Lactobacillus reuteri NCIMB 30242 (LRC) Inhibits Cholesterol Synthesis and Stimulates Cholesterol Excretion in Animal and Cell Models.

In this study, we evaluated the effects of Lactobacillus reuteri NCIMB (LRC™) supplementation on hypercholesterolemia by researching its effects on cellular cholesterol metabolism in hypercholesterolemic rats (KHGASP-22-170) and HepG2 cell line. Rats were separated into six groups after adaptation and were then fed a normal control (NC), a high-cholesterol diet (HC), or a HC supplemented with simvastatin 15 mg/kg body weight (positive control [PC]), LRC 1 × 109 colony-forming units (CFU)/rat/day, LRC 4 × 109 CFU/rat/day, or LRC 1 × 1010 CFU/rat/day (1 × 109, 4 × 109, or 1 × 1010). The rats were dissected to study the effects of LRC on cholesterol metabolism and intestinal excretion at the end of experimental period. We discovered that LRC mainly participated in the restraint of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the uptake of low-density lipoprotein (LDL) cholesterol into tissues, partially in the transport of cholesteryl esters into high density lipoprotein for maturation, and intestinal excretion of cholesterol. These results are supported by the expression of transcription factors and enzymes such as HMG-CoA reductase, SREBP2, CYP7A1, CETP, and LCAT in both messenger RNA (mRNA) and protein levels in serum and hepatic tissue. Furthermore, the LRC treatment in HepG2 significantly reduced the mRNA expression of HMG-CoA reductase, SREBP2, and CEPT and significantly increased the mRNA expression of LDL-receptor, LCAT, and CYP7A1 at all doses. Hence, we suggest that LRC supplementation could alleviate the serum cholesterol level by inhibiting the intracellular cholesterol synthesis, and augmenting excretion of intestinal cholesterol.

Antiobesity Effects of Lactobacillus paracasei Subsp. paracasei, L. casei 431 on High-Fat Diet-Induced Obese Rats.

Obesity is currently regarded as a global concern, and the key objectives of the global health strategy include its prevention and control. Probiotic supplementation can help achieve these objectives. This study aimed to assess whether a probiotic strain Lactobacillus paracasei ssp. paracasei, Lactobacillus casei 431 (henceforth, L. casei 431) possesses antiobesogenic properties. High-fat diet-induced obese Sprague-Dawley rats were treated with L. casei 431 for 10 weeks, and the outcomes were compared with those of rats treated with the antiobesity medication orlistat. Body weights, epididymal fat, and tissues from mice were assessed. Furthermore, serological and histological analyses were performed. Epididymal fat accumulation was significantly reduced in groups administered L. casei 431 and orlistat. Furthermore, L. casei 431 and orlistat treatments lowered serum alanine transaminase, aspartate aminotransferase, and triglyceride (TG) levels. Hematoxylin and eosin staining of the liver and epididymal adipose tissues showed that the L. casei 431-treated groups exhibited reduced lipid buildup and adipocyte size. Furthermore, sterol regulatory element-binding protein 1c, adipose TG lipase, and lipoprotein lipase messenger RNA (mRNA) levels were upregulated, leading to lipid oxidation and degradation, in L. casei 431-supplemented groups. Furthermore, carnitine palmitoyltransferase 1, a major factor in lipolysis, was consistently upregulated at the protein level after L. casei 431 administration. Collectively, these results demonstrate the potential of L. casei 431 in alleviating obesity in rats through optimizing lipid metabolism and some related biomarkers.

SH003 Causes ER Stress-mediated Apoptosis of Breast Cancer Cells via Intracellular ROS Production.

