Outcomes of systemic treatment according to germline mutational status in patients with metastatic pheochromocytoma and paraganglioma.

INTRODUCTION: Metastatic disease affects approximately 15% to 17% of patients with pheochromocytomas and paragangliomas (PPGLs). Unfortunately, treatment options for metastatic PPGLs are limited and rely on small, nonrandomized clinical trials. The impact of germline mutation status on systemic treatment outcomes remains unclear. To address these gaps, we retrospectively evaluated treatment outcomes in patients with PPGL. PATIENTS AND METHODS: Between December 2004 and December 2021, 33 patients were diagnosed with metastatic PPGLs and received systemic treatment at the Department of Oncology, Asan Medical Center, Seoul, South Korea. RESULTS: The median age of the patients was 49. Germline mutations were revealed in nine patients (39.1%) out of 23 who underwent germline testing, with SDHB mutation being the most frequent in 5 patients. Cyclophosphamide, vincristine, and dacarbazine (CVD) chemotherapy was administered to 18 patients, with an objective response rate (ORR) of 22% and a disease control rate (DCR) of 67%. The median progression-free survival (PFS) was 7.9 and the median overall survival (OS) was 36.2 months. Sunitinib was given to 6 patients, which had an ORR of 33%, a DCR of 83%, and a median PFS of 14.6 months. Notably, patients with SDHB/SDHD mutation (4 patients and one patient, respectively) who received CVD treatment had a significantly better OS than those without (median OS 94.0 months vs. 13.7 months, P = .01). CONCLUSION: Our study reveals that CVD and sunitinib are effective treatments for metastatic PPGLs. The results are consistent with previous studies and patients with SDHB and SDHD mutations may benefit most from CVD treatment.

Organ-specific response with first-line atezolizumab-bevacizumab versus lenvatinib for patients with advanced hepatocellular carcinoma.

BACKGROUND: Immune checkpoint inhibitor (ICI)-based treatments have become the mainstay of first-line treatment for unresectable hepatocellular carcinoma (HCC), but there has been a concern that intrahepatic HCC lesions may be less responsive to ICI monotherapy. We aimed to investigate the organ-specific response patterns among unresectable HCC patients treated with first-line atezolizumab-bevacizumab or lenvatinib. METHODS: This retrospective study included 386 patients with Child-Pugh A unresectable HCC who were treated with first-line atezolizumab-bevacizumab (n = 217) or lenvatinib (n = 169). The organ-specific response was separately evaluated according to the site of the lesions: liver, lung, lymph node (LN), and intraabdomen based on a radiological evaluation adopted from RECIST v 1.1. RESULTS: The median age was 60 years. Hepatitis B infection was the most common etiology (n = 270, 69.9%), and 291 (75.4%) patients had a viral etiology. The proportion of patients achieving a ≥ 30% reduction in the tumor burden for each organ category was overall higher in the atezolizumab-bevacizumab group than that in the lenvatinib group: 20.2% vs. 11.8%, 23.0% vs. 12.2%, 27.9% vs. 17.9% and 33.3% vs. 15.0% for intrahepatic, lung, LN, and intraabdominal lesions, respectively. The corresponding values for the subgroup with a viral etiology were 17.3% vs. 8.1%, 18.8% vs. 13.3%, 28.9% vs. 3.6%, and 36.0% vs. 12.5%, respectively. CONCLUSION: Compared to lenvatinib, atezolizumab-bevacizumab was associated with a favorable organ-specific response regardless of the site of the tumor lesions. Unlike anti-PD-1 monotherapy, atezolizumab-bevacizumab had a comparable organ-specific response between intrahepatic and extrahepatic lesions, especially for those with viral etiology HCCs.

Combination Analysis of PCDHGA12 and CDO1 DNA Methylation in Bronchial Washing Fluid for Lung Cancer Diagnosis.

