Norovirus Infection and Disease in an Ecuadorian Birth Cohort: Association of Certain Norovirus Genotypes With Host FUT2 Secretor Status.

BACKGROUND: Although norovirus is the most common cause of gastroenteritis, there are few data on the community incidence of infection/disease or the patterns of acquired immunity or innate resistance to norovirus. METHODS: We followed a community-based birth cohort of 194 children in Ecuador with the aim to estimate (1) the incidence of norovirus gastroenteritis from birth to age 3 years, (2) the protective effect of norovirus infection against subsequent infection/disease, and (3) the association of infection and disease with FUT2 secretor status. RESULTS: Over the 3-year period, we detected a mean of 2.26 diarrheal episodes per child (range, 0-12 episodes). Norovirus was detected in 260 samples (18%) but was not found more frequently in diarrheal samples (79 of 438 [18%]), compared with diarrhea-free samples (181 of 1016 [18%]; P = .919). A total of 66% of children had at least 1 norovirus infection during the first 3 years of life, and 40% of children had 2 infections. Previous norovirus infections were not associated with the risk of subsequent infection. All genogroup II, genotype 4 (GII.4) infections were among secretor-positive children (P < .001), but higher rates of non-GII.4 infections were found in secretor-negative children (relative risk, 0.56; P = .029). CONCLUSIONS: GII.4 infections were uniquely detected in secretor-positive children, while non-GII.4 infections were more often found in secretor-negative children

Comparison of Cytokine Responses in Ecuadorian Children Infected with Giardia, Ascaris, or Both Parasites.

More than 2 billion people are infected with parasites globally, and the majority have coinfections. Intestinal protozoa and helminths induce polarizing CD4(+) T-helper cell 1 (Th1) mediated cytokine responses within the host. Such immune polarization may inhibit the ability of the host to mount an adequate immune response for pathogen clearance to concurrent pathogens. The current study evaluated the plasma cytokine profile in Ascaris and Giardia coinfected children compared with Giardia- and Ascaris-only infected children. Fecal samples and blood samples were collected from asymptomatic 3-year-old children living in the district of Quininde, Ecuador. Stool samples that tested positive for Giardia lamblia-only, Ascaris lumbricoides-only, or G. lamblia and A. lumbricoides coinfections were confirmed by quantitative real-time polymerase chain reaction. Plasma samples from the study subjects were used to quantitate cytokines. A total of 39 patients were evaluated. Children with coinfection had a significant decrease in Th1 cytokine production, interleukin 2 (IL-2) (P < 0.05), IL-12 (P < 0.05), and tumor necrosis factor alpha (P < 0.05) compared with Giardia-only infected children. Coinfected children had an increase in IL-10/interferon gamma (IFN-γ) ratio compared with uninfected (P < 0.05) and Ascaris alone (P < 0.05). The increased IL-10/IFN-γ ratio in the setting of decreased Th1 cytokine response indicates Th2 polarization in the coinfected group. Reduced Th1 cytokines in children coinfected with Ascaris and Giardia may impair the host's ability to eradicate Giardia infection leading to chronic giardiasis

Molecular characterization, expression and localization of a peroxiredoxin from the sheep scab mite, Psoroptes ovis

The sheep scab mite, Psoroptes ovis, induces an intensely pruritic exudative dermatitis which is responsible for restlessness, loss of appetite and weight loss. Within the first 24 h of infection, there is a rapid inflammatory influx of eosinophils and apoptosis of the keratinocytes at the site of infection. The former cell type is capable of a sustained respiratory burst, toxic products of which may directly damage the mite and also contribute to lesion formation. Analysis of a P. ovis expressed sequence tag (EST) database identified a number of antioxidant enzyme-encoding sequences, including peroxiredoxin (thioredoxin peroxidase EC 1.11.1.15), all of which may help the mite endure the potentially toxic skin environment. A full length sequence encoding Po-TPx, a protein of 206 amino acids which showed high homology to a peroxiredoxin from the salivary gland of the tick Ixodes scapularis, was amplified from P. ovis cDNA. Recombinant Po-TPx was expressed in bacteria and antiserum to this protein was used to localize native Po-TPx in mite sections. Peroxiredoxin was localized, amongst other sites, to a subpharyngeal region in mite sections. The recombinant protein was recognized by sera from sheep infested with the mite suggesting that it may be secreted or excreted by the mite and interact with the host immune response

