Integrated analysis of mismatch repair system in malignant astrocytomas

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR) system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI) and MMR gene mutations in a set of 96 low- and high-grade astrocytomas. Forty-one astrocytomas failed to express at least one MMR protein. Loss of MSH2 expression was more frequent in low-grade astrocytomas. Loss of MLH1 expression was associated with MLH1 promoter hypermethylation and MLH1 -93G>A promoter polymorphism. However, MSI was not related with MMR protein expression and only 5% of tumors were MSI-High. Furthermore, the incidence of tumors carrying germline mutations in MMR genes was low and only one glioblastoma was associated with Lynch syndrome. Interestingly, survival analysis identified that tumors lacking MSH6 expression presented longer overall survival in high-grade astrocytoma patients treated only with radiotherapy while MSH6 expression did not modify the prognosis of those patients treated with both radiotherapy and chemotherapy. Our findings suggest that MMR system alterations are a frequent event in malignant astrocytomas and might help to define a subgroup of patients with different outcome.This work was supported by Fondo de Investigación Sanitaria (FIS PI 10/00219), Instituto de Estudios de Ciencias de la Salud de Castilla y León IECSCYL and Junta de Castilla y León y Fondo Social Europeo (Orden EDU/330/2008).Peer Reviewe

Solving vehicle routing problems with asymmetric costs and heterogeneous fleets

[EN] The vehicle routing problem (VRP) is a flourishing research area with clear applications to real-life distribution companies. However, most VRP-related academic articles assume the existence of a homogeneous fleet of vehicles and/or a symmetric cost matrix. These assumptions are not always reasonable in real-life scenarios. To contribute in closing this gap between theory and practice, we propose a hybrid methodology for solving the asymmetric and heterogeneous vehicle routing problem (AHVRP). In our approach, we consider: 1) different types of vehicle loading capacities (heterogeneous fleets); 2) asymmetric distance-based costs. The proposed approach combines a randomised version of a well-known savings heuristic with several local searches specifically adapted to deal with the asymmetric nature of costs. A computational experiment allows us to discuss the efficiency of our approach and also to analyse how routing costs vary when slight departures from the homogeneous fleet assumption are considered.This work has been partially supported by the Ibero-American Program for Science, Technology and Development (CYTED2010-511RT0419, IN3-HAROSA network) and by the Spanish Ministry of Science and Innovation (TRA2010-21644-C03).Herrero, R.; Rodríguez Villalobos, A.; Cáceres-Cruz, J.; Juan, ÁA. (2014). Solving vehicle routing problems with asymmetric costs and heterogeneous fleets. International Journal of Advanced Operations Management. 6(1):58-80. https://doi.org/10.1504/IJAOM.2014.059620S58806

Assessment of fatigue in oncology. Implementation of the Perform Questionnaire

La astenia relacionada con el cáncer constituye uno de los problemas más frecuentes y con mayor repercusión sobre la calidad de vida en los pacientes oncológicos, y a menudo persiste durante meses o años después de finalizado el tratamiento. Su etiología y fisiopatología son complejas y en la mayoría de los casos no bien conocidas, existiendo múltiples interacciones con otras entidades clínicas relacionadas con el cáncer. En cuanto al abordaje terapéutico, debe ser individualizado, incluyendo el tratamiento de los factores contribuyentes, la educación del paciente, el establecimiento de medidas generales, la administración de fármacos y las intervenciones no farmacológicas, entre las que destaca el ejercicio físico. Con el fin de facilitar la detección y evaluación periódica de la astenia en el paciente oncológico dentro de la práctica clínica habitual, se han desarrollado una serie de herramientas que clásicamente pueden agruparse en dos tipos: unidimensionales y multidimensionales. Sin embargo, una de las cuestiones más importantes de las escalas de evaluación de calidad de vida en general y de la astenia en particular es que su desarrollo y validación se haya llevado a cabo en el contexto sociocultural en que se aplicarán. El cuestionario Perform es el único desarrollado y validado íntegramente en población oncológica española.Fatigue-related cancer is one of the most frequent problems and one of the symptoms with more impact in the quality of life in patients with cancer; and often it persists during months or years after the treatment has finished. The etiology and physiopathology are complex and, in most of cases, not well known, existing multiple interactions with other clinical entities related with cancer. The therapeutical approach must be individualized, including the treatment of contributing factors, education of the patient, the implementation of general therapeutic reccomendations, pharmacological treatment and non-pharmacologic interventions, specially exercise. With the aim of detect and assess fatigue-related cancer in the clinical practice, some scales and questionnaires have been developed. Classicaly the have been classified as unidimensional and multidimensional questionnaires. However, one of the most important questions regarding the quality of life scales, and in particular fatigue scales, is that it`s design, development and validation must be performed in the social and cultural context of the population in which the questionnaire is going to be implemented. The Perform Questionnaire is the only scale for the assessment of fatigue-related cancer developed and validated completely in a Spanish population