BACKGROUND/AIM: Breast cancer is one of the most common cancers in women all over the world and new treatment options are urgent. ER stress in cancer cells results in apoptotic cell death, and it is being proposed as a new therapeutic target. SH003, a newly developed herbal medicine, has been reported to have anti-cancer effects. However, its molecular mechanism is not yet clearly defined. MATERIALS AND METHODS: Microarray was performed to check the differential gene expression patterns in various breast cancer cell lines. Cell viability was measured by MTT assays to detect cytotoxic effects. Annexin V-FITC and 7AAD staining, TUNEL assay and DCF-DA staining were analyzed by flow cytometry to evaluate apoptosis and ROS levels, respectively. Protein expression was examined in SH003-breast cancer cells using immunoblotting assays. The expression of C/EBP Homologous Protein (CHOP) mRNA was measured by real-time PCR. The effects of CHOP by SH003 treatment were investigated using transfection method. RESULTS: Herein, we investigated the molecular mechanisms through which SH003 causes apoptosis of human breast cancer cells. Both cell viability and apoptosis assays confirmed the SH003-induced apoptosis of breast cancer cells. Meanwhile, SH003 altered the expression patterns of several genes in a variety of breast cancer cell lines. More specifically, it upregulated gene sets including the response to unfolded proteins, independently of the breast cancer cell subtype. In addition, SH003-induced apoptosis was due to an increase in ROS production and an activation of the ER stress-signaling pathway. Moreover, CHOP gene silencing blocked SH003-induced apoptosis. CONCLUSION: SH003 causes apoptosis of breast cancer cells by upregulating ROS production and activating the ER stress-mediated pathway. Thus, our findings suggest that SH003 can be a potential therapeutic agent for breast cancer.

Current status and trends of pulmonary rehabilitation in South Korea: National level data analysis using Health Insurance Review and Assessment Service (HIRA) database from 2016 to 2018.

In South Korea, there are few studies to understand the current status of pulmonary rehabilitation in clinical practice and develop it. This study aimed to assess the current status and annual changes in the number and pattern of prescriptions for pulmonary rehabilitation before and after its insurance coverage. The trends of pulmonary rehabilitation before and after its insurance coverage commencement were evaluated using the data of 24,380 patients during the 3-year period from 2016 to 2018 that were archived by the National Health Information Database of the Health Insurance Review and Assessment Service in South Korea. The annual total number of patients who received pulmonary rehabilitation was stratified by the type of prescription, sex, age, type of insurance, medical institution, and region. In addition, the frequencies of pulmonary rehabilitation for various diagnoses were investigated using the major codes of the Korean Standard Classification of Disease. The patients who received pulmonary rehabilitation increased by approximately 2 times from 5936 in 2016 (before insurance coverage) to 10,474 in 2019. Before 2017, most patients underwent simple pulmonary rehabilitation coded as MM290. However, since the insurance coverage of rehabilitation exercise for pulmonary disease (MM440), the proportions of patients receiving them increased. Men underwent pulmonary rehabilitation more often than women, and >70% of the patients were aged >60 years. Most patients received pulmonary rehabilitation at tertiary hospitals in Seoul. In 2016, pulmonary rehabilitation was prescribed more frequently for cerebral infarction; after 2017, it was prescribed more frequently for lung cancer. This study summarized the current status and trends of pulmonary rehabilitation in South Korea before and after National Health Insurance Service coverage, which commenced on January 1, 2017. A significant increase in the number of pulmonary rehabilitations was confirmed after the insurance coverage.

Complex regional pain syndrome type II caused by iatrogenic lateral dorsal cutaneous nerve injury: A case report.

