Novel Histone Deacetylase 6 Inhibitor Confers Anti-inflammatory Effects and Enhances Gut Barrier Function

Background/Aims@#The purpose of the current study was to examine the anti-inflammatory effects of CKD-506, a novel histone deacetylase 6 inhibitor, on human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells and to explore the relationship between CKD-506 and gut epithelial barrier function. @*Methods@#Lipopolysaccharide-stimulated human PBMCs from inflammatory bowel disease (IBD) patients were treated with CKD-506, and tumor necrosis factor (TNF)-α expression was measured using an enzyme-linked immunosorbent assay. The proliferation of CD4+ T cells from IBD patients was evaluated using flow cytometric analysis. The effects of CKD-506 on gut barrier function in a cell line and colon organoids, based on examinations of mRNA production, goblet cell differentiation, and E-cadherin recovery, were investigated using quantitative reverse transcription polymerase chain reaction, immunofluorescence, and a fluorescein isothiocyanatedextran permeability assay. @*Results@#Secretion of TNF-α, a pivotal pro-inflammatory mediator in IBD, by lipopolysaccharidetriggered PBMCs was markedly decreased by CKD-506 treatment in a dose-dependent manner and to a greater extent than by tofacitinib or tubastatin A treatment. E-cadherin mRNA expression and goblet cell differentiation increased significantly and dose-dependently in HT-29 cells in response to CKD-506, and inhibition of E-cadherin loss after TNF-α stimulation was significantly reduced both in HT-29 cells and gut organoids. Caco-2 cells treated with CKD-506 showed a significant reduction in barrier permeability in a dose-dependent manner. @*Conclusions@#The present study demonstrated that CKD-506 has anti-inflammatory effects on PBMCs and CD4 T cells and improves gut barrier function, suggesting its potential as a smallmolecule therapeutic option for IBD.

Downregulation of Heat Shock Protein 72 Contributes to Fibrostenosis in Crohn’s Disease

Background/Aims@#Crohn’s disease (CD) with recurrent inflammation can cause intestinal fibrostenosis due to dysregulated deposition of extracellular matrix. However, little is known about the pathogenesis of fibrostenosis. Here, we performed a differential proteomic analysis between normal, inflamed, and fibrostenotic specimens of patients with CD and investigated the roles of the candidate proteins in myofibroblast activation and fibrosis. @*Methods@#We performed two-dimensional difference gel electrophoresis and identified candidate proteins using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and orbitrap liquid chromatography-mass spectrometry. We also verified the levels of candidate proteins in clinical specimens and examined their effects on 18Co myofibroblasts and Caco-2 intestinal epithelial cells. @*Results@#We identified five of 30 proteins (HSP72, HSPA5, KRT8, PEPCK-M, and FABP6) differentially expressed in fibrostenotic CD. Among these proteins, the knockdown of heat shock protein 72 (HSP72) promoted the activation and wound healing of myofibroblasts. Moreover, knockdown of HSP72 induced the epithelial-mesenchymal transition of intestinal epithelial cells by reducing E-cadherin and inducing fibronectin and α-smooth muscle actin, which contribute tofibrosis. @*Conclusions@#HSP72 is an important mediator that regulates myofibroblasts and epithelial-mesenchymal transition in fibrosis of CD, suggesting that HSP72 can serve as a target for antifibrotic therapy.

Comparison of Gait Parameters during Forward Walking under Different Visual Conditions Using Inertial Motion Sensors

