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Abstract Rationale Air pollution is a known asthma trigger and has been associated with short-term asthma symptoms, airway inflammation, decreased lung function, and reduced response to asthma rescue medications. Objectives To assess a causal relationship between air pollution and childhood asthma using data that address temporality by estimating air pollution exposures before the development of asthma and to establish the generalizability of the association by studying diverse racial/ethnic populations in different geographic regions. Methods This study included Latino (n = 3,343) and African American (n = 977) participants with and without asthma from five urban regions in the mainland United States and Puerto Rico. Residential history and data from local ambient air monitoring stations were used to estimate average annual exposure to five air pollutants: ozone, nitrogen dioxide (NO2), sulfur dioxide, particulate matter not greater than 10 μm in diameter, and particulate matter not greater than 2.5 μm in diameter. Within each region, we performed logistic regression to determine the relationship between early-life exposure to air pollutants and subsequent asthma diagnosis. A random-effects model was used to combine the region-specific effects and generate summary odds ratios for each pollutant. Measurements and Main Results After adjustment for confounders, a 5-ppb increase in average NO2 during the first year of life was associated with an odds ratio of 1.17 for physician-diagnosed asthma (95% confidence interval, 1.04–1.31). Conclusions Early-life NO2 exposure is associated with childhood asthma in Latinos and African Americans. These results add to a growing body of evidence that traffic-related pollutants may be causally related to childhood asthma.

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10 -64 ) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation. Whether a person develops a particular disease can depend on both genetic and environmental factors. Many studies have found that people of different races and ethnicities have different likelihoods of acquiring certain diseases. Race and ethnicity are social constructs; that is, they are not necessarily defined biologically. However, shared ancestry will produce genetic links between members of a group. In addition, members of an ethnic group often share a culture or environment that may influence their risk of disease. For example, the ‘Mediterranean diet’ inspired by the dietary habits of Southern Italians has been shown to reduce the risk of heart disease, diabetes and cancer. The addition of chemical groups – such as methyl groups – to DNA strands can affect the activity of nearby genes. Methylation is controlled by both genetic and environmental factors, and altered patterns of DNA methylation are seen in some diseases. It is therefore an ideal biological process to study to determine how race/ethnicity and ancestry contribute to a person’s susceptibility to disease. Galanter et al. have now studied the patterns of methylation found in the blood of 573 people from diverse Latino ethnic sub-groups. The different groups displayed significantly different patterns of methylation at hundreds of locations across the genome. Genetic ancestry explained approximately 75% of the variation in methylation between the sub-groups. In addition, the methylation patterns at DNA locations known to be affected by environmental exposures – for example, by exposure to tobacco while in the womb – were disproportionately likely to be methylated differently in different sub-groups. Now that more is known about the relative effects of race/ethnicity and genetic ancestry on methylation, the next step is to apply this knowledge to disease processes. This will help us to better understand the source of health disparities across different groups of people.

Culicidae mosquitoes are potential vectors of pathogens that affect human health. The correct species identification, as well as the discovery and description of cryptic species, is important in public health for the control and management of specific vectors. In the present study, the diversity of anthropophagous mosquitoes in Quintana Roo, at the border between Mexico and Belize, was evaluated using morphological and molecular data (COI‐DNA Barcoding). A total of 1,413 adult female specimens were collected, belonging to eight genera and 31 morphospecies. Most species formed well‐supported clades. Intraspecific Kimura 2 parameters (K2P) distance average was 0.75%, and a maximum distance of 4.40% was observed for Anopheles crucianss.l. ABGD method identified 28 entities, while 32 entities were identified with the BIN system. In Culex interrogator and Culex nigripalpus a low interspecific genetic distance of 0.1% was observed. One undescribed species belonging to the genus Aedes (Aedesn. sp.) was discovered, but no clear genetic divergence was found between this species and the closely related species Aedes angustivittatus. An intraspecific K2P distance greater than 2.7% was observed in Aedes serratus(3.9%), Anopheles crucianss.l. (4.4%), Culex taeniopus (3.7%), Haemagogus equinus (3.9%), Culex erraticus (5.0%), Psorophora ferox (4.5%), and in Anopheles apicimacula(8.10%); therefore, evidences of cryptic diversity are shown in these species. This study showed that DNA barcodes offer a reliable framework for mosquito species identification in Quintana Roo, except for some closely related species for which it is recommended to use additional nuclear genetic markers such as ITS2, in order to resolve these small discrepancies. DNA barcodes disclose cryptic diversity in anthropophagous mosquitoes.