RATIONALE: Complex regional pain syndrome (CRPS) is a painful condition classified as type I or II depending on the absence or presence of nerve injury, respectively. Injury to the lateral dorsal cutaneous nerve (LDCN), a branch of the sural nerve, is a rare occurrence observed after a sprain or procedures conducted on the lateral side of the ankle. PATIENT CONCERNS: A 38-year-old female, who had undergone prolotherapy for a sprain in the lateral side of the left ankle 3 months ago, presented with persistent causalgia and dysesthesia around the injection site. DIAGNOSIS: An electrodiagnostic study was conducted, which confirmed that the patient had peripheral neuropathy of the left LDCN. Considering the digital infrared thermal imaging and three-phase bone scan findings and the clinical presentation, the condition was diagnosed as CRPS type II due to iatrogenic LDCN injury according to the Budapest diagnostic criteria for CRPS. INTERVENTIONS: The patient was treated with steroid pulse therapy, physical therapy, and transcutaneous electrical nerve stimulation, as well as nonsteroidal anti-inflammatory drugs, pregabalin, and tricyclic antidepressants. OUTCOMES: After 1 month of treatment, allodynia of the left foot persisted, but the pain reduced from 6 points to 3 points on the numeric rating scale. Partial recovery of amplitude and conduction velocity was confirmed in the follow-up electrodiagnostic study. LESSONS: LDCN injury should be considered in patients who complain of persistent lateral ankle and foot paresthesia or pain after sprain or procedures performed on the lateral side of the ankle. Early diagnosis and treatment can lead to a good prognosis when the LDCN injury has progressed to CRPS.

Plasma-Induced Oxidation Products of (-)-Epigallocatechin Gallate with Digestive Enzymes Inhibitory Effects.

(-)-Epigallocatechin gallate (EGCG), the chief dietary constituent in green tea (Camellia sinensis), is relatively unstable under oxidative conditions. This study evaluated the use of non-thermal dielectric barrier discharge (DBD) plasma to improve the anti-digestive enzyme capacities of EGCG oxidation products. Pure EGCG was dissolved in an aqueous solution and irradiated with DBD plasma for 20, 40, and 60 min. The reactant, irradiated for 60 min, exhibited improved inhibitory properties against α-glucosidase and α-amylase compared with the parent EGCG. The chemical structures of these oxidation products 1-3 from the EGCG, irradiated with the plasma for 60 min, were characterized using spectroscopic methods. Among the oxidation products, EGCG quinone dimer A (1) showed the most potent inhibitory effects toward α-glucosidase and α-amylase with IC50 values of 15.9 ± 0.3 and 18.7 ± 0.3 µM, respectively. These values were significantly higher than that of the positive control, acarbose. Compound 1, which was the most active, was the most abundant in the plasma-irradiated reactant for 60 min according to quantitative high-performance liquid chromatography analysis. These results suggest that the increased biological capacity of EGCG can be attributed to the structural changes to EGCG in H2O, induced by cold plasma irradiation.

Coronary CT Angiography CAD-RADS versus Coronary Artery Calcium Score in Patients with Acute Chest Pain.

Background The Coronary Artery Disease Reporting and Data System (CAD-RADS) was established in 2016 to standardize the reporting of coronary artery disease at coronary CT angiography (CCTA). Purpose To assess the prognostic value of CAD-RADS at CCTA for major adverse cardiovascular events (MACEs) in patients presenting to the emergency department with chest pain. Materials and Methods This multicenter retrospective observational cohort study was conducted at four qualifying university teaching hospitals. Patients presenting to the emergency department with acute chest pain underwent CCTA between January 2010 and December 2017. Multivariable Cox regression analysis was used to evaluate risk factors for MACEs, including clinical factors, coronary artery calcium score (CACS), and CAD-RADS categories. The prognostic value compared with clinical risk factors and CACS was also assessed. Results A total of 1492 patients were evaluated (mean age, 58 years ± 14 years [standard deviation]; 759 men). During a median follow-up period of 31.5 months, 103 of the 1492 patients (7%) experienced MACEs. Multivariable Cox regression analysis showed that a moderate to severe CACS was associated with MACEs after adjusting for clinical risk factors (hazard ratio [HR] range, 2.3-4.4; P value range, <.001 to <.01). CAD-RADS categories from 3 to 4 or 5 (HR range, 3.2-8.5; P < .001) and high-risk plaques (HR = 3.6, P < .001) were also associated with MACEs. The C statistics revealed that the CAD-RADS score improved risk stratification more than that using clinical risk factors alone or combined with CACS (C-index, 0.85 vs 0.63 [P < .001] and 0.76 [P < .01], respectively). Conclusion The Coronary Artery Disease Reporting and Data System classification had an incremental prognostic value compared with the coronary artery calcium score in the prediction of major adverse cardiovascular events in patients presenting to the emergency department with acute chest pain. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Vliegenthart in this issue.