BACKGROUND: When suspicious lesions are observed on computer-tomography (CT), invasive tests are needed to confirm lung cancer. Compared with other procedures, bronchoscopy has fewer complications. However, the sensitivity of peripheral lesion through bronchoscopy including washing cytology is low. A new test with higher sensitivity through bronchoscopy is needed. In our previous study, DNA methylation of PCDHGA12 in bronchial washing cytology has a diagnostic value for lung cancer. In this study, combination of PCDHGA12 and CDO1 methylation obtained through bronchial washing cytology was evaluated as a diagnostic tool for lung cancer. METHODS: A total of 187 patients who had suspicious lesions in CT were enrolled. PCDHGA12 methylation test, CDO1 methylation test, and cytological examination were performed using 3-plex LTE-qMSP test. RESULTS: Sixty-two patients were diagnosed with benign diseases and 125 patients were diagnosed with lung cancer. The sensitivity of PCDHGA12 was 74.4% and the specificity of PCDHGA12 was 91.9% respectively. CDO1 methylation test had a sensitivity of 57.6% and a specificity of 96.8%. The combination of both PCDHGA12 methylation test and CDO1 methylation test showed a sensitivity of 77.6% and a specificity of 90.3%. The sensitivity of lung cancer diagnosis was increased by combining both PCDHGA12 and CDO1 methylation tests. CONCLUSION: Checking DNA methylation of both PCDHGA12 and CDO1 genes using bronchial washing fluid can reduce the invasive procedure to diagnose lung cancer.

Prognostic significance of 25-hydroxyvitamin D levels in patients with peripheral T-cell lymphoma.

Vitamin D insufficiency has been linked to unfavourable outcomes in diverse malignancies. However, the prognostic significance of vitamin D levels in peripheral T-cell lymphoma (PTCL) remains unclear. In this study, we thus aimed to assess the prognostic relevance of 25-hydroxyvitamin D [25(OH)D] levels in patients newly diagnosed with PTCL. The analysis included 144 patients with PTCL treated from March 2015 to May 2020. The median 25(OH)D level was 12.2 (1.7-48.8) ng/mL, and 59 (41%) patients had vitamin D deficiency. Patients with vitamin D deficiency demonstrated significantly worse event-free survival (EFS) and overall survival (OS). In the multivariate analysis, vitamin D was independently associated with OS, with a hazard ratio of 1.66 (95% confidence interval, 1.05-2.63, p = 0.030). These findings suggest that vitamin D deficiency significantly correlates with poor survival outcomes in patients with PTCL.

Tracking the pumice rafts from the Fukutoku-Okanoba submarine volcano with Satellites and a Lagrangian Particles trajectory model.

On August 13th, 2021, the Fukutoku-Okanoba, a submarine volcano in the Northwest Pacific Ocean, erupted. Satellites detected various pumice rafts that had drifted westward to reach southern Japan over two months. To cope with the potential danger from pumice rafts, predicting their trajectories is crucial. Using a Lagrangian particle tracking model, the trajectories of the rafts were investigated. The model results showed strong sensitivity to the windage coefficient of pumice rafts, which is uncertain and could cause significant errors. An optimal windage coefficient was estimated by comparing the model results with satellite images using a skill score based on the distance between simulated particles and the nearest observed rafts divided by the travel distance of the particles. The optimal windage coefficients ranged between 2 and 3 % and produced pathways comparable to the observations from satellites. The simulation results showed that the pumice rafts moved from Fukutoku-Okanoba toward the Ryukyu Islands for approximately two months prior to being pushed by the north-easterly wind toward Taiwan against the Kuroshio. The methods presented here may become a valuable tool in managing coastal hazards due to diverse marine debris.

Spatio-temporal structures of satellite-derived water quality indicators along the Korean South Coast.