Evaluation of functional and nutritional potential of a protein concentrate from Pleurotus ostreatus mushroom

Edible mushrooms used as a protein-rich food may be an attractive alternative to conventional protein sources, while promoting its valorization. This work aimed to obtain a protein concentrate from a Pleurotus ostreatus mushroom flour, its characterization, and nutritional and functional properties evaluation. Methodologies applied for extraction and precipitation of protein were optimized - pH 4 and 12, respectively; and flour-solvent ratio of 1:20 w/v. The protein density was increased by 78 %. P. ostreatus flour and concentrate were characterized by proximal composition. The content of total phenolic compounds in the protein concentrate decreased, leading to a positive effect on protein digestibility, while the DPPH radical scavenging activity was not significantly affected. Peptides with molecular weights from 12 to 35 kDa, with possible bioactivity, were identified by electrophoresis. Protein digestibility assessed by in vitro gastrointestinal digestion showed a 4.2-fold higher hydrolysis degree in the protein concentrate than the flour.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE–01–0145–FEDER-000004) funded by the European Regional Development Fund under the scope of Norte 2020–Programa Operacional Regional do Norte and the Project ColOsH PTDC/BTM–SAL/30071/2017 (POCI–01–0145–FEDER–030071). The authors also acknowledge the grant for a postgraduate scholarship (CVU number 922722) provided by National Council of Science and Technology (CONACYT) Mexico.info:eu-repo/semantics/publishedVersio

Melanosis neurocutánea con hidrocefalia obstructiva: A propósito de un caso / Neurocutaneous Melanosis with Obstructive Hydrocephaly: A Case Report

