Characterizing cell type specific transcriptional differences between the living and postmortem human brain.

Single-nucleus RNA sequencing (snRNA-seq) is often used to define gene expression patterns characteristic of brain cell types as well as to identify cell type specific gene expression signatures of neurological and mental illnesses in postmortem human brains. As methods to obtain brain tissue from living individuals emerge, it is essential to characterize gene expression differences associated with tissue originating from either living or postmortem subjects using snRNA-seq, and to assess whether and how such differences may impact snRNA-seq studies of brain tissue. To address this, human prefrontal cortex single nuclei gene expression was generated and compared between 31 samples from living individuals and 21 postmortem samples. The same cell types were consistently identified in living and postmortem nuclei, though for each cell type, a large proportion of genes were differentially expressed between samples from postmortem and living individuals. Notably, estimation of cell type proportions by cell type deconvolution of pseudo-bulk data was found to be more accurate in samples from living individuals. To allow for future integration of living and postmortem brain gene expression, a model was developed that quantifies from gene expression data the probability a human brain tissue sample was obtained postmortem. These probabilities are established as a means to statistically account for the gene expression differences between samples from living and postmortem individuals. Together, the results presented here provide a deep characterization of both differences between snRNA-seq derived from samples from living and postmortem individuals, as well as qualify and account for their effect on common analyses performed on this type of data.

Divergent landscapes of A-to-I editing in postmortem and living human brain.

Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR1 and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries illuminate the nuanced functions and intricate regulatory mechanisms of RNA editing within the human brain.

Temporal dynamics of drinking water sodium levels in coastal areas, Cyprus 2009-2020.

Around the world, groundwater salinity levels are increasing in coastal areas, as a result of its systematic overexploitation for domestic, agricultural and industrial demand and potentially due to climate change manifestations (such as, sea level rise). We hypothesized that the groundwater quality of many Mediterranean coastal areas is already being perturbed, especially for water salinity, depending on the groundwater distance from the seafront. The objectives of this study were: i) to evaluate the magnitude and temporal variance of drinking water sodium (Na) as a metric of salt intake used for public health purposes using drinking water data in Cyprus; and ii) to examine the degree of Na enrichment in drinking water as defined by the seawater coastline distance of each sampling point. Open access governmental data of drinking water Na (n = 3304), daily max ambient air temperature and total rainfall were obtained for the period of 2009-2020 from governmental repositories. Linear mixed-effect regression models of drinking water Na with unsupervised covariance matrix were used. After adjusting for temperature and rainfall data, there was a significant annual increase in drinking water Na levels over time (beta = 0.01; 95 % CI: 0.00, 0.02; p = 0.02) for the coastal areas (<10 km from coastline, cutoff used by the EU Environment Agency), but this was not the case for non-coastal areas (>10 km distance from coastline). The distance of each sampling point from the coastline in Cyprus was negatively associated with drinking water Na in coastal areas (beta = -0.04, 95%CI: -0.06, -0.01; p = 0.002); this was not the case for non-coastal areas. More research is warranted to better understand the impacts of global environmental change on water quality in association with the burden of disease in coastal areas.

Valuing the health benefits of nature-based recreational physical activity in England.

Physical activity (PA) reduces the risk of several non-communicable diseases (NCDs). Natural environments support recreational PA. Using data including a representative cross-sectional survey of the English population, we estimated the annual value of nature-based PA conducted in England in 2019 in terms of avoided healthcare and societal costs of disease. Population-representative data from the Monitor of Engagement with the Natural Environment (MENE) survey (n = 47,580; representing 44,386,756) were used to estimate the weekly volume of nature-based recreational PA by adults in England in 2019. We used epidemiological dose-response data to calculate incident cases of six NCDs (ischaemic heart disease (IHD), ischaemic stroke (IS), type 2 diabetes (T2D), colon cancer (CC), breast cancer (BC) and major depressive disorder (MDD)) prevented through nature-based PA, and estimated associated savings using published costs of healthcare, informal care and productivity losses. We investigated additional savings resulting from hypothetical increases in: (a) visitor PA and (b) visitor numbers. In 2019, 22million adults > 16 years of age in England visited natural environments at least weekly. At reported volumes of nature-based PA, we estimated that 550 cases of IHD, 168 cases of IS, 1,410 cases of T2D, 41 cases of CC, 37 cases of BC and 10,552 cases of MDD were prevented, creating annual savings of £108.7million (95 % uncertainty interval: £70.3million; £150.3million). Nature-based recreational PA in England results in reduced burden of disease and considerable annual savings through prevention of priority NCDs. Strategies that increase nature-based PA could lead to further reductions in the societal burden of NCDs.

