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Abstract Background Anthropogenic activities significantly contribute to the dissemination of antibiotic resistance genes (ARGs), posing a substantial threat to humankind. The development of methods that allow robust ARG surveillance is a long-standing challenge. Here, we use city-scale monitoring of ARGs by using two of the most promising cutting-edge technologies, digital PCR (dPCR) and metagenomics. Methods ARG hot-spots were sampled from the urban water and wastewater distribution systems. Metagenomics was used to provide a broad view of ARG relative abundance and richness in the prokaryotic and viral fractions. From the city-core ARGs in all samples, the worldwide dispersed sul2 and tetW conferring resistance to sulfonamide and tetracycline, respectively, were monitored by dPCR and metagenomics. Results The largest relative overall ARG abundance and richness were detected in the hospital wastewater and the WWTP inlet (up to ≈6,000 ARGs/Gb metagenome) with a large fraction of unclassified resistant bacteria. The abundance of ARGs in DNA and RNA contigs classified as viruses was notably lower, demonstrating a reduction of up to three orders of magnitude compared to contigs associated to prokaryotes. By metagenomics and dPCR, a similar abundance tendency of sul2 and tetW was obtained, with higher abundances in hospital wastewater and WWTP input (≈125–225 ARGs/Gb metagenome). dPCR absolute abundances were between 6,000 and 18,600 copies per ng of sewage DNA (≈105–7 copies/mL) and 6.8 copies/mL in seawater near the WWTP discharging point. Conclusions dPCR was more sensitive and accurate, while metagenomics provided broader coverage of ARG detection. While desirable, a reliable correlation of dPCR absolute abundance units into metagenomic relative abundance units was not obtained here (r2

The relevance of the gut microbiota in some skin inflammatory diseases, including acne vulgaris, has been emphasized. Probiotics could play a role in the modulation of the microbiota, improving the clinical course of this disease. A 12-week randomized, double-blind, placebo-controlled, clinical trial with patients aged 12 to 30 years with acne vulgaris was conducted. The study product was a capsule composed of the probiotic Lacticaseibacillus rhamnosus (CECT 30031) and the cyanobacterium Arthrospira platensis (BEA_IDA_0074B). Patients with improvement in the Acne Global Severity Scale were 10/34 (29.41%) in the placebo group compared with 20/40 (50%) in the probiotic group (p = 0.03). A significant reduction (p = 0.03) in the number of non-inflammatory acne lesions was observed in the probiotic group (–18.60 [–24.38 to –12.82]) vs the placebo group (–10.54 [–17.43 to –3.66]). Regarding the number of total lesions, a reduction almost reaching statistical significance (p = 0.06) was observed in the probiotic group (–27.94 [–36.35 to –19.53]) compared with the placebo group (–18.31 [–28.21 to –8.41]). In addition, patients with improvement attending the Global Acne Grading System were 7/34 (20.58%) in the placebo group vs 17/40 (42.50%) in the probiotic group (p = 0.02). The number of adverse events was similar in both groups. The probiotic used in this study was effective and well tolerated, and it should be considered for acne vulgaris patients.

Summary: Insect physiology and reproduction depend on several terpenoid compounds, whose biosynthesis is mainly unknown. One enigmatic group of insect monoterpenoids are mealybug sex pheromones, presumably resulting from the irregular coupling activity of unidentified isoprenyl diphosphate synthases (IDSs). Here, we performed a comprehensive search for IDS coding sequences of the pest mealybug Planococcus citri. We queried the available genomic and newly generated short- and long-read P. citri transcriptomic data and identified 18 putative IDS genes, whose phylogenetic analysis indicates several gene family expansion events. In vitro testing confirmed regular short-chain coupling activity with five gene products. With the candidate with highest IDS activity, we also detected low amounts of irregular coupling products, and determined amino acid residues important for chain-length preference and irregular coupling activity. This work therefore provides an important foundation for deciphering terpenoid biosynthesis in mealybugs, including the sex pheromone biosynthesis in P. citri.

Raw observations (carrier-phase and code observations) from the Global Navigation Satellite System (GNSS) can now be accessed from Android mobile phones (Version 7.0 onwards). This paves the way for GNSS data to be utilized for low-cost precise positioning or in ionospheric or tropospheric applications. This paper presents results from data collection campaigns using the CAMALIOT mobile app. In the first campaign, 116.3 billion measurements from 11,828 mobile devices were collected from all continents. Although participation decreased during the second campaign, data are still being collected globally. In this contribution, we demonstrate the potential of volunteered geographic information (VGI) from mobile phones to fill data gaps in geodetic station networks that collect GNSS data, e.g. in Brazil, but also how the data can provide a denser set of observations than current networks in countries across Europe. We also show that mobile phones capable of dual-frequency reception, which is an emerging technology that can provide a richer source of GNSS data, are contributing in a substantial way. Finally, we present the results from a survey of participants to indicate that participation is diverse in terms of backgrounds and geography, where the dominant motivation for participation is to contribute to scientific research.

