Acaricidal and Insecticidal Activities of Essential Oils and Constituents of Tasmannia lanceolata (Poir.) A.C.Sm. (Canellales: Winteraceae) Against Tetranychus urticae Koch (Trombidiformes: Tetranychidae) and Myzus persicae Sulzer (Hemiptera: Aphididae).

The negative side effects of synthetic pesticides have drawn attention to the need for environmentally friendly agents to control arthropod pests. To identify promising candidates as botanical pesticides, we investigated the acaricidal and insecticidal activities of 44 plant-derived essential oils (EOs) against Tetranychus urticae Koch and Myzus persicae Sulzer. Among the tested EOs, Tasmannia lanceolata (Poir.) A.C.Sm. (Tasmanian pepper) essential oil (TPEO) exhibited strong acaricidal and insecticidal activity. Mortality rates of 100% and 71.4% against T. urticae and M. persicae, respectively, were observed with TPEO at a concentration of 2 mg/ml. Polygodial was determined to be the primary active component after bioassay-guided isolation of TPEO using silica gel open-column chromatography, gas chromatography, and gas chromatography-mass spectrometry. Polygodial demonstrated acaricidal activity against T. urticae with mortality rates of 100%, 100%, 61.9%, and 61.6% at concentrations of 1, 0.5, 0.25, and 0.125 mg/ml, respectively. Insecticidal activity against M. persicae was also evident, with mortality rates of 88.5%, 85.0%, 46.7%, and 43.3% at respective concentrations of 1, 0.5, 0.25, and 0.125 mg/ml. Insecticidal and acaricidal activities of TPEO were greater than those of Eungjinssag, a commercially available organic agricultural material for controlling mites and aphids in the Republic of Korea. These findings suggest that TPEO is a promising candidate for mites and aphids control.

Field Confirmation of (Z)-9-Heptacosene and (3Z,6Z,9Z)-Tricosatriene as Key Sex Pheromone Components of Korean Conogethes punctiferalis Guenée (Lepidoptera: Crambidae).

Recently, insufficient attractiveness of Conogethes punctiferalis Guenée adult males to sex pheromone, -(E)-10-hexadecenal and (Z)-10-hexadecenal, has been reported. To identify the other essential components of sex pheromone, male and female body extracts were analyzed. Two hydrocarbon components, (Z)-9-heptacosene (Z9-27:HC) and (3Z,6Z,9Z)-tricosatriene (Z3,Z6,Z9-23:HC), were identified from only female body extract. There was a significant difference in the electroantennogram (EAG) response of male antennae to Z3,Z6,Z9-23:HC and Z9-27:HC at all test concentrations compared to the response to the hexane control. In field attraction testing, the addition of Z9-27:HC and Z3,Z6,Z9-23:HC to binary aldehyde pheromones significantly increased trap catches of C. punctiferalis male adults. Based on the female and male body extract analysis and field attraction test, Z9-27:HC and Z3,Z6,Z9-23:HC were determined to be other essential sex pheromone components of the Korean C. punctiferalis population. No significant difference was observed in the number of male captures between the bucket trap and delta trap. Pheromone traps with a color close to yellow shade attracted more male adults than traps with a color close to blue shade.

Acaricidal Activities of Dioscorea japonica Thunb. (Dioscoreales: Dioscoreaceae) Extract and its Constituents Against the Two-spotted Spider Mite, Tetranychus urticae Koch (Trombidiformes: Tetranychidae).