Mechanisms underlying the associations between different types of nature exposure and sleep duration: An 18-country analysis.

Whilst green space has been linked to healthier sleep outcomes, the roles of specific types of nature exposure, potential underlying mechanisms, and between-country variations in nature-sleep associations have received little attention. Drawing on cross-sectional survey data from an 18-country sample of adults (N = 16,077) the current study examined: 1) the relative associations between six different types of nature exposure (streetscape greenery, blue view from home, green space within 1 km, coast within 1 km, green space visits, blue space visits) and insufficient sleep (<6 h vs. 7-10 h per day); 2) whether these relationships were mediated by better mental wellbeing and/or physical activity; and 3) the consistency of these pathways among the different countries. After controlling for covariates, neighbourhood nature measures (green space, coast within 1 km) were not significantly associated with insufficient sleep; but nature visible from home (streetscape greenery, blue views) and recreational visits to green and blue spaces were each associated with less insufficient sleep. Significant nature-sleep associations were mediated, to varying degrees, by better mental wellbeing, but not self-reported physical activity. Country-level heterogeneity in the strength of nature-sleep associations was observed. Increasing nature visible from the home may represent a promising strategy for promoting healthier sleep duration at the population level, whilst nature-based interventions encouraging individuals to spend time in local green/blue spaces may be an appropriate target to assist individuals affected by insufficient sleep.

A mathematical, classical stratification modeling approach to disentangling the impact of weather on infectious diseases: A case study using spatio-temporally disaggregated Campylobacter surveillance data for England and Wales.

Disentangling the impact of the weather on transmission of infectious diseases is crucial for health protection, preparedness and prevention. Because weather factors are co-incidental and partly correlated, we have used geography to separate out the impact of individual weather parameters on other seasonal variables using campylobacteriosis as a case study. Campylobacter infections are found worldwide and are the most common bacterial food-borne disease in developed countries, where they exhibit consistent but country specific seasonality. We developed a novel conditional incidence method, based on classical stratification, exploiting the long term, high-resolution, linkage of approximately one-million campylobacteriosis cases over 20 years in England and Wales with local meteorological datasets from diagnostic laboratory locations. The predicted incidence of campylobacteriosis increased by 1 case per million people for every 5° (Celsius) increase in temperature within the range of 8°-15°. Limited association was observed outside that range. There were strong associations with day-length. Cases tended to increase with relative humidity in the region of 75-80%, while the associations with rainfall and wind-speed were weaker. The approach is able to examine multiple factors and model how complex trends arise, e.g. the consistent steep increase in campylobacteriosis in England and Wales in May-June and its spatial variability. This transparent and straightforward approach leads to accurate predictions without relying on regression models and/or postulating specific parameterisations. A key output of the analysis is a thoroughly phenomenological description of the incidence of the disease conditional on specific local weather factors. The study can be crucially important to infer the elusive mechanism of transmission of campylobacteriosis; for instance, by simulating the conditional incidence for a postulated mechanism and compare it with the phenomenological patterns as benchmark. The findings challenge the assumption, commonly made in statistical models, that the transformed mean rate of infection for diseases like campylobacteriosis is a mere additive and combination of the environmental variables.

Perceived and calculated diet quality improvements in a randomized mHealth weight loss trial.

