Publications by authors named "Chinmoy Sarkar"

57 Publications

N-Acetyl-L-leucine improves functional recovery and attenuates cortical cell death and neuroinflammation after traumatic brain injury in mice.

Sci Rep 2021 Apr 29;11(1):9249. Epub 2021 Apr 29.

Department of Anesthesiology, Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability around the world. Even mild to moderate TBI can lead to lifelong neurological impairment due to acute and progressive neurodegeneration and neuroinflammation induced by the injury. Thus, the discovery of novel treatments which can be used as early therapeutic interventions following TBI is essential to restrict neuronal cell death and neuroinflammation. We demonstrate that orally administered N-acetyl-L-leucine (NALL) significantly improved motor and cognitive outcomes in the injured mice, led to the attenuation of cell death, and reduced the expression of neuroinflammatory markers after controlled cortical impact (CCI) induced experimental TBI in mice. Our data indicate that partial restoration of autophagy flux mediated by NALL may account for the positive effect of treatment in the injured mouse brain. Taken together, our study indicates that treatment with NALL would be expected to improve neurological function after injury by restricting cortical cell death and neuroinflammation. Therefore, NALL is a promising novel, neuroprotective drug candidate for the treatment of TBI.
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http://dx.doi.org/10.1038/s41598-021-88693-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084982PMC
April 2021

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

J Public Health (Oxf) 2021 Apr 9. Epub 2021 Apr 9.

Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK.

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 (β = -0.56, 95% CI, -0.92 to -0.20) and availability (β = 0.06, 95% CI, 0.04 to 0.07). Introducing, food price reduced the alcohol price consumption association (β = -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.
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http://dx.doi.org/10.1093/pubmed/fdab095DOI Listing
April 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Toxicological effects of personal exposure to fine particles in adult residents of Hong Kong.

Environ Pollut 2021 Apr 3;275:116633. Epub 2021 Feb 3.

The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address:

Toxicological studies have demonstrated the associations between fine particle (PM) components and various cytotoxic endpoints. However, few studies have investigated the toxicological effects of source-specific PM at the individual level. To investigate the potential impact of source-specific PM on cytotoxic effects, we performed repeated personal PM monitoring of 48 adult participants in Hong Kong during the winter and summer of 2014-2015. Quartz filters were analyzed for carbonaceous aerosols and water-soluble ions in PM. Teflon filters were collected to determine personal PM mass and metal concentrations. The toxicological effects of personal PM exposure-including cytotoxicity, inflammatory response, and reactive oxygen species (ROS) production-were measured using A549 cells in vitro. Personal PM samples collected in winter were more effective than those collected in summer at inducing cytotoxicity and the expression of proinflammation cytokine IL-6. By contrast, summer personal PM samples induced high ROS production. We performed a series of statistical analyses, Spearman correlation and a source apportionment approach with a multiple linear regression (MLR) model, to explore the sources contributing most significantly to personal PM bioreactivity. Secondary inorganic species and transition metals were discovered to be weak-to-moderately associated with cytotoxicity (r: 0.26-0.55; p < 0.01) and inflammatory response (r: 0.26-0.44; p < 0.05), respectively. Carbonaceous aerosols (i.e., organic and elemental carbon; r: 0.23-0.27; p < 0.05) and crustal material (Mg and Ca) was positively associated with ROS generation. The PMF-MLR models revealed that tailpipe exhaust and secondary sulfate contributed to ROS generation, whereas secondary nitrate was the major contributor to PM cytotoxicity and inflammation. These results improve and variate the arguments for practical policies designed to mitigate the risks posed by air pollution sources and to protect public health.
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http://dx.doi.org/10.1016/j.envpol.2021.116633DOI Listing
April 2021

Exposure to light at night (LAN) and risk of breast cancer: A systematic review and meta-analysis.

Sci Total Environ 2021 Mar 21;762:143159. Epub 2020 Oct 21.

Healthy High Density Cities Lab, HKUrbanLab, The University of Hong Kong, Knowles Building, Pokfulam Road, Pokfulam, Hong Kong, China.

Background: With the unprecedented urbanization light pollution has emerged as a ubiquitous problem, and there has been accumulating evidence on the links between exposure to light at night (LAN) and breast cancer risk. We conducted a systematic review and meta-analysis of published studies on the associations between LAN exposure and breast cancer risk.

Methods: We included all observational human studies wherein the exposure variable was LAN measured in indoor and outdoor environments, and the outcome was breast cancer. We employed summary relative risks (SRR) for breast cancer by comparing highest versus lowest categories of LAN exposure within a random-effects model. The National Toxicology Program's (NTP) Office of Health Assessment and Translation (OHAT) risk of bias rating tool was adopted to assess the risk of bias in individual studies and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline was employed to assess confidence in the body of evidence.

Results: A total 14 studies comprising four cohorts (13,155 cases among 372,802 exposed subjects), nine case-control and one case-referent studies of female subjects (39,462 cases and 20,739 controls) across seven countries and published between 2001 and 20 were included for review. Participants in the highest LAN exposure category were associated with higher risk of breast cancer in reference to those in the lowest (SRR: 1.12; 95% CI: 1.06-1.18; I = 39% for outdoor LAN, and SRR: 1.13; 95%CI: 1.05-1.21; I = 19% for indoor LAN). Pooled evidence identified relatively pronounced association of outdoor LAN exposure and breast cancer among women with estrogen receptor positive (ER+) tumor (SRR: 1.21; 95% CI: 1.04-1.40) and premenopausal status (SRR: 1.21; 95% CI: 1.06-1.37). The final rate of confidence in the body of evidence generated was graded as 'moderate' based on GRADE guideline.

Discussion: LAN exposure was consistently associated with higher breast cancer risk corroborating NTP's recommendations which anticipates excessive LAN as human carcinogen.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143159DOI Listing
March 2021

The nature of cities and the Covid-19 pandemic.

Curr Opin Environ Sustain 2020 Oct 27;46:27-31. Epub 2020 Aug 27.

Healthy High Density Cities Lab, HKUrbanLab, The University of Hong Kong, Knowles Building, Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region; China.

The virtual issue will only include the main essay.
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http://dx.doi.org/10.1016/j.cosust.2020.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451129PMC
October 2020

Spatio-temporal variations and trends of major air pollutants in China during 2015-2018.

Environ Sci Pollut Res Int 2020 Sep 13;27(27):33792-33808. Epub 2020 Jun 13.

Healthy High Density Cities Lab, HKUrbanLab, University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region, China.

