Association between physical activity changes and risk of incident ischemic stroke following cancer diagnosis: A nationwide retrospective cohort study.

BACKGROUND: Physical inactivity is prevalent after cancer treatment, which could increase ischemic stroke risk in cancer survivors. This study investigated the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. METHODS: Using data from the Korean National Health Insurance Service database, 269,943 cancer survivors (mean [SD] age, 56.3 [12.1] years; 45.7% male) with no history of cardiovascular disease were evaluated based on changes in physical activity from pre- to post-diagnosis. Using the Fine-Gray model, subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. RESULTS: After cancer diagnosis, 62.0% remained inactive, 10.1% remained active, 16.6% became active, and 11.4% became inactive. During a mean (SD) follow-up of 4.1 (2.0) years, being active both pre- and post-diagnosis was associated with a 15% decreased risk of ischemic stroke (sHR, 0.85; 95% CI, 0.75-0.96), compared with those who remained inactive. Cancer survivors who became active and inactive post-diagnosis showed a 16% and 11% lower ischemic stroke risk (sHR, 0.84; 95% CI, 0.75-0.93; sHR, 0.89; 95% CI, 0.79-0.99), respectively, than those who remained inactive. Analysis by the primary cancer site did not substantially differ from the main findings. CONCLUSIONS: Physical activity is associated with reduced ischemic stroke risk among cancer survivors. The potential benefits of physical activity are not limited to individuals who were physically active before cancer diagnosis, thus preventive strategies against ischemic stroke should emphasize physical activity throughout the cancer journey.

Higher Physical Activity is Associated with Reduced Lower Urinary Tract Symptoms in Korean Men.

PURPOSE: Identifying and managing risk factors for lower urinary tract symptoms (LUTS) is crucial because it impacts the quality of life of elderly individuals. Lifestyle factors, including physical activity (PA), and their relationship with LUTS have not been well studied. This objective of this study was to investigate the association between PA and LUTS. MATERIALS AND METHODS: A total of 7,296 men were included in this cross-sectional study. PA was quantified in metabolic equivalent (MET)-hours per week, and LUTS severity was assessed using the international prostate symptom score. Logistic regression was used to analyze the association between PA and LUTS, including voiding and storage symptoms. RESULTS: The average age of the participants was 57.8 years, and the prevalence of LUTS was 41.3%. After adjusting for potential confounders, PA was inversely associated with the prevalence and severity of moderate-to-severe LUTS, showing a dose-response pattern (all p for trend <0.01). Compared to the minimal activity group, which engaged in <5 MET-hours per week of PA, the odds ratios for moderate to severe LUTS were 0.83 (95% confidence interval [CI]: 0.72-0.97) for men engaging in 15-30 MET-hours per week, 0.82 (95% CI: 0.71-0.95) for 30-60 MET-hours per week, and 0.72 (95% CI: 0.62-0.84) for ≥60 MET-hours per week. The possible protective effect of PA was still observed in the additional analysis for voiding and storage symptoms showing the same dose-response pattern (all p for trend <0.01). CONCLUSIONS: A higher PA level was associated with a lower prevalence and severity of total, voiding, and storage LUTS in a dose-dependent manner in Korean men.

Trends in underweight and severe underweight disparities in Korean adults and older adults: a nationwide, repeated cross-sectional study.

