Human Plasma Lipid Modulation in Schistosomiasis Mansoni Depends on Apolipoprotein E Polymorphism

Background

Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis.

Methodology/Principal Findings

Blood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C was increased (10% higher; P = 0.0136). Frequency of the common alleles, ε2, ε3 and ε4, was similar (P = 0.3568) between controls (n = 108) and patients (n = 84), implying that APOE genotype did not affect susceptibility to the advanced stage of schistosomiasis. Nevertheless, while patient TC and LDL-C levels were significantly reduced for each allele (except TC in ε2 patients), changes in HDL-C and triglycerides were noted only for the less common ε2 and ε4 alleles. The most striking finding, however, was that accepted regulation of plasma lipid levels by APOE genotype was disrupted by schistosomiasis. Thus, while ε2 controls had higher TC and LDL-C than ε3 carriers, these parameters were lower in ε2 versus ε3 patients. Similarly, the inverse relationship of TG levels in controls (ε2>ε3>ε4) was absent in patients (ε2 or ε4>ε3), and the increase in HDL-C of ε2 or ε4 patients compared to ε3 patients was not seen in the control groups.

Conclusion/Significance

We confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat associated morbidities.     

The Influence of the Environment and Clothing on Human Exposure to Ultraviolet Light

Objection

The aim of this study is to determine the effect of clothing and the environment on human exposure to ultraviolet light.

Methods

The ultraviolet (ultraviolet A and ultraviolet B) light intensity was measured, and air quality parameters were recorded in 2014 in Beijing, China. Three types of clothing (white polyester cloth, pure cotton white T-shirt, and pure cotton black T-shirt) were individually placed on a mannequin. The ultraviolet (ultraviolet A and ultraviolet B) light intensities were measured above and beneath each article of clothing, and the percentage of ultraviolet light transmission through the clothing was calculated.

Results

(1) The ultraviolet light transmission was significantly higher through white cloth than through black cloth; the transmission was significantly higher through polyester cloth than through cotton. (2) The weather significantly influenced ultraviolet light transmission through white polyester cloth; transmission was highest on clear days and lowest on overcast days (ultraviolet A: P=0.000; ultraviolet B: P=0.008). (3) Air quality parameters (air quality index and particulate matter 2.5 and 10) were inversely related to the ultraviolet light intensity that reached the earth’s surface. Ultraviolet B transmission through white polyester cloth was greater under conditions of low air pollution compared with high air pollution.

Conclusion

Clothing color and material and different types of weather affected ultraviolet light transmission; for one particular cloth, the transmission decreased with increasing air pollution.     

Analysis of Complex Patterns of Human Exposure and Immunity to Schistosomiasis mansoni: The Influence of Age,Sex, Ethnicity and IgE

Background

Numerous factors may influence Schistosoma infection intensity and prevalence within endemic communities, including exposure-related factors such as local environment and behaviour, and factors relating to susceptibility to infection such as immunology and genetics. While animal studies performed in the laboratory can be tightly controlled, human populations are highly heterogeneous, varying according to demographic characteristics, genetic background and exposure to infection. The heterogeneous nature of human water contact behaviour in particular makes it difficult to distinguish between a lack of cercarial exposure and reduced susceptibility to infection as the cause for low levels of infection in the field.

Methods and Principal Findings

In this study we investigate risk factors for Schistosoma mansoni infection in a rural Ugandan fishing community receiving treatment as part of a multi-disciplinary longitudinal reinfection study. More specifically, we examine the influence that age, sex and ethnic background have on susceptibility to reinfection after anti-helminth drug treatment, but use individual estimates of cercarial exposure and multivariable methods in an attempt to remove noise created by environmental and behavioural heterogeneities. We then investigate whether schistosome-specific IgE immune responses could account for any remaining variations in susceptibility to reinfection. Our findings suggest that observed ethnic- and sex-related variations in S. mansoni reinfection were due to variations in cercarial exposure, as opposed to biological differences in susceptibility to infection. Age-related differences in reinfection were not explained by exposure, however, and appeared linked to the balance of IgE and IgG₄ to the tegumental antigen SmTAL1 (formerly Sm22.6), which itself was significantly related to resistance to reinfection.