The Chinese government, as a policy response, has continued to invest efforts and resources to implement cost-effective air pollution control technologies and stringent regulation to reduce emissions from the most contributing sectors to protect the environment and public health. The higher density of monitoring stations (> 1600) distributed across China provides a timely opportunity to use them to study in detail the national pollution trends in light of more stringent air pollution control policies. In the present study, air quality datasets comprising hourly concentrations of PM, O, NO, and SO collected across 1309, 1341, 1289, and 1347 monitoring stations respectively were obtained from the National Environmental Monitoring Centre over 4 years (2015-2018) and trend analysis was performed. Results indicate that the overall annual trends for PM and SO were - 2.9 ± 2.7 and - 3.2 ± 3.2 μg/m/year, while the winter trends were - 4.8 ± 5.8 and - 6.9 ± 8.4 μg/m/year respectively across China. The daily maximum 8-h average (DMA8) ozone concentration showed a significant positive trend of 2.4 ± 4.6 μg/m/year, which was comparatively higher in summer at 4.4 ± 9.0 μg/m/year. On the other side, NO trend is not great in number (- 0.45 ± 2.0 μg/m/year). Overall, 62.2%, 61.8%, and 20.9% of PM, SO, and NO monitoring stations were associated with a negative trend of ≥ - 2 μg/m/year. For O DMA8 concentrations, 50.7% of the monitoring stations showed a significant positive trend of ≥ 2 μg/m/year. In light of the Chinese government's increasing impetus on combating air pollution and climate change via new policy regulations, it is important to understand the spatio-temporal distributions and relative contributions of the spectrum of gaseous pollutants to the pollution loads as well as identify changing emission loads across sectors. The results of this study will facilitate the formulation of evidence-based air pollution reduction strategies and policies.
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http://dx.doi.org/10.1007/s11356-020-09646-8DOI Listing
September 2020

Exposure to light at night (LAN) and risk of obesity: A systematic review and meta-analysis of observational studies.

Environ Res 2020 08 12;187:109637. Epub 2020 May 12.

Healthy High Density Cities Lab, HKUrbanLab, The University of Hong Kong, Knowles Building, Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region, China.

Background: There is emerging evidence of the association between light at night (LAN) exposure and weight gain.

Objective: We aim to conduct a systematic review and meta-analysis of observational studies on the association between LAN exposure and risk of obesity in human subjects.

Methods: Peer-reviewed observational studies were systematically searched from MEDLINE (EBSCO), Academic Search Complete (EBSCO), CINAHL Plus (EBSCO) and PubMed up to December 24, 2019. Random-effects models were developed to estimate the associations between LAN exposure and weight-related outcomes of overweight and obesity as measured by body mass index (BMI), waist circumference, waist-hip-ratio and waist-to-height-ratio. The I statistic was used to assess the degree of heterogeneity across studies. The National Toxicology Program's Office of Health Assessment and Translation (OHAT) risk of bias rating tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline were respectively employed to assess the risk of bias and to appraise the quality of the generated evidence.

Results: A total of 12 studies (three with longitudinal and nine of cross-sectional design) published between 2003 and 2019 were included for systematic review, while seven of them fulfilling the inclusion/exclusion criteria were included in the meta-analysis. A higher LAN exposure was significantly associated with 13% higher odds of overweight (BMI≥25 kg/m) (Summary Odds Ratio; SOR: 1.13, 95% CI: 1.10-1.16) with low heterogeneity (I = 27.27%), and 22% higher odds of obesity (BMI≥30 kg/m) (SOR: 1.22, 95% CI: 1.07-1.38) with substantial heterogeneity (I = 85.96%). Stratifying analyses by the levels of measurement of LAN exposures (macro-, meso- and micro-levels) and time of LAN measurement (including before and while sleeping) consistently produced robust estimates, with higher exposure to LAN being positively associated with poorer weight outcomes. Assessment of risk of bias identified substantial detection bias for exposure, with over half of the pooled studies employing subjective LAN measures. The overall evidence of the association between LAN exposure and risk of obesity was rated as 'moderate' as per the GRADE guideline.

Conclusions: Exposure to LAN was reported to be a significant risk factor for overweight and obesity. Prospectively designed future studies with objectively measured multi-level LAN exposures and weight outcomes are required.
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http://dx.doi.org/10.1016/j.envres.2020.109637DOI Listing
August 2020

Cln1-mutations suppress Rab7-RILP interaction and impair autophagy contributing to neuropathology in a mouse model of infantile neuronal ceroid lipofuscinosis.

J Inherit Metab Dis 2020 09 27;43(5):1082-1101. Epub 2020 Apr 27.

Section on Developmental Genetics, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.

Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative lysosomal storage disease (LSD) caused by inactivating mutations in the CLN1 gene. CLN1 encodes palmitoyl-protein thioesterase-1 (PPT1), a lysosomal enzyme that catalyzes the deacylation of S-palmitoylated proteins to facilitate their degradation and clearance by lysosomal hydrolases. Despite the discovery more than two decades ago that CLN1 mutations causing PPT1-deficiency underlies INCL, the precise molecular mechanism(s) of pathogenesis has remained elusive. Here, we report that autophagy is dysregulated in Cln1 mice, which mimic INCL and in postmortem brain tissues as well as cultured fibroblasts from INCL patients. Moreover, Rab7, a small GTPase, critical for autophagosome-lysosome fusion, requires S-palmitoylation for trafficking to the late endosomal/lysosomal membrane where it interacts with Rab-interacting lysosomal protein (RILP), essential for autophagosome-lysosome fusion. Notably, PPT1-deficiency in Cln1 mice, dysregulated Rab7-RILP interaction and preventing autophagosome-lysosome fusion, which impaired degradative functions of the autolysosome leading to INCL pathogenesis. Importantly, treatment of Cln1 mice with a brain-penetrant, PPT1-mimetic, small molecule, N-tert (butyl)hydroxylamine (NtBuHA), ameliorated this defect. Our findings reveal a previously unrecognized role of CLN1/PPT1 in autophagy and suggest that small molecules functionally mimicking PPT1 may have therapeutic implications.
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http://dx.doi.org/10.1002/jimd.12242DOI Listing
September 2020

Air pollution associated respiratory mortality risk alleviated by residential greenness in the Chinese Elderly Health Service Cohort.

Environ Res 2020 04 15;183:109139. Epub 2020 Jan 15.

Healthy High Density Cities Lab, HKUrbanLab, University of Hong Kong, Hong Kong Special Administrative Region.

Background: Although residing in lower surrounding greenness and transient exposure to air pollution are independently associated with higher risk of adverse health outcomes, little is known about their interactions.

Objectives: We examine whether residential neighborhood greenness modifies the short-term association between air pollution and respiratory mortality among the participants of Chinese Elderly Health Service Cohort in Hong Kong.

