High prevalence of non-alcoholic fatty liver disease and metabolic risk factors in Guatemala: A population-based study.

BACKGROUND: There are no data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in general population samples in Guatemala or in other Central American countries. The prevalence and distribution of NAFLD and its associated risk factors were evaluated in a population-based sample of adults in Guatemala. METHODS: Cross-sectional study of 411 men and women 40 years of age or older residing in urban and rural areas of Guatemala. Metabolic outcomes included obesity, central obesity, hypercholesterolemia, diabetes, and metabolic syndrome (MetS). Liver disease outcomes included elevated liver enzymes, elevated Fatty Liver Index (FLI), and elevated FIB-4 score. RESULTS: The overall prevalence of obesity, central obesity, diabetes, and MetS were 30.9, 74.3, 21.6, and 64.2%, respectively. The fully-adjusted prevalence ratios (95% CI) for obesity, central obesity, diabetes, and MetS comparing women to men were 2.83 (1.86-4.30), 1.72 (1.46-2.02), 1.18 (1.03-1.34), and 1.87 (1.53-2.29), respectively. The overall prevalence of elevated liver enzymes (ALT or AST), elevated FLI, and elevated FIB-4 scores were 38.4, 60.1, and 4.1%, respectively. The fully-adjusted prevalence ratios (95% CI) for elevated liver enzymes (either ALT or AST) and elevated FLI score comparing women to men were 2.99 (1.84-4.86) and 1.47 (1.18-1.84), respectively. CONCLUSIONS: The prevalence of metabolic abnormalities and liver outcomes in this general population study was very high. The prevalence of metabolic and liver abnormalities was particularly high among women, an observation that could explain the atypical 1:1 male to female ratio of liver cancer in Guatemala.

Cellular immune responses to platelet factor 4 and heparin complexes in patients with heparin-induced thrombocytopenia.

Essentials The immunogenesis of Heparin-induced thrombocytopenia (HIT) is not well understood. Immunization to platelet factor 4 (PF4)-heparin occurs early in life, before any heparin exposure. PF4 and PF4-heparin complexes induce the proliferation of CD14+ cells. Reduced levels of regulatory cytokines contribute to immune dysregulation in HIT. SUMMARY: Background Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin characterized by thrombocytopenia and thrombotic complications. HIT is caused by pathogenic antibodies that bind to complexes of platelet factor 4 (PF4) and heparin, leading to platelet activation and inducing a hypercoagulable state. Previous studies have shown immunity to PF4-heparin complexes occurs early in life, even before heparin exposure; however, the immunogenesis of HIT is not well characterized. Objectives To investigate cellular proliferation in response to PF4-heparin complexes in patients with HIT. Patients/Methods Peripheral blood mononuclear cells (PBMCs) from healthy controls (n = 30), postoperative cardiac surgery patients who had undergone cardiopulmonary bypass (CPB) (n = 17) and patients with confirmed HIT (n = 41) were cultured with PF4 and PF4-heparin complexes. Cellular proliferation was assessed by [3 H]thymidine uptake and 5-ethynyl-2'-deoxyuridine detection. Results and Conclusions PBMCs proliferated in the presence of PF4, and this was enhanced by the addition of heparin in all study groups. CPB and HIT patients showed significantly greater proliferative responses than healthy controls. PBMC proliferation was antigen-specific, depended on the presence of platelets, and only CD14+ cells were identified as proliferating cells. Culture supernatants were tested for the levels of regulatory cytokines, and both CPB and HIT patients produced significantly lower levels of interleukin-10 and transforming growth factor-ß1 than healthy controls. These findings further demonstrate cellular immune sensitization to PF4-heparin complexes occurs before heparin exposure, and suggests immune dysregulation can contribute to HIT.

Soft X-Ray Second Harmonic Generation as an Interfacial Probe.

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (∼284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.

Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis.

