Estimating the impact of the COVID-19 pandemic on dengue in Brazil.

Atypical dengue prevalence was observed in 2020 in many dengue-endemic countries, including Brazil. Evidence suggests that the pandemic disrupted not only dengue dynamics due to changes in mobility patterns, but also several aspects of dengue surveillance, such as care seeking behavior, care availability, and monitoring systems. However, we lack a clear understanding of the overall impact on dengue in different parts of the country as well as the role of individual causal drivers. In this study, we estimated the gap between expected and observed dengue cases in 2020 using an interrupted time series design with forecasts from a neural network and a structural Bayesian time series model. We also decomposed the gap into the impacts of climate conditions, pandemic-induced changes in reporting, human susceptibility, and human mobility. We find that there is considerable variation across the country in both overall pandemic impact on dengue and the relative importance of individual drivers. Increased understanding of the causal mechanisms driving the 2020 dengue season helps mitigate some of the data gaps caused by the COVID-19 pandemic and is critical to developing effective public health interventions to control dengue in the future.

Prediction models and questionnaires developed to predict vitamin D status in adults: a systematic review.

A systematic review of prediction models/questionnaires developed to identify people with deficient/insufficient vitamin D status shows the potential of self-reported information to estimate vitamin D status. The objective is to identify and compare existing screening tools, developed to identify vitamin D deficiency or insufficiency in adults. A systematic search of literature was conducted using MEDLINE, Scopus, Web of Science and CINAHL databases. Risk of bias and applicability concerns were assessed by quality assessment of diagnostic accuracy studies (QUADAS-2). Data were extracted on socio-demographic, anthropometric, risk factors, serum 25 hydroxyvitamin D [25(OH)D] levels, statistical methods and predictive ability. A total of 12 studies were considered for inclusion for this systematic review after screening of 4851 abstracts and 15 full-text articles. Ten of twelve studies developed prediction models and 2 studies developed questionnaires. The majority of studies had low risk of bias and applicability as assessed by QUADAS-2. All studies included only self-reported predictors of vitamin D status in their final models and development of scores. Sunlight exposure and related factors were important significant contributors to the predictive ability of the models and/or questionnaires. Sensitivity and specificity of the prediction models or questionnaires ranged from 55 to 91% and 35 to 84%, respectively. Six out of twelve studies converted final models to scores associated with vitamin D status. There was no evidence that any of these existing tools have been translated into clinical practice. The prediction models or questionnaires identified in this systematic review were moderately sensitive and specific for identifying people with vitamin D deficiency or insufficiency. The substantial contribution of sunlight exposure to the prediction of vitamin D status highlights the importance of including this information when developing vitamin D screening tools.

Dynamically controlled deposition of colloidal nanoparticle suspension in evaporating drops using laser radiation.

Dynamic control of the distribution of polystyrene suspended nanoparticles in evaporating droplets is investigated using a 2.9 µm high power laser. Under laser radiation a droplet is locally heated and fluid flows are induced that overcome the capillary flow, and thus a reversal of the coffee-stain effect is observed. Suspension particles are accumulated in a localised area, one order of magnitude smaller than the original droplet size. By scanning the laser beam over the droplet, particles can be deposited in an arbitrary pattern. This finding raises the possibility for direct laser writing of suspended particles through a liquid layer. Furthermore, a highly uniform coating is possible by manipulating the laser beam diameter and exposure time. The effect is expected to be universally applicable to aqueous solutions independent of solutes (either particles or molecules) and deposited substrates.

Dynamics of energy condensation in two-dimensional turbulence.

We report a numerical study, supplemented by phenomenological explanations, of "energy condensation" in forced 2D turbulence in a biperiodic box. Condensation is a finite size effect which occurs after the standard inverse cascade reaches the size of the system. It leads to the emergence of a coherent vortex dipole. We show that the time growth of the dipole is self-similar, and it contains most of the injected energy, thus resulting in an energy spectrum which is markedly steeper than the standard k{-5/3} one. Once the coherent component is subtracted, however, the remaining fluctuations have a spectrum close to k{-1}. The fluctuations decay slowly as the coherent part grows.

Discreteness and quasiresonances in weak turbulence of capillary waves.