Methods: We estimated residential surrounding greenness by measuring satellite-derived normalized difference vegetation index (NDVI) from Landsat within catchments of residential addresses of participants who died of respiratory diseases between 1998 and 2011. We first dichotomized NDVI into low and high greenness and used a time-stratified case-crossover approach to estimate the percent excess risk of respiratory mortality associated with fine particulate matter (PM), respirable particulate matter (PM), nitrogen dioxide (NO), and ozone (O). We further classified NDVI into greenness quartiles and introduced an interaction term between air pollution and the assigned median values of the NDVI quartiles into the models to assess the trend of greenness modification on the air pollution and respiratory mortality associations.

Results: Among 3159 respiratory deaths during the follow-up, 2058 were from pneumonia and 947 from chronic obstructive pulmonary disease. Elders living in the low greenness areas were associated with a higher risk of pneumonia mortality attributed to NO (p = 0.049) and O (p = 0.025). The mortality risk of pneumonia showed a decreasing trend for NO (p for trend = 0.041), O (p for trend = 0.006), and PM (p for trend = 0.034) with greenness quartiles increasing from Quartile 1 (lowest) to Quartile 4 (highest).

Conclusions: Our findings suggest that elders living in higher greenness areas are less susceptible to pneumonia mortality associated with air pollution, which provides evidence for optimizing allocation, siting, and quality of urban green space to minimize detrimental health effects of air pollution.
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http://dx.doi.org/10.1016/j.envres.2020.109139DOI Listing
April 2020

Environmental correlates of chronic obstructive pulmonary disease in 96 779 participants from the UK Biobank: a cross-sectional, observational study.

Lancet Planet Health 2019 11;3(11):e478-e490

Healthy High Density Cities Lab, HKUrbanLab, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.

Background: The role of environmental exposures in chronic obstructive pulmonary disease (COPD) remains inconclusive. We examined the association between environmental exposures (PM, greenness, and urbanicity) and COPD prevalence using the UK Biobank cohort data to identify key built environment correlates of COPD.

Methods: In this cross-sectional, observational study we used baseline data for UK Biobank participants. Included participants were aged 39 years and older, white, had available spirometry data, and had complete data for phenotypes and exposures. COPD was defined by spirometry with the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Environmental exposures were PM derived from monitoring data and interpolated using land-use regression at the participants' geocoded residential addresses. Built environment metrics of residential greenness were modelled in terms of normalised difference vegetation index from remotely sensed colour infrared data within a 500 m residential catchment, and an urbanicity index derived from spatial analyses and measured with a 1 km buffer around each participant's residential address. Logistic regression models examined the associations between environmental exposures and COPD prevalence adjusting for a range of confounders. Subgroup analyses by urbanicity and effect modification by white blood cell count as an inflammatory marker were also done.

Findings: We assessed 96 779 participants recruited between April 4, 2006, and Oct 1, 2010, of which 5391 participants had COPD with a prevalence of 5·6%. Each 10 μg/m increment in ambient PM exposure at a participant's residential location was associated with higher odds of COPD (odds ratio 1·55, 95% CI 1·14-2·10). Among the built environment metrics, urbanicity was associated with higher odds of COPD (1·05, 1·01-1·08 per interquartile increment), whereas residential greenness was protective, being associated with lower odds of COPD (0·89, 0·84-0·93 for each interquartile increment in greenness). The results remained consistent in models of COPD defined as per lower limit of normal criteria. The highest quartile of white blood cell count was associated with lower lung function and higher COPD risk with a significant interaction between PM and white blood cell count only in the model of lung function (p=0·0003).

Interpretation: In this study of the built environment and COPD, to our knowledge the largest done in the UK, we found that exposure to ambient PM and urbanicity were associated with a higher risk of COPD. Residing in greener areas, as measured by normalised difference vegetation index, was associated with lower odds of COPD, suggesting the potential value of urban planning and design in minimising or offsetting environmental risks for the prevention and management of COPD.

Funding: University of Hong Kong, UK Biobank, and UK Economic & Social Research Council.
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http://dx.doi.org/10.1016/S2542-5196(19)30214-1DOI Listing
November 2019

cPLA2 activation contributes to lysosomal defects leading to impairment of autophagy after spinal cord injury.

Cell Death Dis 2019 07 11;10(7):531. Epub 2019 Jul 11.

Department of Anesthesiology & Center for Shock, Trauma and Anesthesiology Research (STAR), School of Medicine, University of Maryland, Baltimore, MD, USA.

The autophagy-lysosomal pathway plays an essential role in cellular homeostasis as well as a protective function against a variety of diseases including neurodegeneration. Conversely, inhibition of autophagy, for example due to lysosomal dysfunction, can lead to pathological accumulation of dysfunctional autophagosomes and consequent neuronal cell death. We previously reported that autophagy is inhibited and contributes to neuronal cell death following spinal cord injury (SCI). In this study, we examined lysosomal function and explored the mechanism of lysosomal defects following SCI. Our data demonstrated that expression levels and processing of the lysosomal enzyme cathepsin D (CTSD) are decreased by 2 h after SCI. Enzymatic activity levels of CTSD and another lysosomal enzyme, N-acetyl-alpha-glucosaminidase, are both decreased 24 h post injury, indicating general lysosomal dysfunction. Subcellular fractionation and immunohistochemistry analysis demonstrated that this dysfunction is due to lysosomal membrane permeabilization and leakage of lysosomal contents into the cytosol. To directly assess extent and mechanisms of damage to lysosomal membranes, we performed mass spectrometry-based lipidomic analysis of lysosomes purified from SCI and control spinal cord. At 2 h post injury our data demonstrated increase in several classes of lysosophospholipids, the products of phospholipases (PLAs), as well as accumulation of PLA activators, ceramides. Phospholipase cPLA2, the main PLA species expressed in the CNS, has been previously implicated in mediation of secondary injury after SCI, but the mechanisms of its involvement remain unclear. Our data demonstrate that cPLA2 is activated within 2 h after SCI preferentially in the lysosomal fraction, where it colocalizes with lysosomal-associated membrane protein 2 in neurons. Inhibition of cPLA2 in vivo decreased lysosomal damage, restored autophagy flux, and reduced neuronal cell damage. Taken together our data implicate lysosomal defects in pathophysiology of SCI and for the first time indicate that cPLA2 activation leads to lysosomal damage causing neuronal autophagosome accumulation associated with neuronal cell death.
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http://dx.doi.org/10.1038/s41419-019-1764-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624263PMC
July 2019

PLA2G4A/cPLA2-mediated lysosomal membrane damage leads to inhibition of autophagy and neurodegeneration after brain trauma.

Autophagy 2020 03 25;16(3):466-485. Epub 2019 Jun 25.

Department of Anesthesiology, Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, MD, USA.

