Glycerophospholipid dysregulation after traumatic brain injury.

Brain tissue is highly enriched in lipids, the majority of which are glycerophospholipids. Glycerophospholipids are the major constituents of cellular membranes and play an important role in maintaining integrity and function of cellular and subcellular structures. Any changes in glycerophospholipid homeostasis can adversely affect brain functions. Traumatic brain injury (TBI), an acquired injury caused by the impact of external forces to the brain, triggers activation of secondary biochemical events that include perturbation of lipid homeostasis. Several studies have demonstrated glycerophospholipid dysregulation in the brain and circulation after TBI. This includes spatial and temporal changes in abundance and distribution of glycerophospholipids in the injured brain. This is at least in part mediated by TBI-induced oxidative stress and by activation of lipid metabolism pathways involved in tissue repairing. In this review, we discuss current advances in understanding of the mechanisms and implications of glycerophospholipid dysregulation following TBI.

Association between Residential Greenness and Allostatic Load: A Cohort Study.

The association between residential greenness and allostatic load (AL), a marker of composite physiological burden and predictor of chronic disease, remains understudied. This study comprised 212,600 UK Biobank participants recruited over 2007 and 2010 at the baseline. Residential greenness was modeled as the normalized difference vegetation index (NDVI) from high spatial resolution (0.50 m) color infrared imagery and measured within a 0.5 km radial catchment. AL was measured as a composite index from 13 biomarkers comprising three physiological systems (metabolic, cardiovascular, and inflammatory systems) and two organ systems (liver and kidney). Multilevel mixed-effects generalized linear models with a random intercept for UK Biobank assessment centers were employed to examine the association between residential greenness and AL. Each interquartile range (IQR = 0.24) increment in NDVI greenness was associated with lower AL (beta (ß) = -0.28, 95% confidence interval (CI) = -0.55, -0.01). Consistently, relative to the lowest NDVI greenness quintile, participants in the highest quintile had lower AL (ß = -0.64, 95% CI = -1.02, -0.26). The proportion of the association between greenness and AL mediated by the physical activity was 3.2%. In conclusion, residential greenness was protectively associated with AL, a composite marker of wear and tear and general health.

Associations between Short-Term Exposure to Ambient Air Pollution and Influenza: An Individual-Level Case-Crossover Study in Guangzhou, China.

BACKGROUND: Influenza imposes a heavy burden on public health. Little is known, however, of the associations between detailed measures of exposure to ambient air pollution and influenza at an individual level. OBJECTIVE: We examined individual-level associations between six criteria air pollutants and influenza using case-crossover design. METHODS: In this individual-level time-stratified case-crossover study, we linked influenza cases collected by the Guangzhou Center for Disease Control and Prevention from 1 January 2013 to 31 December 2019 with individual residence-level exposure to particulate matter (PM2.5 and PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO). The exposures were estimated for the day of onset of influenza symptoms (lag 0), 1-7 d before the onset (lags 1-7), as well as an 8-d moving average (lag07), using a random forest model and linked to study participants' home addresses. Conditional logistic regression was developed to investigate the associations between short-term exposure to air pollution and influenza, adjusting for mean temperature, relative humidity, public holidays, population mobility, and community influenza susceptibility. RESULTS: N=108,479 eligible cases were identified in our study. Every 10-µg/m3 increase in exposure to PM2.5, PM10, NO2, and CO and every 5-µg/m3 increase in SO2 over 8-d moving average (lag07) was associated with higher risk of influenza with a relative risk (RR) of 1.028 (95% CI: 1.018, 1.038), 1.041 (95% CI: 1.032, 1.049), 1.169 (95% CI: 1.151, 1.188), 1.004 (95% CI: 1.003, 1.006), and 1.134 (95% CI: 1.107, 1.163), respectively. There was a negative association between O3 and influenza with a RR of 0.878 (95% CI: 0.866, 0.890). CONCLUSIONS: Our findings suggest that short-term exposure to air pollution, except for O3, is associated with greater risk for influenza. Further studies are necessary to decipher underlying mechanisms and design preventive interventions and policies. https://doi.org/10.1289/EHP12145.

