Cross-sectional association between posttraumatic stress and cognition is moderated by pulmonary functioning in world trade center responders.

BACKGROUND: Posttraumatic stress disorder (PTSD) symptomatology and poorer pulmonary function are highly prevalent psychiatric and medical conditions. In the present study, we tested for the individual, additive, and modifying associations of PTSD symptomatology and pulmonary function with cognitive performance. METHODS: In this cross-sectional study, a total of 1,401 World Trade Center (WTC) responders (mean age = 53, SD = 8 years, 92% males) participated in the study. Cogstate assessment measured cognitive performance. PTSD symptomatology was measured using the trauma-specific version of the posttraumatic stress disorder checklist (PCL-17) adapted for the WTC attacks. The 1-second forced expiratory volume and forced vital capacity (FEV1/FVC) ratio was used to measure pulmonary function. Linear regressions with cognitive performance as the outcome were conducted to assess individual, additive, and moderating associations of PTSD symptomatology and pulmonary function. RESULTS: Higher PTSD symptomatology and poorer pulmonary function were negatively associated with cognitive performance. A 10% increase on the FEV1/FVC ratio moderated the association between PTSD symptomatology and cognition, whereby its association with cognition was stronger when PTSD symptomatology was higher (est. = 0.01, 95%CI = 0.004, 0.01, p < 0.001). When stratified by responder type, these associations persisted in trained (est. = 0.01, 95%CI = 0.01, 0.02, p < 0.001), but not in non-trained (est. = 0.004, 95% C.I. = -0.01, 0.02, p = 0.39) responders. CONCLUSIONS: In the presence of higher PTSD, better pulmonary functioning is associated with better cognitive performance. Early intervention efforts to mitigate preventable cognitive decline in high-risk populations should be studied, especially since intervention in one modality may have an impact on others.

The Human Genetic Differences in the Outcomes of mRNA Vaccination against COVID-19: A Prospective Cohort Study.

BACKGROUND: This study aimed to explore how genetic variations in individuals impact neutralization activity post-mRNA vaccination, recognizing the critical role vaccination plays in curbing COVID-19 spread and the necessity of ensuring vaccine efficacy amidst genetic diversity. METHODS: In a 4-week clinical pilot study, 534 healthy subjects received their first COVID vaccine dose, followed by the second dose. Antibody levels were evaluated thrice. From this pool, 120 participants were selected and divided into high- and low-antibody groups based on their levels. Genomic DNA was isolated from peripheral blood mononuclear cells for pilot genome-wide association studies (GWAS) conducted on a single platform. Real-time PCR was used to confirm differences in gene expression identified via GWAS analysis. RESULTS: Three SNPs exceeded the level of p < 1.0 × 10-3. The rs7795433 SNP of the HDAC9 gene (7q21.1) showed the strongest association with COVID-19 vaccination under the additive model (OR = 5.63; p = 3 × 10-5). In the PCR experiments, the AA genotype group showed that the gene expression level of HDAC9 was likely to be decreased in the low-antibody-formation group at the time of vaccination. CONCLUSION: We found that AA genotype holders (rs7795433 SNP of the HDAC9 gene) have a high probability of having a higher antibody count when vaccinated, and GG type holders have a high probability of the opposite. These findings show that the genetic characteristics of vaccinated people may affect antibody production after COVID vaccination.

Interplay of Mediterranean-diet adherence, genetic factors, and metabolic dysfunction-associated steatotic liver disease risk in Korea.

