Synthesis of methyl Alpha-D-Glucoolicosaccharides by Entrapped Dextransucrase from Leuconostoc mesenteroides B-1299

The synthesis of methyl alpha-D-glucooligosaccharides, using sucrose as glucosyl donor and methyl alpha-D-glucopyranoside as acceptor, was studied with dextransucrase from Leuconostoc mesenteroides NRRL B-1299. The enzyme was immobilized by entrapment in alginate. By NMR and mass spectrometry we identified three homologous series (S1-S3) of methyl alpha-D-glucooligosaccharides. Series S2 and S3 were characterized by the presence of alpha(1-2) linkages, in combination with alpha(1-6) bonds. Two parameters, sucrose to acceptor concentration ratio (S/A) and the total sugar concentration (TSC) determined the yield of methyl alpha-D-glucooligosaccharides. The maximum concentration achieved of the first acceptor product, methyl alpha-D-isomaltoside, was 65 mM using a S/A 1:4 and a TSC of 336 g l-1. When increasing temperature, a shift of selectivity towards compounds containing alpha(1-2) bonds was observed. The formation of leucrose as a side process was very significant (reaching values of 32 g l-1) at high sucrose concentrations.We are very grateful to Profs. P. Monsan and M. Remaud-Simeon (INSA, Toulouse) for providing us with dextransucrase. We thank Prof. A. Cortés (ICP, CSIC) for helpful comments. We thank Gobierno Vasco and Instituto Danone for research fellowships. This work was supported by the Spanish Education and Science Ministry (Project BIO2004-03773-C04-01).Peer reviewe

Gas-phase reactivity of OH radicals with ammonia (NH3) and methylamine (CH3NH2) at around 22 K

IInterstellar molecules containing N atoms, such as ammonia (NH3) and methylamine (CH3NH2), could be potential precursors of amino acids like the simplest one, glycine (NH2CH2COOH). The gas-phase reactivity of these N-bearing species with OH radicals, ubiquitous in the interstellar medium, is not known at temperatures of cold dark molecular clouds. In this work, we present the first kinetic study of these OH-reactions at around 22 K and different gas densities ((3.4-16.7)×1016 cm-3) in helium. The obtained rate coefficients, with ±2 uncertainties, k1(OH+NH3) = (2.7±0.1)×10-11 cm3 s-1 k2(OH+CH3NH2) = (3.9±0.1)×10-10 cm3 s-1 can be included in pure gas-phase or gas-grain astrochemical models to interpret the observed abundances of NH3 and CH3NH2. We observed an increase of k1 and k2 with respect to those previously measured by others at the lowest temperatures for which rate coefficients are presently available: 230 K and 299 K, respectively. This increase is about 380 times for NH3 and 20 times for CH3NH2. Although the OH+NH3 reaction is included in astrochemical kinetic databases, the recommended temperature dependence for k1 is based on kinetic studies at temperatures above 200 K. However, the OH+CH3NH2 reaction is not included in astrochemical networks. The observed increase in k1 at ca. 22 K does not significantly change the abundance of NH3 in a typical cold dark interstellar cloud. However, the inclusion of k2 at ca. 22 K, not considered in astrochemical networks, indicates that the contribution of this destruction route for CH3NH2 is not negligible, accounting for 1/3 of the assumed main depletion route (reaction with HCO+) in this IS environment.Las moléculas interestelares que contienen átomos de N, como el amoníaco (NH3) y la metilamina (CH3NH2), podrían ser precursoras potenciales de aminoácidos como el más simple, la glicina (NH2CH2COOH). La reactividad en fase gaseosa de estas especies portadoras de N con radicales OH, omnipresentes en el medio interestelar, no se conoce a temperaturas de nubes moleculares oscuras y frías. En este trabajo, presentamos el primer estudio cinético de estas reacciones OH a alrededor de 22 K y diferentes densidades de gas ((3.4-16.7) × 1016 cm-3) en helio. Los coeficientes de velocidad obtenidos, con ± 2 incertidumbres, k1 (OH + NH3) = (2.7 ± 0.1) × 10-11 cm3 s-1 k2 (OH + CH3NH2) = (3.9 ± 0.1) × 10-10 cm3 s- 1 se puede incluir en modelos astroquímicos de fase gaseosa pura o de grano de gas para interpretar las abundancias observadas de NH3 y CH3NH2. Observamos un aumento de k1 y k2 con respecto a los medidos previamente por otros a las temperaturas más bajas para las que actualmente se dispone de coeficientes de velocidad: 230 K y 299 K, respectivamente. Este aumento es aproximadamente 380 veces para el NH3 y 20 veces para el CH3NH2. Aunque la reacción OH + NH3 está incluida en las bases de datos cinéticas astroquímicas, la dependencia de temperatura recomendada para k1 se basa en estudios cinéticos a temperaturas superiores a 200 K. Sin embargo, la reacción OH + CH3NH2 no está incluida en las redes astroquímicas. El aumento observado en k1 a ca. 22 K no cambia significativamente la abundancia de NH3 en una típica nube interestelar oscura y fría. Sin embargo, la inclusión de k2 en ca. 22 K

Enzymatic acylation of di- and trisaccharides with fatty acids: choosing the appropriate enzyme, support and solvent

