Visit-to-visit variability of metabolic parameters and progression of atherosclerosis in computed tomography: follow up of an asymptomatic cohort.

Background: We aimed to examine whether intra-individual variability in traditional risk factors affects the progression of atherosclerosis on subsequent coronary computed tomography angiography (CCTA). Methods: We conducted a retrospective cohort study using asymptomatic health examination cohort data from Haeundae Paik Hospital in Korea collected between 2010-2020. A total of 387 adults met the inclusion criteria of having at least two CCTAs without specific symptoms with an interval of more than one year and having completed three or more health examinations. Visit-to-visit variability was evaluated using the average real variability (ARV) of body mass index, waist circumference, systolic and diastolic blood pressure, and plasma glucose, total cholesterol, triglyceride, high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol. Progression of coronary artery atherosclerosis was defined as worsening of coronary artery stenosis from baseline to final CCTA. ARV values for various metabolic parameters were stratified into quartiles, and hazard ratios (HRs) and 95% confidence intervals (CIs) for coronary atherosclerosis progression were analyzed using multiple Cox proportional hazards models. Results: There were 126 cases of coronary artery stenosis progression (32.56%) assessed using the Coronary Artery Disease Reporting and Data System during a mean follow up of 3.91 (range, 1-9) years. In the multivariate analysis comparing ARV quartiles for LDL-cholesterol after adjusting for covariates, individuals with higher variability showed an increased risk of stenosis progression: HR 2.23 (95% CI: 1.33-3.73) for the third quartile, HR 1.56 (95% CI: 0.91-2.66) for the fourth quartile (P for trend =0.005). Triglycerides also showed a significant linear trend (P for trend =0.04), and Q4 had a greater risk of stenosis progression (HR, 2.09; 95% CI: 1.24-3.52). Meanwhile, the risk of stenosis progression was significantly reduced as the ARV of HDL-cholesterol increased: HR 0.56 (95% CI: 0.35-0.89) for the third quartile, HR 0.47 (95% CI: 0.27-0.81) for the fourth quartile (P for trend =0.01). Conclusions: High variability in LDL-cholesterol and triglyceride was an independent predictor of coronary artery stenosis progression on subsequent CCTA in our cohort. This finding highlights the importance of maintaining stable state to effectively prevent the progression of coronary artery stenosis in clinical settings.

Orally bioavailable BTK PROTAC active against wild-type and C481 mutant BTKs in human lymphoma CDX mouse models.

Bruton tyrosine kinase (BTK) is an important signaling hub that activates the B-cell receptor (BCR) signaling cascade. BCR activation can contribute to the growth and survival of B-cell lymphoma or leukemia. The inhibition of the BCR signaling pathway is critical for blocking downstream events and treating B-cell lymphomas. Herein, we report potent and orally available proteolysis-targeting chimeras (PROTACs) that target BTK to inactivate BCR signaling. Of the PROTACs tested, UBX-382 showed superior degradation activity for wild-type (WT) and mutant BTK proteins in a single-digit nanomolar range of half-maximal degradation concentration in diffuse large B-cell lymphoma cell line. UBX-382 was effective on 7 out of 8 known BTK mutants in in vitro experiments and was highly effective in inhibiting tumor growth in murine xenograft models harboring WT or C481S mutant BTK-expressing TMD-8 cells over ibrutinib, ARQ-531, and MT-802. Remarkably, oral dosing of UBX-382 for <2 weeks led to complete tumor regression in 3 and 10 mg/kg groups in murine xenograft models. UBX-382 also provoked the cell type-dependent and selective degradation of cereblon neosubstrates in various hematological cancer cells. These results suggest that UBX-382 treatment is a promising therapeutic strategy for B-cell-related blood cancers with improved efficacy and diverse applicability.

Cancer Survivors with Low Hand Grip Strength Have Decreased Quality of Life Compared with Healthy Controls: The Korea National Health and Nutrition Examination Survey 2014-2017.