BACKGROUNDS: Metabolic dysfunction-associated steatotic liver disease (MASLD) has gained attention owing to its severe complications. This study aimed to explore the interaction between Mediterranean-diet (MD) adherence, genetic factors, and MASLD risk in a Korean population. METHODS: In total, 33,133 individuals aged 40 years and older from the Korean Genome and Epidemiology Study (KoGES) were analyzed. Participants were assessed for MASLD based on criteria and MD adherence measured by the Korean version of the Mediterranean-Diet Adherence Screener (K-MEDAS). Individuals were categorized into two groups based on their MD adherence: high adherence (K-MEDAS > 6) and low adherence (K-MEDAS < 5). Single nucleotide polymorphism (SNP) genotypes were obtained using the Korea Biobank array. Logistic regression was used to examine the single-marker variants for genetic associations with MASLD prevalence. RESULTS: Individuals were categorized into MASLD (10,018 [30.2%]) and non-MASLD (23,115 [69.8%]) groups. A significant interaction was observed between the rs780094 glucokinase regulatory protein (GCKR) gene and K-MEDAS on MASLD (p < 10 - 2 ). Of individuals with K-MEDAS > 6, those carrying the minor allele (C) of the GCKR gene rs780094 exhibited a lower risk of MASLD compared to those without the allele (odds ratio [OR] = 0.88 [0.85-0.91], p-value = 5.54e-13). CONCLUSION: The study identified a significant interaction involving the rs780094 variant near the GCKR gene, with carriers of the minor allele exhibiting a lower MASLD risk among those adhering well to the MD. Dietary habits influence the MASLD risk associated with the rs780094 allele, emphasizing the need for personalized nutrition recommendations.

Interstitial Lung Disease and Progressive Pulmonary Fibrosis: a World Trade Center Cohort 20-Year Longitudinal Study.

PURPOSE: World Trade Center (WTC) exposure is associated with obstructive airway diseases and sarcoidosis. There is limited research regarding the incidence and progression of non-sarcoidosis interstitial lung diseases (ILD) after WTC-exposure. ILD encompasses parenchymal diseases which may lead to progressive pulmonary fibrosis (PPF). We used the Fire Department of the City of New York's (FDNY's) WTC Health Program cohort to estimate ILD incidence and progression. METHODS: This longitudinal study included 14,525 responders without ILD prior to 9/11/2001. ILD incidence and prevalence were estimated and standardized to the US 2014 population. Poisson regression modeled risk factors, including WTC-exposure and forced vital capacity (FVC), associated with ILD. Follow-up time ended at the earliest of incident diagnosis, end of study period/case ascertainment, transplant or death. RESULTS: ILD developed in 80/14,525 FDNY WTC responders. Age, smoking, and gastroesophageal reflux disease (GERD) prior to diagnosis were associated with incident ILD, though FVC was not. PPF developed in 40/80 ILD cases. Among the 80 cases, the average follow-up time after ILD diagnosis was 8.5 years with the majority of deaths occurring among those with PPF (PPF: n = 13; ILD without PPF: n = 6). CONCLUSIONS: The prevalence of post-9/11 ILD was more than two-fold greater than the general population. An exposure-response gradient could not be demonstrated. Half the ILD cases developed PPF, higher than previously reported. Age, smoking, and GERD were risk factors for ILD and PPF, while lung function was not. This may indicate that lung function measured after respirable exposures would not identify those at risk for ILD or PPF.

Scalable Learning Framework for Detecting New Types of Twitter Spam with Misuse and Anomaly Detection.

The growing popularity of social media has engendered the social problem of spam proliferation through this medium. New spam types that evade existing spam detection systems are being developed continually, necessitating corresponding countermeasures. This study proposes an anomaly detection-based framework to detect new Twitter spam, which works by modeling the characteristics of non-spam tweets and using anomaly detection to classify tweets deviating from this model as anomalies. However, because modeling varied non-spam tweets is challenging, the technique's spam detection and false positive (FP) rates are low and high, respectively. To overcome this shortcoming, anomaly detection is performed on known spam tweets pre-detected using a trained decision tree while modeling normal tweets. A one-class support vector machine and an autoencoder with high detection rates are used for anomaly detection. The proposed framework exhibits superior detection rates for unknown spam compared to conventional techniques, while maintaining equivalent or improved detection and FP rates for known spam. Furthermore, the framework can be adapted to changes in spam conditions by adjusting the costs of detection errors.

Testing the Reliability and Validity of the Korean Version of the Pittsburgh Sleep Quality Index Using Fitbit Devices: A Cross-Sectional Analysis.

