Associations of Particulate Matter Exposures With Brain Gray Matter Thickness and White Matter Hyperintensities: Effect Modification by Low-Grade Chronic Inflammation.

BACKGROUND: Numerous studies have shown the effect of particulate matter exposure on brain imaging markers. However, little evidence exists about whether the effect differs by the level of low-grade chronic systemic inflammation. We investigated whether the level of c-reactive protein (CRP, a marker of systemic inflammation) modifies the associations of particulate matter exposures with brain cortical gray matter thickness and white matter hyperintensities (WMH). METHODS: We conducted a cross-sectional study of baseline data from a prospective cohort study including adults with no dementia or stroke. Long-term concentrations of particulate matter ≤ 10 µm in diameter (PM10) and ≤ 2.5 µm (PM2.5) at each participant's home address were estimated. Global cortical thickness (n = 874) and WMH volumes (n = 397) were estimated from brain magnetic resonance images. We built linear and logistic regression models for cortical thickness and WMH volumes (higher versus lower than median), respectively. Significance of difference in the association between the CRP group (higher versus lower than median) was expressed as P for interaction. RESULTS: Particulate matter exposures were significantly associated with a reduced global cortical thickness only in the higher CRP group among men (P for interaction = 0.015 for PM10 and 0.006 for PM2.5). A 10 µg/m3 increase in PM10 was associated with the higher volumes of total WMH (odds ratio, 1.78; 95% confidence interval, 1.07-2.97) and periventricular WMH (2.00; 1.20-3.33). A 1 µg/m3 increase in PM2.5 was associated with the higher volume of periventricular WMH (odds ratio, 1.66; 95% confidence interval, 1.08-2.56). These associations did not significantly differ by the level of high sensitivity CRP. CONCLUSION: Particulate matter exposures were associated with a reduced global cortical thickness in men with a high level of chronic inflammation. Men with a high level of chronic inflammation may be susceptible to cortical atrophy attributable to particulate matter exposures.

All-Cause and Cause-Specific Mortality Attributable to Seasonal Influenza: A Nationwide Matched Cohort Study.

BACKGROUND: Although influenza poses substantial mortality burden, most studies have estimated excess mortality using time-aggregated data. Here, we estimated mortality risk and population attributable fraction (PAF) attributed to seasonal influenza using individual-level data from a nationwide matched cohort. METHODS: Individuals with influenza during four consecutive influenza seasons (2013-2017) (n = 5,497,812) and 1:4 age- and sex-matched individuals without influenza (n = 20,990,683) were identified from a national health insurance database. The endpoint was mortality within 30 days after influenza diagnosis. All-cause and cause-specific mortality risk ratios (RRs) attributed to influenza were estimated. Excess mortality, mortality RR, and PAF of mortality were determined, including for underlying disease subgroups. RESULTS: Excess mortality rate, mortality RR, and PAF of all-cause mortality were 49.5 per 100,000, 4.03 (95% confidence interval [CI], 3.63-4.48), and 5.6% (95% CI, 4.5-6.7%). Cause-specific mortality RR (12.85; 95% CI, 9.40-17.55) and PAF (20.7%; 95% CI, 13.2-27.0%) were highest for respiratory diseases. In subgroup analysis according to underlying disorders, PAF of all-cause mortality was 5.9% (95% CI, 0.6-10.7%) for liver disease, 5.8% (95% CI, 2.9-8.5%) for respiratory disease, and 3.8% (95% CI, 1.4-6.1%) for cancer. CONCLUSION: Individuals with influenza had a 4-fold higher mortality risk than individuals without influenza. Preventing seasonal influenza may lead to 5.6% and 20.7% reductions in all-cause and respiratory mortality, respectively. Individuals with respiratory disease, liver disease, and cancer may benefit from prioritization when establishing influenza prevention strategies.

Reduced brain subcortical volumes in patients with glaucoma: a pilot neuroimaging study using the region-of-interest-based approach.