Associations of Urban Built Environment with Cardiovascular Risks and Mortality: a Systematic Review.

With rapid urbanization, built environment has emerged as a set of modifiable factors of cardiovascular disease (CVD) risks. We conducted a systematic review to synthesize evidence on the associations of attributes of urban built environment (e.g. residential density, land use mix, greenness and walkability) with cardiovascular risk factors (e.g. hypertension and arterial stiffness) and major CVD events including mortality. A total of 63 studies, including 31 of cross-sectional design and 32 of longitudinal design conducted across 21 geographical locations and published between 2012 and 2023 were extracted for review. Overall, we report moderately consistent evidence of protective associations of greenness with cardiovascular risks and major CVD events (cross-sectional studies: 12 of 15 on hypertension/blood pressure (BP) and 2 of 3 on arterial stiffness; and longitudinal studies: 6 of 8 on hypertension/BP, 7 of 8 on CVD mortality, 3 of 3 on ischemic heart disease mortality and 5 of 8 studies on stroke hospitalization or mortality reporting significant inverse associations). Consistently, walkability was associated with lower risks of hypertension, arterial stiffness and major CVD events (cross-sectional studies: 11 of 12 on hypertension/BP and 1 of 1 on arterial stiffness; and longitudinal studies: 3 of 6 on hypertension/BP and 1 of 2 studies on CVD events being protective). Sixty-seven percent of the studies were rated as "probably high" risk of confounding bias because of inability to adjust for underlying comorbidities/family history of diseases in their statistical models. Forty-six percent and 14% of the studies were rated as "probably high" risk of bias for exposure and outcome measurements, respectively. Future studies with robust design will further help elucidate the linkages between urban built environment and cardiovascular health, thereby informing planning policies for creating healthy cities.

Association of climatic variables with risk of transmission of influenza in Guangzhou, China, 2005-2021.

BACKGROUND: Climatic variables constitute important extrinsic determinants of transmission and seasonality of influenza. Yet quantitative evidence of independent associations of viral transmissibility with climatic factors has thus far been scarce and little is known about the potential effects of interactions between climatic factors on transmission. OBJECTIVE: This study aimed to examine the associations of key climatic factors with risk of influenza transmission in subtropical Guangzhou. METHODS: Influenza epidemics were identified over a 17-year period using the moving epidemic method (MEM) from a dataset of N = 295,981 clinically- and laboratory-confirmed cases of influenza in Guangzhou. Data on eight key climatic variables were collected from China Meteorological Data Service Centre. Generalized additive model combined with the distributed lag non-linear model (DLNM) were developed to estimate the exposure-lag-response curve showing the trajectory of instantaneous reproduction number (Rt) across the distribution of each climatic variable after adjusting for depletion of susceptible, inter-epidemic effect and school holidays. The potential interaction effects of temperature, humidity and rainfall on influenza transmission were also examined. RESULTS: Over the study period (2005-21), 21 distinct influenza epidemics with varying peak timings and durations were identified. Increasing air temperature, sunshine, absolute and relative humidity were significantly associated with lower Rt, while the associations were opposite in the case of ambient pressure, wind speed and rainfall. Rainfall, relative humidity, and ambient temperature were the top three climatic contributors to variance in transmissibility. Interaction models found that the detrimental association between high relative humidity and transmissibility was more pronounced at high temperature and rainfall. CONCLUSION: Our findings are likely to help understand the complex role of climatic factors in influenza transmission, guiding informed climate-related mitigation and adaptation policies to reduce transmission in high density subtropical cities.

Deregulation of mTORC1-TFEB axis in human iPSC model of GBA1-associated Parkinson's disease.