A numerical study is presented which deals with the kinematics of quasiresonant energy transfer in a system of capillary waves with a discrete wave number space in a periodic box. For a given set of initially excited modes and a given level of resonance broadening, the modes of the system are partitioned into two classes, one active, the other forbidden. For very weak nonlinearity the active modes are very sparse. It is possible that this sparsity explains discrepancies between the values of the Kolmogorov constant measured in numerical simulations of weakly turbulent cascades and the theoretical values obtained from the continuum theory. There is a critical level of nonlinearity below which the set of active modes has finite radius in wave number space. In this regime, an energy cascade to dissipative scales may not be possible and the usual Kolmogorov spectrum predicted by the continuum theory not realized.

Engineering, characterization and in vitro efficacy of the major peanut allergens for use in immunotherapy.

BACKGROUND: Numerous strategies have been proposed for the treatment of peanut allergies, but despite the steady advancement in our understanding of atopic immune responses and the increasing number of deaths each year from peanut anaphylaxis, there is still no safe, effective, specific therapy for the peanut-sensitive individual. Immunotherapy would be safer and more effective if the allergens could be altered to reduce their ability to initiate an allergic reaction without altering their ability to desensitize the allergic patient. METHODS: The cDNA clones for three major peanut allergens, Ara h 1, Ara h 2, and Ara h 3, have been cloned and characterized. The IgE-binding epitopes of each of these allergens have been determined and amino acids critical to each epitope identified. Site-directed mutagenesis of the allergen cDNA clones, followed by recombinant production of the modified allergen, provided the reagents necessary to test our hypothesis that hypoallergenic proteins are effective immunotherapeutic reagents for treating peanut-sensitive patients. Modified peanut allergens were subjected to immunoblot analysis using peanut-positive patient sera IgE, T cell proliferation assays, and tested in a murine model of peanut anaphylaxis. RESULTS: In general, the modified allergens were poor competitors for binding of peanut-specific IgE when compared to their wild-type counterpart. The modified allergens demonstrated a greatly reduced IgE-binding capacity when individual patient serum IgE was compared to the binding capacity of the wild-type allergens. In addition, while there was considerable variability between patients, the modified allergens retained the ability to stimulate T cell proliferation. CONCLUSIONS: These modified allergen genes and proteins should provide a safe immunotherapeutic agent for the treatment of peanut allergy.

A soybean G2 glycinin allergen. 2. Epitope mapping and three-dimensional modeling.

BACKGROUND: Multiple allergens have been documented in soybean extracts. IgE from individuals allergic to soybeans, but not to peanut, has been shown by immunoblot analysis to bind to proteins with a molecular weight of approximately 22 kD. These findings suggested that this unique protein fraction from soybean might be responsible, in part, for soybean allergic reactivity. The objective of the present study was to characterize specific B cell epitopes, to determine if any amino acid was critical to IgE binding and to model the 22-kD G2 soybean allergen to the three-dimensional (3-D) phaseolin molecule. METHODS: B cell epitopes were identified using SPOTs peptide analysis. Structural orientation of the IgE-binding regions was mapped to the 3-D phaseolin molecule using molecular modeling of the protein tertiary structure. RESULTS: Eleven linear epitopes, representing 15 amino acid peptide sequences, bound to IgE in the glycinin molecule. These epitopes were predicted to be distributed asymmetrically on the surface of G2 trimers. CONCLUSIONS: Only 1 epitope could be rendered non-IgE binding by alanine substitutions in the peptide. The nonrandom distribution of the IgE binding sites provides new insight into their organization in trimers in 11S complexes of the G2 glycinin allergen.

A soybean G2 glycinin allergen. 1. Identification and characterization.

BACKGROUND: Multiple allergens have been documented in soybean extracts. IgE from individuals allergic to soybeans, but not to peanut, was shown by immunoblot analysis to bind to proteins with a molecular weight of approximately 21 kD. These findings suggested that unique proteins in soybeans might be responsible for soybean allergic reactivity. The objective of the present study was to identify unique proteins in soybean extracts that bind to specific IgE from soybean-sensitive individuals, and to characterize the allergen using physicochemical methods and IgE binding. METHODS: Two-dimensional and preparative SDS-PAGE/IgE immunoblot analysis was used to identify a 22-kD soybean-specific allergen from crude soybean extracts. N-terminal sequence analysis was used to determine the identification of the protein binding IgE from soybean-sensitive individuals. RESULTS: IgE immunoblot and amino acid sequence analysis identified the 22-kD protein as a member of the G2 glycinin soybean protein family. Further investigation revealed that the IgEs reacted with basic chains from each member of the glycinin family of soybean storage proteins. CONCLUSIONS: Each of the subunits from glycinin, the storage protein that is the most prevalent component of soybean, are major allergens.

