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BackgroundThe objectives were to assess (a) the association between poor oral health and mild cognitive impairment (MCI) in Hispanic/Latino immigrants and (b) potential modification effects on this association by age at immigration.MethodsData were from the Hispanic Community Health Study/Study of Latinos and its ancillary study-the Study of Latinos-Investigation of Neurocognitive Aging. MCI, a binary outcome variable, defined by the National Institute on Aging-Alzheimer's Association criteria. The main exposure was significant tooth loss (STL), defined as a loss of 8 or more teeth, and periodontitis, classified using the Centers for Disease Control and Prevention and American Academy of Periodontology case classification. Multiple logistic regression was used to assess the association between STL/periodontitis and MCI and test moderation effects of age at immigration. The analytical sample comprised 5 709 Hispanic/Latino adult immigrants.ResultsHispanic/Latino immigrants with STL (adjusted odds ratio [AOR] = 1.36, 95% confidence interval [CI]: 1.01-1.85) were more likely to have MCI than those with greater tooth retention. Overall, migration to the United States after age 18 was associated with greater odds of MCI than migration at a younger age. A significant interaction effect between STL and age at immigration revealed that the effect of STL on MCI is even higher in those who immigrated to the United States at ages 35-49 years.ConclusionsSTL is a significant risk factor for MCI and age at immigration had a modification effect on the association between STL and MCI. Better access to dental care, health education on risk factors of MCI, and promotion of good oral health may mitigate the burden of cognitive impairment in Hispanics/Latinos.

Hispanic/Latino adults are a growing segment of the older U.S. population yet are underrepresented in brain aging research. We aimed to characterize brain aging among diverse Hispanic/Latino individuals. Hispanic/Latino individuals (unweighted n = 2273 ages 35-85 years; 56% female) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) population-based study underwent magnetic resonance imaging (MRI) as part of the SOL- Investigation of Neurocognitive Aging MRI (SOL-INCA-MRI) ancillary study (2018-2022). We performed linear regressions to calculate age associations with brain volumes for each outcome (total (global) brain, hippocampal, lateral ventricle, total white matter hyperintensity (WMH), individual cortical lobar, and total cortical gray matter) and tested modification by sex. Older age was associated with smaller gray matter volumes and larger lateral ventricle and WMH volumes. Age-related differences in global brain volumes and gray matter volumes in specific regions (i.e., the hippocampus and temporal and occipital lobes) were less pronounced among women. Our findings warrant further investigation into sex-specific mechanisms of brain aging using longitudinal studies.

Methamphetamine (MA) use is associated with HIV transmission among men who have sex with men (MSM) and lapses in medication adherence. Contingency Management (CM) is effective in reducing MA use, but studies of CM to support adherence to HIV prevention or treatment are limited. We conducted a pilot trial of a CM intervention to reduce MA use and improve PrEP/ART adherence among MSM prescribed a tenofovir (TFV)-based regimen for HIV prevention or treatment. Participants were randomly assigned to receive escalating incentives for either MA abstinence or TFV adherence (based on point-of-care urine testing), and to a monitoring schedule of either 2 or 3 visits/week for 4 weeks. 19 MSM were randomized to either CM for MA use or CM for PrEP/ART adherence (median age: 38; IQR: 28-46) and 15 were living with HIV. Participants attended 95.7% (67/70) of scheduled visits in the 2x/week arm and 74.8% (74/99) in the 3x/week arm. TFV adherence was higher among participants in the TFV adherence arm with 93.5% (n = 72/77) of urine samples positive for TFV, compared to 76.6% (n = 49/64) in the MA abstinence arm (p = 0.007). Participants in the MA abstinence arm had more urine samples negative for MA metabolites (20.3%, n = 13/64) than those receiving CM for TFV adherence (6.5%, n = 5/77; p = 0.021). A CM model for MA abstinence and PrEP/ART adherence using twice-weekly visits and urine testing for MA and TFV for MSM who use MA is feasible and potentially effective as an integrated harm reduction strategy.

BackgroundPatients experiencing systemic patterns of disadvantage, such as racial/ethnic minorities and those with limited English proficiency, are underrepresented in research. This is particularly true for large pragmatic trials of potentially sensitive research topics, such as advance care planning (ACP). It is unclear how phone outreach may affect research participation by underrepresented individuals.ObjectiveTo assess the effect of phone outreach, in addition to standard mail survey recruitment, in a population-based ACP pragmatic trial at three academic health systems in California.DesignRetrospective cohort study PATIENTS: Primary care patients with serious illness were mailed a survey in their preferred language. Patients who did not initially respond by mail received up to three reminder phone calls with the option of survey completion by phone.Main measuresEffect of phone outreach on survey response rate associated with respondent demographic characteristics (e.g., Social Vulnerability Index [SVI], range 0 (low) to 1 (high)).ResultsAcross the health systems, 5998 seriously ill patients were mailed surveys. We obtained completed surveys from 1215 patients (20% response rate); 787 (65%) responded after mail alone and 428 (35%) participated only after phone outreach. Patients recruited after phone outreach compared to mail alone were more socially vulnerable (SVI 0.41 v 0.35, P < 0.001), were more likely to report being a racial/ethnic minority (35% v 28%, P = 0.006), and non-English speaking (16% v 10%, P = 0.005). Age and gender did not differ significantly. The inclusion of phone outreach resulted in a sample that better represented the baseline population than mail alone in racial/ethnic minority (28% mail alone, 30% including phone outreach, 36% baseline population), non-English language preference (10%, 12%, 15%, respectively), and SVI (0.35, 0.37, 0.38, respectively).ConclusionsPhone outreach for a population-based survey in a pragmatic trial concerning a potentially sensitive topic significantly enhanced recruitment of underrepresented seriously ill patients.

PurposeTo assess the association between sexual orientation and screen use (screen time and problematic screen use) in a demographically diverse national sample of early adolescents in the United States.MethodsWe analyzed cross-sectional data from year 2 of the Adolescent Brain Cognitive Development Study (N = 10,339, 2018-2020, ages 10-14 years). Multiple linear regression analyses estimated the association between sexual orientation and recreational screen time, as well as problematic use of video games, social media, and mobile phones.ResultsIn a sample of 10,339 adolescents (48.7% female, 46.0% racial/ethnic minority), sexual minority (compared to heterosexual) identification was associated with 3.72 (95% CI 2.96-4.47) more hours of daily recreational screen time, specifically more time on television, YouTube videos, video games, texting, social media, video chat, and browsing the internet. Possible sexual minority identification (responding "maybe" to the sexual minority question) was associated with 1.58 (95% CI 0.92-2.24) more hours of screen time compared to heterosexual identification. Sexual minority and possible sexual minority identification were associated with higher problematic social media, video games, and mobile phone use.ConclusionsSexual minority adolescents spend a disproportionate amount of time engaging in screen-based activities, which can lead to problematic screen use.