BACKGROUND: Prostate cancer (PCa) is the fifth leading cause of cancer-related deaths worldwide. Many epidemiological studies have investigated the association between prostate cancer and lycopene, however, results have been inconsistent. This study aims to determine the impact of dietary and circulating concentrations of lycopene on PCa risk and to investigate potential dose-response associations. METHODS: We conducted a systematic review and dose-response meta-analysis for the for the association between dietary and circulating lycopene and PCa risk. Eligible studies were published before 1 December 2016 and were identified from PubMed, Web of Science and the Cochrane Library. We estimated pooled relative risk ratios (RR) and 95% confidence intervals (CI) using random and fixed effects models. Linear and nonlinear dose-response relationships were also evaluated for PCa risk. RESULTS: Forty-two studies were included in the analysis, which included 43 851 cases of PCa reported from 692 012 participants. Both dietary intake (RR=0.88, 95% CI: 0.78-0.98, P=0.017) and circulating concentrations (RR=0.88, 95% CI: 0.79-0.98, P=0.019) of lycopene were significantly associated with reduced PCa risk. Sensitivity analyses within the dose-response analysis further revealed a significant linear dose-response for dietary lycopene and PCa risk such that PCa decreased by 1% for every additional 2 mg of lycopene consumed (P=0.026). Additionally, PCa risk decreased by 3.5 to 3.6% for each additional 10 µgdl-1 of circulating lycopene in the linear and nonlinear models respectively (plinear=0.004, pnonlinear=0.006). While there were no associations between lycopene and advanced PCa, there was a trend for protection against PCa aggressiveness (RR=0.74, 95% CI: 0.55-1.00, P=0.052). CONCLUSIONS: Our data demonstrate that higher dietary and circulating lycopene concentrations are inversely associated with PCa risk. This was accompanied by dose-response relationships for dietary and circulating lycopene. However, lycopene was not associated with a reduced risk of advanced PCa. Further studies are required to determine the mechanisms underlying these associations.

Metabolic rewiring in melanoma.

Oncogene-driven metabolic rewiring is an adaptation to low nutrient and oxygen conditions in the tumor microenvironment that enables cancer cells of diverse origin to hyperproliferate. Aerobic glycolysis and enhanced reliance on glutamine utilization are prime examples of such rewiring. However, tissue of origin as well as specific genetic and epigenetic changes determines gene expression profiles underlying these metabolic alterations in specific cancers. In melanoma, activation of the mitogen-activated protein kinase (MAPK) pathway driven by mutant BRAF or NRAS is a primary cause of malignant transformation. Activity of the MAPK pathway, as well as other factors, such as HIF1α, Myc and MITF, are among those that control the balance between non-oxidative and oxidative branches of central carbon metabolism. Here, we discuss the nature of metabolic alterations that underlie melanoma development and affect its response to therapy.

Predicting the composition and formation of solid products in lithium-sulfur batteries by using an experimental phase diagram.

Lithium-sulfur batteries discharge via the transformation of solid sulfur to solid lithium sulfide via the formation of several polysulfide species that have only been observed in solution. Reported here is the first experimental phase diagram of a S8-Li2S-electrolyte system, which is shown to be a practical tool to determine the solution composition and formation of solid (S8 and Li2S) phases in lithium-sulfur batteries. The phase diagram is constructed by the combination of measurements of the total sulfur concentration [S]T and average oxidation state (Sm-) of polysulfide solutions prepared by reaction of S8 and Li2S. The phase diagram is used to predict the equilibrium discharge/charge profile of lithium-sulfur batteries as a function of the amount of electrolyte and the onset of precipitation and dissolution of solid products. High energy batteries should operate with a minimum amount of electrolyte, where both solid S8 and Li2S will be present during most of the charge and discharge of the cell, in which case we predict the observation of only one voltage plateau, instead of the two voltage plateaus commonly reported.

Exogenous Carbohydrate Reduces Cortisol Response from Combined Mental and Physical Stress.

Combined mental and physical stress is associated with exacerbated cortisol production which may increase risk for the progression of cardiovascular disease in individuals working in high-stress occupations (e.g., firefighters, military personnel, etc.). Carbohydrate (CHO) ingestion prior to physical stress may attenuate cortisol concentrations. This project was the first to investigate the effect of CHO ingestion on cortisol response from combined mental and physical stress. 16 men 21-30 years old were randomly assigned a 6.6% CHO beverage or non-CHO control 15 min prior to performing a dual-concurrent-stress challenge. This consisted of physical stress (i.e., steady state exercise) combined with computerized mental challenges. Blood was sampled 70, 40, and 15 min before exercise, immediately at onset of exercise, 10, 20, 30, 35 min during exercise, and 15, 30, 45, and 60 min after exercise. There was a significant main effect for treatment regarding mean cortisol concentrations (F=5.30, P=0.0219). The total area under curve for cortisol was less when CHO was ingested (T7=4.07, P=0.0048). These findings suggest that CHO ingestion immediately prior to combined mental and physical stress may attenuate cortisol responses.

Sustainability assessment of electrokinetic bioremediation compared with alternative remediation options for a petroleum release site.