Antecedentes. Esta rara hamartomatosis melanocítica de la piel y leptomeninges fue descrita por Vichow en 1859 y nombrada como Melanosis Neurocutanea por Von Bogaert en 1948. Puede reconocerse clínicamente por la presencia en la piel de nevus pigmentados de color oscuro, gruesos y pilosos, repartidos en forma "de Baño de asiento" (hipogastrio, nalgas y parte superior de los muslos) con manifestaciones neurológicas expresadas por hidrocefalia, convulsiones y retraso mental. Existe elevado riesgo de malignización de los nevus. La mayoría de los casos son esporádicos, aunque se ha sugerido un patrón de herencia autosómico dominante con expresividad variable (MIM: 249400). Presentación de caso. Paciente femenina de 6 meses de edad, producto de cuarta gestación, a término, normopeso, padres jóvenes no consanguíneos e historia familiar negativo de defecto congénitos. En la exploración física se comprobaron múltiples nevus pigmentados con al distribución y característica de una Melanosis Neurocutánea; a partir de los dos meses se comprobaron fontanela anterior tensa y rápido crecimiento del perímetro cefálico confirmado por TAC una hidrocefalia obstructiva con marcada dilatación de III y IV ventrículo motivo por el cual le fue realizada por Neurocirugía una derivación de LCR ventrículo-peritoneal. Evoluciona con un marcado retraso en el desarrollo psicomotor. Fallece a la edad de 13 meses. Conclusión. Melanosis Neurocutánea asociada a Hidrocefalia obstructiva por Melanosis difusa del S.N.C.Palabras clave: Hidrocefalia; melanosis neurocutánea.ABSTRACTBackground: This rare melonocytic hamartoma of the skin and leptomeninges was first described by Vichow in 1859 and named Neurocutaneous Melanosis by Von Bogaert in 1948. Clinically, it is recognised due to the presence in the skin of dark pigmented, thick and pilose nevi spread like a "seat bath" (hypogastric region, buttocks, the upper part of the thighs), having neurological disorders which are expressed by hydrocephaly, seizures and mental retardation. The risk of malignancy in the nevi is observed. The majority of the cases are sporadic, though a pattern of autosomal dominant heredity with a variable expression (MIM: 249400) is suggested. Case Report: A six-months female patient, born from the fourth pregnancy, in term, normal weight and having young no consanguineous parents and a negative familial history of genetic defects was treated in the neurosurgical consultation. In the physical examination multiple pigmented nevi were observed with a distribution and features which matched with a Neurocutaneous Melanosis; starting from the two months of age, the anterior fontanel was tense and a sudden growing of the cephalic perimeter was observed; confirming with CAT-scan an obstructive hydrocephaly which showed a marked dilatation of the 3rd and 4th ventricles of the brain; this was the reason, to perform by means of a neurosurgery a CSF ventriculoperitoneal shunt. A marked retardation of the psychomotor development was observed, dying at 13 months of age. Conclusion: Neurocutaneous Melanosis associated with an Obstructive Hydrocephaly due to a Diffuse Melanosis of the Central Nervous System (CNS). Key words: Hydrocephaly; neurocutaneous melanosi

Melanosis neurocutánea con hidrocefalia obstructiva: A propósito de un caso / Neurocutaneous Melanosis with Obstructive Hydrocephaly: A Case Report

Antecedentes. Esta rara hamartomatosis melanocítica de la piel y leptomeninges fue descrita por Vichow en 1859 y nombrada como Melanosis Neurocutanea por Von Bogaert en 1948. Puede reconocerse clínicamente por la presencia en la piel de nevus pigmentados de color oscuro, gruesos y pilosos, repartidos en forma "de Baño de asiento" (hipogastrio, nalgas y parte superior de los muslos) con manifestaciones neurológicas expresadas por hidrocefalia, convulsiones y retraso mental. Existe elevado riesgo de malignización de los nevus. La mayoría de los casos son esporádicos, aunque se ha sugerido un patrón de herencia autosómico dominante con expresividad variable (MIM: 249400). Presentación de caso. Paciente femenina de 6 meses de edad, producto de cuarta gestación, a término, normopeso, padres jóvenes no consanguíneos e historia familiar negativo de defecto congénitos. En la exploración física se comprobaron múltiples nevus pigmentados con al distribución y característica de una Melanosis Neurocutánea; a partir de los dos meses se comprobaron fontanela anterior tensa y rápido crecimiento del perímetro cefálico confirmado por TAC una hidrocefalia obstructiva con marcada dilatación de III y IV ventrículo motivo por el cual le fue realizada por Neurocirugía una derivación de LCR ventrículo-peritoneal. Evoluciona con un marcado retraso en el desarrollo psicomotor. Fallece a la edad de 13 meses. Conclusión. Melanosis Neurocutánea asociada a Hidrocefalia obstructiva por Melanosis difusa del S.N.C.Palabras clave: Hidrocefalia; melanosis neurocutánea.ABSTRACTBackground: This rare melonocytic hamartoma of the skin and leptomeninges was first described by Vichow in 1859 and named Neurocutaneous Melanosis by Von Bogaert in 1948. Clinically, it is recognised due to the presence in the skin of dark pigmented, thick and pilose nevi spread like a "seat bath" (hypogastric region, buttocks, the upper part of the thighs), having neurological disorders which are expressed by hydrocephaly, seizures and mental retardation. The risk of malignancy in the nevi is observed. The majority of the cases are sporadic, though a pattern of autosomal dominant heredity with a variable expression (MIM: 249400) is suggested. Case Report: A six-months female patient, born from the fourth pregnancy, in term, normal weight and having young no consanguineous parents and a negative familial history of genetic defects was treated in the neurosurgical consultation. In the physical examination multiple pigmented nevi were observed with a distribution and features which matched with a Neurocutaneous Melanosis; starting from the two months of age, the anterior fontanel was tense and a sudden growing of the cephalic perimeter was observed; confirming with CAT-scan an obstructive hydrocephaly which showed a marked dilatation of the 3rd and 4th ventricles of the brain; this was the reason, to perform by means of a neurosurgery a CSF ventriculoperitoneal shunt. A marked retardation of the psychomotor development was observed, dying at 13 months of age. Conclusion: Neurocutaneous Melanosis associated with an Obstructive Hydrocephaly due to a Diffuse Melanosis of the Central Nervous System (CNS). Key words: Hydrocephaly; neurocutaneous melanosi