Background: Sleep disorders and insomnia are prevalent worldwide, with negative health outcomes. The Pittsburgh Sleep Quality Index (PSQI) is a widely used self-report assessment tool for evaluating sleep quality, comprising seven subdomains. The Korean version of the PSQI (PSQI-K) has been tested for reliability and validity in small sample sizes but lacks large-scale validation using objective measures. Methods: This study was conducted with 268 Korean adults attending health check programs. Participants completed the PSQI-K questionnaire and wore Fitbit devices (Fitbit Inc., USA) to ascertain sleep parameters. Reliability was analyzed using the Cronbach's α coefficient, and construct validity was determined through factor analysis. Criteria validity was assessed by correlating their index scores with Fitbit sleep parameters. We identified the optimal cutoff for detecting sleep disorders. Results: The Cronbach's α coefficient was 0.61, indicating adequate internal consistency. Factor analysis revealed three factors, explaining 48.2% of sleep quality variance. The index scores were negatively correlated with Fitbit sleep efficiency, total sleep time, and number of awakenings (P<0.05). The optimal cutoff point for identifying sleep disorder groups was ≥6. Conclusion: The PSQI-K demonstrated good reliability and validity when correlated with Fitbit sleep parameters, offering a practical screening tool for identifying sleep disorders among Korean adults. Cutoff scores can help identify patients for sleep interventions. However, further large-scale studies are required to validate these findings.

Genetic Variants Linked to Myocardial Infarction in Individuals with Non-Alcoholic Fatty Liver Disease and Their Potential Interaction with Dietary Patterns.

In recent studies, non-alcoholic fatty liver disease (NAFLD) has been associated with a high risk of ischemic heart disease. This study aimed to investigate a genetic variant within a specific gene associated with myocardial infarction (MI) among patients with NAFLD. We included 57,205 participants from a Korean genome and epidemiology study. The baseline population consisted of 45,400 individuals, with 11,805 identified as patients with NAFLD. Genome-wide association studies were conducted for three groups: the entire sample, the healthy population, and patients with NAFLD. We defined the p-value < 1 × 10-5 as the nominal significance and the p-value < 5 × 10-2 as statistically significant for the gene-by-nutrient interaction. Among the significant single-nucleotide polymorphisms (SNPs), the lead SNP of each locus was further analyzed. In this cross-sectional study, a total of 1529 participants (2.8%) had experienced MI. Multivariable logistic regression was performed to evaluate the association of 102 SNPs across nine loci. Nine SNPs (rs11891202, rs2278549, rs13146480, rs17293047, rs184257317, rs183081683, rs1887427, rs146939423, and rs76662689) demonstrated an association with MI in the group with NAFLD Notably, the MI-associated SNP, rs134146480, located within the SORCS2 gene, known for its role in secreting insulin in islet cells, showed the most significant association with MI (p-value = 2.55 × 10-7). Our study identifies candidate genetic polymorphisms associated with NAFLD-related MI. These findings may serve as valuable indicators for estimating MI risk and for conducting future investigations into the underlying mechanisms of NAFLD-related MI.

Brain control of dual-task walking can be improved in aging and neurological disease.

The peak prevalence of multiple sclerosis has shifted into older age groups, but co-occurring and possibly synergistic motoric and cognitive declines in this patient population are poorly understood. Dual-task-walking performance, subserved by the prefrontal cortex, and compromised in multiple sclerosis and aging, predicts health outcomes. Whether acute practice can improve dual-task walking performance and prefrontal cortex hemodynamic response efficiency in multiple sclerosis has not been reported. To address this gap in the literature, the current study examined task- and practice-related effects on dual-task-walking and associated brain activation in older adults with multiple sclerosis and controls. Multiple sclerosis (n = 94, mean age = 64.76 ± 4.19 years) and control (n = 104, mean age = 68.18 ± 7.01 years) participants were tested under three experimental conditions (dual-task-walk, single-task-walk, and single-task-alpha) administered over three repeated counterbalanced trials. Functional near-infrared-spectroscopy was used to evaluate task- and practice-related changes in prefrontal cortex oxygenated hemoglobin. Gait and cognitive performances declined, and prefrontal cortex oxygenated hemoglobin was higher in dual compared to both single task conditions in both groups. Gait and cognitive performances improved over trials in both groups. There were greater declines over trials in oxygenated hemoglobin in dual-task-walk compared to single-task-walk in both groups. Among controls, but not multiple sclerosis participants, declines over trials in oxygenated hemoglobin were greater in dual-task-walk compared to single-task-alpha. Dual-task walking and associated prefrontal cortex activation efficiency improved during a single session, but improvement in neural resource utilization, although significant, was attenuated in multiple sclerosis participants. These findings suggest encouraging brain adaptability in aging and neurological disease.

