Histories of neighborhood socioeconomic status contribute to race differences in later-life cognition.

INTRODUCTION: Neighborhood characteristics are increasingly implicated in cognitive health disparities, but no research has investigated how the historical context of neighborhoods shapes these disparities. METHODS: Four hundred sixty-four Black (55%) and White older adults (Mage = 63.6) were drawn from the Michigan Cognitive Aging Project, a community-based, prospective study of older adults. Participants' addresses at baseline (2017-2020) were geocoded and linked to 2000-2017 measures of neighborhood socioeconomic status (NSES): disadvantage [NDis] and affluence [NAff]. Latent class growth analysis (LCGA) characterized 18 interpolated year trajectories of NSES across 1344 census tracts. Path analysis examined whether NSES trajectory classes mediated the association between race and a global cognition composite. RESULTS: LCGA identified three NDis and two NAff trajectory classes, which were associated with participant race. Only one NDis class was associated with cognition, and it mediated the association between the Black race and cognition. DISCUSSION: Disinvestment in neighborhoods may be particularly salient in race disparities in cognitive function. HIGHLIGHTS: Race is implicated in the likelihood of living in more disadvantaged neighborhoods. Historical trends in neighborhood disadvantage are associated with cognitive function in older adulthood. Identifying patterns of neighborhood change may inform neighborhood-level interventions.

Preclinical Dementia and Economic Well-Being Trajectories of Racially Diverse Older Adults.

ObjectivesThis study examined the magnitude, changes, and racial/ethnic disparities in the economic costs of the 16-year preclinical phase of dementia-a period of cognitive decline without significant impact on daily activities. Methods: The study utilized two dementia algorithms to classify individuals with incident dementia in the Health and Retirement Study. These cases were compared to matched controls in terms of poverty status, labor force participation, and unsecured debts. Results: Older adults classified with dementia were more likely to drop out of the labor force and become poor than similar older adults without dementia. Racial/ethnic disparities in poverty persisted during the preclinical period, with non-Hispanic Black older adults more likely to leave the labor force and Hispanic older adults more likely to have unsecured debt. Discussion: Findings highlight the economic costs during prodromal phase of dementia, emphasizing need for early interventions to reduce financial strain across diverse older adults.

Cost and time-efficient construction of a 3'-end mRNA library from unpurified bulk RNA in a single tube.

The major drawbacks of RNA sequencing (RNA-seq), a remarkably accurate transcriptome profiling method, is its high cost and poor scalability. Here, we report a highly scalable and cost-effective method for transcriptomics profiling called Bulk transcriptOme profiling of cell Lysate in a single poT (BOLT-seq), which is performed using unpurified bulk 3'-end mRNA in crude cell lysates. During BOLT-seq, RNA/DNA hybrids are directly subjected to tagmentation, and second-strand cDNA synthesis and RNA purification are omitted, allowing libraries to be constructed in 2 h of hands-on time. BOLT-seq was successfully used to cluster small molecule drugs based on their mechanisms of action and intended targets. BOLT-seq competes effectively with alternative library construction and transcriptome profiling methods.

A point-of-care pilot randomized intervention to connect patients with cancer-induced financial toxicity to telehealth financial counseling.

PURPOSE: Elevated costs of cancer treatment can result in economic and psychological "financial toxicity" distress. This pilot study assessed the feasibility of a point-of-care intervention to connect adult patients with cancer-induced financial toxicity to telehealth-delivered financial counseling. METHODS: We conducted a three-armed parallel randomized pilot study, allocating newly referred patients with cancer and financial toxicity to individual, group accredited telehealth financial counseling, or usual care with educational material (1:1:1). We assessed the feasibility of recruitment, randomization, retention, baseline and post-intervention COmprehensive Score for Financial Toxicity (COST), and Telehealth Usability Questionnaire (TUQ) scores. RESULTS: Of 382 patients screened, 121 were eligible and enrolled. 58 (48%) completed the intervention (9 individual, 9 group counseling, 40 educational booklet). 29 completed follow-up surveys: 45% female, 17% African American, 79% white, 7% Hispanic, 55% 45-64 years old, 31% over 64, 34% lived in rural areas, 24% had cancer stage I, 21% II, 7% III, 31% IV. Baseline characteristics were balanced across arms, retention status, surveys completion. Mean (SD) COST was 12.4 (6.1) at baseline and 16.0 (8.4) post-intervention. Mean (SD) COST score differences were 6.3 (11.6) after individual counseling, 5.8 (8.5) after group counseling, and 2.5 (6.4) after usual care. Mean TUQ score among nine counseling participants was 5.5 (0.9) over 7.0. Non-parametric comparisons were not statistically meaningful. CONCLUSION: Recruitment and randomization were feasible, while study retention presented challenges. Nine participants reported good usability and satisfaction with telehealth counseling. Larger-scale trials focused on improving participation, retention, and impact of financial counseling among patients with cancer are justified.

Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center: Structure, Innovations, and Initial Outcomes.

INTRODUCTION: The Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE2 triad partnership. METHODS: CaRE2 serves diverse populations in Florida and California using a "molecule to the community and back" model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. RESULTS: Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE2-related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. CONCLUSION: The CaRE2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.

Pediatric primary care provider and staff perspectives on the implementation of electronic health record-based social needs interventions: A mixed-methods study.

Introduction: Interventions to address social needs in clinical settings can improve child and family health outcomes. Electronic health record (EHR) tools are available to support these interventions but are infrequently used. This mixed-methods study sought to identify approaches for implementing social needs interventions using an existing EHR module in pediatric primary care. Methods: We conducted focus groups and interviews with providers and staff (n = 30) and workflow assessments (n = 48) at four pediatric clinics. Providers and staff completed measures assessing the acceptability, appropriateness, and feasibility of social needs interventions. The Consolidated Framework for Implementation Research guided the study. A hybrid deductive-inductive approach was used to analyze qualitative data. Results: Median scores (range 1-5) for acceptability (4.9) and appropriateness (5.0) were higher than feasibility (3.9). Perceived barriers to implementation related to duplicative processes, parent disclosure, and staffing limitations. Facilitators included the relative advantage of the EHR module compared to existing documentation practices, importance of addressing social needs, and compatibility with clinic culture and workflow. Self-administered screening was seen as inappropriate for sensitive topics. Strategies identified included providing resource lists, integrating social needs assessments with existing screening questionnaires, and reducing duplicative documentation. Conclusions: This study offers insight into the implementation of EHR-based social needs interventions and identifies strategies to promote intervention uptake. Findings highlight the need to design interventions that are feasible to implement in real-world settings. Future work should focus on integrating multiple stakeholder perspectives to inform the development of EHR tools and clinical workflows to support social needs interventions.

Parent Perspectives on Electronic Health Record-Based Social Needs Screening and Documentation: A Qualitative Study.

OBJECTIVE: Social needs interventions in clinical settings can improve child health outcomes; however, they are not routinely delivered in routine pediatric care. The electronic health record (EHR) can support these interventions, but parent engagement in the development of EHR-based social needs interventions is lacking. The aim of this study was to assess parent perspectives on EHR-based social needs screening and documentation and identify family-centered approaches for screening design and implementation. METHODS: We enrolled 20 parents from four pediatric primary care clinics. Parents completed a social risk questionnaire from an existing EHR module and participated in qualitative interviews. Parents were asked about the acceptability of EHR-based social needs screening and documentation and preferences for screening administration. A hybrid deductive-inductive approach was used to analyze qualitative data. RESULTS: Parents identified the benefits of social needs screening and documentation but expressed concerns related to privacy, fear of negative outcomes, and use of outdated documentation. Some felt self-administered electronic questionnaires would mitigate parent discomfort and encourage disclosure of social needs, while others felt face-to-face screening would be more effective. Parents stressed the importance of transparency on the purpose of social needs screening and the use of data. CONCLUSIONS: This work can inform the design and implementation of EHR-based social needs interventions that are acceptable and feasible for parents. Findings suggest strategies such as clear communication and multi-modal delivery methods may enhance intervention uptake. Future work should integrate feedback from multiple stakeholders to design and evaluate interventions that are family-centered and feasible to implement in clinical settings.

