Abstract Introduction AMP-activated protein kinase (AMPK) has been reported to stimulate differentiation and proliferation of osteoblasts, but the role of AMPK in the physiology of osteoclasts has ...not been investigated. Method Osteoclasts were differentiated from mouse BMMϕs. TRAP-positive multinucleated cells were considered to be osteoclasts using TRAP staining, and resorption area was determined by incubation of cells on dentine discs. Signaling pathways were investigated using Western blotting and RT-PCR. Results RANKL induced phosphorylation/activation of AMPK-α in BMMϕs and stimulated formation of TRAP-positive multinucleated cells. Pharmacological inhibition of AMPK with compound C and siRNA-mediated knockdown of AMPK-α1, the predominant α-subunit isoform in BMMϕs, increased RANKL-induced formation of TRAP-positive multinucleated cells and bone resorption via activation of the downstream signaling elements p38, JNK, NF-κB, Akt, CREB, c-Fos, and NFATc1. STO-609, an inhibitor of CaMKK, completely blocked the RANKL-induced activation of AMPK-α, but KN-93, an inhibitor of CaMK, did not. siRNA-mediated TAK1 knockdown also blocked RANKL-induced activation of AMPK-α. The AMPK activators metformin, (−)-epigallocatechin-3-gallate, berberine, resveratrol, and α-lipoic acid dose-dependently suppressed formation of TRAP-positive multinucleated cells and bone resorption. Conclusion AMPK negatively regulates RANKL, possibly by acting through CaMKK and TAK1. Thus, the development of AMPK activators may be a useful strategy for inhibiting the resorption of bone that is stimulated under RANKL-activated conditions.
Mounting evidence implicates an association between ambient air pollution and impaired reproductive potential of human. Our study aimed to assess the association between air pollution and ovarian ...reserve in young, infertile women.
Our study included 2276 Korean women who attended a single fertility center in 2016-2018. Women's exposure to air pollution was assessed using concentrations of particulate matter (PM
and PM
), nitrogen dioxide (NO
), carbon monoxide (CO), sulfur dioxide (SO
), and ozone (O
) that had been collected at 269 air quality monitoring sites. Exposure estimates were computed for 1, 3, 6, and 12 months prior to the ovarian reserve tests. Anti-Müllerian hormone (AMH) ratio (defined as an observed-to-expected AMH based on age) and low AMH (defined as < 0.5 ng/mL) were employed as indicators of ovarian reserve. We included a clustering effect of 177 districts in generalized estimating equations approach. A secondary analysis was conducted restricting the analyses to Seoul residents to examine the association in highly urbanized setting.
The mean age was 36.6 ± 4.2 years and AMH level was 3.3 ± 3.1 ng/mL in the study population. Average AMH ratio was 0.8 ± 0.7 and low AMH was observed in 10.3% of women (n=235). The average concentration of six air pollutants was not different between the normal ovarian reserve and low AMH groups for all averaging periods. In multivariable models, an interquartile range (IQR)-increase in 1 month-average PM
was associated with decrease in AMH ratio among total population (β= -0.06, 95% confidence interval: -0.11, 0.00). When we restrict our analysis to those living in Seoul, IQR-increases in 1 and 12 month-average PM
were associated with 3% (95% CI: -0.07, 0.00) and 10% (95% CI: -0.18, -0.01) decrease in AMH ratio. The ORs per IQR increase in the six air pollutants were close to null in total population and Seoul residents.
In a cohort of infertile Korean women, there was a suggestive evidence of the negative association between ambient PM concentration and ovarian reserve, highlighting the potential adverse impact of air pollution on women's fertility.