BackgroundTo slow the spread of the COVID-19 virus, governments across the globe instituted stay-at-home orders leading to increased stress and social isolation. Not surprisingly, alcohol sales increased during this period. While most studies primarily focused on alcohol consumption among college students or adults, this study investigates alcohol misuse among marginalized youth in the USA. We examined risk factors associated with hazardous alcohol use and binge drinking including risk behaviors, life stressors and demographic characteristics.MethodsIn October 2020, youth living with or at high risk for acquiring human immunodeficiency virus (HIV), participating in community-based research to improve HIV prevention and care, were invited to complete an online survey to assess the impact of the stay-at-home orders on multiple aspects of their daily life.ResultsRespondents (n = 478) were on average 23 years old; cisgender (84%), not-heterosexual (86.6%), Latino or Black/African American (73%) and assigned male at birth (83%); 52% reported being employed and 14% reported living with HIV. White participants and those who use drugs had higher odds of hazardous alcohol use and binge drinking, compared with other race categories and non-drug users, respectively.ConclusionContrary to findings from adult studies, we did not observe an increase in hazardous or binge drinking among youth at risk for HIV. Hazardous alcohol use and binge drinking was more likely among White participants, those who use drugs and those who were hazardous/binge drinkers prior to the COVID-19 lockdown, which points to the importance of identifying and treating youth who misuse alcohol early to prevent future alcohol misuse.

Expanding capacity to screen and treat those infected with the hepatitis C virus (HCV) is an essential element of the global elimination strategy. We evaluated the hub-and-spoke Project ECHO training versus telementoring models to educate, train and support HCV care by primary care providers in 13 targeted counties in northern California. A novel provider engagement strategy was used. Provider engagement and retention, time to readiness to treat HCV, and knowledge and confidence were the outcomes of interest. 94 participants from 60 unique clinics in the target counties participated in the ECHO-PLUS programme; 39.4% were physicians, 48.9% were advanced practice providers, and 11.7% were nurses. The median (range) participation time was 5 (1-49) hours. Confidence scores (minimum score = 13 and maximum score = 65) increased by a mean of 14.0 (SD:8.2) and 11.4 (SD:12.0) points for the hub-and-spoke and telementoring programmes, respectively (p = .53), with the largest changes in confidence seen in treating patients per guidelines, managing side effects and in serving as a consultant for HCV in their clinic. Among 24 participants with data on time to treatment, median time from beginner to experienced was 8 h (IQR:6-12) for hub-and-spoke and 2 h (IQR:1-2.4) for the telementoring programme (p = .01). A 'boots on the ground' approach to recruiting HCV champions was effective within rural communities. Both tele-ECHO hub-and-spoke and telementoring approaches to training primary care providers yielded increase in knowledge and confidence in HCV care and amplified the number of patients who were screened and treated. Telementoring accelerated the timeline of novice providers being 'ready to treat'.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic significantly disrupted athletic activities, including those in the Pacific 12 (Pac-12) Conference of the National Collegiate Athletic Association. It is currently unknown how the disruption in training and competition impacted athletes' risk of injury upon resumption of activities.PurposeTo describe and compare the rate, timing, mechanism, and severity of injuries among collegiate athletes across multiple sports in the Pac-12 Conference before and after the COVID-19 pandemic-associated hiatus of intercollegiate athletic activities.Study designDescriptive epidemiology study.MethodsDescriptive and injury data among intercollegiate athletes from both the season before the hiatus and the season after the hiatus were acquired from the Pac-12 Health Analytics Program database. Injury elements (timing of injury onset, injury severity, mechanism, recurrence, outcome, need for procedural intervention, and event segment during which the injury took place) were compared by time using the chi-square test and a multivariate logistic regression model. Subgroup analyses were performed on knee and shoulder injuries among athletes participating in sports with traditionally high rates of knee and shoulder injuries.ResultsA total of 12,319 sports-related injuries across 23 sports were identified, with 7869 pre-hiatus injuries and 4450 post-hiatus injuries. There was no difference in the overall incidence of injury between the pre-hiatus and post-hiatus seasons. However, the proportion of noncontact injuries was higher in the post-hiatus season for football, baseball, and softball players, and the proportion of nonacute injuries in the post-hiatus season was higher among football, basketball, and rowing athletes. Finally, the overall proportion of injuries sustained by football players in the final 25% of competition or practice was higher in the post-hiatus season.ConclusionAthletes competing in the post-hiatus season were observed to have higher rates of noncontact injuries and injuries sustained in the final 25% of competition. This study demonstrates that the COVID-19 pandemic has had varied effects on athletes from different sports, suggesting that many factors must be considered when designing return-to-sports programs for athletes after an extended absence from organized training.

Concurrent use of e-cigarettes and cannabis among adolescents and emerging adults is a growing public health concern. More research is needed describing cannabis use among adolescents and emerging adults who vape. The objective of this study was to characterize cannabis use among adolescents and emerging adults (age 14-20) who reported e-cigarette ever-use, particularly their use of blunts and liquid cannabis vape (LCV) products. Using cross-sectional data from a national online survey, we describe their patterns of cannabis use, detail their use of flavored cannabis and tobacco products, and estimate associations of demographic factors and other current substance use behaviors with levels of blunt and LCV use. Of the 2253 respondents in the sample, 1379 (61 %) reported some form of cannabis use in the past 30 days, among whom 80 % used flavored cannabis (including edibles). Significant associations with current cannabis use were observed on several demographic measures, with current cannabis blunt use more frequent among participants not in school, non-Hispanic Blacks, multiracial respondents, and those whose incomes do not meet their expenses. Other than income, demographic characteristics were generally not associated with LCV use frequency. Use of other substances was associated with more frequent use of both blunts and LCV in the past 30 days, and enrollment in college or the military seems somewhat protective for emerging adults. These findings suggest a need for tailored prevention efforts among high-risk adolescents and emerging adults, potential regulation of added flavors in commercialized cannabis products, and stronger enforcement of retail restrictions for individuals under age 21 more broadly.

Influenza vaccination rates are low. Working with a large US health system, we evaluated three health system-wide interventions using the electronic health record's patient portal to improve influenza vaccination rates. We performed a two-arm RCT with a nested factorial design within the treatment arm, randomizing patients to usual-care control (no portal interventions) or to one or more portal interventions. We included all patients within this health system during the 2020-2021 influenza vaccination season, which overlapped with the COVID-19 pandemic. Through the patient portal, we simultaneously tested: pre-commitment messages (sent September 2020, asking patients to commit to a vaccination); monthly portal reminders (October - December 2020), direct appointment scheduling (patients could self-schedule influenza vaccination at multiple sites); and pre-appointment reminder messages (sent before scheduled primary care appointments, reminding patients about influenza vaccination). The main outcome measure was receipt of influenza vaccine (10/01/2020-03/31/2021). We randomized 213,773 patients (196,070 adults ≥18 years, 17,703 children). Influenza vaccination rates overall were low (39.0%). Vaccination rates for study arms did not differ: Control (38.9%), pre-commitment vs no pre-commitment (39.2%/38.9%), direct appointment scheduling yes/no (39.1%/39.1%), pre-appointment reminders yes/no (39.1%/39.1%); p > 0.017 for all comparisons (p value cut-off adjusted for multiple comparisons). After adjusting for age, gender, insurance, race, ethnicity, and prior influenza vaccination, none of the interventions increased vaccination rates. We conclude that patient portal interventions to remind patients to receive influenza vaccine during the COVID-19 pandemic did not raise influenza immunization rates. More intensive or tailored interventions are needed beyond portal innovations to increase influenza vaccination.

Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate for fat, and its interactions with common and rare variants genome-wide. In main effect meta-analyses, participants consuming more carbohydrate had modestly lower glycemic trait values (e.g., for glycated hemoglobin [HbA1c], -0.013% HbA1c/250 kcal substitution). In GDI meta-analyses, a common African ancestry-enriched variant (rs79762542) reached study-wide significance and replicated in the UK Biobank cohort, indicating a negative carbohydrate-HbA1c association among major allele homozygotes only. Simulations revealed that >150,000 samples may be necessary to identify similar macronutrient GDIs under realistic assumptions about effect size and measurement error. These results generate hypotheses for further exploration of modifiable metabolic disease risk in additional cohorts with African ancestry.Article highlightsWe aimed to identify genetic modifiers of the dietary macronutrient-glycemia relationship using whole-genome sequence data from 10 Trans-Omics for Precision Medicine program cohorts. Substitution models indicated a modest reduction in glycemia associated with an increase in dietary carbohydrate at the expense of fat. Genome-wide interaction analysis identified one African ancestry-enriched variant near the FRAS1 gene that may interact with macronutrient intake to influence hemoglobin A1c. Simulation-based power calculations accounting for measurement error suggested that substantially larger sample sizes may be necessary to discover further gene-macronutrient interactions.

We developed the Life Course Sociodemographics and Neighborhood Questionnaire (LSNEQ) to query older adults about perceived neighborhood greenspaces across the life course (i.e., distance to park, number of neighborhood parks/playgrounds, and neighborhood greenness) and about characteristics hypothesized to confound or moderate/mediate greenspace-health associations. Six perceived life course indices are derived from the LSNEQ: neighborhood socioeconomic status, neighborhood walking/biking, urbanicity, neighborhood amenities, neighborhood park access, and neighborhood greenness. Older adults from St. Louis, Missouri, and Sacramento, California, completed the LSNEQ in 2020-2021. The indices demonstrated borderline acceptable to good internal consistency (alpha = 0.60-0.79) and good to excellent test-retest reliability (ICC = 0.71-0.96) and detected different patterns of park access and neighborhood greenness by racialized group and location. Individuals with index scores indicating more neighborhood walking/biking and greater presence of neighborhood amenities over their life course were more likely to report neighborhood-based walking in older age. Overall, the LSNEQ is a reliable instrument to assess perceptions of life course social determinants of health including neighborhood greenspaces.

Although poor sleep quality and extreme sleep durations have been associated with brain atrophy and dementia, it is unclear whether sleep disturbances contribute to neural injury in the absence of neurodegeneration and cognitive impairment. In 146 dementia-free older adults of the Rancho Bernardo Study of Healthy Aging (76.7 ± 7.8 years at MRI), we examined associations of restriction spectrum imaging metrics of brain microstructure with self-reported sleep quality 6.3 ± 0.7 years prior, and with sleep duration reported 25, 15 and 9 years prior. Worse sleep quality predicted lower white matter restricted isotropic diffusion and neurite density and higher amygdala free water, with stronger associations between poor sleep quality and abnormal microstructure for men. Among women only, short or long sleep duration 25 and 15 years before MRI predicted lower white matter restricted isotropic diffusion and increased free water. Associations persisted after accounting for associated health and lifestyle factors. Sleep patterns were not related to brain volume or cortical thickness. Optimizing sleep behaviors throughout the life-course may help to preserve healthy brain aging.

BackgroundIn response to the COVID-19 pandemic, San Francisco County (SFC) had to shift many nonemergency health care resources to COVID-19, reducing HIV control resources. We sought to quantify COVID-19 effects on HIV burden among men who have sex with men (MSM) as SFC returns to pre-COVID service levels and progresses toward the Ending the HIV Epidemic (EHE) goals.SettingMicrosimulation model of MSM in SFC tracking HIV progression and treatment.MethodsScenario analysis where services affected by COVID-19 [testing, care engagement, pre-exposure prophylaxis (PrEP) uptake, and retention] return to pre-COVID levels by the end of 2022 or 2025, compared against a counterfactual where COVID-19 changes never occurred. We also examined scenarios where resources are prioritized to reach new patients or retain of existing patients from 2023 to 2025 before all services return to pre-COVID levels.ResultsThe annual number of MSM prescribed PrEP, newly acquired HIV, newly diagnosed, and achieving viral load suppression (VLS) rebound quickly after HIV care returns to pre-COVID levels. However, COVID-19 service disruptions result in measurable reductions in cumulative PrEP use, VLS person-years, incidence, and an increase in deaths over the 2020-2035 period. The burden is statistically significantly larger if these effects end in 2025 instead of 2022. Prioritizing HIV care/prevention initiation over retention results in more person-years of PrEP but less VLS person-years and more deaths, influencing EHE PrEP outcomes.ConclusionsEarlier HIV care return to pre-COVID levels results in lower cumulative HIV burdens. Resource prioritization decisions may differentially affect different EHE goals.

Study objectivesPeriodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects.MethodsThe MrOS study and Wisconsin Sleep Cohort Study (N = 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization.ResultsWe found 2 independent loci were significantly associated with PLMS: rs113851554 (p = 3.51 × 10-12, β = 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14); and rs9369062 (p = 3.06 × 10-22, β = 0.2093), a SNP located in the intron region of BTBD9 (6p12); both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS.ConclusionsBecause PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings.

IntroductionLatinos are underrepresented in brain autopsy research on Alzheimer's disease and related dementias (ADRD). The study's purpose is to identify Latinos' attitudes about brain donation (BD) to inform methods by which researchers can increase autopsy consent.MethodsForty Latinos (mean age: 59.4 years) completed a semi-structured interview and were presented with educational information about BD. Participants completed a questionnaire assessing their understanding of BD and willingness to donate their brain for research.ResultsAmong participants, there was near unanimous support for BD to study ADRD after hearing educational information. However, prior to the information presented, participants reported a lack of knowledge about BD and demonstrated a possibility that misunderstandings about BD may affect participation.DiscussionWhile nearly all study participants agree that donating is beneficial for research and for future generations, the lack of BD information must be addressed to help support positive attitudes and willingness for participation.

IntroductionWe investigated associations between neighborhood racial/ethnic segregation and cognitive change.MethodsWe used data (n = 1712) from the Multi-Ethnic Study of Atherosclerosis. Racial/ethnic segregation was assessed using Getis-Ord (Gi*) z-scores based on American Community Survey Census tract data (higher Gi* = greater spatial clustering of participant's race/ethnicity). Global cognition and processing speed were assessed twice, 6 years apart. Adjusted multilevel linear regression tested associations between Gi* z-scores and cognition. Effect modification by race/ethnicity, income, education, neighborhood socioeconomic status, and neighborhood social support was tested.ResultsParticipants were on average 67 years old; 43% were White, 11% Chinese, 29% African American/Black, 17% Hispanic; 40% had high neighborhood segregation (Gi* > 1.96). African American/Black participants with greater neighborhood segregation had greater processing speed decline in stratified analyses, but no interactions were significant.DiscussionSegregation was associated with greater processing speed declines among African American/Black participants. Additional follow-ups and comprehensive cognitive batteries may further elucidate these findings.HighlightsA study of neighborhood racial/ethnic segregation and change in cognition. Study was based on a racially and geographically diverse, population-based cohort of older adults. Racial/ethnic segregation (clustering) was measured by the Getis-ord (Gi*) statistic. We saw faster processing speed decline among Black individuals in segregated neighborhoods.