The structure of 9-year time series data for Sea Surface Temperature (SST), Chlorophyll a (Chl-a) and Total Suspended Solids (TSS), derived from the Visible Infrared Imaging Radiometer Suite (VIIRS), was examined in this study. Authors found that there exists strong seasonality among the three variables with spatial heterogeneity along the Korean South Coast (KSC). In specific, SST was in phase with Chl-a, but out of phase with TSS by six months. A strong inversed spectral power with six-month phase-lag was found between Chl-a and TSS. This could be attributed to different dynamics and environmental settings. For example, Chl-a concentration seemed to have strong positive correlation with SST indicating typical seasonality of marine biogeochemical processes such as primary production; while a strong negative correlation between TSS and SST might have been influenced by changes in physical oceanographic processes, such as stratification and monsoonal wind-driven vertical mixing. In addition, the strong east-west heterogeneity of Chl-a suggests that the marine coastal environments are predominantly governed by distinct local hydrological conditions and human activities associated with land cover and land use, while the east-west spatial pattern revealed in TSS timeseries was associated with the gradient of tidal forcings and topographical changes keeping tidally induced resuspension low eastward.

Regulating POLR3G by MicroRNA-26a-5p as a promising therapeutic target of lung cancer stemness and chemosensitivity.

Cancer stem cells (CSCs) identified in lung cancer exhibit resistance to chemotherapy, radiotherapy, and targeted therapy. Therefore, a technology for controlling CSCs is needed to overcome such resistance to cancer therapy. Various evidences about the association between epithelial-mesenchymal transition related transcriptomic alteration and acquisition of CSC phenotype have been proposed recently. Down-regulated miR-26a-5p is closely related to mesenchymal-like lung cancer cell lines. These findings suggest that miR-26a-5p might be involved in lung cancer stemness. RNA polymerase III subunit G (POLR3G) was selected as a candidate target of miR-26a-5p related to cancer stemness. It was found that miR-26a-5p directly regulates the expression of POLR3G.Overexpression of miR-26a-5p induced a marked reduction of colony formation and sphere formation. Co-treatment of miR-26a-5p and paclitaxel decreased cell growth, suggesting that miR-26a-5p might play a role as a chemotherapy sensitizer. In the cancer genome atlas data, high miR-26a-5p and low POLR3G expression were also related to higher survival rate of patients with lung adenocarcinoma. These results suggest that miR-26a-5p can suppress lung cancer stemness and make cancer cell become sensitive to chemotherapy. This finding provides a novel insight into a potential lung cancer treatment by regulating stemness.

Holocene centennial variability in sea surface temperature and linkage with solar irradiance.

The climate periodically fluctuates on various time scales, however, there remains a lack of consensus on the centennial-scale variabilities and associated driving force. A continuous high-resolution sea surface temperature (SST) record allows for the detection of centennial-scale fluctuations. This study presents a high-resolution SST record covering the last 10,000 years based on the analysis of the alkenone unsaturation index in marine sediment cores off the southwest coast of the Korean Peninsula. Alkenone SST's spectral and wavelet analysis revealed significant periodicities of 414, 190, 135, 102, and 89 years at a > 90% confidence level. These cycles exhibit extreme proximity to the solar activity cycles of 353, 206 (Suess/de Vries cycles), 130, and 104-87 years (Gleissberg cycles), suggesting that the multidecadal to centennial variations in SST are linked to solar forcing. To the best of our knowledge, this is the first high-resolution Holocene SST record that all solar activity cycles on centennial scale match, suggesting centennial-scale variability in the climate system and illustrating the role of solar activity on SST change in the mid-latitude region of the Northern Hemisphere.

Underwater hidden microplastic hotspots: Historical ocean dumping sites.