Lysosomal membrane permeabilization (LMP) is observed under many pathological conditions, leading to cellular dysfunction and death. However, the mechanisms by which lysosomal membranes become leaky are not clear. Our data demonstrate that LMP occurs in neurons following controlled cortical impact induced (CCI) traumatic brain injury (TBI) in mice, leading to impaired macroautophagy (autophagy) and neuronal cell death. Comparison of LC-MS/MS lysosomal membrane lipid profiles from TBI and sham animals suggested a role for PLA2G4A/cPLA2 (phospholipase A2, group IVA [cytosolic, calcium-dependent]) in TBI-induced LMP. Activation of PLA2G4A caused LMP and inhibition of autophagy flux in cell lines and primary neurons. pharmacological inhibition of PLA2G4A attenuated TBI-induced LMP, as well as subsequent impairment of autophagy and neuronal loss, and was associated with improved neurological outcomes. Inhibition of PLA2G4A limited amyloid-β-induced LMP and inhibition of autophagy. Together, our data indicate that PLA2G4A -mediated lysosomal membrane damage is involved in neuronal cell death following CCI-induced TBI and potentially in other neurodegenerative disorders.: AACOCF, arachidonyl trifluoromethyl ketone; ACTB/β-actin, actin, beta; AD, Alzheimer disease; ATG5, autophagy related 5; ATG7, autophagy related 7; ATG12, autophagy related 12; BECN1, beclin 1, autophagy related; C1P, ceramide-1-phosphate; CCI, controlled cortical impact; CTSD, cathepsin D; CTSL, cathepsin L; GFP, green fluorescent protein; IF, immunofluorescence; LAMP1, lysosomal-associated membrane protein 1; LAMP2, lysosomal-associated membrane protein 2; LC-MS/MS, liquid chromatography-tandem mass spectrometry; LMP, Lysosomal membrane permeabilization; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; MAP1LC3/LC3, microtuble-associated protein 1 light chain 3; NAGLU, alpha-N-acetylglucosaminidase (Sanfilippo disease IIIB); PC, diacyl glycerophosphatidylcholine; PE, diacyl glycerophosphatidylethanolamine; PE-O, plasmanyl glycerophosphatidylethanolamine; PE-P, plasmenyl glycerophosphatidylethanolamine; PLA2G4A/cPLA2, phospholipase A2, group IVA (cytosolic, calcium-dependent); RBFOX3, RNA binding protein, fox-1 homolog (C. elegans) 3; RFP, red fluorescent protein; ROS, reactive oxygen species; SQSTM1, sequestosome 1; TUBA1/α-tubulin, tubulin, alpha; TBI, traumatic brain injury; TFEB, transcription factor EB; ULK1, unc-51 like kinase 1.
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http://dx.doi.org/10.1080/15548627.2019.1628538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999646PMC
March 2020

The gene is a negative regulator of autophagy and ULK1 protein stability.

Autophagy 2020 01 7;16(1):140-153. Epub 2019 Apr 7.

Department of Anesthesiology & Shock, Trauma and Anesthesiology Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.

Recent studies indicate a causative relationship between defects in autophagy and dopaminergic neuron degeneration in Parkinson disease (PD). However, it is not fully understood how autophagy is regulated in the context of PD. Here we identify (ubiquitin specific peptidase 24), a gene located in the (Parkinson disease 10 [susceptibility]) locus associated with late onset PD, as a novel negative regulator of autophagy. Our data indicate that USP24 regulates autophagy by affecting ubiquitination and stability of the ULK1 protein. Knockdown of in cell lines and in human induced-pluripotent stem cells (iPSC) differentiated into dopaminergic neurons resulted in elevated ULK1 protein levels and increased autophagy flux in a manner independent of MTORC1 but dependent on the class III phosphatidylinositol 3-kinase (PtdIns3K) activity. Surprisingly, knockdown also improved neurite extension and/or maintenance in aged iPSC-derived dopaminergic neurons. Furthermore, we observed elevated levels of USP24 in the of a subpopulation of idiopathic PD patients, suggesting that USP24 may negatively regulate autophagy in PD.: Bafilomycin/BafA: bafilomycin A; DUB: deubiquitinating enzyme; iPSC: induced pluripotent stem cells; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; nt: non-targeting; PD: Parkinson disease; p-ATG13: phospho-ATG13; PtdIns3P: phosphatidylinositol 3-phosphate; RPS6: ribosomal protein S6; SNPs: single nucleotide polymorphisms; TH: tyrosine hydroxylase; USP24: ubiquitin specific peptidase 24.
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http://dx.doi.org/10.1080/15548627.2019.1598754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984603PMC
January 2020

Detection and Structural Characterization of Ether Glycerophosphoethanolamine from Cortical Lysosomes Following Traumatic Brain Injury Using UPLC-HDMS.

Proteomics 2019 09 19;19(18):e1800297. Epub 2019 Mar 19.

University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD, 21201, USA.

The use of ultra performance liquid chromatography coupled to data independent tandem mass spectrometry with traveling wave ion mobility for detection and structural identification of ether-linked glycerophosphoethanolamine is described. The experimental design generates 4D data (chromatographic retention time, precursor accurate mass, drift time with associated calculated collisional cross-section, and time-aligned accurate mass diagnostic product ions) for each ionization mode. Confident structure identification depends on satisfying 4D data confirmation in both positive and negative ion mode. Using this methodology, a number of ether-linked glycerophosphoethanolamine lipids are structurally elucidated from mouse brain lysosomes. It is further determined that several ether-linked glycerophosphoethanolamine structures are differentially abundant between lysosomes isolated from mouse cortex following traumatic brain injury as compared to that of sham animals. The combined effort of aligning multi-dimensional mass spectrometry data with a well-defined traumatic brain injury model lays the foundation for gaining mechanistic insight in the role lysosomal membrane damage plays in neuronal cell death following brain injury.
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http://dx.doi.org/10.1002/pmic.201800297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565256PMC
September 2019

Are exposures to ready-to-eat food environments associated with type 2 diabetes? A cross-sectional study of 347 551 UK Biobank adult participants.

Lancet Planet Health 2018 10;2(10):e438-e450

Department of Psychiatry, Oxford University, Warneford Hospital, Oxford, UK.

Background: Rapid urbanisation and associated socioeconomic transformations have modified current lifestyles, shifting dietary preferences towards ready-to-eat, calorie-dense food of poor nutritional quality. The effect of ready-to-eat food environments that sell food for instant consumption on the risk of type 2 diabetes has received scant attention. We therefore aimed to examine the association between exposure to ready-to-eat food environments and type 2 diabetes in a large and diverse population sample.