Mutations in the GBA1 gene are the single most frequent genetic risk factor for Parkinson's disease (PD). Neurodegenerative changes in GBA1-associated PD have been linked to the defective lysosomal clearance of autophagic substrates and aggregate-prone proteins. To elucidate novel mechanisms contributing to proteinopathy in PD, we investigated the effect of GBA1 mutations on the transcription factor EB (TFEB), the master regulator of the autophagy-lysosomal pathway (ALP). Using PD patients' induced-pluripotent stem cells (iPSCs), we examined TFEB activity and regulation of the ALP in dopaminergic neuronal cultures generated from iPSC lines harboring heterozygous GBA1 mutations and the CRISPR/Cas9-corrected isogenic controls. Our data showed a significant decrease in TFEB transcriptional activity and attenuated expression of many genes in the CLEAR network in GBA1 mutant neurons, but not in the isogenic gene-corrected cells. In PD neurons, we also detected increased activity of the mammalian target of rapamycin complex1 (mTORC1), the main upstream negative regulator of TFEB. Increased mTORC1 activity resulted in excess TFEB phosphorylation and decreased nuclear translocation. Pharmacological mTOR inhibition restored TFEB activity, decreased ER stress and reduced α-synuclein accumulation, indicating improvement of neuronal protiostasis. Moreover, treatment with the lipid substrate reducing compound Genz-123346, decreased mTORC1 activity and increased TFEB expression in the mutant neurons, suggesting that mTORC1-TFEB alterations are linked to the lipid substrate accumulation. Our study unveils a new mechanism contributing to PD susceptibility by GBA1 mutations in which deregulation of the mTORC1-TFEB axis mediates ALP dysfunction and subsequent proteinopathy. It also indicates that pharmacological restoration of TFEB activity could be a promising therapeutic approach in GBA1-associated neurodegeneration.

The associations of socioeconomic status with incident dementia and Alzheimer's disease are modified by leucocyte telomere length: a population-based cohort study.

Socio-economic status (SES) and biological aging are risk factors for dementia, including Alzheimer's disease, however, it is less clear if the associations with SES vary sufficiently across different biological age strata. We used data from 331,066 UK Biobank participants aged 38-73 with mean follow-up of 12 years to examine if associations between SES (assessed by educational attainment, employment status and household income) and dementia and Alzheimer's disease are modified by biological age (assessed by leucocyte telomere length: LTL). Diagnosis of events was ascertained through hospital admissions data. Cox regressions were used to estimate hazard ratios [HRs]. A consistent dose-response relationship was found, with participants in low SES and shorter LTL strata (double-exposed group) reporting 3.28 (95% confidence interval [CI] 2.57-4.20) and 3.44 (95% CI 2.35-5.04) times higher risks of incident dementia and Alzheimer's disease respectively, compared to those of high SES and longer LTL (least-exposed group). Of interest is a synergistic interaction between SES and LTL to increase risk of dementia (RERI 0.57, 95% CI 0.07-1.06) and Alzheimer's disease (RERI 0.79, 95% CI 0.02-1.56). Our findings that SES and biological age (LTL) are synergistic risk factors of dementia and Alzheimer's disease may suggest the need to target interventions among vulnerable sub-groups.

Neighbourhood residential density, urbanicity and incident dementia and Alzheimer's disease: A 12-year prospective cohort study from the UK Biobank.