Atmospheric deposition of inorganic nutrients to the Western North Pacific Ocean.

We evaluated the potential impacts of atmospheric deposition on marine productivity and inorganic carbon chemistry in the northwestern Pacific Ocean (8-39°N, 125-157°E). The nutrient concentration in atmospheric total suspended particles decreased exponentially with increasing distance from the closest land-mass (Asia), clearly revealing anthropogenic and terrestrial contributions. The predicted mean depositional fluxes of inorganic nitrogen were approximately 34 and 15 µmol m-2 d-1 to the west and east of 140°E, respectively, which were at least two orders of magnitude greater than the inorganic phosphorus flux. On average, atmospheric particulate deposition would support 3-4% of the net primary production along the surveyed tracks, which is equivalent to ~2% of the dissolved carbon increment caused by the penetration of anthropogenic CO2. Our observations generally fell within the ranges observed over the past 18 years, despite an increasing trend of atmospheric pollution in the source regions during the same period, which implies high temporal and spatial variabilities of atmospheric nutrient concentration in the study area. Continued atmospheric anthropogenic nitrogen deposition may alter the relative abundances of nitrogen and phosphorus.

Association of anticoagulant therapy with risk of dementia among patients with atrial fibrillation.

AIMS: To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs). METHODS AND RESULTS: This observational, population-based cohort study enrolled 53 236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age: 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74-0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC. CONCLUSION: In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.

Acer tegmentosum Maxim Inhibits Adipogenesis in 3t3-l1 Adipocytes and Attenuates Lipid Accumulation in Obese Rats Fed a High-Fat Diet.

We investigated the effect of Acer tegmentosum Maxim (ATM) on adipocyte differentiation in 3T3-L1 cells and anti-obesity properties in obese rats fed a high-fat diet (HFD). Cellular lipid content in DMI (dexamethasone, 3-isobutyl-1-methylxanthine, and insulin mixture)-treated cells increased, while ATM treatment caused a significant reduction in lipid accumulation in differentiated 3T3-L1 cells. ATM (60 ug/mL) caused inhibition of adipogenesis via down-regulation of the CCAAT/enhancer binding protein ß (C/EBPß) (48%), C/EBPα (66%), and peroxisome proliferator-activated receptor γ (PPARγ) (64%) expressions in 3T3-L1 cells. Moreover, ATM induced a decrease in the expressions of adipocyte-specific genes, such as adipocyte fatty acid-binding protein-2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL). Protein kinase B (Akt) and glycogen synthase kinase 3ß (GSK3ß) phosphorylation was also decreased by ATM treatment of 3T3-L1 adipocytes. We investigated the anti-obesity effects of ATM on HFD-induced obese rats. Rats fed with an HFD demonstrated elevations in body weight gain, while the administration of ATM reversed body weight (BW) gains and adipose tissue weights in rats fed an HFD. ATM supplementation caused a decrease in the circulating triglyceride and total cholesterol levels and led to inhibition of lipid accumulation in the adipose tissues in HFD-induced obese rats. Epididymal fat exhibited significantly larger adipocytes in the HFD group than it did in the ATM-treated group. These results demonstrate that ATM administration caused a reduction in adiposity via attenuation in adipose tissue mass and adipocyte size.

Inhibitory effect of oolonghomobisflavan B on osteoclastogenesis by suppressing p38 MAPK activation.