BACKGROUND: While numerous neuroimaging studies have demonstrated that glaucoma is associated with smaller volumes of the visual cortices in the brain, only a few studies have linked glaucoma with brain structures beyond the visual cortices. Therefore, the objective of this study was to compare brain imaging markers and neuropsychological performance between individuals with and without glaucoma. METHODS: We identified 64 individuals with glaucoma and randomly selected 128 age-, sex-, and education level-matched individuals without glaucoma from a community-based cohort. The study participants underwent 3 T brain magnetic resonance imaging and neuropsychological assessment battery. Regional cortical thickness and subcortical volume were estimated from the brain images of the participants. We used a linear mixed model after adjusting for potential confounding variables. RESULTS: Cortical thickness in the occipital lobe was significantly smaller in individuals with glaucoma than in the matched individuals (ß = - 0.04 mm, P = 0.014). This did not remain significant after adjusting for cardiovascular risk factors (ß = - 0.02 mm, P = 0.67). Individuals with glaucoma had smaller volumes of the thalamus (ß = - 212.8 mm3, P = 0.028), caudate (ß = - 170.0 mm3, P = 0.029), putamen (ß = - 151.4 mm3, P = 0.051), pallidum (ß = - 103.6 mm3, P = 0.007), hippocampus (ß = - 141.4 mm3, P = 0.026), and amygdala (ß = - 87.9 mm3, P = 0.018) compared with those without glaucoma. Among neuropsychological battery tests, only the Stroop color reading test  score was significantly lower in individuals with glaucoma compared with those without glaucoma (ß = - 0.44, P = 0.038). CONCLUSIONS: We found that glaucoma was associated with smaller volumes of the thalamus, caudate, putamen, pallidum, amygdala, and hippocampus.

Induced Circular Dichroism of Jet-Cooled Phenol Complexes with (R)-(-)-2-Butanol.

The induced circular dichroism (ICD) of phenol complexed with (R)-(-)-2-butanol [PhOH-(-)BOH] in a supersonic jet is investigated using resonant two-photon ionization circular dichroism (R2PICD) spectroscopy. The R2PICD spectrum of PhOH-(-)BOH exhibits nonzero ICD bands near the absorption region of bare PhOH, where (-)BOH is transparent. Two different conformers containing a single hydrogen bond between PhOH and (-)BOH are identified using ultraviolet-ultraviolet hole-burning and infrared ion-dip spectroscopy combined with quantum theoretical calculations. The ICD values of the two conformers are similar to each other. To understand these similar ICD effects of the conformers, the geometrical asymmetry of the PhOH moiety bound to (-)BOH and the coupling strength of the electric transition dipole moments between PhOH and (-)BOH are estimated. Comparing the ICD values of PhOH-(-)BOH with those of PhOH-(-)-l-methyl lactate in the previous report [ Hong , A. ; J. Phys. Chem. Lett. 2018 , 9 , 476 -480 ], we investigate the physical properties that may govern the differences of the ICD values between the two complexes.

Fluorescence-detected circular dichroism spectroscopy of jet-cooled ephedrine.

The resonant two-photon ionization circular dichroism (R2PICD) spectrum represents the cumulative circular dichroism (CD) of one-photon excitation and the subsequent one-photon ionization, whereas the fluorescence-detected circular dichroism (FDCD) spectra exhibit only the CD of one-photon excitation, similar to conventional CD spectra. We obtained the FDCD spectra of jet-cooled ephedrine (EPD) near the origin band of the S0-S1 transition to measure the CD of one-photon absorption and thus the CD of the ionization process in R2PI in comparison with the R2PICD spectra. The CD effects of the ionization following excitation of the A (0-0) and C (930 cm(-1)) bands in the spectrum are small, whereas those of the B band (530 cm(-1)) are anomalously large, leading to opposite CD signs for the FDCD and R2PICD spectra. Based on the intermediate state-selective fragmentation patterns in the R2PI spectra, this large CD effect is attributed to the state-selective isomerization that occurs after excitation of the B band. By comparing the experimental and theoretical spectra, we determined that the B band corresponds to an asymmetric ring distortion mode that involves torsional motions of the side chain, which may facilitate the isomerization process. This study demonstrates that FDCD spectroscopy combined with R2PICD spectroscopy provides a powerful tool to measure the CD effects of the excitation and ionization processes separately in R2PI and thus probe the structural changes that occur during the ionization process following excitation to an intermediate state.

Physical Activity-Induced Modification of the Association of Long-Term Air Pollution Exposure with the Risk of Depression in Older Adults.