INTRODUCTION: An increasing proportion of global population is exposed to urban densification in an aging society. However, little is known of the role of residential density and urbanicity on the risk of developing dementia including Alzheimer's disease. We examined long-term associations between residential density and urbanicity and risks of incident dementia and Alzheimer's disease. METHODS: This prospective cohort study included participants from the UK Biobank who lived at the same residential address, had no self-reported neurological conditions and without dementia at baseline. Residential density was measured as the number of dwelling units within 1-km street neighbourhood of participant's home address. A composite index of urbanicity was developed from neighbourhood-level z-standardized densities of housing, retail, public transport and street centrality. Hazard ratios were derived from Cox proportional hazard models adjusted for known risk factors. RESULTS: The analytic sample included 239,629 participants aged 38-72 years. During a median follow-up of 12.3 years (interquartile range 11.5-13.0 years), 2,176 participants developed dementia and 1,004 Alzheimer's disease. After adjustments for potential risk factors, each 1,000 units/Km2 increment in residential density was associated with higher risks of dementia (hazard ratio [HR]=1.10, 95% confidence interval [CI]: 1.06-1.15) and Alzheimer's disease (HR=1.10, 95% CI: 1.04-1.16). Consistently, categorical models showed that living in neighbourhoods of higher residential density and urbanicity were associated with higher risks of dementia (HR = 1.30, 95% CI: 1.12-1.51 for the highest density quintile compared to the lowest and HR = 1.21, 95% CI: 1.05-1.39 for the highest urbanicity quintile relative to the lowest). The associations were more pronounced in female, age >65 years, and among participants of the low income and those being frail and having shorter leucocyte telomere length (LTL). CONCLUSIONS: Higher residential density and urbanicity was found to be positively associated with elevated risks of dementia and Alzheimer's disease. Optimizing neighbourhood residential density maybe one of the upstream considerations for mitigating against neurodegenerative diseases.

Inhibition of autophagy in microglia and macrophages exacerbates innate immune responses and worsens brain injury outcomes.

Excessive and prolonged neuroinflammation following traumatic brain injury (TBI) contributes to long-term tissue damage and poor functional outcomes. However, the mechanisms contributing to exacerbated inflammatory responses after brain injury remain poorly understood. Our previous work showed that macroautophagy/autophagy flux is inhibited in neurons following TBI in mice and contributes to neuronal cell death. In the present study, we demonstrate that autophagy is also inhibited in activated microglia and infiltrating macrophages, and that this potentiates injury-induced neuroinflammatory responses. Macrophage/microglia-specific knockout of the essential autophagy gene Becn1 led to overall increase in neuroinflammation after TBI. In particular, we observed excessive activation of the innate immune responses, including both the type-I interferon and inflammasome pathways. Defects in microglial and macrophage autophagy following injury were associated with decreased phagocytic clearance of danger/damage-associated molecular patterns (DAMP) responsible for activation of the cellular innate immune responses. Our data also demonstrated a role for precision autophagy in targeting and degradation of innate immune pathways components, such as the NLRP3 inflammasome. Finally, inhibition of microglial/macrophage autophagy led to increased neurodegeneration and worse long-term cognitive outcomes after TBI. Conversely, increasing autophagy by treatment with rapamycin decreased inflammation and improved outcomes in wild-type mice after TBI. Overall, our work demonstrates that inhibition of autophagy in microglia and infiltrating macrophages contributes to excessive neuroinflammation following brain injury and in the long term may prevent resolution of inflammation and tissue regeneration.Abbreviations: Becn1/BECN1, beclin 1, autophagy related; CCI, controlled cortical impact; Cybb/CYBB/NOX2: cytochrome b-245, beta polypeptide; DAMP, danger/damage-associated molecular patterns; Il1b/IL1B/Il-1ß, interleukin 1 beta; LAP, LC3-associated phagocytosis; Map1lc3b/MAP1LC3/LC3, microtubule-associated protein 1 light chain 3 beta; Mefv/MEFV/TRIM20: Mediterranean fever; Nos2/NOS2/iNOS: nitric oxide synthase 2, inducible; Nlrp3/NLRP3, NLR family, pyrin domain containing 3; Sqstm1/SQSTM1/p62, sequestosome 1; TBI, traumatic brain injury; Tnf/TNF/TNF-α, tumor necrosis factor; Ulk1/ULK1, unc-51 like kinase 1.

Autophagy protein ULK1 interacts with and regulates SARM1 during axonal injury.

