Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017-2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients' outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

Clinical and immunological characteristics of a pediatric population with food protein-induced enterocolitis syndrome (FPIES) to fish.

BACKGROUND: Food protein-induced enterocolitis (FPIES) is an uncommon, non-IgE-mediated food allergy that usually debuts in infancy with profuse vomiting, lethargy, and pallor 2-4 h following ingestion of the offending food. Its immune mechanism is not known. We aimed to describe the clinical features and outcome of children with fish-FPIES as well as to investigate on cellular immune response implicated. METHODS: Prospective and follow-up clinical study of children with FPIES by fish over a period between 2004 and 2013 was conducted. Measurement in vitro of both cytokine production in peripheral blood mononuclear cells (PBMCs) and expression of HLA-DR in monocyte-derived dendritic cells stimulated with fish extracts. RESULTS: Sixteen children (seven male and nine female) were included, with a mean age of onset at 10 months. Diagnosis was established after a median of 4 reactions. Twelve patients were treated in emergency room, and two were admitted in intensive care. Patch tests were positive in six patients. Skin prick tests (SPTs) and specific IgE to all fish tested were negative. Only three children reached tolerance at a mean age of 4.5 years. Eight children avoided fish because of positive oral food challenge (OFC) after 6 years of age. Other patients have not been challenged because of parent refusal to OFC or a recent diagnosis. TNF-α was increased in patients, and a significant elevation of the HLA-DR marker was also observed in these patients vs. control donors. CONCLUSIONS: FPIES caused by fish in many cases presents with severe clinical manifestations. Patch test has poor diagnostic value, and OFC is the gold standard to test tolerance. The cytokine TNF-α may be implicated in the clinical symptoms. Higher expression of HLA-DR in dendritic cells has also been detected in our patients.

[Forage use and availability for white tailed deer Odocoileus virginianus thomasi (Artiodactyla: Cervidae) in an experimental unit of Campeche, Mexico]. / Dieta y disponibilidad de forraje del venado cola blanca Odocoileus virginianus thomasi (Artiodactyla: Cervidae) en un campo experimental de Campeche, México.

Forage use and availability for white tailed deer Odocoileus virginianus thomasi (Artiodactyla: Cervidae) in an experimental unit of Campeche, Mexico. In Campeche state, 122 Wildlife Conservation and Management Units have been recently conformed. In these units, eventhough the white tailed deer Odocoileus virginianus thomasi is a game species, no studies on its diet have been undertaken. The objectives of this work were to estimate the botanical composition of the diet and its seasonal change, to determine forage availability, carrying capacity and stocking rate of O. virginianus thomasi. The study was conducted in the experimental unit of Colegio de Postgraduados in Campeche, Mexico, from October 2010 to May 2012. The diet was determined through microhistological analyses of the white tailed deer feces by the use of reference material. Forage availability was determined through the Adelaide's method; the stocking rate, using the grazing pressure factor; and carrying capacity considering forage availability and 35% of utilization efficiency. In this experimental unit, the deer diet included 40 species belonging to 15 families. The highest species richness ocurred during the rainy season with 29 species. However, deers preferred shrubs during all seasons, and herbaceous species during the rainy season. The diet composition, forage availability, carrying capacity and stocking rate varied throughout the year. Carrying capacity ranged from 0.04 to 1.08deer/ha. Additional studies are required to detail about the composition of the diet, habitat availability and use throughout its geographical range, and to detail on nutritional and health aspects.

Dieta y disponibilidad de forraje del venado cola blanca Odocoileus virginianus thomasi (Artiodactyla: Cervidae) en un campo experimental de Campeche, México / Forage use and availability for white tailed deer Odocoileus virginianus thomasi (Artiodactyla: Cervidae) in an experimental unit of Campeche, Mexico

