Controlling shareholders’ ownership structure, foreign investors’ monitoring, and investment efficiency

This study examines the effect of control-ownership wedge (the difference between control rights and cash flow rights) on investment efficiency. Subsequently, the authors analyze how the level of foreign investor monitoring influences the association between control-ownership wedge and investment efficiency. The results of the analyses show that investment efficiency deteriorates as control-ownership wedge increases. This, in turn, suggests that when this wedge increases, agency problems and information asymmetry between controlling and minority shareholders become more severe. The authors also perform an analysis by dividing the samples into four groups based on foreign investor ratio from the least to the greatest. The result shows that control-ownership wedge deteriorates investment efficiency in the group with the least foreign investor ratio. The result reveals that foreign investor monitoring is effective corporate governance mechanism to monitor the controlling shareholders’ investment decisions. We also find that higher control-ownership wedge with over-investment tendency negatively affects firm performance, which implies an inefficient investment behavior. This result suggests that as controlling shareholders’ ownership increases, controlling shareholders becomes more and more reluctant to assume a loss of firm value as a result of reduced investment efficiency. This study provides additional evidence that the greater control-ownership wedge decreases investment efficiency, while recent studies on the relation between control-ownership wedge and investment efficiency suggest mixed evidence. In addition, the results show that foreign investors play an effective monitoring role when controlling shareholders are in position of exercising exclusive power. The results indicate the importance of external investors’ monitoring over investment decisions. Keywords: control-ownership wedge, foreign ownership, investment efficiency, over-investment, under-investment. JEL Classification: G32, M4

The Protective Effects of Melittin on Propionibacterium acnes–Induced Inflammatory Responses In Vitro and In Vivo

Melittin is the main component in the venom of the honey bee (Apis mellifera). It has multiple effects including antibacterial, antiviral, and anti-inflammatory activities in various cell types. However, the anti-inflammatory mechanisms of melittin have not been elucidated in Propionibactierium acnes (P. acnes)–induced keratinocyte or inflammatory skin disease animal models. In this study, we examined the effects of melittin on the production of inflammatory cytokines in heat-killed P. acnes–induced HaCaT cells. Heat-killed P. acnes–treated keratinocytes increased the expression of pro-inflammatory cytokines and Toll-like receptor 2. However, melittin treatment significantly suppressed the expression of these cytokines through regulation of the NF-κB and MAPK signaling pathways. Subsequently, the living P. acnes (1 × 107 CFU) were intradermally injected into the ear of mice. Living P. acnes–injected ears showed cutaneous erythema, swelling, and granulomatous response at 24 hours after injection. However, melittin-treated ears showed markedly reduced swelling and granulomatous responses compared with ears injected with only living P. acnes. These results demonstrate the feasibility of applying melittin for the prevention of inflammatory skin diseases induced by P. acnes

Cystic lymphangioma of the pancreas

Lymphangioma is a benign form of neoplasm arising from the lymphatic system. It occurs as a result of congenital malformations of the lymphatics leading to the obstruction of local lymph flow and the development of lymphangiectasia. Lymphangiomas are common in pediatric patients, in the soft tissues of the neck and the axillae, but lymphangioma of the pancreas is extremely rare, accounting for less than 1% of these tumors. It occurs more frequently in females and is often located in the distal pancreas. Although extremely rare, cystic lymphangioma of the pancreas should be taken into consideration as a differential diagnosis of pancreatic cystic or retroperitoneal lesions, especially in women. Herein, we report on a case of cystic lymphangioma of the distal pancreas in a 37-year-old woman who was treated with complete surgical resection with a review of the literature

Pentoxifylline Attenuates Methionine- and Choline-Deficient-Diet-Induced Steatohepatitis by Suppressing TNF- α

Background. Pentoxifylline (PTX) anti-TNF properties are known to exert hepatoprotective effects in various liver injury models. The aim of this study was to investigate whether PTX has beneficial roles in the development of methionine- and choline-deficient-(MCD-) diet-induced NAFLD SD rats in vivo and TNF-α-induced Hep3B cells in vitro. Methods. SD Rats were classified according to diet (chow or MCD diet) and treatment (normal saline or PTX injection) over a period of 4 weeks: group I (chow + saline, n=4), group II (chow + PTX), group III (MCD + saline), and group IV (MCD + PTX). Hep3B cells were treated with 100 ng/ml TNF-α (24 h) in the absence or presence of PTX (1 mM). Results. PTX attenuated MCD-diet-induced serum ALT levels and hepatic steatosis. In real-time PCR and western blotting analysis, PTX decreased MCD-diet-induced TNF-alpha mRNA expression and proapoptotic unfolded protein response by ER stress (GRP78, p-eIF2, ATF4, IRE1α, CHOP, and p-JNK activation) in vivo. PTX (1 mM) reduced TNF-α-induced activation of GRP78, p-eIF2, ATF4, IRE1α, and CHOP in vitro. Conclusion. PTX has beneficial roles in the development of MCD-diet-induced steatohepatitis through partial suppression of TNF-α and ER stress