Mutational analysis of the IgE-binding epitopes of P34/Gly m Bd 30K.

BACKGROUND: Peanuts and soybeans are 2 foods that have been shown to be responsible for many atopic disorders. Because of their nutritional benefit, soybean proteins are now being used increasingly in a number of food products. Previous studies have documented multiple allergens in soybean extracts, including glycinin, beta-conglycinin, and the P34/Gly m Bd 30K protein. OBJECTIVE: Our overall goal was to identify soybean-specific allergens to begin to understand molecular and immunochemical characteristics of legume proteins. The specific aim of the current investigation was to identify the essential amino acid residues necessary for IgE binding in the 5 distinct immunodominant epitopes of P34/Gly m Bd 30K. METHODS: Serum IgE from 6 clinically sensitive soybean-allergic individuals was used to identify P34/Gly m Bd 30K in the native and single amino acid substituted peptides with use of the SPOTS peptide synthesis technique to determine critical amino acids required for IgE binding. RESULTS: The intensity of IgE binding and epitope recognition by serum IgE from the individuals varied substantially. With use of serum from 6 clinically soybean-sensitive individuals, 2 of the 5 immunodominant epitopes could be mutagenized to non-IgE binding peptides. CONCLUSIONS: Single-site amino acid substitution of the 5 immunodominant epitopes of Gly m Bd 30K with alanine revealed that IgE binding could be reduced or eliminated in epitopes 6 and 16 in the serum obtained from 6 soybean-sensitive patients.

Epitope specificity of the major peanut allergen, Ara h II.

The antigenic and allergenic structure of Ara h II, a major allergen of peanuts, was investigated with the use of four monoclonal antibodies obtained from BALB/c mice immunized with purified Ara h II. Our previous studies with monoclonal antibodies generated to peanut allergens showed this method to be useful for epitope mapping. When used as a solid phase in an ELISA, these monoclonal antibodies captured peanut antigen, which bound human IgE from patients with positive peanut challenge responses. The Ara h II monoclonal antibodies were found to be specific for peanut antigens when binding for other legumes was examined. In ELISA inhibition studies with the monoclonal antibodies, we identified two different antigenic sites on Ara h II. In similar studies with pooled human IgE serum from patients with positive challenge responses to peanuts, we identified two closely related IgE-binding epitopes. These characterized monoclonal antibodies to Ara h II will be useful for future studies to immunoaffinity purify the Ara h II allergen and to use in conjunction with recombinant technology for determining structure-function relationships.

Identification of peanut agglutinin and soybean trypsin inhibitor as minor legume allergens.

Peanuts and soybeans are frequent causes of food hypersensitivity reactions in children. Sera from 12 patients with atopic dermatitis and a positive double-blind placebo-controlled food challenge to peanut and sera from 5 patients with atopic dermatitis and a positive double-blind placebo-controlled food challenge to soybean were used to identify and characterize specific legume allergens. Identification of a minor allergen from peanut and a minor allergen from soybean was accomplished using various physicochemical techniques. The peanut fraction, peanut agglutinin, isolated by anion-exchange chromatography and electrolution and confirmed by amino acid sequencing, bound IgE in only 50% of the peanut challenge positive patients. The soybean fraction, soybean trypsin inhibitor, identified by gel filtration and electroelution and confirmed by amino acid sequencing, bound IgE in only 20% of the soy challenge positive patients. The identification of these two known legume proteins as minor allergens should allow further immunologic and structural investigations to compare the major and minor legume allergens.

Epitope specificity and immunoaffinity purification of the major peanut allergen, Ara h I.