In Campeche state, 122 Wildlife Conservation and Management Units have been recently conformed. In these units, eventhough the white tailed deer Odocoileus virginianus thomasi is a game species, no studies on its diet have been undertaken. The objectives of this work were to estimate the botanical composition of the diet and its seasonal change, to determine forage availability, carrying capacity and stocking rate of O. virginianus thomasi. The study was conducted in the experimental unit of Colegio de Postgraduados in Campeche, Mexico, from October 2010 to May 2012. The diet was determined through microhistological analyses of the white tailed deer feces by the use of reference material. Forage availability was determined through the Adelaide´s method; the stocking rate, using the grazing pressure factor; and carrying capacity considering forage availability and 35% of utilization efficiency. In this experimental unit, the deer diet included 40 species belonging to15 families. The highest species richness ocurred during the rainy season with 29 species. However, deers preferred shrubs during all seasons, and herbaceous species during the rainy season. The diet composition, forage availability, carrying capacity and stocking rate varied throughout the year. Carrying capacity ranged from 0.04 to 1.08deer/ha. Additional studies are required to detail about the composition of the diet, habitat availability and use throughout its geographical range, and to detail on nutritional and health aspects. Rev. Biol. Trop. 62 (2): 699-710. Epub 2014 June 01.

En Campeche, México no existen estudios de la dieta de Odocoileus virginianus thomasi; a pesar de la existencia de 122 Unidades de Manejo para la Conservación de la Vida Silvestre (UMAS) en donde se realiza aprovechamiento del venado cola blanca. Los objetivos del trabajo fueron conocer la composición botánica de la dieta y su cambio estacional, la disponibilidad de forraje, la capacidad de carga y carga animal de O. virginianus thomasi. El trabajo se realizó de octubre 2010 a mayo 2012 en el Campo Experimental del Colegio de Postgraduados en Campeche, México. La composición de la dieta se determinó mediante el análisis de heces de venado y material de referencia con la técnica microhistológica; la disponibilidad de forraje se estimó con el método de Adelaide; la capacidad de carga utilizando la presión de pastoreo y la carga animal considerando el forraje disponible y 35% de eficiencia de utilización. La dieta incluyó 40 especies de 15 familias. La riqueza de especies más alta fue de 29 especies en la época de lluvia; las arbustivas fueron preferidas en las tres épocas del año y las herbáceas en la época de lluvia. La composición de la dieta, disponibilidad de forraje, la capacidad de carga y carga animal variaron a través del año. La capacidad de carga fluctuó entre 0.04 a 1.08 venados/ha.

Rate limiting step precedes C-C bond formation in the archetypical proline-catalyzed intramolecular aldol reaction.

The archetypical proline-catalyzed intramolecular aldol reaction, the Hajos-Parrish-Eder-Sauer-Wiechert reaction, has served as a model reaction for the mechanistic study of the ever-growing class of proline-catalyzed conversions. Experimental measurements of the (13)C kinetic isotope effects for this reaction show conclusively that carbon-carbon bond formation is not rate-limiting.

De novo computational design of retro-aldol enzymes.

The creation of enzymes capable of catalyzing any desired chemical reaction is a grand challenge for computational protein design. Using new algorithms that rely on hashing techniques to construct active sites for multistep reactions, we designed retro-aldolases that use four different catalytic motifs to catalyze the breaking of a carbon-carbon bond in a nonnatural substrate. Of the 72 designs that were experimentally characterized, 32, spanning a range of protein folds, had detectable retro-aldolase activity. Designs that used an explicit water molecule to mediate proton shuffling were significantly more successful, with rate accelerations of up to four orders of magnitude and multiple turnovers, than those involving charged side-chain networks. The atomic accuracy of the design process was confirmed by the x-ray crystal structure of active designs embedded in two protein scaffolds, both of which were nearly superimposable on the design model.

Quantum mechanical design of enzyme active sites.

The design of active sites has been carried out using quantum mechanical calculations to predict the rate-determining transition state of a desired reaction in presence of the optimal arrangement of catalytic functional groups (theozyme). Eleven versatile reaction targets were chosen, including hydrolysis, dehydration, isomerization, aldol, and Diels-Alder reactions. For each of the targets, the predicted mechanism and the rate-determining transition state (TS) of the uncatalyzed reaction in water is presented. For the rate-determining TS, a catalytic site was designed using naturalistic catalytic units followed by an estimation of the rate acceleration provided by a reoptimization of the catalytic site. Finally, the geometries of the sites were compared to the X-ray structures of related natural enzymes. Recent advances in computational algorithms and power, coupled with successes in computational protein design, have provided a powerful context for undertaking such an endeavor. We propose that theozymes are excellent candidates to serve as the active site models for design processes.

