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Youngill Ko,1,2,&ast; Heui Jae Kim,3,&ast; Seung-Mi Lee1 1College of Pharmacy, Daegu Catholic University, Gyeongsan, Republic of Korea; 2The Gyeongbuk Pharmaceutical Association, Gumi, Republic of Korea; 3Pharmacy Department, Daehang Hospital, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Seung-Mi Lee, College of Pharmacy, Daegu Catholic University, 13-13 hayang-ro, Hayang-eup, Gyeongsan, 38430, Republic of Korea, Email seungmi2011@gmail.comPurpose: Health literacy (HL) is crucial in understanding labels of healthcare products. This study aimed to evaluate HL and its impact on comprehending quasi-drug labels, assess consumer perceptions of key label elements and their perceived importance, and provide actionable recommendations for improving label design and health communication.Methods: An online cross-sectional survey of 500 Korean adults (aged 20– 69) was conducted in September 2023 using proportionate stratified sampling based on the 2020 Korean Census. HL was assessed using the Korean Rapid Estimate of Adult Literacy in Medicine (REALM-K). The survey included demographic data, quasi-drug usage patterns, comprehension of 63 quasi-drug terms, and perceptions of label elements. A 5-point Likert scale was used to assess the importance, agreement, and need for improvement of label elements, and statistical analyses included descriptive statistics, chi-square tests, t-tests, Pearson correlation, and logistic regression.Results: Most participants had inadequate HL (68.4%). Adequate HL is strongly associated with higher comprehension of quasi-drug terms (r = 0.783, p < 0.001). Older age (60– 69 years, AOR = 5.97, 95% CI: 1.74– 20.48) and adequate HL (AOR = 28.54, 95% CI: 9.68– 84.15) positively influenced comprehension. Participants with adequate HL rated the importance of label elements, such as “ingredient name” (mean = 4.02, SD = 0.79, p = 0.015) and “contraindications” (mean = 4.68, SD = 0.57, p < 0.001), higher than those with inadequate HL.Conclusion: Significant disparities exist in the comprehension and perceived importance of quasi-drug label elements based on HL levels among Korean adults. Findings emphasize the need for targeted strategies, such as using simplified language and visual aids, to enhance label comprehension. These interventions could improve public health outcomes by increasing understanding of quasi-drug information across diverse HL levels. Future research should focus on developing and testing these targeted interventions to bridge the identified comprehension gap.Keywords: health literacy, quasi-drugs, label comprehension, communication, Korean adults

Hong-Joo Kim,1 Seon-Ki Lee,2 Hyun-Seung Kim,3 Won-Jae Kim,4 Je-Hwang Ryu,5 Min-Kyung Ji,6 Hyun-Pil Lim1 1Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea; 2Department of Prosthodontics, Daejeon Dental Hospital, Wonkwang University, Daejeon, Republic of Korea; 3KJ Meditech Co., Ltd, Gwangju, Republic of Korea; 4Department of Oral Physiology, School of Dentistry, Stem cell Secretome Research Center, Chonnam National University, Gwangju, Republic of Korea; 5Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea; 6Dental 4D Research Center, Chonnam National University, Gwangju, Republic of KoreaCorrespondence: Hyun-Pil Lim, Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea, Tel +82-10-2645-7528, Fax +82-62-530-5639, Email mcnihil@jnu.ac.kr Min-Kyung Ji, Dental 4D Research Center, Chonnam National University, Gwangju, 61186, Republic of Korea, Tel +82-10-8432-3639, Fax +82-62-530-5639, Email perizimin@gmail.comPurpose: Atomic layer deposition (ALD) is a method that can deposit zirconia uniformly on an atomic basis. The effect of deposited zirconia on titanium implants using ALD was evaluated in vivo.Methods: Machined titanium implants (MTIs) were used as the Control. MTIs treated by sandblasting with large grit and acid etching (SA) and MTIs deposited with zirconia using ALD are referred to as Groups S and Z, respectively. Twelve implants were prepared for each group. Six rabbits were used as experimental animals. To evaluate the osteogenesis and osteocyte aspects around the implants, radiological and histological analyses were performed. The bone-to-implant contact (BIC) ratio was measured and statistically analyzed to evaluate the osseointegration capabilities.Results: In the micro-CT analysis, more radiopaque bone tissues were observed around the implants in Groups S and Z. Histological observation found that Groups S and Z had more and denser mature bone tissues around the implants in the cortical bone area. Many new and mature bone tissues were also observed in the medullary cavity area. For the BIC ratio, Groups S and Z were significantly higher than the Control in the cortical bone area (P < 0.017), but there was no significant difference between Groups S and Z.Conclusion: MTIs deposited with zirconia using ALD (Group Z) radiologically and histologically showed more mature bone formation and activated osteocytes compared with MTIs (Control). Group Z also had a significantly higher BIC ratio than the Control. Within the limitations of this study, depositing zirconia on the surface of MTIs using ALD can improve osseointegration in vivo.Keywords: atomic layer deposition, ALD, zirconia, machined titanium implant, bone-to-implant contact ratio, BIC, osseointegration