Racial and Ethnic Differences in Initiation of Menthol Tobacco Smoking and Subsequent Tobacco Use in the Population Assessment of Tobacco and Health Study, Waves 1-4 (2013-2018).

INTRODUCTION: Certain subpopulations in the United States are highly vulnerable to tobacco initiation and addiction, and elimination of disparities among those groups is crucial to reducing the burden of tobacco use. AIMS AND METHODS: This study evaluated the racial and ethnic differences in smoking initiation of menthol flavored cigarettes and cigars among never-users, and in subsequent tobacco use among new users of menthol-flavored products, using longitudinal data from waves 1-4 of the Population Assessment of Tobacco and Health Study. The outcomes of interest were new use of menthol-flavored products, and subsequent past 30-day and past 12-month cigarette and cigar smoking, irrespective of flavors, after initiation. RESULTS: The percentages of new users of menthol-flavored cigarettes and cigars at waves 2-4 were disproportionately higher in non-Hispanic black and Hispanic than in non-Hispanic white people. Adjusting for age and sex, black people who first used any menthol cigars had higher risk of past 30-day use of the same cigar category at the subsequent wave (adjusted risk ratio, aRR 1.48; 95% confidence interval [CI] 1.11 to 1.96) and past 12 months (aRR 1.74; 95% CI 1.55 to 2.63) compared to non-Hispanic white smokers. Black people who first used menthol-flavored cigarettes had marginally higher risk of subsequent past 30-day cigarette use (aRR 1.44; 95% CI 0.99 to 2.10) compared with their non-Hispanic white counterparts. CONCLUSIONS: This study shows that racial and ethnic differences exist in both initiation of menthol-flavored tobacco products and product-specific subsequent use after first using menthol-flavored products; black and Hispanic people have higher rates of initiation; black people also have higher rates of subsequent use. IMPLICATIONS: Use of menthol flavors in tobacco products is confirmed to be a contributor to large disparities in tobacco use; black and Hispanic people are more likely to maintain smoking through use of mentholated products than non-Hispanic white people. The findings suggest educational and regulatory actions on menthol-flavored tobacco products including restricting the selective marketing to vulnerable communities and banning characterizing flavors in cigarettes and cigars may reduce tobacco-related disparities and inform the Food And Drug Administration's evidence-based rulemaking process.

Erratum: Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea.

This corrects the article on p. 419 in vol. 34, PMID: 36478424.

Dysregulation of the PRUNE2/PCA3 genetic axis in human prostate cancer: from experimental discovery to validation in two independent patient cohorts.

Background: We have previously shown that the long non-coding (lnc)RNA prostate cancer associated 3 (PCA3; formerly prostate cancer antigen 3) functions as a trans-dominant negative oncogene by targeting the previously unrecognized prostate cancer suppressor gene PRUNE2 (a homolog of the Drosophila prune gene), thereby forming a functional unit within a unique allelic locus in human cells. Here, we investigated the PCA3/PRUNE2 regulatory axis from early (tumorigenic) to late (biochemical recurrence) genetic events during human prostate cancer progression. Methods: The reciprocal PCA3 and PRUNE2 gene expression relationship in paired prostate cancer and adjacent normal prostate was analyzed in two independent retrospective cohorts of clinically annotated cases post-radical prostatectomy: a single-institutional discovery cohort (n=107) and a multi-institutional validation cohort (n=497). We compared the tumor gene expression of PCA3 and PRUNE2 to their corresponding expression in the normal prostate. We also serially examined clinical/pathological variables including time to disease recurrence. Results: We consistently observed increased expression of PCA3 and decreased expression of PRUNE2 in prostate cancer compared with the adjacent normal prostate across all tumor grades and stages. However, there was no association between the relative gene expression levels of PCA3 or PRUNE2 and time to disease recurrence, independent of tumor grades and stages. Conclusions: We concluded that upregulation of the lncRNA PCA3 and targeted downregulation of the protein-coding PRUNE2 gene in prostate cancer could be early (rather than late) molecular events in the progression of human prostate tumorigenesis but are not associated with biochemical recurrence. Further studies of PCA3/PRUNE2 dysregulation are warranted. Funding: We received support from the Human Tissue Repository and Tissue Analysis Shared Resource from the Department of Pathology of the University of New Mexico School of Medicine and a pilot award from the University of New Mexico Comprehensive Cancer Center. RP and WA were supported by awards from the Levy-Longenbaugh Donor-Advised Fund and the Prostate Cancer Foundation. EDN reports research fellowship support from the Brazilian National Council for Scientific and Technological Development (CNPq), Brazil, and the Associação Beneficente Alzira Denise Hertzog Silva (ABADHS), Brazil. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of New Mexico Comprehensive Cancer Center (CA118100) and the Rutgers Cancer Institute of New Jersey (CA072720).

Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea.

BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited. OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea. METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. RESULTS: Of the 1,163 patients, 695 (59.8%) were men (mean age [years]±standard deviation: 31.6±12.1). Overall, 52.9% (n=615) patients had moderate-to-severe disease (EASI>7). The QoL of 72.3% (n=840) patients was affected moderately-to-severely (DLQI score: 6~30). Systemic immunosuppressants were used ≥1 over past 12 months in 51.9% (n=603) patients, and the most commonly used were cyclosporines (45.7%, n=531) and systemic corticosteroids (40.5%, n=471). Approximately, 10.8% (n=126) patients consulted or received treatment for AD-related eye problem. Of these, 40% (n=50) patients reported poor, very poor, or completely blind status; approximately, 16.7% patients (n=192) reported having depression or anxiety; and 35.5% (n=410) reported suicidal ideation or suicidal attempt. CONCLUSION: A large proportion of patients had moderate-to-severe AD, a compromised QoL, and ocular or mental health comorbidities, indicating a high disease burden despite systemic treatment. These findings highlight the importance of a holistic approach for the evaluation and treatment of patients with AD.

Nutritional assessment formulae for nutritional requirement determination in severe trauma.

BACKGROUND AND OBJECTIVES: It is often difficult to assess the nutritional requirements of severely injured patients. In this study, we aimed to determine whether various nutritional assessment formulas are accurate at assessing the nutritional requirements of trauma patients. METHODS AND STUDY DESIGN: We recruited trauma patients who were admitted to a trauma centre in 2018 and were identified as being at high risk for malnutrition. Energy expenditure was calculated using commonly used prediction equations, and the results were compared to resting energy expenditures measured using indirect calorimetry. RESULTS: Sixty-nine patients (78.9% men; mean age, 53.6 years) collectively underwent 95 indirect calorimetry assessments. The average resting energy expenditure was 1761.8±483.8 kcal/day, and the average respiratory quotient was 0.8±0.2. The correlations between the measured resting energy expenditures and nutritional requirements estimated by each formula were significant but weak (i.e., r-values <0.8). The Penn State formula had the highest r-value (0.742; 95% confidence interval [CI], 0.6359-0.8210), followed by the Faisy formula (0.730; 95% CI, 0.620-0.812). CONCLUSIONS: The formulapredicted nutritional requirements did not adequately correlate with the resting energy expenditures measured by indirect calorimetry. Therefore, we recommend using indirect calorimetry to assess the nutritional requirements of severely injured patients.

Role Value, Occupational Balance, and Quality of Life: A Cross-Sectional Study on Exploring the Urban Older People Perspective in South Korea.

The purpose of this study was to investigate the role value, occupational balance, and quality of life among urban older adults in South Korea. We recruited 90 urban older adults in Seoul, Gyeonggi-do and Chungcheong-do. Assessments used (1) Role Checklist, (2) Life Balance Inventory (LBI), and (3) WHO Quality of Life Scale abbreviated version (WHOQOL-BREF). Our results showed that the roles that were perceived as very valuable were as family members, housekeepers, and guardians (in descending order). The roles that were perceived as less valuable were students, volunteers, and organizational members (in descending order). The activities that individuals were actively pursuing were hygiene management, rest, and healthy eating (in descending order). By contrast, the activities that were not being actively pursued were composing (music, poetry), preparing for event planning, dancing, yoga, and taekwondo. The total score of the Role Checklist and WHOQOL-BREF total (r = 0.343, p < 0.01), K-LBI total and WHOQOL-BREF total (r = 0.386, p < 0.01), and role value total and K-LBI (r = 323, p < 0.01) showed a statistically significant correlation. As a result of the regression analysis, the sub-item of work balance that affected the quality of life was managing appearance (R2 = 51.7, p < 0.001). These data showed that the role of urban older adults in Korea was mainly played within the family. The level of participation was low in the areas of instrumental daily life activities, work, leisure, and social participation. We propose that this population needs to be provided with opportunities for active aging through broader professional participation.