How similar are enzyme active site geometries derived from quantum mechanical theozymes to crystal structures of enzyme-inhibitor complexes? Implications for enzyme design.

Quantum mechanical optimizations of theoretical enzymes (theozymes), which are predicted catalytic arrays of biological functionalities stabilizing a transition state, have been carried out for a set of nine diverse enzyme active sites. For each enzyme, the theozyme for the rate-determining transition state plus the catalytic groups modeled by side-chain mimics was optimized using B3LYP/6-31G(d) or, in one case, HF/3-21G(d) quantum mechanical calculations. To determine if the theozyme can reproduce the natural evolutionary catalytic geometry, the positions of optimized catalytic atoms, i.e., covalent, partial covalent, or stabilizing interactions with transition state atoms, are compared to the positions of the atoms in the X-ray crystal structure with a bound inhibitor. These structure comparisons are contrasted to computed substrate-active site structures surrounded by the same theozyme residues. The theozyme/transition structure is shown to predict geometries of active sites with an average RMSD of 0.64 A from the crystal structure, while the RMSD for the bound intermediate complexes are significantly higher at 1.42 A. The implications for computational enzyme design are discussed.

Piaget - Vygotski: el juego infantil a debate / Piaget - Vygotsky: children’s play on discussion

A fin de proporcionar elementos para resituar el debate entre Piaget y Vygotski, se analiza cómo ambos autores consideraron el juego infantil en un mismo momento histórico. En el estudio de Piaget sobre desarrollo moral, se evidencia su interés por las relaciones entre individuo y sociedad. En Vygotski, se destaca el juego como inicio de la posibilidad de significación por parte del niño. Tras estudiar los presupuestos y hallazgos en cada caso, se propone la compatibilidad de ambos programas, poniéndose no obstante de relieve la especificidad de cada teoría, la naturaleza de sus preguntas, y de su direccionalidad en el desarrollo. Por último, se intenta demostrar que las unidades de análisis utilizadas por un autor no se ven eliminadas en el otro, lo que aporta una prueba más a la compatibilidad propuesta.

Approaches to open fullerenes: a 1,2,3,4,5,6-hexaadduct of C60.

Complete saturation of a single six-membered ring on fullerene C60 has been achieved. The critical step in this first synthesis of a fully characterized 1,2,3,4,5,6-hexaadduct consisted of a remarkable double 5-exo-trig addition of alkoxyl radicals promoted by lead tetraacetate. Two possible opening pathways ([2 + 2 + 2] retrocycloadditions) for the newly synthesized compound were explored using quantum mechanical calculations. We found that the oxa bridges in the hexaadduct prevent ring opening through the retro[2 + 2 + 2] mechanism due to the high activation barrier and endothermicity of the reaction.

Theoretical studies of stereoselectivities of intramolecular aldol cyclizations catalyzed by amino acids.

The effects of different amino acid catalysts and substrate substituents on the stereoselectivity of the title reactions have been studied with the aid of density functional theory methods. Experimental data available in the literature have been compiled. B3LYP/6-31G(d) calculations match the general experimental trends and provide useful insights into the origins of the variations in stereoselectivities. Acyclic primary amino acids allow a greater conformational flexibility in the aldol transition states compared with proline. This makes them poorer enantioselective catalysts with triketone substrates with a methyl ketone side chain. The steric repulsion upon substitution at the terminal methyl group increases the energy difference between anti- and syn-chairs with primary amino acid catalysts and, consequently, the stereoselectivities. Proline, in contrast, is a poor catalyst for the latter reactions because the substituent's steric bulkiness raises the activation energy of the favored C-C bond-forming pathway.

Theory of asymmetric organocatalysis of Aldol and related reactions: rationalizations and predictions.