The diet quality of US adults is poor and cross-sectional analyses suggest self-perception of healthful dietary intake may be overestimated. This analysis assessed the concordance between calculated and perceived diet quality and changes in diet quality among adults seeking weight loss and enrolled in a 12-month randomized behavioral trial. Healthy Eating Index-2015 diet quality (HEI) was calculated from self-administered 24-hour recalls. Perceived diet quality (PDQ) was measured on a 100-point scale. Higher scores indicate better diet quality. Concordance was assessed using the concordance correlation coefficient and Bland-Altman plots. The one hundred and five participants with complete dietary data were mostly female and white. There was good agreement between HEI and PDQ scores at 12 months for less than a third of participants. Most of the disagreement arose from PDQ scores being higher than HEI scores. Even fewer participants had good agreement between HEI changes and PDQ changes. Participants perceived greater improvement in diet quality than indicated by HEI score changes. Concordance was low at 12 months and for change in diet quality. Despite the diet quality of adults seeking weight loss being suboptimal and not improving, many perceived their diet quality and diet quality improvements as better than calculated. Future studies might explore the effect of misperceptions on weight loss outcomes.

Marine Protected Area Expansion and Country-Level Age-Standardized Adult Mortality.

Many countries have adopted targets to increase marine protected areas (MPAs) to limit the degradation of water bodies. Although there is evidence that MPAs can conserve marine life and promote biodiversity, there are limited data on the human health implications of MPAs. Using panel data from 1990, 2000, and 2014, we estimated the country-level associations between MPAs (i.e., percentage of territorial waters designated as marine reserves) and age-standardized mortality (i.e., age-standardized probability of dying between 15 and 60 years from all-causes among ages 15-60/100,000 population) by sex, among 110 countries. We fit mixed-effects linear regression models of mortality as a function of current MPA coverage, gross domestic product growth, year, the prior extent of MPA, electricity coverage, governance, and country-level random effects. We observed a significant inverse association between current MPA coverage and adult mortality. For each 5-percentage-point increase in current MPA coverage, a country had 0.982 times the geometric means of female and male mortality [geometric mean ratio: 0.982 (95% CI 0·976, 0·988)] conditional on past %MPA coverage and other modeled variables. The model showed no significant residual association of mortality with past %MPA conditional on current %MPA and other modeled variables. This is one of the first studies to show a positive association between increasing marine conservation and human health. This macro-level study suggests there may be important co-benefits for human health from expanding MPAs that merit further investigation.

Correction: The Minderoo-Monaco Commission on Plastics and Human Health.

[This corrects the article DOI: 10.5334/aogh.4056.].

Examining demographic and psychosocial factors related to self-weighing behavior during pregnancy and postpartum periods.

Black childbearing individuals in the US experience a higher risk of postpartum weight retention (PPWR) compared to their White counterparts. Given that PPWR is related to adverse health outcomes, it is important to investigate predictors of weight-related health behaviors, such as self-weighing (i.e., using a scale at home). Regular self-weighing is an evidence-based weight management strategy, but there is minimal insight into sociodemographic factors related to frequency. The Postpartum Mothers Mobile Study (PMOMS) facilitated longitudinal ambulatory weight assessments to investigate racial inequities in PPWR. Our objective for the present study was to describe self-weighing behavior during and after pregnancy in the PMOMS cohort, as well as related demographic and psychosocial factors. Applying tree modeling and multiple regression, we examined self-weighing during and after pregnancy. Participants (N = 236) were 30.2 years old on average (SD = 4.7), with the majority being college-educated (53.8%, n = 127), earning at least $30,000 annually (61.4%, n = 145), and self-identifying as non-Hispanic White (NHW; 68.2%, n = 161). Adherence to regular self-weighing (at least once weekly) was highest among participants during pregnancy, with a considerable decline after giving birth. Low-income Black participants (earning < $30,000) were significantly less likely to reach a completion rate of ≥ 80% during pregnancy (AOR = 0.10) or the postpartum period (AOR = 0.16), compared to NHW participants earning at least $30,000 annually. Increases in perceived stress were associated with decreased odds of sustained self-weighing after delivery (AOR = 0.79). Future research should consider behavioral differences across demographic intersections, such as race and socioeconomic status, and the impact on efficacy of self-weighing.

Feasibility and preliminary efficacy of a novel web-based physical activity intervention in adults with overweight/obesity: A pilot randomized controlled trial.