(1) Background: Given the autoimmune nature of Alopecia Areata (AA) and the immunomodulatory properties of probiotics, this trial was conducted to evaluate the efficacy of a probiotic mixture, consisting of Lactobacillus rhamnosus and Bifidobacterium longum strains, as an adjuvant treatment in a group of AA patients. (2) Method: This study was a 24-week, randomized, double-blind, placebo-controlled clinical trial. Twenty-six patients with AA were included in this study, and their clinical progression, along with changes in gut and skin microbiota, were analyzed. (3) Results: A higher proportion of AA patients treated with the probiotic formula showed improvement compared to the placebo group, based on both the reduction in the number of AA plaques (56% vs. 30%) and the affected scalp surface area (45% vs. 20%). For “activity”, “inactivity”, and “regrowth”, an improvement in 55%, 67%, and 55% of patients was, respectively, observed in the probiotic group, compared to 50%, 40%, and 30% in the placebo group. No changes were observed in the gut microbiota during the intervention period. Regarding skin microbiota, changes were detected in the probiotic group, with reductions in characteristic genera during the study. (4) Conclusions: To our knowledge, this is the first clinical trial assessing the efficacy of a probiotic product in patients with AA. This probiotic mixture in a routine clinical practice setting appears to improve the course of patients. In addition, the skin microbiota of scalp lesions was modified using the probiotic treatment.

A new contact model is proposed to improve the simulation of the hydration of granular bentonite mixtures. When these mixtures are abstracted as a discrete set of continuous systems in contact, excessively low predictions of swelling pressures are obtained when simulating the early stages of hydration using a plane axisymmetric approximation. This is especially true for relatively open structured mixtures with an average dry density less than 1.5 Mg/m3. The proposed contact model has allowed improved predictions while maintaining the axisymmetric analysis in the demanding inspection tests analysed. Hence, it is an interesting tool to simulate the whole homogenisation process of open granular bentonite mixtures. However, it is necessary to intensify its validation by analysing new experimental evidence, and to evaluate its development, because given its simplicity it presents some difficulties to reproduce the collapse of the megapores when hydration progresses.

Rosacea is an inflammatory skin disease involving diverse symptoms with a variable clinical progress which can severely impact the patient’s quality of life as well as their mental health. The pathophysiological model of rosacea involves an unbalanced immune system predisposed to excessive inflammation, in addition to vascular and nervous alterations, being certain cutaneous microorganisms’ triggers of the symptoms onset. The gut-skin axis explains a bidirectional interaction between skin and gut microbiota in some inflammatory skin diseases such as atopic dermatitis, psoriasis, or rosacea. The introduction and consolidation of the next-generation sequencing in recent years has provided unprecedented information about the microbiome. However, the characterization of the gut and skin microbiota and the impact of the gut-skin axis in patients with rosacea has been little explored, in contrast to other inflammatory skin diseases such as atopic dermatitis or psoriasis. Furthermore, the clinical evolution of patients with rosacea is not always adequate and it is common for them to present a sustained symptomatology with frequent flare-ups. In this context, probiotic supplementation could improve the clinical evolution of these patients as happens in other pathologies. Through this review we aim to establish and compile the basics and directions of current knowledge to understand the mechanisms by which the microbiome influences the pathogenesis of rosacea, and how modulation of the skin and gut microbiota could benefit these patients.

Objective. To review the scientific literature related to human microbiota and cutaneous T-cell lymphoma. Methodology. An exploratory and systematic review of the articles retrieved from the bibliographic databases MEDLINE (PubMed), Embase, The Cochrane Library, and Scopus, published in the last 10 years with the following descriptors: “lymphoma, T-cell, cutaneous,” “microbiota,” “Mycosis Fungoides,” “Sézary Syndrome,” “lymphoma, primary cutaneous anaplastic large cell,” “Lymphomatoid Papulosis” and “Microbiota,” “microbiota,” “Microbial Community,” and “Microbial Communities.” Results. Of the 87 references retrieved, after applying the inclusion and exclusion criteria, 21 articles were selected. Most studies linking cutaneous T-cell lymphoma and the microbiota focus on the cutaneous microbiome, with Staphylococcus aureus being the main related agent. Skin colonization by this bacterium could be involved in the hyperactivation of the STAT3 inflammatory pathway and in the overproduction of IL-17, both of which are widely related to the development of more aggressive and advanced forms of cutaneous T-cell lymphoma. We also found evidence of a possible relationship between intestinal dysbiosis and the development of cutaneous T-cell lymphoma, observing a decrease in taxonomic variability and an increase in certain genera such as Prevotella in the intestinal microbiome of patients with cutaneous T-cell lymphoma. The possible etiopathogenic mechanism underlying this relationship could be explained by an increase in systemic cytokine release, promoting the hyperactivation of STAT3 at the skin level. Conclusion. There appears to be a relationship between cutaneous T-cell lymphoma and the cutaneous and intestinal microbiome, as well as a possible pathophysiological pathway involved. The possible modulation of the cutaneous and intestinal microbiome or the action on the signaling inflammatory pathway, using pharmacological tools such as JAK inhibitors or IL-17 inhibitors in the latter case, could open the possibility for future therapeutic studies for cutaneous T-cell lymphoma.