Sustainable management practices can be applied to the remediation of contaminated land to maximise the economic, environmental and social benefits of the process. The Sustainable Remediation Forum UK (SuRF-UK) have developed a framework to support the implementation of sustainable practices within contaminated land management and decision making. This study applies the framework, including qualitative (Tier 1) and semi-quantitative (Tier 2) sustainability assessments, to a complex site where the principal contaminant source is unleaded gasoline, giving rise to a dissolved phase BTEX and MTBE plume. The pathway is groundwater migration through a chalk aquifer and the receptor is a water supply borehole. A hydraulic containment system (HCS) has been installed to manage the MTBE plume migration. The options considered to remediate the MTBE source include monitored natural attenuation (MNA), air sparging/soil vapour extraction (AS/SVE), pump and treat (PT) and electrokinetic-enhanced bioremediation (EK-BIO). A sustainability indictor set from the SuRF-UK framework, including priority indicator categories selected during a stakeholder engagement workshop, was used to frame the assessments. At Tier 1 the options are ranked based on qualitative supporting information, whereas in Tier 2 a multi-criteria analysis is applied. Furthermore, the multi-criteria analysis was refined for scenarios where photovoltaics (PVs) are included and amendments are excluded from the EK-BIO option. Overall, the analysis identified AS/SVE and EK-BIO as more sustainable remediation options at this site than either PT or MNA. The wider implications of this study include: (1) an appraisal of the management decision from each Tier of the assessment with the aim to highlight areas for time and cost savings for similar assessments in the future; (2) the observation that EK-BIO performed well against key indicator categories compared to the other intensive treatments; and (3) introducing methods to improve the sustainability of the EK-BIO treatment design (such as PVs) did not have a significant effect in this instance.

Metrological challenges for measurements of key climatological observables: Oceanic salinity and pH, and atmospheric humidity. Part 1: Overview.

Water in its three ambient phases plays the central thermodynamic role in the terrestrial climate system. Clouds control Earth's radiation balance, atmospheric water vapour is the strongest "greenhouse" gas, and non-equilibrium relative humidity at the air-sea interface drives evaporation and latent heat export from the ocean. On climatic time scales, melting ice caps and regional deviations of the hydrological cycle result in changes of seawater salinity, which in turn may modify the global circulation of the oceans and their ability to store heat and to buffer anthropogenically produced carbon dioxide. In this paper, together with three companion articles, we examine the climatologically relevant quantities ocean salinity, seawater pH and atmospheric relative humidity, noting fundamental deficiencies in the definitions of those key observables, and their lack of secure foundation on the International System of Units, the SI. The metrological histories of those three quantities are reviewed, problems with their current definitions and measurement practices are analysed, and options for future improvements are discussed in conjunction with the recent seawater standard TEOS-10. It is concluded that the International Bureau of Weights and Measures, BIPM, in cooperation with the International Association for the Properties of Water and Steam, IAPWS, along with other international organisations and institutions, can make significant contributions by developing and recommending state-of-the-art solutions for these long standing metrological problems in climatology.

Metrological challenges for measurements of key climatological observables, Part 4: Atmospheric relative humidity.

Water in its three ambient phases plays the central thermodynamic role in the terrestrial climate system. Clouds control Earth's radiation balance, atmospheric water vapour is the strongest "greenhouse" gas, and non-equilibrium relative humidity at the air-sea interface drives evaporation and latent heat export from the ocean. In this paper, we examine the climatologically relevant atmospheric relative humidity, noting fundamental deficiencies in the definition of this key observable. The metrological history of this quantity is reviewed, problems with its current definition and measurement practice are analysed, and options for future improvements are discussed in conjunction with the recent seawater standard TEOS-10. It is concluded that the International Bureau of Weights and Measures, (BIPM), in cooperation with the International Association for the Properties of Water and Steam, IAPWS, along with other international organisations and institutions, can make significant contributions by developing and recommending state-of-the-art solutions for this long standing metrological problem, such as are suggested here.

Distinguishing between anti-platelet factor 4/heparin antibodies that can and cannot cause heparin-induced thrombocytopenia.