Suppression of differentiation and/or function of osteoclasts is considered an effective therapeutic strategy for osteolytic bone diseases such as periodontitis and osteoporosis. Evidence regarding the health benefits of oolong tea consumption is accumulating, and tea polyphenols have various pharmacological properties such as anti-cancer and anti-diabetes effects. In this study, we investigated the effect of oolonghomobisflavan B (OFB), a polyphenolic compound in oolong tea, on osteoclast differentiation. OFB suppressed receptor activator of nuclear factor-κB (RANKL)-induced formation of tartate-resistant acid phosphatase-positive multinuclear cells without cytotoxicity. OFB also significantly attenuated p38 phosphorylation, which is essential for RANKL-induced osteoclastogenesis, and inhibited the expressions of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and osteoclast-specific target genes, including dendritic cell-specific transmembrane protein and cathepsin K. Our findings suggest that OFB exhibits an anti-osteoclastogenic activity by inhibiting RANKL-mediated p38 activation, which is useful for the prevention and treatment of osteolytic bone diseases.

Black soldier fly larvae oil as an alternative fat source in broiler nutrition.

The present study was conducted to investigate growth performance, carcass characteristics, short-chain fatty acids, fatty acid composition in abdominal fat, and serum parameters in broiler chickens fed diets containing corn oil, coconut oil, or black soldier fly larvae (BSFL) oil at the level of 50 g per kg of diet during the 30-day-feeding period. A total 450 one-day-old male broiler chicks (Ross 308) were randomly allocated to one of 3 dietary groups. Each treatment had 10 replicates with 15 chicks per replicate. Feed conversion ratio was decreased in the coconut and BSFL oil group compared with the corn oil group. Dietary BSFL oil increased ileal weight-to-length ratio at day 30 after hatch. Dietary BSFL oil increased significantly ileal branched-chain fatty acid (P < 0.05) and moderately total short-chain fatty acid in 15-day-old broilers (P = 0.074). At day 30, ileal propionate was highest in the coconut oil group but cecal propionate was highest (P < 0.05) in the BSFL oil group. Fatty acid composition of abdominal fat was affected by dietary fat sources. Especially, chickens fed diets containing coconut oil or BSFL oil had higher contents (P < 0.05) of saturated fatty acid being dominant in lauric and myristic acids compared with those fed on corn oil. On the other hand, the reverse trend was noted (P < 0.05) as to polyunsaturated fatty acids being dominant in corn oil compared with coconut oil and BSFL oil. Coconut oil vs. corn oil significantly increased total and high-density lipoprotein cholesterol. Finally, BSFL oil vs. corn oil significantly increased total antioxidant capacity in chickens. It is concluded that dietary BSFL oil improves feed conversion ratio and increases the incorporation of medium-chain fatty acids into abdominal fat pad and serum antioxidant capacity in broiler chickens.

In situ procedure for high-efficiency computational modeling of atrial fibrillation reflecting personal anatomy, fiber orientation, fibrosis, and electrophysiology.

We previously reported the feasibility and efficacy of a simulation-guided clinical catheter ablation of atrial fibrillation (AF) in an in-silico AF model. We developed a highly efficient realistic AF model reflecting the patient endocardial voltage and local conduction and tested its clinical feasibility. We acquired > 500 endocardial bipolar electrograms during right atrial pacing at the beginning of the AF ablation procedures. Based on the clinical bipolar electrograms, we generated simulated voltage maps by applying fibrosis and local activation maps adjusted for the fiber orientation. The software's accuracy (CUVIA2.5) was retrospectively tested in 17 patients and feasibility prospectively in 10 during clinical AF ablation. Results: We found excellent correlations between the clinical and simulated voltage maps (R = 0.933, p < 0.001) and clinical and virtual local conduction (R = 0.958, p < 0.001). The proportion of virtual local fibrosis was 15.4, 22.2, and 36.9% in the paroxysmal AF, persistent AF, and post-pulmonary vein isolation (PVI) states, respectively. The reconstructed virtual bipolar electrogram exhibited a relatively good similarities of morphology to the local clinical bipolar electrogram (R = 0.60 ± 0.08, p < 0.001). Feasibility testing revealed an in situ procedural computing time from the clinical data acquisition to wave-dynamics analyses of 48.2 ± 4.9 min. All virtual analyses were successfully achieved during clinical PVI procedures. We developed a highly efficient, realistic, in situ procedural simulation model reflective of individual anatomy, fiber orientation, fibrosis, and electrophysiology that can be applied during AF ablation.