Purpose@#Gait evaluation in patients with dizziness is essential during both initial evaluation and vestibular rehabilitation. Inertial measurement unit (IMU)-based gait analysis systems are clinically applicable in patients with dizziness. Since dizzy patients can utilize visual inputs to compensate for vestibular deficits, it is more difficult for them to walk with their eyes closed (EC). In this study, we compared gait characteristics during forward walking with both eyes open (EO) and EC between healthy subjects and dizzy patients. @*Materials and Methods@#Forty-nine healthy controls (mean age 37.18±10.71 years) and 23 patients with dizziness (mean age 49.25± 15.16 years) were subjected to vestibular and gait analyses. Medical histories, physical examinations, and vestibular function tests ruled out possible vestibular deficits in the controls. Subjects were instructed to walk at a comfortable pace for 10 m under two conditions (EO or EC). Spatiotemporal parameters, kinematics, and simulated kinetics of each gait recording were recorded using a shoe-type IMU system and analyzed. @*Results@#Although gait speeds were slower, stride lengths were smaller, and double support times were increased under the EC, compared to the EO condition, in both healthy subjects and dizzy patients, the difference was more prominent in dizzy patients.Phase coordination index values did not differ significantly in either group. Gait asymmetry (GA) increased significantly under the EC condition, compared to the EO condition, in dizzy patients. @*Conclusion@#GA during forward walking was greater in dizzy patients under an EC condition than under an EO condition.

etection of infectious hypodermal and hematopoietic necrosis virus and white spot syndrome virus in whiteleg shrimp (Penaeus vannamei) imported from Vietnam to South Korea

n this study, whiteleg shrimp (Penaeus vannamei) imported from Vietnam were collected from South Korean markets, and examined for 2 viruses: infectious hypodermal and hematopoietic necrosis virus (IHHNV, recently classified as decapod penstyldensovirus-1), and white spot syndrome virus (WSSV). Among 58 samples, we detected IHHNV in 23 samples and WSSV in 2 samples, using polymerase chain reaction and sequencing analyses.This is the first report of IHHNV and WSSV detection in imported shrimp, suggesting that greater awareness and stricter quarantine policies regarding viruses infecting shrimp imported to South Korea are required.

Audiologic Status of Children with Confirmed Cytomegalovirus Infection: a Case Series

Background@#Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of sensorineural hearing loss (SHNL) in children. Only about 10% to 15% of children with congenital CMV are symptomatic, and most are not diagnosed at birth. About 7% to 15% of clinically asymptomatic patients may develop later complications, including SNHL, which is the most common sequela in clinically asymptomatic patients. In this study, hearing status was investigated in children with confirmed CMV infection and neonatal hearing screening (NHS) histories were reviewed to explore hearing loss caused by CMV. @*Methods@#The medical records of 58 children who were diagnosed with confirmed CMV infection were reviewed for clinical symptoms and signs of CMV infection. Hearing status was evaluated with age-appropriate audiological test batteries. @*Results@#A total of 58 children (M:F = 32:26 patients; age at study: mean, 5.62 years, range, 1-10 years) were diagnosed serologically with CMV infection (14 patients, 21.1%), or diagnosed via PCR of serum (5, 7.9%) and/or PCR from urine (19, 26.8%). Hearing loss was confirmed in 11 children (19.0%), being bilateral in 6 (54.5%), and unilateral in 5 (45.5%). Note that 7 of 17 ears with hearing loss passed NHS and were diagnosed only after re-evaluation when CMV infection was identified. @*Conclusion@#Hearing loss is a serious complication of CMV infection in children. Our results highlight the importance of timely audiological evaluation in children with clinically symptomatic CMV infection even if they pass NHS.

Biological control of Flavobacterium psychrophilum infection in ayu (Plecoglossus altivelis altivelis) using a bacteriophage PFpW-3

The efficacy of using a bacteriophage (phage) to control Flavobacterium psychrophilum (F. psychrophilum) infection of ayu (Plecoglossus altivelis altivelis) was evaluated in this study. Intramuscular challenge failed to induce sufficient infection levels; therefore, a newly designed net-scratch challenge method was also used to induce bacterial infection. Administration of phage PFpW-3 in F. psychrophilum-infected ayu showed notable protective effects, increased survival rates and mean times to death. Additionally, the fate of inoculated bacteria and phage in ayu were investigated. Our results suggest that the phage PFpW-3 could be considered an alternative biocontrol agent against F. psychrophilum infections in ayu culture.