BACKGROUND: Many patients exposed to heparin develop antibodies against platelet factor 4 (PF4) and heparin, yet only those antibodies that activate platelets cause heparin-induced thrombocytopenia (HIT). Patients who produce anti-PF4/heparin antibodies without developing HIT either have antibodies that do not cause platelet activation or produce pathogenic antibodies at levels that are insufficient to cause HIT. Understanding the differences between anti-PF4/heparin antibodies with and without HIT will improve test methods and reduce overdiagnosis. AIMS: To investigate the presence of low levels of platelet-activating antibodies in patients investigated for HIT who had anti-PF4/heparin antibodies but failed to cause platelet activation in the (14) C-serotonin release assay (SRA). MATERIALS/METHODS: We developed a platelet activation assay similar to the SRA using exogenous PF4 without added heparin (PF4-SRA). This assay was able to detect low levels of platelet-activating antibodies. We used this PF4-SRA to test for platelet-activating antibodies in patients investigated for HIT. RESULTS: The PF4-SRA detected platelet-activating antibodies in seven (100%) of seven SRA-positive sera even after the samples were diluted until they were no longer positive in the standard SRA. Platelet-activating antibodies were detected in 14 (36%) of 39 patients who had anti-PF4/heparin antibodies but tested negative in the SRA and did not have clinical HIT. The clinical diagnosis of HIT was confirmed by chart review and concordant with the SRA results. CONCLUSIONS: A subset of heparin-treated patients produce subthreshold levels of platelet-activating anti-PF4/heparin antibodies that do not cause HIT. An increase in the titer of these pathogenic antibodies, along with permissive clinical conditions, could lead to HIT.

Electrokinetic-enhanced bioremediation of organic contaminants: a review of processes and environmental applications.

There is current interest in finding sustainable remediation technologies for the removal of contaminants from soil and groundwater. This review focuses on the combination of electrokinetics, the use of an electric potential to move organic and inorganic compounds, or charged particles/organisms in the subsurface independent of hydraulic conductivity; and bioremediation, the destruction of organic contaminants or attenuation of inorganic compounds by the activity of microorganisms in situ or ex situ. The objective of the review is to examine the state of knowledge on electrokinetic bioremediation and critically evaluate factors which affect the up-scaling of laboratory and bench-scale research to field-scale application. It discusses the mechanisms of electrokinetic bioremediation in the subsurface environment at different micro and macroscales, the influence of environmental processes on electrokinetic phenomena and the design options available for application to the field scale. The review also presents results from a modelling exercise to illustrate the effectiveness of electrokinetics on the supply electron acceptors to a plume scale scenario where these are limiting. Current research needs include analysis of electrokinetic bioremediation in more representative environmental settings, such as those in physically heterogeneous systems in order to gain a greater understanding of the controlling mechanisms on both electrokinetics and bioremediation in those scenarios.

FcγRIIa proteolysis as a diagnostic biomarker for heparin-induced thrombocytopenia.

BACKGROUND: A significant challenge in the management of heparin-induced thrombocytopenia (HIT) patients is making a timely and accurate diagnosis. The readily available enzyme immunoassays (EIAs) have low specificities. In contrast, platelet activation assays have higher specificities, but they are technically demanding and not widely available. In addition, ~ 10% of samples referred for HIT testing are initially classified as indeterminate by the serotonin release assay (SRA), which further delays accurate diagnosis. HIT is characterized by platelet activation, which leads to FcγRIIa proteolysis. This raises the possibility that identification of the proteolytic fragment of FcγRIIa could serve as a surrogate marker for HIT. OBJECTIVES: To determine the specificity of platelet FcγRIIa proteolysis induced by sera from patients with HIT, and to correlate the results with those of the SRA. METHODS/PATIENTS: Sera from HIT patients and control patients with other thrombocytopenic/prothrombotic disorders were tested for their ability to proteolyse FcγRIIa. The results were correlated with anti-platelet factor 4 (PF4)/heparin antibodies (EIA), and heparin-dependent platelet activation (SRA). RESULTS: Only HIT patient samples (20/20) caused heparin-dependent FcγRIIa proteolysis, similar to what was shown by the SRA. None of the samples from the other patient groups or hospital controls caused FcγRIIa proteolysis. Among nine additional samples that tested indeterminate in the SRA, FcγRIIa proteolysis resolved five samples that had a positive anti-PF4/heparin EIA result; three had no FcγRIIa proteolysis, and two were shown to have heparin-dependent FcγRIIa proteolysis CONCLUSIONS: This study suggests that heparin-dependent FcγRIIa proteolysis is at least as specific as the SRA for the diagnosis of HIT.

A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia.