There is a dearth of research on cognitive aging and dementia in Asian Americans, particularly Vietnamese Americans, who are the fourth largest Asian subgroup in the United States. The National Institutes of Health is mandated to make certain that racially and ethnically diverse populations are included in clinical research. Despite the widespread recognition to ensure that research findings can be generalizable to all groups, there are no estimates of the prevalence or incidence of mild cognitive impairment and Alzheimer's disease and related dementias (ADRD) in Vietnamese Americans, nor do we understand ADRD risk and protective factors in this group. In this article, we posit that studying Vietnamese Americans contributes to a better understanding of ADRD in general and offers unique opportunities for elucidating life course and sociocultural factors that contribute to cognitive aging disparities. That is, the unique context of Vietnamese Americans may provide understanding in terms of within-group heterogeneity and key factors in ADRD and cognitive aging. Here, we provide a brief history of Vietnamese American immigration and describe the large but often ignored heterogeneity of Asian Americans in the United States, elucidate how early life adversity and stress might influence late-life cognitive aging, and provide a basis for the role of sociocultural and health factors in the study of Vietnamese cognitive aging disparities. Research with older Vietnamese Americans provides a unique and timely opportunity to more fully delineate the factors that contribute to ADRD disparities for all populations.

BackgroundAngiotensinogen is the proximal precursor of the angiotensin peptide hormones of the renin-angiotensin-aldosterone system (RAAS). Clinical trials are ongoing targeting angiotensinogen for the treatment of hypertension and heart failure. The epidemiology of angiotensinogen is not well defined, particularly its relationship to ethnicity, sex, and blood pressure (BP)/hypertension.ObjectivesThe authors sought to determine the relationship of circulating angiotensinogen levels to ethnicity, sex, BP, incident hypertension, and prevalent hypertension in a modern sex-balanced ethnically diverse cohort.MethodsPlasma angiotensinogen levels were measured in 5,786 participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Linear, logistic, and Cox proportional hazards models were utilized to examine the associations of angiotensinogen with BP, prevalent hypertension, and incident hypertension, respectively.ResultsAngiotensinogen levels were significantly higher in females than males and differed across self-reported ethnicities with the ordering (from highest to lowest): White, Black, Hispanic, and Chinese adults. Higher levels were associated with higher BP and odds of prevalent hypertension, after adjusting for other risk factors. Equivalent relative differences in angiotensinogen were associated with greater differences in BP in males vs females. In males not taking RAAS-blocking medications, a standard deviation increment in log-angiotensinogen was associated with 2.61 mm Hg higher systolic BP (95% CI: 1.49-3.80), while in females the same increment in angiotensinogen was associated with 0.97 mm Hg higher systolic BP (95% CI: 0.30-1.65).ConclusionsSignificant differences in angiotensinogen levels are present between sexes and ethnicities. A positive association is present between levels and prevalent hypertension and BP, which differs between sexes.

Adverse childhood experiences (ACEs) have been associated with poor mental health outcomes in adulthood. Childhood maltreatment is related to both depressive and anxiety symptoms. Our objective was to investigate these associations among low-income, mostly Black and Latino men who have sex with men (MSM), as these may be a particularly vulnerable population group. Data come from a longitudinal study of MSM with varied substance use behaviors (n = 321) collected between August 2014 and April 2022. Cumulative, childhood maltreatment ACEs, and the single ACE of childhood sexual abuse were investigated as potential predictors of self-reported depressive and anxiety symptoms in mixed-effects logistic and ordinal regression models. There was no evidence of a dose-response relationship between the number of ACEs and the predicted probability of depressive and anxiety symptoms. Compared to MSM reporting fewer than five ACEs, those with five or more ACEs had approximately double the odds ratio of reporting depressive (OR = 1.93; 95% CI: 1.04-3.60) and anxiety symptoms (OR = 2.21; 95% CI: 1.05-4.68). The dimension of childhood maltreatment had a more robust prediction of depressive symptoms than the dimension of household dysfunction across all models. The association between childhood sexual abuse history and depressive symptoms remained after adjustment for the other nine ACEs (OR = 2.27; 95% CI: 1.11-4.68). The ordinal logistic model suggested that cumulative ACEs more than triple the odds of being in a higher anxiety category (OR = 3.12; 95% CI: 1.58-6.14), with associations reported for childhood maltreatment ACEs (OR = 1.31; 95% CI: 1.06-1.66) and childhood sexual abuse (OR = 1.93; 95% CI: 0.89-4.21). Childhood maltreatment ACEs, particularly childhood sexual abuse, are salient predictors of depressive and anxiety symptoms among adult urban MSM. Mitigating the impact of childhood maltreatment requires understanding the additional burden of social distress often faced by MSM throughout the life course.

Early events associated with chronic inflammation and cancer involve significant remodeling of the extracellular matrix (ECM), which greatly affects its composition and functional properties. Using lung squamous cell carcinoma (LSCC), a chronic inflammation-associated cancer (CIAC), we optimized a robust proteomic pipeline to discover potential biomarker signatures and protein changes specifically in the stroma. We combined ECM enrichment from fresh human tissues, data-independent acquisition (DIA) strategies, and stringent statistical processing to analyze "Tumor" and matched adjacent histologically normal ("Matched Normal") tissues from patients with LSCC. Overall, 1802 protein groups were quantified with at least two unique peptides, and 56% of those proteins were annotated as "extracellular." Confirming dramatic ECM remodeling during CIAC progression, 529 proteins were significantly altered in the "Tumor" compared to "Matched Normal" tissues. The signature was typified by a coordinated loss of basement membrane proteins and small leucine-rich proteins. The dramatic increase in the stromal levels of SERPINH1/heat shock protein 47, that was discovered using our ECM proteomic pipeline, was validated by immunohistochemistry (IHC) of "Tumor" and "Matched Normal" tissues, obtained from an independent cohort of LSCC patients. This integrated workflow provided novel insights into ECM remodeling during CIAC progression, and identified potential biomarker signatures and future therapeutic targets.

BackgroundRacial inequities in maternal and child health outcomes persist: Black women and birthing people experience higher rates of adverse outcomes than their white counterparts. Similar inequities are seen in coronavirus disease (COVID-19) mortality rates. In response, we sought to explore the intersections of racism and the COVID-19 pandemic impact on the daily lives and perinatal care experiences of Black birthing people.MethodsWe used an intrinsic case study approach grounded in an intersectional lens to collect stories from Black pregnant and postpartum people residing in Fresno County (July-September 2020). All interviews were conducted on Zoom without video and were audio recorded and transcribed. Thematic analysis was used to group codes into larger themes.ResultsOf the 34 participants included in this analysis, 76.5% identified as Black only, and 23.5% identified as multiracial including Black. Their mean age was 27.2 years [SD, 5.8]. Nearly half (47%) reported being married or living with their partner; all were eligible for Medi-Cal insurance. Interview times ranged from 23 to 96 min. Five themes emerged: (1) Tensions about Heightened Exposure of Black Lives Matter Movement during the pandemic; (2) Fear for Black Son's Safety; (3) Lack of Communication from Health Care Professionals; (4) Disrespect from Health Care Professionals; and (5) Misunderstood or Judged by Health Care Professionals. Participants stressed that the Black Lives Matter Movement is necessary and highlighted that society views their Black sons as a threat. They also reported experiencing unfair treatment and harassment while seeking perinatal care.ConclusionsBlack women and birthing people shared that exposure to racism has heightened during the COVID-19 pandemic, increasing their levels of stress and anxiety. Understanding how racism impacts Black birthing people's lives and care experiences is critical to reforming the police force and revising enhanced prenatal care models to better address their needs.

