Prevalence of Dementia and Cognitive Impairment in East Africa Region: A Scoping Review of Population-Based Studies and Call for Further Research.

Background: Population-based research on the prevalence and determinants of dementia, Alzheimer's disease, and cognitive impairment is scarce in East Africa. Objective: To provide an overview of community- and population-based studies among older adults on the prevalence of dementia and cognitive impairment in East Africa, and identify research gaps. Methods: We carried out a literature search using three electronic databases (PubMed, Scopus, Google Scholar) using pertinent search terms. Results: After screening 445 publications, we identified four publications on the population-based prevalence of dementia, and three on cognitive impairment. Prevalence rates varied from 6- 23% for dementia, and 7- 44% for cognitive impairment, among participants aged≥50-70 years. Old age and a lower education level were risk factors for dementia and cognitive impairment. Physical inactivity, lack of a ventilated kitchen, and history of central nervous system infections and chronic headache were associated with increased odds of dementia. Female sex, depression, having no spouse, increased lifetime alcohol consumption, low income, rural residence, and low family support were associated with increased odds of cognitive impairment. Potential misclassification and non-standardized data collection methods are research gaps that should be addressed in future studies. Conclusions: Establishing collaborative networks and partnering with international research institutions may enhance the capacity for conducting population-based studies on dementia and cognitive impairment in East Africa. Longitudinal studies may provide valuable insights on incidence, as well as potential risk and protective factors of dementia and cognitive impairment, and may inform the development of targeted interventions including preventive strategies in the region.

Analyzing Racial Disparities in Pediatric Atopic Comorbidity Emergency Department Visitation using Electronic Health Records.

BACKGROUND: Although atopic diseases and associated co-morbidities are prevalent in children, little is known about racial differences in emergency department (ED) visitation. OBJECTIVE: We sought to examine racial differences in ED visitation among children with allergic comorbidities. METHODS: We conducted a retrospective study of patients (<21 years) who visited the ED at a large pediatric hospital for atopic dermatitis (AD), food allergy (FA), asthma, allergic rhinitis (AR), and eosinophilic esophagitis (EoE) from 2015 to 2019. We determined the probability of ED encounter-free using hazard ratios (HR) and time to recurrence (TTR) of ED encounter for patients identified as Black/African American (AA) and White/European American (EA). We assessed potentially underlying allergic, demographic, and place-based factors, and potential interactions between factors. RESULTS: A total of 30,894 patients (38% AA, 62% EA) had 83,078 ED encounters (38,378 first ED encounters, and 44,700 recurrent ED encounters) during the study period. Asthma and AR showed the highest rate of comorbidity in ED encounters in both AA and EA children. AA children exhibited higher HR for encounter following index AD and asthma encounters. We found an interaction between the type of insurance and race in ED encounters for AD, FA, AR, and EoE. In AA children, those insured by Medicaid demonstrated a higher HR for any encounter compared to those with commercial insurance. Conversely, in EA children, those with Medicaid insurance showed a lower HR compared to their commercially insured peers. Regardless of race, allergic comorbidity increased the HR of ED encounter (1.12-1.62) for all allergic diseases. At 5-years follow up, mean differences in TTR were shorter in AA children compared to EA children in AD, FA, and asthma. CONCLUSION: Identification of disease-specific racial disparities in ED visitation related to atopic diseases is a necessary first step toward the design and implementation of interventions capable of equitably reducing emergency care in atopic comorbid children.

SPIN: sex-specific and pathway-based interpretable neural network for sexual dimorphism analysis.

Sexual dimorphism in prevalence, severity and genetic susceptibility exists for most common diseases. However, most genetic and clinical outcome studies are designed in sex-combined framework considering sex as a covariate. Few sex-specific studies have analyzed males and females separately, which failed to identify gene-by-sex interaction. Here, we propose a novel unified biologically interpretable deep learning-based framework (named SPIN) for sexual dimorphism analysis. We demonstrate that SPIN significantly improved the C-index up to 23.6% in TCGA cancer datasets, and it was further validated using asthma datasets. In addition, SPIN identifies sex-specific and -shared risk loci that are often missed in previous sex-combined/-separate analysis. We also show that SPIN is interpretable for explaining how biological pathways contribute to sexual dimorphism and improve risk prediction in an individual level, which can result in the development of precision medicine tailored to a specific individual's characteristics.

