Key Stratification of Microbiota Taxa and Metabolites in the Host Metabolic Health-Disease Balance.

Human gut microbiota seems to drive the interaction with host metabolism through microbial metabolites, enzymes, and bioactive compounds. These components determine the host health-disease balance. Recent metabolomics and combined metabolome-microbiome studies have helped to elucidate how these substances could differentially affect the individual host pathophysiology according to several factors and cumulative exposures, such as obesogenic xenobiotics. The present work aims to investigate and interpret newly compiled data from metabolomics and microbiota composition studies, comparing controls with patients suffering from metabolic-related diseases (diabetes, obesity, metabolic syndrome, liver and cardiovascular diseases, etc.). The results showed, first, a differential composition of the most represented genera in healthy individuals compared to patients with metabolic diseases. Second, the analysis of the metabolite counts exhibited a differential composition of bacterial genera in disease compared to health status. Third, qualitative metabolite analysis revealed relevant information about the chemical nature of metabolites related to disease and/or health status. Key microbial genera were commonly considered overrepresented in healthy individuals together with specific metabolites, e.g., Faecalibacterium and phosphatidylethanolamine; and the opposite, Escherichia and Phosphatidic Acid, which is converted into the intermediate Cytidine Diphosphate Diacylglycerol-diacylglycerol (CDP-DAG), were overrepresented in metabolic-related disease patients. However, it was not possible to associate most specific microbiota taxa and metabolites according to their increased and decreased profiles analyzed with health or disease. Interestingly, positive association of essential amino acids with the genera Bacteroides were observed in a cluster related to health, and conversely, benzene derivatives and lipidic metabolites were related to the genera Clostridium, Roseburia, Blautia, and Oscillibacter in a disease cluster. More studies are needed to elucidate the microbiota species and their corresponding metabolites that are key in promoting health or disease status. Moreover, we propose that greater attention should be paid to biliary acids and to microbiota-liver cometabolites and its detoxification enzymes and pathways.

Exploring Next Generation Probiotics for Metabolic and Microbiota Dysbiosis Linked to Xenobiotic Exposure: Holistic Approach.

Variation of gut microbiota in metabolic diseases seems to be related to dysbiosis induced by exposure to multiple substances called Microbiota Disrupting Chemicals (MDCs), which are present as environmental and dietary contaminants. Some recent studies have focused on elucidating the alterations of gut microbiota taxa and their metabolites as a consequence of xenobiotic exposures to find possible key targets involved in the severity of the host disease triggered. Compilation of data supporting the triad of xenobiotic-microbiota-metabolic diseases would subsequently allow such health misbalances to be prevented or treated by identifying beneficial microbe taxa that could be Next Generation Probiotics (NGPs) with metabolic enzymes for MDC neutralisation and mitigation strategies. In this review, we aim to compile the available information and reports focused on variations of the main gut microbiota taxa in metabolic diseases associated with xenobiotic exposure and related microbial metabolite profiles impacting the host health status. We performed an extensive literature search using SCOPUS, Web of Science, and PubMed databases. The data retrieval and thorough analyses highlight the need for more combined metagenomic and metabolomic studies revealing signatures for xenobiotics and triggered metabolic diseases. Moreover, metabolome and microbiome compositional taxa analyses allow further exploration of how to target beneficial NGP candidates according to their alleged variability abundance and potential therapeutic significance. Furthermore, this holistic approach has identified limitations and the need of future directions to expand and integrate key knowledge to design appropriate clinical and interventional studies with NGPs. Apart from human health, the beneficial microbes and metabolites identified could also be proposed for various applications under One Health, such as probiotics for animals, plants and environmental bioremediation.

Incorporating the Gut Microbiome in the Risk Assessment of Xenobiotics and Identifying Beneficial Components for One Health.

Three areas of relevance to the gut microbiome in the context of One Health were explored; the incorporation of the microbiome in food safety risk assessment of xenobiotics; the identification and application of beneficial microbial components to various areas under One Health, and; specifically, in the context of antimicrobial resistance. Although challenging, focusing on the microbiota resilience, function and active components is critical for advancing the incorporation of microbiome data in the risk assessment of xenobiotics. Moreover, the human microbiota may be a promising source of beneficial components, with the potential to metabolize xenobiotics. These may have possible applications in several areas, e.g., in animals or plants for detoxification or in the environment for biodegradation. This approach would be of particular interest for antimicrobials, with the potential to ameliorate antimicrobial resistance development. Finally, the concept of resistance to xenobiotics in the context of the gut microbiome may deserve further investigation.