BACKGROUND: Only 14% of adults with obesity attain federal guidelines for physical activity (PA), but few interventions address obesity-specific barriers to PA. We designed the web-based Physical Activity for The Heart (PATH) intervention to address this gap. PURPOSE: Test the feasibility and preliminary efficacy of PATH for promoting PA and reducing cardiovascular disease (CVD) risk in adults with overweight/obesity. METHODS: In a 12-week pilot RCT, participants were randomized to PATH (n = 41) or wait-list control (n = 41) groups. Treatment group received access to PATH and met twice/month with a remote coach. The control group received a self-help PA guide and newsletters on general health. Moderate-to-vigorous PA (MVPA) was assessed via Actigraph-GT3X, steps via Fitbit Charge 2™, weight via smart scale, blood pressure (BP) via Omron BP device, and lipids/HbAIC via dry blood spot. Linear mixed modeling examined between- and within-group differences in PA and CVD risk. RESULTS: The sample (N = 82) was on average 55.9 ± 8.2 years old; mean BMI 35.5 ± 6.2 kg/m2; 57.3% white and 80.5% female. Recruitment lasted 6-months, and 12-week retention was 96.3%. Treatment group accessed PATH ≥twice/week (92.1%), spent ≥10 min/visit (89.5%) and thought the site was culturally appropriate (79%). At 12 wks, the PATH group had greater mean changes in weekly MVPA (+58.9 vs. +0.9 min, p = .024) and daily steps (+1246.4 vs. -64.2 steps, p = .002) compared to the control group. Also, the PATH group improved in weight, BMI, body fat, waist circumference, and BP (p < .05). CONCLUSION: The PATH intervention is feasible/acceptable and demonstrated preliminary efficacy for promoting PA among adults with overweight/obesity.

Aspects of Program Engagement in an Online Physical Activity Intervention and Baseline Predictors of Engagement.

PURPOSE: Participant engagement in an online physical activity (PA) intervention is described and baseline factors related to engagement are identified. DESIGN: Longitudinal Study Within Randomized Controlled Trial. SETTING: Online/Internet. SAMPLE: Primary care patients (21-70 years). INTERVENTION: ActiveGOALS was a 3-month, self-directed online PA intervention (15 total lessons, remote coaching support, and a body-worn step-counter). MEASURES: Engagement was measured across six outcomes related to lesson completion (total number and time to complete), coach contact, and behavior tracking (PA, sedentary). Self-reported baseline factors were examined from seven domains (confidence, environment, health, health care, demographic, lifestyle, and quality of life). ANALYSIS: General linear and nonlinear mixed models were used to examine relationships between baseline factors and engagement outcomes within and across all domains. RESULTS: Seventy-nine participants were included in the sample (77.2% female; 74.7% white non-Hispanic). Program engagement was high (58.2% completed all lessons; PA was tracked ≥3 times/week for 11.3 ± 4.0 weeks on average). Average time between completed lessons (days) was longer than expected and participants only contacted their coach about 1 of every 3 weeks. Individual predictors related to health, health care, demographics, lifestyle, and quality of life were significantly related to engagement. CONCLUSION: Examining multiple aspects of engagement and a large number of potential predictors of engagement is likely needed to determine facilitators and barriers for high engagement in multi-faceted online intervention programs.

Nature contact and general health: Testing multiple serial mediation pathways with data from adults in 18 countries.

The role of neighbourhood nature in promoting good health is increasingly recognised in policy and practice, but consistent evidence for the underlying mechanisms is lacking. Heterogeneity in exposure methods, outcome measures, and population characteristics, little exploration of recreational use or the role of different types of green or blue space, and multiple separate mediation models in previous studies have limited our ability to synthesise findings and draw clear conclusions. We examined multiple pathways linking different types of neighbourhood nature with general health using a harmonised international sample of adults. Using cross-sectional survey data from 18 countries (n = 15,917), we developed a multigroup path model to test theorised pathways, controlling for sociodemographic variables. We tested the possibility that neighbourhood nature (e.g. greenspace, inland bluespace, and coastal bluespace) would be associated with general health through lower air pollution exposure, greater physical activity attainment, more social contact, and higher subjective well-being. However, our central prediction was that associations between different types of neighbourhood nature and general health would largely be serially mediated by recent visit frequency to corresponding environment types, and, subsequently, physical activity, social contact, and subjective well-being associated with these frequencies. Several subsidiary analyses assessed the robustness of the results to alternative model specifications as well as effect modification by sociodemographics. Consistent with this prediction, there was statistical support for eight of nine potential serial mediation pathways via visit frequency which held for a range of alternative model specifications. Effect modification by financial strain, sex, age, and urbanicity altered some associations but did not necessarily support the idea that nature reduced health inequalities. The results demonstrate that across countries, theorised nature-health linkages operate primarily through recreational contact with natural environments. This provides arguments for greater efforts to support use of local green/blue spaces for health promotion and disease prevention.