Urinary Volatile Organic Compound Metabolites Are Associated with Reduced Lung Function in U.S. Children and Adolescents.

(1) Background: Volatile organic compounds (VOCs) are indoor pollutants absorbed by inhalation. The association of several VOCs with lung function in children and adolescents is unknown. (2) Methods: We analyzed 505 participants, 6-17-year-olds from the 2011-2012 National Health and Nutrition Examination Survey. Multiple linear regression models were fitted to estimate the associations of VOC metabolites with spirometry outcomes adjusting for covariates. (3) Results: Urinary metabolites of xylene, acrylamide, acrolein, 1,3-butadiene, cyanide, toluene, 1-bromopropane, acrylonitrile, propylene oxide, styrene, ethylbenzene, and crotonaldehyde were all detected in ≥64.5% of participants. Forced expiratory volume in 1 s (FEV1) % predicted was lower in participants with higher levels of metabolites of acrylamide (ß: -7.95, 95% CI: -13.69, -2.21) and styrene (ß: -6.33, 95% CI: -11.60, -1.07), whereas the FEV1 to forced vital capacity (FVC) ratio % was lower in children with higher propylene oxide metabolite levels (ß: -2.05, 95% CI: -3.49, -0.61). FEV1 % predicted was lower with higher crotonaldehyde metabolite levels only in overweight/obese participants (ß: -15.42, 95% CI: -26.76, -4.08) (Pinteraction < 0.001) and with higher 1-bromopropane metabolite levels only in those with serum cotinine > 1 ng/mL (ß: -6.26, 95% CI: -9.69, -2.82) (Pinteraction < 0.001). (4) Conclusions: We found novel associations of metabolites for acrylamide, propylene oxide, styrene, 1-bromopropane and crotonaldehyde with lower lung function in children and adolescents.

The burden of severe asthma in sub-Saharan Africa: Findings from the African Severe Asthma Project.

Background: Severe asthma is associated with high morbidity, mortality, and health care utilization, but its burden in Africa is unknown. Objective: We sought to determine the burden (prevalence, mortality, and activity and work impairment) of severe asthma in 3 countries in East Africa: Uganda, Kenya, and Ethiopia. Methods: Using the American Thoracic Society/European Respiratory Society case definition of severe asthma, we analyzed for the prevalence of severe asthma (requiring Global Initiative for Asthma [GINA] steps 4-5 asthma medications for the previous year to achieve control) and severe refractory asthma (remains uncontrolled despite treatment with GINA steps 4-5 asthma medications) in a cohort of 1086 asthma patients who had been in care for 12 months and had received all GINA-recommended medications. Asthma control was assessed by the asthma control questionnaire (ACQ). Results: Overall, the prevalence of severe asthma and severe refractory asthma was 25.6% (95% confidence interval [CI], 23.1-28.3) and 4.6% (95% CI, 3.5-6.0), respectively. Patients with severe asthma were (nonsevere vs severe vs severe refractory) older (39, 42, 45 years, P = .011), had high skin prick test reactivity (67.1%, 76.0%, 76.0%, P = .004), had lower forced expiratory volume in 1 second percentage (81%, 61%, 55.5%, P < .001), had lower quality of life score (129, 127 vs 121, P < .001), and had higher activity impairment (10%, 30%, 50%, P < .001). Factors independently associated with severe asthma were hypertension comorbidity; adjusted odds ratio 2.21 (1.10-4.47), P = .027, high bronchial hyperresponsiveness questionnaire score; adjusted odds ratio 2.16 (1.01-4.61), P = .047 and higher ACQ score at baseline 2.80 (1.55-5.08), P = .001. Conclusion: The prevalence of severe asthma in Africa is high and is associated with high morbidity and poor quality of life.

Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations.

Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. Finally, we created a framework for regulatory compliance and developed a PRS clinical report for return to providers and for inclusion in an additional genome-informed risk assessment. The initial experience from eMERGE can inform the approach needed to implement PRS-based testing in diverse clinical settings.

Aryl hydrocarbon receptor and IL-13 signaling crosstalk in human keratinocytes and atopic dermatitis.

Introduction: Atopic dermatitis (AD) is an allergic skin disease mediated by skin barrier impairment and IL-13-driven immune response. Activation of the aryl hydrocarbon receptor (AHR) has shown promise in early clinical trials for AD; however, the mechanism by which AHR partially ameliorates AD is not well known. Methods: Gene expression data from human biopsies were analyzed, and compared to gene expression from RNA-sequencing in our in-vitro HaCaT cell model system. Western blot, ELISA qRT-PCR were used to further explore the relationship between AHR and IL-13 signaling in HaCaT cells. Results: The AHR target gene CYP1A1 was decreased in lesional skin compared with healthy control skin (p = 4.30 × 10-9). Single-cell RNA sequencing (scRNAseq) demonstrated increased AHR expression (p < 1.0 × 10-4) and decreased CYP1A1 expression in lesional AD keratinocytes compared with healthy control keratinocytes (p < 0.001). Activation of AHR by AHR agonists in HaCaT cells reversed IL-13-dependent gene expression of several key genes in AD pathogenesis, most notably the eosinophil chemoattractant CCL26 (eotaxin-3). Differentially expressed genes in keratinocytes of patients with AD substantially overlapped with genes regulated by AHR agonists from HaCaT cells by RNAseq, but in reverse direction. Mechanistically, there was evidence for direct transcriptional effects of AHR; AHR binding motifs were identified in the differentially expressed genes from lesional AD keratinocytes compared to control keratinocytes, and AHR activation did not modify IL-13-dependent signal transducer and activator of transcription 6 (STAT6) translocation to the nucleus. Discussion: Together, these data suggest that the AHR pathway is dysregulated in AD and that AHR modulates IL-13 downstream signaling in keratinocytes through genome-wide, transcriptional regulatory effects.

Ancestry Specific Polygenic Risk Score, Dietary Patterns, Physical Activity, and Cardiovascular Disease.

It is unknown whether the impact of high diet quality and physical activity depends on the level of polygenic risk score (PRS) in different ancestries. Our cross-sectional study utilized de-identified data from 1987-2010 for self-reported European Americans (n = 6575) and African Americans (n = 1606). The high-risk PRS increased ASCVD risk by 59% (Risk Ratio (RR) = 1.59; 95% Confidence Interval:1.16-2.17) in the highest tertile for African Americans and by 15% (RR = 1.15; 1.13-1.30) and 18% (RR = 1.18; 1.04-1.35) in the second and highest tertiles compared to the lowest tertile in European Americans. Within the highest PRS tertiles, high physical activity-diet combinations (Dietary Approaches to Stop High Blood Pressure (DASH), Mediterranean, or Southern) reduced ASCVD risks by 9% (RR = 0.91; 0.85-0.96) to 15% (RR = 0.85; 0.80-0.90) in European Americans; and by 13% (RR = 0.87; 0.78-0.97) and 18% (RR = 0.82; 0.72-0.95) for DASH and Mediterranean diets, respectively, in African Americans. Top molecular pathways included fructose metabolism and catabolism linked to obesity, insulin resistance, and type 2 diabetes. Additional molecular pathways for African Americans were Vitamin D linked to depression and aging acceleration and death signaling associated with cancer. Effects of high diet quality and high physical activity can counterbalance the influences of genetically high-risk PRSs on ASCVD risk, especially in African Americans.

Racial differences in length of stay and readmission for asthma in the all of us research program.

