Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization

Background and Objectives Genetic white matter disorders (GWMD) are of heterogeneous origin, with >100 causal genes identified to date. Classic targeted approaches achieve a molecular diagnosis in only half of all patients. We aimed to determine the clinical utility of singleton whole-exome sequencing and whole-genome sequencing (sWES-WGS) interpreted with a phenotype- and interactome-driven prioritization algorithm to diagnose GWMD while identifying novel phenotypes and candidate genes. Methods A case series of patients of all ages with undiagnosed GWMD despite extensive standard-of-care paraclinical studies were recruited between April 2017 and December 2019 in a collaborative study at the Bellvitge Biomedical Research Institute (IDIBELL) and neurology units of tertiary Spanish hospitals. We ran sWES and WGS and applied our interactome-prioritization algorithm based on the network expansion of a seed group of GWMD-related genes derived from the Human Phenotype Ontology terms of each patient. Results We evaluated 126 patients (101 children and 25 adults) with ages ranging from 1 month to 74 years. We obtained a first molecular diagnosis by singleton WES in 59% of cases, which increased to 68% after annual reanalysis, and reached 72% after WGS was performed in 16 of the remaining negative cases. We identified variants in 57 different genes among 91 diagnosed cases, with the most frequent being RNASEH2B, EIF2B5, POLR3A, and PLP1, and a dual diagnosis underlying complex phenotypes in 6 families, underscoring the importance of genomic analysis to solve these cases. We discovered 9 candidate genes causing novel diseases and propose additional putative novel candidate genes for yet-to-be discovered GWMD. Discussion Our strategy enables a high diagnostic yield and is a good alternative to trio WES/WGS for GWMD. It shortens the time to diagnosis compared to the classical targeted approach, thus optimizing appropriate management. Furthermore, the interactome-driven prioritization pipeline enables the discovery of novel disease-causing genes and phenotypes, and predicts novel putative candidate genes, shedding light on etiopathogenic mechanisms that are pivotal for myelin generation and maintenance

Diet supplementation for 5 weeks with polyphenol-rich cereals improves several functions and the redox state of mouse leucocytes

BACKGROUND: Cereals naturally contain a great variety of polyphenols, which exert a wide range of physiological effects both in vitro and in vivo. Many of their protective effects, including an improvement of the function and redox state of immune cells in unhealthy or aged subjects come from their properties as powerful antioxidant compounds. However, whether cereal-based dietary supplementation positively affects the immune function and cellular redox state of healthy subjects remains unclear. AIM OF THE STUDY: To investigate the effects of supplementation (20% wt/wt) for 5 weeks with four different cereal fractions on healthy mice. METHODS: Several parameters of function and redox state of peritoneal leukocytes were measured. The cereals, named B (wheat germ), C (buckwheat flour), D (fine rice bran) and E (wheat middlings) contained different amounts of gallic acid, p-hydroxybenzoic acid, vanillic acid, sinapic acid, p-coumaric acid, ferulic acid, quercetin, catechin, rutin and oryzanol as major polyphenols. RESULTS: In general, all cereal fractions caused an improvement of the leukocyte parameters studied such as chemotaxis capacity, microbicidal activity, lymphoproliferative response to mitogens, interleukin-2 (IL-2) and tumor necrosis factor (TNFα) release, as well as oxidized glutathione (GSSG), GSSG/GSH ratio, catalase (CAT) activity and lipid oxidative damage. We observed similar effects among the cereal fractions. CONCLUSIONS: The results suggest that some of these effects may due, at least partially, to the antioxidant activity of the polyphenols naturally present in cereals. Since an appropriate function of the leukocytes has been proposed as marker of the health state, a short-term intake of cereals seems to be sufficient to exert a benefit in the health of the general population. However, further studies are needed to assess the optimal doses and to find out which active polyphenols are able to mediate the observed physiological effects before recommending their regular consumption

Estrategias de mejora para hoteles de tres estrellas de Mérida Yucatán

The tourism industry in Mexico actively contributes to its economy. Research in the tourism field favors economic growth. Yucatan is a tourist pole of the country, this is why the quality of the services of the hotel sector has special importance. The increase in the number of 4 and 5 star hotels in the city of Mérida has overshadowed the development of 3 star hotels, mostly family businesses. The search of the loyalty of the guests towards this hotels with basic services is indispensable for their permanence and development. The objective of this research is to analyze the quality of services based on the elements of quality, permanence and loyalty of three-star hotel guests in the city of Mérida Yucatán. A Likert scale was used, consisting of 26 items and five dimensions to be ordered in relative importance, called "Servhotel Mipymes". The quality of five three-star hotels was analyzed and the sample of guests was based on the occupancy rate for each hotel. Among the results it was found that the differences between the perceptions and the expectations of the services of the hotels were minimal, in two dimensions the guest received more than they expected and in the other 3 dimensions their expectations exceeded what they actually received. The general level of quality received by the guests was "Good" with a score of 4.17, however the expectations were not exceeded.La industria turística en México contribuye activamente su economía. Investigaciones en el campo turístico favorecen al crecimiento económico. Yucatán es un polo turístico del país, por lo que la calidad de los servicios del sector hotelero cobra especial importancia. El incremento en el número de hoteles de 4 y 5 estrellas en la ciudad de Mérida ha opacado el desarrollo de hoteles de 3 estrellas, en su mayoría empresas familiares. La búsqueda de la lealtad de los huéspedes hacia esto hoteles con servicios básicos es indispensable para su permanencia y desarrollo. Esta investigación tiene como objetivo analizar la calidad en los servicios con base en los elementos de calidad, permanencia y lealtad de huéspedes de hoteles de tres estrellas de la ciudad de Mérida Yucatán. Se empleó una escala de Likert con 26 reactivos y cinco dimensiones, denominada “Servhotel Mipymes”. Se analizó la calidad de cinco hoteles de tres estrellas. La muestra de huéspedes fue calculada con el índice de ocupación de cada hotel. Entre los resultados se encontró que las diferencias entre las percepciones y las expectativas de los servicios de los hoteles fueron mínimas, en dos dimensiones el huésped recibió más de lo que esperaba y en las otras 3 dimensiones sus expectativas superaron lo que en realidad recibieron. El nivel general de calidad recibida por los huéspedes fue “Buena” con una puntuación de 4.17, sin embargo las expectativas no fueron superadas

Evaluación del plan de atención básica en los municipios descentralizados de Colombia, 2001-2002

IP 1115-04-12979Incluye anexosFacultad Nacional de Salud Publica. -- Vol. 22, no.2 (jul.dic.2004); p.77-89. -- ISSN 0120386.;ARTICULO(S) EN REVISTA: El plan de atencion basica en losmunicipios desentralizados de Colombia, 2001-2003;/ Blanca Myriam Chavez G., Oscar Sierra R., Monica Maria LoperaM., PaulaCristina Montoya T. -- En: Revista