Persistent atrial fibrillation over 3 years is associated with higher recurrence after catheter ablation.

INSTRUCTION: Longer atrial fibrillation (AF) durations have higher recurrence rates after rhythm control. However, there is limited data on the effect of the AF duration on recurrence after atrial fibrillation catheter ablation (AFCA). In the present study, we investigated the rhythm outcome of AFCA according to the AF duration based on the first electrocardiogram (ECG) diagnosis. METHODS AND RESULTS: We included 1005 patients with AF (75% male, 59 ± 11 years old) who underwent AFCA and whose first ECG diagnosis time point was evident. The clinical characteristics and rhythm outcomes were compared based on the AF duration (≤3 years, n = 537; >3 years, n = 468) and AF burden (paroxysmal atrial fibrillation [PAF], n = 387; persistent atrial fibrillation [PeAF], n = 618). Longer AF durations were associated with older age (P = .020), larger left atrial size (P = .009) and a higher number of patients with hypertension (P < .001) or PeAF (P < .001). During 24 ± 22 months of follow-up, the postablation clinical recurrence rate was higher in patients with a longer AF duration (logrank P = .002). The AF recurrence rate was significantly higher in PeAF patients with an AF duration >3 years (logrank P = 0.009), but not in subjects with PAF (logrank P = .939). In a multivariate Cox regression analysis, a longer AF duration was significantly associated with a higher clinical recurrence rate after AFCA in PeAF patients (adjusted hazard ratio, 1.06; range, 1.03-0.10; P = 0.001), but not PAF. CONCLUSION: Although longer AF duration was associated with higher clinical recurrence rates after AFCA, the rate was significant in patients with PeAF lasting >3 years, but not in PAF patients.

Identification of sesamol byproducts produced by plasma treatment with inhibition of advanced glycation endproducts formation and ONOO- scavenging activities.

Little is known of plasma-mediated relations between major food components and their biological capacities. In the present work, the effects of dielectric barrier discharge (DBD) plasma irradiation on pure sesamol and sesame oil were investigated using spectroscopic (LC-MS, NMR) and bioassay methods. Sesamol was degraded when subjected to plasma irradiation for 40 min, and the exposed products exhibited improved anti-glycation capacities against advanced glycation end products (AGEs) formation and better ONOO- scavenging ability. Structures of newly formed compounds were determined spectroscopically. Quantitative LC-MS analysis of the major products generated in sesamol and sesame oil was achieved using isolates 1-4 of purified sesamol plasma treated for 40 min. These results indicate that the predominant chemical changes induced in sesamol and sesame oil by DBD plasma treatment might enhance biological properties.

Long-term fine particulate matter exposure and cardiovascular mortality in the general population: a nationwide cohort study.

BACKGROUND: Although eastern Asian countries are exposed to high levels of air pollution, the impact of long-term exposures to fine particulate matter (PM2.5) air pollution on all-cause and cardiovascular mortality is not well identified. We assessed the relationship between long-term PM2.5 exposure and all-cause/cardiovascular mortalities. METHODS: We included 436,933 subjects who received national health examinations from the Korean National Health Insurance Service-based National Sample Cohort. We matched subjects' residential-address areas with hourly-measurements of PM2.5 concentration data. We estimated the risk of mortality with average PM2.5 exposure during the study period using a Cox proportional-hazards model. RESULTS: During 1,683,271 person·years, all-cause and cardiovascular mortalities were observed in 6432 and 1603 subjects (382 and 95 per 100,000 person·years, respectively). An increase in 10 µg/m3 in PM2.5 was associated with increases in all-cause and cardiovascular mortalities by 3.4 % [2.7-4.1] and 4.7 % [3.6-5.8], respectively (each p < 0.001). PM2.5 was linearly and significantly correlated with these all-cause and cardiovascular mortalities above 18 µg/m3 of PM2.5 (p < 0.001), but it was not significant below 18 µg/m3 of PM2.5. To investigate the specific PM2.5 concentration for raising cardiovascular mortality more, we analyzed the sensitivities/specificities for different PM2.5 levels, and 18 µg/m3 showed the highest Youden's index (sensitivity + specificity-1) with c-index of 0.85 (0.84-0.86). PM2.5 effect on all-cause mortality was more profound in subjects with previous myocardial infarction compared to the opposite population. CONCLUSIONS: In the Korean general population exposed to high-air pollution, long-term PM2.5 exposure was linearly associated with increased risk for all-cause and cardiovascular mortality, especially above 18 µg/m3 of PM2.5.

