Firearm-Related Juvenile Death Rates Correlate With Gun Ownership Rates, Measures of Guns in Circulation, and Leniency of Existing Firearm Laws Among U.S. States.

INTRODUCTION: Firearms now represent the leading cause of death in U.S. children. Therefore, this study aimed to determine if state-level rates of gun ownership, guns in circulation, and strictness of firearm-related laws are related to firearm-related mortality among both juveniles and overall populations. MATERIALS AND METHODS: State firearm mortality rates among the juvenile and overall populations were obtained from 2010 to 2020. The number of weapons registered with the Bureau of Alcohol, Tobacco, Firearms, and Explosives (ATF) and federal firearms licensees for each state were also recorded. Giffords Law Center Scorecard Rankings, a relative measure of the restrictiveness of each state's gun laws, were also collected. Unadjusted linear regressions modeled the relationships between firearm-associated mortality and ATF-registered weapons, federal firearm licensees, Giffords Center rankings, and gun ownership rates. Multivariable (adjusted) analyses were performed to control for poverty, unemployment, and poor mental health. RESULTS: Unadjusted analyses demonstrated that higher gun ownership rates and more lenient gun laws were associated with increased firearm-associated mortality among juveniles. Similarly, these measures as well as increased ATF-registered weapons and ATF federal firearm licensees were associated with increased firearm mortality in the overall population. In the adjusted analyses, more ATF-registered weapons, more ATF federal firearm licensees, higher gun ownership rates, and more lenient firearm laws were associated with increased firearm-related mortality in the overall population, while increased gun ownership and higher Giffords Center rankings were associated with increased firearm-associated mortality in the pediatric population. CONCLUSIONS: To reduce the toll of gun violence in the United States, policymakers should focus on implementing more restrictive firearm laws and reducing the prevalence of guns in their communities.

A comprehensive youth diabetes epidemiological dataset and web portal: Resource Development and Case Studies.

BACKGROUND: The prevalence of Type 2 diabetes (DM) and prediabetes (preDM) has been increasing among youth in recent decades in the United States, prompting an urgent need for understanding and identifying their associated risk factors. Such efforts, however, have been hindered by the lack of easily accessible youth preDM/DM data. OBJECTIVE: We aimed to first build a high quality, comprehensive epidemiological dataset focused on youth preDM/DM. Subsequently, we aimed to make this data accessible by creating a user-friendly web portal to share it and corresponding codes. Through this, we hope to address this significant gap and facilitate youth preDM/DM research. METHODS: Building on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, we cleaned and harmonized hundreds of variables relevant to preDM/DM (fasting plasma glucose level ≥100 mg/dL and/or HbA1C ≥5.7%) for youth aged 12-19 years (n=15,149). We identified individual factors associated with preDM/DM risk using bivariate statistical analyses and predicted preDM/DM status using our Ensemble Integration (EI) framework for multi-domain machine learning. We then developed a user-friendly web portal named Prediabetes/diabetes in youth ONline Dashboard (POND) to share the data and codes. RESULTS: We extracted 95 variables potentially relevant to preDM/DM risk organized into 4 domains (sociodemographic, health status, diet, and other lifestyle behaviors). The bivariate analyses identified 27 significant correlates of preDM/DM (P ≤0.0005, Bonferroni adjusted), including race/ethnicity, health insurance, BMI, added sugar intake, and screen time. Sixteen of these factors were also identified based on the EI methodology (Fisher's P of overlap=7.06x10^-6). In addition to those, the EI approach identified 11 additional predictive variables, including some known (e.g., meat and fruit intake and family income) and less recognized factors (e.g., number of rooms in homes). The factors identified in both analyses spanned over all 4 of the domains mentioned. These data and results, as well as other exploratory tools, can be accessed on POND (https://rstudio-connect.hpc.mssm.edu/POND/). CONCLUSIONS: Using NHANES data, we built one of the largest public epidemiological datasets for studying youth preDM/DM and identified potential risk factors using complementary analytical approaches. Our results align with the multifactorial nature of preDM/DM with correlates across several domains. Also, our data-sharing platform, POND, facilitates a wide range of applications to inform future youth preDM/DM studies.

Associations of a plant-centered diet and lung function across early to mid-adulthood: The CARDIA Lung Study.

