Modulation of the GABAergic pathway for the treatment of fragile X syndrome.

Fragile X syndrome (FXS) is the most common genetic cause of intellectual disability and the most common single-gene cause of autism. It is caused by mutations on the fragile X mental retardation gene (FMR1) and lack of fragile X mental retardation protein, which in turn, leads to decreased inhibition of translation of many synaptic proteins. The metabotropic glutamate receptor (mGluR) hypothesis states that the neurological deficits in individuals with FXS are due mainly to downstream consequences of overstimulation of the mGluR pathway. The main efforts have focused on mGluR5 targeted treatments; however, investigation on the gamma-aminobutyric acid (GABA) system and its potential as a targeted treatment is less emphasized. The fragile X mouse models (Fmr1-knock out) show decreased GABA subunit receptors, decreased synthesis of GABA, increased catabolism of GABA, and overall decreased GABAergic input in many regions of the brain. Consequences of the reduced GABAergic input in FXS include oversensitivity to sensory stimuli, seizures, and anxiety. Deficits in the GABA receptors in different regions of the brain are associated with behavioral and attentional processing deficits linked to anxiety and autistic behaviors. The understanding of the neurobiology of FXS has led to the development of targeted treatments for the core behavioral features of FXS, which include social deficits, inattention, and anxiety. These symptoms are also observed in individuals with autism and other neurodevelopmental disorders, therefore the targeted treatments for FXS are leading the way in the treatment of other neurodevelopmental syndromes and autism. The GABAergic system in FXS represents a target for new treatments. Herein, we discuss the animal and human trials of GABAergic treatment in FXS. Arbaclofen and ganaxolone have been used in individuals with FXS. Other potential GABAergic treatments, such as riluzole, gaboxadol, tiagabine, and vigabatrin, will be also discussed. Further studies are needed to determine the safety and efficacy of GABAergic treatments for FXS

The Scholarship of Critique and Power

Critique can be defined as disciplinary feedback, analysis, or assessment provided to an individual or within a group, be it a classroom or a team. At a fundamental level, it is an exchange of ideas, impressions, evaluations, opinions, reflections, judgments, speculations, or suggestions to oneself or between two or more participants in a defined context. Scholars describe critique as a signature pedagogy in many disciplines, a cornerstone of the educational experience. There has been scant critical analysis of how critique also represents a performance of power with roots in positions of authority, expertise, or assigned roles. Such power dynamics have been explored in some areas within SoTL, for example in scholarship on assessment, epistemic disobedience, social justice, feminist pedagogies, and critical race theory. However, this has generally not been the case within the scholarship on critique. To better understand the dimensions of power in the context of critique we developed a conceptual framework that can be applied at the individual level (teacher to student, student to student) as well as the systemic level (critique as a construct of cultural hegemony in a specific episteme). Drawing from theoretical and pedagogical literature in areas such as cultural studies, whiteness studies, design education, and assessment, the conceptual framework defines power in three main expressions: power as inequity, power as authority, and power as cultural hegemony. The framework can be used to identify and define power within the critique context and to also inform reflection and shift perspectives at various academic levels

Developmental profiles of infants with an FMR1 premutation

Abstract Background Emerging evidence suggests that a subset of FMR1 premutation carriers is at an increased risk for cognitive, emotional, and medical conditions. However, because the premutation is rarely diagnosed at birth, the early developmental trajectories of children with a premutation are not known. Methods This exploratory study examined the cognitive, communication, and social-behavioral profiles of 26 infants with a premutation who were identified through participation in a newborn screening for fragile X syndrome pilot study. In this study, families whose newborn screened positive for an FMR1 premutation were invited to participate in a longitudinal study of early development. Twenty-six infants with the premutation and 21 matched, screen-negative comparison babies were assessed using validated standardized measures at 6-month intervals starting as young as 3 months of age. The babies were assessed up to seven times over a 4-year period. Results The premutation group was not statistically different from the comparison group on measures of cognitive development, adaptive behavior, temperament, or overall communication. However, the babies with the premutation had a significantly different developmental trajectory on measures of nonverbal communication and hyperresponsivity to sensory experiences. They also were significantly more hyporesponsive at all ages than the comparison group. Cytosine-guanine-guanine repeat length was linearly associated with overall cognitive development. Conclusions These results suggest that infants with a premutation may present with subtle developmental differences as young as 12 months of age that may be early markers of later anxiety, social deficits, or other challenges thought to be experienced by a subset of carriers