Conclusions

This study highlights the benefit of taking a multidisciplinary approach in complex field settings; it allows the ecology of a population to be understood and thus more robust conclusions to be made.     

IL-10R Blockade during Chronic Schistosomiasis Mansoni Results in the Loss of B Cells from the Liver and the Development of Severe Pulmonary Disease

In schistosomiasis patients, parasite eggs trapped in hepatic sinusoids become foci for CD4⁺ T cell-orchestrated granulomatous cellular infiltrates. Since the immune response is unable to clear the infection, the liver is subjected to ongoing cycles of focal inflammation and healing that lead to vascular obstruction and tissue fibrosis. This is mitigated by regulatory mechanisms that develop over time and which minimize the inflammatory response to newly deposited eggs. Exploring changes in the hepatic inflammatory infiltrate over time in infected mice, we found an accumulation of schistosome egg antigen-specific IgG1-secreting plasma cells during chronic infection. This population was significantly diminished by blockade of the receptor for IL-10, a cytokine implicated in plasma cell development. Strikingly, IL-10R blockade precipitated the development of portal hypertension and the accumulation of parasite eggs in the lungs and heart. This did not reflect more aggressive Th2 cell responsiveness, increased hepatic fibrosis, or the emergence of Th1 or Th17 responses. Rather, a role for antibody in the prevention of severe disease was suggested by the finding that pulmonary involvement was also apparent in mice unable to secrete class switched antibody. A major effect of anti-IL-10R treatment was the loss of a myeloid population that stained positively for surface IgG1, and which exhibited characteristics of regulatory/anti-inflammatory macrophages. This finding suggests that antibody may promote protective effects within the liver through local interactions with macrophages. In summary, our data describe a role for IL-10-dependent B cell responses in the regulation of tissue damage during a chronic helminth infection.     

Evidence that Life History Characteristics of Wild Birds Influence Infection and Exposure to Influenza A Viruses

We report on life history characteristics, temporal, and age-related effects influencing the frequency of occurrence of avian influenza (AI) viruses in four species of migratory geese breeding on the Yukon-Kuskokwim Delta, Alaska. Emperor geese (Chen canagica), cackling geese (Branta hutchinsii), greater white-fronted geese (Anser albifrons), and black brant (Branta bernicla), were all tested for active infection of AI viruses upon arrival in early May, during nesting in June, and while molting in July and August, 2006–2010 (n = 14,323). Additionally, prior exposure to AI viruses was assessed via prevalence of antibodies from sera samples collected during late summer in 2009 and 2010. Results suggest that geese are uncommonly infected by low pathogenic AI viruses while in Alaska. The percent of birds actively shedding AI viruses varied annually, and was highest in 2006 and 2010 (1–3%) and lowest in 2007, 2008, and 2009 (<0.70%). Contrary to findings in ducks, the highest incidence of infected birds was in late spring when birds first arrived from staging and wintering areas. Despite low prevalence, most geese were previously exposed to AI viruses, as indicated by high levels of seroprevalence during late summer (47%–96% across species; n = 541). Seroprevalence was >95% for emperor geese, a species that spends part of its life cycle in Asia and is endemic to Alaska and the Bering Sea region, compared to 40–60% for the other three species, whose entire life cycles are within the western hemisphere. Birds <45 days of age showed little past exposure to AI viruses, although antibodies were detected in samples from 5-week old birds in 2009. Seroprevalence of known age black brant revealed that no birds <4 years old had seroconverted, compared to 49% of birds ≥4 years of age.     