Three ocean dumping sites located in the Yellow Sea (YS) and East Sea (ES) of South Korea have accumulated terrestrial waste from 1988 to 2015. Most of this waste comprised industrial wastewater and sewage sludge, which are sources of microplastics. In this study, we investigated the spatiotemporal distribution and characteristics of microplastics in surface and core sediments of the YS, South Sea (SS) and ES, including at dumping sites (YDP and EDP). The mean abundance of microplastics in surface sediments was ranked in order of EDP (59,457 ± 49,130 particles/kg d.w.), ES (5,047 ± 9,404 particles/kg d.w.), YDP (3,965 ± 3,213 particles/kg d.w.), SS (314 ± 488 particles/kg d.w.) and YS (288 ± 400 particles/kg d.w.). EDP and YDP showed about 14- and 12-fold higher microplastic abundances, and more diverse polymer compositions, than the ES and YS, respectively. The historical trend of microplastic pollution in age-dated core sediments from EDP and YDP aligned well with the amount of historical ocean dumping. As the level of ocean dumping has gradually reduced since 2006, and was finally banned in 2015, the microplastic abundance decreased accordingly. Interestingly, spherical polystyrene (PS) primary microplastic was the dominant type in EDP sediments (78%) and other surface sediments in the ES (52%). More than 60 million tons of sewage and wastewater sludge were dumped at EDP, and extremely high abundances of up to 130,000 particles/kg d.w. were observed in EDP surface sediments. PS primary microplastics were continuously present in the EDP and ES sediment cores in the dumping period and are suspected to have originated from industrial wastewater sludge. The particle transportation model results showed that PS was dispersed throughout the ES during ocean dumping. In addition, deep circulation can contribute to the dispersion of particles after sinking. These results indicate that ocean dumping sites represent an underwater hotspot and source of microplastics in seafloor sediments.

Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome.

Telomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas (n = 760) and characterize its features using multi-omics profiling. ALT-positive tumors are molecularly distinct from other neuroblastoma subtypes and enriched in a population-based clinical sequencing study cohort for relapsed cases. They display reduced ATRX/DAXX complex abundance, due to either ATRX mutations (55%) or low protein expression. The heterochromatic histone mark H3K9me3 recognized by ATRX is enriched at the telomeres of ALT-positive tumors. Notably, we find a high frequency of telomeric repeat loci with a neuroblastoma ALT-specific hotspot on chr1q42.2 and loss of the adjacent chromosomal segment forming a neo-telomere. ALT-positive neuroblastomas proliferate slowly, which is reflected by a protracted clinical course of disease. Nevertheless, children with an ALT-positive neuroblastoma have dismal outcome.

Super enhancers define regulatory subtypes and cell identity in neuroblastoma.

Half of the children diagnosed with neuroblastoma (NB) have high-risk disease, disproportionately contributing to overall childhood cancer-related deaths. In addition to recurrent gene mutations, there is increasing evidence supporting the role of epigenetic deregulation in disease pathogenesis. Yet, comprehensive cis-regulatory network descriptions from NB are lacking. Here, using genome-wide H3K27ac profiles across 60 NBs, covering the different clinical and molecular subtypes, we identified four major super-enhancer-driven epigenetic subtypes and their underlying master regulatory networks. Three of these subtypes recapitulated known clinical groups; namely, MYCN-amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk NBs. The fourth subtype, exhibiting mesenchymal characteristics, shared cellular identity with multipotent Schwann cell precursors, was induced by RAS activation and was enriched in relapsed disease. Notably, CCND1, an essential gene in NB, was regulated by both mesenchymal and adrenergic regulatory networks converging on distinct super-enhancer modules. Overall, this study reveals subtype-specific super-enhancer regulation in NBs.

Tracking flood debris using satellite-derived ocean color and particle-tracking modeling.

Flood debris associated with Typhoon Lionrock from the Tumen River at the border between Russia and North Korea was traced using ocean color and a Lagrangian particle-tracking model. As debris is transported along with discharged water during floods, a means of tracing floodwater should also allow any associated debris to be tracked. By analyzing the anomalous distribution of colored dissolved organic matter (CDOM) and total suspended sediments (TSS) from the Geostationary Ocean Color Imager (GOCI), the southward movement of the floodwater was tracked along the eastern coast of the Korean Peninsula. This movement was driven by the North Korean Cold Current and was consistent with model results. The similarity between the satellite-derived and modeled datasets shows that CDOM and TSS can be used to track flood-derived debris for several hundreds of kilometers and locate hotspots of debris accumulation.

