Interstitial Cells of Cajal and Enteric Nervous System in Gastrointestinal and Neurological Pathology, Relation to Oxidative Stress

The enteric nervous system (ENS) is organized into two plexuses—submucosal and myenteric—which regulate smooth muscle contraction, secretion, and blood flow along the gastrointestinal tract under the influence of the rest of the autonomic nervous system (ANS). Interstitial cells of Cajal (ICCs) are mainly located in the submucosa between the two muscle layers and at the intramuscular level. They communicate with neurons of the enteric nerve plexuses and smooth muscle fibers and generate slow waves that contribute to the control of gastrointestinal motility. They are also involved in enteric neurotransmission and exhibit mechanoreceptor activity. A close relationship appears to exist between oxidative stress and gastrointestinal diseases, in which ICCs can play a prominent role. Thus, gastrointestinal motility disorders in patients with neurological diseases may have a common ENS and central nervous system (CNS) nexus. In fact, the deleterious effects of free radicals could affect the fine interactions between ICCs and the ENS, as well as between the ENS and the CNS. In this review, we discuss possible disturbances in enteric neurotransmission and ICC function that may cause anomalous motility in the gut

Low Doses of Melatonin to Improve Sleep in Children with ADHD: An Open-Label Trial

Objective. Only a few studies assessing the sleep effects of low doses of melatonin (aMT) have been performed in the past, most of them in adults, and only one in subjects with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to provide evidence of the changes induced by aMT doses as low as 1 mg in the sleep pattern of pediatric patients with ADHD under treatment with methylphenidate (MPH). Methods. Children and adolescents (7–15 years) with ADHD who were receiving extended-release MPH were recruited. A seven-week sleep diary was collected prior to starting a four-week treatment with 1 mg of aMT (30 min before bedtime). Seven-day actigraphic assessments of sleep were performed before and after treatment. Results. Twenty-seven patients (17 males, 62.96%) participated in the study, who had been receiving MPH for 1.57 (1.11) months. A significant increase in sleep duration (TST) was observed after one month of treatment (463 (49) min to 485 (41) min; p < 0.040), with nonsignificant improvements in sleep-onset latency (SOL), nocturnal awakenings, or sleep efficiency. Only minor adverse effects were reported. Conclusion. Low doses of melatonin (1 mg) are able to increase TST in children and adolescents with ADHD receiving treatment with psychostimulants, with an adequate tolerability profile. Further placebo-controlled trials adjusting the time of aMT administration to the individual circadian profile should explore the effects of low doses of this hormone to shorten SOL in this population of patients

Anonymizing cybersecurity data in critical infrastructures: the CIPSEC approach

Cybersecurity logs are permanently generated by network devices to describe security incidents. With modern computing technology, such logs can be exploited to counter threats in real time or before they gain a foothold. To improve these capabilities, logs are usually shared with external entities. However, since cybersecurity logs might contain sensitive data, serious privacy concerns arise, even more when critical infrastructures (CI), handling strategic data, are involved. We propose a tool to protect privacy by anonymizing sensitive data included in cybersecurity logs. We implement anonymization mechanisms grouped through the definition of a privacy policy. We adapt said approach to the context of the EU project CIPSEC that builds a unified security framework to orchestrate security products, thus offering better protection to a group of CIs. Since this framework collects and processes security-related data from multiple devices of CIs, our work is devoted to protecting privacy by integrating our anonymization approach.Peer ReviewedPostprint (published version

Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

Studies suggest that the bidirectional relationship existent between the gut microbiome (GM) and the central nervous system (CNS), or so-called the microbiome–gut–brain axis (MGBA), is involved in diverse neuropsychiatric diseases in children and adults. In pediatric age, most studies have focused on patients with autism. However, evidence of the role played by the MGBA in attention deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood, is still scanty and heterogeneous. This review aims to provide the current evidence on the functioning of the MGBA in pediatric patients with ADHD and the specific role of omega-3 polyunsaturated fatty acids (!-3 PUFAs) in this interaction, as well as the potential of the GM as a therapeutic target for ADHD. We will explore: (1) the diverse communication pathways between the GM and the CNS; (2) changes in the GM composition in children and adolescents with ADHD and association with ADHD pathophysiology; (3) influence of the GM on the !-3 PUFA imbalance characteristically found in ADHD; (4) interaction between the GM and circadian rhythm regulation, as sleep disorders are frequently comorbid with ADHD; (5) finally, we will evaluate the most recent studies on the use of probiotics in pediatric patients with ADHD

