Background Wheezing illnesses cause major morbidity in infants and are frequent precursors to asthma. Objective We sought to examine environmental factors associated with recurrent wheezing in ...inner-city environments. Methods The Urban Environment and Childhood Asthma study examined a birth cohort at high risk for asthma (n = 560) in Baltimore, Boston, New York, and St Louis. Environmental assessments included allergen exposure and, in a nested case-control study of 104 children, the bacterial content of house dust collected in the first year of life. Associations were determined among environmental factors, aeroallergen sensitization, and recurrent wheezing at age 3 years. Results Cumulative allergen exposure over the first 3 years was associated with allergic sensitization, and sensitization at age 3 years was related to recurrent wheeze. In contrast, first-year exposure to cockroach, mouse, and cat allergens was negatively associated with recurrent wheeze (odds ratio, 0.60, 0.65, and 0.75, respectively; P ≤ .01). Differences in house dust bacterial content in the first year, especially reduced exposure to specific Firmicutes and Bacteriodetes, was associated with atopy and atopic wheeze. Exposure to high levels of both allergens and this subset of bacteria in the first year of life was most common among children without atopy or wheeze. Conclusions In inner-city environments children with the highest exposure to specific allergens and bacteria during their first year were least likely to have recurrent wheeze and allergic sensitization. These findings suggest that concomitant exposure to high levels of certain allergens and bacteria in early life might be beneficial and suggest new preventive strategies for wheezing and allergic diseases.
Autozygosity, the proportion of the genome that is homozygous by descent, has been associated with variation in multiple health-related traits impacting evolutionary fitness. Autozygosity (FROH) is ...typically measured from runs of homozygosity (ROHs) that arise when identical-by-descent (IBD) haplotypes are inherited from each parent. Population isolates with a small set of common founders have elevated autozygosity relative to outbred populations.
In this study, we examined whether degree of autozygosity was associated with variation in 96 cardiometabolic traits among 7221 Old Order Amish individuals residing in Lancaster County, PA. We estimated the average length of an ROH segment to be 6350 KB, with each individual having on average 17.2 segments 1.5 KB or larger. Measurements of genome-wide and regional FROH were used as the primary predictors of trait variation in association analysis.
In genome-wide FROH analysis, we did not identify any associations that withstood Bonferroni-correction (p = 0.0005). However, on regional FROH analysis, we identified associations exceeding genome-wide thresholds for two traits: serum bilirubin levels, which were significantly associated with a region on chromosome 2 localized to a region surrounding UGT1A10 (p = 1 × 10- 43), and HbA1c levels, which were significantly associated with a region on chromosome 8 localized near CHRNB3 (p = 8 × 10- 10).
These analyses highlight the potential value of autozygosity mapping in founder populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Environmental exposures in early life appear to play an important role in the pathogenesis of childhood asthma, but the potentially modifiable exposures that lead to asthma remain uncertain.
We ...sought to identify early-life environmental risk factors for childhood asthma in a birth cohort of high-risk inner-city children.
We examined the relationship of prenatal and early-life environmental factors to the occurrence of asthma at 7 years of age among 442 children.
Higher house dust concentrations of cockroach, mouse, and cat allergens in the first 3 years of life were associated with lower risk of asthma (for cockroach allergen: odds ratio per interquartile range increase in concentration, 0.55; 95% CI, 0.36-0.86; P < .01). House dust microbiome analysis using 16S ribosomal RNA sequencing identified 202 and 171 bacterial taxa that were significantly (false discovery rate < 0.05) more or less abundant, respectively, in the homes of children with asthma. A majority of these bacteria were significantly correlated with 1 of more allergen concentrations. Other factors associated significantly positively with asthma included umbilical cord plasma cotinine concentration (odds ratio per geometric SD increase in concentration, 1.76; 95% CI, 1.00-3.09; P = .048) and maternal stress and depression scores.
Among high-risk inner-city children, higher indoor levels of pet or pest allergens in infancy were associated with lower risk of asthma. The abundance of a number of bacterial taxa in house dust was associated with increased or decreased asthma risk. Prenatal tobacco smoke exposure and higher maternal stress and depression scores in early life were associated with increased asthma risk.