OBJECTIVES: Little is known about the disparities in underweight prevalence among the general population in high-income countries. We investigated the trends in underweight prevalence and disparities across sociodemographic groups among Korean adults and older adults. SETTING AND PARTICIPANTS: A series of cross-sectional data on Korean national health checkups for adults aged ≥20 years were analyzed from 2005 to 2016. MEASUREMENTS: Based on body mass index (kg/m2), underweight was graded as mild (17.0-18.49), moderate (16.0-16.9), and severe (<16.0). Underweight prevalence was compared across sociodemographic subgroups in 2015-2016. Trends in underweight disparities were examined from 2005-2006 to 2015-2016. Multivariable-adjusted odds ratios (ORs; 95% confidence intervals, CIs) were calculated using logistic regression. RESULTS: Approximately 11-22 million adults were included in each wave. In 2015-2016, the overall prevalence of underweight was 3.6% (men 2.0%, women 5.2%); severe underweight was 0.2% (men 0.1%, women 0.3%). The prevalence of underweight varied by sex and age groups. In men, those aged ≥80 years had the highest prevalence (overall 7.33%, severe underweight 0.84%). In women, those aged 20-29 years had the highest prevalence of overall underweight (14.57%), whereas those aged ≥80 years had the highest prevalence of severe underweight (1.38%). Compared with individuals in the lowest income quartile, men in the highest income had lower ORs of overall (0.59, 95% CI 0.59-0.60) and severe underweight (0.46, 95% CI 0.44-0.48); women in the highest income quartile had a higher OR of overall (1.12, 95% CI 1.12-1.13) but a lower OR of severe underweight (0.89, 95% CI 0.86-0.92). From 2005-2006 to 2015-2016, severe underweight consistently declined in older men but remained constant in women aged ≥80 years, widening sex disparities among older adults. Severe underweight decreased or leveled off in the highest income quartile but steadily increased in the lowest quartile, worsening income disparities. CONCLUSION: In this nationwide study, underweight was more prevalent among women, older adults aged ≥80 years, and low-income individuals. Disparities in severe underweight widened across sociodemographic subgroups over time.

Association between Chronic Atrophic Gastritis and Bone Mineral Density among Women Older than 40 Years of Age in Korea.

Background: Chronic atrophic gastritis causes hypochlorhydria, hypergastrinemia, and malabsorption of nutrients, leading to lower bone mineral density. The few studies that investigated the association between chronic atrophic gastritis and bone mineral density have reported inconsistent findings. As such, the present study assessed the association between chronic atrophic gastritis and bone mineral density among a large sample of women >40 years of age in Korea. Methods: Data from 8,748 women >40 years of age who underwent esophagogastroduodenoscopy and bone densitometry were analyzed. Chronic atrophic gastritis was diagnosed using esophagogastroduodenoscopy. Bone mineral density of the lumbar vertebrae (L), femur neck, and femur total, measured using dual-energy X-ray absorptiometry, were the primary outcome variables. Low bone mineral density, which could be diagnosed as osteoporosis or osteopenia, was defined and analyzed as a secondary outcome. Linear regression was used to calculate adjusted mean values of bone mineral density. The association between low bone mineral density and chronic atrophic gastritis was analyzed using multiple logistic regression. Results: The adjusted mean bone mineral density for L1-L4 was 1.063±0.003, femur neck (0.826±0.002), and femur total (0.890±0.002) were significantly lower in patients with chronic atrophic gastritis than others (1.073±0.002, 0.836±0.001, 0.898±0.002, respectively; all P<0.01). Women with chronic atrophic gastritis exhibited an increased likelihood for osteopenia or osteoporosis, even after adjusting for age and other confounding factors (odds ratio, 1.25; 95% confidence interval, 1.13-1.40; P<0.01). However, subgroup analysis revealed statistical significance only in postmenopausal women (odds ratio, 1.27; P<0.001). Conclusion: Chronic atrophic gastritis was associated with lower bone mineral density and a higher risk for osteopenia or osteoporosis among postmenopausal women.

Feasibility and Effectiveness of a Ring-Type Blood Pressure Measurement Device Compared With 24-Hour Ambulatory Blood Pressure Monitoring Device.

BACKGROUNDS AND OBJECTIVES: This study aimed to evaluate the applicability and precision of a ring-type cuffless blood pressure (BP) measurement device, CART-I Plus, compared to conventional 24-hour ambulatory BP monitoring (ABPM). METHODS: Forty patients were recruited, and 33 participants were included in the final analysis. Each participant wore both CART-I Plus and ABPM devices on the same arm for approximately 24 hours. BP estimation from CART-I Plus, derived from photoplethysmography (PPG) signals, were compared with the corresponding ABPM measurements. RESULTS: The CART-I Plus recorded systolic blood pressure (SBP)/diastolic blood pressure (DBP) values of 131.4±14.1/81.1±12.0, 132.7±13.9/81.9±11.9, and 128.7±14.6/79.3±12.2 mmHg for 24-hour, daytime, and nighttime periods respectively, compared to ABPM values of 129.7±11.7/84.4±11.2, 131.9±11.6/86.3±11.1, and 124.5±13.6/80.0±12.2 mmHg. Mean differences in SBP/DBP between the two devices were 1.74±6.69/-3.24±6.51 mmHg, 0.75±7.44/-4.41±7.42 mmHg, and 4.15±6.15/-0.67±5.23 mmHg for 24-hour, daytime, and nighttime periods respectively. Strong correlations were also observed between the devices, with r=0.725 and r=0.750 for transitions in SBP and DBP from daytime to nighttime, respectively (both p<0.001). CONCLUSIONS: The CART-I Plus device, with its unique ring-type design, shows promising accuracy in BP estimation and offers a potential avenue for continuous BP monitoring in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06084065.