Hee Kyung Kim,1,&ast; Hyun-Jo Kim,2,&ast; Jae Yun Kim,3 Myung Jin Ban,4 Jiwon Son,5 Yongsung Hwang,5,6 Sung Bin Cho7 1Department of Pathology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea; 2CNP Skin Clinic, Cheonan, Korea; 3Department of Dermatology, Soonchunhyang University Hospital, Cheonan, Korea; 4Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University Hospital, Cheonan, Korea; 5Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan, Korea; 6Department of Integrated Biomedical Science, Soonchunhyang University, Cheonan, Korea; 7Yonsei Seran Dermatology and Laser Clinic, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Sung Bin Cho, Yonsei Seran Dermatology and Laser Clinic, Geumcheon REMAIN CITY 6F, 224 Siheung-daero, Geumcheon-gu, Seoul, 08628, Korea, Tel +82 2-2135-1375, Fax +82 70-8250-1375, Email drsbcho@gmail.comBackground: Single to multiple pulse packs of bipolar, alternating current radiofrequency (RF) oscillations have been used for various medical purposes using invasive microneedle electrodes. This study was designed to evaluate the effects of pulse widths and cycles of RF pulse packs on immediate and delayed thermal tissue reactions in in vivo rat skin.Methods: RF energy at the frequency of 1 MHz and power of 70 W was delivered at each experimental setting into in vivo rat skin at 1.5-mm microneedle penetration, and then, tissue samples were obtained after 1 h and 3, 7, 14, and 21 days and histologically analyzed.Results: A single-pulse-pack RF treatment generated coagulative necrosis zones in the dermal peri-electrode area and zones of non-necrotic thermal reactions in the dermal inter-electrode area. Multiple pulse-pack, RF-treated rat skin specimens revealed that the number and size of peri-electrode coagulative necrosis were markedly decreased by increasing the number of pulse packs and accordingly decreasing the conduction time of each pulse pack. The microscopic changes in RF-induced non-necrotic thermal reaction in the inter-electrode area were more remarkable in specimens treated with RF of 7 or 10 pulse packs than in specimens treated with RF of 1– 4 pulse packs.Conclusion: The gated delivery of multiple RF pulse packs using a bipolar, alternating current, 1-MHz RF system using insulated microneedle electrodes efficiently generates non-necrotic thermal tissue reactions over the upper, mid, and deep dermis and subcutaneous fat in the inter-electrode areas.Keywords: radiofrequency, bipolar, alternating current, gated pulse, tissue reaction, rat