Impact of Cumulative Environmental and Dietary Xenobiotics on Human Microbiota: Risk Assessment for One Health.

Chemical risk assessment in the context of the risk analysis framework was initially designed to evaluate the impact of hazardous substances or xenobiotics on human health. As the need of multiple stressors assessment was revealed to be more reliable regarding the occurrence and severity of the adverse effects in the exposed organisms, the cumulative risk assessment started to be the recommended approach. As toxicant mixtures and their "cocktail effects" are considered to be main hazards, the most important exposure for these xenobiotics would be of dietary and environmental origin. In fact, even a more holistic prism should currently be considered. In this sense, the definition of One Health refers to simultaneous actions for improving human, animal, and environmental health through transdisciplinary cooperation. Global policies necessitate going beyond the classical risk assessment for guaranteeing human health through actions and implementation of the One Health approach. In this context, a new perspective is proposed for the integration of microbiome biomarkers and next generation probiotics potentially impacting and modulating not only human health, but plant, animal health, and the environment.

Culturing and Molecular Approaches for Identifying Microbiota Taxa Impacting Children's Obesogenic Phenotypes Related to Xenobiotic Dietary Exposure.

Integrated data from molecular and improved culturomics studies might offer holistic insights on gut microbiome dysbiosis triggered by xenobiotics, such as obesity and metabolic disorders. Bisphenol A (BPA), a dietary xenobiotic obesogen, was chosen for a directed culturing approach using microbiota specimens from 46 children with obesity and normal-weight profiles. In parallel, a complementary molecular analysis was carried out to estimate the BPA metabolising capacities. Firstly, catalogues of 237 BPA directed-cultured microorganisms were isolated using five selected media and several BPA treatments and conditions. Taxa from Firmicutes, Proteobacteria, and Actinobacteria were the most abundant in normal-weight and overweight/obese children, with species belonging to the genera Enterococcus, Escherichia, Staphylococcus, Bacillus, and Clostridium. Secondly, the representative isolated taxa from normal-weight vs. overweight/obese were grouped as BPA biodegrader, tolerant, or resistant bacteria, according to the presence of genes encoding BPA enzymes in their whole genome sequences. Remarkably, the presence of sporobiota and concretely Bacillus spp. showed the higher BPA biodegradation potential in overweight/obese group compared to normal-weight, which could drive a relevant role in obesity and metabolic dysbiosis triggered by these xenobiotics.

Monitoring the Restoration of a Seventeenth-Century Wooden Artwork Using Laser-Induced Fluorescence and Digital Image Analysis.

The present paper is aimed at demonstrating the capabilities of digital image analysis (DIA) to support conservation of painted artwork. Laser-induced fluorescence (LIF) imaging has been usually used in the diagnosis of wall paintings. In this case, LIF is applied to the case study of a painted wooden canopy, and most successful data processing techniques are presented in the discussion of results. The Jesús del Gran Poder canopy, completed by Francisco Ruiz Gijón in 1692, is an oil panel painting on wood. Eight panels of the canopy have been study by LIF. This technique is capable of remotely acquiring hyperspectral images operating in fluorescence mode following ultraviolet laser excitation. LIF spectra combined with principal component analysis, spectral angle mapper, and DIA provide a chemical mapping of the treated wooden surface of the panels. Besides, LIF spectrum is as a fingerprint of the panels that allows stablishing differences between them. LIF imaging analysis has proven to be a very useful tool for mapping retouching work, tracking previous restorations, and detecting chemicals on the wood in order to monitor restorations.

Characterization of Roman and Arabic Mural Paintings of the Archaeological Site of Cercadilla (Cordoba, Spain).

The archaeological site of Cercadilla (Cordoba, Spain) includes a complete chronological sequence from the 3rd to 12th centuries. The most relevant monument is a Roman palace dated between the end of the 3rd century and the beginning of the 4th century AD. It is believed that it was the headquarters of the Emperor Maximiano Herculeo. A bathtub with mural paintings has been found in the thermal zone of the palace. Regarding the occupation of the archaeological site in the medieval period, it should be pointed out that two houses with mural paintings were found; these belong to the Caliphal era (10th-11th centuries). During the Caliphal era, the archaeological site was mostly occupied by one of the large suburbs surrounding the walled city. Cercadilla was gradually abandoned; this process starts at the beginning of the 11th century. This study is focused on the analysis of pigments and preparatory layers of red and white mural paintings of the Roman period in the bath zone and on the analysis of pigments in mural paintings in two houses of the Caliphal era. In the thermal zone, the walls have a white mural painting with vertical and horizontal red bands, while the walls in the two Caliphal houses present the red mural painting decorated with white stripes. Techniques such as Optical Microscopy (OM), Scanning Electron Microscopy in combination with Energy Dispersive X-ray Microanalysis (SEM-EDX), X-ray Diffraction (XRD), micro X-ray Diffraction (µ-XRD), Wavelength Dispersive X-ray Fluorescence (WD-XRF), and Fourier Transform-Infrared Spectroscopy (FT-IR) have been used to study the mural paintings of this archaeological site. The results allowed to determine the composition of the materials used and to understand the differences between the technologies employed in Roman and Caliphal remains studied.