In recent times, Distributed Ledger Technology (DLT) has gained significant attention for its potential application in the energy sector. Utilizing blockchain and DLT has demonstrated the ability to enhance the resilience of the electric infrastructure, which will support a more flexible infrastructure and advance grid modernization. However, the deployment of these technologies increases the overall attack surface. The MITRE ATT&CK® matrices have been developed to document an adversary’s tactics and techniques based on real-world observations. The MITRE ATT&CK® matrices provide a common taxonomy for offense and defense and have become a valuable conceptual tool across multiple cybersecurity disciplines for conveying threat intelligence, performing testing through red teaming or adversary emulation, and enhancing network and system defenses against intrusions. The MITRE ATT&CK® for Industrial Control Systems (ICS) matrix was created to provide knowledge about adversary behavior in the ICS technology domain. This study analyzes the relevance of various tactics and techniques across a seven-layer DLT engineering and cybersecurity stack, known as the DLT stack, designed by the Cybersecurity Taskforce under IEEE P2418.5 - Standard for Blockchain in Energy working group sponsored by Power and Energy Systems - Smart Buildings, Loads and Customer Systems (PES/SBLC) Technical Committee. Additionally, this paper identifies specific mitigation strategies tailored to the energy ICS environment.

This work analyses the mobilization of infinite natural slopes that are initially partially saturated. Starting from dry conditions (the water table is assumed to be deep, far from the slope surface), the soil shear strength will decrease when the wetting front advances from the surface. First, the geometry of the failure mechanism that can develop because of such strength reduction is determined. Second, after the mobilization causes the progressive reduction in the soil strength, the slide speed reached the minimum strength is determined, obtaining an indicator of the risk derived from failure.

Bladder cancer is around the 10th most diagnosed cancer, although has a considerable mortality. Recent research and new methodologies have discarded the historical dogma that the bladder (and urine) was sterile under normal conditions. Specifically, only a few studies have reported a detailed analysis of the urinary microbiota in patients with bladder cancer, thus exhibiting a remarkable variability due to the low biomass of the urinary microbiota and the influence of many factors. Nevertheless, this research shows us signals that urinary microbiota is a factor to be considered in the pathophysiology of bladder cancer. More importantly, probiotics could be useful as an adjuvant therapy to reduce the recurrence rate or increase the disease-free period after surgery. In vitro studies and animal assays have shown promising results, but the research in this context has also been scarce, and only a few studies have been conducted in humans. In summary, there is little evidence of the possible beneficial effect of probiotics in controlling the overgrowth of genera that could be involved in the carcinogenesis of bladder cancer. This narrative review aims to compile all the evidence to date on the therapeutic potential of probiotics injected directly into the bladder or orally administered.

The use of compacted bentonites in radioactive waste repository barriers is a relevant application of geoenvironmental engineering. The on-site structural characteristics of the bentonites determine the performance and integrity of the barrier. The present work addresses the adaptation of the standardized sand equivalent shaking method for the controlled disaggregation of Wyoming bentonite specimens prepared at low, medium, and high compaction. The evolution of the macrostructural units’ size distribution was determined by sieving at different shaking times. The stability of the compacted material increases with dry density. However, if enough energy is applied in the disaggregation process, the size distribution of the macrostructural units after disaggregation has the same characteristics as that of the uncompacted starting material, regardless of the applied degree of compaction. Since the disaggregation rate is a function of the aggregation level (compaction), it follows that compaction energy is not only spent on reducing porosity but also on generating more stable macrostructural units. These findings pave the way for future research with different materials and test conditions (compaction, moisture, etc.). In addition, the proposed shaking method is adaptable and could also be used in other sectors, such as agriculture, to determine the structural stability of natural soils.

Depressive disorders have a major impact on occupational health and are costly to the economy and the healthcare system. Probiotics are live, non-pathogenic micro-organisms that, when ingested in adequate amounts, can colonize the intestinal tract and confer health benefits on the patient. In recent years, numerous studies have described the potential usefulness of certain probiotic strains in the treatment and prevention of depressive disorders, with differing results. In order to evaluate the possible efficacy and safety of these microorganisms in preventing or ameliorating these disorders, we systematically searched the bibliographic databases MEDLINE (via Pubmed), EMBASE, the Cochrane library, Scopus and Web of science, using the descriptors “Occupational health”, “Probiotics”, “Depressive Disorder” and “Depression” and filters “Humans” and “Clinical Trials”. After applying our inclusion and exclusion criteria, 18 studies were accepted for review and critical analysis. Our analysis suggests that a combination of different probiotic strains, most of them from the genus Bifidobacterium sp. and Lactobacillus sp., could be a good mixture as an adjuvant in the treatment of depressive disorders for the working population.

At the beginning of the SARS-CoV-2 pandemic, developing of new treatments to control the spread of infection and decrease morbidity and mortality are necessary. This prospective, open-label, case-control intervention study evaluates the impact of the oral intake of the probiotic yeast Kluyveromyces marxianus B0399 together with Lactobacillus rhamnosus CECT 30579, administered for 30 days, on the evolution of COVID-19 patients. Analysis of the digestive symptoms at the end of the follow up shows a benefit of the probiotic in the number of patients without pyrosis (100% vs 33.3%; p 0.05) and without abdominal pain (100% vs 62.5%; p 0.04). Results also show a better evolution when evaluating the difference in the overall number of patients without non-digestive symptoms at the end of the follow-up (41.7%, vs 13%; p 0.06). The percentage of improvement in the digestive symptoms (65% vs 88%; p value 0.06) and the global symptoms (digestive and non-digestive) (88.6% vs 70.8%; p value 0.03) is higher in the probiotic group. The probiotic was well tolerated with no relevant side effects and high adherence among patients. In conclusion, this coadjutant treatment seems to be promising, although results should be confirmed in new studies with higher number of patients.