Dose-Dependent Effect of Melatonin on BAT Thermogenesis in Zücker Diabetic Fatty Rat: Future Clinical Implications for Obesity

Experimental data have revealed that melatonin at high doses reduced obesity and improved metabolic outcomes in experimental models of obesity, mainly by enhancing brown adipose tissue (BAT) thermogenesis. A potential dose-response relationship has yet to be performed to translate these promising findings into potential clinical therapy. This study aimed to assess the effects of different doses of melatonin on interscapular BAT (iBAT) thermogenic capacity in Zücker diabetic fatty (ZDF) rats. At 6 wk of age, male ZDF rats were divided into four groups (n = 4 per group): control and those treated with different doses of melatonin (0.1, 1, and 10 mg/kg of body weight) in their drinking water for 6 wk. Body weight (BW) was significantly decreased at doses of 1 and 10 mg/kg of melatonin, but not at 0.1 mg/kg compared with the control, with a similar rate of BW decrease being reached at the dose of 1 mg/kg (by ~11%) and 10 mg/kg (by ~12%). This effect was associated with a dose-dependent increase in the thermal response to the baseline condition or acute cold challenge in the interscapular area measurable by infrared thermography, with the highest thermal response being recorded at the 10 mg/kg dose. Upon histology, melatonin treatment markedly restored the typical brownish appearance of the tissue and promoted a shift in size distribution toward smaller adipocytes in a dose-dependent fashion, with the most pronounced brownish phenotype being observed at 10 mg/kg of melatonin. As a hallmark of thermogenesis, the protein level of uncoupled protein 1 (UCP1) from immunofluorescence and Western blot analysis increased significantly and dose-dependently at all three doses of melatonin, reaching the highest level at the dose of 10 mg/kg. Likewise, all three doses of melatonin modulated iBAT mitochondrial dynamics by increasing protein expression of the optic atrophy protein type 1 (OPA1) fusion marker and decreasing that of the dynamin-related protein1 (DRP1) fission marker, again dose-dependently, with the highest and lowest expression levels, respectively, being reached at the 10 mg/kg dose. These findings highlight for the first time the relevance of the dose-dependency of melatonin toward BW control and BAT thermogenic activation, which may have potential therapeutic implications for the treatment of obesity. To clinically apply the potential therapeutic of melatonin for obesity, we consider that the effective animal doses that should be extrapolated to obese individuals may be within the dose range of 1 to 10 mg/kg.Ministrio de Ciencia e Innovacion (Spain) SAF2016-79794-REuropean CommissionUniversity of Granada & FEDER Andalucia-UGR 2020 B-CTS-102-UGR2

Measuring online tracking and privacy risks on Ecuadorian websites

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes,creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.Online tracking has become a great enabler of massive surveillance so it is now a critical vector for threatening the privacy of users. Despite the benefits of online tracking for personalized advertising, the complexity of the involved platforms makes it a threat for democracy. In this work, online tracking is measured in Ecuador, a country with a developing adoption of online advertising technologies, having the highest Internet penetration rate in Latin America, but lacking regulation for privacy. By finding out the third party connections triggered through the most popular Ecuadorian websites, the concentration of online tracking is measured in Ecuador. Its impact is also analyzed by studying some particularities in government websites, the usage of advanced mechanisms of tracking, and the adoption of transparency practices in advertising platforms. Our final aim is exposing potential privacy violations.This work was partly supported by the Spanish Ministry ofEconomy and Competitiveness (MINECO) through the project“MAGOS”, ref. TEC2017-84197-C4-3-R. J. Parra-Arnau wassupported by the Spanish government under grant TIN2016-80250-R and by the Catalan government under grant 2017SGR 00705 and is currently the recipient of a Juan de la Ciervapostdoctoral fellowship, IJCI-2016-28239, from the SpanishMinistry of Economy and Competitiveness.Peer ReviewedPostprint (author's final draft