Association between serum uric acid level and bone mineral density in men more than 50 years of age.

Background: The results of previous studies on the association between serum uric acid levels and bone mineral density and the risk of osteoporosis are controversial. Fat free mass (FFM) is more strongly associated with bone mineral density (BMD) than it is with body fat mass (BFM). Skeletal muscle mass is assumed to contribute indirectly to the relationship between serum uric acid levels and BMD. Therefore, we aimed to evaluate the association between serum uric acid levels and BMD and abnormal BMD (at least osteopenia) by considering body composition in men aged ≥ 50 years. Methods: This was a retrospective observational cross-sectional study. We used data obtained from 2,991 men aged ≥50 years who completed questionnaires, anthropometric surveys, laboratory tests, and bone mineral density scans. A subgroup analysis of 1,135 men who additionally underwent body composition data analysis using Inbody® was performed. Multiple linear regression analysis was used to explore the relationship between serum uric acid levels and BMD at three sites (L1-L4, Femur neck, Femur total). In addition, multiple logistic regression analysis was performed to determine the association of serum uric acid levels with abnormal BMD (at least osteopenia). Results: Positive correlations between serum uric acid levels and BMD at the three sites (L1-L4, Femur neck, Femur total) were observed in unadjusted and fully adjusted models except the BMD of the femoral neck (P-value=0.054).Furthermore, FFM and skeletal muscle mass index (SMI) showed positive association with serum uric acid level and BMD at three sites, with statistical significance. An increase in serum uric acid level was associated with a lower risk of abnormal BMD after adjusting for confounders including FFM and SMI. Conclusion: Serum uric acid level was positively associated with BMD at three sites and had a protective effect against abnormal BMD after adjusting for multiple confounders, including FFM and SMI, in men aged ≥ 50 years.

Effects of the abdominal fat distribution on the relationship between exposure to air pollutants and thyroid hormones among Korean adult males.

BACKGROUND: Several significant associations between air pollution and thyroid function have been reported, but few studies have identified whether these associations differ by obesity, particularly its regional distribution. We assessed the relationship between ambient air pollution and thyroid hormone, and whether this relationship is modified by abdominal adiposity, as indicated by the waist circumference, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and visceral-to-subcutaneous fat ratio (VSR) in Korean men. METHODS: We included 2440 male adults in the final analysis and used each person's annual average exposure to four air pollutants: particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide, sulfur dioxide (SO2), and carbon monoxide (CO). Abdominal fat deposition was quantified by computed tomography. Serum thyrotropin (TSH) and free thyroxine (FT4) concentrations were measured for thyroid hormone. To evaluate the relationship between air pollution and thyroid hormone according to adiposity, we performed multiple linear regression analysis on the two subgroups stratified by abdominal fat level. RESULTS: Abdominal adiposity was significantly related to FT4 concentration. The exposures to air pollutants were associated with increased TSH and decreased FT4 concentrations. In stratified analysis using abdominal fat traits, ambient air pollution except for SO2 was significantly related to increased TSH and decreased FT4 concentrations in the high adiposity group (all p < 0.05), but not in the normal adiposity group. Among the air pollutants, PM10 showed an association with an increase of TSH concentration in all group with high adiposity, including high VAT, high SAT, and high VSR groups (all p < 0.05). In case of FT4, CO showed a similar pattern. Among the abdominal fat-related traits, the VSR in the high adiposity group had the largest effect on the relationship between exposure to air pollutants and thyroid hormone. CONCLUSIONS: This study suggests the first clue that the relationship between air pollution exposure and thyroid hormone differs according to abdominal fat distribution among Korean adult males.