Background: Extracellular vesicles (EVs) secreted by neuronal cells in vitro have promising therapeutic potential for brain diseases. Optimization of cell culture conditions and methodologies for high-yield isolation of EVs for preclinical and clinical applications, however, remains a challenge. Objective: To probe the cell culture conditions required for optimal EV secretion by human-derived neuronal cells. Methodology: First, we optimized the EV purification protocol using human mesenchymal stromal cell (MSC) cultures. Next, we compared the effects of different variables in human pluripotent stem cell (hPSC)-derived neuronal cultures on EV secretion. EVs were isolated from cell conditioned media (CCM) and control media with no cells (NCC) using ultrafiltration combined with size-exclusion chromatography (SEC). The hPSC neurons were cultured in 2 different media from which EVs were collected at 2 maturation time-points (days 46 and 60). Stimulation with 25 mM KCl was also evaluated as an activator of EV secretion by neurons. The collected SEC fractions were analyzed by nanoparticle tracking analysis (NTA), protein concentration assay, and blinded transmission electron microscopy (TEM). Results: A peak in cup-shaped particles was observed in SEC fractions 7–10 of MSC samples, but not corresponding media controls, indicating successful isolation of EVs. Culture medium had no significant effect on EV yield. The EV yield of the samples did not differ significantly according to the culture media used or the cell maturation time-points. Stimulation of neurons with KCl for 3 h reduced rather than increased the EV yield. Conclusions: We demonstrated successful EV isolation from MSC and neuronal cells using an ultrafiltration-SEC method. The EV yield from MSC and neuronal cultures exhibited a large batch effect, apparently related to the culture media used, highlighting the importance of including NCC as a negative control in all cell culture experiments.

A comprehensive characterization of the human body resistome [sets of antibiotic resistance genes (ARGs)] is yet to be done and paramount for addressing the antibiotic microbial resistance threat. Here, we study the resistome of 771 samples from five major body parts (skin, nares, vagina, gut, and oral cavity) of healthy subjects from the Human Microbiome Project (HMP) and addressed the potential dispersion of ARGs in pristine environments. A total of 28,714 ARGs belonging to 235 different ARG types were found in the HMP proteome dataset (n = 9.1 × 107 proteins analyzed). Our study reveals a distinct resistome profile (ARG type and abundance) between body sites and high interindividual variability. Nares had the highest ARG load (≈5.4 genes/genome) followed by the oral cavity, whereas the gut showed one of the highest ARG richness (shared with nares) but the lowest abundance (≈1.3 genes/genome). The fluroquinolone resistance genes were the most abundant in the human body, followed by macrolide–lincosamide–streptogramin (MLS) or tetracycline. Most ARGs belonged to common bacterial commensals and multidrug resistance trait were predominant in the nares and vagina. Many ARGs detected here were considered as low risk for human health, whereas only a few of them, such as BlaZ, dfrA14, dfrA17, or tetM, were classified as high-risk ARG. Our data also provide hope, since the spread of common ARG from the human body to pristine environments (n = 271 samples; 77 Gb of sequencing data and 2.1 × 108 proteins analyzed) thus far remains very unlikely (only one case found in an autochthonous bacterium from a pristine environment). These findings broaden our understanding of ARG in the context of the human microbiome and the One-Health Initiative of WHO uniting human host–microbes and environments as a whole.

The aim of this study is to assess the consistency in the modelling of thermo-hydraulic problems in clay-based engineered barriers. This study focuses on two aspects: the modelling of vapour pressure as a function of temperature, and the specific heat capacities of liquid water and water vapour in relation to the enthalpy of vaporisation and the internal energy of liquid water and water vapour. Regarding the first aspect, several formulations of the saturated vapour pressure have been inspected, evaluating their accuracy and information provided in the temperature range from 0 to 150 °C. Regarding the second aspect, the enthalpy of vaporisation and the internal energy of water were used to assess the consistency of pairs of specific heat capacity values in the same temperature range. Values from the literature were also inspected. An accurate and simple enough expression for the saturated water vapour pressure with temperature has been identified as the optimal option for modelling. Recommendations on specific heat capacity constant values for liquid water and vapour are suggested to maximise consistency in the studied temperature range. However, the loss of accuracy in the enthalpy or internal energy of vaporisation associated with the inspected specific heat capacity pairs is limited.

