Barrier Failure Research Articles

Blood-retina barrier failure and vision loss in neuron-specific degeneration.

Changes in neuronal activity alter blood flow to match energy demand with the supply of oxygen and nutrients. This functional hyperemia is maintained by interactions between neurons, vascular cells, and glia. However, how changing neuronal activity prevalent at the onset of neurodegenerative disease affects neurovascular elements is unclear. Here, in mice with photoreceptor degeneration, a model of neuron-specific dysfunction, we combined assessment of visual function, neurovascular unit structure, and the blood-retina barrier permeability. We found that the rod loss paralleled remodeling of the neurovascular unit, comprised of photoreceptors, retinal pigment epithelium, and Muller glia. When significant visual function was still present, blood flow became disrupted and blood-retina barrier began to fail, facilitating cone loss and vision decline. Thus, in contrast to the established view, vascular deficit in neuronal degeneration is not a late consequence of neuronal dysfunction, but is present early in the course of disease. These findings further establish the importance of vascular deficit and blood retina barrier function in neuron-specific loss, and highlight it as a target for early therapeutic intervention.

Intravascular Delivery of TAT‐conjugated Focal Adhesion Kinase Protects against Acute Lung Injury

Acute lung injury (ALI), a major cause of high mortality in all age groups, occurs because of endothelial barrier failure. But it lacks a cure. We showed that endothelial focal adhesion kinase (FAK) is barrier protective (PMID: 23033075), suggesting FAK may be a cure for ALI. To test this hypothesis, we purified wild type FAK (FAKWT) and FAK with YàF mutation at tyrosine 925 (FAKMUT), which is expressed in FAK's focal adhesion targeting domain. Then we non‐covalently conjugated the proteins with the cell‐permeable peptide TAT (HIV‐1 transactivator of transcription). We intranasally instilled LPS in anesthetized mice. After 24h, we intravenously infused TAT‐FAKp or TAT‐FAKpY925F. After 4 h, we gave intravenous Evans Blue‐albumin (EBA). After a further 4 h, we assayed ALI in terms of EBA concentration and leukocyte counts in the bronchoalveolar lavage (BAL). Also, by live confocal microscopy of isolated, blood‐perfused lungs, we assayed endothelial F‐actin in terms of the lung endothelial fluorescence of Rhodamin Phalloidin. LPS increased EBA and leukocytes two‐times above baseline (p<0.05 each). TAT‐FAKWT, but not TAT‐FAKpMUT inhibited both responses (p<0.05). Endothelial F‐actin was markedly higher after TAT‐FAKWT than after TAT‐FAKpMUT infusion (p<0.05). LPS‐induced mortality in 5 days was 80% for untreated or TAT‐FAKpMUT infused mice. However, TAT‐FAKpWT infusion decreased the mortality to 25% (p<0.05). Our findings indicate that purified FAK can be effectively given by intravenous injection. TAT‐FAKWT, given well after the initiation of LPS‐induced ALI, markedly increased survival. The protective effect was due to FAK's Y925 residue that is likely responsible for enhancing cortical F‐actin, thereby strengthening the endothelial barrier (PMID:23033075). We propose that intravenous delivery of TAT‐FAKpWT might be effective therapy for ALI (HL36024).Support or Funding InformationNIH: HL36024This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ropivacaine inhibits pressure-induced lung endothelial hyperpermeability in models of acute hypertension