Transition to smoking cessation among dual cigarette and e-cigarette users in the population assessment of tobacco and health study, Waves 3 and 4 (2015-2017).

INTRODUCTION: This study evaluated the patterns of smoking cessation at Wave 4 of the Population Assessment of Tobacco and Health (PATH) Study among established cigarette smokers who were also current e-cigarettes users at Wave 3. METHODS: We assessed changes in smoking frequency at Wave 4 among established cigarette and e-cigarette users at Wave 3. The demographics of participants were analyzed as well as e-cigarettes device types, number of cigarettes smoked and time from waking up until the first cigarette. Unadjusted and adjusted odds ratios as well as percentage of discontinuing cigarettes use at Wave 4 were calculated for the different categories of dual users. RESULTS: Among dual users at Wave 3, 13.1% quit cigarette smoking at Wave 4, whereas half discontinued e-cigarette use and maintained exclusive cigarette smoking. Significant differences in the percentage of smoking cessation were observed across demographic groups - dual users with a bachelor's degree were more likely to quit smoking than dual users who did not finish high school (aOR = 3.06, 95% CI: 1.17-8.00) and smokers aged 25-64 years were less likely to quit smoking than those aged 18-24 years (aOR = 0.49, 95% CI: 0.28-0.86 for smokers aged 25-44 years, and aOR = 0.42, 95% CI: 0.20-0.87 for those aged 45-64). Dual users who smoked more than 15 cigarettes per day were significantly less likely to stop smoking (aOR = 0.38, 95% CI: 0.17-0.88). CONCLUSION: E-cigarettes have the potential to aid in smoking cessation. Questions remain as to whether dual use of e-cigarettes and cigarettes should be encouraged as a transitional phase on the path to smoking cessation.

Social determinants of health and outcomes for children and adults with congenital heart disease: a systematic review.

BACKGROUND: Social determinants of health (SDH) can substantially impact health outcomes. A systematic review, however, has never been conducted on associations of SDH with congenital heart disease (CHD) outcomes. The aim, therefore, was to conduct such a systematic review. METHODS: Seven databases were searched through May 2020 to identify articles on SDH associations with CHD. SDH examined included poverty, uninsurance, housing instability, parental educational attainment, immigration status, food insecurity, and transportation barriers. Studies were independently selected and coded by two researchers based on the PICO statement. RESULTS: The search generated 3992 citations; 88 were included in the final database. SDH were significantly associated with a lower likelihood of fetal CHD diagnosis, higher CHD incidence and prevalence, increased infant mortality, adverse post-surgical outcomes (including hospital readmission and death), decreased healthcare access (including missed appointments, no shows, and loss to follow-up), impaired neurodevelopmental outcomes (including IQ and school performance) and quality of life, and adverse outcomes for adults with CHD (including endocarditis, hospitalization, and death). CONCLUSIONS: SDH are associated with a wide range of adverse outcomes for fetuses, children, and adults with CHD. SDH screening and referral to appropriate services has the potential to improve outcomes for CHD patients across the lifespan. IMPACT: Social determinants of health (SDH) are associated with a wide range of adverse outcomes for fetuses, children, and adults with congenital heart disease (CHD). This is the first systematic review (to our knowledge) on associations of SDH with congenital heart disease CHD outcomes. SDH screening and referral to appropriate services has the potential to improve outcomes for CHD patients across the lifespan.

Assessment of fish biodiversity in four Korean rivers using environmental DNA metabarcoding.