Enzymatic synthesis of fatty acid esters of di- and trisaccharides is limited by the fact that most biological catalysts are inactivated by the polar solvents (e.g. dimethylsulfoxide, dimethylformamide) where these carbohydrates are soluble. This article reviews the methodologies developed to overcome this limitation, namely those involving control over the reaction medium, the enzyme and the support. We have proposed the use of mixtures of miscible solvents (e.g. dimethylsulfoxide and 2-methyl-2-butanol) as a general strategy to acylate enzymatically hydrophilic substrates. We observed that decreasing the hydrophobicity of the medium (i.e. lowering the percentage of DMSO) the molar ratio sucrose diesters vs. sucrose monoesters can be substantially enhanced. The different regioselectivity exhibited by several lipases and proteases makes feasible to synthesize different positional isomers, whose properties may vary considerably. In particular, the lipase from Thermomyces lanuginosus displays a notable selectivity for only one hydroxyl group in the acylation of sucrose, maltose, leucrose and maltotriose, compared with lipase from Candida antarctica. We have examined three immobilisation methods (adsorption on polypropylene, covalent coupling to Eupergit C, and silica-granulation) for sucrose acylation catalyzed by T. lanuginosus lipase. The morphology of the support affected significantly the reaction rate and/or the selectivity of the processWe are grateful to Loreto Bajón (Instituto de Catálisis) for technical help with electron microscopy. We are indebted to Jordi Sucrana (Degusa Texturant Systems, Barcelona, Spain) and Naoya Otomo (Mitsubishi Kagaku Foods Co., Tokyo, Japan) for technical help. We thank Comunidad de Madrid and Ministerio de Ciencia y Tecnología for research fellowships. This work was supported by the E.U. (Project BIO4-CT98-0363), the Spanish CICYT (Projects BIO98-0793 and BIO1999-1710-CE), and Comunidad de Madrid (Project 07G/0042/2000)Peer reviewe

A Resource for Guiding Data Stewards to Make European Rare Disease Patient Registries FAIR

Objective: This paper reports on the development of a dynamic data management planning questionnaire to guide data stewards of the European Reference Network (ERN) rare disease patient registries to make their data findable, accessible, interoperable, and reusable (FAIR). As part of this work, the questionnaire was validated through expert review and aligned with existing resources on rare diseases and FAIR data management. Materials and Methods: The questionnaire was developed for the Data Stewardship Wizard, a tool for data management planning. Knowledge sources on FAIR data, ERN patient registries, and data management were used to compose questions. Ten domain experts validated the questionnaire. The topics in the questionnaire were aligned with existing knowledge bases. Results: A total of 57 questions were included in the questionnaire. Twenty-three references to the FAIR Cookbook and Research Data Management toolkit for Life Sciences were added. Expert validation provided a total of 166 comments on content, structure, and software-related issues. A public instance of the Data Stewardship Wizard was deployed for use by data stewards of ERN patient registries. Discussion: The questionnaire addresses issues that ERNs encounter when making their registries FAIR and follows the implementation choices made by the European rare disease community. A challenging task for future research is to extend the questionnaire to other types of registries and to validate with users. Conclusion: This smart questionnaire is the first model created for the Data Stewardship Wizard that helps ERN patient registries with making their data FAIR. It will assist data stewards in aligning their efforts and providing guidance on FAIR data

Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters

This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

Background: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97\ub71 (95% UI 95\ub78-98\ub71) in Iceland, followed by 96\ub76 (94\ub79-97\ub79) in Norway and 96\ub71 (94\ub75-97\ub73) in the Netherlands, to values as low as 18\ub76 (13\ub71-24\ub74) in the Central African Republic, 19\ub70 (14\ub73-23\ub77) in Somalia, and 23\ub74 (20\ub72-26\ub78) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91\ub75 (89\ub71-93\ub76) in Beijing to 48\ub70 (43\ub74-53\ub72) in Tibet (a 43\ub75-point difference), while India saw a 30\ub78-point disparity, from 64\ub78 (59\ub76-68\ub78) in Goa to 34\ub70 (30\ub73-38\ub71) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4\ub78-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20\ub79-point to 17\ub70-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17\ub72-point to 20\ub74-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view-and subsequent provision-of quality health care for all populations

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

Copyright © 2018 The Author(s). Published by Elsevier Ltd. Background A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8-98·1) in Iceland, followed by 96·6 (94·9-97·9) in Norway and 96·1 (94·5-97·3) in the Netherlands, to values as low as 18·6 (13·1-24·4) in the Central African Republic, 19·0 (14·3-23·7) in Somalia, and 23·4 (20·2-26·8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91·5 (89·1-93·6) in Beijing to 48·0 (43·4-53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point disparity, from 64·8 (59·6-68·8) in Goa to 34·0 (30·3-38·1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view - and subsequent provision - of quality health care for all populations

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016.

BACKGROUND: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. METHODS: Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita

Molecular structure of van der Waals complex of o- and m-methylaniline with CF3Cl, CF3H, CF4 and CH4 studied by laser induced fluorescence spectroscopy and ab initio calculations

The excitation LIF spectra of van der Waals complexes of o- and p-methylaniline and CF3Cl, CF3H, CH4 and CF4 in a supersonic free jet are reported. The spectra show a resolved structure characteristic due to the internal rotational transitions of the methyl group. The equilibrium geometries in the ground state of the complexes have been calculated at MP2/6-31+G∗ level of calculation and the intermolecular interaction have been discussed.Peer reviewe