Background: Pheochromocytoma and paragangliomas (PPGL) are hereditary in approximately 30% to 40% cases. With the advancement of genetic analysis techniques, including next-generation sequencing (NGS), there were attempts to classify PPGL into molecular clusters. With NGS being applied to clinical settings recently, we aimed to review the results of genetic analysis, including NGS, and investigate the association with clinical characteristics in Korean PPGL patients. Methods: We reviewed the medical records of PPGL patients who visited Severance hospital from 2006 to 2019. We documented the clinical phenotype of those who underwent targeted NGS or had known germline mutations of related genes. Results: Among 57 PPGL patients, we found 28 pathogenic germline mutations of susceptibility genes. Before the targeted NGS was implemented, only obvious syndromic feature lead to the Sanger sequencing for the specific genes. Therefore, for the exact prevalence, only patients after the year 2017, when targeted NGS was added, were included (n=43). The positive germline mutations were found in 14 patients; thus, the incidence rate is 32.6%. Patients with germline mutations had a higher likelihood of family history. There were significant differences in the type of PPGLs, percentage of family history, metastasis rate, presence of other tumors, and biochemical profile among three molecular clusters: pseudohypoxic tricarboxylic acid cycle-related, pseudohypoxic von Hippel-Lindau (VHL)/endothelial PAS domain-containing protein 1-related, and kinase-signaling group. Germline mutations were identified in seven PPGL-related genes (SDHB, RET, VHL, NF1, MAX, SDHA, and SDHD). Conclusion We report the expected prevalence of germline mutations in Korean PPGL patients. NGS is a useful and accessible tool for genetic analysis in patients with PPGLs, and further research on molecular classification is needed for precise management.

OBJECTIVES: The purpose of this study was to investigate the role of self-esteem as a moderator of the factors influencing suicidality among middle-schoolers. METHODS: Moderated multiple regression analysis was applied to assess the influence of happiness, depression, and hostility on suicidality and to determine the degree to which self-esteem served as a moderator of those relationships. Data were collected from 268 students at a middle school in Busan, Korea, using a self-administered structured questionnaire. RESULTS: Happiness, depression, and hostility had significant direct effects on suicidality. Self-esteem showed no direct effect, but had a significant moderating effect on the relationship between hostility and suicidal behavior. CONCLUSIONS: These results suggest that various interventions, such as counseling programs, should be designed to alleviate hostility and depression and to enhance happiness and self-esteem among early adolescents.
Adolescent ; Busan ; Counseling ; Depression ; Happiness ; Hostility ; Humans ; Korea

OBJECTIVES: The purpose of this study was to investigate the role of self-esteem as a moderator of the factors influencing suicidality among middle-schoolers. METHODS: Moderated multiple regression analysis was applied to assess the influence of happiness, depression, and hostility on suicidality and to determine the degree to which self-esteem served as a moderator of those relationships. Data were collected from 268 students at a middle school in Busan, Korea, using a self-administered structured questionnaire. RESULTS: Happiness, depression, and hostility had significant direct effects on suicidality. Self-esteem showed no direct effect, but had a significant moderating effect on the relationship between hostility and suicidal behavior. CONCLUSIONS These results suggest that various interventions, such as counseling programs, should be designed to alleviate hostility and depression and to enhance happiness and self-esteem among early adolescents.

OBJECTIVES: The aim of this study was to evaluate the associations of frailty with perceived neighborhood walkability and environmental pollution among community-dwelling older adults in rural areas. METHODS: The participants were 808 community-dwelling men and women aged 65 years and older in 2 rural towns. Comprehensive information, including demographics, socioeconomic status, grip strength, polypharmacy, perceived neighborhood environment (specifically, walkability and environmental pollution), and frailty, was collected from participants using face-to-face interviews conducted between June and August 2018. Perceived neighborhood walkability was measured using 20 items that were selected and revised from the Neighborhood Environment Walkability Scale, the Neighborhood Walkability Checklist from the National Heart Foundation of Australia, and the Physical Activity Neighborhood Environment Survey. The Kaigo-Yobo Checklist was used to assess participants’ frailty. RESULTS: The overall prevalence of frailty in this community-dwelling population was 35.5%. Sex, age, cohabitation status, educational attainment, employment status, grip strength, and polypharmacy were significantly associated with frailty. In the logistic regression analysis, frailty was associated with low perceived neighborhood walkability (adjusted odds ratio [aOR], 0.881; 95% confidence interval [CI], 0.833 to 0.932; p<0.001) and severe perceived neighborhood environmental pollution (aOR, 1.052; 95% CI, 1.017 to 1.087; p=0.003) after adjusting for sex, age, cohabitation status, educational attainment, employment status, monthly income, grip strength, and polypharmacy. CONCLUSIONS More studies are warranted to establish causal relationships between walkability and environmental pollution and frailty.