AimsIncreases in hydrostatic pressure results in endothelial hyperpermeability via eNOS-dependent pathways. Ropivacaine is known to inhibit eNOS activation and to attenuate lung injury. Herein, we sought to determine if ropivacaine regulates pressure-induced lung endothelial hyperpermeability. Main methodsThe effects of ropivacaine on lung permeability were assessed in two models of acute hypertension (AH): the isolated perfused lung preparation where acute increases in left atrial pressure model the hemodynamic changes of severe hypertension, and an animal model of AH induced by norepinephrine. In the IPL model, whole lung filtration coefficient (Kf) was used as the index of lung permeability; pulmonary artery pressure (Ppa), pulmonary capillary pressures (Ppc), and zonal characteristics (ZC) were measured to assess the effects of ropivacaine on hemodynamics and their relationship to Kf2/Kf1. In vivo, ropivacaine effects were investigated on indices of pulmonary edema (changes in PaO2, lung wet-to-dry ratio), changes in plasma volume and nitric oxide (NO) production. Key findingsRopivacaine provided robust protection from pressure-dependent barrier failure; it inhibited pressure-induced increases in Kf without affecting Ppa, Ppc or ZC. In vivo, ropivacaine prevented pressure-induced lung edema and associated hyperpermeability as evidence by maintaining PaO2, lung wet-to-dry ratio and plasma volume in levels similar to sham rats. Ropivacaine inhibited pressure-induced NO production as evidenced by decreased lung nitro-tyrosine content when compared to hypertensive lungs. SignificanceCollectively these data show that ropivacaine inhibits pressure-induced lung endothelial hyperpermeability and suggest that ropivacaine may be a clinically useful agent to prevent endothelial hyperpermeability when pulmonary pressure is acutely increased.

Endothelial mitochondria determine rapid barrier failure in chemical lung injury.

Acid aspiration, which can result from several etiologies, including postoperative complications, leads to direct contact of concentrated hydrochloric acid (HCl) with the alveolar epithelium. As a result, rapid endothelial activation induces alveolar inflammation, leading to life-threatening pulmonary edema. Because mechanisms underlying the rapid endothelial activation are not understood, here we determined responses in real time through optical imaging of alveoli of live mouse lungs. By alveolar micropuncture, we microinfused concentrated HCl in the alveolar lumen. As expected, acid contact with the epithelium caused rapid, but transient, apical injury. However, there was no concomitant membrane injury to the endothelium. Nevertheless, H2O2-mediated epithelial-endothelial paracrine signaling induced endothelial barrier failure, as detected by microvascular dextran leakage and lung water quantification. Remarkably, endothelial mitochondria regulated the barrier failure by activating uncoupling protein 2 (UCP2), thereby inducing transient mitochondrial depolarization that led to cofilin-induced actin depolymerization. Knockdown, or endothelium-targeted deletion of UCP2 expression, blocked these responses, including pulmonary edema. To our knowledge, these findings are the first to mechanistically implicate endothelial mitochondria in acid-induced barrier deterioration and pulmonary edema. We suggest endothelial UCP2 may be a therapeutic target for acid-induced acute lung injury.

M2-polarized macrophages relate the clearance of gastric lanthanum deposition.

Key Clinical MessagePrevious reports have suggested that mucosal barrier failure allows lanthanum to stray into the lamina propria, and macrophages play an important role for the clearance. However, there is no report to analyze the polarity of phagocytizing macrophages. We suggested that M2 macrophage potentially played a major role in the clearance of lanthanum.

Metabolomics analysis of gut barrier dysfunction in a trauma-hemorrhagic shock rat model

Intestinal barrier dysfunction has been implicated in the development of multiorgan dysfunction syndrome caused by the trauma-hemorrhagic shock (THS). However, the mechanisms underlying THS-induced gut barrier injury are still poorly understood. In the present study, we used the metabolomics analysis to test the hypothesis that altered metabolites might be related to the development of THS-induced barrier dysfunction in the large intestine. Under the induction of THS, gut barrier failure was characterized by injury of permeability and mucus layer, which were companied by the decreased expression of zonula occludens-1 in the colon and increased levels of inflammatory factors including tumor necrosis factor-α, interferon-γ, interleukin (IL)-6, and IL-1β in the serum. A total of 16 differential metabolites were identified in colonic tissues from THS-treated rats compared with control rats. These altered metabolites included dihydroxy acetone phosphate, ribose-5-phosphate, fructose, glyceric acid, succinic acid, and adenosine, which are critical intermediates or end products that are involved in pentose phosphate pathway, glycolysis, and tricarboxylic acid cycle as well as mitochondrial adenosine triphosphate biosynthesis. These findings may offer important insight into the metabolic alterations in THS-treated gut injury, which will be helpful for developing effective metabolites-based strategies to prevent THS-induced gut barrier dysfunction.