Multidisciplinary Approach Applied to the Diagnosis of the Facade of the Arciprestal Church of Santa María de Morella (Castellón, Spain).

This paper deals with the development of a multidisciplinary study on the current state of conservation of the facade of the Arciprestal Church of Santa María de Morella (Castellón, Spain), a work of the Gothic period of great historical and artistic value. The aim of this diagnosis was to undertake the preventive conservation actions required and increase the knowledge about the conservation of paintings on stones. During the diagnosis scanning, electron microscopy was demonstrated to be a valuable analytical method for wall paintings on stone. The facade, which since its construction has not undergone major architectural changes, has reached our days as it was configured in its creation, adding the traces of the passage of time and interventions that have suffered polychromies. Because of the conservation situation, it was decided to have an interdisciplinary project for the structural study of the work, an exhaustive study of the materials and their state of conservation. The study of the materials includes the identification of stone supports, mortars, the pictorial technique of the original and added polychromies, and the superficial patinas. On-site studies were carried out by ground penetration radar (GPR) and X-ray fluorescence (XRF). Among the techniques used in laboratory were optical polarized light microscopy (MO-LP), X-ray diffraction (XRD), scanning electron microscopy with microanalysis (SEM-EDX) and Fourier-transform infrared spectroscopy (FTIR). The study allowed to determine the different pathologies of alteration and degradation of stone substrate and polychromies, chromatic alterations, biological patinas, etc. During this study, it was demonstrated that the diagnosis of wall paintings is a complex issue that needs to be addressed in a multidisciplinary approach, where scanning electron microscopy with microanalysis is the key methodology to get a deeper understanding of subsurface characterization of wall paintings and highlight the weathering processes. In a second phase of previous studies, this technique (SEM) has been used in assessing the viability of consolidation systems and cleaning both the stone and the polychrome.

Scanning Microscopy Techniques as an Assessment Tool of Materials and Interventions for the Protection of Built Cultural Heritage.

Scanning microscopy techniques have emerged as powerful scientific tools for analysing materials of architectural or archaeological interest, since the commercialization of the first scanning electron microscopy instrumentation in the early 60s. This study is aimed at reviewing and highlighting the significance of several scanning microscopy techniques employed in the protection of built heritage. The diffusion of scanning electron microscopy with energy-dispersive X-ray spectroscopy analysis (SEM-EDX) is proven to be the widest among the available scanning microscopy techniques, while transmission electron microscopy (TEM) applications are steadily present in the field of built heritage protection. The building material characterization, the weathering mechanism investigation, and the development of compatible and performing conservation materials are some major research areas where the application of the aforementioned techniques is discussed. The range of techniques, along with aspects of instrumentation and sample preparation are, also, considered.

Efficacy and Safety of Plasma Exchange with 5% Albumin to Modify Cerebrospinal Fluid and Plasma Amyloid-ß Concentrations and Cognition Outcomes in Alzheimer's Disease Patients: A Multicenter, Randomized, Controlled Clinical Trial.

BACKGROUND: Studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid-ß (Aß) peptide between cerebrospinal fluid (CSF) and plasma compartments. OBJECTIVE: To determine whether plasma exchange (PE) with albumin replacement was able to modify Aß concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimer's disease (AD). METHODS: In a multicenter, randomized, patient- and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1 : 1) to PE treatment or control (sham) groups. Treated patients received a maximum of 18 PE with 5% albumin (Albutein®, Grifols) with three different schedules: two PE/weekly (three weeks), one PE/weekly (six weeks), and one PE/bi- weekly (12 weeks), plus a six-month follow-up period. Plasma and CSF Aß1-40 and Aß1-42 levels, as well as cognitive, functional, and behavioral measures were determined. RESULTS: CSF Aß1-42 levels after the last PE compared to baseline were marginally higher in PE-treated group versus controls (adjusted means of variation: 75.3 versus -45.5 pg/mL; 95% CI: -19.8, 170.5 versus 135.1, 44.2; p = 0.072). Plasma Aß1-42 levels were lower in the PE-treated group after each treatment period (p < 0.05). Plasma Aß1-40 levels showed a saw-tooth pattern variation associated with PE. PE-treated patients scored better in the Boston Naming Test and Semantic Verbal Fluency (p < 0.05) throughout the study. Neuropsychiatric Inventory scores were higher in controls during the PE phase (p < 0.05). CONCLUSION: PE with human albumin modified CSF and plasma Aß1-42 levels. Patients treated with PE showed improvement in memory and language functions, which persisted after PE was discontinued.