BACKGROUND: The purpose of this study was to investigate the outcomes after fixation using a 3.5-mm locking compression plate (LCP) hook plate for isolated greater tuberosity (GT) fractures of the proximal humerus. METHODS: We evaluated the postoperative radiological and clinical outcomes in nine patients who were followed up at least 1 year with isolated GT fractures. Using the deltopectoral approach, we fixed the displaced GT fragments with a 3.5-mm LCP hook plate (Synthes, West Chester, PA, USA). Depending on the fracture patterns, the hook plate was fixed with or without augmentation using either tension suture or suture anchor fixation. RESULTS: All the patient showed successful bone union. The mean time-to-union was 11 weeks. The radiological and clinical outcomes at the final follow-up were generally satisfactory. The mean visual analogue scale for pain, the University of California at Los Angeles score, the American Shoulder and Elbow Surgeons score, and the subjective shoulder value were 1.4, 30.3, 84.3, and 82.2%, respectively. The mean active forward flexion, abduction, external rotation, and internal rotation of the shoulder were 156.7°, 152.2°, 61.1°, and the 10th thoracic vertebral level, respectively. Only one patient presented with a postoperative complication of shoulder stiffness. The patient was treated through arthroscopic capsular release on the 5th postoperative month. CONCLUSIONS: We conclude that fixation using 3.5-mm LCP hook plates for isolated GT fractures of the proximal humerus is a useful treatment method that provides satisfactory clinical and radiological outcomes.
California ; Elbow ; Follow-Up Studies ; Humans ; Humerus* ; Joint Capsule Release ; Methods ; Postoperative Complications ; Shoulder ; Surgeons ; Suture Anchors ; Sutures

BACKGROUND: The purpose of this study was to investigate the outcomes after fixation using a 3.5-mm locking compression plate (LCP) hook plate for isolated greater tuberosity (GT) fractures of the proximal humerus. METHODS: We evaluated the postoperative radiological and clinical outcomes in nine patients who were followed up at least 1 year with isolated GT fractures. Using the deltopectoral approach, we fixed the displaced GT fragments with a 3.5-mm LCP hook plate (Synthes, West Chester, PA, USA). Depending on the fracture patterns, the hook plate was fixed with or without augmentation using either tension suture or suture anchor fixation. RESULTS: All the patient showed successful bone union. The mean time-to-union was 11 weeks. The radiological and clinical outcomes at the final follow-up were generally satisfactory. The mean visual analogue scale for pain, the University of California at Los Angeles score, the American Shoulder and Elbow Surgeons score, and the subjective shoulder value were 1.4, 30.3, 84.3, and 82.2%, respectively. The mean active forward flexion, abduction, external rotation, and internal rotation of the shoulder were 156.7°, 152.2°, 61.1°, and the 10th thoracic vertebral level, respectively. Only one patient presented with a postoperative complication of shoulder stiffness. The patient was treated through arthroscopic capsular release on the 5th postoperative month. CONCLUSIONS: We conclude that fixation using 3.5-mm LCP hook plates for isolated GT fractures of the proximal humerus is a useful treatment method that provides satisfactory clinical and radiological outcomes.
California ; Elbow ; Follow-Up Studies ; Humans ; Humerus ; Joint Capsule Release ; Methods ; Postoperative Complications ; Shoulder ; Surgeons ; Suture Anchors ; Sutures

Lindera obtusiloba has been used in traditional herbal medicine for the treatment of blood stasis and inflammation. The leaves of Lindera obtusiloba have been reported to exhibit various physiological activities. However, there is little information available on their antiplatelet and antithrombotic activities. Thus, the present study aimed to evaluate the effect of Lindera obtusiloba leaf extract (LLE) on platelet activities, coagulation and thromboembolism. In a platelet aggregation study, LLE significantly inhibited various agonist-induced platelet aggregations in vitro and ex vivo. Furthermore, LLE significantly inhibited collagen-induced thromboxane A2 (TXA2) production in rat platelets. In addition, oral administration of LLE was protective in a mouse model of pulmonary thromboembolism induced by intravenous injection of a mixture of collagen and epinephrine. Interestingly, LLE did not significantly alter prothrombin time (PT) and activated partial thromboplastin time (aPTT). This study indicates that the antithrombotic effects of LLE might be due to its antiplatelet activities rather than anticoagulation. Taken together, these results suggest that LLE may be a candidate preventive and therapeutic agent in cardiovascular diseases associated with platelet hyperactivity.
Administration, Oral ; Animals ; Blood Platelets ; Cardiovascular Diseases ; Collagen ; Epinephrine ; Herbal Medicine ; In Vitro Techniques ; Inflammation ; Injections, Intravenous ; Lindera* ; Mice ; Partial Thromboplastin Time ; Platelet Aggregation ; Prothrombin Time ; Pulmonary Embolism ; Rats ; Thromboembolism ; Thrombosis ; Thromboxane A2

Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. However, more detailed mechanism by which NAR exerts anti-cancer properties still remains unanswered. Thus, in this study, we have shown that NAR down-regulates the level of cyclin D1 in human colorectal cancer cell lines, HCT116 and SW480. NAR inhibited the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. Inhibition of proteasomal degradation by MG132 blocked NAR-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with NAR. In addition, NAR increased the phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine blocked cyclin D1 downregulation by NAR. p38 inactivation attenuated cyclin D1 downregulation by NAR. From these results, we suggest that NAR-mediated cyclin D1 downregulation may result from proteasomal degradation through p38 activation. The current study provides new mechanistic link between NAR, cyclin D1 downregulation and cell growth in human colorectal cancer cells.
Alanine ; Cell Line ; Cell Proliferation ; Citrus paradisi ; Colorectal Neoplasms* ; Cyclin D1* ; Down-Regulation* ; Flavonoids ; Half-Life ; Humans ; Phosphorylation ; Point Mutation

PURPOSE: To investigate the clinical characteristics of first-degree relatives with primary open-angle glaucoma (POAG). METHODS: Forty-four POAG patients (22 pairs of eyes from 2 first-degree relatives) were followed for an average of 3.3 years. Baseline characteristics and follow-up data were analyzed. Baseline data consisted of baseline intraocular pressure (IOP), central corneal thickness (CCT), spherical equivalent, visual field mean deviation (VF MD) and average retinal nerve fiber layer (RNFL) thickness measured using optical coherence tomography (OCT). Follow-up data consisted of mean follow-up IOP, mean IOP reduction from baseline (%) and progression rates determined by linear regression analysis of either VF MD value or OCT RNFL thickness. Mean data of both eyes and the worse eye were compared between first-degree relatives of the same family. RESULTS: Among the 22 families, 16 pairs of eyes were from parent/offspring and 6 from siblings. No difference in mean baseline IOP and CCT were found between first-degree relatives. The older patients in parent-offspring families showed significantly more advanced glaucoma in terms of both VF and RNFL thickness, but were less myopic; however, no differences in variables were found between relatives in the 6 families composed of siblings. Among the 22 families, worse baseline VF MD was observed in younger patients compared with the older patients in 4 families. Mean follow-up IOP, mean IOP reduction from baseline, and progression rate did not differ between the older and the younger patient in each family. CONCLUSIONS: In our study, similar characteristics in terms of baseline IOP, IOP response to medication, and glaucoma progression rate were found in members of the same family. However, in some of the families, the younger patient had poorer baseline severity and more aggressive characteristics compared with the older patient, suggesting the clinical course of the disease may vary among first-degree relatives.
Follow-Up Studies ; Glaucoma ; Glaucoma, Open-Angle* ; Humans ; Intraocular Pressure ; Linear Models ; Nerve Fibers ; Retinaldehyde ; Siblings ; Tomography, Optical Coherence ; Visual Fields

PURPOSE: To evaluate the characteristics and relationship between peripapillary choroidal thickness (pCT), lamina cribrosa thickness (LCT), and peripapillary outer retinal layer thickness (pORT) as determined using spectral domain optical coherence tomography (SD-OCT) enhanced depth imaging (EDI). METHODS: In total, 255 participants were included (87 healthy subjects, 87 glaucoma suspects (GS), and 81 glaucoma cases). The pORT, defined as the thickness between the posterior outer plexiform layer and the retinal pigment epithelium (RPE) interface, and the pCT, between the outer margin of the RPE and the choroidal-scleral interface, were manually measured using EDI scanning of the circumpapillary retinal nerve fiber layer (RNFL). LCT was determined by EDI scanning of the optic nerve head (ONH). Baseline characteristics, including axial length (AXL) and the SD-OCT measurements of the participants, were compared among the three groups. The correlation between putative factors and pCT was determined using univariate and multivariate linear regression analyses. RESULTS: In all three groups, both pORT and pCT were thinnest in the inferior area among the four quadrants. In the healthy group, the mean peripapillary RNFL, pORT, and LCT were significantly greater in comparison with those of the GS and glaucoma groups (p < 0.001, p < 0.038, and p < 0.001, respectively). The pCT demonstrated no significant differences among the three groups (p = 0.083). Only age and AXL were associated with pCT by multivariate analysis. CONCLUSIONS: The pCT is substantially thinner in the inferior area of the ONH. In addition, the pCT demonstrates the strongest correlation with age and AXL, but was not associated with glaucoma or LCT.
Choroid/*pathology ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/*diagnosis ; Humans ; Male ; Middle Aged ; Prospective Studies ; Reproducibility of Results ; Retina/*pathology ; Severity of Illness Index ; Tomography, Optical Coherence/*methods