The role of small airway dysfunction in asthma control and exacerbations:a longitudinal, observational analysis using data from the ATLANTIS study

Background Although small airway disease is a feature of asthma, its association with relevant asthma outcomes remains unclear. The ATLANTIS study was designed to identify the combination of physiological and imaging variables that best measure the presence and extent of small airway disease in asthma, both cross-sectionally and longitudinally. In this longitudinal analysis, we evaluated which small airway parameters studied were most strongly associated with asthma control, exacerbations, and quality of life.Methods In this observational cohort study, participants with mild, moderate, or severe stable asthma were recruited between June 30, 2014, and March 3, 2017, via medical databases and advertisements in nine countries worldwide. Eligible participants were aged 18-65 years with a clinical asthma diagnosis for at least 6 months. Participants were followed up for 1 year, with visits at baseline, 6 months, and 12 months. Physiological tests included spirometry, lung volumes, impulse oscillometry, multiple breath nitrogen washout (MBNW), and percentage decrease in forced vital capacity during methacholine challenge. CT densitometry was performed to evaluate small airway disease. We examined the associations between these measurements and asthma exacerbations, asthma control, and quality of life using univariate and multivariate analyses. A composite ordinal score comprising percent predicted R5-20 (resistance of small-to-mid-sized airways), AX (area of reactance), and X5 (reactance of more central, conducting small airways at 5 Hz) was constructed.Findings 773 participants (median age 46 years [IQR 34-54]; 450 [58%] female) were included in this longitudinal study. Univariate analyses showed that components of impulse oscillometry, lung volumes, MBNW, and forced expiratory flow at 25-75% of FVC were significantly correlated with asthma control and exacerbations (Spearman correlations 0.20-0.25, p<0.0001 after Bonferroni correction). As a composite of impulse oscillometry, the ordinal score independently predicted asthma control and exacerbations in a multivariate analysis with known exacerbation predictors. CT parameters were not significantly correlated with asthma control, exacerbation, or quality of life.Interpretation Small airway disease, as measured by physiological tests, is longitudinally associated with clinically important asthma outcomes, such as asthma control and exacerbations. Copyright (C) 2022 Elsevier Ltd. All rights reserved

Extended Y chromosome haplotypes resolve multiple and unique lineages of the Jewish priesthood

It has been known for over a decade that a majority of men who self report as members of the Jewish priesthood (Cohanim) carry a characteristic Y chromosome haplotype termed the Cohen Modal Haplotype (CMH). The CMH has since been used to trace putative Jewish ancestral origins of various populations. However, the limited number of binary and STR Y chromosome markers used previously did not provide the phylogenetic resolution needed to infer the number of independent paternal lineages that are encompassed within the Cohanim or their coalescence times. Accordingly, we have genotyped 75 binary markers and 12 Y-STRs in a sample of 215 Cohanim from diverse Jewish communities, 1,575 Jewish men from across the range of the Jewish Diaspora, and 2,099 non-Jewish men from the Near East, Europe, Central Asia, and India. While Cohanim from diverse backgrounds carry a total of 21 Y chromosome haplogroups, 5 haplogroups account for 79.5% of Cohanim Y chromosomes. The most frequent Cohanim lineage (46.1%) is marked by the recently reported P58 T->C mutation, which is prevalent in the Near East. Based on genotypes at 12 Y-STRs, we identify an extended CMH on the J-P58* background that predominates in both Ashkenazi and non-Ashkenazi Cohanim and is remarkably absent in non-Jews. The estimated divergence time of this lineage based on 17 STRs is 3,190 ± 1,090 years. Notably, the second most frequent Cohanim lineage (J-M410*, 14.4%) contains an extended modal haplotype that is also limited to Ashkenazi and non-Ashkenazi Cohanim and is estimated to be 4.2 ± 1.3 ky old. These results support the hypothesis of a common origin of the CMH in the Near East well before the dispersion of the Jewish people into separate communities, and indicate that the majority of contemporary Jewish priests descend from a limited number of paternal lineages