Normal Lung Function and Mortality in World Trade Center Responders and National Health and Nutrition Examination Survey III Participants.

Rationale: Low FEV1 is a biomarker of increased mortality. The association of normal lung function and mortality is not well described. Objectives: To evaluate the FEV1-mortality association among participants with normal lung function. Methods: A total of 10,999 Fire Department of the City of New York (FDNY) responders and 10,901 Third National Health and Nutrition Examination Survey (NHANES III) participants, aged 18-65 years with FEV1 ⩾80% predicted, were analyzed, with FEV1 percent predicted calculated using Global Lung Function Initiative Global race-neutral reference equations. Mortality data were obtained from linkages to the National Death Index. Cox proportional hazards models estimated the association between FEV1 and all-cause mortality, controlling for age, sex, race/ethnicity, smoking history, and, for FDNY, work assignment. Cohorts were followed for a maximum of 20.3 years. Measurements and Main Results: We observed 504 deaths (4.6%) of 10,999 for FDNY and 1,237 deaths (9.4% [weighted]) of 10,901 for NHANES III. Relative to FEV1 ⩾120% predicted, mortality was significantly higher for FEV1 100-109%, 90-99%, and 80-89% predicted in the FDNY cohort. In the NHANES III cohort, mortality was significantly higher for FEV1 90-99% and 80-89% predicted. Each 10% higher predicted FEV1 was associated with 15% (hazard ratio, 0.85; 95% confidence interval, 0.80-0.91) and 23% (hazard ratio, 0.77; 95% confidence interval, 0.71-0.84) lower mortality for FDNY and NHANES III, respectively. Conclusions: In both cohorts, higher FEV1 is associated with lower mortality, suggesting higher FEV1 is a biomarker of better health. These findings demonstrate that a single cross-sectional measurement of FEV1 is predictive of mortality over two decades, even when FEV1 is in the normal range.

Non-inferiority trials with time-to-event data: clarifying the impact of censoring.

In non-inferiority (NI) trials with time-to-event data, different types and patterns of censoring may occur, but their impact on trial results is not entirely clear. We investigated the influence of informative and non-informative censoring by conducting extensive simulation studies under the assumption that the NI margin is defined as a maximum acceptable hazard ratio and scenarios typically observed in recent NI trials. We found that while non-informative censoring tends to only affect the power, informative censoring can impact the treatment effect estimates, type I error rate, and power. The magnitude of these effects depends on the between-group differences in the failure and informative censoring risks, as well as the correlation between censoring and failure times, among other factors. The adverse impact of informative censoring was generally decreased with larger NI margins.

Association and risk factors of pediatric pulmonary hypertension with obstructive sleep apnea: A national study utilizing the Kids' Inpatient Database (KID).

STUDY OBJECTIVE: Assess the prevalence of and risk factors for pediatric pulmonary hypertension (PH) in the 2016 Kids' Inpatient Database (KID), including obstructive sleep apnea (OSA) and obesity. METHODS: Retrospective cross-sectional cohort study utilizing 6,081,132 weighted pediatric discharges from the 2016 KID. Study variables included age, length of stay, mortality, gender, hospital region, primary payer, race, median household income for patient's ZIP code, OSA, central sleep apnea (CSA), obesity, Down syndrome, sickle cell disease (SCD), thalassemia, congenital heart disease (CHD), hypertension, asthma and chronic lung disease of prematurity (CLDP). PH was the primary outcome of interest. Bivariate and multivariable logistic regression models were utilized with odds ratios and 95 % confidence intervals. RESULTS: The mean age was 3.76 years, the mean hospital length of stay was 3.85 days, 48.9 % were male, 52.6 % had government health insurance, 51.0 % were White, 16.1 % were Black, 21.1 % were Hispanic, 5.0 % were Asian or Pacific Islander, 0.80 % were Native American and 6.1 % identified as "other". The prevalence of PH was 0.21 % (12,777 patients). There were 37,631 patients with OSA and the prevalence of PH among this cohort was 3.3 %, over 10x greater than the overall prevalence of PH in the 2016 KID (0.21 %). Risk factors associated with PH included CLDP, CHD, Down syndrome, asthma, OSA, CSA, hypertension, SCD, obesity, race/ethnicity, government insurance, age, male gender (p < 0.0001), and hospital region (p = 0.0002). CONCLUSIONS: Several risk factors were independently associated with PH, such as OSA, CSA, obesity, asthma, and insurance status. Prospective multi-institutional studies are needed to assess the relationships between these risk factors, severity metrics, and causative links in the development of PH; in addition to identifying children with OSA who are most likely to benefit from cardiopulmonary screening prior to adenotonsillectomy. LEVEL OF EVIDENCE: Level III.