Autophagy is a cellular catabolic pathway generally thought to be neuroprotective. However, autophagy and in particular its upstream regulator, the ULK1 kinase, can also promote axonal degeneration. We examined the role and the mechanisms of autophagy in axonal degeneration using a mouse model of contusive spinal cord injury (SCI). Consistent with activation of autophagy during axonal degeneration following SCI, autophagosome marker LC3, ULK1 kinase, and ULK1 target, phospho-ATG13, accumulated in the axonal bulbs and injured axons. SARM1, a TIR NADase with a pivotal role in axonal degeneration, colocalized with ULK1 within 1 h after SCI, suggesting possible interaction between autophagy and SARM1-mediated axonal degeneration. In our in vitro experiments, inhibition of autophagy, including Ulk1 knockdown and ULK1 inhibitor, attenuated neurite fragmentation and reduced accumulation of SARM1 puncta in neurites of primary cortical neurons subjected to glutamate excitotoxicity. Immunoprecipitation data demonstrated that ULK1 physically interacted with SARM1 in vitro and in vivo and that SAM domains of SARM1 were necessary for ULK1-SARM1 complex formation. Consistent with a role in regulation of axonal degeneration, in primary cortical neurons ULK1-SARM1 interaction increased upon neurite damage. Supporting a role for autophagy and ULK1 in regulation of SARM1 in axonal degeneration in vivo, axonal ULK1 activation and accumulation of SARM1 were both decreased after SCI in Becn1+/- autophagy hypomorph mice compared to wild-type (WT) controls. These findings suggest a regulatory crosstalk between autophagy and axonal degeneration pathways, which is mediated through ULK1-SARM1 interaction and contributes to the ability of SARM1 to accumulate in injured axons.

The association between workplace built environment and metabolic health: A systematic review and meta-analysis.

BACKGROUND: Metabolic health is one of the key determinants of healthy living. Specifically, maintaining healthy weight, regulation of blood pressure, lipids and glucose over the life course have been reported to be protective on chronic diseases and premature mortality. With the global workforce spending, on average, one-third of the weekly time budget in the workplace, the role of workplace environment in enhancing metabolic health becomes important. However, there has thus far been no review synthesizing evidence on the links between workplace built environment and metabolic health. METHODS: A systematic review and meta-analysis was conducted synthesizing evidence on the associations of built environment attributes measured within the workplace neighbourhood and metabolic health. A total of 16 studies that fulfilled the inclusion/exclusion criteria were identified via systematic search of English language peer-refereed publications up to July 2021, in six databases. A systematic coding system was developed, indicating significant findings in expected/unexpected directions including null findings, and the quality of the pooled study was assessed. The Weighted-Z test method that accounts for the study quality was used to examine the strength of evidence. RESULTS: A quarter of the pooled studies were categorized to be of high quality. Among the workplace built environment attributes of access to/density of recreational facilities, street pattern, access to/density of destinations and services, and land use mix, very strong evidence was found for the association between access to/density of destinations and services and metabolic health (p < 0.001); specifically, access to full service establishments such as supermarkets, grocery stores and restaurants (p = 0.001). A relatively weak association between proximity to workplace and metabolic health (p = 0.019) was also reported. DISCUSSION: Given the lack of high quality studies, overall confidence in the currently available evidence is 'low'. Well-designed longitudinal studies with rigorous measurements for exposures and outcome variables are necessary.

Community-level ambient fine particulate matter and seasonal influenza among children in Guangzhou, China: A Bayesian spatiotemporal analysis.