BACKGROUND: This study addresses the limited research on racial disparities in asthma hospitalization outcomes, specifically length of stay (LOS) and readmission, across the U.S. METHODS: We analyzed in-patient and emergency department visits from the All of Us Research Program, identifying various risk factors (demographic, comorbid, temporal, and place-based) associated with asthma LOS and 30-day readmission using Bayesian mixed-effects models. RESULTS: Of 17,233 patients (48.0% White, 30.7% Black, 19.7% Hispanic/Latino, 1.3% Asian, and 0.3% Middle Eastern and North African) with 82,188 asthma visits, Black participants had 20% shorter LOS and 12% higher odds of readmission, compared to White participants in multivariate analyses. Public-insured patients had 14% longer LOS and 39% higher readmission odds than commercially insured patients. Weekend admissions resulted in a 12% shorter LOS but 10% higher readmission odds. Asthmatics with chronic diseases had a longer LOS (range: 6-39%) and higher readmission odds (range: 9-32%) except for those with allergic rhinitis, who had a 23% shorter LOS. CONCLUSIONS: A comprehensive understanding of the factors influencing asthma hospitalization, in conjunction with diverse datasets and clinical-community partnerships, can help physicians and policymakers to systematically address racial disparities, healthcare utilization and equitable outcomes in asthma care.

Integrative analysis identifies gene signatures mediating the effect of DNA methylation on asthma severity and lung function.

DNA methylation (DNAm) changes play a key role in regulating gene expression in asthma. To investigate the role of epigenetics and transcriptomics change in asthma, we used publicly available DNAm (asthmatics, n = 96 and controls, n = 46) and gene expression (asthmatics, n = 79 and controls, n = 39) data derived from bronchial epithelial cells (BECs). We performed differential methylation/expression and weighted co-methylation/co-expression network analyses to identify co-methylated and co-expressed modules associated with asthma severity and lung function. For subjects with both DNAm and gene expression data (asthmatics, n = 79 and controls, n = 39), machine-learning technique was used to prioritize CpGs and differentially expressed genes (DEGs) for asthma risk prediction, and mediation analysis was used to uncover DEGs that mediate the effect of DNAm on asthma severity and lung function in BECs. Finally, we validated CpGs and their associated DEGs and the asthma risk prediction model in airway epithelial cells (AECs) dataset. The asthma risk prediction model based on 18 CpGs and 28 DEGs showed high accuracy in both the discovery BEC dataset with area under the receiver operating characteristic curve (AUC) = 0.99 and the validation AEC dataset (AUC = 0.82). Genes in the three co-methylated and six co-expressed modules were enriched in multiple pathways including WNT/beta-catenin signaling and notch signaling. Moreover, we identified 35 CpGs correlated with DEGs in BECs, of which 17 CpGs including cg01975495 (SERPINE1), cg10528482 (SLC9A3), cg25477769 (HNF1A) and cg26639146 (CD9), cg17945560 (TINAGL1) and cg10290200 (FLNC) were replicated in AECs. These DEGs mediate the association between DNAm and asthma severity and lung function. Overall, our study investigated the role of DNAm and gene expression change in asthma and provided an insight into the mechanisms underlying the effects of DNA methylation on asthma, asthma severity and lung function.

Gender-based violence in the context of armed conflict in Northern Ethiopia.