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

Evidence of Adaptation to Climate and Diet in Siberians

One of the greatest challenges modern humans faced as they migrated into Eurasia was a cold climate. This was especially true of Siberia, where mean January temperatures of -40ºC are common and temperatures of -70ºC have been recorded. Humans adapted to this environment in multiple ways, but the role of genetic adaptation has been unclear. In this dissertation, I address this question with large-scale genomic data, and statistical and informatics-based methods designed to find ``signals of selection". Using this approach, I find strong evidence of positive natural selection acting on missense variants in three genes, PLA2G2A, PLIN1 and ANGPTL8, all with essential functions in lipid metabolism and brown adipose tissue function. In addition, I find strong support for the adaptive introgression of a small region on chromosome 1 from a Denisovan-like archaic hominid into modern humans. This region appears to have introgressed in Central Siberia and then later spread into Europe and the New World. Lastly, I advance the hypothesis that these adaptive variants are related to the very low breast cancer rate found in many traditional circumpolar populations. Molecular evidence indicates these same genes play important roles in breast tumor growth and proliferation, and these variants may confer a protective phenotype. Together these findings illustrate how local adaptation to climate and diet can lead to changes in metabolic function and disease susceptibility

Simulating Emulating

(Statement of Responsibility) by Brian Hallmark(Thesis) Thesis (B.A.) -- New College of Florida, 2001(Supplements) Accompanying materials: CD-ROM included(Electronic Access) RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE(Bibliography) Includes bibliographical references.(Source of Description) This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.(Local) Faculty Sponsor: McDonald, Patric

Genomics in Personalized Nutrition: Can You “Eat for Your Genes”?

Genome-wide single nucleotide polymorphism (SNP) data are now quickly and inexpensively acquired, raising the prospect of creating personalized dietary recommendations based on an individual’s genetic variability at multiple SNPs. However, relatively little is known about most specific gene–diet interactions, and many molecular and clinical phenotypes of interest (e.g., body mass index [BMI]) involve multiple genes. In this review, we discuss direct to consumer genetic testing (DTC-GT) and the current potential for precision nutrition based on an individual’s genetic data. We review important issues such as dietary exposure and genetic architecture addressing the concepts of penetrance, pleiotropy, epistasis, polygenicity, and epigenetics. More specifically, we discuss how they complicate using genotypic data to predict phenotypes as well as response to dietary interventions. Then, several examples (including caffeine sensitivity, alcohol dependence, non-alcoholic fatty liver disease, obesity/appetite, cardiovascular, Alzheimer’s disease, folate metabolism, long-chain fatty acid biosynthesis, and vitamin D metabolism) are provided illustrating how genotypic information could be used to inform nutritional recommendations. We conclude by examining ethical considerations and practical applications for using genetic information to inform dietary choices and the future role genetics may play in adopting changes beyond population-wide healthy eating guidelines

Association between Dietary Fatty Acid Intake and Liver Steatosis and Fibrosis in a Sample of Mexican-Origin Hispanic Adults with Overweight or Obesity

Rates of non-alcoholic fatty liver disease (NAFLD) vary dramatically among Hispanic subpopulations, with Mexican-origin (MO) Hispanics experiencing a disproportionate burden. This study examined dietary fatty acid (FA) intake among overweight and obese MO Hispanic adults in the United States (US) and evaluated its association with liver steatosis and fibrosis. Participants (N = 285, MO Hispanic adults) completed 24-h dietary recalls to assess dietary FA exposure. Liver steatosis and fibrosis were estimated using transient elastography (FibroScan®). Multiple regression analysis tested relationships between FA intakes and liver steatosis or fibrosis, adjusting for age, sex, body mass index (BMI) and total energy. A total of 51% (n = 145) of participants were suspected to have NAFLD and 20% self-reported a type 2 diabetes diagnosis. No significant association was observed between Linoleic Acid and α-Linolenic Acid (LA:ALA) ratio, or omega-6 to omega-3 (n-6:n-3) ratio and liver steatosis. However, a one-point increase in the LA:ALA ratio resulted in a 1.01% increase in the liver fibrosis scores (95% CI: [1.00, 1.03]; p = 0.03), and a one-point increase in the n-6:n-3 ratio resulted in a 1.02% increase in liver fibrosis score (95% CI: [1.01, 1.03]; p = 0.01). Further research is needed to determine if modulation of FA intake could reduce NAFLD risk in this high-risk population

