Antioxidation and anti-inflammatory effects of gamma-irradiated silk sericin and fibroin in H 2O2-induced HaCaT Cell

Oxidative stress in skin cells can induce the formation of reactive oxygen species (ROS), which are critical for pathogenic processes such as immunosuppression, inflammation, and skin aging. In this study, we confirmed improvements from gamma-irradiated silk sericin (I-sericin) and gamma-irradiated silk fibroin (I-fibroin) to skin cells damaged by oxidative stress. We found that I-sericin and I-fibroin effectively attenuated oxidative stress-induced ROS generation and decreased oxidative stress-induced inflammatory factors COX-2, iNOS, tumor necrosis factor-α, and interleukin-1β compared to the use of non-irradiated sericin or fibroin. I-sericin and Ifibroin effects were balanced by competition with skin regenerative protein factors reacting to oxidative stress. Taken together, our results indicated that, compared to non-irradiated sericin or fibroin, I-sericin, and I-fibroin had anti-oxidation and antiinflammation activity and protective effects against skin cell damage from oxidative stress. Therefore, gamma-irradiation may be useful in the development of cosmetics to maintain skin health.

A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-κB pathway

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Age, Body Mass Index, and Spur Size Associated with Patients’ Symptoms in Plantar Fasciitis

Background@#Plantar fasciitis is a common cause of heel pain affecting 10% of the general population. This study aimed to investigate the specific symptoms in patients with plantar fasciitis using the Foot and Ankle Outcome Score (FAOS) questionnaire and their relationship with demographic and radiographic factors. @*Methods@#We retrospectively analyzed 73 consecutive patients (mean age, 53.8 ± 10.0 years; 20 men and 53 women) with plantar fasciitis who had visited our foot and ankle clinic and undergone weight-bearing foot X-ray examinations. Their demographic data, anteroposterior and lateral talo-first metatarsal angles, intermetatarsal and hallux valgus angles, and responses to the FAOS questionnaire were recorded. @*Results@#The quality-of-life subscale showed the lowest score of all FAOS subscales. Age was significantly correlated with quality of life (r = 0.297, p = 0.011), and body mass index was correlated with the function in sports and recreational activities (r = –0.251, p = 0.032). Age and body mass index were statistically significantly correlated with calcaneal spur size (r = 0.274, p = 0.027 and r = 0.324, p = 0.008, respectively). The calcaneal spur size was significantly correlated with pain (r= –0.348, p = 0.004), function in daily living (r = –0.410, p = 0.001), and function in sports and recreational activities (r= –0.439, p < 0.001). @*Conclusions@#Demographic factors were associated with specific symptoms in patients with plantar fasciitis. Calcaneal spur size was the only radiographic parameter correlated with symptoms. These findings help communicate with patients, set appropriate treatment goals, and evaluate treatment effectiveness.

Biomechanics of Hip and Hip Replacement Arthroplasty / 대한정형외과학회잡지

The biomechanics study of the hip is aims to understand and explore the dynamic principles of weight transfer through the hip joint. This basic science knowledge can be applied in a variety of areas, including degenerative joint diseases and hip replacement arthroplasty. In particular, understanding of the biomechanics of the hip has led to the development of materials, design and fixation of implants, and it can be applied in various areas, such as the selection of surgical methods and the location of the implant. Moreover, it is essential to have good knowledge of the biomechanics of the hip to achieve better clinical results for patients. Therefore, this paper introduces the basic knowledge and biomechanical characteristics of a normal hip and hip replacement arthroplasty, which are needed to approach the biomechanics of the hip.

Application of computer-aided diagnosis in breast ultrasound interpretation: improvements in diagnostic performance according to reader experience