A new approach to the assessment of flooding and dampness hazards in cultural heritage, applied to the historic centre of Seville (Spain).

Flooding and dampness have caused considerable damage to historic towns and cities and have become more frequent in recent years. The aim of this paper is to analyse the hazards of flooding and dampness in historic cities to establish a methodology that prioritises preventive conservation actions and restorations. The case study concerns the historic centre of Seville (Spain) and parish churches built between the 13th and 18th centuries. Geographic information system (GIS) software has been used to assess hazards caused by flooding and dampness along with a Delphi consultation process surveying a multidisciplinary group of seven experts-archaeologists, geologists, chemists, architects, engineers and environmentalists-to gain a general overview of the hazards affecting each area of the city. Currently, the historic centre of Seville is at a very low risk of flooding due to the engineering works being undertaken to divert the river course. For flooding to occur, water levels would need to rise over 6 to 12m along the different sections of the defensive walls; as a result, the historic centre has not been flooded since 1961, when these defences broke. However, there is a continual presence of dampness due to the proximity of the river, the presence of underground water and the permeability of the subsoil, resulting in continual damage to the lower sections of the monuments studied. Hence, hazard maps of flooding and dampness need to be dovetailed. This new approach provides tools for decision-makers in the current crisis, allowing them to prioritise strategies that will minimise damage in a town, as the urban unit where territorial policies could be applied.

Preservation of resin-dentin interfaces treated with benzalkonium chloride adhesive blends.

Reducing collagen degradation within hybrid layers may contribute to the preservation of adhesive interfaces. This study evaluated the stability of resin-dentin interfaces treated with benzalkonium chloride (BAC)-modified adhesive blends and assessed collagen degradation in dentin matrices treated with BAC. The etch-and-rinse adhesive, Adper Single Bond Plus, modified with 0.5% and 1.0% BAC, was evaluated for microtensile bond strength (µTBS) and nanoleakage (NL) after 24 h and 1 yr. Thirty completely demineralized dentin beams from human molars were dipped for 60 s in deionized water (DW; control), or in 0.5% or 1.0% BAC, and then incubated in simulated body fluid (SBF). Collagen degradation was assessed by quantification of the dry mass loss and the amount of hydroxyproline (HYP) released from hydrolyzed specimens after 1 or 4 wk. Although all groups demonstrated a significant increase in NL after 1 yr, adhesive modified with 0.5% BAC showed stable bond strength after 1 yr (9% decrease) relative to the control (44% decrease). Significantly less HYP release and dry mass loss were observed for both 0.5% and 1.0% BAC relative to the control. This in vitro study demonstrates that BAC contributes to the preservation of resin-dentin bonds for up to 1 yr by reducing collagen degradation.

Risk assessment of particle dispersion and trace element contamination from mine-waste dumps.

In this study, a model to delimit risk zones influenced by atmospheric particle dispersion from mine-waste dumps is developed to assess their influence on the soil and the population according to the concentration of trace elements in the waste. The model is applied to the Riotinto Mine (in SW Spain), which has a long history of mining and heavy land contamination. The waste materials are separated into three clusters according to the mapping, mineralogy, and geochemical classification using cluster analysis. Two of the clusters are composed of slag, fresh pyrite, and roasted pyrite ashes, which may contain high concentrations of trace elements (e.g., >1 % As or >4 % Pb). The average pollution load index (PLI) calculated for As, Cd, Co, Cu, Pb, Tl, and Zn versus the baseline of the regional soil is 19. The other cluster is primarily composed of sterile rocks and ochreous tailings, and the average PLI is 3. The combination of particle dispersion calculated by a Gaussian model, the PLI, the surface area of each waste and the wind direction is used to develop a risk-assessment model with Geographic Information System GIS software. The zone of high risk can affect the agricultural soil and the population in the study area, particularly if mining activity is restarted in the near future. This model can be applied to spatial planning and environmental protection if the information is complemented with atmospheric particulate matter studies.

The epidemiology of blood component transfusion in Catalonia, Northeastern Spain.