Computational studies have led to models to understand some classic and contemporary asymmetric reactions involving organocatalysts. The Hajos-Parrish-Eder-Sauer-Wiechert reaction and intermolecular aldol reactions as well as Mannich reactions and oxyaminations catalyzed by proline and other amino acids, and Diels-Alder reactions catalyzed by MacMillan's chiral amine organocatalysts have been studied with density functional theory. Quantitative predictions for several new catalysts and reactions are provided.

El conocimiento de dominio moral en la psicología del desarrollo: un análisis de las tesis de turiel / Domain moral knowledge in developmental psychology: an analysis of turiel's theses

Este artículo se propone plantear los problemas que suscita el conocimiento de dominio moral propuesto por Turiel, al compararlo con la teoría piagetiana de la que proviene y con la perspectiva contextualista. En primer lugar, vamos a presentar los criterios utilizados por este autor para definir la especificidad del dominio moral y para diferenciarlo del convencional, así como los presupuestos teóricos que le permitieron tal diferenciación, especificando los criterios utilizados y las dificultades conceptuales propias de esta perspectiva. En segundo lugar, se identificarán la notas que distinguen esta versión “constructivista” de dominio de la herencia piagetiana. En tercer lugar, se contrastará la perspectiva turieliana con la contextualista, dado que su confrontación en términos teóricos y empíricos es característica de la situación de la investigación contemporánea en psicología moral. Sobre esta base, replantearemos las condiciones de posibilidad de la psicología del desarrollo moral: la teoría del conocimiento moral, por un lado, y la filosofía moral, por el otro.

The role of steric and electronic interactions in the stereocontrol of the asymmetric 1,3-dipolar reactions of 5-ethoxy-3-p-(S)-tolylsulfinylfuran-2(5H)-ones with diazoalkanes: theoretical calculations and experimental evidences.

The addition of diazomethane and diazoethane to (5S,SS)- and (5R,SS)-5-ethoxy-3-p-tolylsulfinylfuran-2(5H)-ones (1a and 1b) and their 4-methylderivatives (2a and 2b) proceeded in almost quantitative yields and complete regioselectivity. The observed pi-facial selectivity is determined by the configurations at both C-5 and the sulfinyl group, the later being the most important. The syn adducts were almost exclusively obtained from 1a and 2a in apolar solvents but the pi-facial selectivity was strongly decreased in more polar solvents. On the other hand, the major adducts from 1b and 2b were the anti ones and such predominance was slightly increased with solvent polarity. The exo-selectivity was complete in all the cases except for the anti approach to compounds 2a (in polar solvents) and 2b. The role of the sulfinyl group in this behavior was inferred by comparison of these results with those obtained in reactions of diazoalkanes with 5-methoxyfuran-2(5H)-one (3). Steric interactions seem to be the main ones responsible for the observed exo selectivity of reactions with diazoethane, but electronic factors, which can be modulated by the solvent, are also significant in the pi-facial selectivity control. DFT computational methods are able to correctly predict the reactivity, regioselectivity, and pi-facial selectivity exhibited by 5-alkoxyfuranones as well as their changes with the solvent polarity. A C-H.O hydrogen bond, involving the oxygen atom of the 5-alkoxy group at dipolarophiles and the endo-hydrogen atom at dipoles, seems to play a key role in the electronic interactions influencing the stereochemical course of these reactions.

1,3-dipolar cycloaddition of 2-dialkylaminothioisomünchnones with aliphatic aldehydes: synthesis of beta-lactams and thiiranes, structure elucidation, and rationale for chemoselective fragmentation of cycloadducts.

A series of highly funtionalized beta-lactams and thiiranes can be generated on treatment of 1,3-thiazolium-4-olates (thioisomünchnones) with aliphatic aldehydes. Although in some cases a variety of products have been obtained, the present paper now provides a mechanistic rationale to explain the product distribution based on stereoelectronic effects. Thus, ring fragmentation of the initial [3+2] cycloadduct is essentially dictated by the electronic character of the aryl substituent on the nitrogen atom of the parent thioisomünchnone. However, further evolution of such cycloadducts into beta-lactams or thiiranes is governed by steric effects to a large extent. Evidence for such interactions has been obtained by computing PM3-optimized diastereomeric transition structures in the reaction of a thioisomünchnone with a chiral aliphatic aldehyde.