TMAO and Gut Microbial-Derived Metabolites TML and γBB Are Not Associated with Thrombotic Risk in Patients with Venous Thromboembolism

Background: The present work evaluates the association between circulating concentrations of Trimethylamine-N-oxide (TMAO), gamma butyrobetaine (gamma BB), and trimetyllisine (TML) in controls and patients with venous thromboembolism (VTE) with coagulation parameters. Methods: The study involved 54 VTE patients and 57 controls. Platelet function, platelet hyperreactivity, platelet adhesiveness, thrombosis-associated parameters, and thrombin generation parameters were studied. Plasma TMAO, gamma BB, and TML determination was performed using an ultra-high-performance liquid chromatography system coupled with mass spectrometry. Results: No differences were found for TMAO, gamma BB, or TML concentrations between controls and VTE patients. In thrombin generation tests, TMAO, gamma BB, and TML showed a positive correlation with lag time and time to peak. TMAO, gamma BB, and TML negatively correlated with peak height. No significant differences were observed regarding TMAO, gamma BB, and TML concentrations between the two blood withdrawals, nor when the control and VTE patients were analyzed separately. No correlation was observed between these gut metabolites and platelet function parameters. Conclusions: No differences were found regarding TMAO, gamma BB, and TML concentrations between the control and VTE groups. Some correlations were found; however, they were mild or went in the opposite direction of what would be expected if TMAO and its derivatives were related to VTE risk

Environmental determinants of total IgE among school children living in the rural Tropics: importance of geohelminth infections and effect of anthelmintic treatment

BACKGROUND: The environmental factors that determine the elevated levels of polyclonal IgE observed in populations living in the Tropics are poorly understood but may include geohelminth infections. We investigated the association between geohelminth infections and total IgE levels in school children in rural tropical Ecuador, and assessed the effect on IgE of repeated anthelmintic treatments over a period of 12 months. The study was nested within a cluster-randomized study that randomized 68 schools to receive either 400 mg of albendazole every 2 months over a year or no treatment. We studied random samples of children completing follow-up and representing four groups stratified by the presence of geohelminth infection at baseline and treatment allocation. We measured levels of total IgE and anti-A. lumbricoides IgG (used as a measure of past and current geohelminth infectious exposure) in blood samples collected at the start of the study and after 12 months. RESULTS: We observed elevated levels of total IgE (compared to standard reference values) at the start of the study in this population of school children (geometric mean, 1,004 IU/mL, range 12 to 22,608 IU/mL)) and baseline IgE levels were strongly associated with parameters of geohelminth infection but not with age, nutritional and socioeconomic status. After 12 months, levels of IgE fell significantly in the treatment (by 35.1%) and no treatment (by 10.4%) groups, respectively, but the fall was significantly greater in the treatment group. Falls in IgE were independently associated with albendazole treatment, having a baseline geohelminth infection and with high baseline levels of anti-A. lumbricoides IgG. Increases in IgE at 12 months were associated with the presence of geohelminth infections and increasing levels of anti-A. lumbricoides IgG at 12 months independent of treatment allocation. CONCLUSION: The data provide evidence that geohelminth infections are an important determinant of total IgE in school children in the rural Tropics and that periodic anthelmintic treatments over 12 months are associated with reductions in IgE. The failure of anthelmintic treatment to reduce IgE levels to that considered normal in industrialized countries may be attributed to continued exposure of children to geohelminths or to the effects of infections in early life in programming a long-lasting Th2-biassed immunity

Modelling wind turbine power curves based on Frank’s copula

Presented at: 21st International Conference on Renewable Energies and Power Quality (ICREPQ’23)In the study of wind turbines, one of the most relevant and useful indicators is the power curve. It has been shown to be of paramount importance in evaluating turbine performance and therefore reducing operation and maintenance (O&M) costs. Various techniques can be applied to model and obtain the shape of this curve, which relates the electrical power generated by a turbine to the wind speed. Statistical copulas are used in this paper, a tool used in other fields such as econometrics, and whose potential lies in its ability to capture the complex dependency between the variables involved. In particular, the Frank copula is applied to obtain a probabilistic model of the power curve of a wind turbine. This model is compared with the Gaussian Mixture Model, a technique widely used to obtain parametric probabilistic models. As a result of this comparison, it is observed that the Frank copula model fits the power curve of the wind turbine with greater precision and reliability, which would allow its use for prediction and fault detection

Polynomial Heuristic Algorithms for Inconsistency Characterization in Firewall Rule Sets