Light History Influences the Response of Fluvial Biofilms to Zn Exposure

Fluvial biofilms are subject to multistress situations in natural ecosystems, such as the co‐occurrence of light intensity changes and metal toxicity. However, studies simultaneously addressing both factors are rare. This study evaluated in microcosm conditions the relationship between short‐term light intensity changes and Zn toxicity on fluvial biofilms with long‐term photoacclimation to different light conditions. Biofilms that had long‐term photoacclimation to 25 μmol photons · m^?2 · s^?1 (low light [LL] biofilms), 100 μmol photons · m^?2 · s^?1 (medium light [ML] biofilms), and 500 μmol photons · m^?2 · s^?1 (high light [HL] biofilms) were characterized by different structural (Chlorophyll‐a [Chl‐a], total biomass‐AFDW, EPS, algal groups, and diatom taxonomy) and physiological attributes (ETR‐I curves and photosynthetic pigments). HL biofilms showed higher light saturation intensity and a higher production of xanthophylls than LL biofilms. In contrast, LL biofilms had many structural differences; a higher proportion of diatoms and lower AFDW and EPS contents than ML and HL biofilms. A clear effect of light intensity changes on Zn toxicity was also demonstrated. Zn toxicity was enhanced when a sudden increase in light intensity also occurred, mainly with LL biofilms, causing higher inhibition of both the Φ′_PSII and the Φ_PSII. A decoupling of NPQ from de‐epoxidation reaction (DR) processes was also observed, indicating substantial damage to photoprotective mechanisms functioning in biofilms (i.e., xanthophyll cycle of diatoms) due to Zn toxicity. This study highlights the need to take into account environmental stress (e.g., light intensity changes) to better assess the environmental risks of chemicals (e.g., metals).     

Influence of Exposure to Single versus Multiple Toxins of Bacillus thuringiensis subsp. israelensis on Development of Resistance in the Mosquito Culex quinquefasciatus (Diptera: Culicidae)

The impending widespread use of transgenic crop plants encoding a single insecticidal toxin protein of Bacillus thuringiensis has focused attention on the perceived risk of rapid selection of resistance in target insects. We have used Bacillus thuringiensis subsp. israelensis toxins as a model system and determined the speed and magnitude of evolution of resistance in colonies of the mosquito Culex quinquefasciatus during selection for 28 consecutive generations with single or multiple toxins. The parental strain was synthesized by combining approximately 500 larvae from each of 19 field collections obtained from the states of California, Oregon, Louisiana, and Tennessee. At least 10,000 larvae were selected in each generation of each line at an average mortality level of 84%. The susceptibilities of the parental and selected lines were compared in parallel tests in every third generation by using fresh suspensions of toxin powders. The normal toxin complement of B. thuringiensis subsp. israelensis consists of four toxins, CryIVA, CryIVB, CryIVD, and CytA. Resistance became evident first in the line that was selected with a single toxin (CryIVD), attaining the highest level (resistance ratio [RR], >913 at 95% lethal concentration) by generation F(inf28) when the study was completed. Resistance evolved more slowly and to a lower level (RR, >122 by F(inf25)) in the line selected with two toxins (CryIVA+CryIVB) and lower still (RR, 91 by F(inf28)) in the line selected with three toxins (CryIVA+CryIVB+ CryIVD). Resistance was remarkably low (RR, 3.2) in the line selected with all four toxins. The results reveal the importance of the full complement of toxins found in natural populations of B. thuringiensis subsp. israelensis as an effective approach to resistance management.     

Effects of Ozone Exposure on Resistance of Wheat Genotypes to Pyrenophora tritici-repentis

Three spring wheat genotypes, susceptible, moderately resistant or resistant to Pyrenophora tritici-repentis (tan spot fungus) were exposed to charcoal-filtered air and to approx. 80, 160, 240 (g m^?3 ozone for five consecutive days (7 h per day). Visible leaf injury on seedling plants (three-leaf stage) was only observed after fumigation with 160 or 240 (g m^?3 O₃. Amount of injury was four-fold and 10-fold on the susceptible genotype when compared to resistant or moderately resistant genotype at the two highest concentration of ozone, respectively. Genotypic differences to O₃ tolerance were detected at the seedling growth stage (three-leaf stage) and flowering stage but not at the stem elongation stage. A significant increase in tan spot lesion area was observed only on O₃ predisposed second top most leaves of the susceptible genotype at all the three levels of ozone. Predisposition did not enhance tan spot development in resistant and moderately resistant genotypes. In a test with 12 wheat genotypes, a highly significant positive correlation (r = 0· 986, p < 0· 0001) was observed between ozone sensitivity (percent leaf area damaged due to 240 (g m^?3 ozone exposure) and tan spot development (mm² lesion area) following inoculation with P. tritici-repentis. It indicates that wheat genotypes resistant to the tan spot fungus might be tolerant to ozone damage.     

