dipolar Coupling (RDC) is an NMR parameter that provides global orientation information of molecules but necessitates the use of an anisotropic orientation medium for the partial alignment of the target molecule with respect to the magnetic field. Importantly, anisotropic paramagnetic tags have been successful as orienting media in biomolecular NMR applications but their use in small organic molecules remains imperfect due to challenges in designing functional lanthanide complexes with varying degrees of bonding in the Ln(III) inner coordination sphere. In this study, we propose a strategy for the synthesis of the lanthanide tag 4-mercaptomethylpyridine-2,6-dicarboxylic acid, 4-MMDPA and the measurement of RDCs in a target molecule using several paramagnetic lanthanide complexes. Graphical Abstrac

Application of high-voltage electrical discharges and other alternative technologies for microbial cell lysis and extraction of biocompounds

International audienceMicrobial synthesis offers an interesting alternative to chemical synthesis and a means to complement chemical synthesis to produce molecules of interest. Microbial compounds can either be synthesized intracellularly or extracellularly, and the intracellular ones can be challenging to recover via physical cell disruption methods given the number of variables to be accounted for. Despite this drawback, physical cell disruption technologies continue to prove their effectiveness at recovering high-value compounds resulting from microbial synthesis. High-voltage electrical discharges or HVEDs are very commonly utilized to recover high-value compounds from plant matter and thus valorize biomass which would have otherwise provided little economic value. An increasing body of work has contributed to not only concretizing HVEDs’ utility but also disrupting microbial cells and expanding the technique’s range of applicability