Sea swimming and snorkeling in tropical coastal blue spaces and mental well-being: Findings from Indonesian island communities during the COVID-19 pandemic.

The COVID-19 pandemic has considerable mental health impacts. Immersive nature-based interventions, such as swimming or snorkeling, may help mitigate the global mental health crisis caused by the pandemic. To investigate this, we collected cross-sectional data from residents of coastal villages (n = 308) in Kepulauan Selayar, Indonesia. Analysis of Covariance (ANCOVA) was used with mental well-being as the outcome variable, operationalized as the Mental Component Summary (MCS) scores from the SF-12 (12-item Short Form Health Survey). After adjusting for covariates, the activity of sea swimming or snorkeling was found to be significantly associated with better mental well-being (η2 = 0.036; p < 0.01). Predictive margins analysis revealed that those who engaged in sea swimming or snorkeling for one to three days a week gained a 2.7 increase in their MCS scores, compared to those who did not. A non-linear dose-response relationship was detected: for those swimming or snorkeling more than three days per week, there was only an increase of 1.7 MCS score compared to the 0-day. Overall this study contributes to the expanding of evidence base, showing that interactions with blue spaces can be beneficial for mental health, especially in a potentially stressful time such as the current pandemic. Management implications: The positive association between the activity of swimming or snorkeling in open seas and the mental well-being of rural coastal communities in Indonesia during the COVID-19 pandemic indicates that access to coastal blue spaces is important in a time of uncertainties and high stress. Ensuring that local communities have continuous access to these spaces is the key challenge for all relevant stakeholders, particularly in light of the growing privatization of the local coastal environment for the sake of tourism. However, considering the importance that these blue spaces hold for the mental well-being of local communities, intensive dialogue amongst these stakeholders must be pursued to ensure that the development of the area does not jeopardize the collective well-being of the people already living there.

The Association between Neighborhood Walkability and Physical Activity in a Behavioral Weight Loss Trial Testing the Addition of Remotely Delivered Feedback Messages to Self-Monitoring.

Adding feedback messages (FB) to self-monitoring (SM) may reinforce behavior change. However, socio-environmental conditions (e.g., limited access to parks or low walkability) may limit one's ability to respond to FB focused on physical activity (PA). In this analysis, we hypothesized that high neighborhood walkability will positively modify the treatment effect of FB on PA, and residents of high walkability neighborhoods will achieve higher PA levels at 12 months than those in low walkability neighborhoods. The study is a secondary analysis of a 12-month behavioral weight-loss trial. Adults with overweight/obesity were randomized to SM + FB (n = 251) or SM alone (n = 251). SM + FB group received smartphone pop-up messages thrice/week tailored to their PA SM data. The assessment included neighborhood walkability via Walk Score (low [<50] vs. high [≥50]), moderate to vigorous PA (MVPA) and step count via Fitbit Charge 2™, and weight via smart scale. We report adjusted linear regression coefficients (b) with standard errors (SE). The analysis included participants who were primarily white, female, and with obesity. In adjusted models, neighborhood walkability did not moderate the effect of treatment assignment on log-transformed (ln) MVPA or steps count over 12 months. The SM + FB group had greater lnMVPA than the SM group, but lnMVPA and steps were similar between walkability groups. There were no significant interactions for group and time or group, time, and walkability. These findings suggest that adding FB to SM had a small but significant positive impact on PA over 12 months, but neighborhood walkability did not moderate the treatment effect of FB on PA.

Interindividual Variability in Self-Monitoring of Blood Pressure Using Consumer-Purchased Wireless Devices.