BACKGROUND: Influenza is a major preventable infectious respiratory disease. However, there is little detailed long-term evidence of its associations with PM2.5 among children. We examined the community-level associations between exposure to ambient PM2.5 and incident influenza in Guangzhou, China. METHODS: We used data from the city-wide influenza surveillance system collected by Guangzhou Centre for Disease Control and Prevention (GZCDC) over the period 2013 and 2019. Incident influenza was defined as daily new influenza (both clinically diagnosed and laboratory confirmed) cases as per standard diagnostic criteria. A 200-meter city-wide grid of daily ambient PM2.5 exposure was generated using a random forest model. We developed spatiotemporal Bayesian hierarchical models to examine the community-level associations between PM2.5 and the influenza adjusting for meteorological and socioeconomic variables and accounting for spatial autocorrelation. We also calculated community-wide influenza cases attributable to PM2.5 levels exceeding the China Grade 1 and World Health Organization (WHO) regulatory thresholds. RESULTS: Our study comprised N = 191,846 children from Guangzhou aged ≤19 years and diagnosed with influenza between January 1, 2013 and December 31, 2019. Each 10 µg/m3 increment in community-level PM2.5 measured on the day of case confirmation (lag 0) and over a 6-day moving average (lag 0-5 days) was associated with higher risks of influenza (RR = 1.05, 95% CI: 1.05-1.06 for lag 0 and RR = 1.15, 95% CI: 1.14-1.16 for lag 05). We estimated that 8.10% (95%CI: 7.23%-8.57%) and 20.11% (95%CI: 17.64%-21.48%) influenza cases respectively were attributable to daily PM2.5 exposure exceeding the China Grade I (35 µg/m3) and the WHO limits (25 µg/m3). The risks associated with PM2.5 exposures were more pronounced among children of the age-group 10-14 compared to other age groups. CONCLUSIONS: More targeted non-pharmaceutical interventions aimed at reducing PM2.5 exposures at home, school and during commutes among children may constitute additional influenza prevention and control polices.

Associations of residential walkability and greenness with arterial stiffness in the UK Biobank.

BACKGROUND: Arterial stiffness is a key non-invasive marker of early vascular ageing, however, little is known of its associations with urban built environment. We examined the associations of objectively-measured residential walkability and greenness with arterial stiffness in a large UK-wide population cohort. METHODS: We employed data from the baseline UK Biobank cohort comprising adult participants recruited over the period of 2006 to 2010. Residential walkability index, defined as a function of density (residential, retail and public transit), street-level design, and destination accessibility was measured using a 1-Km dwelling catchment, while greenness was modelled as the mean Normalized Difference Vegetation Index (NDVI) of 0.5-metre resolution assessed within a 0.5-Km catchment. Arterial stiffness index (ASI) was measured non-invasively from the pulse waveform. Linear regression models were developed to examine associations of walkability and greenness with arterial stiffness. Restricted cubic spline (RCS) models were developed to examine dose-response relationships. We also examined effect modifications by sex and age, as well as the interaction effect of greenness and walkability. RESULTS: This cross-sectional study used a target sample of 169,704 UK Biobank participants aged ≥ 39 years. After full adjustments, in reference to the lowest walkability exposure quartile, those in the highest were associated with lower ASI (ß = -0.083 m/s, 95% CI: -0.14 to -0.03, p = 0.005). Participants in the third and fourth NDVI greenness exposure quartiles were also associated with lower ASI (ß = -0.074 m/s, -0.14 to -0.01, p < 0.020 for the third and ß = -0.293 m/s, -0.36 to -0.23, p < 0.001 for the fourth quartiles in reference to the first). The inverse association between NDVI greenness and ASI was more pronounced among women (p < 0.001), older adults (p = 0.011) and among participants in the highest walkability quartile (p < 0.001). CONCLUSION: Designing more walkable and greener residential environments can be a preventive intervention aimed at lowering the population distribution of vascular ageing and associated cardiovascular risks.

Alcohol affordability: implications for alcohol price policies. A cross-sectional analysis in middle and older adults from UK Biobank.