Changes in cocoa properties induced by the alkalization process: A review

[EN] Alkalization, also known as "Dutching," is an optional, but very useful, step taken in the production chain of cocoa to darken its color, modify its taste, and increase natural cocoa solubility. Over the years, various attempts have been made to design new and more effective alkalization methods. Moreover, different authors have attempted to elucidate the impact of alkalization on the physicochemical, nutritional, functional, microbiological, and sensory characteristics of alkalized cocoa. The aim of this review is to provide a clear guide about not only the conditions that can be applied to alkalize cocoa, but also the reported effects of alkalization on the nutritional, functional, microbiological, and sensory characteristics of cocoa. The first part of this review describes different cocoa alkalization systems and how they can be tuned to induce specific changes in cocoa properties. The second part is a holistic analysis of the effects of the alkalization process on different cocoa features, performed by emphasizing the biochemistry behind all these transformations.European Regional Development Fund, Grant/Award Number: Project RTC-2016-5241-2; Ministerio deEconomia y Competitividad, Grant/Award Number: Project RTC-2016-5241-2Valverde-Garcia, D.; Pérez-Esteve, É.; Barat Baviera, JM. (2020). Changes in cocoa properties induced by the alkalization process: A review. Comprehensive Reviews in Food Science and Food Safety. 19(4):2200-2221. https://doi.org/10.1111/1541-4337.12581S22002221194Ilesanmi Adeyeye, E. (2016). Proximate, Mineral And Antinutrient Compositions Of Natural Cocoa Cake, Cocoa Liquor And Alkalized Cocoa Powders. Journal of Advanced Pharmaceutical Science And Technology, 1(3), 12-28. doi:10.14302/issn.2328-0182.japst-15-855Ajandouz, E. H., Tchiakpe, L. S., Ore, F. D., Benajiba, A., & Puigserver, A. (2001). Effects of pH on Caramelization and Maillard Reaction Kinetics in Fructose-Lysine Model Systems. Journal of Food Science, 66(7), 926-931. doi:10.1111/j.1365-2621.2001.tb08213.xAndres-Lacueva, C., Monagas, M., Khan, N., Izquierdo-Pulido, M., Urpi-Sarda, M., Permanyer, J., & Lamuela-Raventós, R. M. (2008). Flavanol and Flavonol Contents of Cocoa Powder Products: Influence of the Manufacturing Process. Journal of Agricultural and Food Chemistry, 56(9), 3111-3117. doi:10.1021/jf0728754Andruszkiewicz, P. J., D’Souza, R. N., Altun, I., Corno, M., & Kuhnert, N. (2019). Thermally-induced formation of taste-active 2,5-diketopiperazines from short-chain peptide precursors in cocoa. Food Research International, 121, 217-228. doi:10.1016/j.foodres.2019.03.015Aprotosoaie, A. C., Luca, S. V., & Miron, A. (2015). Flavor Chemistry of Cocoa and Cocoa Products-An Overview. Comprehensive Reviews in Food Science and Food Safety, 15(1), 73-91. doi:10.1111/1541-4337.12180Aremu, C. Y., Agiang, M. A., & Ayatse, J. O. I. (1995). Nutrient and antinutrient profiles of raw and fermented cocoa beans. Plant Foods for Human Nutrition, 48(3), 217-223. doi:10.1007/bf01088443Bandi J. P. Kubicek K. &Raboud P. B.(1984).Installation for solubilizing cocoa. US4438681A.Baigrie, B. D. (1994). Cocoa flavour. Understanding Natural Flavors, 268-282. doi:10.1007/978-1-4615-2143-3_17Bartella, L., Di Donna, L., Napoli, A., Siciliano, C., Sindona, G., & Mazzotti, F. (2019). A rapid method for the assay of methylxanthines alkaloids: Theobromine, theophylline and caffeine, in cocoa products and drugs by paper spray tandem mass spectrometry. Food Chemistry, 278, 261-266. doi:10.1016/j.foodchem.2018.11.072Bauermeister J.