PURPOSE: The purpose of this study was to evaluate the usefulness of applying computer-aided diagnosis (CAD) to breast ultrasound (US), depending on the reader's experience with breast imaging. METHODS: Between October 2015 and January 2016, two experienced readers obtained and analyzed the grayscale US images of 200 cases according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon and categories. They additionally applied CAD (S-Detect) to analyze the lesions and made a diagnostic decision subjectively, based on grayscale US with CAD. For the same cases, two inexperienced readers analyzed the grayscale US images using the BI-RADS lexicon and categories, added CAD, and came to a subjective diagnostic conclusion. We then compared the diagnostic performance depending on the reader's experience with breast imaging. RESULTS: The sensitivity values for the experienced readers, inexperienced readers, and CAD (for experienced and inexperienced readers) were 91.7%, 75.0%, 75.0%, and 66.7%, respectively. The specificity values for the experienced readers, inexperienced readers, and CAD (for experienced and inexperienced readers) were 76.6%, 71.8%, 78.2%, and 76.1%, respectively. When diagnoses were made subjectively in combination with CAD, the specificity significantly improved (76.6% to 80.3%) without a change in the sensitivity (91.7%) in the experienced readers. After subjective combination with CAD, both of the sensitivity and specificity improved in the inexperienced readers (75.0% to 83.3% and 71.8% to 77.1%). In addition, the area under the curve improved for both the experienced and inexperienced readers (0.84 to 0.86 and 0.73 to 0.80) after the addition of CAD. CONCLUSION: CAD is more useful for less experienced readers. Combining CAD with breast US led to improved specificity for both experienced and inexperienced readers.

A Genome-Wide Association Study Identifies UTRN Gene Polymorphism for Restless Legs Syndrome in a Korean Population

OBJECTIVE: Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population. METHODS: We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results. RESULTS: In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10−6) in MPHOSPH6 on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10−6) and rs9390170 (OR=0.6778, p=7.67×10−6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170 in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10−18) in BTBD9 was associated with RLS. CONCLUSION: From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by UTRN, is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.

Phosphorylated S6 Kinase-1 as Predictive Marker of Lapatinib Efficacy in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients

PURPOSE: The 40S ribosomal protein S6 kinase-1 (S6K1) is a crucial downstream effector of the PI3K/AKT/mTOR pathway. S6K1 overexpression is found in 10% to 30% of breast cancers and is associated with aggressive disease and poor prognosis. Herein, we investigated the relationship between the expression of phosphorylated S6K1 (p-S6K1) and efficacy of lapatinib in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. METHODS: We retrospectively analyzed the data of 36 patients with HER2-positive metastatic breast cancer treated with lapatinib between January 2010 and September 2014. The p-S6K1 expression status of the primary tumor was assessed via immunohistochemistry using a mouse monoclonal antibody. RESULTS: Fourteen of the 36 patients (38.9%) had p-S6K1-positive tumors. The median progression-free survival (PFS) of patients with p-S6K1-positive tumors was significantly longer than that of patients with p-S6K1-negative tumors (13.4 months vs. 7.1 months, p=0.025). In multivariate analysis, p-S6K1 positivity remained an independent, favorable predictive factor for PFS (hazard ratio, 0.32; 95% confidence interval, 0.11–0.97; p=0.044). CONCLUSION: The high expression of p-S6K1 was significantly associated with prolonged PFS, suggesting that p-S6K1 can be a potential biomarker for predicting the efficacy of lapatinib in patients with HER2-positive metastatic breast cancer.

Clinical Implications of Snoring Time (%) in Patients with Obstructive Sleep Apnea / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Snoring is the vibration sound of respiratory structures when air stream flows through the narrowed airway during sleep. In this study, we aimed to determine the clinical meaning of snoring time (%) of patients who have simple snoring or obstructive sleep apnea (OSA). MATERIALS AND METHODS: We performed a retrospective review of 240 cases of clinical data and polysomnography, which were diagnosed with either simple snoring (n=53) or OSA (n=187). Clinical data included anthropometric measurements such as body mass index, neck and waist circumference (WC), and wasit-hip ratio (WHR). Snoring time (%) was calculated as the total time of snoring per hour of sleep. RESULTS: In the female group, snoring time (%) increased in OSA compared to simple snoring, which showed a negative correlation with N3 (r=-0.395, p=0.002) and a positive correlation with the arousal index (r=0.39, p=0.003). Moreover, in females, snoring time (%) showed significant correlations with respiratory indexes: hypopnea index (p=0.008), apnea-hypopnea index (p=0.049), and lowest SpO₂ (p=0.003). WC and WHR showed significant correlations with snoring time (%) in both male and female. CONCLUSION: Snoring time (%) of females showed important clinical associations with sleep quality and respiratory index. Therefore, snoring may have an important role in the pathogenesis of OSA in females.