Effect of anti-obesity agent HSG4112 on overweight and obese patients following 12 weeks of oral treatment: a study protocol for a randomised, double-blind, placebo-controlled, parallel-group, phase 2a clinical trial.

BACKGROUND: Glaceum Inc. has proposed HSG4112, a structural analogue of glabridin, as a novel anti-obesity compound. Animal studies and phase I human trials have shown that HSG4112 improves energy consumption, normalises weight, and is safe and drug-resistant. Based on these results, the company plans to conduct a phase 2a clinical trial to determine the safety and efficacy of HSG4112 in overweight and obese patients. METHODS: A 16-week randomised, double-blind, placebo-controlled, parallel-group trial will be conducted at five large hospitals in South Korea to assess the safety and efficacy of HSG4112 in overweight and obese patients. Participants who meet the inclusion/exclusion criteria will be assigned a subject number and randomly assigned to one of the four treatment groups (one group receiving a placebo) in a 1:1:1:1 ratio. The study's primary outcome will be to monitor the change in body weight (kg) from baseline to the end of treatment while monitoring safety and tolerability. DISCUSSION: This trial will evaluate the efficacy and safety of HSG4112 in overweight and obese adults. Upon proving the safety and effectiveness of the newly developed mechanism, it might significantly improve the perception of the product among medical personnel and obese patients. Furthermore, it may aid in managing chronic conditions that require long-term treatment. Trial registration: ClinicalTrials.gov, identifier [NCT05197556].

Exploring the Category and Use Cases on Digital Therapeutic Methodologies.

OBJECTIVES: As the Fourth Industrial Revolution advances, there is a growing interest in digital technology. In particular, the use of digital therapeutics (DTx) in healthcare is anticipated to reduce medical expenses. However, analytical research on DTx is still insufficient to fuel momentum for future DTx development. The purpose of this article is to analyze representative cases of different types of DTx from around the world and to propose a classification system. METHODS: In this exploratory study examining DTx interaction types and representative cases, we conducted a literature review and selected seven interaction types that were utilized in a large number of cases. Then, we evaluated the specific characteristics of each DTx mechanism by reviewing the relevant literature, analyzing their indications and treatment components. A representative case for each mechanism was provided. RESULTS: Cognitive behavioral therapy, distraction therapy, graded exposure therapy, reminiscence therapy, art therapy, therapeutic exercise, and gamification are the seven categories of DTx interaction types. Illustrative examples of each variety are provided. CONCLUSIONS: Efforts from both the government and private sector are crucial for success, as standardization can decrease both the expense and the time required for government-led DTx development. The private sector should partner with medical facilities to stimulate potential demand, carry out clinical research, and produce scholarly evidence.

A genome-wide by PM10 exposure interaction study for blood pressure in Korean adults.

Blood pressure (BP) is a typical complex trait, and the genetic susceptibility of individuals to changes in BP induced by air pollution exposure is different. Although interactions of exposure to air pollutants with several candidate genes have been identified, genome-wide interaction studies (GWISs) are needed to understand the association between them with BP. Therefore, we aimed to discover the unique genetic loci for BP that interact with exposure to air pollutants in Korean adults. We ultimately included 1868 participants in the discovery step and classified them into groups of those with low-to-moderate exposure and high exposure to average annual concentration of particulate matter with an aerodynamic diameter ≤ 10 µm (PM10). Because none of the single nucleotide polymorphisms (SNPs) achieved a genome-wide level of significance of pint < 5 × 10-8 for either systolic BP (SBP) or diastolic BP (DBP), we considered the top 10 ranking SNPs for each BP trait. To validate these suggestive SNPs, we finally selected six genetic variants for SBP and five variants for DBP, respectively. In a replication result for SBP, only one SNP (rs12914147) located in an intergenic region of the NR2F2 showed a significant interaction. We also identified several genetic susceptibility loci (e.g., CHST11, TEK, and ITGA1) implicated in candidate mechanisms such as inflammation and oxidative stress in the discovery step, although their interaction effects were not replicated. Our study reports the first GWIS finding to our knowledge, and the association between exposure to PM10 and BP levels may be determined in part by several newly discovered genetic suggestive loci, including NR2F2.