Plant essential oils (PEOs) are being studied as a potential alternative to synthetic pesticides in agriculture. PEOs have the potential to control pests both directly, by being toxic or repellent to pests, and indirectly, by activating plant’s defense mechanisms. In this study, the effectiveness of five PEOs (Achillea millefolium, Allium sativum, Rosmarinus officinallis, Tagetes minuta, and Thymus zygis) on controlling Tuta absoluta and their impact on the predator Nesidiocoris tenuis was examined. The study revelead that PEOs from A. millefolium and A. sativum-sprayed plants significantly reduced the number of T. absoluta-infested leaflets and did not affect the establishment and reproduction of N. tenuis. Additionally, the spraying of A. millefolium and A. sativum increased the expression of defense genes in the plants, triggering the release of herbivory-induced plant volatiles (HIPVs), such as C6 green leaf volatiles, monoterpenes, and aldehydes, which can be messengers in tritrophic interactions. The results suggest that PEOs from A. millefolium and A. sativum can provide a dual benefit for controlling arthropod pests, as they can directly exhibit toxicity against these pests while also activating plant defense mechanisms. Overall, this study provides new insights into using PEOs as a sustainable solution for controlling pests and diseases in agriculture, by reducing synthetic pesticides and promoting the use of natural predators.

Although electrokinetic treatments for soil remediation and ground improvement have gradually undergone significant experimental development, one of the most important physical phenomena has received very little attention in recent years. Electroosmotic flow, especially in unsaturated conditions, has not been simulated in domains of more than one dimension. In the present work, a modification of the M4EKR code was used to study water movement in partially saturated soils under electrokinetic treatments. Two different configurations were studied: electrodes placed in electrolyte wells and electrodes directly inserted into the soil, and the treatment was started under unsaturated conditions for both. Due to the unrestricted availability of fluid in the first case, soil saturation is inevitable, but in the second case, only a spatial redistribution of water content can be observed. A detailed analysis of a variety of configurations involving several electrolyte wells showed that the number of electrodes, the distance between them and, above all, the ratio between the two magnitudes determines the efficiency of soil saturation and the energy consumed in the process.

Alopecia areata is a multifactorial autoimmune-based disease with a complex pathogenesis. As in all autoimmune diseases, genetic predisposition is key. The collapse of the immune privilege of the hair follicle leading to scalp loss is a major pathogenic event in alopecia areata. The microbiota considered a bacterial ecosystem located in a specific area of the human body could somehow influence the pathogenesis of alopecia areata, as it occurs in other autoimmune diseases. Moreover, the Next Generation Sequencing of the 16S rRNA bacterial gene and the metagenomic methodology have provided an excellent characterization of the microbiota. The aim of this narrative review is to examine the published literature on the cutaneous and intestinal microbiota in alopecia areata to be able to establish a pathogenic link. In this review, we summarize the influence of the microbiota on the development of alopecia areata. We first introduce the general pathogenic mechanisms that cause alopecia areata to understand the influence that the microbiota may exert and then we summarize the studies that have been carried out on what type of gut and skin microbiota is found in patients with this disease.

The aim of this 12-week randomized, double-blind, placebo-controlled trial was to determine the efficacy and safety of a probiotic mixture in the reduction of psoriasis severity. Ninety 18–70-year-old adults with plaque psoriasis were randomized into probiotic and placebo groups. At 12-week follow-up, 66.7% of patients in the probiotic group and 41.9% in the placebo group showed a reduction in Psoriasis Area and Severity Index of up to 75% (p

This work describes the development of a numerical module with a multiphysics structure to simulate the thermo-hydro-chemo-mechanical behavior of compacted bentonites. First, the conceptual model, based on the state-of-the-art formulation for clay-based engineered barriers in deep geological repositories, is described. Second, the advantages of multiphysics-based modules are highlighted. Then, the guidelines to develop a code using such tools are outlined, presenting an example of implementation. Finally, the simulation of three tests that illustrate the behavior of compacted bentonites assesses the scope of the developed code. The satisfactory results obtained, and the relative simplicity of implementation, show the opportunity of the modeling strategy proposed. Keywords: Deep geological repository, Clay-based barrier, Compacted bentonite, Multiphysics modeling, Thermo-hydro-chemo-mechanical behavior

The objective of this narrative review was to check the influence of the human microbiota in the pathogenesis of acne and how the treatment with probiotics as adjuvant or alternative therapy affects the evolution of acne vulgaris. Acne is a chronic inflammatory skin disease involving the pilosebaceous units. The pathogenesis of acne is complex and multifactorial involving genetic, metabolic, and hormonal factors in which both skin and gut microbiota are implicated. Numerous studies have shown the bidirectionality between the intestinal microbiota and skin homeostasis, a communication mainly established by modifying the immune system. Increased data on the mechanisms of action regarding the relevance of Cutibacterium acnes, as well as the importance of the gut–skin axis, are becoming known. Diverse and varied in vitro studies have shown the potential beneficial effects of probiotics in this context. Clinical trials with both topical and oral probiotics are scarce, although they have shown positive results, especially with oral probiotics through the modulation of the intestinal microbiota, generating an anti-inflammatory response and restoring intestinal integrity, or through metabolic pathways involving insulin-like growth factor I (IGF-1). Given the aggressiveness of some standard acne treatments, probiotics should continue to be investigated as an alternative or adjuvant therapy.