Analysis of an agent-based model for predicting the behavior of bighead carp (Hypophthalmichthys nobilis) under the influence of acoustic deterrence

Bighead carp (Hypophthalmichthys nobilis) are an invasive, voracious, highly fecund species threatening the ecological integrity of the Great Lakes. This agent-based model and analysis explore bighead carp behavior in response to acoustic deterrence in an effort to discover properties that increase likelihood of deterrence system failure. Results indicate the most significant (p < 0.05) influences on barrier failure are the quantity of detritus and plankton behind the barrier, total number of bighead carp successfully deterred by the barrier, and number of native fishes freely moving throughout the simulation. Quantity of resources behind the barrier influence bighead carp to penetrate when populations are resource deprived. When native fish populations are low, an accumulation of phytoplankton can occur, increasing the likelihood of an algal bloom occurrence. Findings of this simulation suggest successful implementation with proper maintenance of an acoustic deterrence system has potential of abating the threat of bighead carp on ecological integrity of the Great Lakes.

Pressure-dependent NOS activation contributes to endothelial hyperpermeability in a model of acute heart failure

Aims: Acute increases in left ventricular end diastolic pressure (LVEDP) can induce pulmonary edema (PE). The mechanism(s) for this rapid onset edema may involve more than just increased fluid filtration. Lung endothelial cell permeability is regulated by pressure-dependent activation of nitric oxide synthase (NOS). Herein, we demonstrate that pressure-dependent NOS activation contributes to vascular failure and PE in a model of acute heart failure (AHF) caused by hypertension.Methods and results: Male Sprague–Dawley rats were anesthetized and mechanically ventilated. Acute hypertension was induced by norepinephrine (NE) infusion and resulted in an increase in LVEDP and pulmonary artery pressure (Ppa) that were associated with a rapid fall in PaO2, and increases in lung wet/dry ratio and injury scores. Heart failure (HF) lungs showed increased nitrotyrosine content and ROS levels. L-NAME pretreatment mitigated the development of PE and reduced lung ROS concentrations to sham levels. Apocynin (Apo) pretreatment inhibited PE. Addition of tetrahydrobiopterin (BH4) to AHF rats lung lysates and pretreatment of AHF rats with folic acid (FA) prevented ROS production indicating endothelial NOS (eNOS) uncoupling.Conclusion: Pressure-dependent NOS activation leads to acute endothelial hyperpermeability and rapid PE by an increase in NO and ROS in a model of AHF. Acute increases in pulmonary vascular pressure, without NOS activation, was insufficient to cause significant PE. These results suggest a clinically relevant role of endothelial mechanotransduction in the pathogenesis of AHF and further highlights the concept of active barrier failure in AHF. Therapies targetting the prevention or reversal of endothelial hyperpermeability may be a novel therapeutic strategy in AHF.

Delay in antibiotic therapy results in fatal disease outcome in murine pneumococcal pneumonia