Environmental DNA (eDNA) metabarcoding is a cost-effective novel approach to estimate biodiversity in an ecosystem. In this study, the MiFish pipeline was employed to test if the system methodology is sufficiently reliable to estimate fish biodiversity in Korean rivers. A total of 125 unique haplotypes and 73 species were identified at the species level from 16 water samples collected from a single survey in four Korean rivers (Hyeongsan, Taehwa, Seomjin, and Nakdong). Among the four rivers, the highest species richness was recorded in the Seomjin River (52 species), followed by the Taehwa (42 species) and Hyeongsan (40 species) rivers. The Nakdong River (26 species) presented the lowest species richness and number of endemic species, presumably due to its metropolitan location and anthropogenic impacts, such as dams or weirs. We were also able to detect that five exotic species (Carassius cuvieri, Cyprinus carpio, Cyprinus megalophthalmus, Lepomis macrochirus, and Micropterus salmoides) are widely distributed in all surveyed rivers, a situation that might be problematic in terms of conservation. Our findings indicate that the eDNA metabarcoding technique is one of the most cost-effective scientific tools available for the management and conservation of the freshwater fish resources available in Korea. However, the low number of 12S sequences of endemic species in the database and low resolution of the MiFish region for differentiating several taxa should be upgraded for their wide use.

An approach to evaluate myocardial perfusion defect assessment for projection-based DECT: A phantom study.

INTRODUCTION: Dual-energy CT (DECT) can improve the accuracy of myocardial perfusion CT with projection-based monochromatic (DECT-MCE) and quantification of myocardial iodine in material decomposition (DECT-MD) reconstructions. However, evaluation of multiple reconstructions is laborious and the optimal reconstruction to detect myocardial perfusion defects is unknown. METHODS: Left ventricular (LV) phantoms with artificial perfusion defects were scanned using DECT and single energy cardiac computed tomography angiography (SECT). Reconstructions of DECT-MCE at 40, 70, 100 and 140 keV, DECT-MD pairs of water, iodine, iron and fat, and SECT were evaluated using a 17-segment myocardial model. The diagnostic performance of each reconstruction was calculated on a per-segment basis and compared across DECT reconstructions. RESULTS: Over 34 phantoms with artificial perfusion defects were found in 64/578 (11%) of segments, the sensitivity of DECT-MCE at 40, 70, 100, and 140 keV was 100% (95% confidence interval (CI): 93-100), 100% (95% CI: 93-100), 71% (95% CI: 56-83), and 25% (95% CI: 14-40), respectively, with a significant decline between 70 keV and 100 keV (p < 0.001). The specificity of DECT-MCE was 100% at all energies (95% CI: 99-100). As a group, the DECT-MD iodine background reconstructions had significantly lower sensitivity than the remaining modes (2.1% [95% CI, 0.05-11.1], vs. 100% [95% CI, 92.6-100], p < 0.001). Specificity of all material pair modes remained 100%. CONCLUSIONS: Using LV phantom models, the approach with the best sensitivity and specificity to assess myocardial perfusion defects with DECT are reconstructions of DECT-MCE at 40 or 70 KeV and DECT-MD without iodine background.

Mode of silver clearance following 28-day inhalation exposure to silver nanoparticles determined from lung burden assessment including post-exposure observation periods.