The acaricidal activities of 86 plant extracts were investigated under laboratory conditions. The ethanol extract of Dioscorea japonica Thunb. root showed the strongest acaricidal activity, with 89.3% mortality against two-spotted spider mite, Tetranychus urticae Koch adults at a 2 mg/ml concentration. Bioassay-guided isolation of D. japonica root extract using silica gel open column chromatography, gas chromatography (GC), and gas chromatography-mass spectrometry (GC-MS) identified palmitic acid as the primary active compound. The acaricidal activities of palmitic acid against T. urticae were 91.2% and 69.7% at concentrations of 1 and 0.5 mg/ml, respectively. Among nine saturated fatty acids with carbon chains ranging from C8 to C26, the most vigorous acaricidal activity was observed with octanoic acid, followed by palmitic acid, and decanoic acid at a 1 mg/ml concentration. The acaricidal activity of the other fatty acids was less than 40% mortality at a 1 mg/ml concentration. These results indicate that a suitable carbon length is essential for fatty acids to exhibit acaricidal activity. The acaricidal efficacy of Eungjinssag (EJSG), an organic agricultural material authorized for the management of mites in the Republic of Korea, was compared to D. japonica root extract. At concentrations above 1 mg/ml, the acaricidal activity of D. japonica root extract was stronger than that of EJSG. The results of this study show that D. japonica root extract and palmitic acid are promising candidates as new environmentally-friendly control agents against two-spotted spider mite, which is one of the most severely damaging agricultural arthropod pests.

Recent trends in opioid prescriptions in Korea from 2002 to 2015 based on the Korean NHIS-NSC cohort.

OBJECTIVES: Opioids are prescribed to treat moderate to severe pain. We investigated recent trends in opioid (morphine, oxycodone, fentanyl, and hydromorphone) prescriptions using data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2015. METHODS: The morphine milligram equivalent (MME) was calculated to standardize the relative potency of opioids. The number (cases) or amount (MME) of annual opioid prescriptions per 10,000 registrants was computed to analyze trends in opioid prescriptions after age standardization. Joinpoint regression analysis was conducted to calculate the annual percentage change and average annual percentage change (AAPC). RESULTS: The number (cases) of prescriptions per 10,000 registrants increased from 0.07 in 2002 to 41.23 in 2015 (AAPC, 76.0%; 95% confidence interval [CI], 61.6 to 91.7). The MME per 10,000 registrants increased from 15.06 in 2002 to 40,727.80 in 2015 (AAPC, 103.0%; 95% CI, 78.2 to 131.3). The highest AAPC of prescriptions and MME per 10,000 registrants were observed in the elderly (60-69 years) and in patients treated at general hospitals. Fentanyl prescriptions increased most rapidly among the 4 opioids. CONCLUSIONS: Consumption of opioids greatly increased in Korea over the 14-year study period.

Development of chitosan-coated nanoemulsions of two sulfides present in onion (Allium cepa) essential oil and their nematicidal activities against the pine wood nematode, Bursaphelenchus xylophilus.

Pine wood nematode, Bursaphelenchus xylophilus, is a plant parasitic nematode which causes severe damage to several Pinus species. Two natural compounds, dipropyl trisulfide (DPTS) and methyl propyl trisulfide (MPTS), showed strong nematicidal activity against the pine wood nematode, presenting 4.24 and 17.81 µg/mL LC50 values, respectively. However, hydrophobicity and low stability have limited their practical use in the field as nematicides. To overcome these problems, chitosan-coated nanoemulsions of DPTS and MPTS were developed. The optimum chitosan concentration for the delivery system of the two sulfides was 0.5%. Optimized chitosan-coated nanoemulsions of sulfides have a uniform size distribution (mean diameter = 203.7 and 207.7 nm, mean polydispersity index = 0.176 and 0.178) with sufficient colloidal stability (mean zeta potential = +40 and +45 mV). The LC50 values of DPTS and MPTS nanoemulsions coated with 0.5% chitosan against the pine wood nematode were 5.01 and 16.60 µg/mL, respectively. In addition, chitosan coating improved the long-term storage stability and persistence of nematicidal activity of the nanoemulsions. This study indicates that the chitosan-coated nanoemulsion is a suitable formulation for sulfides as novel nematicides against the pine wood nematode for field application.

Beneficial Effects of a Specially Designed Home Meal Replacement on Cardiometabolic Parameters in Individuals with Obesity: Preliminary Results of a Randomized Controlled Clinical Trial.