BackgroundCommunity-acquired pneumonia (CAP) remains a major cause of death worldwide. Mechanisms underlying the detrimental outcome despite adequate antibiotic therapy and comorbidity management are still not fully understood.MethodsTo model timely versus delayed antibiotic therapy in patients, mice with pneumococcal pneumonia received ampicillin twice a day starting early (24 h) or late (48 h) after infection. Clinical readouts and local and systemic inflammatory mediators after early and late antibiotic intervention were examined.ResultsEarly antibiotic intervention rescued mice, limited clinical symptoms and restored fitness, whereas delayed therapy resulted in high mortality rates. Recruitment of innate immune cells remained unaffected by antibiotic therapy. However, both early and late antibiotic intervention dampened local levels of inflammatory mediators in the alveolar spaces. Early treatment protected from barrier breakdown, and reduced levels of vascular endothelial growth factor (VEGF) and perivascular and alveolar edema formation. In contrast, at 48 h post infection, increased pulmonary leakage was apparent and not reversed by late antibiotic treatment. Concurrently, levels of VEGF remained high and no beneficial effect on edema formation was evident despite therapy. Moreover, early but not late treatment protected mice from a vast systemic inflammatory response.ConclusionsOur data show that only early antibiotic therapy, administered prior to breakdown of the alveolar–capillary barrier and systemic inflammation, led to restored fitness and rescued mice from fatal streptococcal pneumonia. The findings highlight the importance of identifying CAP patients prior to lung barrier failure and systemic inflammation and of handling CAP as a medical emergency.

Developing leading indicators-based decision support algorithms and probabilistic models using Bayesian network to predict kicks while drilling

Abstract Predicting a kick timely and efficiently is often a challenging task due to the complexities of drilling and other well intervention activities. This work proposes a leading indicators-based approach to assess drilling operations for predicting kicks and preventing blowouts. A cause-based methodology is proposed to develop sets of leading indicators for different categories and organizational levels. Leading indicators are divided into two broad sections – real-time indicators and long-term organizational safety performance indicators. With the real-time indicators, various decision support algorithms are developed which would help to understand a kick progression scenario effectively. Probabilistic barrier failure models for different stages of drilling are also developed to assess performance of primary well control barrier – hydrostatic head. To predict barrier failure events effectively, Bayesian network models are developed combining organizational, operational and real-time indicators. The probability distribution for observing changes in real-time parameters when a kick is in progression are also determined. This study would allow both predictive (causes to effects) and diagnostic (effects to causes) reasoning of kicks and blowouts for better understanding of well control system while drilling. Developed risk models enable informed decision making with a relatively clear picture of the risk of barrier failure and provide useful information on actions required to prevent escalation of well control events.

Studies on flexible rockfall barriers for failure modes, mechanisms and design strategies: a case study of Western China

A field investigation on the actual protective performance of a flexible rockfall barrier along a mountain road in western China is presented in this paper. The total area of the flexible rockfall barrier under investigation was approximately 20,000 m2. Five typical failure modes of the flexible rockfall barrier were revealed, including steel post buckling, connection failure, ring net destruction, steel cable rope breakage and anchorage point failure. In addition, component rusting, which leads to decrease in durability, was noted. Furthermore, failure mechanisms were analysed, and the main factors that were found to induce flexible rockfall barrier failure included the sliding capacity of the cable ropes at the end post support positions, the boundary conditions of the steel posts and the compatibility between the energy dissipating devices and connected cable ropes. From these observations, corresponding design strategies were proposed. In addition, an improved flexible rockfall barrier system was constructed, and its effectiveness was verified by a full-scale impact test using 5000 kJ of impact energy. Finally, the impact deflection, impact force, cable force and energy dissipation of the improved flexible rockfall barrier system were studied in combination with a non-linear numerical simulation which could be a useful tool for design of flexible barrier systems.

A Monte Carlo-Based Probabilistic Barrier Failure Model for Arbitrary Fire Environment

Failure of building assemblies is a combined results of both heat attack and the mechanical response of the assembly components. The latter could change the integrity of a fire barrier and the pattern of heat transfer. The prediction of failure becomes more complicated when it comes to non-standard fires where real-world experiments are limited. 2-D or 3-D numerical models may provide useful results but their sophistication of use still drives the needs for simple models that offer quick results. A probabilistic barrier failure model is developed to simulate the dynamic process of barrier failure and reflect its stochastic nature. The model comprises a deterministic heat transfer and component response submodel that calculates one-dimensional heat transfer and component responses in fire such as the fall-off of gypsum boards. Further, a Monte Carlo-based probabilistic barrier failure model is created by sampling the influential factors that affect the failure of components. The fire barriers applied in the model include light timber frame and light steel frame assemblies as well as cross laminated timber assembly, but the model is open to other assemblies where data are available. The model results are validated against five room fire tests with good agreements, and an example calculation demonstrates that in a real fire the failure of fire barriers may occur earlier or later than that in the standard fire.