Background: The influence of the microbiome on neurological diseases has been studied for years. Recent findings have shown a different composition of gut microbiota detected in patients with multiple sclerosis (MS). The role of this dysbiosis is still unknown. Objective: We analyzed the gut microbiota of 15 patients with active relapsing-remitting multiple sclerosis (RRMS), comparing with diet-matched healthy controls. Method: To determine the composition of the gut microbiota, we performed high-throughput sequencing of the 16S ribosomal RNA gene. The specific amplified sequences were in the V3 and V4 regions of the 16S ribosomal RNA gene. Results: The gut microbiota of RRMS patients differed from healthy controls in the levels of the Lachnospiraceae, Ezakiella, Ruminococcaceae, Hungatella, Roseburia, Clostridium, Shuttleworthia, Poephyromonas, and Bilophila genera. All these genera were included in a logistic regression analysis to determine the sensitivity and the specificity of the test. Finally, the ROC (receiver operating characteristic) and AUC with a 95% CI were calculated and best-matched for Ezakiella (AUC of 75.0 and CI from 60.6 to 89.4) and Bilophila (AUC of 70.2 and CI from 50.1 to 90.4). Conclusions: There is a dysbiosis in the gut microbiota of RRMS patients. An analysis of the components of the microbiota suggests the role of some genera as a predictive factor of RRMS prognosis and diagnosis.

Plant-based bioproduction of insect sex pheromones has been proposed as an innovative strategy to increase the sustainability of pest control in agriculture. Here, we describe the engineering of transgenic plants producing (Z)-11-hexadecenol (Z11-16OH) and (Z)-11-hexadecenyl acetate (Z11-16OAc), two main volatile components in many Lepidoptera sex pheromone blends. We assembled multigene DNA constructs encoding the pheromone biosynthetic pathway and stably transformed them into Nicotiana benthamiana plants. The constructs contained the Amyelois transitella AtrΔ11 desaturase gene, the Helicoverpa armigera fatty acyl reductase HarFAR gene, and the Euonymus alatus diacylglycerol acetyltransferase EaDAct gene in different configurations. All the pheromone-producing plants showed dwarf phenotypes, the severity of which correlated with pheromone levels. All but one of the recovered lines produced high levels of Z11-16OH, but very low levels of Z11-16OAc, probably as a result of recurrent truncations at the level of the EaDAct gene. Only one plant line (SxPv1.2) was recovered that harboured an intact pheromone pathway and which produced moderate levels of Z11-16OAc (11.8 μg g-1 FW) and high levels of Z11-16OH (111.4 μg g-1). Z11-16OAc production was accompanied in SxPv1.2 by a partial recovery of the dwarf phenotype. SxPv1.2 was used to estimate the rates of volatile pheromone release, which resulted in 8.48 ng g-1 FW per day for Z11-16OH and 9.44 ng g-1 FW per day for Z11-16OAc. Our results suggest that pheromone release acts as a limiting factor in pheromone biodispenser strategies and establish a roadmap for biotechnological improvements.

A significant part of the critical comments by Prof. Janssen, in relation to the work presented in [...]

The main objective of the work is to address the effective behavior of girls and boys through Triadic Motor Games (TMG). A chasing game “The Maze” was applied on two class groups with a total of 42 players, 18 girls, and 24 boys, who were 12- and 13-year-old secondary school students. An observational methodology was adopted, with a nomothetic, punctual, and multidimensional design. We used a mixed registry system that two expert observers later applied through an observational methodology, obtaining sufficient record-quality levels. THEME was applied to detect temporary regularities, while cross-tabulations and growth trees were applied with the SPSS v.24 tool to reveal whether girls and boys played in similar or distinct ways. The fact that the specific decision groups within the physical education class are different for girls and boys (p < 0.005) is worth reflecting on. The game’s TMG complexity was addressed through roles and subroles, giving rise to a certain motor asymmetry in relation to gender, which is an expression of behaviors lacking in playful neutrality. Through a mixed-methods approach, a study was built using observational methodology that reveals more varied motor solutions in girls, while male behavior showed greater specialization of roles and subroles, and the linkage of these solutions with the favorable modification of the marker. Identifying relevant variables when playing TMG allows a better understanding of girls and boys by analyzing their relationships, which are sometimes paradoxical, in a practical context.

There is a lack of motivation in children and adolescents to do physical exercise and at the same time a worldwide obesity epidemic. Gamification and active videogames can be used to increase the motivation of young people, promoting healthy habits. In this work we explore different studies on active videogames, eSports and gamification applied to physical exercise and health promotion. Main findings include positive effects in a reduction in body weight and in the promotion to continue performing of physical exercise. It also contributes to increase the motivation in children and adolescents to practice exercise. The personalization of user experience and emerging technologies (big data, wearables, smart technologies, etc.) are presented as promising opportunities to keep the engagement in game-based program and gamification of physical exercise.