Relationship of Vertigo and Postural Instability in Patients With Vestibular Schwannoma

OBJECTIVES: Growth of vestibular schwannomas (VS) causes progressive vestibular symptoms and postural instability. Since the tumor grows slowly, compensation of decaying vestibular input may decrease subjective symptoms of dizziness. This study aims to estimate the relationship of subjective vestibular symptoms and objective postural instability in patients with VS. METHODS: A retrospective review of 18 patients newly diagnosed with VS and with subjective vertigo symptoms was performed. The results of vestibular function tests including the sensory organization test (SOT) using computerized dynamic posturography, caloric test, and self-report measures of subjective dizziness handicap (Dizziness Handicap Inventory) and visual analogue scale were compared according to the onset of vertigo symptoms. RESULTS: In VS patients, SOT showed decreased equilibrium score for all vestibular function related conditions, condition (C) 5 and 6, and composite (COMP) score. COMP scores were not correlated with visual analogue scale or Dizziness Handicap Inventory scores. Acute onset group included six patients and insidious onset group, 12 patients. Equilibrium scores for C5 and C6, and COMP scores were lower for insidious onset group, but the difference was not statistically significant. CONCLUSION: Our findings confirmed postural instability is prevalent in VS patients. SOT parameters did not differ significantly between acute onset and insidious onset groups, but increased tumor size and canal weakness were noted in the insidious onset group. Clinicians should consider that postural instability is likely present even in patients who do not complain of acute vertigo, and appropriate counseling should be discussed with the patients.

Prognostic Factors Affecting Surgical Outcomes in Squamous Cell Carcinoma of External Auditory Canal

OBJECTIVES: Carcinomas of the external auditory canal (EAC) are rare, and management remains challenging. Previous studies seeking prognostic factors for EAC cancers included cancers other than carcinomas. In this study, we analyzed the treatment outcomes of, prognostic factors for, and survival rates associated with specifically squamous cell carcinoma (SCC) of the EAC. METHODS: A retrospective review of 26 consecutive patients diagnosed with SCCs of the EAC in a 10-year period was performed in terms of clinical presentation, stage, choice of surgical procedure, and adjunct therapy. Overall survival (OS) and recurrence-free survival (RFS) were calculated and univariate analysis of prognostic factors was performed. RESULTS: The median age of the 26 patients with SCCs of the EAC was 63 years (range, 40 to 72 years), and 16 males and 10 females were included. According to the modified University of Pittsburgh staging system, the T stages were T1 in 11, T2 in six, T3 in four, and T4 in five cases. The surgical procedures employed were wide excision in three cases, lateral temporal bone resection (LTBR) in 17, and extended LTBR in four, and subtotal temporal bone resection in two. Two patients underwent neoadjuvant chemotherapy, and two underwent adjuvant chemotherapy. One patient received preoperative radiation therapy, and eleven received postoperative radiation therapy. Of the possibly prognostic factors examined, advanced preoperative T stage and advanced overall stage were significant predictors of RFS, but not of OS. CONCLUSION: The advanced T stage and overall stage were associated with decreased survival after surgical treatment in patients with SCC of the EAC, highlighting the importance of clinical vigilance and early detection.

Biological control of Flavobacterium psychrophilum infection in ayu (Plecoglossus altivelis altivelis) using a bacteriophage PFpW-3 / 대한수의학회지

The efficacy of using a bacteriophage (phage) to control Flavobacterium psychrophilum (F. psychrophilum) infection of ayu (Plecoglossus altivelis altivelis) was evaluated in this study. Intramuscular challenge failed to induce sufficient infection levels; therefore, a newly designed net-scratch challenge method was also used to induce bacterial infection. Administration of phage PFpW-3 in F. psychrophilum-infected ayu showed notable protective effects, increased survival rates and mean times to death. Additionally, the fate of inoculated bacteria and phage in ayu were investigated. Our results suggest that the phage PFpW-3 could be considered an alternative biocontrol agent against F. psychrophilum infections in ayu culture.