(1989).Process for making cacao powder by disagglomeration and cacao powder granulate by subsequent agglomeration. EP0310790A2.Beg, M. S., Ahmad, S., Jan, K., & Bashir, K. (2017). Status, supply chain and processing of cocoa - A review. Trends in Food Science & Technology, 66, 108-116. doi:10.1016/j.tifs.2017.06.007Biehl B.(1986).Cocoa fermentation and problem of acidity over‐fermentation and low cocoa flavour.Selangor Malaysia: Incorporated Society of Planters.Serra Bonvehí, J., & Ventura Coll, F. (2000). Evaluation of purine alkaloids and diketopiperazines contents in processed cocoa powder. European Food Research and Technology, 210(3), 189-195. doi:10.1007/pl00005510Borthwick, A. D., & Da Costa, N. C. (2015). 2,5-diketopiperazines in food and beverages: Taste and bioactivity. Critical Reviews in Food Science and Nutrition, 57(4), 718-742. doi:10.1080/10408398.2014.911142Chalin M. L.(1972).Method of dutching cocoa. US3868469A.Rainer Cremer, D. (2000). The reaction kinetics for the formation of Strecker aldehydes in low moisture model systems and in plant powders. Food Chemistry, 71(1), 37-43. doi:10.1016/s0308-8146(00)00122-9De Vuyst, L., & Weckx, S. (2016). The cocoa bean fermentation process: from ecosystem analysis to starter culture development. Journal of Applied Microbiology, 121(1), 5-17. doi:10.1111/jam.13045Del Rio, D., Costa, L. G., Lean, M. E. J., & Crozier, A. (2010). Polyphenols and health: What compounds are involved? Nutrition, Metabolism and Cardiovascular Diseases, 20(1), 1-6. doi:10.1016/j.numecd.2009.05.015Domínguez-Rodríguez, G., Marina, M. L., & Plaza, M. (2017). Strategies for the extraction and analysis of non-extractable polyphenols from plants. Journal of Chromatography A, 1514, 1-15. doi:10.1016/j.chroma.2017.07.066El Gharras, H. (2009). Polyphenols: food sources, properties and applications - a review. International Journal of Food Science & Technology, 44(12), 2512-2518. doi:10.1111/j.1365-2621.2009.02077.xEllis L. D.(1990).Process for making dark cocoa. US5114730A.Ellis L. D. (1992).Process for making dark cocoa. US5114730A.Lu, F., Rodriguez-Garcia, J., Van Damme, I., Westwood, N. J., Shaw, L., Robinson, J. S., … Charalampopoulos, D. (2018). Valorisation strategies for cocoa pod husk and its fractions. Current Opinion in Green and Sustainable Chemistry, 14, 80-88. doi:10.1016/j.cogsc.2018.07.007Franco, R., Oñatibia-Astibia, A., & Martínez-Pinilla, E. (2013). Health Benefits of Methylxanthines in Cacao and Chocolate. Nutrients, 5(10), 4159-4173. doi:10.3390/nu5104159Germann, D., Stark, T. D., & Hofmann, T. (2019). Formation and Characterization of Polyphenol-Derived Red Chromophores. Enhancing the Color of Processed Cocoa Powders: Part 1. Journal of Agricultural and Food Chemistry, 67(16), 4632-4642. doi:10.1021/acs.jafc.9b01049Germann, D., Stark, T. D., & Hofmann, T. (2019). Formation and Characterization of Polyphenol-Derived Red Chromophores. Enhancing the Color of Processed Cocoa Powders: Part 2. Journal of Agricultural and Food Chemistry, 67(16), 4643-4651. doi:10.1021/acs.jafc.9b01050Gobert, J., & Glomb, M. A. (2009). Degradation of Glucose: Reinvestigation of Reactive α-Dicarbonyl Compounds†. Journal of Agricultural and Food Chemistry, 57(18), 8591-8597. doi:10.1021/jf9019085Gu, L., House, S. E., Wu, X., Ou, B., & Prior, R. L. (2006). Procyanidin and Catechin Contents and Antioxidant Capacity of Cocoa and Chocolate Products. Journal of Agricultural and Food Chemistry, 54(11), 4057-4061. doi:10.1021/jf060360rGültekin-Özgüven, M., Berktaş, I., & Özçelik, B. (2016). Change in stability of procyanidins, antioxidant capacity and in-vitro bioaccessibility during processing of cocoa powder from cocoa beans. LWT - Food Science and Technology, 72, 559-565. doi:10.1016/j.lwt.2016.04.065Hagerman, A. E. (1992). Tannin—Protein Interactions. Phenolic Compounds in Food and Their Effects on Health I, 236-247. doi:10.1021/bk-1992-0506.ch019Holkar, C. R., Jadhav, A. J., & Pinjari, D. V. (2019). A