Human Health Risks of Exposure to Estuary Waters

The convergence of data strongly suggests the presence of an estuary-related toxin (pfiesteria piscicida or similar organism) that produces adverse human health effects. A diversity of methodological approaches is necessary to answer important preliminary questions about the clinical syndrome, its immediate public health risk, prioritize ongoing scientific studies and direct future research. These include intensive case and multiple-case studies; case-control studies; and epidemiological cohort studies that are conducted in parallel with basic science research. Findings to date indicate the estuary-related toxin is neurotoxic to persons with high levels of exposure. The most pronounced effects are neurocognitive and include problems with complex attention, memory, and visual contrast sensitivity. The disturbances are detectable with standard neuropsychological procedures. Although the most debilitating effects are reversible, the possibility of a sensitization phenomenon exists. The Estuary Clinical Syndrome joins other well-documented outbreaks of human illness for which the specific toxin agent remains to be identified. The methodological approaches for identifying and investigating this newly identified syndrome in the absence of a known toxin may provide a model for the early investigation of other emerging toxins and related illnesses.     

Influence of Fuels,Weather and the Built Environment on the Exposure of Property to Wildfire

Wildfires can pose a significant risk to people and property. Billions of dollars are spent investing in fire management actions in an attempt to reduce the risk of loss. One of the key areas where money is spent is through fuel treatment – either fuel reduction (prescribed fire) or fuel removal (fuel breaks). Individual treatments can influence fire size and the maximum distance travelled from the ignition and presumably risk, but few studies have examined the landscape level effectiveness of these treatments. Here we use a Bayesian Network model to examine the relative influence of the built and natural environment, weather, fuel and fuel treatments in determining the risk posed from wildfire to the wildland-urban interface. Fire size and distance travelled was influenced most strongly by weather, with exposure to fires most sensitive to changes in the built environment and fire parameters. Natural environment variables and fuel load all had minor influences on fire size, distance travelled and exposure of assets. These results suggest that management of fuels provided minimal reductions in risk to assets and adequate planning of the changes in the built environment to cope with the expansion of human populations is going to be vital for managing risk from fire under future climates.     

Exposure of the Human Body to Professional and Domestic Induction Cooktops Compared to the Basic Restrictions

We investigated whether domestic and professional induction cooktops comply with the basic restrictions defined by the International Commission on Non‐Ionizing Radiation Protection (ICNIRP). Based on magnetic field measurements, a generic numerical model of an induction cooktop was derived in order to model user exposure. The current density induced in the user was simulated for various models and distances. We also determined the exposure of the fetus and of young children. While most measured cooktops comply with the public exposure limits at the distance specified by the International Electrotechnical Commission (standard IEC 62233), the majority exceeds them at closer distances, some of them even the occupational limits. The maximum current density in the tissue of the user significantly exceeds the basic restrictions for the general public, reaching the occupational level. The exposure of the brains of young children reaches the order of magnitude of the limits for the general public. For a generic worst‐case cooktop compliant with the measurement standards, the current density exceeds the 1998 ICNIRP basic restrictions by up to 24 dB or a factor of 16. The brain tissue of young children can be overexposed by 6 dB or a factor of 2. The exposure of the tissue of the central nervous system of the fetus can exceed the limits for the general public if the mother is exposed at occupational levels. This demonstrates that the methodology for testing induction cooktops according to IEC 62233 contradicts the basic restrictions. This evaluation will be extended considering the redefined basic restrictions proposed by the ICNIRP in 2010. Bioelectromagnetics 33:695–705, 2012. © 2012 Wiley Periodicals, Inc.     