CDH13 and HCRTR2 May Be Associated with Hypersomnia Symptom of Bipolar Depression: A Genome-Wide Functional Enrichment Pathway Analysis

Although bipolar disorder is highly heritable, the identification of specific genetic variations is limited because of the complex traits underlying the disorder. We performed a genome-wide association study of bipolar disorder using a subphenotype that shows hypersomnia symptom during a major depressive episode. We investigated a total of 2,191 cases, 1,434 controls, and 703,012 single nucleotide polymorphisms (SNPs) in the merged samples obtained from the Translational Genomics Institute and the Genetic Association Information Network. The gene emerging as the most significant by statistical analysis was rs1553441 (odds ratio=0.4093; p=1.20x10-5; Permuted p=6.0x10-6). However, the 5x0-8 threshold for statistical significance required in a genome-wide association study was not achieved. The functional enrichment pathway analysis showed significant enrichments in the adhesion, development-related, synaptic transmission-related, and cell recognition-related pathways. For further evaluation, each gene of the enriched pathways was reviewed and matched with genes that were suggested to be associated with psychiatric disorders by previous genetic studies. We found that the cadherin 13 and hypocretin (orexin) receptor 2 genes may be involved in the hypersomnia symptom during a major depressive episode of bipolar disorder.

Rectourethral Fistula: Systemic Review of and Experiences With Various Surgical Treatment Methods

PURPOSE: A rectourethral fistula (RUF) is an uncommon complication resulting from surgery, radiation or trauma. Although various surgical procedures for the treatment of an RUF have been described, none has gained acceptance as the procedure of choice. The aim of this study was to review our experience with surgical management of RUF. METHODS: The outcomes of 6 male patients (mean age, 51 years) with an RUF who were operated on by a single surgeon between May 2005 and July 2012 were assessed. RESULTS: The causes of the RUF were iatrogenic in four cases (two after radiation therapy for rectal cancer, one after brachytherapy for prostate cancer, and one after surgery for a bladder stone) and traumatic in two cases. Fecal diversion was the initial treatment in five patients. In one patient, fecal diversion was performed simultaneously with definitive repair. Four patients underwent staged repair after a mean of 12 months. Rectal advancement flaps were done for simple, small fistula (n = 2), and flap interpositions (gracilis muscle flap, n = 2; omental flap, n = 1) were done for complex or recurrent fistulae. Urinary strictures and incontinence were observed in patients after gracilis muscle flap interposition, but they were resolved with simple treatments. The mean follow-up period was 28 months, and closure of the fistula was achieved in all five patients (100%) who underwent definitive repairs. The fistula persisted in one patient who refused further definitive surgery after receiving only a fecal diversion. CONCLUSION: Depending on the severity and the recurrence status of RUF, a relatively simple rectal advancement flap repair or a more complex gracilis muscle or omental flap interposition can be used to achieve closure of the fistula.

The Difference in Comorbidities and Behavioral Aspects between Internet Abuse and Internet Dependence in Korean Male Adolescents

OBJECTIVE: This study examined the differences in psychiatric comorbidities and behavioral aspects in accordance with the severity of Internet addiction in male adolescents. METHODS: One hundred and twenty-five adolescents from four middle and high schools in Seoul were enrolled in this study. The subjects were divided into non-addict, abuse, and dependence groups according to a diagnostic interview by psychiatrists. The psychiatric comorbidities and behavioral aspects of subjects were evaluated through psychiatric clinical interviews based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition), the Children's Depression Inventory, the State-Trait Anxiety Inventory, the Internet Addiction Test, and a self-reported questionnaire about behavioral aspects. RESULTS: The psychiatric comorbidity distributions were significantly different in the abuse and dependence groups, particularly in terms of attention-deficit hyperactivity disorder and mood disorder items. The Children's Depression Inventory, the State-Trait Anxiety Inventory, and the Internet Addiction Test scores were also significantly different among the three groups. There were significant differences in 10 of the 20 items of the Internet Addiction Test between the non-addict, abuse, and dependence groups. There were significant differences in seven items between the non-addict and abuse groups, but no differences between subjects in the abuse and dependence groups. Significant differences were observed in three items between the abuse and dependence groups, but there were no significant differences between the non-addict and abuse groups. In terms of behavioral aspects, scores for abusive, sexual, and decreased social interest behaviors were highest in the dependence group, and lowest in the non-addict group. However, the behavioral aspects of decreased interpersonal relationships did not show this difference between groups. CONCLUSION: This study suggests that there are differences in psychiatric comorbidities and behavioral aspects between adolescent males with characteristics of Internet abuse and Internet dependence.