Connexin 40 regulates lung endothelial permeability in acute lung injury via the ROCK1-MYPT1- MLC20 pathway.

Increased pulmonary vascular permeability is a hallmark of acute lung injury (ALI). Connexin 40 (Cx40) is a gap junctional protein abundantly present in the lung microvascular endothelium. Yet, the role of Cx40 in the regulation of lung vascular permeability and its underlying mechanisms are unclear. Here, we tested the hypothesis that Cx40 participates in regulation of lung endothelial permeability via a mechanism involving a Rho-associated protein kinase (ROCK) dependent regulation of myosin light chain (MLC). In murine models of intratracheal acid- or LPS-induced lung injury, genetic deficiency of Cx40 attenuated key features of ALI including vascular barrier failure. In human pulmonary microvascular endothelial cells (PMVECs), thrombin-induced loss of transendothelial electrical resistance was attenuated by a Cx40-inhibiting mimetic peptide (40GAP27), Cx40-specific shRNA, or ROCK inhibitor Y27632. In isolated perfused mouse lungs, platelet-activating factor-induced lung weight gain was abrogated by gap junction blocker carbenoxolone, 40GAP27, Y27632, or genetic deficiency of Cx40. Phosphorylation of MLC20 increased drastically in both LPS-treated PMVECs and HCl-treated mouse lungs. Expression of ROCK1 was increased in both LPS-treated PMVECs and HCl-treated mouse lungs, and paralleled by phosphorylation of MLC20. Coimmunoprecipitation experiments revealed protein-protein interaction between ROCK1 and Cx40. LPS-induced upregulation of ROCK1 and phosphorylation of MLC20 were blocked by knockdown of Cx40. LPS caused phosphorylation of myosin phosphatase targeting subunit 1, which could be abrogated by Y27632 or Cx40-shRNA. Our findings reveal a role of Cx40 in regulation of ROCK1 and MLC20 that contributes critically to lung vascular barrier failure in ALI.

Novel mechanisms regulating endothelial barrier function in the pulmonary microcirculation

The pulmonary epithelial and vascular endothelial cell layers provide two sequential physical and immunological barriers that together form a semi-permeable interface and prevent alveolar and interstitial oedema formation. In this review, we focus specifically on the continuous endothelium of the pulmonary microvascular bed that warrants strict control of the exchange of gases, fluid, solutes and circulating cells between the plasma and the interstitial space. The present review provides an overview of emerging molecular mechanisms that permit constant transcellular exchange between the vascular and interstitial compartment, and cause, prevent or reverse lung endothelial barrier failure under experimental conditions, yet with a clinical perspective. Based on recent findings and at times seemingly conflicting results we discuss emerging paradigms of permeability regulation by altered ion transport as well as shifts in the homeostasis of sphingolipids, angiopoietins and prostaglandins.

Gut-origin sepsis in the critically ill patient: pathophysiology and treatment.

Gut permeability is increased in critically ill patients, and associated with the development of the systemic inflammatory response syndrome and multiple organ dysfunction syndrome (MODS). The pathogenetic link(s) and potential therapies are an area of intense research over the last decades. We thoroughly reviewed the literature on gut-origin sepsis and MODS in critically ill patients, with emphasis on the implicated pathophysiological mechanisms and therapeutic interventions. Intestinal barrier failure leading to systemic bacterial translocation associated with MODS was the predominant pathophysiological theory for several years. However, clinical studies with critically ill patients failed to provide the evidence of systemic spread of gut-derived bacteria and/or their products as a cause of MODS. Newer experimental data highlight the role of the mesenteric lymph as a carrier of gut-derived danger-associated molecular patterns (DAMPs) to the lung and the systemic circulation. These substances are recognized by pattern recognition receptor-bearing cells in diverse tissues and promote proinflammatory pathways and the development MODS. Therefore, the gut becomes a pivotal proinflammatory organ, driving the systemic inflammatory response through DAMPs release in mesenteric lymph, without the need for systemic bacterial translocation. There is an emerging need for application of sensitive non-invasive and easily measured biomarkers of early intestinal injury (e.g., citrulline, intestinal fatty acid protein, and zonulin) in our everyday clinical practice, guiding the early pharmacological intervention in critically ill patients to restore or prevent intestinal injury and improve their outcomes.