BACKGROUND: Gender-based violence (GBV) particularly against women is unfortunately common during armed conflicts. No rigorous and comprehensive empirical work has documented the extent of GBV and its consequences that took place during the two years of devastating armed conflict in Northern Ethiopia. This study aims to assess GBV and its consequences in war-torn areas of northern Ethiopia. METHODS: We used a qualitative method augmented by quantitative method to enroll research participants. We conducted in-depth interviews to characterize the lived experiences of GBV survivors. All interviews were conducted confidentially. The data were collected to the point of data saturation. All interviews were transcribed verbatim into local language, translated into English, and analyzed using a thematic analysis approach. We also used reports from healthcare facilities and conducted a descriptive analysis of the demographic characteristics of study participants. RESULTS: One thousand one hundred seventy-seven persons reported GBV to healthcare providers. The qualitative study identified several forms of violence (sexual, physical, and psychological). Gang rape against women including minors as young as 14 years old girls was reported. Additionally, the perpetrators sexually violated women who were pregnant, and elderly women as old as 65 years, who took refuge in religious institutions. The perpetrators committed direct assaults on the body with items (e.g., burning the body with cigarette fire) or weapons, holding women and girls as captives, and deprivation of sleep and food. GBV survivors reported stigma, prejudice, suicide attempts, nightmares, and hopelessness. GBV survivors dealt with the traumatic stress by outmigration (leaving their residences), seeking care at healthcare facilities, self-isolation, being silent, dropping out of school, and seeking counseling. CONCLUSION: GBV survivors were subjected to multiple and compounding types of violence, with a wide range of adverse health consequences for survivors and their families. GBV survivors require multifaceted interventions including psychological, health, and economic support to rehabilitate them to lead a productive life.

Ancestry Specific Polygenic Risk Score, Dietary Patterns, Physical Activity, and Cardiovascular Disease.

Background: It is unknown whether the impact of high diet-quality and physical activity (PA) depends on the level of polygenic risk score (PRS) in different ancestries. Objective: Determine the associations and interactions between high-risk PRSs, dietary patterns, and high PA with atherosclerotic cardiovascular disease (ASCVD) in European Americans (EAs) and African Americans (AAs). Another aim determined the molecular pathways of PRS-mapped genes and their relationships with dietary intake. Methods: Cross-sectional analyses utilized de-identified data from 1987-2010 from 7-National Heart, Lung, and Blood Institute Candidate Gene Association Resource studies from the Database of Genotypes and Phenotypes studies for EAs (n=6,575) and AAs (n=1,606). Results: The high-risk PRS increased ASCVD risk by 59% (Risk Ratio=1.59;95% Confidence Interval:1.16-2.17) in the highest tertile for AAs and by 15% (RR=1.15;1.13-1.30) and 18% (RR=1.18;1.04-1.35) in the second and highest tertiles compared to the lowest tertile in EAs. Within the highest PRS tertiles, high PA-diet combinations (Dietary Approaches to Stop High Blood Pressure (DASH), or Mediterranean, or Southern) reduced ASCVD risks by 9% (RR=0.91;0.85-0.96) to 15% (RR=0.85;0.80-0.90) in EAs; and by 13% (RR=0.87;0.78-0.97) and 18% (RR=0.82;0.72-0.95) for the DASH and Mediterranean diets, respectively in AAs. Top molecular pathways included fructose metabolism and catabolism linked to obesity, insulin resistance, and type 2 diabetes in both ancestries. Additional molecular pathways for AAs were Vitamin D linked to depression and aging acceleration; and death signaling associated with cancer. Conclusions: Effects of high diet-quality and high PA can counterbalance the influences of genetically high-risk PRSs on ASCVD risk, especially in AAs.

Atopic dermatitis and ocular allergy: common mechanisms and uncommon questions.

PURPOSE OF REVIEW: Atopic dermatitis (AD) and ocular allergy aka allergic eye disease (AED) are two common conditions that often coexist in patients. However, molecular connections between these two conditions are incompletely understood. While common etiologic components including Th2 immune signaling have been suggested for AD and AED, the mechanism how current Th2-targetd therapies (dupilumab, tralokinumab) for AD can augment conjunctivitis is not well understood. RECENT FINDINGS: Differentially regulated genes and pathways relevant for AD disease manifestation are known. In contrast, similar information is not yet available for AED, which could be largely addressed by emerging noninvasive ocular sampling techniques. Emerging evidence indicated a reduction in goblet cell number and mucin production in a subpopulation of AD patients with AD leading to adverse ocular outcomes, while other potential mechanisms could also be involved. Involvement of particular barrier function protein(s) in AED needs further investigation. SUMMARY: Modern cytokine-targeted therapies for AD showed elevated risk for developing conjunctivitis. Recently developed noninvasive sampling techniques should be leveraged to identify AD endotypes associated with AED and with dupilumab-associated ocular outcomes.