Diagnosis of Obesity: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The prevalence of obesity has consistently increased worldwide, and many obesity-related diseases are emerging as major health problems. Body mass index (BMI) is used to define obesity and is highly correlated with body fat mass. Moreover, obesity-related morbidities increase linearly with the increase in BMI. The Korean Society for the Study of Obesity defined overweight as a BMI ≥23 kg/m2 and obesity as a BMI ≥25 kg/m2, based on a significant increase in obesity-related diseases. A waist circumference of ≥90 cm in men and ≥85 cm in women are defined as abdominal obesity, which is also correlated with obesity-related diseases. These diagnostic criteria are the same as in the previous version; however, the updated guidelines put greater emphasis on the use of morbidity as the basis for obesity and abdominal obesity diagnoses. These new guidelines will help to identify and manage high-risk groups for obesity-related comorbidities among Korean adults.

Diagnosis of Obesity: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The prevalence of obesity has consistently increased worldwide, and many obesity-related diseases are emerging as major health problems. Body mass index (BMI) is used to define obesity and is highly correlated with body fat mass. Moreover, obesity-related morbidities increase linearly with the increase in BMI. The Korean Society for the Study of Obesity defined overweight as a BMI ≥23 kg/m2 and obesity as a BMI ≥25 kg/m2, based on a significant increase in obesity-related diseases. A waist circumference of ≥90 cm in men and ≥85 cm in women are defined as abdominal obesity, which is also correlated with obesity-related diseases. These diagnostic criteria are the same as in the previous version; however, the updated guidelines put greater emphasis on the use of morbidity as the basis for obesity and abdominal obesity diagnoses. These new guidelines will help to identify and manage high-risk groups for obesity-related comorbidities among Korean adults.

Inhibition of glutaminase 1 activity reverses airway hyperresponsiveness and decreases IL-1ß+ M1s and IL-17 producing ILC3s in high-fat diet-fed obese mice.

In obesity, disturbed glutamine metabolism contributes to enhanced inflammation by inducing alterations in immune cells. As macrophages and innate lymphoid cells (ILCs) are known to be involved in the pathogenesis of obesity-related asthma, we tested our hypothesis that altered glutamine metabolism may link obesity to airway hyperresponsivenss (AHR), a cardinal feature of asthma, focusing on these innate immune cells. Four-week-old male C57BL/6 mice were fed a high-fat diet (HFD) for 13 wk in the presence or absence of BPTES [Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide, a selective inhibitor of glutaminase 1 which converts glutamine to glutamate] and their blood, lung, and adipose tissues were analyzed. We then conducted in vitro experiments using bone marrow-derived macrophages (BMDMs) and mouse alveolar macrophage cell line. Furthermore, we investigated plasma glutamine and glutamate levels in obese and nonobese asthmatics. BPTES treatment prevented HFD-induced AHR and significantly decreased IL-1ß+ classically activated macrophages (M1s) and type 3 ILCs (ILC3s) which increased in the lungs of HFD-fed obese mice. In in vitro experiments, BPTES treatment or glutamine supplement significantly reduced the proportion of IL-1ß+NLRP3+ M1s in lipopolysaccharide-stimulated BMDMs and mouse alveolar macrophage cell line. BPTES treatment also significantly reduced the IL-17 producing ILC3s differentiated from ILCs in naïve mouse lung. In addition, plasma glutamate/glutamine ratios were significantly higher in obese asthmatics compared to nonobese asthmatics. Inhibition of glutaminolysis reverses AHR in HFD-induced obese mice and decreases IL-1ß + NLRP3+ M1s and IL-17 producing ILC3s, which suggests altered glutamine metabolism may have a role in the pathogenesis of obesity-related AHR.

Association of intraabdominal fat with the risk of incident chronic kidney disease according to body mass index among Korean adults.