Prognosis of Sudden Low Frequency Hearing Loss during Long-term Follow-up / 대한평형의학회지

OBJECTIVES: The prognosis of sudden low frequency hearing loss (SLFHL) is relatively good, but recurrences of hearing loss and possible progression to Meniere's disease is still a clinically important concern. This study was conducted to confirm the rate at which SLFHL proceeds to Meniere's disease. METHODS: We retrospectively analyzed the medical records of 160 SLFHL patients who were followed up for more than 6 months from September 2005 to August 2013. Progression, initial hearing level, recovery and recurrence of hearing loss were reviewed. RESULTS: 106 patients (66.25%) had complete hearing recovery, 32 (20%) had recurrent hearing loss. Of the 32 recurrent group, 15 (9.38%) had progressed to Meniere's disease after average of 1.7±1.4 years. The mean age of nonrecurrent group was higher than recurrent group (55.3±14.6 and 48.0±13.4, respectively, p=0.011). The threshold of 250Hz was significantly higher in the nonrecurrent group compared with recurrent group (p=0.047). CONCLUSIONS: In patients with SLFHL, recurrence at relatively young age should be considered with the possibility of progression to Meniere's disease.

Role of Emotional Distress in Prolongation of Dizziness: A Cross-Sectional Study

BACKGROUND AND OBJECTIVES: Dizziness is a common condition in outpatient clinics. Comorbid conditions such as anxiety and/or depression often complicate a patient’s ability to cope with dizziness. The purpose of the present study was to explore the extent of psychiatric distress using the Hospital Anxiety and Depression Scale (HADS) and to compare the results with the subjective severity of dizziness. SUBJECTS AND METHODS: The cross-sectional study included a total of 456 consecutive patients presenting with acute (n=327) and chronic (n=127) dizziness symptoms. The HADS was used to estimate emotional distress and compare between patients with acute and chronic dizziness symptoms. Also, we calculated correlations between subjective dizziness handicap scores and emotional distress using the total and subscale scores of the Dizziness Handicap Inventory (DHI), Disability Scale (DS), and HADS. RESULTS: The HADS total and subscale scores were significantly increased in patients with chronic dizziness (p<0.01) compared with those with acute symptoms. In patients with symptoms of both acute and chronic dizziness, moderate correlations were evident between the DHI and HADS total scores. When we compared DHI subscale scores with the HADS scores, the emotional DHI subscale scores correlated more highly with the HADS total scores and the scores on the anxiety and depression subscales, than did the functional or physical DHI subscale scores. CONCLUSIONS: Increased levels of distress measured using the HADS in patients with chronic symptoms suggest that emotional status of the patients may contribute to prolongation of dizziness symptoms from the acute phase.

Assessment of Attentional Demand in Patients with Dizziness Using Dual Task Test / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Even patients with compensated peripheral vestibular dysfunction may report a sense of disequilibrium during daily activities, which often fail conventional vestibular function tests as attentional demand required for postural control may increase in these patients. The study aims to assess the feasibility of dual task test using concurrent cognitive tasks in a modified clinical test of sensory interaction on balance (mCTSIB) to measure increased attentional demand for posture control. SUBJECTS AND METHOD: Nineteen patients suspected with chronic dizziness were recruited by history reviews and physical examinations. Data for center of pressure (COP) variability and mean velocity during mCTSIB on a force long plate were analyzed, and time taken to react to the auditory stimuli were used to measure the attentional demand required for adequate postural control during platform perturbation. RESULTS: The mean COP range and velocity during mCTSIB were comparable between single and dual task conditions in patients with dizziness. Reaction time (RT) to auditory stimulus of 1 kHz pure tone in patients with chronic dizziness was also comparable to normal subjects. Interestingly, there was a tendency for increased RT in patients with documented caloric weakness, suggesting that attentional demand is increased in these patients. CONCLUSION: RT of dual task tests using auditory stimuli during mCTSIB may provide additional information about increased attentional demand for postural control in patients with vestibular dysfunction.