The microRNA (miRNA) cargo contained in plasma extracellular vesicles (EVs) offers a relatively little explored source of biomarkers for brain diseases that can be obtained noninvasively. Methods to isolate EVs from plasma, however, are still being developed. For EV isolation, it is important to ensure the removal of vesicle-free miRNAs, which account for approximately two-thirds of plasma miRNAs. Membrane particle precipitation-based EV isolation is an appealing method because of the simple protocol and high yield. Here, we evaluated the performance of a precipitation-based method to obtain enriched EV-specific miRNAs from a small volume of rat plasma. We performed size-exclusion chromatography (SEC) on precipitation-isolated EV pellets and whole plasma. The SEC fractions were analysed using Nanoparticle Tracking Analysis (NTA), protein and miRNA concentration assays, and droplet digital polymerase chain reaction for four miRNAs (miR-142-3p, miR-124-3p, miR-23a, miR-122). Precipitation-isolated EVs and selected SEC fractions from the plasma were also analysed with transmission electron microscopy (TEM). Precipitation-based EV isolation co-precipitated 9% to 15% of plasma proteins and 21% to 99% of vesicle-free miRNAs, depending on the individual miRNAs. In addition, the amount of miR-142-3p, found mainly in EV fractions, was decreased in the EV fractions, indicating that part of it was lost during precipitation-based isolation. Western blot and TEM revealed both protein and lipoprotein contamination in the precipitation-isolated EV-pellets. Our findings indicate that a precipitation-based method is not sufficient for purifying plasma EV-contained miRNA cargo. The particle number measured by NTA is high, but this is mostly due to the contaminating lipoproteins. Although a part of the vesicle-free miRNA is removed, vesicle-free miRNA still dominates in plasma EV pellets isolated by the precipitation-based method.

Resumen: La Comunidad Autónoma Valenciana aprobó a finales del pasado año la Ley 10/2016 que modificaba varios aspectos de la ley territorial que regulaba diferentes aspectos en torno a la designación de senadores en representación de la Comunidad Autónoma. La nueva norma introduce, de forma novedosa en nuestro derecho, la posibilidad de revocación del senador designado por el parlamento autonómico, además de establecer la obligatoriedad del senador de comparecencia ante la cámara designante como forma de rendición de cuentas. La posibilidad de revocación del senador por pérdida de confianza de la cámara autonómica planteaba dudas de constitucionalidad por, entre otros, posible vulneración de la prohibición de mandato imperativo de los miembros de las Cortes Generales, ya resueltas por la STC 123/2017. El presente artículo, al hilo del análisis de la norma valenciana y su encaje constitucional, reflexiona sobre la naturaleza del mandato representativo y la peculiar función de la cámara de representación territorial. Abstract: The Valencian Autonomous Community approved at the end of last year the Law 10/2016 that modified several aspects of the territorial law that regulated different aspects about the appointment of senators in representation of the Autonomous Community. The new norm introduces, in a novel way in our right, the possibility of revocation of the senator appointed by the autonomic parliament, in addition to establishing the mandatory of the senator of appearance in the designating chamber as a form of accountability. The possibility of revocation of the senator due to loss of confidence of the autonomous chamber raises doubts of constitutionality by, among others, possible violation of the prohibition of imperative mandate of the members of the Cortes Generales, already resolved by STC 123/2017. This article, along the lines of the analysis of the Valencian norm and its constitutional reserve, reflects over the nature of the representative mandate and the peculiar function of the chamber of territorial representation.

Abstract Traumatic brain injury (TBI) induces a wide variety of cellular and molecular changes that can continue for days to weeks to months, leading to functional impairments. Currently, there are no pharmacotherapies in clinical use that favorably modify the post-TBI outcome, due in part to limited understanding of the mechanisms of TBI-induced pathologies. Our system biology analysis tested the hypothesis that chronic transcriptomics changes induced by TBI are controlled by altered DNA-methylation in gene promoter areas or by transcription factors. We performed genome-wide methyl binding domain (MBD)-sequencing (seq) and RNA-seq in perilesional, thalamic, and hippocampal tissue sampled at 3 months after TBI induced by lateral fluid percussion in adult male Sprague-Dawley rats. We investigated the regulated molecular networks and mechanisms underlying the chronic regulation, particularly DNA methylation and transcription factors. Finally, we identified compounds that modulate the transcriptomics changes and could be repurposed to improve recovery. Unexpectedly, DNA methylation was not a major regulator of chronic post-TBI transcriptomics changes. On the other hand, the transcription factors Cebpd, Pax6, Spi1, and Tp73 were upregulated at 3 months after TBI (False discovery rate

The occupational health impact of respiratory infectious diseases is costly to the economy and the health care system. Probiotics are non-pathogenic live microorganisms that, when ingested in adequate amounts, can colonize the intestinal tract, and enhance the immune system. In recent years, numerous studies have described the possible usefulness of certain probiotic strains in the treatment and prevention of respiratory tract infections, with disparate results. In order to assess the possible efficacy and safety of these microorganisms to prevent or ameliorate respiratory tract infections, we systematically searched the bibliographic databases MEDLINE (via Pubmed), EMBASE, The Cochrane library, Scopus, and Web of science, using the descriptors “Respiratory Tract Infections”, “Probiotics”, “Occupational Health”, “Humans”, and “Clinical Trials”. After applying our inclusion and exclusion criteria, 18 studies were accepted for review and critical analysis. Our analysis suggests that a combination of different probiotics, most of them in the genus Bifidobacterium sp. and Lactobacillus sp., could be a good mix to strengthen the immune system and reduce the symptoms of URTIs in the healthy working population.