critical review on the possible remediation of sediment in cocoa/coffee flavored milk. Trends in Food Science & Technology, 86, 199-208. doi:10.1016/j.tifs.2019.02.035Huang, Y., & Barringer, S. A. (2010). Alkylpyrazines and Other Volatiles in Cocoa Liquors at pH 5 to 8, by Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS). Journal of Food Science, 75(1), C121-C127. doi:10.1111/j.1750-3841.2009.01455.xHurst, W. J., Krake, S. H., Bergmeier, S. C., Payne, M. J., Miller, K. B., & Stuart, D. A. (2011). Impact of fermentation, drying, roasting and Dutch processing on flavan-3-ol stereochemistry in cacao beans and cocoa ingredients. Chemistry Central Journal, 5(1). doi:10.1186/1752-153x-5-53International Cocoa Organization(2017).Annual report 2014/2015 Retrieved fromhttps://www.icco.org/about-us/international-cocoa-agreements/cat_view/1-annual-report.html.Mazor Jolić, S., Radojčić Redovniković, I., Marković, K., Ivanec Šipušić, Đ., & Delonga, K. (2011). Changes of phenolic compounds and antioxidant capacity in cocoa beans processing. International Journal of Food Science & Technology, 46(9), 1793-1800. doi:10.1111/j.1365-2621.2011.02670.xKofink, M., Papagiannopoulos, M., & Galensa, R. (2007). (-)-Catechin in Cocoa and Chocolate: Occurence and Analysis of an Atypical Flavan-3-ol Enantiomer. Molecules, 12(7), 1274-1288. doi:10.3390/12071274Kongor, J. E., Hinneh, M., de Walle, D. V., Afoakwa, E. O., Boeckx, P., & Dewettinck, K. (2016). Factors influencing quality variation in cocoa (Theobroma cacao) bean flavour profile — A review. Food Research International, 82, 44-52. doi:10.1016/j.foodres.2016.01.012Kopp G. M. Hennen J. C. Seyller M. &Brandstetter B.(2010).Process for producing high flavour cocoa. EP2241190A1.Kruszewski, B., & Obiedziński, M. W. (2020). Impact of Raw Materials and Production Processes on Furan and Acrylamide Contents in Dark Chocolate. Journal of Agricultural and Food Chemistry, 68(8), 2562-2569. doi:10.1021/acs.jafc.0c00412Lan, X., Liu, P., Xia, S., Jia, C., Mukunzi, D., Zhang, X., … Xiao, Z. (2010). Temperature effect on the non-volatile compounds of Maillard reaction products derived from xylose–soybean peptide system: Further insights into thermal degradation and cross-linking. Food Chemistry, 120(4), 967-972. doi:10.1016/j.foodchem.2009.11.033Li, Y., Feng, Y., Zhu, S., Luo, C., Ma, J., & Zhong, F. (2012). The effect of alkalization on the bioactive and flavor related components in commercial cocoa powder. Journal of Food Composition and Analysis, 25(1), 17-23. doi:10.1016/j.jfca.2011.04.010Li, Y., Zhu, S., Feng, Y., Xu, F., Ma, J., & Zhong, F. (2013). Influence of alkalization treatment on the color quality and the total phenolic and anthocyanin contents in cocoa powder. Food Science and Biotechnology, 23(1), 59-63. doi:10.1007/s10068-014-0008-5Lima, L. J. R., Kamphuis, H. J., Nout, M. J. R., & Zwietering, M. H. (2011). Microbiota of cocoa powder with particular reference to aerobic thermoresistant spore-formers. Food Microbiology, 28(3), 573-582. doi:10.1016/j.fm.2010.11.011MALEYKI, M. J. A., & ISMAIL, A. (2010). ANTIOXIDANT PROPERTIES OF COCOA POWDER. Journal of Food Biochemistry, 34(1), 111-128. doi:10.1111/j.1745-4514.2009.00268.xMartín, M. Á., & Ramos, S. (2017). Health beneficial effects of cocoa phenolic compounds: a mini-review. Current Opinion in Food Science, 14, 20-25. doi:10.1016/j.cofs.2016.12.002Martin, M. A., Goya, L., & Ramos, S. (2013). Potential for preventive effects of cocoa and cocoa polyphenols in cancer. Food and Chemical Toxicology, 56, 336-351. doi:10.1016/j.fct.2013.02.020Méndez-Albores, A., De Jesús-Flores, F., Castañeda-Roldan, E., Arámbula-Villa, G., & Moreno-Martı́nez, E. (2004). The effect of toasting and boiling on the fate of B-aflatoxins