Efficacy and Toxicity of Mammalian Target Rapamycin Inhibitors in Patients with Metastatic Renal Cell Carcinoma with Renal Insufficiency: The Korean Cancer Study Group GU 14-08 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the efficacy and toxicity of mammalian target rapamycin inhibitors in Korean patients with metastatic renal cell carcinoma (mRCC) with chronic renal insufficiency not requiring dialysis. MATERIALS AND METHODS: Korean patients with mRCC and chronic renal insufficiency not requiring dialysis treated with everolimus or temsirolimus between January 2008 and December 2014 were included. Patient characteristics, clinical outcomes, and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) durations were evaluated according to the degree of renal impairment. RESULTS: Eighteen patients were considered eligible for the study (median age, 59 years). The median glomerular filtration rate was 51.5 mL/min/1.73 m². The best response was partial response in six patients and stable disease in 11 patients. The median PFS and OS durations were 8 months (95% confidence interval [CI], 0 to 20.4) and 32 months (95% CI, 27.5 to 36.5), respectively. The most common non-hematologic and grade 3/4 adverse events included stomatitis, fatigue, flu-like symptoms, and anorexia as well as elevated creatinine level. CONCLUSION: Mammalian target rapamycin inhibitors were efficacious and did not increase toxicity in Korean patients with mRCC and chronic renal insufficiency not requiring dialysis.

Use of Medical Subject Headings (MeSH) in the Journal of the Korean Orthopaedic Association / 대한정형외과학회잡지

PURPOSE: The purpose of this study was to analyze the equality between author key words used in the Journal of the Korean Orthopaedic Association and controlled vocabulary or medical subject headings (MeSH). MATERIALS AND METHODS: A total of 1,058 English key words in 320 papers (average 3.3 words in a paper) from 2009 to 2012 were eligible for this study. We classified them according to matched, partially matched, and non-matched terms. The partially matched terms were further dissected into entry terms, qualifiers, anteriorly or posteriorly matched, abbreviations, and pleurals. After descriptive analysis, we assayed patterns of errors in using MeSH, and reviewed frequently used non-MeSH terms. RESULTS: The rate of matched terms was 23.5% for an average of four years, and 34.8% for 2013, which is on the rise by year. The rate of partially matched terms was 34.8%, and that of non-matched terms was 41.7% for an average of four years. The most frequently used key words were Knee and Total knee arthroplasty (17 times), followed by Osteoarthritis (9), Femur, Hip, and Total hip arthroplasty (8). CONCLUSION: Use of proper keywords aligned with the international standards such as MeSH is important to be properly cited. The authors should pay attention and be educated on correct use of MeSH as key words.

Molecular characterization of tetracycline- and quinolone-resistant Aeromonas salmonicida isolated in Korea

The antibiotic resistance of 16 Aeromonas (A.) salmonicida strains isolated from diseased fish and environmental samples in Korea from 2006 to 2009 were investigated in this study. Tetracycline or quinolone resistance was observed in eight and 16 of the isolates, respectively, based on the measured minimal inhibitory concentrations. Among the tetracycline-resistant strains, seven of the isolates harbored tetA gene and one isolate harbored tetE gene. Additionally, quinolone-resistance determining regions (QRDRs) consisting of the gyrA and parC genes were amplified and sequenced. Among the quinolone-resistant A. salmonicida strains, 15 harbored point mutations in the gyrA codon 83 which were responsible for the corresponding amino acid substitutions of Ser83-->Arg83 or Ser83-->Asn83. We detected no point mutations in other QRDRs, such as gyrA codons 87 and 92, and parC codons 80 and 84. Genetic similarity was assessed via pulsed-field gel electrophoresis, and the results indicated high clonality among the Korean antibiotic-resistant strains of A. salmonicida.

Cyclosporine Induced Breast Fibroadenoma in Kidney Transplanted Patient / 대한신장학회지

A 43-year-old woman who had received kidney transplantation 2 years before was admitted for masses on both axilla. Masses had variable sizes, and were round or oval-shaped with echogenicity on breast ultrasound. Pathologic examination using fine needle aspiration showed masses were fibroadenoma, fibroadenoid hyperplasia, and fat necrosis. We switched cyclosporine to tacrolimus. After 6 months of conversion, breast masses decreased in size on the follow-up breast USG.

Plasmid profiling of Flavobacterium psychrophilum isolates from ayu (Plecoglossus altivelis altivelis) and other fish species in Japan

In order to evaluate the genetic variability of the causative agent of cold water disease (CWD), plasmid profiling was used to characterize Flavobacterium (F.) psychrophilum isolates (n = 169). Size analysis of plasmids in F. psychrophilum isolates (n = 128) from several fish species demonstrated that six kinds of plasmids were harbored, and ayu isolates had different profiles compared to other isolates. Moreover, multiple isolates (n = 41) from CWD outbreaks in 2002 to 2003 at a single ayu farm were examined to determine differences between isolates from successive outbreaks and showed different profiles by the sources of seedlings.