Methods: We conducted a cross-sectional study of adult male and female participants from the baseline phase of the UK Biobank cohort. Participants in this cohort were aged 37-73 years and resided in one of 21 cities in the UK. Ready-to-eat food environments, which we determined from a modelled and linked built environment database, were objectively measured within 1-km catchment areas of the residential streets of participants and were expressed as metrics of density and proximity to the participants' homes. We used logistic regression models to examine the associations between exposure to ready-to-eat food environments and the odds of type 2 diabetes, adjusting for individual covariates such as physical activity. As sensitivity analyses, we investigated the associations between the street distance to the nearest ready-to-eat food outlet and type 2 diabetes. We also tested post hoc for effect modification by sex, income, body-mass index, and location of the UK Biobank collection centre.

Findings: Of 502 635 UK Biobank participants enrolled between March 13, 2006, and Oct 1, 2010, the sample analysed included 347 551 (69·1%) participants. The density of ready-to-eat food environments within a 1-km catchment area was associated with higher odds of type 2 diabetes for participants in the groups with highest exposure to restaurants and cafeterias (odss ratio 1·129, 95% CI 1·05-1·21; p=0·0007) and a composite measure of ready-to-eat outlet density (1·112, 1·02-1·21; p=0·0134) compared with those with no exposure. Exposure to hot and cold takeaways was only significantly associated with higher odds of type 2 diabetes at the second highest exposure category that we examined (1·076, 1·01-1·14; p=0·0171), representing a density of 0·75-2·15 units per km. A protective effect with distance decay was observed: participants in the highest quintile of street distance to nearest ready-to-eat food outlet reported lower odds of type 2 diabetes than those in the lowest quintile (0·842, 0·78-0·91; p<0·0001 for restaurants and cafeterias; and 0·913, 0·85-0·98; p=0·0173 for hot and cold takeaways). These effects were most pronounced in overweight participants (p=0·0329), but there was no evidence of interaction by sex, income, or UK Biobank collection centre.

Interpretation: Access to ready-to-eat food environments was positively associated with type 2 diabetes. Top-down policies aimed at minimising unhealthy food access could potentially reduce unhealthy consumption and risks of chronic diseases. Further long-term studies are needed to effectively guide such interventions.

Funding: University of Hong Kong, UK Biobank, and UK Economic & Social Research Council.
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http://dx.doi.org/10.1016/S2542-5196(18)30208-0DOI Listing
October 2018

Correction to: Examining the interaction of fast-food outlet exposure and income on diet and obesity: evidence from 51,361 UK biobank participants.

Int J Behav Nutr Phys Act 2018 09 25;15(1):93. Epub 2018 Sep 25.

UKCRC Centre for Diet and Activity Research (CEDAR), MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.

Furthermore, these errors were mistakenly introduced by the Production team managing this article and, as such were not the fault of the authors.
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http://dx.doi.org/10.1186/s12966-018-0713-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157058PMC
September 2018

The Environmental Exposures and Inner- and Intercity Traffic Flows of the Metro System May Contribute to the Skin Microbiome and Resistome.

Cell Rep 2018 07;24(5):1190-1202.e5

Systems Biology and Bioinformatics Group, School of Biological Sciences, Faculty of Sciences, The University of Hong Kong, Hong Kong S.A.R., China; Systems Biology & Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany. Electronic address:

The skin functions as the primary interface between the human body and the external environment. To understand how the microbiome varies within urban mass transit and influences the skin microbiota, we profiled the human palm microbiome after contact with handrails within the Hong Kong Mass Transit Railway (MTR) system. Intraday sampling time was identified as the primary determinant of the variation and recurrence of the community composition, whereas human-associated species and clinically important antibiotic resistance genes (ARGs) were captured as p.m. signatures. Line-specific signatures were notably correlated with line-specific environmental exposures and city characteristics. The sole cross-border line appeared as an outlier in most analyses and showed high relative abundance and a significant intraday increment of clinically important ARGs (24.1%), suggesting potential cross-border ARG transmission, especially for tetracycline and vancomycin resistance. Our study provides an important reference for future public health strategies to mitigate intracity and cross-border pathogen and ARG transmission.
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http://dx.doi.org/10.1016/j.celrep.2018.06.109DOI Listing
July 2018

Examining the interaction of fast-food outlet exposure and income on diet and obesity: evidence from 51,361 UK Biobank participants.

Int J Behav Nutr Phys Act 2018 07 24;15(1):71. Epub 2018 Jul 24.

UKCRC Centre for Diet and Activity Research (CEDAR), MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.

Background: Household income (as a marker of socioeconomic position) and neighbourhood fast-food outlet exposure may be related to diet and body weight, which are key risk factors for non-communicable diseases. However, the research evidence is equivocal. Moreover, understanding the double burden of these factors is a matter of public health importance. The purpose of this study was to test associations of neighbourhood fast-food outlet exposure and household income, in relation to frequency of consumption of processed meat and multiple measures of adiposity, and to examine possible interactions.

Methods: We employed an observational, cross-sectional study design. In a cohort of 51,361 adults aged 38-72 years in Greater London, UK, we jointly classified participants based on household income (£/year, four groups) and GIS-derived neighbourhood fast-food outlet proportion (counts of fast-food outlets as a percentage of all food outlets, quartiles). Multivariable regression models estimated main effects and interactions (additive and multiplicative) of household income and fast-food outlet proportion on odds of self-reported frequent processed meat consumption (> 1/week), measured BMI (kg/m), body fat (%), and odds of obesity (BMI ≥ 30).

Results: Income and fast-food proportion were independently, systematically associated with BMI, body fat, obesity and frequent processed meat consumption. Odds of obesity were greater for lowest income participants compared to highest (OR = 1.54, 95% CI: 1.41, 1.69) and for those most-exposed to fast-food outlets compared to least-exposed (OR = 1.51, 95% CI: 1.40, 1.64). In jointly classified models, lowest income and highest fast-food outlet proportion in combination were associated with greater odds of obesity (OR = 2.43, 95% CI: 2.09, 2.84), with relative excess risk due to interaction (RERI = 0.03). Results were similar for frequent processed meat consumption models. There was no evidence of interaction on a multiplicative scale between fast-food outlet proportion and household income on each of BMI (P = 0.230), obesity (P = 0.054) and frequent processed meat consumption (P = 0.725).

Conclusions: Our study demonstrated independent associations of neighbourhood fast-food outlet exposure and household income, in relation to diet and multiple objective measures of adiposity, in a large sample of UK adults. Moreover, we provide evidence of the double burden of low income and an unhealthy neighbourhood food environment, furthering our understanding of how these factors contribute jointly to social inequalities in health.
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http://dx.doi.org/10.1186/s12966-018-0699-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497220PMC
July 2018

Association between adiposity outcomes and residential density: a full-data, cross-sectional analysis of 419 562 UK Biobank adult participants.

Lancet Planet Health 2017 Oct 5;1(7):e277-e288. Epub 2017 Oct 5.

Healthy High Density Cities Lab, HKUrbanLab, University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Psychiatry, Oxford University, Warneford Hospital, Oxford, UK.