Development and validation of asthma risk prediction models using co-expression gene modules and machine learning methods.

Asthma is a heterogeneous respiratory disease characterized by airway inflammation and obstruction. Despite recent advances, the genetic regulation of asthma pathogenesis is still largely unknown. Gene expression profiling techniques are well suited to study complex diseases including asthma. In this study, differentially expressed genes (DEGs) followed by weighted gene co-expression network analysis (WGCNA) and machine learning techniques using dataset generated from airway epithelial cells (AECs) and nasal epithelial cells (NECs) were used to identify candidate genes and pathways and to develop asthma classification and predictive models. The models were validated using bronchial epithelial cells (BECs), airway smooth muscle (ASM) and whole blood (WB) datasets. DEG and WGCNA followed by least absolute shrinkage and selection operator (LASSO) method identified 30 and 34 gene signatures and these gene signatures with support vector machine (SVM) discriminated asthmatic subjects from controls in AECs (Area under the curve: AUC = 1) and NECs (AUC = 1), respectively. We further validated AECs derived gene-signature in BECs (AUC = 0.72), ASM (AUC = 0.74) and WB (AUC = 0.66). Similarly, NECs derived gene-signature were validated in BECs (AUC = 0.75), ASM (AUC = 0.82) and WB (AUC = 0.69). Both AECs and NECs based gene-signatures showed a strong diagnostic performance with high sensitivity and specificity. Functional annotation of gene-signatures from AECs and NECs were enriched in pathways associated with IL-13, PI3K/AKT and apoptosis signaling. Several asthma related genes were prioritized including SERPINB2 and CTSC genes, which showed functional relevance in multiple tissue/cell types and related to asthma pathogenesis. Taken together, epithelium gene signature-based model could serve as robust surrogate model for hard-to-get tissues including BECs to improve the molecular etiology of asthma.

Selection, optimization, and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse populations.

Polygenic risk scores (PRS) have improved in predictive performance supporting their use in clinical practice. Reduced predictive performance of PRS in diverse populations can exacerbate existing health disparities. The NHGRI-funded eMERGE Network is returning a PRS-based genome-informed risk assessment to 25,000 diverse adults and children. We assessed PRS performance, medical actionability, and potential clinical utility for 23 conditions. Standardized metrics were considered in the selection process with additional consideration given to strength of evidence in African and Hispanic populations. Ten conditions were selected with a range of high-risk thresholds: atrial fibrillation, breast cancer, chronic kidney disease, coronary heart disease, hypercholesterolemia, prostate cancer, asthma, type 1 diabetes, obesity, and type 2 diabetes. We developed a pipeline for clinical PRS implementation, used genetic ancestry to calibrate PRS mean and variance, created a framework for regulatory compliance, and developed a PRS clinical report. eMERGE's experience informs the infrastructure needed to implement PRS-based implementation in diverse clinical settings.

Analysis of ancestry-specific polygenic risk score and diet composition in type 2 diabetes.