BACKGROUND: Lung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. METHODS: Diet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet for 20 beneficially rated foods and 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes and cross-sectional differences in a repeated measures regression model, adjusting for clinically relevant covariates. RESULTS: The study included 3,787 Black and White men and women aged 18-30 in 1985-86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß ± SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß ± SE per 1 SD change APDQS 1.71 ± 0.46, p < 0.001). The association was not different between never and ever smokers (pint = 0.07 for FVC and 0.32 for FEV1). In sensitivity analyses where current asthma diagnosis and cardiorespiratory fitness were further adjusted, results remained similar. Cross-sectional analysis at each exam year also showed significant differences in lung function according to diet after covariate adjustment. CONCLUSIONS: In this 30-year longitudinal cohort study, long-term adherence to a nutritionally-rich plant-centered diet was associated with cross-sectional differences in lung function as well as slower decline in lung function, highlighting diet quality as a potential treatable trait supporting long-term lung health.

Trends in mortality due to tracheal, bronchial, and lung cancer across the BRICS: An age-period-cohort analysis based on the Global Burden of Disease Study 1990-2019.

BACKGROUND: Tracheal, bronchus, and lung cancer (TBL) is a major cause of mortality and top contributor to productivity loss in large emerging economies such as the BRICS (Brazil, Russia, India, China, and South Africa). We examined the time trends of TBL mortality across the BRICS to better understand the disease burden in these countries and inform public health and healthcare resource allocation. METHODS: TBL mortality-related data between 1990 and 2019 were obtained from the Global Burden of Disease Study 2019 and analyzed using age-period-cohort models. Net drift (local drift) was used to describe the expected age-adjusted TBL mortality rate over time overall (each age group); the longitudinal age curve was used to reflect the age effect; the period rate ratios (RRs) were used to reflect the period effect; and the cohort RR was used to reflect the cohort effect. RESULTS: In 2019, there were 958.3 thousand TBL deaths across the BRICS, representing 46.9% of the global TBL deaths. From 1990 to 2019, the age-standardized mortality rate (ASMR) of TBL decreased in Russia, Brazil, and South Africa while increased in China and India, with the largest reduction reported in Russia (-29.6%) and the largest increase in China (+22.4%). India showed an overall increase (+15.7%) in TBL mortality but the mortality risk decreased among individuals born after 1990 (men) and 1995 (women). Although South Africa and Brazil experienced an overall decline in TBL mortality, their recent birth cohorts, such as Brazilian individuals born after 1985 (men) and 1980 (women), and South African men born after 1995, had an increasing TBL mortality risk. China has experienced an overall increase in TBL mortality, with the mortality risk rising among individuals born after 1995 for both men and women. Russia, which had the highest TBL mortality among the BRICS countries in 1990, has demonstrated significant improvement over the past three decades. CONCLUSIONS: Over the past 30 years, the BRICS accounted for an increasing proportion of global TBL mortality. TBL mortality increased in older women in all the BRICS countries except Russia. Among the recent birth cohort, the risk of TBL mortality increased in Brazil, China, and South Africa. More effective efforts are needed in the BRICS to reduce the burden of TBL and help achieve the United Nation's Sustainable Development Goals.

Medical financial hardship between young adult cancer survivors and matched individuals without cancer in the United States.

BACKGROUND: Young adult cancer survivors face medical financial hardships that may lead to delaying or forgoing medical care. This study describes the medical financial difficulties young adult cancer survivors in the United States experience in the post-Patient Protection and Affordable Care Act period. METHOD: We identified 1009 cancer survivors aged 18 to 39 years from the National Health Interview Survey (2015-2022) and matched 963 (95%) cancer survivors to 2733 control individuals using nearest-neighbor matching. We used conditional logistic regression to examine the association between cancer history and medical financial hardship and to assess whether this association varied by age, sex, race and ethnicity, and region of residence. RESULTS: Compared with those who did not have a history of cancer, young adult cancer survivors were more likely to report material financial hardship (22.8% vs 15.2%; odds ratio = 1.65, 95% confidence interval = 1.50 to 1.81) and behavior-related financial hardship (34.3% vs 24.4%; odds ratio = 1.62, 95% confidence interval = 1.49 to 1.76) but not psychological financial hardship (52.6% vs 50.9%; odds ratio = 1.07, 95% confidence interval = 0.99 to 1.16). Young adult cancer survivors who were Hispanic or lived in the Midwest and South were more likely to report psychological financial hardship than their counterparts. CONCLUSIONS: We found that young adult cancer survivors were more likely to experience material and behavior-related financial hardship than young adults without a history of cancer. We also identified specific subgroups of young adult cancer survivors that may benefit from targeted policies and interventions to alleviate medical financial hardship.