Effect of the Look-back period for the estimation of the incidence rates using administrative data

Introduction Administrative data are widely used to estimate epidemiologic indicators. The look-back period is needed to define baseline population for the incidence. However, short look-back period is known to overestimate incidence of diseases misclassifying prevalent cases to incident cases. A short look-back period with longer observation period causes misclassification more inconsistent. Objectives and Approach The purpose of the study is to estimate the incidence rate of uterine leiomyoma by adjusting the misclassification error. We selected 319,608 women aged 15- 54 in 2002 from Korean National Health Insurance Service (KNHIS) cohort data. 34,445 cases were identified during 2002 - 2013. We applied 1-year look-back period as of 2003 and the actual look-back period increases with year, which incurs inconsistent misclassification error. Multiple regression model was used to estimate the number of incidence cases of the 11th look-back year for each year. Annual and adjusted annual incidence rates of uterine leiomyoma were calculated and compared. Results The annual number of patients(X1) is linearly related with the number of misclassification cases, and the number of misclassification cases are logarithmically associated with the look-back periods(X2). The regression equation was 0.07217 (y= 0.07217+ 0.00003213* X1 + 0.07992*ln(X2), R2=94.3). Crude incidence rate of uterine leiomyoma during the study period was 11.7% (35,992 cases) and adjusted rate was 10.5% (32,477cases). The annual incidence and adjusted annual incidence increased by 2.29 times and 2.86 times between 2003 and 2013, respectively. With look-back period of 11 years, 4,588(53.8 %) patients with uterine leiomyoma were estimated to have prior history of the disease. Conclusion/Implications We proposed an adjustment for the misclassification error according to look-back periods. The method is applicable to estimate various healthcare events such as disease incidences and healthcare usage. Although the regression model showed very strong R-squared, follow-up study after several years is needed to validate the study results

Metabolic bulk volume predicts survival in a homogeneous cohort of stage II/III diffuse large B-cell lymphoma patients undergoing R-CHOP treatment

PurposeAccurate risk stratification can improve lymphoma management, but current volumetric 18F-fluorodeoxyglucose (FDG) indicators require time-consuming segmentation of all lesions in the body. Herein, we investigated the prognostic values of readily obtainable metabolic bulk volume (MBV) and bulky lesion glycolysis (BLG) that measure the single largest lesion.MethodsThe study subjects were a homogeneous cohort of 242 newly diagnosed stage II or III diffuse large B-cell lymphoma (DLBCL) patients who underwent first-line R-CHOP treatment. Baseline PET/CT was retrospectively analyzed for maximum transverse diameter (MTD), total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), MBV, and BLG. Volumes were drawn using 30% SUVmax as threshold. Kaplan–Meier survival analysis and the Cox proportional hazards model assessed the ability to predict overall survival (OS) and progression-free survival (PFS).ResultsDuring a median follow-up period of 5.4 years (maximum of 12.7 years), events occurred in 85 patients, including progression, relapse, and death (65 deaths occurred at a median of 17.6 months). Receiver operating characteristic (ROC) analysis identified an optimal TMTV of 112 cm3, MBV of 88 cm3, TLG of 950, and BLG of 750 for discerning events. Patients with high MBV were more likely to have stage III disease; worse ECOG performance; higher IPI risk score; increased LDH; and high SUVmax, MTD, TMTV, TLG, and BLG. Kaplan–Meier survival analysis showed that high TMTV (p = 0.005 and < 0.001), MBV (both p < 0.001), TLG (p < 0.001 and 0.008), and BLG (p = 0.018 and 0.049) were associated with significantly worse OS and PFS. On Cox multivariate analysis, older age (> 60 years; HR, 2.74; 95% CI, 1.58–4.75; p < 0.001) and high MBV (HR, 2.74; 95% CI, 1.05–6.54; p = 0.023) were independent predictors of worse OS. Older age (hazard ratio [HR], 2.90; 95% CI, 1.74–4.82; p < 0.001) and high MBV (HR, 2.36; 95% CI, 1.15-6.54; p = 0.032) were also independent predictors of worse PFS. Furthermore, among subjects ≤60 years, high MBV remained the only significant independent predictor of worse OS (HR, 4.269; 95% CI, 1.03–17.76; p = 0.046) and PFS (HR, 6.047; 95% CI, 1.73–21.11; p = 0.005). Among subjects with stage III disease, only greater age (HR, 2.540; 95% CI, 1.22–5.30; p = 0.013) and high MBV (HR, 6.476; 95% CI, 1.20–31.9; p = 0.030) were significantly associated with worse OS, while greater age was the only independent predictor of worse PFS (HR, 6.145; 95% CI, 1.10–4.17; p = 0.024).ConclusionsMBV easily obtained from the single largest lesion may provide a clinically useful FDG volumetric prognostic indicator in stage II/III DLBCL patients treated with R-CHOP

Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy

Recessive mutations in chromosome 10 open reading frame 2 (C10orf2) are relevant in infantile-onset spinocerebellar ataxia (IOSCA). In this study, we investigated the causative mutation in a Korean family with combined phenotypes of IOSCA, sensorimotor polyneuropathy, and myopathy. We investigated recessive mutations in a Korean family with two individuals affected by IOSCA. Causative mutations were investigated using whole exome sequencing. Electrophysiological analyses and muscle and nerve biopsies were performed, along with magnetic resonance imaging (MRI) of the brain and lower extremities. Compound heterozygous mutations c.1460C>T and c.1485-1G>A in C10orf2 were identified as causative of IOSCA. Skeletal muscle showed mitochondrial DNA (mtDNA) deletions. Both patients showed a period of normal development until 12–15 months, followed by ataxia, athetosis, hearing loss, and intellectual disability. Electrophysiological findings indicated motor and sensory polyneuropathies. Muscle biopsy revealed variations in the size and shape of myofibers with scattered, small, and angulated degenerating myofibers containing abnormal mitochondria; these observations are consistent with myopathy and may be the result of mtDNA deletions. Sural nerve biopsy revealed an axonal neuropathy. High-signal-intensity lesions in the middle cerebellar peduncles were correlated with clinical severity, and MRI of the lower legs was compatible with the hypothesis of length-dependent axonal degeneration. We identified novel compound heterozygous mutations of the C10orf2 gene as the cause of IOSCA with sensorimotor polyneuropathy and myopathy. Signs of motor neuropathy and myopathy were discovered for the first time in IOSCA patients with C10orf2 mutations. These results suggest that the clinical spectrum of IOSCA caused by C10orf2 mutations may be more variable than previously reported. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-014-0405-1) contains supplementary material, which is available to authorized users

In Vitro and in Vivo Phototoxicity on Gastric Mucosa Induced by Methylene Blue

BACKGROUND: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity. METHODS: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm RESULTS: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P \u3c 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P \u3c 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10. CONCLUSIONS: : Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period

TAP1 and TAP2 Gene Polymorphisms in Korean Patients with Allergic Rhinitis

Antigen peptides are actively transported across the endoplasmic reticulum by the transporters associated with antigen presentation (TAP). TAP genes polymorphism could influence the selection process that determines which antigen peptides play a role in the pathogenesis of allergic rhinitis. The aim of this study was to investigate the association of TAP genes polymorphism with allergic rhinitis. TAP1 and TAP2 genotyping were performed on 110 allergic rhinitis patients and 107 healthy controls. TAP1 polymorphic residues at codons 333 and 637, and TAP2 polymorphic residues at codons 379, 565, 651, and 665 were analyzed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Analysis of TAP1 gene polymorphism demonstrated decreased frequencies of Ile/Val genotype at codon 333, Asp/Gly genotype at codon 637, and haplotype A and B in allergic rhinitis patients when compared to controls (p<0.05). However, there was no significant difference in the genotype, phenotype, or allele frequencies at four TAP2 codons between controls and allergic rhinitis patients. In conclusion, TAP1 gene polymorphism may be an important factor contributing to the genetic susceptibility in the development of allergic rhinitis in the Korean population

Quantitative CT-based image registration metrics provide different ventilation and lung motion patterns in prone and supine positions in healthy subjects

Background Previous studies suggested that the prone position (PP) improves oxygenation and reduces mortality among patients with acute respiratory distress syndrome (ARDS). However, the mechanism of this clinical benefit of PP is not completely understood. The aim of the present study was to quantitatively compare regional characteristics of lung functions in the PP with those in the supine position (SP) using inspiratory and expiratory computed tomography (CT) scans. Methods Ninety subjects with normal pulmonary function and inspiration and expiration CT images were included in the study. Thirty-four subjects were scanned in PP, and 56 subjects were scanned in SP. Non-rigid image registration-based inspiratory-expiratory image matching assessment was used for regional lung function analysis. Tissue fractions (TF) were computed based on the CT density and compared on a lobar basis. Three registration-derived functional variables, relative regional air volume change (RRAVC), volumetric expansion ratio (J), and three-dimensional relative regional displacement (s*) were used to evaluate regional ventilation and deformation characteristics. Results J was greater in PP than in SP in the right middle lobe (P = 0 .025), and RRAVC was increased in the upper and right middle lobes (P < 0.001). The ratio of the TF on inspiratory and expiratory scans, J, and RRAVC at the upper lobes to those at the middle and lower lobes and that ratio at the upper and middle lobes to those at the lower lobes of were all near unity in PP, and significantly higher than those in SP (0.98–1.06 vs 0.61–0.94, P < 0.001). Conclusion We visually and quantitatively observed that PP not only induced more uniform contributions of regional lung ventilation along the ventral-dorsal axis but also minimized the lobar differences of lung functions in comparison with SP. This may help in the clinicians search for an understanding of the benefits of the application of PP to the patients with ARDS or other gravitationally dependent pathologic lung diseases. Trial registration Retrospectively registered.This research was supported by a Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A1A09082160) and Korea Environment Industry & Technology Institute (KEITI) through Environmental Health Action Program, funded by Korea Ministry of Environment (MOE) (2018001360001)