Recently revised OECD inhalation toxicity testing guidelines require measurements of lung burden immediately after and for periods following exposure for nanomaterials. Lung burden is a function of pulmonary deposition and retention of nanoparticles. Using lung burden studies as per OECD guidelines, it may be possible to assess clearance mechanisms of nanoparticles. In this study, male rats were exposed to silver nanoparticle (AgNP) aerosols (18.1-19.6 nm) generated from a spark generator. Exposure groups consisted of (1) control (fresh air), (2) low (31.2 ± 8.5 µg/m3), (3) moderate (81.8 ± 11.4 µg/m3), and (4) high concentrations (115.6 ± 30.5 µg/m3). Rats were exposed for 6-h/day, 5-days/week for 4 weeks (28-days) based on the revised OECD test guideline 412. Bronchoalveolar lavage (BAL) fluids were collected on post-exposure observation (PEO)-1 and PEO-7 days and analyzed for inflammatory cells and inflammatory biomarkers. The lung burdens of Ag from AgNPs were measured on PEO-1, PEO-7, and PEO-28 days to obtain quantitative mass concentrations per lung. Differential counting of blood cells and inflammatory biomarkers in BAL fluid and histopathological evaluation of lung tissue indicated that exposure to the high concentrations of AgNP aerosol induced inflammation at PEO-1, slowly resolved at PEO-7 and completely resolved at PEO-28 days. Lung burden measurement suggested that Ag from AgNPs was cleared through two different modes; fast and slow clearance. The fast clearance component was concentration-dependent with half-times ranging from two to four days and clearance rates of 0.35-0.17/day-1 from low to high concentrations. The slow clearance had half-times of 100, 57, and 76 days and clearance rates of 0.009, 0.012, and 0.007/day-1 for the high, moderate and low concentration exposure. The exact mechanism of clearance is not known currently. The fast clearance component which was concentration-dependent could be dependent on the dissolution of AgNPs and the slow clearance would be due to slow clearance of the low dissolution AgNPs secondary particles originating from silver ions reacting with biogenic anions. These secondary AgNPs might be cleared by mechanisms other than dissolution such as mucociliary escalation, translocation to the lymphatic system or other organs.

Pharmacokinetic Analysis and Biomarker-Assisted Safety Assessment of Acetaminophen in Combination With Ojeok-san Compared With Acetaminophen Alone.

Acetaminophen and Ojeok-san are both frequently used analgesics. In this study, we evaluated acetaminophen pharmacokinetics (PK) and changes in microRNA-122 (miR-122) levels after multiple dosing of acetaminophen with or without Ojeok-san. An open-label, 1-sequence, 2-period, 2-treatment crossover study was conducted in 18 subjects. In period 1, 500 mg of acetaminophen was administered 3 times on day 1 and once on day 2. In period 2, after the administration of 14.47 g of Ojeok-san twice on day 2 and 3 times daily on days 3 to 7, Ojeok-san and acetaminophen were coadministered 3 times each on day 8 and once each on day 9. The geometric mean ratios (90% confidence intervals) of acetaminophen with Ojeok-san to acetaminophen alone were 0.98 (0.87 to 1.10) and 1.02 (0.98 to 1.05) for the maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve during the dosing interval (AUC0-τ ), respectively, of acetaminophen at steady state. The alanine aminotransferase (ALT) levels were within the reference range in all the participants throughout the study period, although the mean fold changes in both serum miR-122 and ALT levels from baseline tended to increase on days 2 to 5. In conclusion, the PK properties of acetaminophen were not significantly affected by Ojeok-san coadministration. For osteoarthritis patients taking acetaminophen with or without Ojeok-san, monitoring potential liver toxicity using miR-122 as a biomarker may be useful.

Adolescents' Social Norms across Family, Peer, and School Settings: Linking Social Norm Profiles to Adolescent Risky Health Behaviors.

Social norms around adolescent risky health behaviors have been often studied in separate developmental settings (e.g., family norms, peer norms), and little is known regarding the overall patterns of social norms across contexts and how they influence adolescent risky health behaviors. This study explored profiles of social norms around risky health behaviors across family, peer, and school settings, using data from 11,086 adolescents (50% female; 49% White, 22% Black, 18% Latinx, 8% Asian American, 3% other race/ethnicities) in the National Longitudinal Study of Adolescent to Adult Health. Five profiles of social norms around risky health behaviors emerged. Only a small portion of the sample experienced either congruent-restrictive (6%) or congruent-permissive (10%) social norms across settings. The majority experienced incongruent social norms, including the developmentally normative-low risk (39%), developmentally normative-high risk (40%), and resilient (5%) profiles. Adolescents with the congruent-restrictive profile and developmentally normative-low risk profiles exhibited the least risky health behaviors over time, followed by those with the resilient profile, and adolescents with the developmentally normative-high risk and the congruent-permissive profile exhibited the greatest risky health behaviors over time. Each profile was associated with unique developmental, socio-demographic, and psychosocial characteristics. The findings highlighted the complexity of social norms across contexts and the developmental versus risky natures of these social norm profiles.