We investigate the impact on episodic memory function of the stresses from exposure to a large-scale, unanticipated natural disaster, the 2004 Indian Ocean tsunami which killed 5% of the study population. Analysis focuses on adults aged 45y and older at the time of measurement, which is almost two decades post-tsunami. Data are drawn from the 2024 follow-up of the Study of the Tsunami Aftermath and Recovery, a population-representative longitudinal study of people living along the coast of Aceh, Indonesia, at the time of the baseline conducted 10 months before the tsunami. Comparisons are drawn using several different memory measurements including widely-used word-, story-, and picture-based assessments as well as a recently-developed protocol that measures olfactory-related memory adjusting for olfactory function. Leveraging plausibly exogenous variation in exposure to the tsunami, measured at the community- and individual-levels and reported shortly after the event, olfactory-related episodic memory is significantly worse among the exposed indicating sustained adverse effects of tsunami exposure on memory nearly 20 years later. In contrast, word-, story- and picture-based memory measures do not vary with tsunami-exposure, they are related to measures of olfactory function, and all of these measures vary significantly with education. Olfactory memory, however, does not. We conclude, first, that olfactory memory provides information about episodic memory in a population with limited education that is not captured in word- story- and picture-based assessments. Second, exposure to stress has a causal negative impact on memory function, even 20 years after exposure.

Exposure to infectious disease in early life may have long-term ramifications for health and lifespan. However, reducing pathogen exposure may not be uniformly beneficial. The rise of modern sanitation and reduction of infectious diseases has been implicated in increasing levels of allergy and immune dysregulation: termed, the “hygiene hypothesis.” This study leverages quasi-experimental variation from combining pre-campaign hookworm exposure with the Rockefeller Sanitary Commission’s de-worming campaign in the early 20th century to rigorously examine the impacts of childhood hookworm exposure on adult lifespan and morbidity. Findings show de-worming before age five leads to 2.5 additional months of life in a large sample of adult death records. Further, decreasing hookworm exposure is related to improvements in biomarkers for inflammation and skin-tested allergies, in contrast to predictions of the “hygiene hypothesis”. Placebo tests using health outcomes that should not be affected by de-worming do not show similar patterns. Overall, childhood de-worming leads to improvements in morbidity and lifespan decades later.

Cardiovascular disease is among the most common causes of death around the world. As rising incomes in low and middle-income countries are accompanied by increased obesity, the burden of disease shifts towards non-communicable diseases, and lower-income settings make up a growing share of cardiovascular disease deaths. Comparative investigation of the roles of body composition, behavioral and socioeconomic factors across countries can shed light on both the biological and social drivers of cardiovascular disease more broadly. Comparing rigorously-validated measures of HDL and non-HDL cholesterol among adults in the United States and in Aceh, Indonesia, we show that Indonesians present with adverse cholesterol biomarkers relative to Americans, despite being younger and having lower body mass index. Adjusting for age, the gaps increase. Body composition, behaviors, demographic and socioeconomic characteristics that affect cholesterol do not explain between-country HDL differences, but do explain non-HDL differences, after accounting for medication use. On average, gender differences are inconsistent across the two countries and persist after controlling observed characteristics. Leveraging the richness of the Indonesian data to draw comparisons of males and females within the same household, the gender gaps among Indonesians are not explained for HDL cholesterol but attenuated substantially for non-HDL cholesterol. This finding suggests that unmeasured household resources play an important role in determining non-HDL cholesterol. More generally, they appear to be affected by social and biological forces in complex ways that differ across countries and potentially operate differently for HDL and non-HDL biomarkers. These results point to the value of rigorous comparative studies to advance understanding of cardiovascular risks across the globe.

The hypothalamic–pituitary–thyroid (HPT) axis is fundamental to human biology, exerting central control over energy expenditure and body temperature. However, the consequences of normal physiologic HPT-axis variation in populations without diagnosed thyroid disease are poorly understood. Using nationally representative data from the 2007 to 2012 National Health and Nutrition Examination Survey, we explore relationships with demographic characteristics, longevity, and socio-economic factors. We find much larger variation across age in free T3 than other HPT-axis hormones. T3 and T4 have opposite relationships to mortality: free T3 is inversely related and free T4 is positively related to the likelihood of death. Free T3 and household income are negatively related, particularly at lower incomes. Finally, free T3 among older adults is associated with labor both in terms of unemployment and hours worked. Physiologic TSH/T4 explain only 1.7% of T3 variation, and neither are appreciably correlated to socio-economic outcomes. Taken together, our data suggest an unappreciated complexity of the HPT-axis signaling cascade broadly such that TSH and T4 may not be accurate surrogates of free T3. Furthermore, we find that subclinical variation in the HPT-axis effector hormone T3 is an important and overlooked factor linking socio-economic forces, human biology, and aging.

Despite significant research on the effects of stress on the hypothalamic–pituitary–adrenal (HPA) axis, questions remain regarding long-term impacts of large-scale stressors. Leveraging data on exposure to an unanticipated major natural disaster, the 2004 Indian Ocean tsunami, we provide causal evidence of its imprint on hair cortisol levels fourteen years later. Data are drawn from the Study of the Tsunami Aftermath and Recovery, a population-representative longitudinal study of tsunami survivors who were living along the coast of Aceh, Indonesia, when the tsunami hit. Annual rounds of data, collected before, the year after and 2 y after the disaster provide detailed information about tsunami exposures and self-reported symptoms of post-traumatic stress. Hair samples collected 14 y after the tsunami from a sample of adult participants provide measures of cortisol levels, integrated over several months. Hair cortisol concentrations are substantially and significantly lower among females who were living, at the time of the tsunami, in communities directly damaged by the tsunami, in comparison with similar females living in other, nearby communities. Differences among males are small and not significant. Cortisol concentrations are lowest among those females living in damaged communities who reported elevated post-traumatic stress symptoms persistently for two years after the tsunami, indicating that the negative effects of exposure were largest for them. Low cortisol is also associated with contemporaneous reports of poor self-rated general and psychosocial health. Taken together, the evidence points to dysregulation in the HPA axis and “burnout” among these females fourteen years after exposure to the disaster.