Hee Jeong Kim,1,&ast; Jisun Lee,1,2,&ast; Hyun Jung Lee1,2 1Department of Obstetrics and Gynecology, Kyungpook National University Hospital, Daegu, Republic of Korea; 2Department of Obstetrics and Gynecology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Hyun Jung Lee, Department of Obstetrics and Gynecology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea, Tel +821035328741, Fax +82534237905, Email hyunjunglee@knu.ac.krAbstract: In patients with acute abdomen, especially during pregnancy, it is difficult to suspect myoma torsion initially due to its rarity. However, when these patients have a solid mass in the pelvis, torsion of uterine fibroids or adnexa and large infarct inside leiomyoma are the main diagnoses that must be differentiated. We report a case of uterine myoma torsion mimicking ovarian torsion in the second trimester of pregnancy that was successfully managed by laparoscopic myomectomy. A 31-year-old pregnant woman with severe right lower abdominal pain at 21 + 2 weeks of gestation was transferred. On ultrasonography, the appendix appeared normal but a solid mass (7.0× 4.0 cm) containing a cystic portion was observed on the right side of the uterus. The mass had no blood flow and tenderness appeared on the transducer pressure. Pelvic magnetic resonance imaging revealed a 7 cm edematous mass with low signal intensity on T2-weighted image, instead of a normal-looking right ovary. These findings led to suspicion of right ovarian torsion. One day after admission, the patient’s symptoms worsened with acute elevation in C-reactive protein (CRP) (4.55 mg/dL) and neutrophile-to-lymphocyte ratio (NLR) (10.1), despite the use of analgesics and tocolytics, and uterine contractions were not controlled. Emergency surgery was performed, and the final diagnosis was a uterine leiomyoma torsion. Laparoscopic myomectomy was successfully performed, and symptoms were relieved after operation. She had full term vaginal delivery without complication. The differential diagnosis between myoma torsion and ovarian torsion is challenging in patients with acute abdomen during pregnancy. To exclude ovarian torsion, a comparison with an asymptomatic contralateral normal ovary will be very helpful. When fibroids are found in mothers with an acute abdomen, follow-up of NLR and CRP is related to preterm labor and can be a reference point for considering surgery.Keywords: ovarian torsion, leiomyoma, pregnancy, laparoscopy, myomectomy

Seung Hoon Lee,1,&ast; Hyung-Jin Kim,1,&ast; Gi-Su Oh,1 Su-Bin Lee,1 Dipendra Khadka,1 Wal Cao,1 Seong-Kyu Choe,1 Hyeok Shim,2 Chang-Deok Kim,3 Tae Hwan Kwak,4 Hong-Seob So1,4 1Department of Microbiology, Wonkwang University School of Medicine, Iksan, Jeonbuk, 54538, Republic of Korea; 2Department of Hemato-Oncology, Wonkwang University School of Medicine, Iksan, Jeonbuk, 54538, Republic of Korea; 3Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea; 4R&D Center, NADIANBIO Ltd, Iksan, Jeonbuk, 54538, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Hong-Seob So, Department of Microbiology, Wonkwang University School of Medicine, 460 Iksan-Daero, Iksan, Jeonbuk, 54538, Republic of Korea, Tel +82-63-850-6950, Fax +82-63-855-6777, Email jeanso@wku.ac.krBackground: Dunnione has anti-inflammatory properties arising from its ability to alter the ratio of NAD+/NADH through NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action, followed by subsequent inhibition of NF-κB and inflammatory cytokines. Psoriasis is a chronic, inflammatory skin disorder in which the IL-23/Th17 axis plays an important role in inflammation. However, it is unclear whether modulation of NAD+ levels affects psoriasis, such as skin inflammation. Therefore, in this study, we investigated the effect of NAD+/NADH ratio modulation on imiquimod (IMQ)-induced, psoriasis-like skin inflammation in mice.Methods: Psoriasis-like skin inflammation was generated by daily topical application of IMQ cream. The severity of dermatitis was assessed using the Psoriasis Area Severity Index (PASI) and histochemistry. Expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay and quantitative PCR. Acetylation of NF-κB p65 and STAT3 was determined by Western blotting.Results: Dunnione improved IMQ-induced epidermal hyperplasia and inflammation, consistent with decreased levels of inflammatory cytokines (IL-17, IL-22, and IL-23) in skin lesions. Moreover, we found that an increase in the NAD+/NADH ratio by dunnione restored SIRT1 activity, thereby reduced imiquimod-induced STAT3 acetylation, which modulates the expression of psoriasis-promoting inflammatory cytokines, such as IL-17, IL-22, and IL-23.Conclusion: Pharmacological modulation of cellular NAD+ levels could be a promising therapeutic approach for psoriasis-like skin disease.Keywords: psoriasis, NQO1, NAD+, SIRT1, inflammatory cytokine

Renal Fanconi syndrome (RFS) affects the proximal tubular resorption in the nephrons. This causes excessive loss of key solutes through the urine. In a canine patient, we successfully managed the renal tubular acidosis and proteinuria caused by RFS via transplantation of canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs). cAT-MSCs were administered ten times at intervals of 2-4 weeks. The post-therapy check-up revealed that the cAT-MSC treatment improved the renal tubular acidosis and proteinuria. Hence, a cAT-MSC transplant may be considered as an adjuvant therapy in veterinary medicine to initiate and maintain relief of RFS-induced acidosis and proteinuria.