We aimed to investigate if a home meal replacement (HMR), designed with a low ω-6/ω-3 fatty acid ratio, improves cardiometabolic parameters, including metabolic syndrome (MetS) in obese individuals. We conducted a monocentric, controlled, randomized crossover trial. The HMR contains higher protein and fat content, lower carbohydrate content, and a lower ω6FA/ω3FA ratio than the regular diet. Sixty-four participants were randomized into two groups and switched to the other group following a 4-week intervention. While subjects in the HMR group were provided three HMRs daily, those in the control group were requested to maintain their regular dietary pattern. We conducted paired t-tests, repeated measures analysis of variance, and McNemar tests before and after the intervention. Body mass index (BMI) and weight were lower in the HMR group after adjusting for age, sex, and total energy intake and significantly changed in the between-group differences. The waist circumference, systolic blood pressure, triglycerides, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were reduced in the HMR group (all p < 0.05). The percentage of subjects with MetS significantly decreased from 39.1% at baseline to 28.1% post-intervention (p = 0.035). Using the HMR for 4 weeks reduced the BMI, weight, and MetS prevalence in individuals with obesity. This trial was registered at clinicaltrials.gov (NCT04552574).

Development of cellulose nanocrystal-stabilized Pickering emulsions of massoia and nutmeg essential oils for the control of Aedes albopictus.

We investigated the larvicidal potential of 10 plant essential oils (EOs) against the Asian tiger mosquito Aedes albopictus. Among the EOs, larvicidal activity against Ae. albopictus was strongest in those derived from massoia (Massoia aromatica) and nutmeg (Myristica fragrans). Larvicidal activities of massoia and nutmeg EOs against Ae. albopictus were 95.0% and 85.0% at 50 µg/mL, respectively. A total of 4 and 14 compounds were identified from massoia and nutmeg, respectively, and two massoia lactones, C10 and C12, were isolated from massoia EO. Among the identified compounds, benzyl salicylate, terpinolene, C12 massoia lactone, sabinene, benzyl benzoate, methyl eugenol, and C10 massoia lactone exhibited the strong larvicidal activity. Cellulose nanocrystal (CNC)-stabilized Pickering emulsions of massoia and nutmeg EOs were developed to overcome the insolubility of EOs in water. CNC/massoia and CNC/nutmeg emulsions were stable for at least 10 days, and larvicidal activities of CNC/massoia PE and CNC/nutmeg were higher than those of crude massoia and nutmeg EOs. This study presents a CNC-stabilized PE, a suitable formulation for EOs, as a potential larvicide against Ae. albopictus.

Metformin use in cancer survivors with diabetes reduces all-cause mortality, based on the Korean National Health Insurance Service between 2002 and 2015.

ABSTRACT: Malignant neoplasms are the leading cause of death in Korea. We aimed to examine if metformin use in cancer survivors reduces all-cause mortality. This study was retrospectively designed based on data from the Korean National Health Insurance Service-National Health Screening Cohort (HEALS) between 2002 and 2015. The Kaplan-Meier estimator and log-rank test was performed to estimate the survival function according to metformin usage (3721 metformin non-users with diabetes, 5580 metformin users with diabetes, and 24,483 non-diabetic individuals). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated using Cox proportional hazards regression models.The median follow-up duration was 4.2 years. The HRs (95% CIs) for all-cause mortality of metformin users and the non-diabetic group were 0.762 (0.683-0.850) and 1.055 (0.966-1.152) in men and 0.805 (0.649-0.999), and 1.049 (0.873-1.260) in women, respectively, compared with metformin non-users among diabetic cancer survivors, in a fully adjusted model. After stratifying metformin users into pre- and post-diagnosis of cancers, adjusted HRs (95% CIs) of pre- and post-diagnosis metformin users for all-cause mortality were 0.948 (0.839-1.071) and 0.530 (0.452-0.621) in men and 1.163 (0.921-1.469) and 0.439 (0.323-0.596) in women, respectively.Metformin use in cancer survivors with diabetes reduced overall mortality rates. In particular, metformin use after cancer diagnosis, not before cancer diagnosis, was inversely associated with overall mortality.Active treatment with metformin for diabetic cancer survivors after cancer diagnosis can improve their survival rates.

Increased Omega-3 Fatty Acid Intake Is Inversely Associated with Subclinical Inflammation in Healthy Elderly Men, Based on the 2015-2018 Korean National Health and Nutrition Examination Survey.