PURPOSE: Evidence suggests that long-term air pollution exposures may induce depression; however, the influence of physical activity on this effect is unclear. We investigated modification of the associations between air pollution exposures and depression by the intensity of physical activity. MATERIALS AND METHODS: This cross-sectional study included 1454 Korean adults. Depression was defined as a Geriatric Depression Scale score ≥8. Concentrations of particulate matter (PM10 and PM2.5: diameter ≤10 µm and ≤2.5 µm, respectively) and nitrogen dioxide (NO2) level at each participant's residential address were estimated. Based on metabolic equivalents, physical activity intensity was categorized as inactive, minimally active, or health-enhancing physical activity (HEPA). RESULTS: Each 1-part per billion (ppb) NO2 concentration increase was significantly associated with a 6% [95% confidence interval (CI), 4%-8%] increase in depression risk. In older adults (≥65 years), a 1-ppb NO2 increase was associated (95% CI) with a 4% (1%-7%), 9% (5%-13%), and 21% (9%-33%) increase in depression risk in the inactive, minimally active, and HEPA groups, respectively. Compared with the inactive group, the minimally active (p=0.039) and HEPA groups (p=0.004) had higher NO2 exposure-associated depression risk. Associations of PM10 and PM2.5 with depression did not significantly differ by the intensity of physical activity. CONCLUSION: We suggest that older adults who vigorously exercise outdoors may be susceptible to air pollution-related depression.

Alzheimer's disease-like cortical atrophy mediates the effect of air pollution on global cognitive function.

Little is known about the effect of air pollution on Alzheimer's disease (AD)-specific brain structural pathologies. There is also a lack of evidence on whether this effect leads to poorer cognitive function. We investigated whether, and the extent to which, AD-like cortical atrophy mediated the association between air pollution exposures and cognitive function in dementia-free adults. We used cross-sectional data from 640 participants who underwent brain magnetic resonance imaging and the Montreal Cognitive Assessment (MoCA). Mean cortical thickness (as the measure of global cortical atrophy) and machine learning-based AD-like cortical atrophy score were estimated from brain images. Concentrations of particulate matter with diameters ≤ 10 µm (PM10) and ≤ 2.5 µm (PM2.5) and nitrogen dioxide (NO2) were estimated based on each participant's residential address. Following the product method, a mediation effect was tested by conducting a series of three regression analyses (exposure to outcome; exposure to mediator; and exposure and mediator to outcome). A 10 µg/m3 increase in PM10 (ß = -1.13; 95 % CI, -1.73 to -0.53) and a 10 ppb increase in NO2 (ß = -1.09; 95 % CI, -1.40 to -0.78) were significantly associated with a lower MoCA score. PM10 (ß = 0.27; 95 % CI, 0.06 to 0.48) and NO2 (ß = 0.35; 95 % CI, 0.25 to 0.45) were significantly associated with an increased AD-like cortical atrophy score. Effects of PM10 and NO2 on MoCA scores were significantly mediated by mean cortical thickness (proportions mediated: 25 %-28 %) and AD-like cortical atrophy scores (13 %-16 %). The findings suggest that air pollution exposures may induce AD-like cortical atrophy, and that this effect may lead to poorer cognitive function in dementia-free adults.

The Incidence and Risk Factors of Renal Insufficiency among Korean HIV infected Patients: The Korea HIV/AIDS Cohort Study.

Renal insufficiency is one of the common issues in people living with human immunodeficiency virus (PLHIV). We studied the incidence and risk factors for renal insufficiency in male PLHIV using the Korea HIV/acquired immunodeficiency syndrome (AIDS) Cohort Study. Among the 830 enrolled patients, 32 (3.9%) cases of renal insufficiency occurred over 9576 patient-years of follow-up. The incidence of renal insufficiency in HIV-infected men in this study was 3.3 per 1000 patient-years. Diabetes mellitus, dyslipidemia, tenofovir or non-nucleoside reverse transcriptase inhibitor exposure for >1 year, and AIDS-defining illness were risk factors for renal insufficiency.

Cohort profile: the Environmental-Pollution-Induced Neurological EFfects (EPINEF) study: a multicenter cohort study of Korean adults.

The general population is exposed to numerous environmental pollutants, and it remains unclear which pollutants affect the brain, accelerating brain aging and increasing the risk of dementia. The Environmental-Pollution-Induced Neurological Effects study is a multi-city prospective cohort study aiming to comprehensively investigate the effect of different environmental pollutants on brain structures, neuropsychological function, and the development of dementia in adults. The baseline data of 3,775 healthy elderly people were collected from August 2014 to March 2018. The eligibility criteria were age ≥50 years and no self-reported history of dementia, movement disorders, or stroke. The assessment included demographics and anthropometrics, laboratory test results, and individual levels of exposure to air pollution. A neuroimaging sub-cohort was also recruited with 1,022 participants during the same period, and brain magnetic resonance imaging and neuropsychological tests were conducted. The first follow-up environmental pollutant measurements will start in 2022 and the follow-up for the sub-cohort will be conducted every 3-4 years. We have found that subtle structural changes in the brain may be induced by exposure to airborne pollutants such as particulate matter 10 µm or less in diameter (PM10), particulate matter 2.5 µm or less in diameter (PM2.5) and Mn10, manganese in PM10; Mn2.5, manganese in PM2.5. PM10, PM2.5, and nitrogen dioxide in healthy adults. This study provides a basis for research involving large-scale, long-term neuroimaging assessments in community-based populations.