Effect of pH on the production of hydrolytic enzymes of industrial interest by Bacillus licheniformis using sewage sludge as a low-cost culture médium

Management of sewage sludge has become a topic of increasing importance. This is because the treatment and final destination of these wastes are not growing at the same rate at which generated what is necessary to add the limited storage capacity of wastewater treatment plants or waste transfer centers. Current policies of different governments aims, among others, promote proecological management of sewage sludge, replacing traditional methods by new methods that lead to their stabilization and safe recycling. These methods can lead to the recovery of valuable raw materials from potentially dangerous others in order to permit their use in agriculture, industry or energy production. Moreover, exists a great enzyme market, mainly those with hydrolytic activities such as proteases, lipases or cellulases. Although its use has many advantages, the competitiveness of the enzymes compared with chemicals is limited by its high production costs. The use of a less expensive culture media and the stimulation of the production of these enzymes can significantly reduce production costs. Therefore, the use of tertiary materials as alternative substrates, available in large quantities and at lower cost, is an interesting option. In this work we have studied the effect of pH on the fermentation of sewage sludge by Bacillus licheniformis, a hydrolytic enzymes producer microorganism, in order to obtain several products for specific agronomic applications

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. [Results]: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. [Conclusions]: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.This work was supported by funds provided through the Gene Partnership and the Manton Center for Orphan Disease Research at Boston Children’s Hospital and the Center for Biomedical Informatics at Harvard Medical School and by generous donations in-kind of genomic sequencing services by Life Technologies (Carlsbad, CA, USA) and Complete Genomics (Mountain View, CA, USA).Peer Reviewe

Analysis of the Yield of Radish (Raphanus Sativus L.) Fertilized with Compost Based on Organic Waste from Markets and its Relationship with its Stomatal Density

For higher yields in vegetable cultivation, the availability of soil nutrients must be improved. Therefore, the aim of this research was to establish the relationship between stomatal density and the yield of the radish crop fertilized with compost made from organic market waste. A completely randomized block design was used, which consisted of 3 blocks and 5 treatments, which were T1, T2, T3, T4 and T5 with 00, 10, 15, 15, 20 and 25 g compost/plant respectively. The physical characteristics of the plants were evaluated from sowing to harvest and the data obtained were processed by analysis of variance and Duncan's test. Chemical analysis of the compost and soil was carried out, as well as a foliar analysis to determine the nutrient concentration by treatment. The results determined that the treatment (T4) stood out in plant length with 28.96 cm, plant weight with 43.33 g, yield of 10.82 t/ha and bulb diameter of 3.92 cm; likewise, in the concentration of nutrients in the leaves, the treatment (T5) highlighted in N with 5.94%, Ca 4.84%, Mg 1.29%, Zn 64.58 ppm and a stomatal density of 642 stomas/mm2. It is concluded that, at an adequate dose of compost, the concentration of nutrients increases, as well as the stomatal density, resulting in higher yields