(1) Background: Subclinical inflammation as a risk factor of cardiovascular diseases was clinically measured using C-reactive protein (CRP) level. (2) Methods: This study was cross-sectionally designed based the 2015-2018 Korean National Health and Nutrition Examination Survey (KNHANES). The ratio of daily omega-3 fatty acids to energy intake (ω3FA ratio) was classified into four quartile groups (Q1, <0.3%; Q2, 0.3%-<0.6%; Q3, 0.6%-<1.0%; and Q4, ≥1.0% in both sexes). Logistic regression analysis was conducted to investigate the association between the ω3FA ratio and subclinical inflammation defined as CRP levels ≥3 mg/dL. (3) Results: The ω3FA ratio in subjects without and with subclinical inflammation was 0.8% and 0.7% in men (p-value = 0.001), and 0.8% and 0.8% in women (p-value = 0.491), respectively. The prevalence of subclinical inflammation in males decreased with increasing quartile of ω3FA ratio (12.9%, 9.6%, 7.4%, and 7.7%, p-value = 0.033), while female prevalence was not significant among quartile groups. Compared to Q1, odds ratios (95% confidence intervals) for subclinical inflammation of Q2, Q3, and Q4 were 0.740 (0.465-1.177), 0.564 (0.341-0.930), and 0.549 (0.317-0.953) in males, and 1.066 (0.653-1.741), 1.105 (0.600-1.718), and 0.934 (0.556-1.571) in females after full adjustment. (4) Conclusion: The ω3FA ratio is associated with subclinical inflammation in men.

Association between statin use and all-cause mortality in cancer survivors, based on the Korean health insurance service between 2002 and 2015.

BACKGROUND AND AIMS: Cancer is the number one cause of death in Korea. This study aimed to investigate if statin use in cancer survivors was inversely associated with all-cause mortality. METHODS AND RESULTS: Data from the 2002 to 2015 National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) were used. The Kaplan-Meier estimator was used to estimate the survival function according to statin usage. Cox proportional hazards regression models were adopted after stepwise adjustment for potential confounders to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. The median follow-up duration was 10.0 years. Statin users had a higher percentage of diabetes and hypertension in both sexes. Survival rates of statin users were higher than non-users (p-values <0.001 in men and 0.021 in women). Compared to non-users, the HRs (95% CIs) of statin users for all-cause mortality were 0.327 (0.194-0.553) in men and 0.287 (0.148-0.560) in women after adjustment for potential confounding factors. CONCLUSIONS: Statin users in cancer survivors had higher survival rate than non-users in both sexes.

Inverse Association Between Statin Use and Overall Cancer Incidence in Individuals With Hypercholesterolemia, Based on the Korean Health Insurance Service Between 2002 and 2015.

The Korean National Health Insurance Service provided the Health Screening Cohort Database. To investigate the cumulative effect of statins on cancer development, we defined statin users as those who used statins during 2002 to 2003 at baseline. Statin users were divided into high and low users. Statin nonusers were defined as individuals who had never used statins during the entire period of 2002 to 2015, despite having hypercholesterolemia. In total, 17 737 statin users and 13 412 statin nonusers were included in the final analyses. The median follow-up duration was 12.6 years. Compared with nonusers, the hazard ratios (95% confidential intervals) for any cancer incidence of low users and high users were 1.047 (0.941-1.164) and 0.663 (0.589-0.747) in men and 1.057 (0.938-1.190) and 0.592 (0.517-0.678) in women, respectively, after fully adjusting for possible confounding factors. An inverse association between statin use and any cancer incidence in individuals with hypercholesterolemia was observed.

High Receipt of Statins Reduces the Risk of Lung Cancer in Current Smokers With Hypercholesterolemia: The National Health Insurance Service-Health Screening Cohort.