during pinole preparation. Journal of Food Engineering, 65(4), 585-589. doi:10.1016/j.jfoodeng.2004.02.024Miller, K. B., Hurst, W. J., Payne, M. J., Stuart, D. A., Apgar, J., Sweigart, D. S., & Ou, B. (2008). Impact of Alkalization on the Antioxidant and Flavanol Content of Commercial Cocoa Powders. Journal of Agricultural and Food Chemistry, 56(18), 8527-8533. doi:10.1021/jf801670pOlam. (2017).The De Zaan cocoa manual. The Netherlands: Archer Daniels Midland Company BV.ODUNS, A. A., & LONGE, O. G. (1998). Nutritive value of hot water- or cocoa-pod ash solution-treated cocoa bean cake for broiler chicks. British Poultry Science, 39(4), 519-525. doi:10.1080/00071669888700Ofosu, I. W., Ankar-Brewoo, G. M., Lutterodt, H. E., Benefo, E. O., & Menyah, C. A. (2019). Estimated daily intake and risk of prevailing acrylamide content of alkalized roasted cocoa beans. Scientific African, 6, e00176. doi:10.1016/j.sciaf.2019.e00176Okiyama, D. C. G., Navarro, S. L. B., & Rodrigues, C. E. C. (2017). Cocoa shell and its compounds: Applications in the food industry. Trends in Food Science & Technology, 63, 103-112. doi:10.1016/j.tifs.2017.03.007Ortega, N., Romero, M.-P., Macià, A., Reguant, J., Anglès, N., Morelló, J.-R., & Motilva, M.-J. (2008). Obtention and Characterization of Phenolic Extracts from Different Cocoa Sources. Journal of Agricultural and Food Chemistry, 56(20), 9621-9627. doi:10.1021/jf8014415Pia, A. K. R., Pereira, A. P. M., Costa, R. A., Alvarenga, V. O., Freire, L., Carlin, F., & Sant’Ana, A. S. (2019). The fate of Bacillus cereus and Geobacillus stearothermophilus during alkalization of cocoa as affected by alkali concentration and use of pre-roasted nibs. Food Microbiology, 82, 99-106. doi:10.1016/j.fm.2019.01.009Quelal-Vásconez, M. A., Lerma-García, M. J., Pérez-Esteve, É., Arnau-Bonachera, A., Barat, J. M., & Talens, P. (2020). Changes in methylxanthines and flavanols during cocoa powder processing and their quantification by near-infrared spectroscopy. LWT, 117, 108598. doi:10.1016/j.lwt.2019.108598Quelal‐Vásconez, M. A., Lerma‐García, M. J., Pérez‐Esteve, É., Talens, P., & Barat, J. M. (2020). Roadmap of cocoa quality and authenticity control in the industry: A review of conventional and alternative methods. Comprehensive Reviews in Food Science and Food Safety, 19(2), 448-478. doi:10.1111/1541-4337.12522Razzaque, M. A., Saud, Z. A., Absar, N., Karim, M. R., & Hashinaga, F. (2000). Purification and Characterization of Polyphenoloxidase from Guava Infected with Fruit-rot Disease. Pakistan Journal of Biological Sciences, 3(3), 407-410. doi:10.3923/pjbs.2000.407.410Rimbach, G., Melchin, M., Moehring, J., & Wagner, A. (2009). Polyphenols from Cocoa and Vascular Health—A Critical Review. International Journal of Molecular Sciences, 10(10), 4290-4309. doi:10.3390/ijms10104290Rodríguez, P., Pérez, E., & Guzmán, R. (2009). Effect of the types and concentrations of alkali on the color of cocoa liquor. Journal of the Science of Food and Agriculture, 89(7), 1186-1194. doi:10.1002/jsfa.3573Saltini, R., Akkerman, R., & Frosch, S. (2013). Optimizing chocolate production through traceability: A review of the influence of farming practices on cocoa bean quality. Food Control, 29(1), 167-187. doi:10.1016/j.foodcont.2012.05.054Sarmadi, B., Aminuddin, F., Hamid, M., Saari, N., Abdul-Hamid, A., & Ismail, A. (2012). Hypoglycemic effects of cocoa (Theobroma cacao L.) autolysates. Food Chemistry, 134(2), 905-911. doi:10.1016/j.foodchem.2012.02.202Sarmadi, B., Ismail, A., & Hamid, M. (2011). Antioxidant and angiotensin converting enzyme (ACE) inhibitory activities of cocoa (Theobroma cacao L.) autolysates. Food Research International, 44(1), 290-296. doi:10.1016/j.foodres.2010.10.017Scalone, G. L. L., Textoris-Taube, K., De Meulenaer, B., De