Association between Dietary Fatty Acid Intake and Liver Steatosis and Fibrosis in a Sample of Mexican-Origin Hispanic Adults with Overweight or Obesity

Rates of non-alcoholic fatty liver disease (NAFLD) vary dramatically among Hispanic subpopulations, with Mexican-origin (MO) Hispanics experiencing a disproportionate burden. This study examined dietary fatty acid (FA) intake among overweight and obese MO Hispanic adults in the United States (US) and evaluated its association with liver steatosis and fibrosis. Participants (N = 285, MO Hispanic adults) completed 24-h dietary recalls to assess dietary FA exposure. Liver steatosis and fibrosis were estimated using transient elastography (FibroScan®). Multiple regression analysis tested relationships between FA intakes and liver steatosis or fibrosis, adjusting for age, sex, body mass index (BMI) and total energy. A total of 51% (n = 145) of participants were suspected to have NAFLD and 20% self-reported a type 2 diabetes diagnosis. No significant association was observed between Linoleic Acid and α-Linolenic Acid (LA:ALA) ratio, or omega-6 to omega-3 (n-6:n-3) ratio and liver steatosis. However, a one-point increase in the LA:ALA ratio resulted in a 1.01% increase in the liver fibrosis scores (95% CI: [1.00, 1.03]; p = 0.03), and a one-point increase in the n-6:n-3 ratio resulted in a 1.02% increase in liver fibrosis score (95% CI: [1.01, 1.03]; p = 0.01). Further research is needed to determine if modulation of FA intake could reduce NAFLD risk in this high-risk population

Tables: 10

1 Historical relationships among languages are used as a proxy for social history in many non-linguistic settings, including the fields of cultural and molecular anthropology. Linguists have traditionally assembled this information using the standard comparative method. While providing extremely nuanced linguistic information, this approach is time consuming and labor intensive. Conversely, computational approaches are appreciably quicker, but can potentially introduce significant error. Furthermore, current methods often use cognate sets that were themselves coded by historical linguists, thus reducing the benefit of computational approaches. Here we develop a method, based on the ALINE distance, to extract feature-sensitive relationships from paired glosses, datasets that require minimal contribution from trained linguists beyond transcription from primary sources. We validate our results by comparison with data generated independently via the comparative method, and quantify error rates using consistency indices. To showcase our method’s utility and to demonstrate its robustness at local and regional scales, we apply it to two language datasets from eastern Indonesia. As linguistic datasets proliferate, scalable computational methods that mimic historical linguistic reconstruction will become increasingly necessary

Geomicrobiological Changes in Two Ephemeral Desert Playa Lakes in the Western United States

The geochemistry and microbiology of two ephemeral playa lakes in the Western United States, Surprise Valley Alkali Lake (SVAL) and Eldorado Playa (EP), were examined over one wetting cycle, revealing dramatic temporal changes in suspended mineralogy, aqueous chemistry, and bacterial populations. In SVAL the predominant suspended mineral changed from smectite to vermiculite and clinoptilolite, which led to a depletion of soluble Mg2+. Nitrate became depleted in both playas as a result of biological nitrogen demand imparted by unusually dense microbial communities reaching 1 × 108 cultivable heterotrophs per ml of water. One hundred eighty eight bacterial isolates were obtained, representing sixty phylotypes and four phyla: Actinobacteria, Bacteroidetes, Proteobacteria, and Firmicutes. Phylogenetic analyses suggested that the microbial communities reflected different phases of succession, with SVAL changing from a diverse community with abundant Yonghaparkia to a less diverse late summer community with abundant Bacteroidetes and Proteobacteria such as Loktanella, Rhodobaca, Saccharospirillum, Flexibacter, and phylogenetically novel members of the Flexibacteriaceae. In EP, a diverse assemblage of bacteria often associated with soils was replaced very quickly by a much less even community dominated by Yonghaparkia, Sandarakinorhabdus, and relatives of Belliella baltica. Strikingly, the early summer microbial community from SVAL was not significantly different from the EP community that developed within one week of flooding, even though these playas are almost 1000 km apart, whereas sympatric communities in different phases of succession were different. To our knowledge, this is one of the first geomicrobiological studies of a recharge playa, the dominant playa type worldwide