Survival and Heat Resistance of Listeria monocytogenes after Exposure to Alkali and Chlorine

A strain of Listeria monocytogenes isolated from a drain in a food-processing plant was demonstrated, by determination of D values, to be more resistant to the lethal effect of heat at 56 or 59°C following incubation for 45 min in tryptose phosphate broth (TPB) at pH 12.0 than to that of incubation for the same time in TPB at pH 7.3. Cells survived for at least 6 days when they were suspended in TPB at pHs 9.0, 10.0, and 11.0 and stored at 4 or 21°C. Cells of L. monocytogenes incubated at 37°C for 45 min and then stored for 48 or 144 h in TPB at pH 10.0 were more resistant to heat treatment at 56°C than were cells stored in TPB at pH 7.3. The alkaline-stress response in L. monocytogenes may induce resistance to otherwise lethal thermal-processing conditions. Treatment of cells in 0.05 M potassium phosphate buffer (pH 7.00 ± 0.05) containing 2.0 or 2.4 mg of free chlorine per liter reduced populations by as much as 1.3 log₁₀ CFU/ml, while treatment with 6.0 mg of free chlorine per liter reduced populations by as much as 4.02 log₁₀ CFU/ml. Remaining subpopulations of chlorine-treated cells exhibited some injury, and cells treated with chlorine for 10 min were more sensitive to heating at 56°C than cells treated for 5 min. Contamination of foods by L. monocytogenes cells that have survived exposure to processing environments ineffectively cleaned or sanitized with alkaline detergents or disinfectants may have more severe implications than previously recognized. Alkaline-pH-induced cross-protection of L. monocytogenes against heat has the potential to enhance survival in minimally processed as well as in heat-and-serve foods and in foods on holding tables, in food service facilities, and in the home. Cells surviving exposure to chlorine, in contrast, are more sensitive to heat; thus, the effectiveness of thermal processing in achieving desired log₁₀-unit reductions is not compromised in these cells.     

Influence of Statolon on Resistance of Mice to Influenza

Various interferon inducers are known to elicit protection against lethal or infecting doses of certain viral agents. Because of the relatively high morbidity rate of influenza and its seasonal occurrence, we wished to determine whether statolon-induced interferon might be effective in controlling this disease. Mice were treated intraperitoneally with statolon and challenged with influenza A(2) virus by the intranasal route. Although interferon was present in the serum at the time of virus administration, no change in mortality rate was observed. There was, however, a significant increase in the mean survival time of treated animals. Similar results were obtained when Newcastle disease virus was used as the interferon inducer. To determine the effect of the route of challenge, other mice were treated with statolon or Newcastle disease virus and inoculated with mengovirus by the intranasal or intraperitoneal route. The results demonstrated that the treated mice were protected to similar degree against challenge by either route. It is suggested that the relative ineffectiveness of interferon in protecting mice against influenza is due to an intrinsic characteristic of the virus itself rather than the type of interferon induced or the route of virus challenge.     

Metabolic Changes Reveal the Development of Schistosomiasis in Mice

Schistosomiasis is a parasitic zoonosis caused by small trematode worms called schistosomes, amongst which Schistosoma japonicum (S. japonicum) is endemic in Asia. In order to understand the schistosome-induced changes in the host metabolism so as to facilitate early diagnosis of schistosomiasis, we systematically investigated the dynamic metabolic responses of mice biofluids and liver tissues to S. japonicum infection for five weeks using ¹H NMR spectroscopy in conjunction with multivariate data analysis. We were able to detect schistosomiasis at the third week post-infection, which was one week earlier than “gold standard” methods. We found that S. japonicum infection caused significant elevation of urinary 3-ureidopropionate, a uracil catabolic product, and disturbance of lipid metabolism, stimulation of glycolysis, depression of tricarboxylic acid cycle and disruption of gut microbiota regulations. We further found that the changes of 3-ureidopropionate and overall metabolic changes in both urinary and plasma samples were closely correlated with the time-course of disease progression. Furthermore, such changes together with liver tissue metabonome were clearly associated with the worm-burdens. These findings provided more insightful understandings of host biological responses to the infection and demonstrated that metabonomic analysis is potentially useful for early detection of schistosomiasis and comprehension of the mechanistic aspects of disease progression.     