BACKGROUND: The association between abdominal visceral adipose tissue and the risk of incident chronic kidney disease according to body mass index in the Asian population, remains unclear. We evaluated the impact of abdominal adiposity stratified by body mass index on the risk of incident chronic kidney disease. METHODS: A cohort study included 11,050 adult participants who underwent health check-ups and re-evaluated the follow-up medical examination at a single university-affiliated healthcare center. Cross-sectional abdominal adipose tissue areas were measured using computed tomography. The primary outcome was progression to chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73m2). The highest quartile of visceral adipose tissue was used for the cut-off of central obesity. RESULTS: During the mean of 5.6 follow-up years, 104 incident chronic kidney disease cases were identified. The risk for chronic kidney disease incidence was significantly increased in the 3rd and 4th quartile ranges of visceral adipose tissue [hazard ratio (95% confidence interval)]: 4.59 (1.48-14.30) and 7.50 (2.33-24.20), respectively. In the analysis stratified by body mass index, the chronic kidney disease incidence risk was increased in the highest quartile range of visceral adipose tissue in the normal weight group: 7.06 (1.35-37.04). However, there was no significant relationship between visceral adipose tissue and chronic kidney disease in the obese group. Compared to the subjects with normal weight and absent central obesity, the hazard ratio for chronic kidney disease incidence was 2.32 (1.26-4.27) among subjects with normal weight and central obesity and 1.81 (1.03-3.15) among subjects with obesity and central obesity. CONCLUSION: Visceral adipose tissue was a significant risk factor for subsequent chronic kidney disease progression, and the association was identified only in the normal weight group. Normal-weight central obesity was associated with excess risk of chronic kidney disease, similar to the risk in the group with obesity and central obesity.

Association of Body Shape Index with Cerebral Small Vessel Disease.

INTRODUCTION: A body shape index (ABSI) is an anthropometric index designed to reflect the influence of visceral fat. ABSI has been previously associated with various atherosclerosis, metabolic diseases, and cardiovascular diseases; however, relatively few studies have been conducted on cerebrovascular disease. In this study, we evaluated the association between ABSI and cerebral small vessel disease (cSVD) in health check-up participants. METHODS: We evaluated consecutive health check-up participants between January 2006 and December 2013. As subtypes of cSVD, we quantitatively measured the volume of white matter hyperintensity (WMH) and qualitatively measured the presence of silent brain infarct (SBI) and cerebral microbleed (CMB). ABSI was calculated according to the following formula: ABSI (m11/6/kg-2/3) = waist circumference (m)/(body mass index [kg/m2]2/3 × height [m]1/2). RESULTS: A total of 3,219 health check-up participants were assessed (median age, 56 years; male sex, 54.0%). In the multivariable analysis, ABSI was significantly associated with WMH volume (ß = 0.107, 95% confidence interval [CI] = 0.013-0.200), SBI (adjusted odds ratio [aOR] = 1.62, 95% CI = 1.14-2.31), and CMB (aOR = 1.64, 95% CI = 1.16-2.33) after adjusting for confounders (per 100 m11/6/kg-2/3). Furthermore, ABSI showed a dose-response relationship with the burden of each cSVD pathology. CONCLUSIONS: High ABSI was associated with a higher burden of cSVD in health check-up participants. As ABSI showed close associations with all subtypes of cSVD, visceral fat may be a common risk factor penetrating cSVD pathologies.

Allergic Diseases and Risk of Incident Dementia and Alzheimer's Disease.