Comprehensive risk assessment of high sulfur-containing gas well

Well integrity has been a growing concern of oil and gas industry, especially in the years of cheap oil. The failure of well integrity may cause undesirable events or even devastating consequences such as safety hazards or loss of containment. In this paper, a novel calculation model of wellbore integrity comprehensive risk has been presented. Firstly, the risk hazard associated with well barrier failure modes are identified based on the relevant literature. The risk factors of well integrity in production phase are investigated in detail. The risk matrix based on Borda number analytical method and Analytic Hierarchy Process (AHP) is then presented to assess the risks of well integrity in production safety. Finally, the case of XX high sour gas well is empirically investigated to validate the model. The results indicate that 27 risk factors are identified for XX gas well in production. In addition, it is found that the XX gas well is prone to suffer damage in presence of H2S and CO2, furthermore, the Borda number analytical results also show that the most important factor affecting the well integrity is effect of string corrosion, followed by the corrosion of string sealing accessories and the corrosion environment of material applicability. Therefore, the appropriate measures should be taken to reduce the corrosion of string and sealing accessories, thus prolonging the service life of the equipment. The case of XX high sour gas field verifies the feasibility and applicability of the risk matrix method in wellbore integrity risk assessment. The innovative assessment method provides methodological reference and guidance for the application of the limited resources, in addition, it also has practical information for well integrity engineers to improve the performance of safety management, thus ensuring well safety during production.

Elevated faecal ovotransferrin concentrations are indicative for intestinal barrier failure in broiler chickens

Intestinal health is critically important for the welfare and performance of poultry. Enteric diseases that cause gut barrier failure result in high economic losses. Up till now there is no reliable faecal marker to measure gut barrier failure under field conditions. Therefore, the aim of the present study was to identify a faecal protein marker for diminished intestinal barrier function due to enteric diseases in broilers. To assess this, experimental necrotic enteritis and coccidiosis in broilers were used as models for gut barrier failure. Ovotransferrin was identified as a marker for gut barrier failure using a proteomics approach on samples from chickens with necrotic enteritis. These results were confirmed via ELISA on samples derived from both necrotic enteritis and coccidiosis trials, where faecal ovotransferrin levels were significantly correlated with the severity of gut barrier failure caused by either coccidiosis or necrotic enteritis. This indicates that faecal ovotransferrin quantification may represent a valuable tool to measure gut barrier failure caused by enteric pathogens.

Evaluation of cement sheath integrity subject to enhanced pressure

Well-cementing (cementation) is an influential stage of a wellbore completion, as the cement sheath is responsible for providing a complete zonal isolation. Therefore, it is of utmost importance to understand the cement mechanical failure mechanisms since well cement failure and interfacial debonding between the cement and casing and cement and rock formations can lead to a barrier failure. During the wellbore lifetime, a cement sheath is subjected to pressure loading variations. This paper demonstrates the results of an experimental-numerical study to investigate the cement sheath integrity after being subjected an enhanced pressure. A constitutive model specifically formulated for the modelling of quasi-brittle materials is applied to the investigation of cement sheath integrity, incorporating both compression and tensile damage mechanisms. Laboratory experiments are carried out to obtain strength properties of cement class G followed by calibration of the model parameters based on the obtained experimental results. A three-dimensional finite element framework employing the constitutive model for cement sheath and a surface-based cohesive behaviour for the interfaces is developed for integrity investigations. The effects of different orientations of in-situ stresses, different stiffness's of surrounding rock, and the eccentricity of the casing within the wellbore on the integrity of the cement and interfaces are investigated. The significance of cement sheath centralisation and elevated risk of cement mechanical failure caused by wellbore operations in anisotropic fields with soft rocks formation were highlighted. Furthermore, the relatively high magnitude of tensile damage (cracking index) within the cement sheath confirms the importance of tensile properties to be incorporated into the constitutive modelling.