Kimpe, N., Wöstemeyer, J., & Voigt, J. (2019). Cocoa-specific flavor components and their peptide precursors. Food Research International, 123, 503-515. doi:10.1016/j.foodres.2019.05.019Schroder, T., Vanhanen, L., & Savage, G. P. (2011). Oxalate content in commercially produced cocoa and dark chocolate. Journal of Food Composition and Analysis, 24(7), 916-922. doi:10.1016/j.jfca.2011.03.008Shankar, M. U., Levitan, C. A., Prescott, J., & Spence, C. (2009). The Influence of Color and Label Information on Flavor Perception. Chemosensory Perception, 2(2), 53-58. doi:10.1007/s12078-009-9046-4Singh, P., Kesharwani, R. K., & Keservani, R. K. (2017). Antioxidants and Vitamins. Sustained Energy for Enhanced Human Functions and Activity, 385-407. doi:10.1016/b978-0-12-805413-0.00024-7Tanaka M. &Terauchi M.(1999).Cocoa powder rich in polyphenols process for producing the same and modified cocoa containing the same. US6485772B1.Taş, N. G., & Gökmen, V. (2016). Effect of alkalization on the Maillard reaction products formed in cocoa during roasting. Food Research International, 89, 930-936. doi:10.1016/j.foodres.2015.12.021Terink J. &Brandon M. J.(1981).Alkalized cocoa powders and foodstuffs containing such powders. US4435436A.Todorovic, V., Milenkovic, M., Vidovic, B., Todorovic, Z., & Sobajic, S. (2017). Correlation between Antimicrobial, Antioxidant Activity, and Polyphenols of Alkalized/Nonalkalized Cocoa Powders. Journal of Food Science, 82(4), 1020-1027. doi:10.1111/1750-3841.13672Tomas-Barberán, F. A., Cienfuegos-Jovellanos, E., Marín, A., Muguerza, B., Gil-Izquierdo, A., Cerdá, B., … Espín, J. C. (2007). A New Process To Develop a Cocoa Powder with Higher Flavonoid Monomer Content and Enhanced Bioavailability in Healthy Humans. Journal of Agricultural and Food Chemistry, 55(10), 3926-3935. doi:10.1021/jf070121jTotlani, V. M., & Peterson, D. G. (2005). Reactivity of Epicatechin in Aqueous Glycine and Glucose Maillard Reaction Models:  Quenching of C2, C3, and C4 Sugar Fragments. Journal of Agricultural and Food Chemistry, 53(10), 4130-4135. doi:10.1021/jf050044xTotlani, V. M., & Peterson, D. G. (2006). Influence of Epicatechin Reactions on the Mechanisms of Maillard Product Formation in Low Moisture Model Systems. Journal of Agricultural and Food Chemistry, 55(2), 414-420. doi:10.1021/jf0617521Trout R. B.(2001).Method for making dutched cocoa. EP1278428B1.Turcotte, A.-M., Scott, P. M., & Tague, B. (2013). Analysis of cocoa products for ochratoxin A and aflatoxins. Mycotoxin Research, 29(3), 193-201. doi:10.1007/s12550-013-0167-xWang, R., Wang, T., Zheng, Q., Hu, X., Zhang, Y., & Liao, X. (2012). Effects of high hydrostatic pressure on color of spinach purée and related properties. Journal of the Science of Food and Agriculture, 92(7), 1417-1423. doi:10.1002/jsfa.4719Wiant M. J. William R. Lynch W. R. &LeFreniere R. C.(1989).Method for producing deep red and black cocoa. US5009917A.Wissgott U.(1988).Process of alkalization of cocoa in aqueous phase. US4784866A.Wollgast, J., & Anklam, E. (2000). Review on polyphenols in Theobroma cacao: changes in composition during the manufacture of chocolate and methodology for identification and quantification. Food Research International, 33(6), 423-447. doi:10.1016/s0963-9969(00)00068-5Zhang, L., Xia, Y., & Peterson, D. G. (2014). Identification of Bitter Modulating Maillard-Catechin Reaction Products. Journal of Agricultural and Food Chemistry, 62(33), 8470-8477. doi:10.1021/jf502040eZhu, Q. Y., Holt, R. R., Lazarus, S. A., Ensunsa, J. L., Hammerstone, J. F., Schmitz, H. H., & Keen, C. L. (2002). Stability of the Flavan-3-ols Epicatechin and Catechin and Related Dimeric Procyanidins Derived from Cocoa. Journal of Agricultural and Food Chemistry, 50(6), 1700-1705. doi:10.1021/jf011228