The effect of body fatness on regional brain imaging markers and cognitive function in healthy elderly mediated by impaired glucose metabolism.

Brain atrophy is related to vascular risk factors and can increase cognitive dysfunction risk. This community-based, cross-sectional study investigated whether glucose metabolic disorders due to body fatness are linked to regional changes in brain structure and a decline in neuropsychological function in cognitively healthy older adults. From 2016 to 2019, 429 participants underwent measurements for cortical thickness and subcortical volume using 3 T magnetic resonance imaging and for cognitive function using the neuropsychological screening battery. The effects of body fatness mediated by impaired glucose metabolism on neuroimaging markers and cognitive function was investigated using partial least square structural equation modeling. Total grey matter volume (ß = -0.020; bias-corrected (BC) 95% confidence interval (CI) = -0.047 to -0.006), frontal (ß = -0.029; BC 95% CI = -0.063 to -0.005) and temporal (ß = -0.022; BC 95% CI = -0.051 to -0.004) lobe cortical thickness, and hippocampal volume (ß = -0.029; BC 95% CI = -0.058 to -0.008) were indirectly related to body fatness. Further, frontal/temporal lobe thinning was associated with recognition memory (ß = -0.005; BC 95% CI = -0.012 to -0.001/ß = -0.005; BC 95% CI = -0.013 to -0.001) and delayed recall for visual information (ß = -0.005; BC 95% CI = -0.013 to -0.001/ß = -0.005; BC 95% CI = -0.013 to -0.001). Additionally, the smaller the hippocampal volume, the lower the score in recognition memory (ß = -0.005; BC 95% CI = -0.012 to -0.001), delayed recall for visual information (ß = -0.005; BC 95% CI = -0.012 to -0.001), and verbal learning (ß = -0.008; BC 95% CI = -0.017 to -0.002). Our findings indicate that impaired glucose metabolism caused by excess body fatness affects memory decline as well as regional grey matter atrophy in elderly individuals with no neurological disease.

Estimating the disease burden of lung cancer attributable to residential radon exposure in Korea during 2006-2015: A socio-economic approach.

Estimating the lung cancer disease burden can provide evidence for public health practitioners, researchers, and policymakers. This study uses claim data from lung cancer patients for 2006-2015 from the Korean National Health Insurance Service to estimate the lung cancer burdens attributable to residential radon in Korea using disability-adjusted life years (DALY) and patients' annual economic burden with societal perspectives using the cost-of-illness (COI) method. The number of patients increased during our study period (from 35,866 to 59,168). The disease burden and that attributable to residential radon, respectively, increased from 517.57 to 695.74 and 64.62 (95%; CIs 61.33-67.69) to 86.99 (95%; CIs 82.7-91.1) DALYs per 100,000 patients. The percentage of years lost due to disability among the DALY doubled from 8% to 17%. The cost for all the patients was US$2.33 billion, with US$292 (95%; CIs 278-306) million attributable to residential radon. During the last decade, the lung cancer disease burden increased by 1.34 times, with a doubled percentage of non-fatal burden and average annual growth rate of 9.5% of the total cost. Hence, the burden and cost of lung cancer in Korean provinces have been steadily increasing. The findings could be used as input data for future cost-effectiveness analysis of policies regarding radon reduction.

Association between exposure to polycyclic aromatic hydrocarbons and brain cortical thinning: The Environmental Pollution-Induced Neurological EFfects (EPINEF) study.