The Electrical Isolation of the Left Atrial Posterior Wall in Catheter Ablation of Persistent Atrial Fibrillation.

OBJECTIVES: This study explored whether complete electrical isolation of the left atrial (LA) posterior wall improves the rhythm outcome of catheter ablation of persistent atrial fibrillation (AF). BACKGROUND: Although the STAR AF2 (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) proved no additional benefit of empirical extra-pulmonary vein (PV) LA ablation, the long-term recurrence rate after circumferential PV isolation (CPVI) alone remains high. METHODS: We randomly assigned 217 patients with persistent AF (83.1% men, age 58.7 ± 10.8 years, 73.3% long-standing persistent AF) to ablation with CPVI alone (CPVI group) or CPVI with a POsterior wall Box Isolation (POBI group). The endpoint of the POBI group was the elimination of the posterior atrial potentials by roof and posterior inferior lines and touch-up focal ablation. RESULTS: After a mean follow-up of 16.2 ± 8.8 months, the clinical recurrence rate did not significantly differ between the 2 groups (23.8% vs. 26.5%; p = 0.779) in the CPVI and POBI groups. The recurrence rate for atrial tachycardias (16.0% vs. 11.1%; p = 0.913) and cardioversion rates (6.7% vs. 13.7%; p = 0.093) to control clinical recurrences also did not significantly differ between the 2 groups. At the final follow-up, sinus rhythm was maintained without antiarrhythmic drug in 50.5% and 55.9% in the CPVI and POBI groups, respectively (p = 0.522). No significant difference was found in the major complication rates between the 2 groups, but the total ablation time was significantly longer in the POBI group (4,289 ± 1,837 s vs. 5,365 ± 2,358 s; p < 0.001). CONCLUSIONS: In patients with persistent AF, an empirical complete POBI did not improve the rhythm outcome of catheter ablation or influence the type of recurrent atrial arrhythmia. (Comparison of Circumferential Pulmonary Vein Isolation Alone Versus Linear Ablation in Addition to Circumferential Pulmonary Vein Isolation for Catheter Ablation in Persistent Atrial Fibrillation: Prospective Randomized Controlled Trial; NCT02721121).

Improved Population-Based Clinical Outcomes of Patients with Atrial Fibrillation by Compliance with the Simple ABC (Atrial Fibrillation Better Care) Pathway for Integrated Care Management: A Nationwide Cohort Study.

BACKGROUND: An integrated care approach might be of benefit for clinical outcomes of patients with atrial fibrillation (AF). This study evaluated whether compliance with the Atrial fibrillation Better Care (ABC) pathway for integrated care management ("A" Avoid stroke; "B" Better symptom management; "C" Cardiovascular risk and Comorbidity optimization) would improve population-based clinical outcomes in a nationwide AF cohort. METHODS AND RESULTS: From the Korea National Health Insurance Service database, a total of 204,842 nonvalvular AF patients were enrolled between January 1, 2005 and December 31, 2015. Patients that fulfilled all criteria of the ABC pathway were defined as the "ABC" group, and those who did not were the "Non-ABC" group.Over a mean follow-up of 6.2 ± 3.5 years, the ABC pathway compliant group had lower rates of all-cause death (0.80 vs. 2.72 per 100 person-years, p < 0.001) and the composite outcome of "death, ischemic stroke, major bleeding, and myocardial infarction" (2.34 vs. 5.92 per 100 person-years, p < 0.001) compared with the Non-ABC compliant group. Adjusted Cox multivariable regression showed that the ABC group had a significantly lower risk of all-cause death (adjusted hazard ratio [HR] 0.82; 95% confidence interval [CI], 0.78-0.86) and the composite outcome (adjusted HR 0.86; 95% CI, 0.83-0.89). With the increasing numbers of ABC pathway criteria fulfilled, the risk of all-cause death and composite outcome were progressively lowered. CONCLUSION: In the first study of a nationwide population cohort, we show that compliance with the simple ABC pathway is associated with improved clinically relevant outcomes of patients with AF. Given the high health care burden associated with AF, such a streamlined holistic approach to AF management should be implemented, to improve the care of such patients.