SynGAP regulates synaptic plasticity and cognition independently of its catalytic activity.

SynGAP is an abundant synaptic GTPase-activating protein (GAP) critical for synaptic plasticity, learning, memory, and cognition. Mutations in SYNGAP1 in humans result in intellectual disability, autistic-like behaviors, and epilepsy. Heterozygous Syngap1-knockout mice display deficits in synaptic plasticity, learning, and memory and exhibit seizures. It is unclear whether SynGAP imparts structural properties at synapses independently of its GAP activity. Here, we report that inactivating mutations within the GAP domain do not inhibit synaptic plasticity or cause behavioral deficits. Instead, SynGAP modulates synaptic strength by physically competing with the AMPA-receptor-TARP excitatory receptor complex in the formation of molecular condensates with synaptic scaffolding proteins. These results have major implications for developing therapeutic treatments for SYNGAP1-related neurodevelopmental disorders.

Variation in Home Healthcare Use by Dementia Status Among a National Cohort of Older Adults.

BACKGROUND: Medicare-funded home healthcare (HHC) delivers skilled nursing, therapy, and related services through visits to the patient's home. Nearly one-third (31%) of HHC patients have diagnosed dementia, but little is currently known regarding how HHC utilization and care delivery differ for persons living with dementia (PLwD). METHODS: We drew on linked 2012-2018 Health and Retirement Study and Medicare claims for a national cohort of 1 940 community-living older adults. We described differences in HHC admission, length of stay, and referral source by patient dementia status and used weighted, multivariable logistic and negative binomial models to estimate the relationship between dementia and HHC visit type and intensity while adjusting for sociodemographic characteristics, health and functional status, and geographic/community factors. RESULTS: PLwD had twice the odds of using HHC during a 2-year observation period, compared to those without dementia (odds ratio [OR]: 2.03; p < .001). They were more likely to be referred to HHC without a preceding hospitalization (49.4% vs 32.1%; p < .001) and incurred a greater number of HHC episodes (1.4 vs 1.0; p < .001) and a longer median HHC length of stay (55.8 days vs 40.0 days; p < .001). Among post-acute HHC patients, PLwD had twice the odds of receiving social work services (unadjusted odds ratio [aOR]: 2.15; p = .008) and 3 times the odds of receiving speech-language pathology services (aOR: 2.92; p = .002). CONCLUSIONS: Findings highlight HHC's importance as a care setting for community-living PLwD and indicate the need to identify care delivery patterns associated with positive outcomes for PLwD and design tailored HHC clinical pathways for this patient subpopulation.

Drivers of Community-Entry Home Health Care Utilization Among Older Adults.

OBJECTIVES: A growing proportion of Medicare home health (HH) patients are "community-entry," meaning referred to HH without a preceding hospitalization. We sought to identify factors that predict community-entry HH use among older adults to provide foundational information regarding care needs and circumstances that may prompt community-entry HH referral. DESIGN: Nationally representative cohort study. SETTING AND PARTICIPANTS: Health and Retirement Study (HRS) respondents who were aged ≥65 years, community-living, and enrolled in Medicare between 2012 and 2018 (n = 11,425 unique individuals providing 27,026 two-year observation periods). METHODS: HRS data were linked with standardized HH patient assessments. Community-entry HH utilization was defined as incurring one or more HH episode with no preceding hospitalization or institutional post-acute care stay (determined via assessment item indicating institutional care within 14 days of HH admission) within 2 years of HRS interview. Weighted, multivariable logistic regression was used to model community-entry HH use as a function of individual, social support, and community characteristics. RESULTS: The overall rate of community-entry HH utilization across observation periods was 13.4%. Older adults had higher odds of community-entry HH use if they were Medicaid enrolled [adjusted odds ratio (aOR) = 1.49, P = .001], had fair or poor overall health (aOR = 1.48, P < .001), 3+ activities of daily living limitations (aOR = 1.47, P = .007), and had fallen in the past 2 years (aOR = 1.43, P < .001). Compared with those receiving no caregiver help, individuals were more likely to use community-entry HH if they received family or unpaid help only (aOR = 1.81, P < .001), both family and paid help (aOR = 2.79, P < .001), or paid help only (aOR: 3.46, P < .001). CONCLUSIONS AND IMPLICATIONS: Findings indicate that community-entry HH serves a population with long-term care needs and coexisting clinical complexity, making this an important setting to provide skilled care and prevent avoidable health care utilization. Results highlight the need for ongoing monitoring of community-entry HH accessibility as this service is a key component of home-based care for a high-need subpopulation.