Hee Jun Kim,1 Sunjoo Boo,1 Timothy J Meeker2 1Research Institute of Nursing Science, College of Nursing, Ajou University, Suwon, 16499, Gyeonggi, Republic of Korea; 2Department of Neurosurgery, Johns Hopkins Medical Institute, Baltimore, MD, 21287, USACorrespondence: Sunjoo BooResearch Institute of Nursing Science, College of Nursing, Ajou University, 164, World Cup-ro, Yeongtong-gu, Suwon, Gyeonggi, 16499, Republic of KoreaTel +82-31-219-7032Fax +82 31 219 7020Email sjboo@ajou.ac.krBackground: Pain is a global health issue with a significant impact on young adults. Adverse effects caused by inappropriate pain management among university students are related to poor mental/physical health. This study aimed to explore pain prevalence, management, and interference among university students in South Korea.Methods: Pain intensity, painful body areas, pain management, and pain interference were measured in a convenience sample of 404 students. Descriptive statistics are reported, and a multivariable binomial logistic regression was conducted to reveal factors associated with pain interference.Results: The prevalence of acute and chronic pain was 73.5%, while 7.8% reported chronic pain (≥ 3 months). Half of university students who experienced pain reported at least four painful body areas. The average pain intensity during the past 6 months was 4.8/10. About 56% of university students who experienced pain used over-the-counter pain pills for pain management. Rest and massage were the most used non-pharmacological pain management strategies. Mood was the most reported pain interference complaint amongst university students. Greater pain interference was associated with longer pain duration, more painful body areas, and greater pain intensity.Discussion: Pain is highly prevalent among South Korean university students. Pain management programs, including education about appropriate methods of pain relief, should be developed for university students. Attention should be given to university students with widespread acute and chronic pain of high intensity to mitigate the negative impacts caused by pain interference.Keywords: pain, pain management, prevalence, young adults

A 3-year-old castrated male ferret was suspected to have lymphoma based on a markedly enlarged mesenteric lymph node. Hodgkin's-like lymphoma (HLL) was suspected because numerous Reed-Sternberg-like cells were observed in the fine-needle aspiration biopsy of the mesenteric lymph node. In the post-mortem histopathology, neoplastic cells were invasively proliferated not only in the mesenteric lymph nodes, but also in the liver and spleen. Immunohistochemically, most neoplastic cells were positive for vimentin and BLA-36, weakly positive for CD20, and negative for Pax5, CD79a, CD3, CD45, and Iba-1, demonstrating similarity to human Hodgkin's lymphoma (HL). In addition, a prominent programmed cell death protein 1 (PD-1) expression was observed at the sites showing malignant tumour proliferation. HLL in non-human beings can be morphologically and immunophenotypically similar to human HL, but the prognosis and clinical outcome may differ. This is the first study analysing the PD-1 expression in a ferret, suggesting that PD-1 can be a novel diagnostic and prognostic factor in a similar manner to humans.

Hee Jun Kim,1 Hyunjeong Park,2 Hee-Soon Juon3 1Research Institute of Nursing Science, College of Nursing, Ajou University, Suwon, 16499, Republic of Korea; 2Department of Nursing, Towson University, Towson, MD, 21252, USA; 3Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, 19107, USACorrespondence: Hee Jun KimResearch Institute of Nursing Science, College of Nursing, Ajou University, 206 World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, Republic of KoreaTel +82 31-219-7024Fax +82 31-219-7020Email hkim20@ajou.ac.krPurpose: The association between depression and chronic pain is well established. However, few studies have examined the pathways from depression to chronic pain. The present cross-cultural study aimed to test the mediating effects of pain catastrophizing on associations between depression and chronic pain (eg, pain severity, pain intensity) among Korean American elderly.Patients and Methods: A total of 132 elderly Korean Americans with chronic pain were recruited from elderly daycare centers and Korean ethnic churches in the community. For mediation analyses, structural equation modeling with full information maximum likelihood estimation method was used. The bias-corrected bootstrap confidence interval (CI) method for inferential tests of the indirect effects was also conducted in mediation analysis.Results: The results indicated that the proportion of comorbid depression and chronic pain was 45.7%. Elderly Korean Americans with depression scored higher in pain severity, pain interference, and pain catastrophizing than those without depression. Pain catastrophizing was found to have a significant mediating effect on the relationship between depression and pain severity (indirect effect = 0.147, Bootstrap 95% CI = [0.079, 0.226]), controlling for demographic covariates, comorbidities and pain area. Pain catastrophizing also mediated the relationship between depression and pain interference (indirect effect =0.164, Bootstrap 95% CI = [0.097, 0.244]), controlling for the covariates.Conclusion: These findings add to the literature by providing evidence that pain catastrophizing plays a role in high levels of pain severity and pain interference comorbid chronic pain and depression in Asian elderly immigrants. Appropriate culturally tailored programs to redirect pain catastrophizing cognitive process should be developed and provided for elderly Asian Americans to reduce chronic pain disparity.Keywords: Korean immigrants, cross-cultural, comorbid, mediation