Destination of floating plastic debris released from ten major rivers around the Korean Peninsula.

Using a Lagrangian particle tracking model the coastal accumulation of debris from 10 major Chinese and Korean rivers discharging to the seas around the Korean Peninsula is investigated. The amount of debris from each river is proportional to the population over the catchment area of the river and the mismanaged plastic waste (MPW) ratio of the country the river belongs to. The debris generally washes up on the coast near the originating river mouth. When only the debris originating from the rivers on the Korean Peninsula is considered the model results are consistent with the observations for the Korean coast reported in previous studies in that the amount of microplastic and macroplastic are greater near the Han and Nakdong Rivers. The amount of debris from Chinese rivers calculated based on the MPW ratios is 75 times greater than that from the rivers on the Korean Peninsula and if the Chinese rivers are added the model the results differ from the observed patterns. Macroplastic distribution also exhibits a similar discrepancy between the model and observation results if debris from the Chinses Rivers are taken into account. Observed data from Korea's Marine Litter Information System show that the accumulation of foreign-originating macroplastic most of which is Chinese is highest around the southwestern corner of the Korean Peninsula. Debris from the Chinese Yangtze and Yellow Rivers reproduces this observed distribution. Based on the observational data more debris originates from Korea than from foreign sources but Chinese-originating debris is dominant in the model. There are two possibilities for this discrepancy. The first is the presence of sinking due to biofouling; if 50% of the plastic sinks every 20 days or so the model results become similar to the observations. The second is the large difference in the MPW ratios between China and Korea employed in the model. Reducing the Chinese MPW ratio to 25% or lower the model results more closely reflect the observations made along the Korean coast.

Potential predictability of skipjack tuna (Katsuwonus pelamis) catches in the Western Central Pacific.

The Pacific Island countries have a substantial socio-economic dependency on fisheries. Skipjack tuna is one of the most important species in the Western Central Pacific (WCP) and its catches in this region exhibit a spatio-temporal variability influenced by ocean conditions, mainly the El Niño-Southern Oscillation (ENSO). This study investigates the relationship between skipjack tuna catch amounts and environmental variables in the equatorial Pacific during 1990-2014, and evaluates the potential predictability of the catches based on their statistical relationship. A series of regressed and reconstructed spatial patterns of upper-ocean temperature, salinity, currents and precipitation represent ENSO-like variability, and their principal component time series are used to estimate the predictability of skipjack tuna catches in the Federated States of Micronesia (FSM). ENSO-like variability depicted from 100 m temperature and 5 m salinity in the equatorial Pacific exhibit a significant predictability for the annual catch amount in the FSM for several years with a training period of > 20 years. This suggests that the subsurface temperature or near surface salinity can be a better predictor of ecosystem variability than widely used sea surface temperature. Applications of this result to other species could have broad implications for the fishery industry in the WCP.

Application of satellite remote sensing in monitoring dissolved oxygen variabilities: A case study for coastal waters in Korea.

Dissolved oxygen (DO) is one of the critical parameters representing water quality in coastal environments. However, it is labor- and cost-intensive to maintain monitoring systems of DO since in situ measurements of DO are needed in high spatial and temporal resolution to establish proper management plans of coastal regions. In this study, we applied statistical analyses between long-term monitoring datasets and satellite remote sensing datasets in the eastern coastal region of the Yellow Sea. Pearson correlation analysis of long-term water quality monitoring datasets shows that water temperature and DO are highly correlated. Stepwise multiple regression analysis among DO and satellite-derived environmental variables shows that the in situ DO can be estimated by the combination of the present sea surface temperature (SST), the chlorophyll-a, and the SST in the month prior. The high skill score of our proposed model to derive DO is validated by two error measures, the Absolute Relative Error, 1-ARE (89.2%), and Index of Agreement, IOA (78.6%). By applying the developed model to the Moderate Resolution Imaging Spectroradiometer (MODIS) and Visible Infrared Imaging Radiometer Suite (VIIRS) products, spatial and temporal changes in satellite-derived DO can be observed in Saemangeum offshore in the Yellow Sea. The analysis results show that there is a significant decrease in estimated DO between summer of 2003 versus 2012 indicating summer coastal deoxygenation due probably to the Saemangeum reclamation. This study shows the potential capability of satellite remote sensing in monitoring in situ DO in both high temporal and spatial resolution, which will be beneficial for effective and efficient management of coastal environments.