BACKGROUND: Epidemiologic information on blood component usage can help improve the utilization of transfusion resources. STUDY DESIGN AND METHODS: Crosssectional survey in 2007 that included every hospital in Catalonia. Clinical data of blood recipients, including the four-digit International Classification of Diseases, 9th Revision, Clinical Modification codes and the indication for transfusion, were prospectively collected according to an established protocol. RESULTS: In total, 19,148 red blood cell (RBC) units, 1812 platelet (PLT) doses, and 3070 plasma units, transfused into 8019 patients (median age, 71 years; 52% males), were surveyed. Half the RBC units were used by patients older than 70 years. Specific diagnosis and procedures with the highest RBC use were lower limb orthopedic surgery (10.6% of all units) and gastrointestinal hemorrhage (6%). Therapeutic plasmapheresis (8.1%) and heart valve surgery (7.2%) were the procedures with the highest plasma use. Oncohematology patients accounted for 73% of transfused PLTs, more that two-thirds being administered for hemorrhage prophylaxis. Acute hemorrhage was the most common indication for RBC and plasma transfusion. Among all blood recipients, 80% received only RBCs and 6.9% received only plasma and/or PLTs, without concomitant RBCs. The population transfusion incidence rates were 35 RBC units, three PLT doses, and 6 plasma units per 1000 population-year. Demographic changes anticipate a 30% increase in RBC transfusion by year 2030. CONCLUSIONS: These results allow for identification of blood uses that are susceptible to improvement, help appraise the expected yield of blood safety measures, and will assist in planning the future blood supply.

Hiperaldosteronismo primario / Primary hyperaldosteronism

El hiperaldosteronismo primario se caracteriza por una hiperproducción de aldosterona por la glándula suprarrenal, con supresión de la actividad de la renina plasmática. Los hallazgos clínicos son poco específicos y en algunos pacientes cursan de forma asintomática aunque en casi todos los casos se encuentra una HTA moderada o grave difícil de controlar y síntomas neuromusculares como astenia y parestesias. Presentamos el caso de una paciente de 33 años que consulta en el servicio de urgencias por dolor torácico y cortejo vegetativo (AU)

Primary hyperaldosteronism is characterised by an excessive production of aldosterone by the adrenal gland, with suppression of plasma renin activity. Clinical findings are not very specific and in some patients it is asymptomatic although in almost all cases there is moderately to severely high blood pressure that is difficult to control and neuromuscular symptoms such as asthenia and paresthesia. We present the case of a 33 year old patient who came to the emergency department due to chest pain and symptoms related to the parasympathetic nervous system (AU)

Pseudoxantoma elástico / Pseudoxanthoma elasticum

El pseudoxantoma elástico es una enfermedad hereditaria del tejido conectivo caracterizada por calcificación y fragmentación progresivas de las fibras elásticas en distintos tejidos. La prevalencia de la enfermedad se estima en 1 de cada 25,000 a 100,000 habitantes y es dos veces más frecuente en mujeres. Su diagnóstico precoz ayuda a prevenir las futuras complicaciones que estos pacientes pueden desarrollar (AU)

Pseudoxanthoma elasticum is a genetic disorder of the connective tissue characterised by progressive calcification and fragmentation of the elastic fibres in different body tissues. It has an estimated prevalence of 1 case in 25,000 to 100,000 population and is twice as common in women. Early diagnosis helps to prevent further complications these patients could develop (AU)

Amyloid-targeted therapeutics in Alzheimer's disease: use of human albumin in plasma exchange as a novel approach for Abeta mobilization.

A clinical investigation program was carried out to replace endogenous albumin of patients with mild to moderate Alzheimer's disease (AD) with 5% Human Albumin Grifols(R) through a plasma exchange (PE) schedule, in order to alter the dynamic equilibrium between albumin-bound Abeta in plasma and Abeta in cerebrospinal fluid. In a pilot proof-of-concept study, 7 patients underwent 6 PE in 3 weeks and 1 year of follow-up. Plasma Abeta determinations demonstrated a variation pattern in levels in relation with the PEs. Cognitive status scores (MMSE and ADAS-Cog) were more stable than expected. In a phase II clinical trial, 29 patients were randomized into PEtreated and control groups with 1 year follow-up. Interim results point toward the occurrence of Abeta40 mobilization in the PE-treated patients, who scored better in cognitive tests (differences at 9 months: 2.5 in MMSE and 5.5 in ADAS-cog). These results suggest that a PE program with 5% Human Albumin Grifols may have a promising role in the treatment of mild to moderate AD.