BACKGROUND: Engagement with self-monitoring of blood pressure (BP) declines, on average, over time but may vary substantially by individual. OBJECTIVES: We aimed to describe different 1-year patterns (groups) of self-monitoring of BP behaviors, identify predictors of those groups, and examine the association of self-monitoring of BP groups with BP levels over time. METHODS: We analyzed device-recorded BP measurements collected by the Health eHeart Study-an ongoing prospective eCohort study-from participants with a wireless consumer-purchased device that transmitted date- and time-stamped BP data to the study through a full 12 months of observation starting from the first day they used the device. Participants received no instruction on device use. We applied clustering analysis to identify 1-year self-monitoring, of BP patterns. RESULTS: Participants had a mean age of 52 years and were male and White. Using clustering algorithms, we found that a model with three groups fit the data well: persistent daily use (9.1% of participants), persistent weekly use (21.2%), and sporadic use only (69.7%). Persistent daily use was more common among older participants who had higher Week 1 self-monitoring of BP frequency and was associated with lower BP levels than the persistent weekly use or sporadic use groups throughout the year. CONCLUSION: We identified three distinct self-monitoring of BP groups, with nearly 10% sustaining a daily use pattern associated with lower BP levels.

Urban green space and mental health among people living alone: The mediating roles of relational and collective restoration in an 18-country sample.

Rates of living alone, especially in more urbanised areas, are increasing across many industrialised countries, with associated increases in feelings of loneliness and poorer mental health. Recent studies have suggested that access to nature (e.g. parks and green spaces) can reduce the stressors associated with loneliness, partly through providing opportunities to nurture personal relationships (relational restoration) and engage in normative community activities (collective restoration). Such associations might vary across different household compositions and socio-demographic or geographical characteristics, but these have not been thoroughly tested. Using data collected across 18 countries/territories in 2017-2018, we grouped urban respondents into those living alone (n = 2062) and those living with a partner (n = 6218). Using multigroup path modelling, we tested whether the associations between neighbourhood greenspace coverage (1-km-buffer from home) and mental health are sequentially mediated by: (a) visits to greenspace; and subsequently (b) relationship and/or community satisfaction, as operationalisations of relational and collective restoration, respectively. We also tested whether any indirect associations varied among subgroups of respondents living alone. Analyses showed that visiting green space was associated with greater mental well-being and marginally lower odds of using anxiety/depression medication use indirectly, mediated via both relationship and community satisfaction. These indirect associations were equally strong among respondents living alone and those living with a partner. Neighbourhood green space was, additionally, associated with more visits among respondents living with a partner, whereas among those living alone, this was sensitive to the green space metric. Within subgroups of people living alone, few overall differences were found. Some indirect pathways were, nevertheless, stronger in males, under 60-year-olds, those with no financial strain, and residents in warmer climates. In conclusion, supporting those living alone, as well as those living with a partner, to more frequently access their local greenspaces could help improve mental health via promoting relational and collective restoration.

A study of gene expression in the living human brain.

A goal of medical research is to determine the molecular basis of human brain health and illness. One way to achieve this goal is through observational studies of gene expression in human brain tissue. Due to the unavailability of brain tissue from living people, most such studies are performed using tissue from postmortem brain donors. An assumption underlying this practice is that gene expression in the postmortem human brain is an accurate representation of gene expression in the living human brain. Here, this assumption - which, until now, had not been adequately tested - is tested by comparing human prefrontal cortex gene expression between 275 living samples and 243 postmortem samples. Expression levels differed significantly for nearly 80% of genes, and a systematic examination of alternative explanations for this observation determined that these differences are not a consequence of cell type composition, RNA quality, postmortem interval, age, medication, morbidity, symptom severity, tissue pathology, sample handling, batch effects, or computational methods utilized. Analyses integrating the data generated for this study with data from earlier landmark studies that used tissue from postmortem brain donors showed that postmortem brain gene expression signatures of neurological and mental illnesses, as well as of normal traits such as aging, may not be accurate representations of these gene expression signatures in the living brain. By using tissue from large cohorts living people, future observational studies of human brain biology have the potential to (1) determine the medical research questions that can be addressed using postmortem tissue as a proxy for living tissue and (2) expand the scope of medical research to include questions about the molecular basis of human brain health and illness that can only be addressed in living people (e.g., "What happens at the molecular level in the brain as a person experiences an emotion?").