Phthalate exposure in the neonatal intensive care unit is associated with development of bronchopulmonary dysplasia.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is a serious yet common morbidity of preterm birth. Although prior work suggests a possible role for phthalate exposure in the development of BPD, no study has rigorously evaluated this. Our objective was to determine whether hospital-based phthalate exposure is associated with the development of BPD and to identify developmental windows sensitive to exposure. STUDY DESIGN: This is a prospective multicenter cohort study of 360 preterm infants born at 23-33 weeks gestation participating in the Developmental Impact of NICU Exposures (DINE) cohort. 939 urine specimens collected during the NICU stay were analyzed for biomarkers of phthalate exposure by liquid chromatography with tandem mass spectrometry. The modified Shennan definition was used to diagnose bronchopulmonary dysplasia. Reverse distributed-lag modeling identified developmental windows sensitive to specific phthalate exposure, controlling for relevant covariates including sex and respiratory support. RESULTS: Thirty-five percent of participants were diagnosed with BPD. Exposure to specific phthalate mixtures at susceptible points in preterm infant development are associated with later diagnosis of BPD in models adjusted for use of respiratory support. The weighted influence of specific phthalate metabolites in the mixtures varied by sex. Metabolites of di(2-ethylhexyl) phthalate, a phthalate previously linked to neonatal respiratory support equipment, drove this association, particularly among female infants, at 26- to 30-weeks post-menstrual age. CONCLUSIONS: This is the largest and only multi-site study of NICU-based phthalate exposure and clinical impact yet reported. In well-constructed models accounting for infant sex and respiratory support, we found a significant positive association between ultimate diagnosis of BPD and prior exposure to phthalate mixtures with DEHP predominance at 26- to 30-weeks PMA or 34-36-weeks PMA. This information is critically important as it identifies a previously unrecognized and modifiable contributing factor to BPD.

Genome-wide association and replication studies for handedness in a Korean community-based cohort.

INTRODUCTION: Handedness is a conspicuous characteristic in human behavior, with a worldwide proportion of approximately 90% of people preferring to use the right hand for many tasks. In the Korean population, the proportion of left-handedness is relatively low at approximately 7%-10%, similar to that in other East-Asian cultures in which the use of the left hand for writing and other public activities has historically been oppressed. METHODS: In this study, we conducted two genome-wide association studies (GWASs) between right-handedness and left-handedness, and between right-handedness and ambidexterity using logistic regression analyses using a Korean community-based cohort. We also performed association analyses with previously reported variants and our findings. RESULTS: A total of 8806 participants were included for analysis, and the results identified 28 left-handedness-associated and 15 ambidexterity-associated loci; of these, two left-handedness loci (NEIL3 [rs11726465] and SVOPL [rs117495448]) and one ambidexterity locus (PDE8B/WDR41 [rs118077080]) showed near genome-wide significance. Association analyses with previously reported variants replicated ANKS1B (rs7132513) in left-handedness and ANKIB1 (rs2040498) in ambidexterity. CONCLUSION: The variants and positional candidate genes identified and replicated in this study were largely associated with brain development, cerebral asymmetry, neurological processes, and neuropsychiatric diseases in line with previous findings. As the first East-Asian GWAS related to handedness, these results may provide an intriguing reference for further human neurologic research in the future.