On the regulation of personal data distribution in online advertising platforms

Online tracking is the key enabling technology of modern online advertising. In the recently established model of real-time bidding (RTB), the web pages tracked by ad platforms are shared with advertising agencies (also called DSPs), which, in an auction-based system, may bid for user ad impressions. Since tracking data are no longer confined to ad platforms, RTB poses serious risks to privacy, especially with regard to user profiling, a practice that can be conducted at a very low cost by any DSP or related agency, as we reveal here. In this work, we illustrate these privacy risks by examining a data set with the real ad-auctions of a DSP, and show that for at least 55% of the users tracked by this agency, it paid nothing for their browsing data. To mitigate this abuse, we propose a system that regulates the distribution of bid requests (containing user tracking data) to potentially interested bidders, depending on their previous behavior. In our approach, an ad platform restricts the sharing of tracking data by limiting the number of DSPs participating in each auction, thereby leaving unchanged the current RTB architecture and protocols. However, doing so may have an evident impact on the ad platform’s revenue. The proposed system is designed accordingly, to ensure the revenue is maximized while the abuse by DSPs is prevented to a large degree. Experimental results seem to suggest that our system is able to correct misbehaving DSPs, and consequently enhance user privacy.Peer ReviewedPostprint (author's final draft

Melatonin induces fat browning by transdifferentiation of white adipocytes and de novo differentiation of mesenchymal stem cells

This research was partially supported by grant SAF2016-79794R from the Ministerio de Ciencia e Innovacion (Spain), European Regional Development Fund (ERDF), University of Granada and FEDER Funds grant number B-CTS-102-UGR20. The authors thank Antonio Tirado for their technical assistance.The role of melatonin in obesity control is extensively accepted, but its mechanism of action is still unclear. Previously we demonstrated that chronic oral melatonin acts as a brown-fat inducer, driving subcutaneous white adipose tissue (sWAT) into a brown-fat-like function (beige) in obese diabetic rats. However, immunofluorescence characterization of beige depots in sWAT and whether melatonin is a beige-fat inducer by de novo differentiation and/or transdifferentiation of white adipocytes are still undefined. Lean (ZL) and diabetic fatty (ZDF) Zücker rats were subdivided into two groups, control (C) and oral melatonin-supplemented (M, 10 mg kg−1 day−1) for 6 weeks. Mesenchymal stem cells (MSCs) were isolated from both rat inguinal fat and human lipoaspirates followed by adipogenesis assays with or without melatonin (50 nM for 12 h in a 24 h period, 12 h+/12 h−) mimicking the light/dark cycle. Immunofluorescence and western-blot assays showed the partial transdifferentiation of white adipocytes in both ZL and ZDF rats, with increasing thermogenic and beige markers, UCP1 and CITED1 and decreasing white adipocyte marker ASC-1 expression. In addition, melatonin increased UCP1, CITED1, and PGC1- α expression in differentiated adipocytes in both rats and humans. These results demonstrate that melatonin increases brown fat in obese diabetic rats by both adipocyte transdifferentiation and de novo differentiation. Furthermore, it promotes beige MSC adipogenesis in humans. This may contribute to the control of body weight attributed to melatonin and its metabolic benefits in human diabesity.Spanish Government SAF2016-79794REuropean Commission B-CTS-102-UGR20University of Granad

The preventive and protective role of melatonin in SARS-CoV-2 infection: a retrospective study

This study has investigated the protective role of melatonin against SARS-CoV-2 infection. For this purpose, 62 adults were recruited who were in daily relatively high doses of melatonin intaking, with the particularity that they started taking it before the beginning of the COVID-19 pandemic and continued to present. A continuous validation process has been carried out with a series of questionnaires to identify the risk factors, whether they were contacts, were infected, if yes, the level of disease severity, need for treatment, hospitalization, etc. According to the dose of melatonin the individuals took/are taking, they were divided into two groups: a) those taking 20 mg (n = 27) and, b) those taking ≥ 40 mg (n = 32). For statistical analysis, the shi2 test and Fisher's exact test were used. The number of infected subjects with positive PCR was 7 (11.9%). Only one required medication, the rest had a very favorable clinical evolution, mild in three cases and asymptomatic in three others. While in their environment this percentage is 22.05% (chi2 = 2.928; p < 0.087). Melatonin offers a good safety profile, is well tolerated and can play an important role in the different levels of COVID-19 prevention

La presencia del otro en los procesos de formación humana

En este libro se vincula la mirada a la semiótica como alternativa para formar docentes a partir de su propuesta sobre didáctica clínica. Seguidamente, se pueden reconocer los aportes de la lingüística a la educación. Además se enuncia al trabajo autobiográfico como estrategia de la investigación cualitativa y otra, como estrategia de formación humana. Finalmente, se presenta un marco de referencia sobre la virtualidad y sus implicaciones en los procesos de formación