BACKGROUND: Increasing the price of alcohol reduces alcohol consumption and harm. The role of food complementarity, transaction costs and inflation on alcohol demand are determined and discussed in relation to alcohol price policies. METHODS: UK Biobank (N = 502,628) was linked by region to retail price quotes for the years 2007 to 2010. The log residual food and alcohol prices, and alcohol availability were regressed onto log daily alcohol consumption. Model standard errors were adjusted for clustering by region. RESULTS: Associations with alcohol consumption were found for alcohol price (ß = -0.56, 95% CI, -0.92 to -0.20) and availability (ß = 0.06, 95% CI, 0.04 to 0.07). Introducing, food price reduced the alcohol price consumption association (ß = -0.26, 95% CI, -0.50 to -0.03). Alcohol (B = 0.001, 95% CI, 0.0004 to 0.001) and food (B = 0.001, 95% CI, 0.0005 to 0.0006) price increased with time and were associated (ρ = 0.57, P < 0.001). CONCLUSION: Alcohol and food are complements, and the price elasticity of alcohol reduces when the effect of food price is accounted for. Transaction costs did not affect the alcohol price consumption relationship. Fixed alcohol price policies are susceptible to inflation.

Characteristics and health risks of personal exposure to particle-bound PAHs for Hong Kong adult residents: From ambient pollution to indoor exposure.

Research on individual level polycyclic aromatic hydrocarbons (PAHs) exposure is scarce. Moreover, the independent contribution of ambient- and indoor-origin PAHs to personal exposure remains poorly studied. We performed simultaneous ambient, residential indoor, and personal exposure measurements in a panel of healthy adults to investigate particle-bound PAHs, focusing on their carcinogenic congeners (cPAHs). Average PAH concentrations were much higher in ambient and residential indoor than personal exposure, with distinct seasonal variations. We employed chrysene as a tracer to investigate residential indoor and personal PAHs exposure by origin. Personal cPAH exposure was largely attributable to ambient-origin exposures (95.8%), whereas a considerable proportion of residential indoor PAHs was likely attributable to indoor emissions (33.8%). Benzo[a]pyrene equivalent (BaPeq) concentrations of cPAH accounted for 95.2%-95.6% of total carcinogenic potential. Uncertainties in estimated PAHs (and BaPeq) exposure and cancer risks for adults were calculated using the Monte Carlo simulation. Cancer risks attributable to ambient, residential indoor, and personal cPAH inhalation exposures ranged from 4.0 × 10-6 to 1.0 × 10-5 . A time-activity weighted model was employed for personal PAH exposure estimations. Estimated cPAH exposures demonstrate high cancer risks for adults in Hong Kong, suggesting that exposure to indoor-generated PAHs should be of great concern to the general population.

Structure-specific, accurate quantitation of plasmalogen glycerophosphoethanolamine.

Changes in plasmalogen glycerophosphoethanolamine (PE-P) composition (structure and abundance) are a key indicator of altered lipid metabolism. Differential changes in the levels of PE-P have been reported in different disease states, including neurodegenerative diseases. Of particular interest, traumatic brain injury (TBI) has resulted in altered expression of glycerophospholipid profiles, including PE-P. To date, most analytical assays assessing PE-P have focused on general lipidomic workflows to evaluate the relative, semi-quantitative abundance of PE-P during disease progression. This approach provides a broad evaluation of PE-P, yet often lacks specificity and sensitivity for individual PE-P structures which is a necessity for robust quantitative data. The present study highlights the development of a targeted, quantitative method using a HILIC separation and selective reaction monitoring mass spectrometry for the confident identification and accurate quantitation of PE-P. Our innovative method incorporates both the sn-1 alkyl vinyl ether and sn-2 acyl chain as product ion transitions, for specific and sensitive quantitation of 100 PE-P structures. Our method also uniquely allowed for the unambiguous assignment and quantitation of di-unsaturated sn-1 PE-P structures, which to date have not been conclusively quantified. Application of this assay to a TBI mouse model resulted in distinct temporal profiles for plasma PE-P up to 28 days post injury. Plasma PE-P were significantly increased 24 h after induced TBI, followed by a gradual reduction to sham concentrations by day 28. Overall, we established a structure-specific, quantitative assay for identification and quantitation of a comprehensive set of PE-P structures with demonstrated relevance to brain injury.