Persistence of Emotional Distress in Unaccompanied Migrant Children and Adolescents Primarily From the Northern Triangle of Central America.

Importance: In the US, unaccompanied migrant children and adolescents (hereinafter referred to as children) are predominantly from Central America's Northern Triangle. While unaccompanied migrant children are at high risk for psychiatric sequelae due to complex traumatic exposures, longitudinal investigations of psychiatric distress after resettlement are lacking. Objective: To identify factors associated with emotional distress and longitudinal changes in emotional distress among unaccompanied migrant children in the US. Design, Setting, and Participants: For this retrospective cohort study, the 15-item Refugee Health Screener (RHS-15) was administered between January 1, 2015, and December 31, 2019, to unaccompanied migrant children as part of their medical care to detect emotional distress. Follow-up RHS-15 results were included if they were completed before February 29, 2020. Median follow-up interval was 203 days (IQR, 113-375 days). The study was conducted in a federally qualified health center that provides medical, mental health, and legal services. Unaccompanied migrant children who completed the initial RHS-15 were eligible for analysis. Data were analyzed from April 18, 2022, to April 23, 2023. Exposures: Traumatic events before migration, during migration, during detention, and after resettlement in the US. Main Outcomes and Measures: Emotional distress, including symptoms of posttraumatic stress disorder, anxiety, and depressive symptoms, as indicated by the RHS-15 (ie, score ≥12 on items 1-14 or ≥5 on item 15). Results: In total, 176 unaccompanied migrant children completed an initial RHS-15. They were primarily from Central America's Northern Triangle (153 [86.9%]), were mostly male (126 [71.6%]), and had a mean (SD) age of 16.9 (2.1) years. Of the 176 unaccompanied migrant children, 101 (57.4%) had screen results above the positive cutoff. Girls were more likely to have positive screen results than boys (odds ratio, 2.48 [95% CI, 1.15-5.34]; P = .02). Follow-up scores were available for 68 unaccompanied migrant children (38.6%). On the follow-up RHS-15, most scored above the positive cutoff (44 [64.7%]). Three-quarters of unaccompanied migrant children who scored above the positive cutoff initially continued to have positive scores at follow-up (30 of 40), and half of those with negative screen scores initially had positive scores at follow-up (14 of 28). Female vs male unaccompanied migrant children (unstandardized ß = 5.14 [95% CI, 0.23-10.06]; P = .04) and initial total score (unstandardized ß = 0.41 [95% CI, 0.18-0.64]; P = .001) were independently associated with increased follow-up RHS-15 total score. Conclusions and Relevance: The findings suggest that unaccompanied migrant children are at high risk for emotional distress, including symptoms of depression, anxiety, and posttraumatic stress. The persistence of emotional distress suggests that unaccompanied migrant children would benefit from ongoing psychosocial and material support after resettlement.

An IoMT-Based Melanoma Lesion Segmentation Using Conditional Generative Adversarial Networks.

Currently, Internet of medical things-based technologies provide a foundation for remote data collection and medical assistance for various diseases. Along with developments in computer vision, the application of Artificial Intelligence and Deep Learning in IOMT devices aids in the design of effective CAD systems for various diseases such as melanoma cancer even in the absence of experts. However, accurate segmentation of melanoma skin lesions from images by CAD systems is necessary to carry out an effective diagnosis. Nevertheless, the visual similarity between normal and melanoma lesions is very high, which leads to less accuracy of various traditional, parametric, and deep learning-based methods. Hence, as a solution to the challenge of accurate segmentation, we propose an advanced generative deep learning model called the Conditional Generative Adversarial Network (cGAN) for lesion segmentation. In the suggested technique, the generation of segmented images is conditional on dermoscopic images of skin lesions to generate accurate segmentation. We assessed the proposed model using three distinct datasets including DermQuest, DermIS, and ISCI2016, and attained optimal segmentation results of 99%, 97%, and 95% performance accuracy, respectively.

Individual reserve in aging and neurological disease.