Association between body mass index and mortality in the Korean elderly: A nationwide cohort study.

The objective of this study was to investigate the relationship between body mass index (BMI) and mortality in the elderly. This study was a nation-wide population-based retrospective cohort study of the National Health Insurance System-Senior Database (NHIS-SD). In this study, a total of 75,856 subjects were identified and selected from among 251,593 individuals aged ≥ 65 years who underwent health screening at least once between 2009 and 2012 and who had no history of diabetes, cardiovascular disease, stroke, cancer, or chronic obstructive pulmonary disease (COPD). The subjects of this study were followed-up until 2013 to identify the total mortality and the cause-specific mortality of 6 groups divided according to BMI. The hazard ratio (HR) by reference group (23 ≤ BMI < 25 kg/m2) of each group was calculated. A significant increase in the HR with a decreased BMI was observed in the group with a BMI < 23 kg/m2, whereas the HR in the group with a BMI ≥ 25 kg/m2 was not significantly different than that of the reference group (23 ≤ BMI < 25 kg/m2). This pattern was also seen in the subgroup analyses in relation to age, smoking history, alcohol use, exercise level, and socioeconomic status. In this study, we found that a low BMI was a risk factor for death in the elderly and that no significant difference in mortality was seen in the elderly with a BMI of 25 or over. In terms of an optimal BMI in the elderly, it is important to maintain an appropriately healthy range of BMI with the aim of preventing weight loss.

RORA Polymorphism Interacts with Childhood Maltreatment in Determining Anxiety Sensitivity by Sex: A Preliminary Study in Healthy Young Adults.

OBJECTIVE: Recent studies have reported associations of retinoid-related orphan receptor alpha (RORA) gene single nucleotide polymorphisms (SNPs) with depression and anxiety disorders. Based on these, we attempt to test whether RORA polymorphism is associated with anxiety sensitivity (AS), the intermediate phenotype of depression and anxiety disorders. Considering gene-environment interactions and sex differences in AS, childhood maltreatment (CM) and sex were considered as confounders. METHODS: Two-hundred and five healthy young Korean adults (female: 98, male: 107; age, 23.0±3.2 years) completed genotyping for the RORA SNP rs11071547, as well as measures for AS and CM. Generalized linear models were used to examine the main and interaction effects of RORA genotype, CM, and sex in determining AS. RESULTS: The main effect of RORA polymorphisms was not found (p=0.760) whereas the main effect of CM and interaction effects among sex, genotype, and maltreatment were significant on AS. In separate analyses by sex, the interaction effect between RORA genotype and maltreatment was significant only in males (p＜0.001). In females, the main effects of genotype and CM were significant (both were p＜0.001), in which both a history of CM and C genotype tended to be associated with higher AS. CONCLUSION: The association between RORA polymorphism and AS might differ by sex. The interaction between RORA polymorphism and CM was significant only in males whereas RORA genotype and CM independently associated with AS in females. Further studies are encouraged to confirm the relationship between RORA polymorphism and AS.

Association between serum ferritin and hemoglobin levels and bone health in Korean adolescents: A nationwide population-based study.