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells1-14. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies15-17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRβ). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial ( NCT03970382 ). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

BackgroundReporting retention data is critical to determining the soundness of a study's conclusions (internal validity) and broader generalizability (external validity). Although selective attrition can lead to overestimates of effects, biased conclusions, or overly expansive generalizations, retention rates are not reported in many longitudinal studies.MethodsWe examined multiple child- and family-level factors potentially associated with retention in a longitudinal study of younger siblings of children with autism spectrum disorder (ASD; n = 304) or typical development (n = 163). The sample was followed from the first year of life to 36 months of age, for up to 7 visits.ResultsOf the 467 infant siblings who were consented and participated in at least one research visit, 397 (85.0%) were retained to study completion at 36 months. Retention rates did not differ by familial risk group (ASD-risk vs. Low-risk), sex, race, ethnicity, age at enrollment, number of children in the family, maternal employment, marital status, or parent concerns about the child at enrollment. A stepwise regression model identified 4 variables that, together, provided the most parsimonious predictive model of study retention: maternal education, maternal age at child's birth, travel distance to the study site, and diagnostic outcome classification at the final study visit.ConclusionsThe retained and not-retained groups did not differ on most demographic and clinical variables, suggesting few threats to internal and external validity. The significantly higher rate of retention of children diagnosed with ASD (95%) than typically developing children (83%) may, however, present biases when studying recurrence risk. We conclude by describing engagement and tracking methods that can be used to maximize retention in longitudinal studies of children at risk of ASD.

IntroductionOsimertinib is an effective treatment for metastatic NSCLC. Occasionally, thoracic radiation therapy (TRT) is delivered to patients receiving osimertinib to treat residual or progressing pulmonary tumors. Anecdotal reports suggest that the delivery of TRT in combination with osimertinib may be associated with a high risk of severe pneumonitis.MethodsA retrospective study was performed at a single academic medical center in the United States to investigate the incidence of severe pneumonitis among patients treated with combined TRT and osimertinib between June 2016 and December 2021. Baseline patient characteristics, tumor size and location, and dosimetric parameters were evaluated. The highest grade of radiation pneumonitis that developed within 6 months of treatment was scored in accordance with the Common Terminology Criteria for Adverse Events version 5.0.ResultsA total of 16 patients were identified who were treated with combined TRT and osimertinib. All had a diagnosis of metastatic NSCLC. Treatment-related grade greater than or equal to 2 pneumonitis developed in 56%, grade greater than or equal to 3 in 37.5%, and grade 4 in 6.3%; no patient developed grade 5 pneumonitis. Median time to any-grade pneumonitis was 29 days (1-84 d); all patients had symptom resolution with expectant management or oral steroid therapies. All patients discovered to have grade greater than or equal to 3 pneumonitis (n = 6) received TRT to tumors located within 2 cm of the proximal bronchial tree, including tumors abutting the proximal bronchial tree (n = 2) and within the mediastinum (n = 1).ConclusionsThe combination of TRT with osimertinib was associated with a high rate of severe pneumonitis that required oral steroid medications. Larger studies are needed to validate these findings and to understand the clinical and treatment factors that influence this risk and how they can be mitigated.

AimThe objective of the parent study was to examine attitudes and experiences regarding counselling about preconception care among Black and/or Latina women in the United States with type 2 diabetes (T2DM). Here, we present emergent findings from a secondary analysis of caregiving.MethodsIn this qualitative descriptive study, we used conventional content analysis to identify themes from semi-structured interviews with 32 Black and/or Latina women ages 18-40 who have T2DM in the United States recruited from online platforms and snowball sampling.ResultsCaregiving responsibilities both motivate and disrupt diabetes self-management behaviours. Caregiving largely meant taking care of children, but women also had responsibilities to adult family members and romantic partners. Women were motivated to manage their diabetes in order to prevent negative health effects on their children and to stay healthy so they could fulfil caregiving responsibilities. However, caregiving competed for time, energy and money with self-management. Struggling to balance caregiving and self-management caused stress that women felt was intrinsically unhealthy and undermined self-management.ConclusionsYoung adult women with T2DM identified different ways that the roles and responsibilities in the family could affect their diabetes self-management. Providers and policymakers should develop health-promoting interventions that accommodate caregiving responsibilities.

BackgroundThe impact of adopting a race-free estimated glomerular filtration rate (eGFR) creatinine (eGFRcr) equation on racial differences in chronic kidney disease (CKD) progression among people with human immunodeficiency virus (PWH) is unknown.MethodsWe defined eGFR stages using the original race-adjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr equation and the new race-free CKD-EPI eGFRcr equation. We then estimated 5-year probabilities of transitioning from baseline kidney function to more advanced eGFR stages and examined the association of race (black vs white) with rates of CKD progression using Markov models.ResultsWith the race-adjusted eGFRcr equation, black participants (n = 31 298) had a lower risk of progressing from eGFR stage 1 to 2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], .73-.82), an equal risk of progressing from stage 2 to 3 (1.00; .92-.07) and a 3-fold risk of progressing from stage 3 to 4 or 5 (3.06; 2.60-3.62), compared with white participants (n = 27 542). When we used the race-free eGFRcr equation, 16% of black participants were reclassified into a more severe eGFR stage at baseline. The reclassified black individuals had a higher prevalence of CKD risk factors than black PWH who were not reclassified. With the race-free eGFRcr equation, black participants had a higher risk of disease progression across all eGFR stages than white participants.ConclusionsThe original eGFRcr equation systematically masked a subgroup of black PWH who are at high-risk of CKD progression. The new race-free eGFRcr equation unmasks these individuals and may allow for earlier detection and management of CKD.

Pangenomics is emerging as a powerful computational paradigm in bioinformatics. This field uses population-level genome reference structures, typically consisting of a sequence graph, to mitigate reference bias and facilitate analyses that were challenging with previous reference-based methods. In this work, we extend these methods into transcriptomics to analyze sequencing data using the pantranscriptome: a population-level transcriptomic reference. Our toolchain, which consists of additions to the VG toolkit and a standalone tool, RPVG, can construct spliced pangenome graphs, map RNA sequencing data to these graphs, and perform haplotype-aware expression quantification of transcripts in a pantranscriptome. We show that this workflow improves accuracy over state-of-the-art RNA sequencing mapping methods, and that it can efficiently quantify haplotype-specific transcript expression without needing to characterize the haplotypes of a sample beforehand.