The antigenic and allergenic structure of Ara h I, a major allergen of peanuts, was investigated with the use of seven monoclonal antibodies obtained from BALB/c mice immunized with purified Ara h I. Previous work with monoclonal antibodies produced to allergens has primarily been done with inhalant allergens. Only recently have the major allergens of various foods been determined so that investigations with monoclonal antibodies into the allergenic epitopes could begin. When used as a solid phase in an ELISA, these monoclonal antibodies captured peanut antigen, which bound human IgE from patients with positive results to challenges to peanuts. The Ara h I monoclonal antibodies were found to be specific for peanut antigens when binding for other legumes was examined. In ELISA inhibition studies with the monoclonal antibodies, we identified four different antigenic sites on Ara h I. In related studies with pooled human IgE serum from patients with positive results to challenges to peanuts, we identified three similar IgE-binding epitopes. As a means of purifying the Ara h I allergen, we prepared an immunoaffinity column with monoclonal antibody 8D9. We eluted from this column the allergen Ara h I, which had a mean molecular weight of 63.5 kd and which bound human IgE from individual and pooled serum of patients with peanut sensitivity.

Allergenicity of peanut and soybean extracts altered by chemical or thermal denaturation in patients with atopic dermatitis and positive food challenges.

Peanuts and soybeans are two of the six most common foods to cause food hypersensitivity reactions in children. We used the serum of 10 patients with atopic dermatitis and positive double-blind, placebo-controlled, food challenges to peanut and two patients with atopic dermatitis and positive double-blind, placebo-controlled, food challenges to soybean to investigate the change in IgE-specific and IgG-specific binding to these proteins altered by either chemical or thermal denaturation. We used IgE- and IgG-specific ELISA-inhibition analyses to compare these effects on the crude peanut and crude soy extracts, as well as on the major allergenic fractions of both proteins. Heating the soy proteins at various temperatures and time intervals did not significantly change the IgE- or IgG-specific binding of the soy positive pooled serum. When the peanut proteins were subjected to similar heating experiments, the IgE- and IgG-specific binding did not change. When these same proteins were treated with enzymes in the immobilized digestive enzyme assay system used to mimic human digestion, the binding of IgE to the crude peanut and crude soy extracts was reduced; 100-fold for peanut and 10-fold for soybean. Therefore it appears that thermal denaturation of peanut and soybean protein extracts does not enhance or reduce IgE- and IgG-specific binding activity. Chemical denaturation appears to minimally reduce the binding of these proteins.

Identification and characterization of a second major peanut allergen, Ara h II, with use of the sera of patients with atopic dermatitis and positive peanut challenge.

Peanuts are frequently a cause of food hypersensitivity reactions in children. Serum from nine patients with atopic dermatitis and a positive double-blind, placebo-controlled, food challenge to peanut were used in the process of identification and purification of the peanut allergens. Identification of a second major peanut allergen was accomplished with use of various biochemical and molecular techniques. Anion exchange chromatography of the crude peanut extract produced several fractions that bound IgE from the serum of the patient pool with positive challenges. By measuring antipeanut specific IgE and by IgE-specific immunoblotting we have identified an allergic component that has two closely migrating bands with a mean molecular weight of 17 kd. Two-dimensional gel electrophoresis of this fraction revealed it to have a mean isoelectric point of 5.2. According to allergen nomenclature of the IUIS Subcommittee for Allergen Nomenclature this allergen is designated, Ara h II (Arachis hypogaea).

Effect of soy protein ingestion on total and specific immunoglobulin G concentrations in neonatal porcine serum measured by enzyme-linked immunosorbent assay.

Crossbred neonatal pigs from spring and summer farrowings were used to evaluate the systemic humoral immune response in porcine serum after ingestion of soy protein. At 10 to 12 d of age (average BW 3.8 kg), pigs were randomly allotted to three treatment groups according to litter, weight, and sex. Treatments were intermittent gavage feedings two or three times daily for six consecutive days with nonfat dry milk (NFDM) or textured vegetable protein (TVP) and a nongavaged control group. Pigs were weaned at 20 to 22 d of age (average BW 5.7 kg) and fed a corn-soybean meal-based starter diet. Total serum immunoglobulin G (IgG) and IgG concentrations specific for soy protein were measured by ELISA. Blood samples were taken at 1 d of age after colostrum intake and at 4-d intervals from the beginning of treatment to 31 d of age. When averaged from d 1 to 31, spring-farrowed pigs had greater (P less than .005) total IgG and soy-protein-specific IgG concentrations than did summer-farrowed pigs (8.70 vs 6.51 mg/mL and 1.59 vs .55 micrograms/mL, respectively). Total serum IgG concentrations changed with time (P = .005); they initially decreased, then recovered after weaning. These changes were independent of treatment, sex, or farrowing season. Soy-protein-specific IgG concentrations also changed with time (P = .003); however, this trend was dependent on season (P = .014). Summer-farrowed pigs exhibited a more rapid and severe decrease in serum IgG concentrations specific for soy protein than did spring-farrowed pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of a major peanut allergen, Ara h I, in patients with atopic dermatitis and positive peanut challenges.