Zebrafish spop promotes ubiquitination and degradation of mavs to suppress antiviral response via the lysosomal pathway.

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathways are required to be tightly controlled to initiate host innate immune responses. Fish mitochondrial antiviral signaling (mavs) is a key determinant in the RLR pathway, and its ubiquitination is associated with mavs activation. Here, we identified the zebrafish E3 ubiquitin ligase Speckle-type BTB-POZ protein (spop) negatively regulates mavs-mediated the type I interferon (IFN) responses. Consistently, overexpression of zebrafish spop repressed the activity of IFN promoter and reduced host ifn transcription, whereas knockdown spop by small interfering RNA (siRNA) transfection had the opposite effects. Accordingly, overexpression of spop dampened the cellular antiviral responses triggered by spring viremia of carp virus (SVCV). A functional domain assay revealed that the N-terminal substrate-binding MATH domain regions of spop were necessary for IFN suppression. Further assays indicated that spop interacts with mavs through the C-terminal transmembrane (TM) domain of mavs. Moreover, zebrafish spop selectively promotes K48-linked polyubiquitination and degradation of mavs through the lysosomal pathway to suppress IFN expression. Our findings unearth a post-translational mechanism by which mavs is regulated and reveal a role for spop in inhibiting antiviral innate responses.

Spatiotemporal Patterns of Hospitalizations Among Older Adults With Co-Presence of Cancer and Dementia in US Counties: 2013-2018.

We assessed the spatiotemporal patterns of hospitalization with comorbid cancer and dementia. Using the 2013-2018 inpatient claims data for Medicare fee-for-service (FFS) beneficiaries, we calculated hospitalization rates by dividing the total admissions from individuals with the co-presence of a major cancer (breast, prostate, lung, and colorectal) and dementia diagnoses with the total counts of FFS beneficiaries aged 65 or older. We identified 22 hotspots with high hospitalization rates that showed heterogeneous spatial and temporal utilization patterns. The odds of a county being a hotspot increased significantly with the county-level percentage of dual Medicare-Medicaid beneficiaries (aOR 1.05; 95% CI: 1.04-1.07) and the prevalence of cancer (aOR 1.73; 95% CI: 1.59-1.89), while decreased significantly with increasing degree of rurality (aOR .82; 95% CI: .79-.85) and decreased yearly over time (aOR .72; 95% CI: .68-.75). The identified hotspots and factors at the county-level may help understand healthcare utilization patterns and assess resource allocation for this unique patient group.

Utilizing residential histories to assess environmental exposure and socioeconomic status over the life course among mesothelioma patients.

Background: Exposure misclassification based solely on the address at cancer diagnosis has been widely recognized though not commonly assessed. Methods: We linked 1,015 mesothelioma cases diagnosed during 2011-2015 from the New York State Cancer Registry to inpatient claims and LexisNexis administrative data and constructed residential histories. Percentile ranking of exposure to ambient air toxics and socioeconomic status (SES) were based on the National Air Toxic Assessment and United States Census data, respectively. To facilitate comparisons over time, relative exposures (REs) were calculated by dividing the percentile ranking at individual census tract by the state-level average and subtracting one. We used generalized linear regression models to compare the RE in the past with that at cancer diagnosis, adjusting for patient-level characteristics. Results: Approximately 43.7% of patients had residential information available for up to 30 years, and 96.0% up to 5 years. The median number of unique places lived was 4 [interquartile range (IQR), 2-6]. The time-weighted-average RE from all addresses available had a median of -0.11 (IQR, -0.50 to 0.30) for air toxics and -0.28 (IQR, -0.65 to 0.25) for SES. RE associated with air toxics (but not SES) was significantly higher for earlier addresses than addresses at cancer diagnosis for the 5-year [annual increase =1.24%; 95% confidence interval (CI): 0.71-1.77%; n=974] and 30-year (annual increase =0.36%; 95% CI: 0.25-0.48%; n=444) look-back windows, respectively. Conclusions: Environmental exposure to non-asbestos air toxics among mesothelioma patients may be underestimated if based solely on the address at diagnosis. With geospatial data becoming more readily available, incorporating cancer patients' residential history would lead to reduced exposure misclassification and accurate health risk estimates.