Background: Obesity is a major health issue and an important public health target for urban design. However, the evidence for identifying the optimum residential density in relation to obesity has been far from compelling. We examined the association of obesity with residential density in a large and diverse population sample drawn from the UK Biobank to identify healthy-weight-sustaining density environments.

Methods: For this full-data, cross-sectional analysis, we used UK Biobank data for adult men and women aged 37-73 years from 22 cities across the UK. Baseline examinations were done between 2006 and 2010. Residential unit density was objectively assessed within a 1 km street catchment of a participant's residence. Other activity-influencing built environment factors were measured in terms of density of retail, public transport, and street-level movement density, which were modelled from network analyses of through movement of street links within the defined catchment. We regressed adiposity indicators of body-mass index (BMI; kg/m), waist circumference (cm), whole body fat (kg), and obesity (WHO criteria of BMI ≥30 kg/m) on residential density (units per km), adjusting for activity-influencing built environment factors and individual covariates. We also investigated effect modification by age, sex, employment status, and physical activity. We used a series of linear continuous and logistic regression models and non-linear restricted cubic spline models as appropriate.

Findings: Of 502 649 adults in the prospective cohort, 419 562 (83·5%) participants across 22 UK Biobank assessment centres met baseline data requirements and were included in the analytic sample. The fitted restricted cubic spline adiposity-residential density dose-response curve identified a turning point at a residential density of 1800 residential units per km. Below a residential density of 1800 units per km, an increment of 1000 units per km was positively related with adiposity, being associated with higher BMI (β 0·19 kg/m, 95% CI 0·14 to 0·24), waist circumference (β 0·41 cm, 0·28 to 0·54), and whole body fat (β 0·40 kg, 0·30 to 0·50), and with increased odds of obesity (odds ratio [OR] 1·10, 1·07 to 1·14). Beyond 1800 units per km, residential density had a protective effect on adiposity and was associated with lower BMI (β -0·22 kg/m, -0·25 to -0·20), waist circumference (β -0·54 cm, -0·61 to -0·48), and whole body fat (β -0·38 kg, -0·43 to -0·33), and with decreased odds of obesity (OR 0·91, 0·90 to 0·93). Subgroup analyses identified more pronounced protective effects of residential density among individuals who were younger, female, in employment, and accumulating higher levels of physical activity, except in the case of whole body fat, for which the protective effects were stronger in men.

Interpretation: Housing-level policy related to the optimisation of healthy density in cities might be a potential upstream-level public health intervention towards the minimisation and offsetting of obesity; however, further research based on accumulated prospective data is necessary for evidencing specific pathways. The findings might mean that governments, such as the UK Government, who are attempting to prevent suburban densification by, for example, prohibiting the subdivision of single lot housing and the conversion of domestic gardens to housing lots, will potentially have the effect of inhibiting the conversion of suburbs into more healthy places to live.

Funding: University of Hong Kong, UK Biobank, and UK Economic & Social Research Council.
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http://dx.doi.org/10.1016/S2542-5196(17)30119-5DOI Listing
October 2017

The effect of street-level greenery on walking behavior: Evidence from Hong Kong.

Soc Sci Med 2018 07 9;208:41-49. Epub 2018 May 9.

Department of Urban Planning, Tongji University, Shanghai, China. Electronic address:

Accumulating evidence shows that urban greenspaces have great health benefits, but establishing a causal relationship is difficult. It is often hypothesized that walking and physical activity are mediators in the relationship between urban greenspaces and health outcomes. Furthermore, most urban greenspace-physical activity studies have focused on parks rather than on landscaped streets, even though the latter are the most popular places for physical activity. The lack of research attention for landscaped streets is largely due to the fact that street greenery is difficult to measure, especially at eye level. Using readily available Google Street View images, we developed methods and tools to assess the availability of eye-level street greenery. A two-layered study was developed that 1) examined the association between urban greenspaces and the odds of walking (versus not walking) for 90,445 participants in the Hong Kong Travel Characteristics Survey and 2) carried out sensitivity analysis of the association between urban greenspaces and total walking time for a subset of 6770 participants. Multilevel regression models were developed to reveal the associations between street greenery and walking behaviors while controlling for sociodemographic characteristics and other activity-influencing built environment factors, taking into account the inherent clustering within the data. The results showed that both street greenery and the number of parks were associated with higher odds of walking; street greenery but not parks was associated with total walking time. Our results suggest that walking behavior is at least as strongly affected by eye-level street greenery as by parks. They also implicitly support the health benefits of urban greenspaces via walking and physical activity. With the large sample size, our findings pertain to the entire population of Hong Kong. Furthermore, the use of Google Street View is a sound and effective way to assess eye-level greenery, which may benefit further health studies.
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http://dx.doi.org/10.1016/j.socscimed.2018.05.022DOI Listing
July 2018

Commuting Mode Choice in a High-Density City: Do Land-Use Density and Diversity Matter in Hong Kong?

Int J Environ Res Public Health 2018 05 4;15(5). Epub 2018 May 4.

Department of Urban Planning, Tongji University, Shanghai 200092, China.

Hong Kong is a densely populated and transit-oriented Chinese city, which provides an ideal urban environment with which to study the various successful facets of land use policy as a model for potential replication to curb increasing car use in other Chinese cities. We examine the commuting mode choice of 203,900 households living in 4768 street blocks in Hong Kong from 2011 census. A street block is the smallest planning unit, made up of one or more housing estates with a homogenous built environment and socioeconomic status. The built environment is measured using the five framework, an international dimensioning framework for classifying and measuring attributes of the built environment for physical activity and travel behaviors. Generalized, multi-level mixed models were applied to detect the associations between travel choice and built environment characteristics, while adjusting for socioeconomic status. Design and destination accessibility had greater effects on the choices to walk and take public transport than on the choice to drive. Density and diversity had only marginal effects on mode choice. Unexpectedly, distance to the urban center had the opposite effect on automobile use to that found in Western studies. Hong Kong residents living close to the urban center were more likely to drive for commuting trips. The contrasting findings between our study and Western studies suggest that the associations between a high-density built environment and travel choice vary with urban context.
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http://dx.doi.org/10.3390/ijerph15050920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981959PMC
May 2018

Lysosomal damage after spinal cord injury causes accumulation of RIPK1 and RIPK3 proteins and potentiation of necroptosis.

Cell Death Dis 2018 05 1;9(5):476. Epub 2018 May 1.

Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, MD, USA.

