Hiperinsulinismo congénito: una revisión de los tratamientos más recientes y potenciales en desarrollo

El hiperinsulinismo congénito es una patología asociada en un gran número de casos a alteraciones de los canales KATP, en la que se libera de forma desmesurada insulina, provocando así una grave hipoglucemia que puede afectar al desarrollo de los niños que la padecen, e incluso puede ser mortal. El diazóxido, el fármaco usado por excelencia como tratamiento de dicha patología en muchos de los casos es ineficaz llegando a tener que recurrir a medidas drásticas como lo es la pancreatectomía, en la que se extirpa parte del páncreas y que puede llegar a causar patologías derivadas de dicha intervención quirúrgica como la incorrecta función exocrina del páncreas o incluso que posteriormente se derive a una diabetes. En este contexto, la necesaria búsqueda de nuevos tratamientos que medien la enfermedad es algo indispensable. En esta revisión bibliográfica se analizan algunos de los fármacos actuales, recientes y potencialmente aplicables a los pacientes que no responden a diazóxido y que suponen avance en la clínica de la enfermedad. Entre los fármacos analizados destacan la exendina (9-39), el CRN02481, el lanreótido, el sirolimus, la nifedipina, el octreótido, los anticuerpos TB-222-023 y TB-001-003, el HM15136 y el dasiglucagón, cada uno de naturaleza y mecanismos de acción distintos, y cuyos puntos a analizar incluyen la efectividad del tratamiento y la aparición de efectos adversos. También se ha realizado un análisis bibliométrico con tal de conocer el interés y los recursos invertidos en la investigación de las diferentes terapias. Además, se ha investigado acerca de las terapias no farmacológicas como la edición genética mediante el uso de CRISPR-Cas9, que supone una prometedora línea de investigación y que pese a estar lejos de poder ser aplicada a la clínica ha mostrado buenos resultados en ratones. Todas estas opciones abren un amplio abanico de tratamientos que puedan remediar la hipoglucemia que padecen los pacientes y suponen una potencial línea de investigación

The Importance of Brand Values in Family Business

Only a small body of literature exists on linking key marketing concepts in family business contexts and those studies that do exist show a significant bias towards brand management. Both the relevance of the subject and the lack of research assuming this challenge to date justify the interest and timeliness of this literature review.Based on this interest—and the existing research opportunities—this article presents the concept of brand, together with a framework for its analysis in family business contexts. The paper summarizes the six main lines of research proposed, three from the perspective of identity management, and three from the perspective of stakeholders. The last section presents a series of interesting aspects for carrying out future research

Presentación y editorial de fundación de adComunica

Editorial fundacional y presentación de los contenidos del númeroEditorial foundational content and presentation of the issu

Zoonotic implications of onchocerca species on human health

The genus Onchocerca includes several species associated with ungulates as hosts, although some have been identified in canids, felids, and humans. Onchocerca species have a wide geographical distribution, and the disease they produce, onchocerciasis, is generally seen in adult individuals because of its large prepatency period. In recent years, Onchocerca species infecting animals have been found as subcutaneous nodules or invading the ocular tissues of humans; the species involved are O. lupi, O. dewittei japonica, O. jakutensis, O. gutturosa, and O. cervicalis. These findings generally involve immature adult female worms, with no evidence of being fertile. However, a few cases with fertile O. lupi, O. dewittei japonica, and O. jakutensis worms have been identified recently in humans. These are relevant because they indicate that the parasite's life cycle was completed in the new host-humans. In this work, we discuss the establishment of zoonotic Onchocerca infections in humans, and the possibility of these infections to produce symptoms similar to human onchocerciasis, such as dermatitis, ocular damage, and epilepsy. Zoonotic onchocerciasis is thought to be an emerging human parasitic disease, with the need to take measures such as One Health Strategies, in order to identify and control new cases in humans

Delving into Android Malware Families with a Novel Neural Projection Method

[Abstract] Present research proposes the application of unsupervised and supervised machine-learning techniques to characterize Android malware families. More precisely, a novel unsupervised neural-projection method for dimensionality-reduction, namely, Beta Hebbian Learning (BHL), is applied to visually analyze such malware. Additionally, well-known supervised Decision Trees (DTs) are also applied for the first time in order to improve characterization of such families and compare the original features that are identified as the most important ones. The proposed techniques are validated when facing real-life Android malware data by means of the well-known and publicly available Malgenome dataset. Obtained results support the proposed approach, confirming the validity of BHL and DTs to gain deep knowledge on Android malwar