Background/objectivesObesity, defined as excessive fat accumulation that represents a health risk, is increasing in adults and children, reaching global epidemic proportions. Body mass index (BMI) correlates with body fat and future health risk, yet differs in prediction by fat distribution, across populations and by age. Nonetheless, few genetic studies of BMI have been conducted in ancestrally diverse populations. Gene expression association with BMI was assessed in the Multi-Ethnic Study of Atherosclerosis (MESA) in four self-identified race and ethnicity (SIRE) groups to identify genes associated with obesity.Subjects/methodsRNA-sequencing was performed on 1096 MESA participants (37.8% white, 24.3% Hispanic, 28.4% African American, and 9.5% Chinese American) and linear models were used to assess the association of expression from each gene for its effect on BMI, adjusting for age, sex, sequencing center, study site, five expression and four genetic principal components in each self-identified race group. Sample-size-weighted meta-analysis was performed to identify genes with BMI-associated expression across ancestry groups.ResultsWithin individual SIRE groups, there were zero to three genes whose expression is significantly (p

Translating our knowledge of the biological aging from animal models to humans may give rise to novel approaches of targeting multiple aging-related diseases simultaneously and increasing health span. Here, for the first time, we use transcriptomic signatures of monocytes to identify biological aging pathways underlying multiple aging-related diseases in humans. The ordinal logistic regression was used to cross-sectionally investigate transcriptomics of the comorbidity index in 1264 community-based Multi-Ethnic Study of Atherosclerosis (MESA) adults, 47% Caucasian, 32% Hispanic, 21% African American, and 51% female, aged 55-94 years. The comorbidity index was defined as the number of prevalent aging-related diseases including cardiovascular disease, type-2 diabetes, hypertension, cancer, dementia, chronic kidney disease, chronic obstructive pulmonary disease, and hip fracture. We identified 708 gene transcripts associated with the comorbidity index (FDR

BackgroundBlack men who have sex with men (MSM) experience disproportionate rates of HIV infection in the USA, despite being no more likely to engage in sexual risk behaviors than other MSM racial/ethnic groups. HIV pre-exposure prophylaxis (PrEP) has been shown to reduce risk of HIV acquisition; however, rates of PrEP use among Black MSM remain low. Clinical, psychosocial, and structural factors have been shown to impact PrEP use and adherence among Black MSM. Care coordination of HIV prevention services has the potential to improve PrEP use and adherence for Black MSM, as it has been shown to improve HIV-related care outcomes among people living with HIV.MethodsClient-centered care coordination (C4) is a multi-level intervention designed to address clinical, psychosocial, and structural barriers to HIV prevention services for Black MSM within HPTN 073, a PrEP demonstration project among Black MSM in three cities in the USA. The current study examined the implementation process of C4, specifically investigating the activities, cost, time, and outcomes associated with the C4 intervention.ResultsOn average, participants engaged in five care coordination encounters. The vast majority of care coordination activities were conducted by counselors, averaging 30 min per encounter. The cost of care coordination was relatively low with a mean cost of $8.70 per client encounter.ConclusionAlthough client-centered care coordination was initially implemented in well-resourced communities with robust HIV research and service infrastructure, our findings suggest that C4 can be successfully implemented in resource constrained communities.

ImportanceUnderstanding the causes of infant mortality shapes public health, surveillance, and research investments. However, the association of single-locus (mendelian) genetic diseases with infant mortality is poorly understood.ObjectiveTo determine the association of genetic diseases with infant mortality.Design, setting, and participantsThis cohort study was conducted at a large pediatric hospital system in San Diego County (California) and included 546 infants (112 infant deaths [20.5%] and 434 infants [79.5%] with acute illness who survived; age, 0 to 1 year) who underwent diagnostic whole-genome sequencing (WGS) between January 2015 and December 2020. Data analysis was conducted between 2015 and 2022.ExposureInfants underwent WGS either premortem or postmortem with semiautomated phenotyping and diagnostic interpretation.Main outcomes and measuresProportion of infant deaths associated with single-locus genetic diseases.ResultsAmong 112 infant deaths (54 girls [48.2%]; 8 [7.1%] African American or Black, 1 [0.9%] American Indian or Alaska Native, 8 [7.1%] Asian, 48 [42.9%] Hispanic, 1 [0.9%] Native Hawaiian or Pacific Islander, and 34 [30.4%] White infants) in San Diego County between 2015 and 2020, single-locus genetic diseases were the most common identifiable cause of infant mortality, with 47 genetic diseases identified in 46 infants (41%). Thirty-nine (83%) of these diseases had been previously reported to be associated with childhood mortality. Twenty-eight death certificates (62%) for 45 of the 46 infants did not mention a genetic etiology. Treatments that can improve outcomes were available for 14 (30%) of the genetic diseases. In 5 of 7 infants in whom genetic diseases were identified postmortem, death might have been avoided had rapid, diagnostic WGS been performed at time of symptom onset or regional intensive care unit admission.Conclusions and relevanceIn this cohort study of 112 infant deaths, the association of genetic diseases with infant mortality was higher than previously recognized. Strategies to increase neonatal diagnosis of genetic diseases and immediately implement treatment may decrease infant mortality. Additional study is required to explore the generalizability of these findings and measure reduction in infant mortality.

IntroductionClinical research focused on aging, Alzheimer's disease and related dementias (ADRD), and caregiving often does not recruit Asian Americans and Pacific Islanders (AAPIs).MethodsWith funding from the National Institute on Aging, we designed and launched the Collaborative Approach for AAPIs Research and Education (CARE), a research recruitment registry to increase AAPIs' participation in ADRD, aging, and caregiving research. We present the design of this novel recruitment program.ResultsCARE uses community-based participatory research methods that are culturally and linguistically appropriate. Since CARE's launch, it has enrolled >7000 AAPIs in a 1-year period. The majority enrolled in CARE via community organizations and reported never having participated in any kind of research before. CARE also engages researchers by establishing a recruitment referral request protocol.DiscussionCARE provides a promising venue to foster meaningful inclusion of AAPIs who are under-represented in aging and dementia-related research.

Abstract Background The COVID-19 pandemic posed numerous obstacles to psychosocial wellbeing for children. We conducted a longitudinal study to evaluate child mental health and social risks during the pandemic. Methods Participants were 172 caregivers of children aged 6–11 years old who attended well child visits within 6 months before pandemic onset at an urban safety net hospital in the US. Prepandemic data was extracted from the electronic medical record, and surveys were administered at three time points between August 2020 and July 2021. We measured mental health symptoms with the Pediatric Symptom Checklist-17, social risks (e.g., food and housing insecurity) with the THRIVE questionnaire, and school modality (in-person, hybrid, remote). Results Compared to pre-pandemic, children had significantly higher PSC-17 total scores (overall mental health symptoms) and THRIVE total scores (total burden of social risks) at all three mid-pandemic waves. Using longitudinal mixed models accounting for time, social risks, and school modality, both social risks (B = 0.37, SE = 0.14, p

The COVID-19 pandemic posed a grave threat not only to Indigenous people’s health and well-being, but also to Indigenous communities and societies. This applies also to the Indigenous peoples of the Arctic, where unintentional effects of public health actions to mitigate the spread of virus may have long-lasting effects on vulnerable communities. This study aim was to identify and describe Sámi perspectives on how the Sámi society in Sweden was specifically affected by the pandemic and associated public health actions during 2020–2021. A mixed-method qualitative case study approach was employed, including a media scoping review and stakeholder interviews. The media scoping review included 93 articles, published online or in print, from January 2020 to 1 September 2021, in Swedish or Norwegian, regarding the pandemic-related impacts on Sámi society in Sweden. The review informed a purposeful selection of 15 stakeholder qualitative interviews. Thematic analysis of the articles and interview transcripts generated five subthemes and two main themes: “weathering the storm” and “stressing Sámi culture and society”. These reflect social dynamics which highlight stressors towards, and resilience within, the Sámi society during the pandemic. The results may be useful when evaluating and developing public health crisis response plans concerning or affecting the Sámi society in Sweden.