Necroptosis, a regulated necrosis pathway mediated by the receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3), is induced following spinal cord injury (SCI) and thought to contribute to neuronal and glial cell death. However, mechanisms leading to activation of necroptosis after SCI remain unclear. We have previously shown that autophagy, a catabolic pathway facilitating degradation of cytoplasmic proteins and organelles in a lysosome-dependent manner, is inhibited following SCI in rats. Our current data confirm that inhibition of autophagy also occurs after thoracic contusive SCI in the mouse model, as indicated by accumulation of both the autophagosome marker, LC3-II and autophagy cargo protein, p62/SQSTM1. This was most pronounced in the ventral horn neurons and was caused by rapid inhibition of lysosomal function after SCI. Interestingly, RIPK1, RIPK3, and the necroptosis effector protein MLKL also rapidly accumulated after SCI and localized to neurons with disrupted autophagy, suggesting that these events may be related. To determine if lysosomal dysfunction could contribute to induction of necroptosis, we treated PC12 cells and primary rat cortical neurons with lysosomal inhibitors. This led to rapid accumulation of RIPK1 and RIPK3, confirming that they are normally degraded by the lysosomal pathway. In PC12 cells lysosomal inhibition also sensitized cells to necroptosis induced by tumor necrosis factor α (TNFα) and caspase inhibitor. Imaging studies confirmed that RIPK1 partially localized to lysosomes in both untreated and lysosomal inhibitor treated cells. Similarly, we detected presence of RIPK1, RIPK3 and MLKL in both cytosol and at lysosomes after SCI in vivo. Furthermore, stimulation of autophagy and lysosomal function with rapamycin treatment led to decreased accumulation of RIPK1 and attenuated cell death after SCI. These data suggest that lysosomal dysfunction after SCI may contribute to both inhibition of autophagy and sensitize cells to necroptosis by promoting RIPK1 and RIPK3 accumulation.
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http://dx.doi.org/10.1038/s41419-018-0469-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913300PMC
May 2018

Residential greenness and prevalence of major depressive disorders: a cross-sectional, observational, associational study of 94 879 adult UK Biobank participants.

Lancet Planet Health 2018 04 4;2(4):e162-e173. Epub 2018 Apr 4.

Department of Psychiatry, Oxford University, Warneford Hospital, Oxford, UK.

Background: Increased urbanisation and the associated reduced contact of individuals with natural environments have led to a rise in mental disorders, including depression. Residential greenness, a fundamental component of urban design, has been shown to reduce the public health burden of mental disorders. The present study investigates the association between residential green exposure and prevalence of major depressive disorders using a large and diverse cross-sectional dataset from the UK Biobank.

Methods: In this cross-sectional, observational, associational study, we used baseline data from the UK Biobank cohort of participants aged 37-73 years from across the UK. Environmental exposure data were derived from a modelled and linked built environment database. Residential greenness was assessed with a 0·5 m resolution Normalised Difference Vegetation Index, which is derived from spectral reflectance measurements in remotely sensed colour infrared data and measured within geocoded dwelling catchments. Other environment metrics included street-level movement density, terrain, and fine particulate exposures. A series of logistic models examined associations between residential greenness and odds of major depressive disorder after adjusting for activity-influencing environments and individual covariates.

Findings: Of 122 993 participants with data on major depressive disorder, the study analytical sample comprised 94 879 (77·1%) participants recruited across ten UK Biobank assessment centres between April 29, 2009, and Oct 1, 2010. A protective effect of greenness on depression was consistently observed, with 4·0% lower odds of major depressive disorder per interquartile increment in Normalised Difference Vegetation Index greenness (odds ratio 0·960, 95% CI 0·93-0·99; p=0·0044). Interaction analyses indicated that the beneficial effects of greenness were more pronounced among women, participants younger than 60 years, and participants residing in areas with low neighbourhood socioeconomic status or high urbanicity.

Interpretation: The results point to the benefits of well designed green environments on mental health. Further longitudinal studies are needed to decipher causal pathways. In the UK, policies aimed at optimising allocation and design of green spaces might help preserve psychological ecosystem services, thereby, improving the mental wellbeing of populations and enhancing the mental capital of cities.

Funding: University of Hong Kong, UK Biobank, and the UK Economic & Social Research Council.
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http://dx.doi.org/10.1016/S2542-5196(18)30051-2DOI Listing
April 2018

Do Transit-Oriented Developments (TODs) and Established Urban Neighborhoods Have Similar Walking Levels in Hong Kong?

Int J Environ Res Public Health 2018 03 20;15(3). Epub 2018 Mar 20.

College of Architecture and Landscape, Peking University, Beijing 100871, China.

A sharp drop in physical activity and skyrocketing obesity rate has accompanied rapid urbanization in China. The urban planning concept of transit-oriented development (TOD) has been widely advocated in China to promote physical activity, especially walking. Indeed, many design features thought to promote walking-e.g., mixed land use, densification, and well-connected street network-often characterize both TODs and established urban neighborhoods. Thus, it is often assumed that TODs have similar physical activity benefits as established urban neighborhoods. To verify this assumption, this study compared walking behaviors in established urban neighborhoods and transit-oriented new towns in Hong Kong. To address the limitation of self-selection bias, we conducted a study using Hong Kong citywide public housing scheme, which assigns residents to different housing estates by flat availability and family size rather than personal preference. The results show new town residents walked less for transportation purpose than urban residents. New town residents far from the transit station (800-1200 m) walked less for recreational purpose than TOD residents close to a rail transit station (<400 m) or urban residents. The observed disparity in walking behaviors challenges the common assumption that TOD and established urban neighborhoods have similar impact on walking behavior. The results suggest the necessity for more nuanced planning strategies, taking local-level factors into account to promote walking of TOD residents who live far from transit stations.
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http://dx.doi.org/10.3390/ijerph15030555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877100PMC
March 2018

Neighbourhood walkability and incidence of hypertension: Findings from the study of 429,334 UK Biobank participants.

Int J Hyg Environ Health 2018 04 3;221(3):458-468. Epub 2018 Feb 3.

Department of Psychiatry, Oxford University, Warneford Hospital, Oxford OX3 7JX, United Kingdom.

Background: With an estimated one billion hypertension cases worldwide, the role of the built environment in its prevention and control is still uncertain. The present study aims to examine the associations between neighbourhood walkability and hypertension in a large and diverse population-based cohort.

Materials And Methods: We examined the association between neighbourhood walkability and blood pressure outcomes for N = 429,334 participants drawn from the UK Biobank and aged 38-73 years. Neighbourhood walkability was objectively modelled from detailed building footprint-level data within multi-scale functional neighbourhoods (1.0-, 1.5- and 2.0-kilometer street catchments of geocoded dwelling). A series of linear and modified Poisson regression models were employed to examine the association between walkability and outcomes of diastolic blood pressure (DBP in mmHg), systolic blood pressure (SBP in mmHg) and prevalent hypertension adjusting for socio-demographic, lifestyle and related physical environmental covariates. We also examined the relationship between walkability and change in blood pressure for a sub-sample of participants with follow-up data and tested for interaction effects of age, sex, employment status, neighbourhood SES, residential density and green exposure.