Summary Background Compared with open resection, laparoscopic resection of rectal cancers is associated with improved short-term outcomes, but high-level evidence showing similar long-term outcomes ...is scarce. We aimed to compare survival outcomes of laparoscopic surgery with open surgery for patients with mid-rectal or low-rectal cancer. Methods The Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was an open-label, non-inferiority, randomised controlled trial done between April 4, 2006, and Aug 26, 2009, at three centres in Korea. Patients (aged 18–80 years) with cT3N0–2M0 mid-rectal or low-rectal cancer who had received preoperative chemoradiotherapy were randomly assigned (1:1) to receive either open or laparoscopic surgery. Randomisation was stratified by sex and preoperative chemotherapy regimen. Investigators were masked to the randomisation sequence; patients and clinicians were not masked to the treatment assignments. The primary endpoint was 3 year disease-free survival, with a non-inferiority margin of 15%. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00470951. Findings We randomly assigned 340 patients to receive either open surgery (n=170) or laparoscopic surgery (n=170). 3 year disease-free survival was 72·5% (95% CI 65·0–78·6) for the open surgery group and 79·2% (72·3–84·6) for the laparoscopic surgery group, with a difference that was lower than the prespecified non-inferiority margin (–6·7%, 95% CI −15·8 to 2·4; p<0·0001). 25 (15%) patients died in the open group and 20 (12%) died in the laparoscopic group. No deaths were treatment related. Interpretation Our results show that laparoscopic resection for locally advanced rectal cancer after preoperative chemoradiotherapy provides similar outcomes for disease-free survival as open resection, thus justifying its use. Funding National Cancer Center, South Korea.
Cervical enamel projections (CEPs) represent a unique developmental and anatomical anomaly wherein the enamel structure extends apically beyond the cemento‐enamel junction of the tooth. In this ...scoping review, the existing literature on CEPs was evaluated to delineate their characteristics, prevalence, predilection for specific teeth and surfaces, clinical significance, and management approaches. Searches were conducted on MEDLINE (PubMed), Cochrane Library, and Embase databases using the keywords “enamel projection(s)” or “ectopic enamel.” In total, 24 studies meeting inclusion criteria were included in the review. The prevalence of CEPs varied widely (8.3%–85.1%), predominantly manifesting as grade I or grade III. Mandibular first and second molars exhibited a higher incidence of CEPs, with a notable predilection for buccal surfaces. The consensus in most studies was that CEPs are associated with localized periodontal diseases. Recommendations inclined toward the removal of ectopic enamel during periodontal surgery to enhance periodontal attachment formation. However, decision‐making should involve careful consideration of the benefits and drawbacks based on individual circumstances.
Evidence indicates that air pollution contributes to cardiopulmonary mortality. There is ongoing debate regarding the size and shape of the pollution–mortality exposure–response relationship. There ...are also growing appeals for estimates of pollution–mortality relationships that use public data and are based on large, representative study cohorts.
Our goal was to evaluate fine particulate matter air pollution (Formula: see text) and mortality using a large cohort that is representative of the U.S. population and is based on public data. Additional objectives included exploring model sensitivity, evaluating relative effects across selected subgroups, and assessing the shape of the Formula: see text–mortality relationship.
National Health Interview Surveys (1986–2014), with mortality linkage through 2015, were used to create a cohort of 1,599,329 U.S. adults and a subcohort with information on smoking and body mass index (BMI) of 635,539 adults. Data were linked with modeled ambient Formula: see text at the census-tract level. Cox proportional hazards models were used to estimate Formula: see text–mortality hazard ratios for all-cause and specific causes of death while controlling for individual risk factors and regional and urban versus rural differences. Sensitivity and subgroup analyses were conducted and the shape of the Formula: see text–mortality relationship was explored.
Estimated mortality hazard ratios, per Formula: see text long-term exposure to Formula: see text, were 1.12 (95% CI: 1.08, 1.15) for all-cause mortality, 1.23 (95% CI: 1.17, 1.29) for cardiopulmonary mortality, and 1.12 (95% CI: 1.00, 1.26) for lung cancer mortality. In general, Formula: see text–mortality associations were consistently positive for all-cause and cardiopulmonary mortality across key modeling choices and across subgroups of sex, age, race-ethnicity, income, education levels, and geographic regions.