Sex Differences in Diet and Physical Activity Behaviors Among Racial/Ethnic Minority Adolescents with High Metabolic Risk.

Certain dietary and physical activity (PA) behaviors may differentially predispose male and female adolescents to obesity and diabetes; however, sex differences in dietary and PA behaviors and in factors that impact these behaviors (e.g., self-efficacy, social support) in this population remain unknown. Using data from a community-based adolescent diabetes prevention intervention conducted in East Harlem in New York City, we examined sex differences in baseline characteristics including clinical measurements, lifestyle behaviors, and behavioral determinants. Among 147 overweight/obese adolescents aged 13-19 years, 61.9% were girls, 69.7% were of Hispanic ethnicity, 24.8% were non-Hispanic Black, and 60.5% were diagnosed with prediabetes. Boys had higher metabolic risk scores than girls (3.8 vs. 3.3, p = 0.002) despite girls reporting more perceived barriers to healthy eating and PA. Boys reported doing more moderate to vigorous PA but also had more sedentary behaviors than girls. Boys reported higher self-efficacy and more peer support for PA. Girls reported more depressive symptoms and were more likely to compare their body images to those in magazines/social media. Overall, among a sample of urban adolescents with high metabolic risk, we found significant sex differences in many dietary and PA behaviors and related factors, which could be used to inform tailored strategies for weight management to reduce cardiometabolic risk among youth from similar high-risk populations.

County-Level Social Vulnerability, Metropolitan Status, and Availability of Home Health Services.

This cross-sectional study assesses county-level differences in home-based medical care and home health care by social vulnerability and metropolitan status.

Cost-effectiveness of physical activity interventions for prevention and management of cognitive decline and dementia-a systematic review.

BACKGROUND: Although increasing physical activity (PA) has been suggested to prevent and manage cognitive decline and dementia, its economic impact on healthcare systems and society is largely unknown. This study aimed to summarize evidence on the cost-effectiveness of PA interventions to prevent and manage cognitive decline and dementia. METHODS: Electronic databases, including PubMed/MEDLINE, Embase, and ScienceDirect, were searched from January 2000 to July 2023. The search strategy was driven by a combination of subject-heading terms related to physical activity, cognitive function, dementia, and cost-effectiveness. Selected studies were included in narrative synthesis, and extracted data were presented in narrative and tabular forms. The risk of bias in each study was assessed using the Consolidated Health Economic Evaluation Reporting Standards and Consensus on Health Economic Criteria list. RESULTS: Five of the 11 identified studies focused on individuals with existing dementia. Six of the 11 identified studies focused on individuals with no existing dementia, including 3 on those with mild cognitive impairment (MCI), and 3 on those with no existing MCI or dementia. PA interventions focused on individuals with no existing dementia were found to be cost-effective compared to the control group. Findings were mixed for PA interventions implemented in individuals with existing dementia. CONCLUSIONS: PA interventions implemented before or during the early stage of cognitive impairment may be cost-effective in reducing the burden of dementia. More research is needed to investigate the cost-effectiveness of PA interventions in managing dementia. Most existing studies used short-term outcomes in evaluating the cost-effectiveness of PA interventions in the prevention and management of dementia; future research should consider adding long-term outcomes to strengthen the study design.

Facilitating youth diabetes studies with the most comprehensive epidemiological dataset available through a public web portal.

The prevalence of type 2 diabetes mellitus (DM) and prediabetes (preDM) is rapidly increasing among youth, posing significant health and economic consequences. To address this growing concern, we created the most comprehensive youth-focused diabetes dataset to date derived from National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018. The dataset, consisting of 15,149 youth aged 12 to 19 years, encompasses preDM/DM relevant variables from sociodemographic, health status, diet, and other lifestyle behavior domains. An interactive web portal, POND (Prediabetes/diabetes in youth ONline Dashboard), was developed to provide public access to the dataset, allowing users to explore variables potentially associated with youth preDM/DM. Leveraging statistical and machine learning methods, we conducted two case studies, revealing established and lesser-known variables linked to youth preDM/DM. This dataset and portal can facilitate future studies to inform prevention and management strategies for youth prediabetes and diabetes.