BACKGROUND: Cancer survivors experience decreased physical function and reduced muscle strength, which leads to lower quality of life (QOL). The hand grip strength (HGS) can be a predictor of poor health-related QOL as a parameter of sarcopenia. The purpose of this study was to investigate the relationship between low HGS and QOL in cancer survivors and healthy controls. METHODS: We analyzed 392 cancer survivors and 1,176 healthy controls from the Korea National Health and Nutrition Examination Survey, 2014-2017. We defined low HGS as 2 standard deviation values for healthy young Korean adults from a previous study. QOL was evaluated using the European Quality of Life Scale-Five Dimensions. A complex sample logistic regression model was used to assess the relationship between each dimension of low HGS and QOL. RESULTS: The odds ratios (ORs) for decreased QOL were significantly higher in male cancer survivors with low HGS on self-care (OR, 8.51; 95% confidence interval [CI], 1.69-42.83) and usual activities (OR, 6.63; 95% CI, 1.22-36.03). The ORs for problems in mobility (OR, 5.87; 95% CI, 2.04-16.91), usual activities (OR, 14.46; 95% CI, 3.84-54.44), pain/discomfort (OR, 4.90; 95% CI, 2.00-12.01), and anxiety/depression (OR, 6.43; 95% CI, 2.16-19.12) were significantly high in female cancer survivors with low HGS. However, healthy controls showed no significant relationship between low HGS and QOL. CONCLUSION: For cancer survivors, low HGS was associated with poor QOL in some domains. Strategies to increase muscle strength must be considered to improve the QOL of cancer survivors.

Effect of Increasing Tobacco Prices on Stages of Smoking Cessation: A Korean Nationwide Data Analysis.

BACKGROUND: In 2015, tobacco prices significantly increased in Korea as part of the government's smoking cessation policy. This study examined the changes in the stages of smoking cessation among Korean male smokers before and after the implementation of the tobacco price policy, and identified the predictors of such changes. METHODS: The study population comprised 3,533 male current smokers (age ≥19 years) who participated in the Korea National Health and Nutrition Survey in 2012, 2013, 2015, and 2016. Current smokers were defined as persons who had smoked ≥100 cigarettes during their lifetime and are continuing to smoke. In accordance with the transtheoretical model, smokers were classified into the precontemplation stage (no plan to quit), contemplation stage, and preparation stage (planning to quit within 6 months). We examined the changes in the smoking cessation stages before and after the implementation of the policy. Multivariate logistic regression analysis was conducted to identify factors related to the likelihood of continuing smoking, after adjustments for potential confounders. RESULTS: Immediately after the policy implementation, the percentage of smokers in the precontemplation stage decreased from 65.6% to 60.8% (P=0.014). However, this effect was temporary. Significant risk factors for remaining in the precontemplation stage were older age (odds ratio [OR], 1.010; 95% confidence interval [CI], 1.002-1.018; P=0.004), being in the lowest income quartile (OR, 1.226; 95% CI, 1.001-1.502; P=0.049), and manual worker or unemployed status (OR, 1.256; 95% CI, 1.036-1523; P=0.020). CONCLUSION: Increasing tobacco prices only temporarily change the stage of smoking cessation among Korean male smokers.

CT-defined visceral adipose tissue thresholds for identifying metabolic complications: a cross-sectional study in the United Arab Emirates.

OBJECTIVES: Visceral adipose tissue (VAT) is closely related to obesity complications. We aimed to determine the optimal sex-specific and age-specific VAT thresholds for predicting metabolic complications among individuals living in the United Arab Emirates (UAE). DESIGN: Retrospective cross-sectional study. SETTING: We reviewed medical records of adults who visited a hospital in the UAE. PARTICIPANTS: A total of 369 subjects were included in the final analysis after application of inclusion and exclusion criteria. PRIMARY OUTCOME MEASURES: The prevalence of metabolic syndrome (MES). RESULTS: MES measures excluding waist circumference were present in 73.4% of women and 78.5% of men. VAT areas adjusted for age were significantly greater in the MES group compared with the non-MES group regardless of sex (p<0.05 for all relations); however, subcutaneous adipose tissue areas adjusted for age were not significantly different. Areas under the curve used to predict MES were statistically significant for VAT and visceral to subcutaneous fat ratios among both men and women. Identified cut-off values of VAT to predict MES were 132.0 cm2 in both sexes for individuals under the age of 50 years. For those over 50 years of age, VAT thresholds were greater in women compared with men (173 cm2 vs 124.3 cm2, respectively). CONCLUSIONS: Optimal VAT cut-offs to predict MES were 132 cm2 for individuals under 50 years old living in the UAE. These measures are potential target visceral fat values that could be used to reduce obesity-related morbidity in populations with pre-existing metabolic complications.