OBJECTIVE: To examine the associations between the allergic triad (asthma, allergic rhinitis, atopic dermatitis) and risk of dementia. METHODS: Participants comprised 6,785,948 adults aged ≥40 years who participated in a national health examination in 2009 without any history of dementia before baseline. From 2009 to 2017, we prospectively investigated the associations between physician-diagnosed allergic diseases and risk of incident dementia (all-cause, Alzheimer's disease [AD], vascular dementia [VaD]) ascertained using national health insurance claims data. RESULTS: During 8.1 years of follow-up, 260,705 dementia cases (195,739 AD, 32,789 VaD) were identified. Allergic diseases were positively associated with dementia risk. Compared with individuals without allergic diseases, multivariable hazard ratios (HRs) of all-cause dementia were 1.20 (95% confidence interval [CI] 1.19-1.22) in those with asthma, 1.10 (95% CI 1.09-1.12) with allergic rhinitis, 1.16 (95% CI 1.11-1.21) with atopic dermatitis, and 1.13 (95% CI 1.12-1.14) with any of these allergies. Similarly, individuals with any of the allergic triad had a higher risk of AD (HR 1.16, 95% CI 1.14-1.17) and VaD (HR 1.04; 95% CI 1.01-1.06) than those without any allergic disease. As the number of comorbid allergic diseases increased, the risk of dementia increased linearly (Ptrend ≤ 0.002). Compared with individuals without allergies, those with all three allergic diseases had substantially increased risk of all-cause dementia (HR 1.54, 95% CI 1.35-1.75), AD (HR 1.46; 95% CI 1.25-1.70), and VaD (HR 1.99, 95% CI 1.44-2.75). INTERPRETATION: Asthma, allergic rhinitis, and atopic dermatitis were significantly associated with increased risk of all-cause dementia and subtypes, with dose-effect relationships with the severity of allergic diseases. ANN NEUROL 2023;93:384-397.

Association between long-term air pollution exposure and insulin resistance independent of abdominal adiposity in Korean adults.

Significant associations between air pollution (AP) and insulin resistance (IR) have been reported in limited populations or certain patient groups, but few studies have addressed this association in the general population, especially in Asians. Although abdominal fat is a major contributor to IR, previous studies have not fully controlled for its effect in the association between AP and IR. We investigated the association between exposure to AP and IR in Korean adults in the general population and whether this association is maintained even after controlling for the effects of abdominal fat, particularly visceral fat. This was a cross-sectional study. Data were obtained for Korean adults who participated in screening health checkups at Seoul National University Health Examination Center from 2006 to 2014. A total of 4251 men and women aged 22-84 years were included. IR was represented by the homeostasis model assessment of insulin resistance (HOMA-IR). Adiposity traits such as visceral adipose tissue (VAT) and subcutaneous adipose tissue areas were measured by computed tomography. We assessed the annual mean concentrations of air pollutants, including particulate matter with an aerodynamic diameter of 10 µm or less (PM10), nitrogen dioxide, sulfur dioxide, and carbon monoxide. HOMA-IR was significantly associated with increased annual mean exposure to PM10 in both men (ß = 0.15; 95% CI 0.09, 0.22) and women (ß = 0.16; 95% CI 0.09, 0.23), and these associations were maintained even after controlling for VAT area (both p < 0.05). The adjusted mean HOMA-IR increased gradually with the level of long-term PM10 exposure (low, intermediate, and high exposure) (all p for trend < 0.001) in the subgroup analysis. After adjusting for possible confounding factors, including VAT area, the annual mean exposure to PM10 was significantly associated with the presence of IR in both men (OR 1.18; 95% CI 1.03, 1.35) and women (OR 1.44; 95% CI 1.18, 1.76). Other air pollutants, such as NO2, SO2 and CO, did not show any significant associations with HOMA-IR or the presence of IR. Persistent exposure to PM10 is the main independent risk factor for IR and exhibits a dose-dependent association regardless of visceral fatness in both men and women.

Bifidobacterial carbohydrate/nucleoside metabolism enhances oxidative phosphorylation in white adipose tissue to protect against diet-induced obesity.

BACKGROUND: Comparisons of the gut microbiome of lean and obese humans have revealed that obesity is associated with the gut microbiome plus changes in numerous environmental factors, including high-fat diet (HFD). Here, we report that two species of Bifidobacterium are crucial to controlling metabolic parameters in the Korean population. RESULTS: Based on gut microbial analysis from 99 Korean individuals, we observed the abundance of Bifidobacterium longum and Bifidobacterium bifidum was markedly reduced in individuals with increased visceral adipose tissue (VAT), body mass index (BMI), blood triglyceride (TG), and fatty liver. Bacterial transcriptomic analysis revealed that carbohydrate/nucleoside metabolic processes of Bifidobacterium longum and Bifidobacterium bifidum were associated with protecting against diet-induced obesity. Oral treatment of specific commercial Bifidobacterium longum and Bifidobacterium bifidum enhanced bile acid signaling contributing to potentiate oxidative phosphorylation (OXPHOS) in adipose tissues, leading to reduction of body weight gain and improvement in hepatic steatosis and glucose homeostasis. Bifidobacterium longum or Bifidobacterium bifidum manipulated intestinal sterol biosynthetic processes to protect against diet-induced obesity in germ-free mice. CONCLUSIONS: Our findings support the notion that treatment of carbohydrate/nucleoside metabolic processes-enriched Bifidobacterium longum and Bifidobacterium bifidum would be a novel therapeutic strategy for reprograming the host metabolic homeostasis to protect against metabolic syndromes, including diet-induced obesity. Video Abstract.