Peanuts are among the most common causes of immediate hypersensitivity reactions to foods. Serum from nine patients with atopic dermatitis and a positive double-blind, placebo-controlled, food challenge to peanut were used to begin the process of identification and purification of the major peanut allergens. Identification of a major peanut allergen was accomplished by use of anion-exchange column chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, ELISA, thin-layer isoelectric focusing, and IgE-specific immunoblotting. Anion-exchange chromatography revealed several fractions that bound IgE from the serum of the challenge-positive patient pool. By measuring antipeanut-specific IgE in the ELISA and in IgE-specific immunoblotting, we identified an allergenic component with two Coomassie brilliant blue staining bands by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a mean molecular weight of 63.5 kd. Examination of this fraction by the IgE antipeanut ELISA with individual serum and by the ELISA-inhibition assay with pooled serum, we identified this fraction as a major allergen. Thin-layer isoelectric focusing and immunoblotting of this 63.5 kd fraction revealed it to have an isoelectric point of 4.55. Based on allergen nomenclature of the IUIS Subcommittee for Allergen Nomenclature, this allergen is designated, Ara h I (Arachis hypogaea).

Antibody response to milk proteins in patients with milk-protein intolerance documented by challenge.

To evaluate the role of specific antibody response to milk proteins in patients with milk-protein intolerance, allergen-specific IGE, IgG, and IgG4 to these proteins were measured by ELISA. Bovine casein, gamma globulin (GG), beta-lactoglobulin, and lactalbumin were the milk proteins used. Antibody production to these proteins were analyzed in 18 patients who underwent milk-protein challenges (eight positive and 10 negative) and in five normal children used in the analysis. ELISA results for specific IgE, IgG, and IgG4 to these specific proteins demonstrated no statistically different response to the four milk proteins among the three patient groups by multivariate analysis. When the specific antibody results from the positive challenge group, the negative challenge group, and the normal group were combined, the IgE and IgG4 to GG and the IgG to casein were significantly higher (p less than 0.01) than the corresponding specific antibody to the other proteins tested. The IgG or IgG4 to GG would differentiate the positive from the negative challenge group (p less than 0.05) but were not significantly different from the normal control group. Contrary to previously published studies, these results indicate IgG specific for the milk proteins are not increased in patients with milk-protein intolerance. The data also support the concept that IgE and IgG4 are not elevated in these patients. Therefore, there appears to be no pathogenic role for these specific immunoglobulins in milk-protein intolerance.

Enzyme-linked immunosorbent assay and immunoblotting determination of antibody response to major component proteins of soybeans in patients with soy protein intolerance.

To evaluate the role of food-specific antibody response to soy protein and its fractions in patients with soy protein intolerance, allergen-specific IgG and IgE to these proteins were measured by enzyme-linked immunosorbent assays (ELISAS) and immunoblotting. A crude soy extract and the 7S, 11S, and whey fractions were isolated from commercial defatted soy flakes. Of 23 patients who underwent standardized soy challenges, seven were positive. The ELISA results showed no statistically different responses between the challenge-positive and challenge-negative groups in IgG or IgE specific to either the crude soy extract or the 7S, 11S, and whey fractions (p greater than .3 for all variables). In comparing the soy-positive patients, the level of IgE specific for 7S and 11S was significantly different compared with whey; the level of IgE specific for crude soy extract and 7S was significantly different compared with whey. The immunoblots reveal that IgG and IgE are present in varying amounts to multiple fractions of the soy protein. The study does not provide evidence for a pathogenic role of serum food-specific antibodies in soy protein intolerance.