Abstract
Telomere length (TL) attrition, epigenetic age acceleration, and mitochondrial DNA copy number (mtDNAcn) decline are established hallmarks of aging. Each has been individually associated ...with Alzheimer’s dementia, cognitive function, and pathologic Alzheimer’s disease (AD). Epigenetic age and mtDNAcn have been studied in brain tissue directly but prior work on TL in brain is limited to small sample sizes and most studies have examined leukocyte TL. Importantly, TL, epigenetic age clocks, and mtDNAcn have not been studied jointly in brain tissue from an AD cohort. We examined dorsolateral prefrontal cortex (DLPFC) tissue from N = 367 participants of the Religious Orders Study (ROS) or the Rush Memory and Aging Project (MAP). TL and mtDNAcn were estimated from whole genome sequencing (WGS) data and cortical clock age was computed on 347 CpG sites. We examined dementia, MCI, and level of and change in cognition, pathologic AD, and three quantitative AD traits, as well as measures of other neurodegenerative diseases and cerebrovascular diseases (CVD). We previously showed that mtDNAcn from DLPFC brain tissue was associated with clinical and pathologic features of AD. Here, we show that those associations are independent of TL. We found TL to be associated with β-amyloid levels (beta = − 0.15,
p
= 0.023), hippocampal sclerosis (OR = 0.56,
p
= 0.0015) and cerebral atherosclerosis (OR = 1.44,
p
= 0.0007). We found strong associations between mtDNAcn and clinical measures of AD. The strongest associations with pathologic measures of AD were with cortical clock and there were associations of mtDNAcn with global AD pathology and tau tangles. Of the other pathologic traits, mtDNAcn was associated with hippocampal sclerosis, macroscopic infarctions and CAA and cortical clock was associated with Lewy bodies. Multi-modal age acceleration, accelerated aging on both mtDNAcn and cortical clock, had greater effect size than a single measure alone. These findings highlight for the first time that age acceleration determined on multiple genomic measures, mtDNAcn and cortical clock may have a larger effect on AD/AD related disorders (ADRD) pathogenesis than single measures.
Abstract
We conducted a search for narrowband radio signals over four observing sessions in 2020–2023 with the
L
-band receiver (1.15–1.73 GHz) of the 100 m diameter Green Bank Telescope. We pointed ...the telescope in the directions of 62 TESS Objects of Interest, capturing radio emissions from a total of ∼11,680 stars and planetary systems in the ∼9′ beam of the telescope. All detections were either automatically rejected or visually inspected and confirmed to be of anthropogenic nature. We also quantified the end-to-end efficiency of radio SETI pipelines with a signal injection and recovery analysis. The UCLA SETI pipeline recovers 94.0% of the injected signals over the usable frequency range of the receiver and 98.7% of the injections when regions of dense radio frequency interference are excluded. In another pipeline that uses incoherent sums of 51 consecutive spectra, the recovery rate is ∼15 times smaller at ∼6%. The pipeline efficiency affects calculations of transmitter prevalence and SETI search volume. Accordingly, we developed an improved Drake figure of merit and a formalism to place upper limits on transmitter prevalence that take the pipeline efficiency and transmitter duty cycle into account. Based on our observations, we can state at the 95% confidence level that fewer than 6.6% of stars within 100 pc host a transmitter that is continuously transmitting a narrowband signal with an equivalent isotropic radiated power (EIRP) > 10
13
W. For stars within 20,000 ly, the fraction of stars with detectable transmitters (EIRP > 5 × 10
16
W) is at most 3 × 10
−4
. Finally, we showed that the UCLA SETI pipeline natively detects the signals detected with AI techniques by Ma et al.
Characterization of patterns of wheezing and allergic sensitization in early life may allow for identification of specific environmental exposures impacting asthma development.
To define respiratory ...phenotypes in inner-city children and their associations with early-life environmental exposures.
Data were collected prospectively from 442 children in the URECA (Urban Environment and Childhood Asthma) birth cohort through age 7 years, reflecting symptoms (wheezing), aeroallergen sensitization, pulmonary function, and body mass index. Latent class mixed models identified trajectories of wheezing, allergic sensitization, and pulmonary function. Cluster analysis defined nonoverlapping groups (termed phenotypes). Potential associations between phenotypes and early-life environmental exposures were examined.