Abstract The IL-1 family of cytokines, which now includes 11 members, is well known to participate in inflammation. Although the most recently recognized IL-1 family cytokines (IL-1F5–11) have been shown to be expressed in airway epithelial cells, the regulation of their expression and function in the epithelium has not been extensively studied. We investigated the regulation of IL-1F5–11 in primary normal human bronchial epithelial cells. Messenger (m)RNAs for IL-1F6 and IL-1F9, but not IL-1F5, IL-1F8 or IL-1F10, were significantly up-regulated by TNF, IL-1β, IL-17 and the Toll-like receptor (TLR)3 ligand double-stranded (ds)RNA. mRNAs for IL-1F7 and IL-1F11 (IL-33) were weakly up-regulated by some of the cytokines tested. Notably, mRNAs for IL-1F6 and IL-1F9 were synergistically enhanced by the combination of TNF/IL-17 or dsRNA/IL-17. IL-1F9 protein was detected in the supernatant following stimulation with dsRNA or a combination of dsRNA and IL-17. IL-1F6 protein was detected in the cell lysate but was not detected in the supernatant. We screened for the receptor for IL-1F9 and found that lung fibroblasts expressed this receptor. We found that IL-1F9 activated mitogen-activated protein kinases and the transcription factor NF-κB in primary normal human lung fibroblasts. IL-1F9 also stimulated the expression of the neutrophil chemokines IL-8 and CXCL3 and the Th17 chemokine CCL20 in lung fibroblasts. These results suggest that epithelial activation by TLR3 (e.g., by respiratory viral infection) and exposure to cytokines from Th17 cells (IL-17) and inflammatory cells (TNF) may amplify neutrophilic inflammation in the airway via induction of IL-1F9 and activation of fibroblasts.

Background. Between 50% and 80% of asthma exacerbations are associated with viral respiratory tract infections (RTIs), yet the influence of viral pathogen diversity on asthma outcomes is poorly understood because of the limited scope and throughput of conventional viral detection methods. Methods. We investigated the capability of the Virochip, a DNA microarray—based viral detection platform, to characterize viral diversity in RTIs in adults with and without asthma. Results. The Virochip detected viruses in a higher proportion of samples (65%) than did culture isolation (17%) while exhibiting high concordance (98%) with and comparable sensitivity (97%) and specificity (98%) to pathogen-specific polymerase chain reaction. A similar spectrum of viruses was identified in the RTIs of each patient subgroup; however, unexpected diversity among human coronaviruses (HCoVs) and human rhinoviruses (HRVs) was revealed. All but one of the HCoVs corresponded to the newly recognized HCoV-NL63 and HCoV-HKU1 viruses, and >20 different serotypes of HRVs were detected, including a set of 5 divergent isolates that formed a distinct genetic subgroup. Conclusions. The Virochip can detect both known and novel variants of viral pathogens present in RTIs. Given the diversity detected here, larger-scale studies will be necessary to determine whether particular substrains of viruses confer an elevated risk of asthma exacerbation.

Abstract Rationale Obesity is associated with increased asthma morbidity, lower drug responsiveness to inhaled corticosteroids, and worse asthma control. However, most prior investigations on obesity and asthma control have not focused on pediatric populations, considered environmental exposures, or included minority children. Objectives To examine the association between body mass index categories and asthma control among boys and girls; and whether these associations are modified by age and race/ethnicity. Methods Children and adolescents ages 8–19 years (n = 2,174) with asthma were recruited from the Genes-environments and Admixture in Latino Americans (GALA II) Study and the Study of African Americans, Asthma, Genes, and Environments (SAGE II). Ordinal logistic regression was used to estimate odds ratios (OR) and their confidence intervals (95% CI) for worse asthma control. Measurements and Main Results In adjusted analyses, boys who were obese had a 33% greater chance of having worse asthma control than their normal-weight counterparts (OR, 1.33; 95% CI, 1.04–1.71). However, for girls this association varied with race and ethnicity (P interaction = 0.008). When compared with their normal-weight counterparts, obese African American girls (OR, 0.65; 95% CI, 0.41–1.05) were more likely to have better controlled asthma, whereas Mexican American girls had a 1.91 (95% CI, 1.12–3.28) greater odds of worse asthma control. Conclusions Worse asthma control is uniformly associated with increased body mass index in boys. Among girls, the direction of this association varied with race/ethnicity.