The Endotoxemia Marker Lipopolysaccharide-Binding Protein is Reduced in Overweight-Obese Subjects Consuming Pomegranate Extract by Modulating the Gut Microbiota: A Randomized Clinical Trial.

Gut microbiota dysbiosis, intestinal barrier failure, obesity, metabolic endotoxemia, and pro-inflammatory status promote cardiovascular risk. However, the modulation of the gut microbiome to prevent endotoxemia in obesity has been scarcely studied. We investigated the association between gut microbiota modulation and plasma lipopolysaccharide-binding protein (LBP), a surrogate marker of endotoxemia, in overweight-obese individuals. In a randomized trial, 49 overweight-obese subjects (body mass index> 27 kg m-2 ) with mild hypelipidemia daily consumed, in a cross-over fashion, two doses (D1 and D2, lasting 3 weeks each) of pomegranate extract (PE) or placebo alternating with 3 weeks of wash-out periods. A significant decrease (p < 0.05) of plasma LBP and a marginal decrease (p = 0.054) of high-sensitivity C-reactive protein were observed, but only after PE-D2 administration (656 mg phenolics). 16S rDNA sequencing analyses revealed the increase of microorganisms important for maintaining normal balance of gut microbiota and gut barrier function, particularly Bacteroides, Faecalibacterium, Butyricicoccus, Odoribacter, and Butyricimonas. PE-D2 also decreased pro-inflammatory microorganisms including Parvimonas, Methanobrevibacter, and Methanosphaera. Remarkably, plasma LBP reduction was significantly associated (p < 0.05) with both Faecalibacterium and Odoribacter increase and Parvimonas decrease. Consumption of PE decreased endotoxemia in overweight-obese individuals by reshaping the gut microbiota, mainly through the modulation of Faecalibacterium, Odoribacter, and Parvimonas.

An Assessment of the Probability of Subsurface Contamination of Aquifers From Oil and Gas Wells in the Wattenberg Field, Modified for Water-Well Location

Summary The United States National Science Foundation has funded a sustainability-research network focused on natural-gas development in the Rocky Mountain region of the United States. The objective of this specific study is the assessment of the use of existing water wells to monitor the risk of contamination by the migration of fracturing fluids or hydrocarbons to freshwater aquifers. An additional objective of the study is to modify existing risk estimates using the spatial relationships between the existing water wells and producing oil wells. This will allow estimates of single-barrier failure and multiple-barrier failure, resulting in contamination projections for oil and gas wells in areas without surrounding water wells to detect migration, dependent on well-construction type. Since 1970, the Wattenberg Field in Colorado has had a large number of oil and gas wells drilled. These wells are interspaced tightly with agricultural and urban development from the nearby Denver metropolitan area. This provides a setting with numerous water wells that have been drilled within this area of active petroleum development. Data from 17,948 wells drilled were collected and analyzed in Wattenberg Field, allowing wells to be classified by construction type and analyzed for barrier failure and source of aquifer contamination. The assessment confirms that although natural-gas migration occurring in poorly constructed wellbores is infrequent, it can happen, and the migration risk is determined by the well-construction standards. The assessment also confirms that there has been no occurrence of hydraulic-fracturing-fluid contamination of freshwater aquifers through wellbores. The assessment determines both the spatial proximity of oil and gas wells and surface-casing depth to water wells to then determine the utility of water wells to monitor migration in oil wells.