Biodegradation of mono-, di- and trifluoroacetate by microbial cultures with different origins

This work focused on the biodegradation of three structurally related fluoroacetates (FAs), mono- (MFA), di- (DFA) and trifluoroacetate (TFA), using as microbial inocula samples collected from a site with a long history of industrial contamination and activated sludge obtained from a municipal wastewater treatment plant. Biodegradation experiments were carried out under different modes of substrate supplementation, which included (i) FAs fed as sole carbon sources; (ii) FAs (only for DFA and TFA) fed in co-metabolism with sodium acetate; and (iii) mixtures of MFA with DFA or TFA. Biodegradation of the target compounds was assessed through fluoride ion release. Defluorination was obtained in the cultures fed with MFA, while DFA and TFA were recalcitrant in all tested conditions. When present in mixture, DFA was shown to inhibit biodegradation of MFA, while TFA had no effect. A total of 13 bacterial isolates obtained from MFA degrading cultures were found to degrade 20mgL-1 of this compound, as single strains, when supplemented as a sole carbon source. Sequencing of the 16S rRNA gene indicated that among these degrading bacteria only Delftia acidovorans had been previously reported to be able to degrade MFA. This work shows that, despite their similar chemical structures, biodegradation of the three tested FAs is very distinct and draws attention to the unknown impacts that the accumulation of DFA and TFA may have in the environment as a result of their high recalcitrance.info:eu-repo/semantics/publishedVersio

Delving into Android Malware Families with a Novel Neural Projection Method

Present research proposes the application of unsupervised and supervised machine-learning techniques to characterize Android malware families. More precisely, a novel unsupervised neural-projection method for dimensionality-reduction, namely, Beta Hebbian Learning (BHL), is applied to visually analyze such malware. Additionally, well-known supervised Decision Trees (DTs) are also applied for the first time in order to improve characterization of such families and compare the original features that are identified as the most important ones. The proposed techniques are validated when facing real-life Android malware data by means of the well-known and publicly available Malgenome dataset. Obtained results support the proposed approach, confirming the validity of BHL and DTs to gain deep knowledge on Android malware.This work is partially supported by Instituto Nacional de Ciberseguridad (INCIBE) and developed by Research Institute of Applied Sciences in Cybersecurity (RIASC)

Cerebrospinal fluid neopterin analysis in neuropediatric patients: establishment of a new cut off-value for the identification of inflammatory-immune mediated processes

OBJECTIVE: A high level of cerebrospinal fluid (CSF) neopterin is a marker of central nervous system inflammatory-immune mediated processes. We aimed to assess data from 606 neuropediatric patients, describing the clinical and biochemical features of those neurological disorders presenting CSF neopterin values above a new cut-off value that was defined in our laboratory. METHODS: To establish the new CSF neopterin cut-off value, we studied two groups of patients: Group 1 comprised 68 patients with meningoencephalitis, and Group 2 comprised 52 children with a confirmed peripheral infection and no central nervous system involvement. We studied 606 CSF samples from neuropediatric patients who were classified into 3 groups: genetic diagnosis (A), acquired/unknown etiologic neurologic diseases (B) and inflammatory-immune mediated processes (C). RESULTS: The CSF neopterin cut-off value was 61 nmol/L. Out of 606 cases, 56 presented a CSF neopterin level above this value. Group C had significantly higher CSF neopterin, protein and leukocyte values than the other groups. Sixteen of twenty-three patients in this group had a CSF neopterin level above the cut-off, whereas three and seven patients presented increased leukocyte and protein values, respectively. A significant association was found among CSF neopterin, proteins and leukocytes in the 606 patients. White matter disturbances were associated with high CSF neopterin concentrations. CONCLUSIONS: Although children with inflammatory-immune mediated processes presented higher CSF neopterin values, patients with other neurological disorders also showed increased CSF neopterin concentrations. These results stress the importance of CSF neopterin analysis for the identification of inflammatory-immune mediated processes

Teladorsagia circumcincta beta tubulin: the presence of the E198L polymorphism on its own is associated with benzimidazole resistance.