A Randomized Controlled Trial of Sertraline in Young Children With Autism Spectrum Disorder.

Objective: Selective serotonin reuptake inhibitors like sertraline have been shown in observational studies and anecdotal reports to improve language development in young children with fragile X syndrome (FXS). A previous controlled trial of sertraline in young children with FXS found significant improvement in expressive language development as measured by the Mullen Scales of Early Learning (MSEL) among those with comorbid autism spectrum disorder (ASD) in post hoc analysis, prompting the authors to probe whether sertraline is also indicated in nonsyndromic ASD. Methods: The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 58 children with ASD aged 24 to 72 months. Results: 179 subjects were screened for eligibility, and 58 were randomized to sertraline (32) or placebo (26). Eight subjects from the sertraline arm and five from the placebo arm discontinued. Intent-to-treat analysis showed no significant difference from placebo on the primary outcomes (MSEL expressive language raw score and age equivalent combined score) or secondary outcomes. Sertraline was well tolerated, with no difference in side effects between sertraline and placebo groups. No serious adverse events possibly related to study treatment occurred. Conclusion: This randomized controlled trial of sertraline treatment showed no benefit with respect to primary or secondary outcome measures. For the 6-month period, treatment in young children with ASD appears safe, although the long-term side effects of low-dose sertraline in early childhood are unknown. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02385799