Five phenotypes were identified and mainly differentiated by patterns of wheezing and allergic sensitization (low wheeze/low atopy; low wheeze/high atopy; transient wheeze/low atopy; high wheeze/low atopy; high wheeze/high atopy). Asthma was most often present in the high-wheeze phenotypes, with greatest respiratory morbidity among children with frequent wheezing and allergic sensitization. These phenotypes differentially related to early-life exposures, including maternal stress and depression, antenatal environmental tobacco smoke, house dust microbiome, and allergen content (all P < 0.05). Prenatal smoke exposure, maternal stress, and depression were highest in the high-wheeze/low-atopy phenotype. The high-wheeze/high-atopy phenotype was associated with low household microbial richness and diversity. Early-life aeroallergen exposure was low in high-wheeze phenotypes.
Patterns of wheezing, allergic sensitization, and lung function identified five respiratory phenotypes among inner-city children. Early-life environmental exposure to stress, depression, tobacco smoke, and indoor allergens and microbes differentially associate with specific phenotypes.
Genetically isolated populations that arise due to recent bottleneck events have reduced genetic variation reflecting the common set of founders. Increased genetic relatedness among members of ...isolated populations puts them at increased risk for some recessive disorders that are rare in outbred populations. To assess the burden on reproductive health, we compared frequencies of adverse reproductive outcomes between Amish couples who were both heterozygous carriers of a highly penetrant pathogenic or likely pathogenic variant and noncarrier couples from the same Amish community. In addition, we evaluated whether overall genetic relatedness of parents was associated with reproductive outcomes. Of the 1824 couples included in our study, 11.1% were at risk of producing a child with an autosomal recessive disorder. Carrier couples reported a lower number of miscarriages compared to noncarrier couples (p = 0.02), although the number of stillbirths (p = 0.3), live births (p = 0.9), and number of pregnancies (p = 0.9) did not differ significantly between groups. In contrast, higher overall relatedness between spouses was positively correlated with number of live births (p < 0.0001), pregnancies (p < 0.0001), and stillbirths (p = 0.03), although not with the number of miscarriages (p = 0.4). These results highlight a complex association between relatedness of parents and reproductive health outcomes in this community.
Founder populations may be enriched with certain genetic variants of high clinical impact compared to nonfounder populations due to bottleneck events and genetic drift. Using exome sequencing (ES), ...we quantified the load of pathogenic variants that may be clinically actionable in 6136 apparently healthy adults living in the Lancaster, PA Old Order Amish settlement. We focused on variants in 78 genes deemed clinically actionable by the American College of Medical Genetics and Genomics (ACMG) or Geisinger's MyCode Health Initiative. ES revealed 3191 total variants among these genes including 480 nonsynonymous variants. After quality control and filtering, we applied the ACMG/AMP guidelines for variant interpretation and classified seven variants, across seven genes, as either pathogenic or likely pathogenic. Through genetic drift, all seven variants, are highly enriched in the Amish compared to nonfounder populations. In total, 14.7% of Lancaster Amish individuals carry at least one of these variants, largely explained by the 13% who harbor a copy of a single variant in APOB. Other studies report combined frequencies of pathogenic/likely pathogenic (P/LP) variants in actionable genes between 2.0% and 6.2% in outbred populations. The Amish population harbors fewer actionable variants compared to similarly characterized nonfounder populations but have a higher frequency of each variant identified, offering opportunities for efficient and cost‐effective targeted precision medicine.
Chronic urticaria with concomitant systemic symptoms may be seen in several rheumatologic and autoinflammatory conditions. Although most of these conditions tend to improve with corticosteroids, ...symptoms often recur with dose tapering. The appearance of the rash in addition to the symptom pattern and laboratory data must be considered to differentiate potential causes. We presented a unique case of chronic urticaria with fevers and arthralgias. A diagnosis was made, and the patient had rapid improvement with targeted therapy.
Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and ...federal public health agencies investigated the first case of COVID-19 in Illinois, USA.
Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient's symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested.
Patient 1—a woman in her 60s—returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2.
Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected.
None.
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