The Effect of Depression, Impulsivity, and Resilience on Smartphone Addiction in University Students / 신경정신의학

OBJECTIVES: The aim of this study was to examine the effect of depression, impulsivity, and resilience on smartphone addiction in university students. METHODS: A total of 322 students from two universities in Seoul were enrolled in this study. Participants were divided into a risk user group and normal user group according to results using the Korean smartphone addiction scale. We additionally surveyed smartphone use patterns of the participants. The Beck Depression Inventory (BDI), Barratt Impulsiveness Scale (BIS), and Conner-Davidson Resilience Scale (CD-RS) were also used for measurement of the participants' severity of depression, impulsivity, and resilience. RESULTS: The risk user group spent more time using a smartphone on weekdays than the normal user group. The risk user group showed significantly higher scores on BDI, BIS than the normal user group. The risk user group showed significantly lower scores on CD-RS than the normal user group. Results of multiple regression analysis showed that impulsivity was a significant factor affecting smartphone addiction in university students. CONCLUSION: These results suggest that smartphone addiction is influenced by impulsivity. Students with high impulsivity may be vulnerable to smartphone addiction. Further research regarding the underlying mechanisms of these associations is needed.

Use of laparoscopy for diagnosing experimentally induced acute pancreatitis in dogs

Diagnosis of acute pancreatitis in dogs remains a significant challenge despite the development of advanced diagnostic methodologies. Visual inspection and pancreas biopsy using laparoscopy are generally considered to be procedures free of complications when conducted on healthy animals. However, the usefulness of laparoscopy for diagnosing acute pancreatitis has not been assessed. In the present study, the efficacy of laparoscopy for diagnosing acute pancreatitis in dogs was evaluated in animals with experimentally induced acute pancreatitis. Gross appearance of the pancreatic area was examined by laparoscopy to survey for the presence of edema, adhesions, effusion, pseudocysts, hemorrhage, and fat necrosis. Laparoscopic biopsy was performed and the histopathologic results were compared to those of pancreatic samples obtained during necropsy. The correlation between laparoscopy and histopathologic findings of the pancreas was evaluated. The presence of adhesions, effusion, and hemorrhage in the pancreatic area observed by laparoscopy significantly correlated with the histopathologic results (p < 0.05). There was no significant relationship between the histopathologic and laparoscopic biopsy findings. Results of this study suggested that laparoscopic evaluation of gross lesions has clinical significance although the laparoscopic biopsy technique has some limitations. This method combined with additional diagnostic tools can be effective for diagnosing acute pancreatitis in dogs.

Disseminated Herpes Zoster in an Immunocompetent Elderly Patient

Herpes zoster is a cutaneous infection that is characterized by an acute vesicobullous rash with ipsilateral one or two dermatomal distribution and painful allodynia, while predominantly being found in the elderly. Extensive cutaneous dissemination has been reported in immune-compromised patients, such as those who suffer from HIV infections, cancer, chemotherapy, and corticosteroid therapy patients. However, we report a case of disseminated herpes zoster infection in an immuno-competent elderly individual.

Perspectives of Integrative Cancer Genomics in Next Generation Sequencing Era

The explosive development of genomics technologies including microarrays and next generation sequencing (NGS) has provided comprehensive maps of cancer genomes, including the expression of mRNAs and microRNAs, DNA copy numbers, sequence variations, and epigenetic changes. These genome-wide profiles of the genetic aberrations could reveal the candidates for diagnostic and/or prognostic biomarkers as well as mechanistic insights into tumor development and progression. Recent efforts to establish the huge cancer genome compendium and integrative omics analyses, so-called "integromics", have extended our understanding on the cancer genome, showing its daunting complexity and heterogeneity. However, the challenges of the structured integration, sharing, and interpretation of the big omics data still remain to be resolved. Here, we review several issues raised in cancer omics data analysis, including NGS, focusing particularly on the study design and analysis strategies. This might be helpful to understand the current trends and strategies of the rapidly evolving cancer genomics research.

Perspectives of Integrative Cancer Genomics in Next Generation Sequencing Era

The explosive development of genomics technologies including microarrays and next generation sequencing (NGS) has provided comprehensive maps of cancer genomes, including the expression of mRNAs and microRNAs, DNA copy numbers, sequence variations, and epigenetic changes. These genome-wide profiles of the genetic aberrations could reveal the candidates for diagnostic and/or prognostic biomarkers as well as mechanistic insights into tumor development and progression. Recent efforts to establish the huge cancer genome compendium and integrative omics analyses, so-called "integromics", have extended our understanding on the cancer genome, showing its daunting complexity and heterogeneity. However, the challenges of the structured integration, sharing, and interpretation of the big omics data still remain to be resolved. Here, we review several issues raised in cancer omics data analysis, including NGS, focusing particularly on the study design and analysis strategies. This might be helpful to understand the current trends and strategies of the rapidly evolving cancer genomics research.