BACKGROUND AND OBJECTIVE: Cognitive and physical functions correlate and delineate aging and disease trajectories. Whereas cognitive reserve (CR) is well-established, physical reserve (PR) is poorly understood. We, therefore, developed and evaluated a novel and more comprehensive construct, individual reserve (IR), comprised of residual-derived CR and PR in older adults with and without multiple sclerosis (MS). We hypothesized that: (a) CR and PR would be positively correlated; (b) low CR, PR, and IR would be associated with worse study outcomes; (c) associations of brain atrophy with study outcomes would be stronger in lower compared to higher IR due to compensatory mechanisms conferred by the latter. METHODS: Older adults with MS (n = 66, mean age = 64.48 ± 3.84 years) and controls (n = 66, mean age = 68.20 ± 6.09 years), underwent brain MRI, cognitive assessment, and motoric testing. We regressed the repeatable battery for the assessment of neuropsychological status and short physical performance battery on brain pathology and socio-demographic confounders to derive independent residual CR and PR measures, respectively. We combined CR and PR to define a 4-level IR variable. The oral symbol digit modalities test (SDMT) and timed-25-foot-walk-test (T25FW) served as outcome measures. RESULTS: CR and PR were positively correlated. Low CR, PR and IR were associated with worse SDMT and T25FW performances. Reduced left thalamic volume, a marker of brain atrophy, was associated with poor SDMT and T25FW performances only in individuals with low IR. The presence of MS moderated associations between IR and T25FW performance. CONCLUSION: IR is a novel construct comprised of cognitive and physical dimensions representing collective within-person reserve capacities.

Association of Lung Function Decline with All-Cause and Cancer-Cause Mortality after World Trade Center Dust Exposure.

Rationale: In numerous cohorts, lung function decline is associated with all-cause and cardiovascular-cause mortality, but the association between the decrease in forced expiratory volume in 1 second (FEV1) and cancer-cause mortality, particularly after occupational/environmental exposure(s), is unclear. Exposure to dust/smoke from the World Trade Center (WTC) disaster caused inflammation and lung injury in Fire Department of the City of New York rescue/recovery workers. In addition, prior research found that >10% of the cohort experienced greater than twice the age-related decrease in FEV1 (⩾64 ml/yr). Objectives: To evaluate the association of longitudinal lung function with all-cause and cancer-cause mortality after exposure to the WTC disaster. Methods: We conducted a prospective cohort study using longitudinal prebronchodilator FEV1 data for 12,264 WTC-exposed firefighters and emergency medical service providers. All-cause and cancer-cause mortality were ascertained using National Death Index data from September 12, 2001, through December 31, 2021. Joint longitudinal survival models evaluated the association of baseline FEV1 and change in FEV1 from baseline with all-cause and cancer-cause mortality adjusted for age, race/ethnicity, height, smoking, work assignment (firefighters vs. emergency medical service providers), and WTC exposure. Results: By December 31, 2021, 607 of the 12,264 individuals in the cohort (4.9%) had died (crude rate = 259.5 per 100,000 person-years), and 190 of 12,264 (1.5%) had died from cancer (crude rate = 81.2 per 100,000 person-years). Baseline FEV1 was ⩾80% predicted in 10,970 of the 12,264 (89.4%); final FEV1 was ⩾80% in 9,996 (81.5%). Lower FEV1 at baseline was associated with greater risk for all-cause mortality (hazard ratio [HR] per liter = 2.32; 95% confidence interval [95% CI] = 1.98-2.72) and cancer-cause mortality (HR per liter = 1.99; 95% CI = 1.49-2.66). Longitudinally, each 100-ml/yr decrease in FEV1 was associated with an 11% increase in all-cause mortality (HR = 1.11; 95% CI = 1.06-1.15) and a 7% increase in cancer-cause mortality (HR = 1.07; 95% CI = 1.00-1.15). Compared with FEV1 decrease <64 ml/yr, those with FEV1 decrease ⩾64 ml/yr had higher all-cause (HR = 2.91; 95% CI = 2.37-3.56) and cancer-cause mortality (HR = 2.68; 95% CI = 1.90-3.79). Conclusions: Baseline FEV1 and longitudinal FEV1 decrease are associated with increased risk of all-cause and cancer-cause mortality in a previously healthy occupational cohort, the majority of whom had normal lung function, after intense exposure to dust/smoke. Further investigation is needed to define pathways by which lung function impacts mortality after an irritant exposure.