BACKGROUND: Drug-induced immune thrombocytopenia (DITP) can be confirmed by the demonstration of drug-dependent platelet antibodies in vitro; however, laboratory testing is not readily accessible and test methods are not standardized. OBJECTIVE: To identify drugs with the strongest evidence for causing DITP based on clinical and laboratory criteria. PATIENTS/METHODS: We developed a grading system to evaluate the quality of DITP laboratory testing. The 'DITP criteria' were: (i) Drug (or metabolite) was required for the reaction in vitro; (ii) Immunoglobulin binding was demonstrated; (iii) Two or more laboratories obtained positive results; and (iv) Platelets were the target of immunoglobulin binding. Laboratory diagnosis of DITP was considered definite when all criteria were met and probable when positive results were reported by only one laboratory. Two authors applied the DITP criteria to published reports of each drug identified by systematic review. Discrepancies were independently adjudicated. RESULTS: Of 153 drugs that were clinically implicated in thrombocytopenic reactions, 72 (47%) were associated with positive laboratory testing. Of those, 16 drugs met criteria for a definite laboratory diagnosis of DITP and thus had the highest probability of causing DITP. Definite drugs were: quinine, quinidine, trimethoprim/sulfamethoxazole, vancomycin, penicillin, rifampin, carbamazepine, ceftriaxone, ibuprofen, mirtazapine, oxaliplatin and suramin; the glycoprotein IIbIIIa inhibitors abciximab, tirofiban and eptifibatide; and heparin. CONCLUSIONS: We identified drugs with the strongest evidence for an association with immune thrombocytopenia. This list may be helpful for ranking potential causes of thrombocytopenia in a given patient.

Effect of fertilizer formulation and bioaugmentation on biodegradation and leaching of crude oils and refined products in soils.

The effects of soil characteristics and oil types as well as the efficacy of two fertilizer formulations and three bioaugmentation packages in improving the bioremediation of oil-contaminated soils were assessed as a means of ex situ treatment selection and optimization through seven laboratory microcosm studies. The influence of bioremediation on leaching of oil from the soil was also investigated. The studies demonstrated the benefits ofbiostimulation to overcome nutrient limitation, as most of the soils were nutrient depleted. The application of both liquid and pelleted slow-release N and P fertilizers increased both the hydrocarbon biodegradation rates (by a factor of 1.4 to 2.9) and the percentage of hydrocarbon mass degraded (by > 30% after 12 weeks and 80% after 37 weeks), when compared with the unamended soils. Slow-release fertilizers can be particularly useful when multiple liquid applications are not practical or cost-effective. Bioaugmentation products containing inoculum plus fertilizer also increased biodegradation by 20% to 37% compared with unamended biotic controls; however, there was no clear evidence of additional benefits due to the inocula, compared with fertilizer alone. Therefore biostimulation is seen as the most cost-effective bioremediation strategy for contaminated soils with the levels of crude oil and refined products used in this study. However, site-specific considerations remain essential for establishing the treatability of oil-contaminated soils.

The effect of co-impregnated acids on the performance of Zn-based broad spectrum respirator carbons.

Impregnated activated carbons (IACs) that are used in multi-gas respirator applications usually contain copper and/or zinc impregnants. Co-impregnating with properly selected acids can improve the distribution of the metallic impregnant on the carbon and improve the gas adsorption capacity of the IAC. In this work a comparative study of some common acids co-impregnated with a zinc nitrate (Zn(NO(3))(2)) precursor is performed. The IACs were heated in an inert atmosphere at temperatures which promoted the thermal decomposition of Zn(NO(3))(2) to zinc oxide (ZnO). The gas adsorption properties of the IACs were tested using ammonia (NH(3)), sulphur dioxide (SO(2)) and hydrogen cyanide (HCN) challenge gases. Powder X-ray diffraction (XRD) was used to identify the impregnant species present after heating and to study impregnant distribution. Gravimetric analysis was used to determine the impregnant loading, and help to identify the impregnant species after heating. The interactions between the co-impregnated acid and Zn(NO(3))(2) precursor during heating are discussed. The relationship between impregnant species and gas adsorption capacity is discussed.

The effect of heating temperature and nitric acid treatments on the performance of Cu- and Zn-based broad spectrum respirator carbons.

Impregnated activated carbons (IACs) that are used in broad spectrum gas mask applications have historically contained copper and/or zinc impregnants. The addition of an oxidizing agent, such as nitric acid (HNO(3)) can be useful in distributing the metallic impregnants uniformly on the activated carbon substrate. In this work, we study IACs prepared from copper nitrate (Cu(NO(3))(2)) and zinc nitrate (Zn(NO(3))(2)) precursors as a function of HNO(3) content present in the impregnating solution and as a function of heating temperature. The gas adsorption capacity of the IACs was determined by dynamic flow testing using sulfur dioxide (SO(2)), ammonia (NH(3)), hydrogen cyanide (HCN) and cyclohexane (C(6)H(12)) challenge gases under dry and humid conditions. The thermal decomposition and distribution of the impregnant on the activated carbon substrate is studied using X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermal analysis techniques. Relationships between gas adsorption capacity, impregnant distribution and the species of surface impregnants are discussed.