Posttreatment controllers (PTCs) are rare HIV-infected individuals who can limit viral rebound after antiretroviral therapy interruption (ATI), but the mechanisms of this remain unclear. To investigate these mechanisms, we quantified various HIV RNA transcripts (via reverse transcription droplet digital PCR [RT-ddPCR]) and cellular transcriptomes (via RNA-seq) in blood cells from PTCs and noncontrollers (NCs) before and two time points after ATI. HIV transcription initiation did not significantly increase after ATI in PTCs or in NCs, whereas completed HIV transcripts increased at early ATI in both groups and multiply-spliced HIV transcripts increased only in NCs. Compared to NCs, PTCs showed lower levels of HIV DNA, more cell-associated HIV transcripts per total RNA at all times, no increase in multiply-spliced HIV RNA at early or late ATI, and a reduction in the ratio of completed/elongated HIV RNA after early ATI. NCs expressed higher levels of the IL-7 pathway before ATI and expressed higher levels of multiple cytokine, inflammation, HIV transcription, and cell death pathways after ATI. Compared to the baseline, the NCs upregulated interferon and cytokine (especially TNF) pathways during early and late ATI, whereas PTCs upregulated interferon and p53 pathways only at early ATI and downregulated gene translation during early and late ATI. In NCs, viral rebound after ATI is associated with increases in HIV transcriptional completion and splicing, rather than initiation. Differences in HIV and cellular transcription may contribute to posttreatment control, including an early limitation of spliced HIV RNA, a delayed reduction in completed HIV transcripts, and the differential expression of the IL-7, p53, and TNF pathways. IMPORTANCE The findings presented here provide new insights into how HIV and cellular gene expression change after stopping ART in both noncontrollers and posttreatment controllers. Posttreatment control is associated with an early ability to limit increases in multiply-spliced HIV RNA, a delayed (and presumably immune-mediated) ability to reverse an initial rise in processive/completed HIV transcripts, and multiple differences in cellular gene expression pathways. These differences may represent correlates or mechanisms of posttreatment control and may provide insight into the development and/or monitoring of therapeutic strategies that are aimed at a functional HIV cure.

GoalsWe sought to determine whether race/ethnicity is associated with hospitalization outcomes among patients admitted with acute cholangitis.BackgroundFew studies have evaluated the association between race and outcomes in patients with acute cholangitis.StudyWe analyzed United States hospitalizations from 2009 to 2018 using the Nationwide Inpatient Sample (NIS). We included patients 18 years old or above admitted with an ICD9/10 diagnosis of cholangitis. Race/ethnicity was categorized as White, Black, Hispanic, or Other. We used multivariable regression to determine the association between race/ethnicity and in-hospital outcomes of interest, including endoscopic retrograde cholangiopancreatography (ERCP), early ERCP (

Structurally racist policies and practices of the past are likely to be a driving factor in current day differences in exposure to air pollution and may contribute to observed racial and ethnic disparities in adverse birth outcomes in the United States (U.S.). Non-Hispanic Black women in the U.S. experience poorer health outcomes during pregnancy and throughout the life course compared to non-Hispanic White women. This disparity holds even among non-Hispanic Black women with higher socioeconomic status. Reasons for this finding remain unclear, but long-term environmental exposure, either historical exposure or both historical and ongoing exposure, may contribute. Structural racism likely contributes to differences in social and environmental exposures by race in the U.S. context, and these differences can affect health and wellbeing across multiple generations. In this paper, we briefly review current knowledge and recommendations on the study of race and structural racism in environmental epidemiology, specifically focused on air pollution. We describe a conceptual framework and opportunities to use existing historical data from multiple sources to evaluate multi-generational influences of air pollution and structurally racist policies on birth and other relevant health outcomes. Increased analysis of this kind of data is critical for our understanding of structural racism's impact on multiple factors, including environmental exposures and adverse health outcomes, and identifying how past policies can have enduring legacies in shaping health and well-being in the present day. The intended purpose of this manuscript is to provide an overview of the widespread reach of structural racism, its potential association with health disparities and a comprehensive approach in environmental health research that may be required to study and address these problems in the U.S. The collaborative and methodological approaches we highlight have the potential to identify modifiable factors that can lead to effective interventions for health equity.

Studies have found that offline and online racism are linked to mental health issues including depressive and anxiety symptoms among racially minoritized emerging adults. To cope with these symptoms, racially minoritized emerging adults may resort to substance use. Thus, we examined the relationship between offline and online racism and recent smoking behaviors (past 30 days), and whether depressive and anxiety symptoms (DAS) mediate this relationship. We hypothesized that offline and online racism would be associated with a greater probability of recent smoking through depressive/anxiety symptoms. With data from 338 participants (Mage = 23.28, SD = 2.38), we conducted a path analysis of offline racism (Everyday Discrimination Scale) and online racism (Perceived Online Racism Scale) predicting recent smoking (recent cigarette smoking, recent marijuana use, recent vaping) via depressive (Patient Health Questionnaire-9)/anxiety (Generalized Anxiety Disorder-7) symptoms. Offline racism was directly associated with recent cigarette smoking while online racism was directly associated with recent vaping. No significant indirect associations were observed with cigarette smoking and vaping. Both online and offline racism were indirectly associated with recent marijuana use via depressive/anxiety symptoms. Our findings suggest that there are nuanced differences between the impact that online and offline racism experiences may have on the DAS, and smoking behaviors of racially minoritized emerging adults. Implications for research are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Autonomy support is a concept that is derived from self-determination theory. Autonomy refers to the freedom to act as one chooses. The current study aimed to examine if autonomy support was associated with dried blood spot validated pre-exposure prophylaxis (PrEP) adherence, and whether the association was mediated by PrEP adherence goal setting and progress toward PrEP adherence goals. Our sample was drawn from Black men who have sex with men (MSM) from across three cities (Chapel Hill, NC; Los Angeles, CA; and Washington, DC) in the United States between February 2013 and September 2014. We used logistic regression to evaluate associations between study variables and path analysis to test mediation effects. Participants were, on average, 28 [standard deviation (SD) = 1.12] years old and 25% were unemployed. We found that MSM who experienced high autonomy support were more likely to adhere to PrEP [odds ratio (OR) = 1.17; 95% confidence interval: 1.00-1.38]. MSM who set PrEP adherence goals were more likely to adhere to PrEP. Moreover, MSM who reported making progress toward their goals were also more likely to adhere to PrEP. Finally, client perception of coordination quality enhanced the magnitude of the association between goal setting and goal progress and the effect size of goal progress on PrEP adherence. Autonomy support, goal setting, goal monitoring/evaluation, and care coordination quality influenced PrEP adherence among Black MSM. Our findings indicate that while it is important to set goals for PrEP adherence, goal setting may need to be accompanied by progress monitoring to achieve the maximal effect.