Young cancer survivors have lower bone mineral density compared with healthy controls: a nationwide population-based study in Korea.

Direct effects of cancer cells and various cancer treatments can cause bone loss in cancer survivors. The aim of this study was to assess the risk of bone loss in Korean cancer survivors, and the relationship between body composition and bone mineral density (BMD). We hypothesized that cancer survivors would have lower BMD than healthy people, and increased muscle mass has a protective effect on BMD. We measured BMD and body composition in 259 cancer survivors (99 men and 160 women). Subjects were selected from the Korean National Health and Nutrition Survey conducted from 2008 to 2011. Body composition and BMD were measured by dual-energy X-ray absorptiometry. We examined the linear trend of lumbar BMD according to tertiles of lean mass (LM) and fat mass (FM) by linear regression, adjusting for age, alcohol consumption, smoking, exercise, 25-hydroxyvitamin D, height, protein intake, and menopausal status. Cancer survivors under 50 years of age had lower lumbar BMD compared with healthy controls (0.93 ± 0.04 g/cm2 vs. 1.02 ± 0.01 g/cm2, p = 0.032 in males; 0.95 ± 0.02 g/cm2 vs. 0.98 ± 0.01 g/cm2, p = 0.015 in females). Lumbar BMD significantly increased from the lowest to highest tertiles of LM in male (p for trend < 0.001) and marginally significantly increased in female survivors (p for trend = 0.060). In this study of Korean cancer survivors, young survivors were at higher risk of having low lumbar BMD. Higher LM had beneficial effects on BMD in cancer survivors. To prevent osteoporosis and fractures, efforts to increase lean body mass, including bone, are needed for young cancer survivors.

FBXW7-mediated stability regulation of signal transducer and activator of transcription 2 in melanoma formation.

In this study, we provide critical evidence that STAT2 stability regulation plays an essential role in melanoma cell proliferation and colony growth. We found that the interaction of FBXW7 and STAT2 induced STAT2 destabilization via a ubiquitination-mediated proteasomal degradation pathway. Notably, GSK3ß-mediated STAT2 phosphorylation facilitated STAT2-FBXW7 interactions via the DNA binding domain of STAT2 and domains 1, 2, 6, and 7 of FBXW7 WD40. Importantly, the inverse correlation between protein levels of STAT2 and FBXW7 were observed not only in human melanoma cells but also in a human skin cancer tissue array. The relationship between protein levels of STAT2 and FBXW7, cell proliferation, and colony growth were similarly observed in the melanoma cell lines SK-MEL-2, -5, and -28. Moreover, STAT2 knockdown in melanoma cells suppressed melanoma cell proliferation and colony formation. These data demonstrated that FBXW7-mediated STAT2 stability regulation plays an essential role in melanoma cell proliferation and cancer growth.

RSK2-Mediated ELK3 Activation Enhances Cell Transformation and Breast Cancer Cell Growth by Regulation of c-fos Promoter Activity.

Ribosomal S6 kinase 2 (RSK2), regulated by Ras/Raf/MEKs/ERKs, transmits upstream activation signals to downstream substrates including kinases and transcription and epigenetic factors. We observed that ELK members, including ELK1, 3, and 4, highly interacted with RSK2. We further observed that the RSK2-ELK3 interaction was mediated by N-terminal kinase and linker domains of RSK2, and the D and C domains of ELK3, resulting in the phosphorylation of ELK3. Importantly, RSK2-mediated ELK3 enhanced c-fos promoter activity. Notably, chemical inhibition of RSK2 signaling using kaempferol (a RSK2 inhibitor) or U0126 (a selective MEK inhibitor) suppressed EGF-induced c-fos promoter activity. Moreover, functional deletion of RSK2 by knockdown or knockout showed that RSK2 deficiency suppressed EGF-induced c-fos promoter activity, resulting in inhibition of AP-1 transactivation activity and Ras-mediated foci formation in NIH3T3 cells. Immunocytofluorescence assay demonstrated that RSK2 deficiency reduced ELK3 localization in the nucleus. In MDA-MB-231 breast cancer cells, knockdown of RSK2 or ELK3 suppressed cell proliferation with accumulation at the G1 cell cycle phase, resulting in inhibition of foci formation and anchorage-independent cancer colony growth in soft agar. Taken together, these results indicate that a novel RSK2/ELK3 signaling axis, by enhancing c-Fos-mediated AP-1 transactivation activity, has an essential role in cancer cell proliferation and colony growth.