This large, nationwide, representative cohort of U.S. adults provides robust evidence that long-term Formula: see text exposure contributes to cardiopulmonary mortality risk. The ubiquitous and involuntary nature of exposures and the broadly observed effects across subpopulations underscore the public health importance of breathing clean air. https://doi.org/10.1289/EHP4438.
Summary Background In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung ...Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital. Methods We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission. Findings 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% 23/117 vs 5% 3/58 in group B vs 1% 4/500 in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2–17, IQR 5–10). The median incubation period was significantly shorter in group A than in group C (5 days IQR 4–8 vs 11 days 6–12; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure. Interpretation Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. Funding None.
Studies of source apportionment (SA) for particulate matter (PM) air pollution have enhanced understanding of dominant pollution sources and quantification of their contribution. Although there have ...been many SA studies in South Korea over the last two decades, few studies provided an integrated understanding of PM sources nationwide. The aim of this study was to summarize findings of PM SA studies of South Korea and to explore study characteristics.
We selected studies that estimated sources of PM10 and PM2.5 performed for 2000–2017 in South Korea using Positive Matrix Factorization and Chemical Mass Balance. We reclassified the original PM sources identified in each study into seven categories: motor vehicle, secondary aerosol, soil dust, biomass/field burning, combustion/industry, natural source, and others. These seven source categories were summarized by using frequency and contribution across four regions, defined by northwest, west, southeast, and southwest regions, by PM10 and PM2.5. We also computed the population-weighted mean contribution of each source category. In addition, we compared study features including sampling design, sampling and lab analysis methods, chemical components, and the inclusion of Asian dust days.
In the 21 selected studies, all six PM10 studies identified motor vehicle, soil dust, and combustion/industry, while all 15 PM2.5 studies identified motor vehicle and soil dust. Different from the frequency, secondary aerosol produced a large contribution to both PM10 and PM2.5. Motor vehicle contributed highly to both, whereas the contribution of combustion/industry was high for PM10. The population-weighted mean contribution was the highest for the motor vehicle and secondary aerosol sources for both PM10 and PM2.5. However, these results were based on different subsets of chemical speciation data collected at a single sampling site, commonly in metropolitan areas, with short overlap and measured by different lab analysis methods.
We found that motor vehicle and secondary aerosol were the most common and influential sources for PM in South Korea. Our study, however, suggested a caution to understand SA findings from heterogeneous study features for study designs and input data.
Display omitted
We explored the most common and influential sources for PM in South Korea. Study characteristics are important for understanding estimated PM sources.
We prospectively investigated the association between a change of serum vascular endothelial growth factor (VEGF) level after transcatheter arterial chemoembolization (TACE) and hepatocellular ...carcinoma (HCC) patient prognosis. The study involved 147 patients with unresectable HCC treated at the National Cancer Center, Korea, between July and December 2005. Serum samples were collected from each patient before TACE, and 1–2 days and 1 month after TACE. Serum VEGF concentrations were measured using an enzyme‐linked immunosorbent assay (ELISA). The loge(VEGF/platelets) increased transiently 1–2 days after TACE and declined thereafter. Frequency of previous TACE did not correlate with loge(VEGF/platelets). This study found that loge(VEGF/platelets) 1–2 days after TACE, but not loge(VEGF/platelets) at baseline, was strongly correlated with vascular or nodal invasion and AJCC (American Joint Committee on Cancer)/UICC (International Union Against Cancer) stage, and was significantly greater in men. Relative changes in serum VEGF/platelet levels 1–2 days after TACE (ΔVEGF) > 0.5 were directly correlated with tumor size, vascular invasion and modified UICC and AJCC/UICC stage (P < 0.05 for each). Additionally, ΔVEGF > 0.5 was significantly correlated with newly developed extrahepatic metastases one and six months after TACE (P = 0.005 and 0.003, respectively). Progression free survival of patients with ΔVEGF > 0.5 was significantly worse (P < 0.001) and ΔVEGF > 0.5 was an independent prognostic factor for PFS (hazard ratio, 3.111; P < 0.001). This study showed that a high increment in serum VEGF level 1–2 days after TACE in HCC patients was associated with distant metastasis and unfavorable outcomes. (Cancer Sci 2008; 99: 2037–2044)