Annual exposure to PM10 is related to cerebral small vessel disease in general adult population.

Ambient air pollution is one of the most important global health issues. Although several studies have been reported the associations between air pollution and brain function or structure, impact of the air pollution on cerebral small vessel disease (cSVD) have rarely been explored in Asian adult population. We evaluated the association between exposure to air pollutants and cSVD in Korean asymptomatic adults. This cross-sectional study included 3257 participants of a health screening program from January 2006 to December 2013. All participants performed brain magnetic resonance imaging. To assess the cSVD, we considered three features such as white matter hyperintensities (WMH), silent lacunar infarction (SLI), and cerebral microbleeds (CMBs). The annual average exposure to air pollutants [particulate matter ≤ 10 µm in aerodynamic diameter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO)] was generated. The mean [standard deviation (SD)] age of the total 3257 participants was 56.5 (9.5) years, and 54.0% of them were male. Among all the included participants, 273 (8.4%) had SLI and 135 (4.1%) had CMBs. The mean volume (± SD) of WMH was 2.72 ± 6.57 mL. In result of linear regression analysis, the volume of WMH was associated with various potential factors including age, height, weight, smoking and alcohol consumption status, blood pressure (BP), hypertension, and diabetes mellitus. SLI-positive group, compared to the SLI-negative group, was older, shorter, and had higher BP as well as higher frequency of hypertension and diabetes mellitus. After adjusting for covariates, the annual average concentration of PM10 was significantly associated with the volume of WMH [ß (95% CI) for Model 1 = 0.082 (0.038- 0.125), p < 0.001; ß (95% CI) for Model 2 = 0.060 (0.013, 0.107), p = 0.013]. CMBs were not associated with the annual average concentration of PM10. No significant associations of NO2, SO2, and CO with cSVD were observed. In conclusion, PM10 exposure is associated with significant increases in brain WMH' volume and silent lacunar infarcts in asymptomatic adults.

The Atherogenic Index of Plasma is Associated With Cerebral Small Vessel Disease: A Cross-Sectional Study.

Objective: Recently, the lipid profile of atherogenic dyslipidemia has become important in cerebrovascular diseases. Atherogenic index of plasma (AIP), an index that reflects this lipid profile as a single number, has been proposed, but there are still few related studies in cerebrovascular disease. In this study, we evaluated the relationship between AIP and cerebral small vessel disease (cSVD) in health check-up participants. Methods: We assessed consecutive health check-ups participants between 2006 and 2013. cSVD was measured including the following three subtypes: white matter hyperintensity (WMH), lacuens, and cerebral microbleeds (CMBs). WMH quantitatively measured the volume, and lacunes and CMBs qualitatively evaluated the presence. AIP was calculated according to the following formula based on blood test results: AIP=log [triglyceride (mg/dL)/high-density lipoprotein cholesterol (mg/dL)]. Results: A total of 3,170 participants were evaluated (mean age: 56.5 years, male sex: 53.8%). In multivariable linear regression analysis, AIP (ß=0.129, 95% confidence interval [CI]=0.003-0.255) was associated with WMH. Age, hypertension, diabetes, lipid-lowering agents, and intracranial atherosclerosis were also associated with WMH volume. In multivariable logistic regression analysis, AIP (adjusted odds ratio=1.72 1.79, 95% CI=1.03-2.90) showed close association with lacunes. Age and intracranial atherosclerosis were also related to lacunes. CMBs did not show a statistically significant association with AIP. Conclusion: High AIP was associated with cSVD in health check-up participants. Since this close relationship was only seen in WMH and lacunes, these subtypes may have arisen from a more atherosclerosis-related pathology.