The Correlation between Cognition Screening Scores and Gait Status from Three-Dimensional Gait Analysis.

BACKGROUND AND PURPOSE: Gait impairment in patients with cognitive decline has received considerable attention over the past several decades. However, gait disturbance in dementia is often underdiagnosed. The Mini Mental State Examination (MMSE) is the most widely used screening test for dementia, and the Montreal Cognitive Assessment (MoCA) has been developed for more accurate assessments of mild cognitive impairment (MCI). The purpose of this study was to determine the correlation between gait status and the scores on these screening tests for dementia. METHODS: We recruited 18 patients with MCI and 19 patients with early-stage dementia. All of the participants were examined using the Korean versions of the MMSE and MoCA developed for screening dementia (MMSE-DS and MoCA-K, respectively) and a neuropsychological test to determine cognitive function. A three-dimensional motion-capture system was used to perform objective measurements of gait in all participants. We evaluated the correlation between the screening scores and gait parameters. RESULTS: The MoCA-K score was significantly correlated with the walking speed (r=0.408, p<0.05) and stride length (r=0.334, p<0.05). After adjusting for age, the MoCA-K score remained correlated with the walking speed (r=0.331, p<0.05), whereas the MMSE-DS score (r=0.264, p=0.11) and stride length (r=0.206, p=0.22) were not. The neuropsychological test revealed that walking speed and stride length were significantly correlated with memory and frontal lobe function. CONCLUSIONS: We found that the MoCA-K reflects the gait status in patients with cognitive decline more accurately than does the MMSE-DS. Our results suggest that the MoCA-K has more advantages than the MMSE-DS as a screening tool for dementia.

Epimagnolin targeting on an active pocket of mammalian target of rapamycin suppressed cell transformation and colony growth of lung cancer cells.

Mammalian target of rapamycin (mTOR) has a pivotal role in carcinogenesis and cancer cell proliferation in diverse human cancers. In this study, we observed that epimagnolin, a natural compound abundantly found in Shin-Yi, suppressed cell proliferation by inhibition of epidermal growth factor (EGF)-induced G1/S cell-cycle phase transition in JB6 Cl41 cells. Interestingly, epimagnolin suppressed EGF-induced Akt phosphorylation strongly at Ser473 and weakly at Thr308 without alteration of phosphorylation of MAPK/ERK kinases (MEKs), extracellular signal-regulated kinase (ERKs), and RSK1, resulting in abrogation of the phosphorylation of GSK3ß at Ser9 and p70S6K at Thr389. Moreover, we found that epimagnolin suppressed c-Jun phosphorylation at Ser63/73, resulting in the inhibition of activator protein 1 (AP-1) transactivation activity. Computational docking indicated that epimagnolin targeted an active pocket of the mTOR kinase domain by forming three hydrogen bonds and three hydrophobic interactions. The prediction was confirmed by using in vitro kinase and adenosine triphosphate-bead competition assays. The inhibition of mTOR kinase activity resulted in the suppression of anchorage-independent cell transformation. Importantly, epimagnolin efficiently suppressed cell proliferation and anchorage-independent colony growth of H1650 rather than H460 lung cancer cells with dependency of total and phosphorylated protein levels of mTOR and Akt. Inhibitory signaling of epimagnolin on cell proliferation of lung cancer cells was observed mainly in mTOR-Akt-p70S6K and mTOR-Akt-GSK3ß-AP-1, which was similar to that shown in JB6 Cl41 cells. Taken together, our results indicate that epimagnolin potentiates as chemopreventive or therapeutic agents by direct active pocket targeting of mTOR kinase, resulting in sensitizing cancer cells harboring enhanced phosphorylation of the mTORC2-Akt-p70S6k signaling pathway.

Magnolin targeting of ERK1/2 inhibits cell proliferation and colony growth by induction of cellular senescence in ovarian cancer cells.