2-O-digalloyl-1,3,4,6-tetra-O-galloyl-ß-D-glucose isolated from Galla Rhois suppresses osteoclast differentiation and function by inhibiting NF-κB signaling.

Natural compounds isolated from medicinal herbs and plants have immense significance in maintaining bone health. Hydrolysable tannins have been shown to possess a variety of medicinal properties including antiviral, anticancer, and anti-osteoclastogenic activities. As a part of a study on the discovery of alternative agent against skeletal diseases, we isolated a hydrolysable tannin, 2-O-digalloyl-1,3,4,6-tetra-Ogalloyl- ß-D-glucose (DTOGG), from Galla Rhois and examined the effect on osteoclast formation and function. We found that DTOGG significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation by downregulating the expression of the key regulator in osteoclastogenesis as well as osteoclast-related genes. Analysis of RANKL/RANK signaling revealed that DTOGG impaired activation of IκBα and p65 in the nuclear factor kappa-lightchain- enhancer of activated B cells (NF-κB) signaling pathway. Furthermore, DTOGG reduced bone resorbing activity of osteoclasts, compared to the vehicle-treated control. These results suggest that DTOGG could be a useful natural compound to manage osteoclast-mediated skeletal diseases. [BMB Reports 2019; 52(6): 409-414].

Effects of inhaler therapy on mortality in patients with tuberculous destroyed lung and airflow limitation.

PURPOSE: Although patients with tuberculous destroyed lung (TDL) receive long-acting muscarinic antagonist (LAMA) inhaler therapy, its effectiveness is not clear. This study evaluated the effect of LAMA inhaler therapy on mortality in patients with TDL and airflow limitation. PATIENTS AND METHODS: A retrospective cohort of 683 patients with TDL and airflow limitation was analyzed in this study. The mortality was compared between 177 patients treated with LAMA inhalers >360 days (LAMA group) and 506 patients not treated with LAMA inhalers or treated with LAMA inhalers for <360 days (non-LAMA group). Risk factors for mortality were analyzed with Cox proportional hazards models and survival analysis was performed after propensity score matching. RESULTS: Patients in the LAMA group appeared to have worse baseline characteristics, older mean age, lower lung function, higher X-ray severity, and were more likely to receive long-term oxygen therapy than those in the non-LAMA group. On multivariate analysis, LAMA inhaler usage was independently associated with lower risk of mortality (HR, 0.405; P=0.006) after adjusting age, gender, body mass index, smoking history, Charlson Comorbidity Index, lung function, X-ray severity, and long-term oxygen therapy. After propensity score matching to adjust for the above unbalanced baseline characteristics, patients in the LAMA group tended to have a better prognosis than those in the non-LAMA group (121 patients in each group, 5-year mortality rate: 2.5% vs 9.1%, P=0.057). If we performed the same analysis of propensity score matching even after excluding patients with corticosteroids/long-acting beta-2 agonist (ICS/LABA) usage, patients in the LAMA group had a better prognosis than those in the non-LAMA group (64 patients in each group, 5-year mortality rate: 3.1% vs 14.1%, P=0.039). CONCLUSION: LAMA inhaler treatment might reduce mortality in patients with TDL and airflow limitation.