(1) Background: Localized cutaneous leishmaniasis is a neglected vector-borne disease that has become a serious public health problem in the Yucatan Peninsula. Although more than 60% of cases originate from the state of Quintana Roo, it is one of the least explored areas in terms of incriminating vectors of the Leishmania parasite. Additionally, cases of leishmaniasis have increased substantially in that region in recent years. For this reason, we explored and provided primary evidence of Leishmania DNA in sand fly species from four localities during outbreaks of leishmaniasis in Quintana Roo. We also contributed information on the regional genetic diversity of Leishmania parasites. (2) Methods: Sand flies were collected during several periods from November 2022 to April 2023 using Mosquito Light Circle and Shannon traps, as well as an active entomological search in refuges. For Leishmania detection, we amplified a fragment of 300–350 bp of the internal transcribed spacer subunit 1 (ITS-1). (3) Results: Of the 242 females collected, we detected Leishmania DNA in 25 specimens represented by Bichromomyia olmeca (1), Psathyromyia shannoni (17), Lutzomyia cruciata (4), Psathyromyia undulata (2), and Dampfomyia deleoni (1). The detection of Leishmania in these last two species represents new records for the Yucatan Peninsula and for Mexico. Leishmania (Leishmania) mexicana was the only species detected in the Phlebotominae species, with prevalence values that ranked between 7.41% and 33.33% from specimens collected in the sylvatic areas of Cozumel Island and Petcacab. (4) Conclusions: This study provides the first evidence of infection of Da. deleoni and Pa. undulata by L. (L.) Mexicana. In addition, the presence of three dominant haplotypes in all the evaluated localities was evidenced using the analysis of genetic diversity, and the locality of Petcacab was the one with the circulation of two new haplotypes not previously described in Mexico or neighboring countries. These results highlight the importance of intensive epidemiological surveillance due to the dynamics of transmission of Leishmania between different species.

The detection of viral pathogens is of critical importance in biology, medicine, and agriculture. Unfortunately, existing techniques to screen for a broad spectrum of viruses suffer from severe limitations. To facilitate the comprehensive and unbiased analysis of viral prevalence in a given biological setting, we have developed a genomic strategy for highly parallel viral screening. The corner-stone of this approach is a long oligonucleotide (70-mer) DNA microarray capable of simultaneously detecting hundreds of viruses. Using virally infected cell cultures, we were able to efficiently detect and identify many diverse viruses. Related viral serotypes could be distinguished by the unique pattern of hybridization generated by each virus. Furthermore, by selecting microarray elements derived from highly conserved regions within viral families, individual viruses that were not explicitly represented on the microarray were still detected, raising the possibility that this approach could be used for virus discovery. Finally, by using a random PCR amplification strategy in conjunction with the microarray, we were able to detect multiple viruses in human respiratory specimens without the use of sequence-specific or degenerate primers. This method is versatile and greatly expands the spectrum of detectable viruses in a single assay while simultaneously providing the capability to discriminate among viral subtypes.

In the United States, asthma prevalence and mortality are the highest among Puerto Ricans and the lowest among Mexicans. Case-control association studies are a powerful strategy for identifying genes of modest effect in complex diseases. However, studies of complex disorders in admixed populations such as Latinos may be confounded by population stratification. We used ancestry informative markers (AIMs) to identify and correct for population stratification among Mexican and Puerto Rican subjects participating in case-control studies of asthma. Three hundred and sixty-two subjects with asthma (Mexican: 181, Puerto Rican: 181) and 359 ethnically matched controls (Mexican: 181, Puerto Rican: 178) were genotyped for 44 AIMs. We observed a greater than expected degree of association between pairs of AIMs on different chromosomes in Mexicans (P < 0.00001) and Puerto Ricans (P < 0.00002) providing evidence for population substructure and/or recent admixture. To assess the effect of population stratification on association studies of asthma, we measured differences in genetic background of cases and controls by comparing allele frequencies of the 44 AIMs. Among Puerto Ricans but not in Mexicans, we observed a significant overall difference in allele frequencies between cases and controls (P = 0.0002); of 44 AIMs tested, 8 (18%) were significantly associated with asthma. However, after adjustment for individual ancestry, only two of these markers remained significantly associated with the disease. Our findings suggest that empirical assessment of the effects of stratification is critical to appropriately interpret the results of case-control studies in admixed populations.

Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk. We included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function. RSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2-11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted. A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population.