Ras/Raf/MEKs/ERKs and PI3 K/Akt/mTOR signaling pathways have key roles in cancer development and growth processes, as well as in cancer malignance and chemoresistance. In this study, we screened the therapeutic potential of magnolin using 15 human cancer cell lines and combined magnolin sensitivity with the CCLE mutaome analysis for relevant mutation information. The results showed that magnolin efficacy on cell proliferation inhibition were lower in TOV-112D ovarian cancer cells than that in SKOV3 cells by G1 and G2/M cell cycle phase accumulation. Notably, magnolin suppressed colony growth of TOV-112D cells in soft agar, whereas colony growth of SKOV3 cells in soft agar was not affected by magnolin treatment. Interestingly, phospho-protein profiles in the MAPK and PI3 K signaling pathways indicated that SKOV3 cells showed marked increase of Akt phosphorylation at Thr308 and Ser473 and very weak ERK1/2 phosphorylation levels by EGF stimulation. The phospho-protein profiles in TOV-112D cells were the opposite of those of SKOV3 cells. Importantly, magnolin treatment suppressed phosphorylation of RSKs in TOV-112D, but not in SKOV3 cells. Moreover, magnolin increased SA-ß-galactosidase-positive cells in a dose-dependent manner in TOV-112D cells, but not in SKOV3 cells. Notably, oral administration of Shin-Yi fraction 1, which contained magnolin approximately 53%, suppressed TOV-112D cell growth in athymic nude mice by induction of p16Ink4a and p27Kip1 . Taken together, targeting of ERK1 and ERK2 is suitable for the treatment of ovarian cancer cells that do not harbor the constitutive active P13 K mutation and the loss-of-function mutations of the p16 and/or p53 tumor suppressor proteins.

Relationship between Age at Menarche and Metabolic Syndrome in Premenopausal Women: Korea National Health and Nutrition Examination Survey 2013-2014.

BACKGROUND: Early menarche may be associated with increased risk of cardiovascular disease. The aim of this study was to evaluate the relationship between age at menarche and metabolic syndrome (MetS) in Korean premenopausal women. METHODS: We used nationally representative data from the Korea National Health and Nutrition Examination Survey from 2013 to 2014, and 3,023 premenopausal women aged 20-55 years were our subjects. We defined early menarche as age at first menstrual period less than 12 years. Multivariable logistic regression analysis was used to evaluate the relationship between age at menarche and MetS after adjusting for current age, and socioeconomic, lifestyle, and reproductive variables. RESULTS: MetS was much more common in women aged 40-55 years than in women aged 20-39 years (4.1% vs. 15.1%). Compared with women who experienced menarche at age 12-15 years, the risk of MetS in the early menarche group was not higher in either age group, after adjusting for current age, and socioeconomic, lifestyle, and reproductive variables (odds ratio [OR], 1.767; 95% confidence interval [CI], 0.718-4.351 in those aged 20-39 years; OR, 1.780; 95% CI, 0.775-4.085 in those aged 40-55 years). The risk of MetS in women with menarche at age ≥16 years was not higher than in women with menarche at age 12-15 years. CONCLUSION: Early or late menarche was not associated with an increased risk of MetS in premenopausal Korean women. Even before menopause, current age has a major influence on the development of MetS.

Relationship between Dry Eye Syndrome and Frequency of Coffee Consumption in Korean Adults: Korea National Health and Nutrition Examination Survey V, 2010-2012.

BACKGROUND: Dry eye syndrome is a common health problem in the adult population. Many risk factors including age, sex, prior eye surgery, various chronic diseases, and lifestyle factors can affect its development. We have evaluated the risk of dry eye syndrome based on the frequency of coffee consumption among Korean adult population. METHODS: A total of 9,752 adults with age 19 years and older were randomly selected between 2010 and 2012. They have all participated in the National Health and Nutrition Examination Survey V of Korea. Dry eye syndrome was being diagnosed by the physicians at some points in the participant's lifetime. The average daily coffee intake was divided into the following: less than 1 cup, 1 to 2 cups, and 3 cups or more. Various physio-environmental factors and medical conditions were used as correction variables to assess the risk of dry eye syndrome in relation to the frequency of coffee consumption. RESULTS: The prevalence of dry eye syndrome decreased to 9.2%, 8.8%, and 6.3% as coffee consumption increased from less than 1 cup to 1-2 cups and more than 3 cups, respectively. However, there was no significant relationship between the frequency of coffee consumption and the risk of dry eye syndrome after adjusting various risk factors. CONCLUSION: There is no relationship between the frequency of coffee consumption and risk of dry eye syndrome.