Boram Lee,1 Bo-Kyung Kim,2 Hyeong-Jun Kim,3 In Chul Jung,4 Ae-Ran Kim,1 Hyo-Ju Park,1 O-Jin Kwon,1 Jun-Hwan Lee,1,5 Joo-Hee Kim6,7 1Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 2Department of Neuropsychiatry, School of Korean Medicine, Pusan National University, Yangsan-si, Gyeongsangnam-do, Republic of Korea; 3Department of Oriental Gynecology, Jecheon Oriental Hospital of Semyung University, Jecheon, Republic of Korea; 4Department of Neuropsychiatry, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea; 5Korean Medicine Life Science, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 6Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Sangji University, Wonju-si, Gangwon-do, Republic of Korea; 7Research Institute of Korean Medicine, Sangji University, Wonju-si, Gangwon-do 26339, Republic of KoreaCorrespondence: Joo-Hee KimDepartment of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Sangji University, 83, Sangjidae-gil, Wonju-si, Gangwon-do, Republic of KoreaTel +82 33 741 9268Fax +82 33 741 9141Email jhkim714v@gmail.comPurpose: To evaluate the efficacy and safety of electroacupuncture in treating insomnia.Patients and Methods: In a multicenter, randomized, assessor-blinded, controlled trial, 150 patients with DSM-5-diagnosed insomnia with Insomnia Severity Index (ISI) scores ≥ 15 were randomly assigned to three different groups that underwent 10 sessions of electroacupuncture, sham-electroacupuncture, or usual care for 4 weeks from October 2015 to June 2016 at four Korean medicine hospitals, Republic of Korea. The primary outcome included the ISI score at Week 4; the secondary outcomes included evaluations of Pittsburgh Sleep Quality Index (PSQI), sleep diary, Hospital Anxiety and Depression Scale (HADS), EuroQoL five dimension (EQ-5D), Patient Global Impression of Change (PGIC), and salivary melatonin and cortisol levels. Assessments were performed at baseline (Week 0) and at Weeks 2, 4, 8, and 12.Results: Compared with the usual care group, electroacupuncture group showed a greater improvement in ISI, PSQI, sleep diary-derived variables and HADS and EQ-5D scores at Week 4. The effects mostly persisted until Week 12. There were no significant differences between electroacupuncture and sham-electroacupuncture groups at Week 4 in all outcome measures, except sleep diary-derived sleep efficiency. However, the ISI score showed a significant difference between these groups at Weeks 8 and 12. Treatment success as per PGIC was significantly and borderline higher for electroacupuncture compared with usual care and sham-electroacupuncture, respectively. No significant changes in salivary melatonin and cortisol levels before and after treatment were observed in all groups. No serious adverse events were reported. Blinding was maintained in the sham-electroacupuncture group.Conclusion: Ten sessions of electroacupuncture can improve the sleep quality of patients with insomnia without serious adverse effects. Thus, it can be recommended as an effective, safe, and well-tolerated intervention.Keywords: electroacupuncture, insomnia, sleep initiation and maintenance disorders, randomized controlled trial