BACKGROUND: Although some studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) induces neurodevelopmental disturbances in children and neurodegeneration in animals, the neurotoxic effect of PAH exposure is unclear in adults. The aim was to examine the associations of PAH exposure with brain structure and neuropsychological function in adults without known neurological diseases. METHODS: This study included 421 men and 528 women dwelling in four cities in the Republic of Korea. Urinary concentrations of four PAH metabolites (1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, and 2-hydroxyfluorene) were obtained. Participants underwent brain 3 T magnetic resonance imaging and neuropsychological tests. Cortical thickness and volume were estimated using the region-of-interest method. Separate generalized linear models were constructed for each sex, adjusting for age, years of education, cohabitation status, income, tobacco use, alcohol consumption, and vascular risk factors. RESULTS: The mean (standard deviation) age was 68.3 (6.6) years in men and 66.4 (6.1) years in women. In men, those in quartile 4 (versus quartile 1, the lowest) of urinary 2-naphthol concentration had cortical thinning in the global (ß = -0.03, P = .02), parietal (ß = -0.04, P = .01), temporal (ß = -0.06, P < .001), and insular lobes (ß = -0.05, P = .02). Higher quartiles of urinary 2-naphthol concentration were associated with cortical thinning in the global (P = .01), parietal (P = .004), temporal (P < .001), and insular lobes (P = .01). In women, those in quartile 4 (versus quartile 1) of urinary 1-hydroxypyrene concentration had cortical thinning in the frontal (ß = -0.03, P = .006) and parietal lobes (ß = -0.03, P = .003). Higher quartiles of urinary 1-hydroxypyrene concentration were associated with cortical thinning in the frontal (P = .006) and parietal lobes (P = .001). In both sexes, verbal learning and memory scores significantly declined with an increase in quartile of urinary 1-hydroxypyrene concentration. CONCLUSIONS: PAH exposure was associated with cortical thinning and decline in verbal learning and memory function in cognitively healthy adults. This suggests PAHs as an environmental risk factor for neurodegeneration.

Cohort Profile: Firefighter Research on the Enhancement of Safety and Health (FRESH), a Prospective Cohort Study on Korean Firefighters.

Firefighters have a high risk of developing cardiovascular and mental disorders due to their physical and chemical environments. However, in Korea, few studies have been conducted on environmental risk of firefighters. The Firefighter Research on the Enhancement of Safety and Health (FRESH) study aimed to discover the risk factors for cardiovascular disease and mental disorders among firefighters. Former and current firefighters were recruited from three university hospitals. A total of 1022 participants completed baseline health examinations from 2016 to 2017. All participants were scheduled for follow-ups every 2 years. Baseline health survey, laboratory testing of blood and urine samples, blood heavy metal concentration, urine polycyclic aromatic hydrocarbons (PAHs) metabolites, stress-related hormone test, natural killer cell activity, as well as physical and mental health examinations that focused on cardiovascular and mental disorders, were conducted. In addition, 3 Tesla (3T) brain magnetic resonance imaging (MRI) and neuropsychological tests were also performed to investigate structural and functional changes in the brains of 352 firefighters aged >40 years or new hires with less than 1 year of service.

Isomer-Specific Induced Circular Dichroism Spectroscopy of Jet-Cooled Phenol Complexes with (-)-Methyl l-Lactate.

Induced circular dichroism (ICD) is the CD observed in the absorption of an achiral molecule bound to a transparent chiral molecule through noncovalent interactions. ICD spectroscopy has been used to probe the binding between molecules, such as protein-ligand interactions. However, most ICD spectra have been measured in solution, which only exhibit the averaged CD values of all conformational isomers in solution. Here, we obtained the first isomer-selective ICD spectra by applying resonant two-photon ionization CD spectroscopy to jet-cooled phenol complexes with (-)-methyl l-lactate (PhOH-(-)ML). The well-resolved CD bands in the spectra were assigned to two conformers, which contained different types of hydrogen-bonding interactions between PhOH and (-)ML. The ICD values of the two conformers have different signs and magnitudes, which were explained by differences both in the geometrical asymmetries of PhOH bound to (-)ML and in the electronic coupling strengths between PhOH and (-)ML.

Electronic Circular Dichroism Spectroscopy of Jet-Cooled Phenylalanine and Its Hydrated Clusters.

We obtained resonant two-photon ionization circular dichroism (R2PICD) spectra of jet-cooled phenylalanine (Phe) and its hydrated clusters (Phe(H2O)n, n = 1-2) near the origin band of the S0-S1 transition. The R2PICD spectra of Phe exhibit well-resolved CD bands of six different conformers present in the jet, which vary in sign and magnitude depending on their conformations. We revised the previous structural assignments of the Phe conformers based on the comparison between the experimental and theoretical CD signs, infrared spectra, and rotational band contours. The R2PICD spectra of Phe(H2O)n reveal that hydration with one or two water molecule(s) does not affect the CD signs of Phe conformers but significantly increases their CD magnitudes. Furthermore, conformational selection by solvation alters relative populations of Phe conformers, leading to a sign inversion in the CD spectra of Phe(H2O)n compared with that of Phe monomer.