Adventitial Cystic Disease of the Femoral Vein: a Case Report with the CT Venography

Fewer than 20 cases of adventitial cystic disease of the vein have been reported in the worldwide literature. This small number of reported cases may be due not only to the disease's low incidence, but also to the difficulty in making the proper diagnosis. Many techniques have been used to investigate this disease, but venography has been the traditional diagnostic tool. In this report we present a case of adventitial cystic disease that was well demonstrated by CT venography.

Clinical Feasibility and Usefulness of CT Fluoroscopy-Guided Percutaneous Transhepatic Biliary Drainage in Emergency Patients with Acute Obstructive Cholangitis

OBJECTIVE: To evaluate the feasibility of CT fluoroscopy (CTF)-guided percutaneous transhepatic biliary drainage (PTBD) in emergency patients with acute obstructive cholangitis. MATERIALS AND METHODS: The study included 28 patients admitted to the emergency center due to obstructive jaundice and found to require urgent biliary drainage, as well as judged to have a suitable peripheral bile duct for a CTF-guided puncture (at least 4 mm in width). Prior to the CTF-guided puncture, a CT scan was performed to evaluate bile duct dilatation and the underlying causes of biliary obstruction. If the patient was judged to be a suitable candidate, a CTF-guided PTBD was performed in the same CT unit without additional fluoroscopic guidance. Technical feasibility of the procedure was investigated with the evaluation of overall success rate and causes of failure. RESULTS: A hepatic puncture was attempted at the left lobe in 23 patients and right lobe in five patients. The procedure was successful in 24 of 28 patients (86%) Successful biliary puncture was achieved on the first attempt in 16 patients, the second attempt in five patients, and the third attempt in three patients. The causes of failure included guide wire twisting in one patient, biliary puncture failure in two patients, and poor visualization of the guide wire in one patient. There were no significant procedure-related complication. CONCLUSION: The CTF-guided PTBD is technically feasible and highly successful in patients judged to have a suitable indication. Moreover, although the procedure is unfamiliar and inconvenient to interventionalists, it has economical advantages in that it saves time and manpower. We believe this method can be used in the emergency patients requiring urgent biliary drainage as an alternative for the fluoroscopy-guided PTBD.

The effect of remifentanil for reducing myoclonus during induction of anesthesia with etomidate / 대한마취과학회지

BACKGROUND: Myoclonic movement is a common problem during induction of anesthesia with etomidate. We investigated the influences of pretreatment with remifentanil on etomidate induced myoclonus. METHODS: Ninety ASA class I patients were divided randomly into three groups. Group NS received normal saline 2 ml as placebo (n = 30), group R0.5 and group R1.0 were pretreated with remifentanil 0.5 microgram/kg (n = 30) or 1.0 microgram/kg (n = 30) 1 minute before induction with etomidate 0.3 mg/kg. Orotracheal intubation was performed after administration of rocuronium 0.5 mg/kg. We assessed the incidence, onset, duration and intensity of myoclonus. Mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS) were recorded during induction. RESULTS: Twenty five patients developed myoclonus in group NS (83.3%), 3 patients in group R0.5 developed myoclonus (10%), as did 5 patients in group R1.0 (16.7%). Moderate to severe myoclonus of grade 3 and 4 were found 66.7% of patients in group NS, whereas no patients in both remifentanil pretreated groups developed this grade of myoclonus. The duration of myoclonus was reduced significantly in the remifentanil groups: 93.8 +/- 59.5 sec in group NS, 49.3 +/- 34.9 sec in group R0.5, 36.0 +/- 27.0 sec in group R1.0 (P < 0.05). HR was decreased by pretreatment with remifentanil prior to induction, while MAP and HR were decreased after induction with etomidate (P < 0.05). BIS changes were not different among the three groups. The dose dependent differences between the two remifentanil doses were not noticed. CONCLUSIONS: Pretreatment with remifentanil significantly reduced the incidence, duration and intensity of etomidate induced myoclonus.