Ik-Seung Chee, 1, 2 Hyun-Jin Kim, 2 Young Lee, 3 Jee Wook Kim 4, 5 1Department of Psychiatry, Chungnam National University Hospital, Daejeon, Republic of Korea; 2Department of Psychiatry, Chungnam National University Sejong Hospital, Sejong, Republic of Korea; 3Department of Dermatology, Chungnam National University Hospital, Daejeon, Republic of Korea; 4Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Gyeonggi, Republic of Korea; 5Department of Psychiatry, Hallym University College of Medicine, Chuncheon, Gangwan, Republic of KoreaCorrespondence: Jee Wook KimDepartment of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, 7 Keunjaebong-gil, Hwaseong-si, Gyeonggi-do 18450, Republic of KoreaTel +82 31 8086 2340Fax +82 31 8086 2029Email kimakins@hanmail.netPurpose: To examine the relationships of body dysmorphic disorder (BDD) with psychiatric symptoms and quality of life in dermatological patients.Patients and Methods: A total of 154 female patients with dermatological disease underwent a comprehensive clinical assessment that included the Body Dysmorphic Disorder Examination-Self Report (BDDE-SR), Symptom Checklist 90-Revised (SCL-90-R), and Skindex-29. Dermatological disease was categorized as follows: inflammatory dermatoses (reference category), isolated lesions, and unclassified dermatoses. The BDDE-SR and SCL-90-R scores were used to evaluate BDD and psychiatric symptoms, respectively. Dermatological quality of life was measured with the Skindex-29.Results: The BDDE-SR score was significantly associated with the SCL-90-R and Skindex-29 total and subscores, even after controlling for age, body mass index, and dermatological diagnosis. The variables that contributed most to the BDDE-SR score were the SCL-90-R depression score and Skindex-29 emotion scores. Additional analyses revealed that the BDDE-SR score was higher in participants with unclassified dermatoses, but neither the SCL-90-R score nor Skindex-29 score was related to any dermatological diagnosis.Conclusion: The BDD symptoms were especially prominent in the unclassified dermatoses group and were highly related to psychiatric symptoms and a poor quality of life in our dermatological patients. Further research including studies involving psychiatric interviews to confirm the BDD diagnosis and symptoms will improve our understanding of BDD in dermatological patients.Keywords: body dysmorphic disorder, psychiatric symptoms, quality of life: dermatological disease, unclassified dermatoses

Hyo Jin Kim, Solyi Lee, Hak Moo Cho, Kyung Woo Kim, Hey Ran Choi, Si Ra Bang Department of Anesthesiology and Pain Medicine, Inje University Seoul Paik Hospital, Seoul, KoreaCorrespondence: Si Ra BangDepartment of Anesthesiology and Pain Medicine, Inje University Seoul Paik Hospital, Seoul, KoreaTel +82-2-2270-0095Fax +82-2-2270-0094Email sira1045@naver.comAbstract: Retropharyngeal deep neck infection sometimes necessitates securing of the airway and surgery for drainage. Airway management in patients with deep neck infection is challenging for anesthesiologists. A 56-year-old woman diagnosed with deep neck infection was admitted for incision and drainage. In the first operation for incision and drainage, indirect videolaryngoscope was utilized to confirm the airway before tracheal intubation, and the patient was intubated successfully. In the second operation for wound closure, dexmedetomidine administration and high-flow nasal cannulation were used during monitored anesthesia care throughout a subsequent procedure. The outcome in the present case suggests that indirect videolaryngoscope, dexmedetomidine, and high-flow nasal cannula can facilitate effective management during surgery in patients with retropharyngeal deep neck space infection.Keywords: dexmedetomidine, high-flow nasal cannula, indirect laryngoscope, neck infection

Do Sun Kwon,1,* Yong Jun Choi,2,* Tae Hee Kim,2 Min Kwang Byun,2 Jae Hwa Cho,2 Hyung Jung Kim,2 Hye Jung Park2 1Department of Internal Medicine, Hallym Hospital, Incheon, Korea; 2Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea*These authors contributed equally to this workCorrespondence: Hye Jung Park Department of Internal MedicineGangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-Ro, Gangnam-Gu, Seoul 60273, Republic of KoreaTel +82-2-2019-3302Fax +82-2-3463-3882Email craft7820@yuhs.acPurpose: The forced mid-expiratory flow (FEF25-75%) value is a potentially sensitive marker of obstructive peripheral airflow. We aimed to assess whether FEF25-75% can be an early predictor of chronic obstructive pulmonary disease (COPD).Patients and Methods: Between July 1, 2007 and June 31, 2009, we identified 3624 patients who underwent a pulmonary function test (PFT) in Gangnam Severance Hospital. We selected 307 patients aged over 40 years without COPD who had normal PFT results at baseline and who had follow-up PFT records more than 1 year later. A FEF25-75% z-score less than − 0.8435 was considered low. We defined COPD as a forced expiratory volume in one second/forced vital capacity value of less than 0.7 before July 31, 2019.Results: Among 307 patients, 91 (29.6%) had low FEF25-75% at baseline. After 10 years, the incidence rate of COPD in the low FEF25-75% group was significantly higher than that in the normal FEF25-75% group (41.8% vs 7.4%; P-value< 0.001). The Cox proportional hazard model showed that age (hazard ratio [HR] 1.09; P-value< 0.001), smoking status (occasional smoker HR, 4.59; P-value< 0.001 and long-term smoker HR, 2.18; P-value=0.023), and low FEF25-75% (HR, 3.31; P-value< 0.001) were predictive factors for the development of COPD.Conclusion: The FEF25-75% value in patients with normal lung function is a useful predictor for the development of COPD. We should carefully monitor patients who present with low FEF25-75% values, even if they have normal lung function.Keywords: COPD, respiratory function tests, tobacco