Temperament and Character in Cannabis and Methamphetamine Abusers

OBJECTIVES: This study aims to identify temperament and characteristics of cannabis and methamphetamine abusers for elucidating psycho-biological variables related to certain substance abuse. METHODS: A total of 320 patients who registered in the 'Hepatitis C cohorts study of intravenous drug users' between March 2006 and March 2010 participated in this study. Data on demographic variables were obtained and the Temperament and Character Inventory (TCI) and measures for nicotine dependence, alcohol dependence, depression and anxiety were assessed. After comparing TCI between cannabis, methamphetamine, and co-abusers, correlations between TCI and other clinical variables were examined. RESULTS: The methamphetamine abuser group showed significantly higher scores in Novelty Seeking (NS2) and Harm Avoidance (HA3) in temperament than the cannabis abuser and co-abuser groups, whereas the cannabis abuser group had higher scores in purposefulness (SD2), congruent second nature (SD5), and self-directedness (SD) in character than the methamphetamine abuser group. In addition, temperaments and characters correlated with various psychiatric symptoms. CONCLUSIONS: We found the differences in temperament and characters among cannabis abusers, methamphetamine abusers. These findings might contribute to further understanding of mechanisms of cannabis and methamphetamine abuse.

Effectiveness of head-up tilt test for the diagnosis of syncope in children and adolescents / 소아과

PURPOSE: We aimed to examine the effectiveness of the head-up tilt test (HUT) for the diagnosis of syncope or presyncope in children and adolescents. METHODS: HUT results and clinical features of 160 children and adolescents with syncope or presyncope were studied from May 2003 through March 2008 at the Chonbuk National University Hospital. The children and adolescents were subjected to 70degrees HUT for 45 minutes. The testees were divided into 2 groups: group I (children) comprising 39 children in the age range 7-12 years (mean, 10.59+/-1.60 years) and group II (adolescents) comprising 121 adolescents in the age range 13-20 years (mean, 15.93+/-2.28 years). Positive result rates of the HUT and types of hemodynamic response to the test in the 2 groups were compared. RESULTS: Of the 160 testees, 92 (57.5%) showed positive HUT results; they showed 3 patterns of response to tilting. Twelve patients showed a predominantly vasodepressor response; 10 patients showed a cardioinhibitory response; and 70 patients showed a mixed response. The positive result rates were 43.6% (17/39) and 62.0% (75/121) in groups I and II, respectively. Mixed response was the predominant positive hemodynamic response in both the groups. CONCLUSION: The HUT is a useful diagnostic tool for evaluating the condition of pediatric patients, including adolescents, with syncope. Further, it may be considered as the first step for evaluating the condition of such patients.

A New Reporter Vector System Based on Flow-Cytometry to Detect Promoter Activity

In this study, we report the development of a new dual reporter vector system for the analysis of promoter activity. This system employs green fluorescence emitting protein, EGFP, as a reporter, and uses red fluorescence emitting protein, DsRed, as a transfection control in a single vector. The expression of those two proteins can be readily detected via flow cytometry in a single analysis, with no need for any further manipulation after transfection. As this system allows for the simultaneous detection of both the control and reporter proteins in the same cells, only transfected cells which express the control protein, DsRed, can be subjected to promoter activity analysis, via the gating out of all un-transfected cells. This results in a dramatic increase in the promoter activity detection sensitivity. This novel reporter vector system should prove to be a simple and efficient method for the analysis of promoter activity.

A Gartner duct cyst of the vagina causing dysuria and dyschezia in a Yorkshire Terrier

A 5 year-old, intact female Yorkshire terrier was referred for dysuria and dyschezia. The radiographic and ultrasound examination showed a round shaped mass caudal to the urinary bladder that contained anechoic fluid within the thin walls. During surgery, the cyst was noted to be attached to the outer wall of the vagina, not connected to the vaginal lumen. Cystic fluid was removed and the cystic wall was resected. Then the remaining cystic wall was omentalized to prevent a recurrence. Histological examination confirmed that the cyst was of Wolffian duct origin. In this case, a large Gartner duct cyst causing urological problems was diagnosed and removed by surgical resection.