High ambient temperatures associations with children and young adult injury emergency department visits in NYC.

Injury is a significant health burden for children and young adult and may be an increasing concern in a warming climate. Research reveals many impacts to children's health associated with hot weather and heatwave events, including a growing literature on the association between high ambient temperature and injury, which may vary by intent such as injury resulting from violence. However, little is known about how this association varies across different types of injury and subgroups of young people. We examined relationships between warm season ambient temperature and intentional and unintentional injury among children and young adults in New York City (NYC). Within a case-crossover design, our study observed injury-related emergency department (ED) visits from the New York Statewide Planning and Research Cooperative System administrative dataset. Injuries were categorized as unintentional or intentional injuries during the warm season (May through September) in NYC from 2005 to 2011 among patients (0, 1-4, 5-9, 10-14, 15-19, 20-25 years old (y.o.)). Conditional logistic regression models with distributed lag non-linear functions were used to model the cumulative odds ratio (OR) injury-related ED visit over 0-5 lag days. Analyses were stratified by age group and sex to understand how associations vary across young people of different age and sex. There were a total of 572 535 injury-related ED visits. The largest effect of elevated temperature (daily minimum 77°F vs 48°F) was for unintentional injury among 5-9 y.o. (OR 1.32, 95% CI 1.23, 1.42) and for intentional injury among 20-25 y.o. (OR 1.54, 95% CI 1.28, 1.85). Further stratified analyses revealed that the highest risk of unintentional injury was among 5-9 y.o. males and 20-25 y.o. males for intentional injury. Our results suggest that high ambient temperatures are associated with higher odds of unintentional and intentional injuries among children. This work adds to a growing body of literature demonstrating the adverse impacts of heat on children, and suggests the need for messaging to parents and children about adopting adaptive strategies to prevent injuries when it is hot outside.

Longitudinal Assessment of Association Between Tobacco Use and Tobacco Dependence Among Adults: Latent Class Analysis of the Population Assessment of Tobacco and Health Study Waves 1-4.

INTRODUCTION: With increasing tobacco product varieties, understanding tobacco use (TU) profiles and their associations with tobacco dependence (TD) has also become increasingly challenging. AIMS AND METHODS: We aimed to identify TU profiles and their associations with TD over time, and to identify subgroups with high risk of TD. We included 3463 adult recent tobacco users who had complete TU and TD data across waves 1-4 of the Population Assessment of Tobacco and Health (PATH) study. We used a composite index of TD and a summed TD score from an established 16-item TD measure. We applied a latent class analysis to identify TU profiles based on participants' usage of eight common tobacco product groups at each survey wave and to check the stability of the TU profiles over time. We then used generalized estimating equations regressions to evaluate the longitudinal TU-TD association, adjusting for potential confounders. RESULTS: We identified three distinct TU profiles that remained consistent across four survey waves: Dominant cigarette users (62%-68%), poly users with high propensity of using traditional cigarettes, e-cigarettes, and cigars (24%-31%), and dominant smokeless product users (7%-9%). Covariate-adjusted models showed that TD was significantly lower among the poly users and the dominant smokeless users, compared to that among the dominant cigarette users. CONCLUSIONS: Both TU profiles and their associations with TD were stable over time at the population level. Poly users and smokeless product users were consistently associated with lower TD than cigarette-dominant users, suggesting the need for tailored tobacco cessation interventions for users with different TU profiles. IMPLICATIONS: The finding of consistent TU profiles across four survey waves extends the current literature in capturing TU patterns in an evolving tobacco product landscape. The finding of the overall higher level of TD among the cigarette-dominant users compared to the other TU latent profiles (the Cig+eCig+Cigar dominant poly users and the dominant smokeless product users) can help identify high-risk groups for potential interventions. Our application of innovative statistical methods to high-quality longitudinal data from the PATH study helps improve the understanding of the dynamic TU-TD relationship over time.