BACKGROUND: Carbohydrate and protein dietary proportions have been debated as to whether higher or lower levels are optimal for diabetes metabolic control. OBJECTIVE: The objective of this study was to investigate the associations, interactions, and mediational relationships between a polygenic risk score (PRS), carbohydrate and protein intake, and physical activity level on type 2 diabetes (T2DM) by genetic ancestry, in European Americans and African Americans. A secondary objective examined the biological pathways associated with the PRS-linked genes and their relationships to dietary intake. METHODS: We performed a cross-sectional study in 9,393 participants: 83.3% European Americans and 16.7% African Americans from 7-NHLBI Care studies obtained from the database of Genotypes and Phenotypes. The main outcome was T2DM. Carbohydrate and protein intake derived from food frequency questionnaires were calculated as percent calories. Data were analyzed using multivariable generalized estimation equation models to derive odds ratios (OR) and 95% confidence intervals (CI). Ancestry-specific PRSs were constructed using joint-effects Summary Best Linear Unbiased Estimation in the train dataset and replicated in the test dataset. Mediation analysis was performed using VanderWeele's method. RESULTS: The PRS in the highest tertile was associated with higher risk of T2DM in European Americans (OR = 1.25;CI = 1.03-1.51) and African Americans (OR = 1.54;1.14-2.09). High carbohydrate and low protein intake had lower risks of T2DM when combined with the PRS after adjusting for covariates. In African Americans, high physical activity combined with the high PRS and high protein diet was associated with a 28% lower incidence of T2DM when compared to low physical activity. In mediational models in African Americans, the PRS-T2DM association was mediated by protein intake in the highest tertile by 55%. The top PRS tertile had the highest magnitude of risks with metabolic factors that were significantly associated with T2DM, especially in European Americans. We found metabolic pathways associated with the PRS-linked genes that were related to insulin/IGF and ketogenesis/ketolysis that can be activated by moderate physical activity and intermittent fasting for better T2DM control. CONCLUSIONS: Clinicians may want to consider diets with a higher portion of carbohydrates than protein, especially when the burden of high-risk alleles is great in patients with T2DM. In addition, clinicians and other medical professionals may want to emphasize the addition of physical activity as part of treatment regimen especially for African Americans. Given the metabolic pathways we identified, moderate physical activity and intermittent fasting should be explored. Researchers may want to consider longitudinal or randomized clinical trials to determine the predictive ability of different dietary patterns to inhibit T2DM in the presence of obesity and an elevated PRS.

Multi-omics profiling approach in food allergy.

The prevalence of food allergy (FA) among children is increasing, affecting nearly 8% of children, and FA is the most common cause of anaphylaxis and anaphylaxis-related emergency department visits in children. Importantly, FA is a complex, multi-system, multifactorial disease mediated by food-specific immunoglobulin E (IgE) and type 2 immune responses and involving environmental and genetic factors and gene-environment interactions. Early exposure to external and internal environmental factors largely influences the development of immune responses to allergens. Genetic factors and gene-environment interactions have established roles in the FA pathophysiology. To improve diagnosis and identification of FA therapeutic targets, high-throughput omics approaches have emerged and been applied over the past decades to screen for potential FA biomarkers, such as genes, transcripts, proteins, and metabolites. In this article, we provide an overview of the current status of FA omics studies, namely genomic, transcriptomic, epigenomic, proteomic, exposomic, and metabolomic. The current development of multi-omics integration of FA studies is also briefly discussed. As individual omics technologies only provide limited information on the multi-system biological processes of FA, integration of population-based multi-omics data and clinical data may lead to robust biomarker discovery that could translate into advances in disease management and clinical care and ultimately lead to precision medicine approaches.

Airway transcriptome networks identify susceptibility to frequent asthma exacerbations in children.

BACKGROUND: Frequent asthma exacerbators, defined as those experiencing more than 1 hospitalization in a year for an asthma exacerbation, represent an important subgroup of individuals with asthma. However, this group remains poorly defined and understudied in children. OBJECTIVE: Our aim was to determine the molecular mechanisms underlying asthma pathogenesis and exacerbation frequency. METHODS: We performed RNA sequencing of upper airway cells from both frequent and nonfrequent exacerbators enrolled in the Ohio Pediatric Asthma Repository. RESULTS: Through molecular network analysis, we found that nonfrequent exacerbators display an increase in modules enriched for immune system processes, including type 2 inflammation and response to infection. In contrast, frequent exacerbators showed expression of modules enriched for nervous system processes, such as synaptic formation and axonal outgrowth. CONCLUSION: These data suggest that the upper airway of frequent exacerbators undergoes peripheral nervous system remodeling, representing a novel mechanism underlying pediatric asthma exacerbation.