BACKGROUND: The incidence and mortality of lung cancer have risen steadily with the increasing popularity of tobacco smoking. Observational studies suggest that statins, which are widely used to lower cholesterol, may prevent lung cancer; however, other studies have produced conflicting results. We investigated the effect of statin receipt on lung cancer risk in Korean men according to smoking status. PATIENTS AND METHODS: We collected data from the 2002-2015 National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). We included a total of 16,588 men in the final analysis. We classified the participants as having high or low statin receipt or as not receiving statins. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer risk by statin receipt after adjusting for potential confounders. RESULTS: We identified 363 patients with a new diagnosis of lung cancer from 2005 to 2015. Compared to participants who did not receive statins, high statin receipt resulted in a reduced lung cancer risk (HR = 0.64; 95% CI, 0.47, 0.85) after adjustment for confounders. Among current smokers, the fully adjusted HR for high statin receipt compared to those who did not receive statin therapy was 0.50 (95% CI, 0.32, 0.79). CONCLUSION: High statin receipt was associated with lower risk of lung cancer in Korean men with hypercholesterolemia, especially current smokers.

Trends in socioeconomic costs of morbid obesity among Korean adults, 2009-2013: Data from National Health Insurance Service.

As the prevalence of morbid obesity increased in Korea, the estimation of the accurate socioeconomic costs by morbid obesity was required; we analysed national medical costs through the big data. From 2009 year to 2013 year, Direct Costs (DC) for medical costs, transit costs and nursing costs and Indirect Costs (IC) for Future Income Loss (FIL) and Productivity Loss (PL) of morbid obesity (BMI≥30) were calculated, and socioeconomic costs were estimated by applying Population Attributable Risk (PAR) proportion according to obesity related diseases. From 10 year follow up research, Relative risk (RR) for morbid obesity related disease was analysed in comparison with control group. The high RR disease were congestive heart failure (RR 3.204 CI 2.421-3.987), hypertension (RR 3.13 CI 3.058-3.202), type 2 DM (RR 3.112 CI 2.973-3.251), pulmonary embolism (RR 2.969 CI 1.812-4.126), dyslipidemia (RR 2.283 CI 2.221-2.345) and ischaemic heart disease (RR 2.187 CI 2.068-2.306) in order. The socioeconomic costs by morbid obesity tended to increase 1.47 times from 2009 year (492 billion KRW) to 2013 year (726.2 billion KRW). The growth of the prevalence and the socioeconomic costs by morbid obesity in Korea are required not only the personal care issue but also social and national strategies for the future morbid obesity control.

Attenuation of acetylcholine activated potassium current (I KACh) by simvastatin, not pravastatin in mouse atrial cardiomyocyte: possible atrial fibrillation preventing effects of statin.

Statins, 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, are associated with the prevention of atrial fibrillation (AF) by pleiotropic effects. Recent clinical trial studies have demonstrated conflicting results on anti-arrhythmia between lipophilic and hydrophilic statins. However, the underlying mechanisms responsible for anti-arrhythmogenic effects of statins are largely unexplored. In this study, we evaluated the different roles of lipophilic and hydrophilic statins (simvastatin and pravastatin, respectively) in acetylcholine (100 µM)-activated K+ current (IKACh, recorded by nystatin-perforated whole cell patch clamp technique) which are important for AF initiation and maintenance in mouse atrial cardiomyocytes. Our results showed that simvastatin (1-10 µM) inhibited both peak and quasi-steady-state IKACh in a dose-dependent manner. In contrast, pravastatin (10 µM) had no effect on IKACh. Supplementation of substrates for the synthesis of cholesterol (mevalonate, geranylgeranyl pyrophosphate or farnesyl pyrophosphate) did not reverse the effect of simvastatin on IKACh, suggesting a cholesterol-independent effect on IKACh. Furthermore, supplementation of phosphatidylinositol 4,5-bisphosphate, extracellular perfusion of phospholipase C inhibitor or a protein kinase C (PKC) inhibitor had no effect on the inhibitory activity of simvastatin on IKACh. Simvastatin also inhibits adenosine activated IKACh, however, simvastatin does not inhibit IKACh after activated by intracellular loading of GTP gamma S. Importantly, shortening of the action potential duration by acetylcholine was restored by simvastatin but not by pravastatin. Together, these findings demonstrate that lipophilic statins but not hydrophilic statins attenuate IKACh in atrial cardiomyocytes via a mechanism that is independent of cholesterol synthesis or PKC pathway, but may be via the blockade of acetylcholine binding site. Our results may provide important background information for the use of statins in patients with AF.