El programa constructivista ante las representaciones colectivas y sociales / The constructivist program facing collective and social representations

Las ideas de Piaget sobre la moral infantil se formularon durante una discusión crítica con las tesis de Durkheim referidas a la presión social que sobre los individuos ejercen las representaciones colectivas. De ahí la necesidad de estudiar esta categoría en el pensamiento del sociólogo francés, así como sus relaciones con las prácticas sociales y la ciencia. En segundo lugar, se busca presentar los argumentos con que Piaget cuestiona algunos de sus rasgos. Ahora bien, las representaciones sociales han sustituido a las representaciones colectivas en la psicología social contemporánea, lo que obliga a vincularlas con el programa constructivista. Se plantean entonces dos cuestiones, por una parte, las relaciones entre la formación de ideas infantiles sobre la sociedad y la influencia de las representaciones sociales; por el otro, si la modificación e internalización de las representaciones sociales requeriría de la actividad intelectual de los individuos. Se defenderá una relación de compatibilidad entre representaciones sociales y constructivismo.

Conformation of secondary amides. A predictive algorithm that correlates DFT-calculated structures and experimental proton chemical shifts.

The magnetic deshielding caused by the amido group on CON-CHalpha protons of secondary amides can easily be correlated with DFT-based structures at the B3LYP/6-31G level of theory via a novel algorithm that refines previous models, such as the classical McConnell equation. The shift is given by delta = a + 2.16 cos2(alpha - 35)/d, where alpha denotes the virtual dihedral angle resulting from linking the carbonyl and the alpha-carbons and d is the distance (A) between the shifted proton and the carbonyl oxygen. Notably, in this equation a is a parameter that can be optimized for different solvents, namely, CDCl3, DMSO-d6, and D2O. For the development of these correlations, the preferential conformation of amides is taken from the optimized structures in the gas phase obtained at the DFT level. The deshielding on anti and gauche protons in both rotamers of (Z)-acetamides and E/Z isomers of formamides has been evaluated. This methodology has proved to be highly reliable, allowing us to discard ab initio or DFT conformational arrangements when shifts calculated by the above-mentioned equation differ from the experimental values. Thus, the anti disposition between the CHalpha proton and the N-H bond appears to be the more stable conformation of simple amides. For amides bearing only one proton at Calpha, a local syn minimum can equally be characterized. The rotational barriers around the CON-alkyl bond along with the pyramidalization of the amido group have also been reassessed. As the conformation is taken away from anti or local syn minima, the nonplanarity of the amido group appears to increase.

El conocimiento de los niños sobre la sociedad según el constructivismo y la teoría de las representaciones sociales / Children´s knowledge about society in the view of constructivism and social representations theory

Hemos comparado los aspectos metodológicos y fundamentos teóricos de investigaciones psicogenéticas con otras provenientes de la psicología social referidas a los conocimientos sociales de los niños. Especialmente, las distintas preguntas que han guiado las indagaciones, así como los diseños de investigación y el análisis de los datos. Hemos contrapuesto, particularmente, y desde el punto de vista teórico y metodológico, las indagaciones que sostienen el carácter socialmente transmitido de las representaciones sociales, pero sin elaboración intelectual de los niños, con las indagaciones del programa "critico" de psicología genética, que sostienen la construcción de hipótesis o teorías de los sujetos, pero en un contexto de transmisión de representaciones sociales. A este respecto se comparan sistemáticamente dos investigaciones sobre la autoridad escolar. En cambio, encontramos que los estudios "críticos" sobre conocimientos sociales son compatibles con las indagaciones de los psicólogos sociales que recuperan las ideas de Piaget acerca de la construcción de ideas morales pero las vinculan con la autoridad de status, vinculadas a la representación social de género. Se abre un campo de estudios de posible colaboración basado en que el programa "critico" psicogenético y la corriente de la psicología de Duveen y Leman tienen en común una perspectiva relacional entre conocimiento individual y representaciones sociales.