It is important to identify risk factors for low bone mass at a young age. An influence of iron store on bone health in the general population has been reported but has not been studied in adolescents. This study aimed to investigate the relationship between hemoglobin and serum ferritin levels and bone mineral content (BMC) in South Korean adolescents.This study was based on data collected during the 2009to 2010 Korea National Health and Nutrition Examination Survey. We included 1321 participants aged 10 to 18 years. BMC was measured at the femur and lumbar spine using dual-energy x-ray absorptiometry, and hemoglobin and serum ferritin levels were examined.In boys, hemoglobin and serum ferritin levels were positively associated with BMC of the total femur and lumbar spine after adjusting for confounders, and hemoglobin levels significantly increased as BMC increased at all sites (P for trend = .001 for total femur, .01 for femur neck, and <.001 for lumbar spine). Likewise, serum ferritin levels showed increasing trends according to increasing BMC of the total femur and lumbar spine in boys (P for trend = .04 for total femur; and <.001 for lumbar spine). However, these associations were not observed in girls.This study suggests a positive relationship between serum ferritin and hemoglobin levels and BMC in South Korean adolescent boys.

Lethal and sub-lethal effects of elevated CO2 concentrations on marine benthic invertebrates and fish.

Concern about leakage of carbon dioxide (CO2) from deep-sea storage in geological reservoirs is increasing because of its possible adverse effects on marine organisms locally or at nearby coastal areas both in sediment and water column. In the present study, we examined how elevated CO2 affects various intertidal epibenthic (benthic copepod), intertidal endobenthic (Manila clam and Venus clam), sub-tidal benthic (brittle starfish), and free-living (marine medaka) organisms in areas expected to be impacted by leakage. Acute lethal and sub-lethal effects were detected in the adult stage of all test organisms exposed to varying concentrations of CO2, due to the associated decline in pH (8.3 to 5.2) during 96-h exposure. However, intertidal organisms (such as benthic copepods and clams) showed remarkable resistance to elevated CO2, with the Venus clam being the most tolerant (LpH50 = 5.45). Sub-tidal species (such as brittle starfish [LpH50 = 6.16] and marine medaka [LpH50 = 5.91]) were more sensitive to elevated CO2 compared to intertidal species, possibly because they have fewer defensive capabilities. Of note, the exposure duration might regulate the degree of acute sub-lethal effects, as evidenced by the Venus clam, which showed a time-dependent effect to elevated CO2. Finally, copper was chosen as a model toxic element to find out the synergistic or antagonistic effects between ocean acidification and metal pollution. Combination of CO2 and Cu exposure enhances the adverse effects to organisms, generally supporting a synergistic effect scenario. Overall, the significant variation in the degree to which CO2 adversely affected organisms (viz., working range and strength) was clearly observed, supporting the general concept of species-dependent effects of elevated CO2.

Postmarketing surveillance study of the efficacy and safety of phentermine in patients with obesity.

BACKGROUND: Obesity is a complex problem that is now considered a chronic metabolic disease. In Korea, phentermine has been widely used for the treatment of obesity in the primary care setting since 2004. However, there have been very few studies on the safety and efficacy of phentermine. To investigate the safety and efficacy of this drug, a postmarketing surveillance study was performed. METHODS: A total of 795 patients with obesity (body mass index ≥ 25 kg/m(2)) were enrolled from 30 primary care centers in Korea from September 2006 to November 2007. Patients were examined to ascertain safety and efficacy at 4-, 8-, and 12-week intervals. The criterion for efficacy was defined as a weight loss ≥ 5% of body weight. RESULTS: Of the 795 enrolled patients, 735 (92.5%) were evaluated in safety assessments and 711 (89.4%) was included in efficacy assessments. A total of 266 adverse events (AEs) were reported by 218 patients (30.6%), and no serious AEs were reported. Among 711 patients, 324 patients (45.6%) lost ≥ 5% of their body weight. The mean weight loss was 3.8 ± 4.0 kg. CONCLUSION: AEs are commonly associated with phentermine, even though phentermine is effective for weight loss and relatively well-tolerated.