Firewalls provide the first line of defence of nearly all networked institutions today. However, Firewall ACLs could have inconsistencies, allowing traffic that should be denied or vice versa. In this paper, we analyze the inconsistency characterization problem as a separate problem of the diagnosis one, and propose formal definitions in order to characterize one-to-many inconsistencies. We identify the combinatorial part of the problem that generates exponential complexities in combined diagnosis and characterization algorithms proposed by other authors. Then we propose a decomposition of the combinatorial problem in several smaller combinatorial ones, which can effectively reduce the complexity of the problem. Finally, we propose an approximate heuristic and algorithms to solve the problem in worst case polynomial time. Although many algorithms have been proposed to address this problem, all of them are combinatorial. The presented algorithms are an heuristic way to solve the problem with polynomial complexity. There are no constraints on how rule field ranges are expressed

Effect of infant viral respiratory disease on childhood asthma in a non-industrialized setting

Background There are limited data from non-industrialized settings on the effects of early life viral respiratory disease on childhood respiratory illness. We followed a birth cohort in tropical Ecuador to understand how early viral respiratory disease, in the context of exposures affecting airway inflammation including ascariasis, affect wheezing illness, asthma, and rhinoconjunctivitis in later childhood. Methods A surveillance cohort nested within a birth cohort was monitored for respiratory infections during the first 2 years in rural Ecuador and followed for 8 years for the development of wheeze and rhinoconjunctivitis. Nasal swabs were examined for viruses by polymerase chain reaction and respiratory symptom data on recent wheeze and rhinoconjunctivitis were collected by periodic questionnaires at 3, 5, and 8 years. Stools from pregnant mothers and periodically from children aged 2 years were examined microscopically for soil-transmitted helminths. Atopy was measured by allergen skin prick testing at 2 years. Spirometry, fractional exhaled nitric oxide measurement, and nasal washes were performed at 8 years. Associations between clinically significant respiratory disease (CSRD) and wheezing or rhinoconjunctivitis at 3, 5, and 8 years were estimated using multivariable logistic regression. Results Four hundred and twenty six children were followed of which 67.7% had at least one CSRD episode; 12% had respiratory syncytial virus (RSV)+CSRD and 36% had rhinovirus (RHV)+CSRD. All-cause CSRD was associated with increased wheeze at 3 (OR 2.33 [95% confidence intervals (CI) 1.23–4.40]) and 5 (OR: 2.12 [95% CI 1.12–4.01]) years. RHV+CSRD was more strongly associated with wheeze at 3 years in STH-infected (STH-infected [OR 13.41, 95% CI 1.56–115.64] vs. uninfected [OR 1.68, 95% CI 0.73–3.84]) and SPT+ (SPT+ [OR 9.42, 95% CI 1.88–47.15] versus SPT- [OR 1.92, 95% CI 0.84–4.38]) children. No associations were observed between CSRD and rhinoconjunctivitis. Discussion CSRD was significantly associated with childhood wheeze with stronger associations observed for RHV+CSRD in SPT+ and STH-infected children

Imidazopurinones are markers of physiological genomic damage linked to DNA instability and glyoxalase 1-associated tumour multidrug resistance

Glyoxal and methylglyoxal are reactive dicarbonyl metabolites formed and metabolized in physiological systems. Increased exposure to these dicarbonyls is linked to mutagenesis and cytotoxicity and enhanced dicarbonyl metabolism by overexpression of glyoxalase 1 is linked to tumour multidrug resistance in cancer chemotherapy. We report herein that glycation of DNA by glyoxal and methylglyoxal produces a quantitatively important class of nucleotide adduct in physiological systems—imidazopurinones. The adduct derived from methylglyoxal-3-(2′-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6/7-methylimidazo-[2,3-b]purine-9(8)one isomers—was the major quantitative adduct detected in mononuclear leukocytes in vivo and tumour cell lines in vitro. It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell permeable glyoxalase 1 inhibitor. Unexpectedly, the DNA content of methylglyoxal-derived imidazopurinone and oxidative marker 7,8-dihydro-8-oxo-2′-deoxyguanosine were increased moderately in glyoxalase 1-linked multidrug resistant tumour cell lines. Together these findings suggest that imidazopurinones are a major type of endogenous DNA damage and glyoxalase 1 overexpression in tumour cells strives to counter increased imidazopurinone formation in tumour cells likely linked to their high glycolytic activity