Low dietary energy intake is associated with sarcopenia in cancer survivors: An analysis based on the Korean National Health and Nutrition Examination Survey 2008-2011.

As cancer survivors increase, management of their long-term health consequences becomes important. Sarcopenia could negatively affect on their clinical outcome and quality of life. We hypothesized that sarcopenia would be more prevalent in cancer survivors and that are associated with dietary intake. This study was conducted to compare nutritional intake and body composition, considering sarcopenia, between cancer survivors and healthy individuals using Korean National Health and Nutrition Examination Surveys conducted from 2008 to 2011. The participants were 259 adult cancer survivors and 1,295 healthy counterparts who underwent body composition tests and had no chronic diseases. Sarcopenia was defined as a condition with a skeletal muscle mass below the cut-off value (men < 6.58 kg/m2 and women < 4.59 kg/m2) adjusted for height. The prevalence of sarcopenia was higher in non-obese male cancer survivors (32.6% vs 16.0%, P=0.034) compared with healthy individuals. On the contrary, sarcopenia was more common in obese female survivors (35.1% vs 15.0%, P=0.005) than their healthy counterparts. Multivariable logistic analyses revealed that age increase by 1 year (aOR=1.025; 95% CI: 1.001-1.049), male gender (aOR=3.688; 95% CI: 6.061-90.910), and a lower BMI (aOR=33.201; 95% CI: 13.639-80.823) were significantly associated with the increased risk of sarcopenia. Increased energy intake by 100 kcal/day (aOR=0.930; 95% CI: 0.869-0.995) had a protective effect against sarcopenia. Our results suggest that male cancer survivors are high risk group of sarcopenia, especially when they are non-obese. More dietary energy intake may be needed to prevent sarcopenia.

Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis. Moreover, a molecular docking study revealed that kaempferol inhibited FGFR3 activity by binding to the active pocket of the FGFR3 kinase domain. Kaempferol forms hydrogen bonds with the FGFR3 backbone oxygen of Glu555 and Ala558 and the side chain of Lys508. Notably, the inhibition of bFGF-FGFR3-RSK2 signaling by kaempferol suppresses the proliferation and migration of RA FLSs and the release of activated T-cell-mediated inflammatory cytokines, such as IL-17, IL-21, and TNF-α. We further found that activated phospho-FGFR3 and -RSK2 were more highly observed in RA than in OA synovium. The hyperplastic lining and sublining lymphoid aggregate layers of RA synovium showed p-RSK2-expressing CD68+ macrophages with high frequency, while pRSK2-expressing CD4+ T-cells was observed at a lower frequency. Notably, kaempferol administration in collagen-induced arthritis mice relieved the frequency and severity of arthritis. Kaempferol reduced osteoclast differentiation in vitro and in vivo relative to the controls and was associated with the inhibition of osteoclast markers, such as tartrate-resistant acid phosphatase, integrin ß3, and MMP9. Conclusively, our data suggest that bFGF-induced FGFR3-RSK2 signaling may play a critical role during the initiation and progression of RA in terms of FLS proliferation and enhanced osteoclastogenesis, and that kaempferol may be effective as a new treatment for RA.

Dynamic Energy Balance and Obesity Prevention.

Dynamic energy balance can give clinicians important answers for why obesity is so resistant to control. When food intake is reduced for weight control, all components of energy expenditure change, including metabolic rate at rest (resting energy expenditure [REE]), metabolic rate of exercise, and adaptive thermogenesis. This means that a change in energy intake influences energy expenditure in a dynamic way. Mechanisms associated with reduction of total energy expenditure following weight loss are likely to be related to decreased body mass and enhanced metabolic efficiency. Reducing calorie intake results in a decrease in body weight, initially with a marked reduction in fat free mass and a decrease in REE, and this change is maintained for several years in a reduced state. Metabolic adaptation, which is not explained by changes in body composition, lasts for more than several years. These are powerful physiological adaptations that induce weight regain. To avoid a typically observed weight-loss and regain trajectory, realistic weight loss goals should be established and maintained for more than 1 year. Using a mathematical model can help clinicians formulate advice about diet control. It is important to emphasize steady efforts for several years to maintain reduced weight over efforts to lose weight. Because obesity is difficult to reverse, clinicians must prioritize obesity prevention. Obesity prevention strategies should have high feasibility, broad population reach, and relatively low cost, especially for young children who have the smallest energy gaps to change.