Recent Advances in the Characterization of Genetic Factors Involved in Human Susceptibility to Infection by Schistosomiasis

Human resistance to infection by schistosomes is associated to a strong Th2 immune. However a persistent Th2 response can cause severe kidney and liver disease in human. In this review, we mainly focused on the control of infection levels caused by schistosomes. Several experimental models allowed us to better understand the immunological mechanisms of the host against schistosome infection. High IgE and eosinophil levels are associated with resistance to infection by schistosomes and this effect is counterbalanced by IgG4. IgE and eosinophils are highly dependent on IL-4, IL-13, and Il-5, which are three main Th2 cytokines. We also examined the genetic factors involved in human susceptibility to infection by schistosomiasis. Infection levels are mainly regulated by a major locus SM1, in 5q31-q33 region, which contains the genes encoding for the IL-4, IL-13, and Il-5 cytokines. An association between an IL13 polymorphism, rs1800925, and infection levels has been shown. This polymorphism synergistically acts with another polymorphism (rs324013) in the STAT6 gene, encoding for the signal transducer of the IL13 pathway. This pathway has also been involved in atopic disorders. As helminthiasis, atopy is the result of aberrant Th2 cytokine response to allergens, with an increased production of IL-4, IL-13, Il-9 and Il-5, with high amounts of allergen-specific and total IgE and eosinophilia. However, the Th2 immune response is protective in helminthiasis but aggravating in atopic disorders. Several studies reported interplay between helminthic infections and allergic reactions. The different results are discussed here.     

Review of Information Resources to Support Human Exposure Assessment Models

Efforts to model human exposures to chemicals are growing more sophisticated and encompass increasingly complex exposure scenarios. The scope of such analyses has increased, growing from assessments of single exposure pathways to complex evaluations of aggregate or cumulative chemical exposures occurring within a variety of settings and scenarios. In addition, quantitative modeling techniques have evolved from simple deterministic analyses using single point estimates for each necessary input parameter to more detailed probabilistic analyses that can accommodate distributions of input parameters and assessment results. As part of an overall effort to guide development of a comprehensive framework for modeling human exposures to chemicals, available information resources needed to derive input parameters for human exposure assessment models were compiled and critically reviewed. Ongoing research in the area of exposure assessment parameters was also identified. The results of these efforts are summarized and other relevant information that will be needed to apply the available data in a comprehensive exposure model is discussed. Critical data gaps in the available information are also identified. Exposure assessment modeling and associated research would benefit from the collection of additional data as well as by enhancing the accessibility of existing and evolving information resources.     

The Relation Between Human Exposure to Mercury and Thyroid Hormone Status

The aim of this study was to investigate total mercury (THg) and methylmercury (MeHg) exposure of 75 mother-child pairs in relation to their thyroid hormone status (thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (fT3), thyroxine (T4), and free thyroxine (fT4)). THg and MeHg in blood samples were measured by atomic absorption spectrometry and gas chromatography-inductively coupled plasma-mass spectrometry, respectively. The median THg and MeHg levels in maternal blood, cord blood, and blood of 6-month-old children were 0.50, 0.53, and 0.32 and 0.22, 0.32, and 0.08 μg/L, respectively. There were significant correlations between paired maternal-cord blood levels for THg and MeHg, with a greater transplacental transport of MeHg compared with THg (mean cord/maternal blood ratio, 1.80 vs. 1.24). The maternal blood THg was found to be a better predictor of TSH levels in children than their current THg exposure. There was a positive correlation between maternal THg and children's TSH. T3 and fT3 levels in children were negatively related to cord blood THg in the majority (Caucasian) subgroup, whereas these associations were positive in the Roma subgroup. Mothers with dental amalgam fillings had significantly lower T4 and fT4 levels. Moreover, fT4 in the mothers of boys negatively correlated with maternal THg levels. MeHg exposure lowered T3 levels in the mothers of girls. Our results suggest that low-level exposure to Hg can affect thyroid hormone status during prenatal and early postnatal exposure depending on the form of Hg, gender, ethnicity, lifestyle, or socioeconomic status (dental amalgam fillings).