[Disappearance of intrahepatic bile duct hepatocellular carcinoma after endoscopic retrograde cholangiopancreatography and transarterial chemoinfusion: a case report].

Invasion of the bile duct by hepatocellular carcinoma (HCC), which is called intrahepatic bile duct HCC, is rare and has a poor prognosis. Early diagnosis and surgical resection is important for treatment. A 58-year-old man who underwent hepatic resection for HCC 4 years ago and received transarterial chemoembolization (TACE) 2 years after the operation for recurred HCC presented with jaundice. CT scan revealed a tumor in the common bile duct without intrahepatic lesion. Therefore, ERCP was done to perform biopsy and biliary drainage. Histological examination was compatible with hepatocellular carcinoma. However, the tumor could not be visualized at angiography and thus, only transarterial chemoinfusion was performed without embolization. The tumor had disappeared on follow-up CT scan, and the patient has been disease free for 23 months without evidence of recurrence. Herein, we report a case of intrahepatic bile duct HCC which disappeared after ERCP.

Intratracheal bleomycin causes airway remodeling and airflow obstruction in mice.

In addition to parenchymal fibrosis, fibrotic remodeling of the distal airways has been reported in interstitial lung diseases. Mechanisms of airway wall remodeling, which occurs in a variety of chronic lung diseases, are not well defined and current animal models are limited. The authors quantified airway remodeling in lung sections from subjects with idiopathic pulmonary fibrosis (IPF) and controls. To investigate intratracheal bleomycin as a potential animal model for fibrotic airway remodeling, the authors evaluated lungs from C57BL/6 mice after bleomycin treatment by histologic scoring for fibrosis and peribronchial inflammation, morphometric evaluation of subepithelial connective tissue volume density, TUNEL (terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling) assay, and immunohistochemistry for transforming growth factor ß1 (TGFß1), TGFß2, and the fibroblast marker S100A4. Lung mechanics were determined at 3 weeks post bleomycin. IPF lungs had small airway remodeling with increased bronchial wall thickness compared to controls. Similarly, bleomycin-treated mice developed dose-dependent airway wall inflammation and fibrosis and greater airflow resistance after high-dose bleomycin. Increased TUNEL(+) bronchial epithelial cells and peribronchial inflammation were noted by 1 week, and expression of TGFß1 and TGFß2 and accumulation of S100A4(+) fibroblasts correlated with airway remodeling in a bleomycin dose-dependent fashion. IPF is characterized by small airway remodeling in addition to parenchymal fibrosis, a pattern also seen with intratracheal bleomycin. Bronchial remodeling from intratracheal bleomycin follows a cascade of events including epithelial cell injury, airway inflammation, profibrotic cytokine expression, fibroblast accumulation, and peribronchial fibrosis. Thus, this model can be utilized to investigate mechanisms of airway remodeling.

Comparative analysis of effects of cytokine gene adjuvants on DNA vaccination against Mycobacterium tuberculosis heat shock protein 65.

DNA-based vaccines generate potent cellular immunity as well as humoral immunity. It seems evident that cytokines play a crucial role in generation of effector T cell subsets and in determining the magnitude of the response by DNA vaccines. In this study, we compared the effects of several TH1 cytokine genes as adjuvant in DNA vaccination using mycobacterial Hsp65 as a model antigen. Our results demonstrated that although the overall immune response to Hsp65 was enhanced by co-injection of Hsp65 DNA with cytokine genes, each cytokine gene was shown to affect different immune response elements. Co-injection of Hsp65 DNA with IL-12 or GM-CSF led to an increase in IFN-gamma production and represented potent protections against Mycobacterium tuberculosis challenge, while that with Eta-1, IL-12 or IL-18 gene led to an elevated IgG2a/IgG1 ratio. Interestingly, co-administration of Flt3L gene was shown to enhance the Ag-specific CTL response. These results show that the direction and magnitude of immune response in DNA vaccination against Hsp65 of M. tuberculosis could be modulated in different ways by co-injection of an appropriate cytokine gene as adjuvant.