Waitlist and Posttransplant Outcomes of Children and Young Adults With Hypertrophic Cardiomyopathy.

BACKGROUND: Heart transplantation (HT) is standard therapy for end-stage hypertrophic cardiomyopathy (HCM); however, few studies have described outcomes of older children and young adults with HCM listed for HT. Our objective was to compare waitlist and post-HT outcomes among pediatric and young adult patients with HCM and dilated cardiomyopathy (DCM). METHODS: The Scientific Registry of Transplant Recipients was queried for patients with HCM and DCM listed at ≤25 years of age. Patient characteristics, waitlist and post-HT survival were compared between younger (≤5 years of age) and older (>5 to ≤25 years of age) HCM patients and between HCM and DCM patients. RESULTS: Among 6252 patients listed for HT at ≤25 years of age with DCM and HCM, 3926 and 250 were in the older cohort and 1944 and 132 were in the younger cohort, respectively. Older HCM patients were less likely to be critically ill at listing compared with younger HCM patients (P = .0001). Waitlist mortality was similar between HCM and DCM patients in both age cohorts. Post-HT survival in HCM patients was similar between the age cohorts. In the younger cohort, early post-HT survival was worse in HCM compared with DCM (P = .009), with no difference in long-term survival. Survival was similar between the older cohorts. CONCLUSIONS: Older children and young adults with HCM are less critically ill than the younger cohort and show waitlist and post-HT survival similar to DCM patients. The young children with HCM had worse early posttransplantation survival, though long-term survival was same as DCM.

Lifestage Sex-Specific Genetic Effects on Metabolic Disorders in an Adult Population in Korea: The Korean Genome and Epidemiology Study.

Although many genome-wide association studies (GWASs) have evaluated the association with metabolic disorders, the current study is the first attempt to analyze the genetic risk factors for various metabolic disorders according to sex and age groups of the life course in Korean adults. A total population of 50,808 people were included in this GWAS. The genetic traits for eight metabolic phenotypes were investigated in peri-, and postmenopausal women compared to a younger group or men of corresponding age groups. The metabolic phenotypes include general obesity, abdominal obesity, hypertension, type 2 diabetes, hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein cholesterolemia, and metabolic syndrome. In the total participants, GWAS results for eight metabolic phenotypes found 101 significant loci. Of these, 15 loci were the first reported to be associated with the risk of metabolic disorder. Interestingly, some of the significant loci presented the association with the various phenotypes, which presented when there was a correlation between phenotypes. In addition, we analyzed divided by gender and age (young adult, peri-menopausal group, older adult), and specifically identified specific loci in peri-menopausal women. Meanwhile, several genetic factors associated with metabolic disorders were newly reported in our study. In particular, several genes were significantly associated with one of the metabolic phenotypes in only a single specific group. These findings suggest that menopausal transition rather than aging itself potentiates the influence of genetic risks on metabolic disorders. In addition, some genetic loci with low frequencies may play a role in the metabolic disturbances in a specific sex and age group. The genetic traits derived from our study may contribute to understanding the genetic risk factors for metabolic disorders in the Korean population.

Classification of early age facial growth pattern and identification of the genetic basis in two Korean populations.

Childhood to adolescence is an accelerated growth period, and genetic features can influence differences of individual growth patterns. In this study, we examined the genetic basis of early age facial growth (EAFG) patterns. Facial shape phenotypes were defined using facial landmark distances, identifying five growth patterns: continued-decrease, decrease-to-increase, constant, increase-to-decrease, and continued-increase. We conducted genome-wide association studies (GWAS) for 10 horizontal and 11 vertical phenotypes. The most significant association for horizontal phenotypes was rs610831 (TRIM29; ß = 0.92, p-value = 1.9 × 10-9) and for vertical phenotypes was rs6898746 (ZSWIM6; ß = 0.1103, p-value = 2.5 × 10-8). It is highly correlated with genes already reported for facial growth. This study is the first to classify and characterize facial growth patterns and related genetic polymorphisms.