Depression in Individuals With Diabetic Retinopathy in the US National Health and Nutrition Examination Survey, 2005-2008.

PURPOSE: To examine the relationship between diabetic retinopathy (DR) and depression in the United States. DESIGN: Retrospective, cross-sectional study. METHODS: National Health and Nutrition Examination Survey (NHANES) participants between 2005 and 2008 (ages 40-85 years) were included. Prevalence of major depression among DR stages as determined by retinal imaging was estimated. Multivariable models assessed associations between depression and DR. RESULTS: Depression was more common in those with moderate to severe DR (16%) than in those with no DR (7%), mild nonproliferative diabetic retinopathy (NPDR, 6%), or proliferative DR (5%). In a model with DR stages that adjusted for demographic factors, there was an association between moderate to severe DR and depression (odds ratio [OR], 2.46, 95% CI, 1.03-5.85). CONCLUSIONS: Depression was more prevalent in those with moderate to severe NPDR than in those with no DR, mild NPDR, or proliferative DR. This relationship is statistically significant after adjustment for demographic factors.

Association Between Serum Vitamin D Levels and Myopia in the National Health and Nutrition Examination Survey (2001-2006).

PURPOSE: To assess the relationship between serum vitamin D levels and myopia in people aged 12-50 years using the National Health and Nutrition Examination Survey (NHANES) database. METHODS: Demographics, vision, and serum vitamin D levels from NHANES (2001-2006) were analyzed. Multivariate analyses were performed to examine the relationship between serum vitamin D levels and myopia while controlling for sex, age, ethnicity, education level, serum vitamin A, and poverty status. The main outcome was presence or absence of myopia, defined as a spherical equivalent of -1 diopters or more. RESULTS: Of the 11669 participants, 5,310 (45.5%) had myopia. The average serum vitamin D concentration was 61.6 ± 0.9 nmol/L for the myopic group and 63.1 ± 0.8 nmol/L for the non-myopic group (p = .01). After adjusting for all covariates, having higher serum vitamin D was associated with lower odds of having myopia (odds ratio 0.82 [0.74-0.92], p = .0007). In linear regression modeling that excluded hyperopes (spherical equivalent > +1 diopters), there was a positive relationship between spherical equivalent and serum vitamin D levels. Specifically, as serum vitamin D doubled, spherical equivalent increased by 0.17 (p = .02) indicating a positive dose-response relationship between vitamin D and myopia. CONCLUSIONS: Participants with myopia, on average, had lower serum concentrations of vitamin D compared to those without myopia. While further studies are needed to determine the mechanism, this study suggests that higher vitamin D levels are associated with lower incidence of myopia.

An improved reporter identifies ruxolitinib as a potent and cardioprotective CaMKII inhibitor.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) hyperactivity causes cardiac arrhythmias, a major source of morbidity and mortality worldwide. Despite proven benefits of CaMKII inhibition in numerous preclinical models of heart disease, translation of CaMKII antagonists into humans has been stymied by low potency, toxicity, and an enduring concern for adverse effects on cognition due to an established role of CaMKII in learning and memory. To address these challenges, we asked whether any clinically approved drugs, developed for other purposes, were potent CaMKII inhibitors. For this, we engineered an improved fluorescent reporter, CaMKAR (CaMKII activity reporter), which features superior sensitivity, kinetics, and tractability for high-throughput screening. Using this tool, we carried out a drug repurposing screen (4475 compounds in clinical use) in human cells expressing constitutively active CaMKII. This yielded five previously unrecognized CaMKII inhibitors with clinically relevant potency: ruxolitinib, baricitinib, silmitasertib, crenolanib, and abemaciclib. We found that ruxolitinib, an orally bioavailable and U.S. Food and Drug Administration-approved medication, inhibited CaMKII in cultured cardiomyocytes and in mice. Ruxolitinib abolished arrhythmogenesis in mouse and patient-derived models of CaMKII-driven arrhythmias. A 10-min pretreatment in vivo was sufficient to prevent catecholaminergic polymorphic ventricular tachycardia, a congenital source of pediatric cardiac arrest, and rescue atrial fibrillation, the most common clinical arrhythmia. At cardioprotective doses, ruxolitinib-treated mice did not show any adverse effects in established cognitive assays. Our results support further clinical investigation of ruxolitinib as a potential treatment for cardiac indications.