Background: The COVID-19 pandemic has been accompanied by substantial increases in adverse mental health, particularly among the young. However, it remains unclear to what extent increases in population scores on mental health assessments are due to changes in prevalence, rather than severity of symptoms. Further, it is not obvious that widely used assessments of aggregate symptoms retain their typical interpretation during an event that directly disrupts behavior. Methods: Pre-pandemic data on workers age 18-69y in the 2019 National Health Interview Survey are reweighted to match distributions of demographic characteristics of Duke University employees surveyed nine months into the pandemic. The latter population was at low risk of infection or economic insecurity. Prevalence, severity, and scores for each of nine symptoms are compared overall and by age group. Outcomes: Elevated psychological distress is primarily driven by increases in prevalence of particular symptoms. Prevalence of trouble concentrating increased six-fold from 9.6% to 72.5%. Other symptoms increased by over one-third; feeling anxious, having little interest, feeling depressed, sleep problems and being irritable, while some symptoms rose only 10% or less. Severity also increased but magnitudes are small relative to prevalence changes. Escalation in prevalence and severity are greatest for the youngest. Interpretation: Some of the least prevalent symptoms pre-pandemic became the most prevalent during the pandemic, affecting interpretation of indices validated pre-pandemic. Clinical and policy interventions should focus on specific symptoms that increased including trouble concentrating and anxiety.

Background:Non-Hispanic Black populations have suffered much greater per capita COVID-19 mortality than White populations. Previous work has shown that rates of Black and White mortality have converged over time. Understanding of COVID-19 disparities over time is complicated by geographic changes in prevalence, and some prior research has claimed that regional shifts in COVID-19 prevalence may explain the convergence. Methods: Using county-level COVID-19 mortality data stratified by race, we investigate the trajectory of Black and White per capita mortality from June 2020–January 2021. We use a county fixed-effects model to estimate changes within counties, then extend our models to leverage county-level variation in prevalence to study the effects of prevalence versus time trajectories in mortality disparities. Findings: Over this period, cumulative mortality rose by 61% and 90% for Black and White populations respectively, decreasing the mortality ratio by 0.4 (25.8%). These trends persisted when a county-level fixed-effects model was applied. Results revealed that county-level changes in prevalence nearly fully explain changes in mortality disparities over time. Interpretation:Results suggest mechanisms underpinning convergence in Black/White mortality are not driven by fixed county-level characteristics or changes in the regional dispersion of COVID-19, but instead by changes within counties. Further, declines in the Black/White mortality ratio over time appear primarily linked to county-level changes in COVID-19 prevalence rather than other county-level factors that may vary with time. Research into COVID-19 disparities should focus on mechanisms that operate within-counties and are consistent with a prevalence-disparity relationship.

Background: E-cigarettes or electronic nicotine delivery systems (ENDS) are designed to deliver nicotine-containing aerosol via inhalation. Little is known about the health effects of flavoured ENDS aerosol when inhaled. Methods: Aerosol from ENDS was generated using a smoking machine. Various types of ENDS devices or a tank system prefilled with liquids of different flavours, nicotine carrier, variable nicotine concentrations and with modified battery output voltage were tested. A convenience sample of commercial fluids with flavour names of tobacco, piña colada, menthol, coffee and strawberry were used. Flavouring chemicals were identified using gas chromatography/mass spectrometry. H292 human bronchial epithelial cells were directly exposed to 55 puffs of freshly generated ENDS aerosol, tobacco smoke or air (controls) using an air–liquid interface system and the Health Canada intense smoking protocol. The following in vitro toxicological effects were assessed: (1) cell viability, (2) metabolic activity and (3) release of inflammatory mediators (cytokines). Results: Exposure to ENDS aerosol resulted in decreased metabolic activity and cell viability and increased release of interleukin (IL)-1β, IL-6, IL-10, CXCL1, CXCL2 and CXCL10 compared to air controls. Cell viability and metabolic activity were more adversely affected by conventional cigarettes than most tested ENDS products. Product type, battery output voltage and flavours significantly affected toxicity of ENDS aerosol, with a strawberry-flavoured product being the most cytotoxic. Conclusions: Our data suggest that characteristics of ENDS products, including flavours, may induce inhalation toxicity. Therefore, ENDS users should use the products with caution until more comprehensive studies are performed.

Levels and distributions of depression symptoms 8-10 months after the onset of the COVID-19 pandemic are reported in a population of faculty, staff, and students at Duke University who faced minimal infection and economic disruption due to the pandemic. Almost 5,000 respondents age 18-81 years who completed the 20-item Center for Epidemiological Studies-Depression (CES-D) battery reported high rates of depression symptoms with more than 40% reporting levels that indicate risk of moderate depression and 25% indicating risk of severe depression. There is a very steep age gradient with the highest levels reported by the youngest respondents of whom over 40% are at risk of severe depression. Symptoms are worse among those who report the demands of work often interfere with family responsibilities but these pressures neither explain the high reported rates nor the steep age gradient. Severe depression risks are highest among students. High levels of depression symptoms during the pandemic appear to be persistent and not confined to those at greatest risk of infection or economic insecurity.