Fragile X Newborn Screening: Lessons Learned From a Multisite Screening Study

BACKGROUND: Delays in the diagnosis of children with fragile X syndrome (FXS) suggest the possibility of newborn screening as a way to identify children earlier. However, FXS does not have a proven treatment that must be provided early, and ethical concerns have been raised about the detection of infants who are carriers. This article summarizes major findings from a multisite, prospective, longitudinal pilot screening study. METHODS: Investigators in North Carolina, California, and Illinois collaborated on a study in which voluntary screening for FXS was offered to parents in 3 birthing hospitals. FXS newborn screening was offered to >28 000 families to assess public acceptance and determine whether identification of babies resulted in any measurable harms or adverse events. Secondary goals were to determine the prevalence of FMR1 carrier gene expansions, study the consent process, and describe early development and behavior of identified children. RESULTS: A number of publications have resulted from the project. This article summarizes 10 "lessons learned" about the consent process, reasons for accepting and declining screening, development and evaluation of a decision aid, prevalence of carriers, father participation in consent, family follow-up, and maternal reactions to screening. CONCLUSIONS: The project documented public acceptance of screening as well as the challenges inherent in obtaining consent in the hospital shortly after birth. Collectively, the study provides answers to a number of questions that now set the stage for a next generation of research to determine the benefits of earlier identification for children and families

The challenges of clinical trials in fragile X syndrome

RATIONALE: Advances in understanding the underlying mechanisms of conditions such as fragile X syndrome (FXS) and autism spectrum disorders have revealed heterogeneous populations. Recent trials of novel FXS therapies have highlighted several challenges including subpopulations with possibly differential therapeutic responses, the lack of specific outcome measures capturing the full range of improvements of patients with FXS, and a lack of biomarkers that can track whether a specific mechanism is responsive to a new drug and whether the response correlates with clinical improvement. OBJECTIVES: We review the phenotypic heterogeneity of FXS and the implications for clinical research in FXS and other neurodevelopmental disorders. RESULTS: Residual levels of fragile X mental retardation protein (FMRP) expression explain in part the heterogeneity in the FXS phenotype; studies indicate a correlation with both cognitive and behavioral deficits. However, this does not fully explain the extent of phenotypic variance observed or the variability of drug response. Post hoc analyses of studies involving the selective mGluR5 antagonist mavoglurant and the GABAB agonist arbaclofen have uncovered significant therapeutic responses following patient stratification according to FMR1 promoter methylation patterns or baseline severity of social withdrawal, respectively. Future studies designed to quantify disease modification will need to develop new strategies to track changes effectively over time and in multiple symptom domains. CONCLUSION: Appropriate selection of patients and outcome measures is central to optimizing future clinical investigations of these complex disorders

A Comparison of Univariate and Multivariate Forecasting Models Predicting Emergency Department Patient Arrivals during the COVID-19 Pandemic

The COVID-19 pandemic has heightened the existing concern about the uncertainty surrounding patient arrival and the overutilization of resources in emergency departments (EDs). The prediction of variations in patient arrivals is vital for managing limited healthcare resources and facilitating data-driven resource planning. The objective of this study was to forecast ED patient arrivals during a pandemic over different time horizons. A secondary objective was to compare the performance of different forecasting models in predicting ED patient arrivals. We included all ED patient encounters at an urban teaching hospital between January 2019 and December 2020. We divided the data into training and testing datasets and applied univariate and multivariable forecasting models to predict daily ED visits. The influence of COVID-19 lockdown and climatic factors were included in the multivariable models. The model evaluation consisted of the root mean square error (RMSE) and mean absolute error (MAE) over different forecasting horizons. Our exploratory analysis illustrated that monthly and weekly patterns impact daily demand for care. The Holt–Winters approach outperformed all other univariate and multivariable forecasting models for short-term predictions, while the Long Short-Term Memory approach performed best in extended predictions. The developed forecasting models are able to accurately predict ED patient arrivals and peaks during a surge when tested on two years of data from a high-volume urban ED. These short-and long-term prediction models can potentially enhance ED and hospital resource planning