Results: Neighbourhood walkability within one-kilometer street catchment was beneficially associated with all the three blood pressure outcomes, independent of all other factors. Each interquartile increment in walkability was associated with the lower blood pressure outcomes of DBP (β = -0.358, 95% CI: -0.42, -0.29 mmHg), SBP (β = -0.833, 95% CI: -0.95, -0.72 mmHg) as well as reduced hypertension risk (RR = 0.970, 95% CI: 0.96, 0.98). The results remained consistent across spatial and temporal scales and were sensitive to sub-groups, with pronounced protective effects among female participants, those aged between 50 and 60 years, in employment, residing in deprived, high density and greener areas.

Conclusion: This large population-based cohort found evidence of protective association between neighbourhood walkability and blood pressure outcomes. Given the enduring public health impact of community design on individual behaviour and lifestyle, of particular interest, are the targetted upstream-level interventions in city design aimed at optimizing walkability. Further long term studies are required to assess its sustained effects upon hypertension prevention and control.
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http://dx.doi.org/10.1016/j.ijheh.2018.01.009DOI Listing
April 2018

Exploring the Impacts of Housing Condition on Migrants' Mental Health in Nanxiang, Shanghai: A Structural Equation Modelling Approach.

Int J Environ Res Public Health 2018 Jan 29;15(2). Epub 2018 Jan 29.

Department of Architecture and Civil Engineering, City University of Hong Kong, Hong Kong, China.

Although rapid urbanization and associated rural-to-urban migration has brought in enormous economic benefits in Chinese cities, one of the negative externalities include adverse effects upon the migrant workers' mental health. The links between housing conditions and mental health are well-established in healthy city and community planning scholarship. Nonetheless, there has thusfar been no Chinese study deciphering the links between housing conditions and mental health accounting for macro-level community environments, and no study has previously examined the nature of the relationships in locals and migrants. To overcome this research gap, we hypothesized that housing conditions may have a direct and indirect effects upon mental which may be mediated by neighbourhood satisfaction. We tested this hypothesis with the help of a household survey of 368 adult participants in Nanxiang Town, Shanghai, employing a structural equation modeling approach. Our results point to the differential pathways via which housing conditions effect mental health in locals and migrants. For locals, housing conditions have direct effects on mental health, while as for migrants, housing conditions have indirect effects on mental health, mediated via neighborhood satisfaction. Our findings have significant policy implications on building an inclusive and harmonious society. Upstream-level community interventions in the form of sustainable planning and designing of migrant neighborhoods can promote sense of community, social capital and support, thereby improving mental health and overall mental capital of Chinese cities.
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http://dx.doi.org/10.3390/ijerph15020225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858294PMC
January 2018

The relationship between alcohol use and long-term cognitive decline in middle and late life: a longitudinal analysis using UK Biobank.

J Public Health (Oxf) 2018 06;40(2):304-311

Department of Psychiatry, University of Oxford, Oxford, UK.

Background: Using UK Biobank data, this study sought to explain the causal relationship between alcohol intake and cognitive decline in middle and older aged populations.

Methods: Data from 13 342 men and women, aged between 40 and 73 years were used in regression analysis that tested the functional relationship and impact of alcohol on cognitive performance. Performance was measured using mean reaction time (RT) and intra-individual variation (IIV) in RT, collected in response to a perceptual matching task. Covariates included body mass index, physical activity, tobacco use, socioeconomic status, education and baseline cognitive function.

Results: A restricted cubic spline regression with three knots showed how the linear (β1 = -0.048, 95% CI: -0.105 to -0.030) and non-linear effects (β2 = 0.035, 95% CI: 0.007-0.059) of alcohol use on mean RT and IIV in RT (β1 = -0.055, 95% CI: -0.125 to -0.034; β2 = 0.034, 95% CI: 0.002-0.064) were significant adjusting for covariates. Cognitive function declined as alcohol use increased beyond 10 g/day. Decline was more apparent as age increased.

Conclusions: The relationship between alcohol use and cognitive function is non-linear. Consuming more than one UK standard unit of alcohol per day is detrimental to cognitive performance and is more pronounced in older populations.
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http://dx.doi.org/10.1093/pubmed/fdx186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051452PMC
June 2018

Residential greenness and adiposity: Findings from the UK Biobank.

Authors:
Chinmoy Sarkar

Environ Int 2017 09 25;106:1-10. Epub 2017 May 25.

Healthy High Density Cities Lab, HKUrbanLab, University of Hong Kong, Knowles Building, Pokfulam Road, Hong Kong. Electronic address:

Background: With the rapid urbanization and prevailing obesity pandemic, the role of residential green exposures in obesity prevention has gained renewed focus. The study investigated the effects of residential green exposures on adiposity using a large and diverse population sample drawn from the UK Biobank.

Materials And Methods: This was a population based cross-sectional study of 333,183 participants aged 38-73years with individual-level data on residential greenness and built environment exposures. Residential greenness was assessed through 0.50-metre resolution normalized difference vegetation index (NDVI) derived from spectral reflectance measurements in remotely sensed colour infrared data and measured around geocoded participants' dwelling. A series of continuous and binary outcome models examined the associations between residential greenness and markers of adiposity, expressed as body-mass index (BMI) in kg/m, waist circumference (WC) in cm, whole body fat (WBF) in kg and obesity (BMI≥30kg/m) after adjusting for other activity-influencing built environment and individual-level confounders. Sensitivity analyses involved studying effect modification by gender, age, urbanicity and SES as well as examining relationships between residential greenness and active travel behaviour.

Results: Residential greenness was independently and consistently associated with lower adiposity, the association being robust to adjustments. An interquartile increment in NDVI greenness was associated with lower BMI (β=-0.123kg/m, 95% CI: -0.14, -0.10kg/m), WC (β=-0.551cm, 95% CI: -0.61, -0.50cm), and WBF (β=-0.138kg, 95% CI: -0.18, -0.10kg) as well as a reduced relative risk of obesity (RR=0.968, 95% CI: 0.96, 0.98). Residential greenness was beneficially related with active travel, being associated with higher odds of using active mode for non-work travel (OR=1.093, 95% CI: 1.08, 1.11) as well as doing >30min walking (OR=1.039, 95% CI: 1.03, 1.05).

Conclusion: Residing in greener areas was associated with healthy weight outcomes possibly through a physical activity-related mechanism. Green allocation and design may act as upstream-level public health interventions ameliorating the negative health externalities of obesogenic urban environments. Further prospective studies are needed to identify potential causal pathways and thereby effectively guide such interventions.
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http://dx.doi.org/10.1016/j.envint.2017.05.016DOI Listing
September 2017