Liveable residential space, residential density, and hypertension in Hong Kong: A population-based cohort study.

BACKGROUND: Hypertension is a leading preventable risk factor of chronic disease and all-cause mortality. Housing is a fundamental social determinant of health. Yet, little is known about the impacts of liveable residential space and density on hypertension. METHODS AND FINDINGS: This retrospective observational study (median follow-up of 2.2 years) leveraged the FAMILY Cohort, a large territory-wide cohort in Hong Kong, Special Administrative Region, People's Republic of China to quantify associations of objectively measured liveable space and residential density with blood pressure outcomes among adults aged ≥16 years. Blood pressure outcomes comprised diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP), and hypertension. Liveable space was measured as residential floor area, and density was assessed using the number of residential units per building block and neighborhood residential unit density within predefined catchments. Multivariable regression models examined associations of liveable floor area and residential density with prevalent and incident hypertension. We investigated effect modifications by age, sex, income, employment status, and housing type. Propensity score matching was further employed to match a subset of participants who moved to smaller residences at follow-up with equivalent controls who did not move, and generalized linear models examined the impact of moving to smaller residences upon blood pressure outcomes. Our fully adjusted models of prevalent hypertension outcomes comprised 30,439 participants at baseline, while 13,895 participants were available for incident models at follow-up. We found that each interquartile range (IQR) increment in liveable floor area was associated with lower DBP (beta [ß] = -0.269 mm Hg, 95% confidence interval [CI]: -0.419 to -0.118, p < 0.001), SBP (ß = -0.317 mm Hg, -0.551 to -0.084, p = 0.008), MAP (ß = -0.285 mm Hg, -0.451 to -0.119 with p < 0.001), and prevalent hypertension (odds ratio [OR] = 0.955, 0.918 to 0.993, p = 0.022) at baseline. Each IQR increment in residential units per building block was associated with higher DBP (ß = 0.477 mm Hg, 0.212 to 0.742, p = <0.001), SBP (ß = 0.750 mm Hg, 0.322 to 1.177, p = <0.001), MAP (ß = 0.568 mm Hg, 0.269 to 0.866, p < 0.001), and prevalent hypertension (OR = 1.091, 1.024 to 1.162, p = 0.007). Each IQR increase in neighborhood residential density within 0.5-mi street catchment was associated with lower DBP (ß = -0.289 mm Hg, -0.441 to -0.137, p = <0.001), SBP (ß = -0.411 mm Hg, -0.655 to -0.168, p < 0.001), MAP (ß = -0.330 mm Hg, -0.501 to -0.159, p = <0.001), and lower prevalent hypertension (OR = 0.933, 0.899 to 0.969, p < 0.001). In the longitudinal analyses, each IQR increment in liveable floor area was associated with lower DBP (ß = -0.237 mm Hg, -0.431 to -0.043, p = 0.016), MAP (ß = -0.244 mm Hg, -0.444 to -0.043, p = 0.017), and incident hypertension (adjusted OR = 0.909, 0.836 to 0.988, p = 0.025). The inverse associations between larger liveable area and blood pressure outcomes were more pronounced among women and those residing in public housing. In the propensity-matched analysis, participants moving to residences of lower liveable floor area were associated with higher odds of incident hypertension in reference to those who did not move (OR = 1.623, 1.173 to 2.199, p = 0.002). The major limitations of the study are unmeasured residual confounding and loss to follow-up. CONCLUSIONS: We disentangled the association of micro-, meso-, and macrolevel residential densities with hypertension and found that higher liveable floor area and neighborhood scale residential density were associated with lower odds of hypertension. These findings suggest adequate housing in the form of provisioning of sufficient liveable space and optimizing residential density at the building block, and neighborhood levels should be investigated as a potential population-wide preventive strategy for lowering hypertension and associated chronic diseases.