Clostridiodes difficile can lead to a range of situations from the absence of symptoms (colonization) to severe diarrhea (infection). Disruption of gut microbiota provides an ideal environment for infection to occur. Comparison of gut microbiota of infected and colonized subjects could provide relevant information on susceptible groups or protectors to the development of infection, since the presence of certain genera could be related to the inhibition of transition from a state of colonization to infection. Through high-throughput sequencing of 16S rDNA gene, we performed alpha and beta diversity and composition studies on 15 infected patients (Group CDI), 15 colonized subjects (Group P), and 15 healthy controls (Group CTLR). A loss of alpha diversity and richness and a different structure have been evidenced in the CDI and P groups with respect to the CTRL group, but without significant differences between the first two. In CDI and P groups, there was a strong decrease in phylum Firmicutes and an expansion of potential pathogens. Likewise, there was a loss of inhibitory genus of C. difficile germination in infected patients that were partially conserved in colonized subjects. Therefore, infected and colonized subjects presented a gut microbiota that was completely different from that of healthy controls, although similar to each other. It is in composition where we found that colonized subjects, especially in minority genera, presented differences with respect to those infected.

During the last years, numerous studies have described the presence of significant gut and skin dysbiosis in some dermatological diseases such as atopic dermatitis, psoriasis and acne, among others. How the skin and the gut microbiome play a role in those skin conditions is something to explore, which will shed light on understanding the origin and implication of the microbiota in their pathophysiology. Several studies provide evidence for the influence of probiotic treatments that target the modulation of the skin and intestinal microbiota in those disorders and a positive influence of orally administered probiotics on the course of these dermatosis. The pathologies in which the therapeutic role of the probiotic has been explored are mainly atopic dermatitis, psoriasis and acne. This article aims to review these three dermatological diseases, their relationship with the human microbiota and specially the effect of probiotics usage. In addition, the pathophysiology in each of them and the hypotheses about possible mechanisms of the action of probiotics will be described.

Understanding the characteristics of the vaginal microbiota of our patients allows us to carry out both a personalized therapeutic approach and a closer follow-up in those with microbiota susceptible to dysbiosis. This trial pursues the analysis of the vaginal microbiota of premenopausal women and its fluctuations within a four-week follow-up period. Vaginal samples of 76 fertile women were taken at a baseline visit and at a final visit (day 28 ± 5). To perform a phylogenetic study, we employed massive sequencing techniques to detect the 16S rRNA gene of the vaginal microbiota. The most prevalent vaginal microbial community was type I (34.87%), dominated by Lactobacillus crispatus. Vaginal microbial community types II (Lactobacillus gasseri) and V (Lactobacillus jensenii) were underrepresented in our population. When repeating the sampling process four weeks later, 75% of our patients maintained their initial bacterial community. In the follicular phase, the most recurrent microbiota was type III (Lactobacillus iners); in the periovulatory phase, types III and IV (microbial diversity); finally, in the luteal phase, the most frequent type was IV. The most prevalent vaginal bacterial community in our population was dominated by L. crispatus. The vaginal microbiota was resistant to changes in its bacterial community in 75% of our patients, even between consecutive menstrual cycles.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a high impact on the comfort of those who are affected and long-term treated with corticosteroids with limited efficacy and a high prevalence of relapses. Because of the limited effectiveness of these treatments, new strategies for recovery from AD lesions are continually being explored. In this article, we describe the gut microbiome changes achieved in a recently published clinical trial with the probiotic formulation Bifidobacterium animalis subsp. lactis CECT 8145, Bifidobacterium longum CECT 7347, and Lacticaseibacillus casei CECT 9104 (formerly Lactobacillus casei CECT 9104), showing a significant improvement in SCORAD (scoring atopic dermatitis) index in children (4–17 years) with AD (Clinicaltrials.gov identifier: NCT02585986). The present gut microbiome post hoc study showed no significant changes in diversity (Shannon and Simpson indexes) after probiotic consumption. In the probiotic group, genera Bacteroides, Ruminococcus, and Bifidobacterium significantly increased their levels while Faecalibacterium decreased, compared to the placebo group. Faecalibacterium showed the highest presence and significant positive correlation with AD severity (SCORAD index), whereas Abyssivirga, Bifidobacterium, and Lactococcus were inversely correlated. The results suggest that the consumption of the probiotic formulation here assayed modulates the gut microbiome with significant changes in genera Bacteroides and Faecalibacterium. In turn, the improvement in SCORAD correlates with a decrease in Faecalibacterium and an increase in Bifidobacterium, among others.

Este estudio desvela los rasgos representativos de los juegos y su relación con el contexto sociocultural que refleja la obra Días geniales o lúdicros de Rodrigo Caro, del siglo XVII español. Se analizan 59 juegos desde una perspectiva etnomotriz, tomando tres objetos de estudio: material, espacio, y tiempo, desde de la perspectiva de la lógica interna (texto) y también desde la óptica de la lógica externa (contexto). Se observan diferencias en los juegos según categorías de edades (infantil, juvenil y adulto) y se constata que todavía se encuentran lejos los rasgos que caracterizan al deporte moderno, se emplean pocos materiales de juego de uso especializado y se comparten espacios artificiales y el uso de zonas abiertas, situadas mayoritariamente en la misma localidad, no siendo de uso exclusivo para estos juegos. En relación al tiempo, se observa la ausencia del control y rigidez temporal de los juegos, así como una organización temporal abierta y cerrada respecto al ritmo del calendario festivo.