BACKGROUND NlmCategory: BACKGROUND content: "Benzimidazole resistance is associated with isotype-1 \xCE\xB2-tubulin gene F200Y, E198A and F167Y SNPs. In this study, the recently described polymorphism E198L was reported and analysed in Teladorsagia circumcincta." - Label: METHODS NlmCategory: METHODS content: "The benzimidazole phenotypic resistance was measured by the faecal egg count reduction test (FECRT) and the egg hatch test (EHT) using a discriminating dose (DD) in 39 sheep flocks. Around 1000 larvae collected before and after treatment were used for DNA extraction. The resistant species identified in all flocks was T. circumcincta. The resistance alleles frequencies were measured for F200Y and E198A. A 371-bp fragment of the isotype-1 \xCE\xB2-tubulin gene was analysed, including the three codons of interest, and a new pyrosequencing assay was designed for testing E198L." - Label: RESULTS NlmCategory: RESULTS content: "The percentage of resistant flocks was 35% by FECRT or 26% by EHT; however, F200Y and E198A SNPs were absent in T. circumcincta. The amplification of a 371-bp fragment confirmed the absence of F167Y and F200Y in 6 resistant flocks. Regarding codon 198, all samples after treatment carried a leucine (CTA). A pyrosequencing assay analysed the allele frequencies for the first two bases at codon 198 independently, G/C and A/T. The correlation between C and T frequencies was almost 1 (r\xE2\x80\x89=\xE2\x80\x890.929, P\xE2\x80\x89<\xE2\x80\x890.0001) and the mean value of both was calculated to measure the leucine frequency; this value ranged between 10.4-80.7% before treatment, and 82.3-92.8% after treatment. High and similar correlations were reported between the genotypic variables (C frequency, T frequency or mean of both frequencies) and phenotypic resistance (r\xE2\x80\x89>\xE2\x80\x890.720, P\xE2\x80\x89<\xE2\x80\x890.0001), although negatively associated with the FECRT and positively with the EHT. According to multivariate linear regression analysis, the T frequency was the most significant variable influencing the phenotypic resistance (FECRT or EHT; P\xE2\x80\x89<\xE2\x80\x890.0001). In the EHT, 67.1% of the phenotypic variability is associated with the T frequency but in the FECRT only 33.4%; therefore, the EHT using a DD seems to detect the genotypic resistance more accurately than the FECRT." - Label: CONCLUSIONS NlmCategory: CONCLUSIONS content: The E198L polymorphism can confer BZ resistance on its own in T. circumcincta

Teladorsagia circumcincta beta tubulin: the presence of the E198L polymorphism on its own is associated with benzimidazole resistance

[EN] BACKGROUND: Benzimidazole resistance is associated with isotype-1 β-tubulin gene F200Y, E198A and F167Y SNPs. In this study, the recently described polymorphism E198L was reported and analysed in Teladorsagia circumcincta. METHODS: The benzimidazole phenotypic resistance was measured by the faecal egg count reduction test (FECRT) and the egg hatch test (EHT) using a discriminating dose (DD) in 39 sheep flocks. Around 1000 larvae collected before and after treatment were used for DNA extraction. The resistant species identified in all flocks was T. circumcincta. The resistance alleles frequencies were measured for F200Y and E198A. A 371-bp fragment of the isotype-1 β-tubulin gene was analysed, including the three codons of interest, and a new pyrosequencing assay was designed for testing E198L. RESULTS: The percentage of resistant flocks was 35% by FECRT or 26% by EHT; however, F200Y and E198A SNPs were absent in T. circumcincta. The amplification of a 371-bp fragment confirmed the absence of F167Y and F200Y in 6 resistant flocks. Regarding codon 198, all samples after treatment carried a leucine (CTA). A pyrosequencing assay analysed the allele frequencies for the first two bases at codon 198 independently, G/C and A/T. The correlation between C and T frequencies was almost 1 (r = 0.929, P  0.720, P < 0.0001), although negatively associated with the FECRT and positively with the EHT. According to multivariate linear regression analysis, the T frequency was the most significant variable influencing the phenotypic resistance (FECRT or EHT; P < 0.0001). In the EHT, 67.1% of the phenotypic variability is associated with the T frequency but in the FECRT only 33.4%; therefore, the EHT using a DD seems to detect the genotypic resistance more accurately than the FECRT. CONCLUSIONS: The E198L polymorphism can confer BZ resistance on its own in T. circumcinctaSIThis study was funded by the Spanish “Ramón y Cajal” Programme of the Ministry of Economy and Competitiveness (MMV, RYC‑2015‑18368), and the Cooperativa Bajo Duero, COBADU. EVG was funded by FPU16/03536, JG by Ramon Areces Foundation, VCGA by Junta de Castilla y León and Fondo Social Europeo (LE082‑18), MCP by the Stopping Transmission Of intestinal Parasites (STOP) project (EDCTP2 programme; RIA2017NCT‑1845) and MMV by the Spanish “Ramon y Cajal” Programme (RYC‑2015‑18368