National-scale empirical models for air pollution can include hundreds of geographic variables. The impact of model parsimony (i.e., how model performance differs for a large versus small number of ...covariates) has not been systematically explored. We aim to (1) build annual-average integrated empirical geographic (IEG) regression models for the contiguous U.S. for six criteria pollutants during 1979-2015; (2) explore systematically the impact on model performance of the number of variables selected for inclusion in a model; and (3) provide publicly available model predictions. We compute annual-average concentrations from regulatory monitoring data for PM10, PM2.5, NO2, SO2, CO, and ozone at all monitoring sites for 1979-2015. We also use ~350 geographic characteristics at each location including measures of traffic, land use, land cover, and satellite-based estimates of air pollution. We then develop IEG models, employing universal kriging and summary factors estimated by partial least squares (PLS) of geographic variables. For all pollutants and years, we compare three approaches for choosing variables to include in the PLS model: (1) no variables, (2) a limited number of variables selected from the full set by forward selection, and (3) all variables. We evaluate model performance using 10-fold cross-validation (CV) using conventional and spatially-clustered test data. Models using 3 to 30 variables selected from the full set generally have the best performance across all pollutants and years (median R2 conventional clustered CV: 0.66 0.47) compared to models with no (0.37 0) or all variables (0.64 0.27). Concentration estimates for all Census Blocks reveal generally decreasing concentrations over several decades with local heterogeneity. Our findings suggest that national prediction models can be built by empirically selecting only a small number of important variables to provide robust concentration estimates. Model estimates are freely available online.
Postpolypectomy surveillance guidelines for colorectal cancer introduced the concept of 'risk stratification'; however, few studies have been conducted for validation of its usefulness. The aim of ...this study was to assess the 5-year incidence of advanced neoplasia recurrence based on the risk stratification scheme of the guidelines and to identify its risk factors.
A prospective study of surveillance colonoscopy after screening colonoscopy was carried out at the Seoul National University Hospital Healthcare System Gangnam Center. 3803 asymptomatic Koreans aged 50-69 were enrolled prospectively and 5-year cumulative adenoma rates were analysed according to three risk groups: normal (no baseline adenoma), low-risk (1-2 adenomas <10 mm) and high-risk (an advanced adenoma or ≥ 3 adenomas) groups. The RR was computed by HR using Cox proportional regression after multivariate adjustments. The primary outcome was the 5-year cumulative rate of recurrent advanced adenoma in each risk category and the secondary outcome was its predictive factors.
Among 3803 subjects enrolled between 2003 and 2005, 2452 were followed-up within 5 years: 1242, 671 and 539 in the normal, low-risk and high-risk groups, respectively. Compared with the normal group, the low-risk group had a sufficiently low 5-year incidence and did not show an increased risk for subsequent advanced adenoma (2.4% vs 2.0%, HR=1.14, 95% CI 0.61 to 2.17). Conversely, a significantly higher 5-year rate (12.2%) and early recurrence (4.6, 7.4 and 9.6% at 1, 2 and 3 years) of advanced adenoma were revealed in the high-risk group. Among various patients and adenoma characteristics, only high-risk adenoma (HR=5.95, 95% CI 3.66 to 9.68) along with a number of ≥ 3 (HR=3.06, 95% CI 1.51 to 6.57) and size ≥ 10 mm (HR=3.02, 95% CI 1.80 to 5.06) were independent predictors.
The surveillance interval for low-risk patients could be extended beyond 5 years. Colonoscopic surveillance should be targeted to high-risk patients, and 3-year follow-up after initial polypectomy may be appropriate.
PDF