IntroductionUnited States consumers spend over two billion dollars a year on intimate care products. These products, along with scented menstrual products, are marketed for odor control, perceived "freshness," and vaginal/vulvar cleanliness. However, these scent-altering products may increase exposure to carcinogenic and endocrine-disrupting chemicals. Prior research has not adequately characterized demographic differences in product use. The objective of our study is to examine racial/ethnic and educational differences in menstrual and intimate care product use among people who menstruate.MethodsWe pooled data from two US-based cross sectional studies to examine demographic characteristics and product use in 661 participants aged 18-54 years. Participants reported use of scented and unscented menstrual products (tampons, sanitary pads, and menstrual cups) and intimate care products (vaginal douches, sprays, wipes, and powders). We examined differences by race/ethnicity and education using log-binomial regression and latent class analysis (LCA), which can identify groups based on product use patterns.ResultsOur sample was 33.4% Black, 30.9% Latina, 18.2% White, and 16.2% another identity. Approximately half the population had a bachelor's degree or more; 1.4% identified as transgender and 1.8% as non-binary. In adjusted models, scent-altering products (i.e., scented menstrual and intimate care products) were more likely to be used by those with less formal education (p

BackgroundIn the United States, disparities in gestational age at birth by maternal race, ethnicity, and geography are theorized to be related, in part, to differences in individual- and neighborhood-level socioeconomic status (SES). Yet, few studies have examined their combined effects or whether associations vary by maternal race and ethnicity and United States Census region.MethodsWe assembled data from 34 cohorts in the Environmental influences on Child Health Outcomes (ECHO) program representing 10,304 participants who delivered a liveborn, singleton infant from 2000 through 2019. We investigated the combined associations of maternal education level, neighborhood deprivation index (NDI), and Index of Concentration at the Extremes for racial residential segregation (ICERace) on gestational weeks at birth using linear regression and on gestational age at birth categories (preterm, early term, post-late term relative to full term) using multinomial logistic regression.ResultsAfter adjustment for NDI and ICERace, gestational weeks at birth was significantly lower among those with a high school diploma or less (-0.31 weeks, 95% CI: -0.44, -0.18), and some college (-0.30 weeks, 95% CI: -0.42, -0.18) relative to a master's degree or higher. Those with a high school diploma or less also had an increased odds of preterm (aOR 1.59, 95% CI: 1.20, 2.10) and early term birth (aOR 1.26, 95% CI: 1.05, 1.51). In adjusted models, NDI quartile and ICERace quartile were not associated with gestational weeks at birth. However, higher NDI quartile (most deprived) associated with an increased odds of early term and late term birth, and lower ICERace quartile (least racially privileged) associated with a decreased odds of late or post-term birth. When stratifying by region, gestational weeks at birth was lower among those with a high school education or less and some college only among those living in the Northeast or Midwest. When stratifying by race and ethnicity, gestational weeks at birth was lower among those with a high school education or less only for the non-Hispanic White category.ConclusionIn this study, maternal education was consistently associated with shorter duration of pregnancy and increased odds of preterm birth, including in models adjusted for NDI and ICERace.

BackgroundEvidence-based interventions to protect against cognitive decline among older adults at risk for Alzheimer's disease and related dementias (ADRD) are urgently needed. Rehabilitation approaches to support memory and behavioral/lifestyle interventions are recognized as promising strategies for preserving or improving cognitive health, although few previous interventions have combined both approaches. This paper describes the protocol of the Brain Boosters intervention, which synergistically combines training in compensatory and healthy lifestyle behaviors and supports implementation and tracking of new behaviors with a digital application.MethodsThe study utilizes a single-site, single-blinded, randomized controlled design to compare a structured lifestyle and compensatory aid intervention to an education-only self-guided intervention. We plan to enroll 225 community-dwelling adults (25% from underrepresented groups) aged 65 + who endorse subjective cognitive decline (SCD) and low baseline levels of healthy lifestyle behaviors. Both interventions will be administered in group format, consisting of 15 two-hour classes that occur weekly for ten weeks and taper to bi-monthly and monthly, for an intervention duration of 6 months. Participants in both interventions will receive education about a variety of memory support strategies and healthy lifestyle behaviors, focusing on physical and cognitive activity and stress management. The structured intervention will also receive support in adopting new behaviors and tracking set goals aided by the Electronic Memory and Management Aid (EMMA) digital application. Primary outcomes include global cognition (composite of memory, attention, and executive function tests) and everyday function (Everyday Cognition Questionnaire). Data will be collected at baseline and outcome visits, at approximately 6, 12, and 18 months. Qualitative interviews, self-report surveys (e.g., indicators of self-determination, health literacy) and EMMA data metrics will also be used to identify what components of the intervention are most effective and for whom they work.DiscussionSuccessful project completion will provide valuable information about how individuals with SCD respond to a compensation and preventative lifestyle intervention assisted by a digital application, including an understanding of factors that may impact outcomes, treatment uptake, and adherence. The work will also inform development, scaling, and personalization of future interventions that can delay disability in individuals at risk for ADRD.Trial registrationClinicalTrials.gov. (NCT05027789, posted 8/30/2021).

BackgroundTransactive Response DNA Binding Protein 43 kDa (TDP-43) pathology is frequently found in cases with Alzheimer's disease (AD). TDP-43 pathology is associated with hippocampal atrophy and greater AD severity denoted by cognition and clinical representation. Current TDP-43 pathology studies are predominantly based on non-Hispanic White cohorts.ObjectiveWe sought to evaluate the presence of TDP-43 pathology across ethnoracial groups utilizing the National Alzheimer's Coordinating Center; a database containing data from over 29 institutions across the United States. Cases (N = 1135: Hispanics/Latinos = 29, African Americans/Black Americans = 51, Asians/Asian Americans = 10, American Indians/Alaskan Natives = 2, non-Hispanic White = 1043) with intermediate/high AD having data on TDP-43 pathology in the amygdala, hippocampus, entorhinal cortex, and neocortex were included.MethodsTDP-43 pathology frequency in each neuroanatomic region among ethnoracial groups were compared using generalized linear mixed effects models with center as a random effect adjusting for age at death, education, and gender.ResultsAlthough groups were imbalanced, there was no significant difference across ethnoracial groups based on TDP-43 pathology (p = 0.84). With respect to neuroanatomical regions evaluated, there were no significant differences across ethnoracial groups (p-values > 0.06). There were also no significant differences for age at death and gender ratios across ethnoracial groups based on TDP-43 pathology. Although not statistically significant, TDP-43 pathology was present less often in Hispanic/Latinos (34%) when compared to non-Hispanic Whites (46%).ConclusionWhile this is a preliminary evaluation, it highlights the need for diverse cohorts and on TDP-43 pathology research across ethnoracial groups. This is the first study to our knowledge having a focus on the neuroanatomical distribution of TDP-43 deposits in Hispanic/Latino decedents with AD.