Delphi Survey for Designing a Intervention Research Study on Childhood Obesity Prevention.

BACKGROUND: The prevalence of childhood obesity in South Korea has increased owing to economic improvement and the prevailing Westernized dietary pattern. As the incidence of chronic diseases caused by obesity is also expected to increase, effective interventions to prevent childhood obesity are needed. Therefore, we conducted a Delphi study to determine the priorities of a potential intervention research on childhood obesity prevention and its adequacy and feasibility. METHODS: The two-round Delphi technique was used with a panel of 10 childhood obesity experts. The panelists were asked to rate "priority populations," "methods of intervention," "measurement of outcomes," "future intervention settings," and "duration of intervention" by using a structured questionnaire. Finally, a portfolio analysis was performed with the adequacy and feasibility indexes as the two axes. RESULTS: For priority populations, the panel favored "elementary," "preschool," and "middle and high school" students in this order. Regarding intervention settings, the panelists assigned high adequacy and feasibility to "childcare centers" and "home" for preschool children, "school" and "home" for elementary school children, and "school" for adolescents in middle and high school. As the age of the target population increased, the panelists scored increasing numbers of anthropometric, clinical, and intermediate outcomes as highly adequate and feasible for assessing the effectiveness of the intervention. CONCLUSION: According to the results of the Delphi survey, the highest-priority population for the research on childhood obesity prevention was that of elementary school students. Various settings, methods, outcome measures, and durations for the different age groups were also suggested.

Influenza Vaccination Coverage Rate according to the Pulmonary Function of Korean Adults Aged 40 Years and Over: Analysis of the Fifth Korean National Health and Nutrition Examination Survey.

Influenza vaccination is an effective strategy to reduce morbidity and mortality, particularly for those who have decreased lung functions. This study was to identify the factors that affect vaccination coverage according to the results of pulmonary function tests depending on the age. In this cross-sectional study, data were obtained from 3,224 adults over the age of 40 who participated in the fifth National Health and Nutrition Examination Survey and underwent pulmonary function testing in 2012. To identify the factors that affect vaccination rate, logistic regression analysis was conducted after dividing the subjects into two groups based on the age of 65. Influenza vaccination coverage of the entire subjects was 45.2%, and 76.8% for those aged 65 and over. The group with abnormal pulmonary function had a higher vaccination rate than the normal group, but any pulmonary dysfunction or history of COPD did not affect the vaccination coverage in the multivariate analysis. The subjects who were 40-64 years-old had higher vaccination coverage when they were less educated or with restricted activity level, received health screenings, and had chronic diseases. Those aged 65 and over had significantly higher vaccination coverage only when they received regular health screenings. Any pulmonary dysfunction or having COPD showed no significant correlation with the vaccination coverage in the Korean adult population.

Molecular Targeting of ERKs/RSK2 Signaling Axis in Cancer Prevention.

RSK2 is a downstream signaling protein of ERK1 and ERK2 and plays a key role in physiological homeostasis. For this reason, RSK2 is a highly conserved protein among the p90RSK family members. In its location in the signaling pathway, RSK2 is a kinase just upstream of transcription and epigenetic factors, and a few kinases involved in cell cycle regulation and protein synthesis. Moreover, activation of RSK2 by growth factors is directly involved in cell proliferation, anchorage-independent cell transformation and cancer development. Direct evidences regarding the etiological roles of RSK2 in cancer development in humans have been published by our research group illustrating that elevated total- and phospho-RSK2 protein levels mediated by ERK1 and ERK2 are higher in skin cancer tissues compared to normal skin tissues. Notably, it has been shown that RSK2 ectopic expression in JB6 Cl41 cells induces cell proliferation and anchorage- independent cell transformation. Importantly, knockdown of RSK2 suppresses Ras-mediated foci formation and anchorage-independent colony growth of cancer cells. Kaempferol is a one of the natural compounds showing selectivity in inhibiting RSK2 activity in epidermal growth factor-induced G1/S cell cycle transition and cell transformation. Thus, ERKs/RSK2 signaling axis is an important target signaling molecule in chemoprevention.