Hong Jun Kim, Jae Joon Han, Chi Hoon Maeng, Sun Kyung Baek Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of KoreaCorrespondence: Sun Kyung Baek Division of Hematology-Oncology, Department of Internal MedicineKyung Hee University School of Medicine, 23, Kyungheedae-ro, Dongdaemoon-gu, Seoul 130-872, KoreaTel +82.2-958-8362Fax +82.2-968-1848Email wkiki@naver.comBackground: Lenvatinib, a novel multi-target tyrosine kinase inhibitor, has been approved for treating differentiated thyroid cancer. Herein, we describe a rare case of acute pancreatitis that developed during lenvatinib treatment in a 65-year-old man with recurrent thyroid cancer.Case Presentation: The patient was admitted to our department following a complaint of acute-onset epigastric pain and indigestion. He had been receiving lenvatinib since 34 days. Although his serum amylase and lipase levels were normal, he had acute-onset persistent epigastric pain and typical computed tomography findings, which were consistent with those of acute pancreatitis. As other common etiologies were excluded, it was concluded that the patient had lenvatinib-induced acute pancreatitis. On admission day 14, he could consume food orally, after conservative care, including drug cessation, intravenous hydration, and pain control.Conclusion: Physicians should consider acute pancreatitis as a differential diagnosis for patients complaining of abdominal pain while on lenvatinib, regardless of hyperamylasemia or hyperlipasemia. Systematic collection of data on acute pancreatitis development during lenvatinib treatment should be considered, and further research is warranted to identify the mechanism of acute pancreatitis associated with multi-target tyrosine kinase inhibitors such as lenvatinib.Keywords: differentiated thyroid cancer, hyperlipasemia, tyrosine kinase inhibitors

Hong Jun Kim,1 Hong-Kyu Kim2 1Division of Hematology-Oncology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 2Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of KoreaCorrespondence: Hong-Kyu KimDepartment of Surgery, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul 03080, Republic of KoreaTel +82-2-958-8188Email limittango@gmail.comBackground: Hepatic portal venous gas (HPVG) is a pathological condition characterized by gas in the portal venous system and its branches. The clinical manifestations of HPVG range from benign to life-threatening conditions. Here, we present a rare case of HPVG accompanied by free air in a healthy young patient without any suspicious etiology.Case Presentation: A 28-year-old man without any specific medical history complained of sudden-onset dyspnea. On admission, his vital signs were stable, and the laboratory tests and physical examinations were within normal range. A plain chest and abdominal film revealed subphrenic free air and HPVG. Contrast-enhanced computed tomography (CT) showed extensive portal venous gas throughout the liver; however, there were no abnormal findings indicative of the etiology. Considering the stable vital signs and the lack of physical findings suggesting a surgical acute abdomen, the patient was managed conservatively. On admission day 3, the subphrenic free air and HPVG shown in the initial study had almost resolved, with no new symptoms. He was discharged on the fourth day after admission without any complications. Esophagogastroduodenoscopy, colonoscopy, and colonography protocol CT scan showed no significant abnormalities.Conclusion: This case suggests that idiopathic HPVG could appear in healthy patients complaining only of vague symptoms. Initial conservative management could be considered if HPVG does not result from a life-threatening condition that needs immediate management, and if the patient is stable.Keywords: hepatic portal venous gas, pneumoperitoneum, pneumoretroperitoneum, idiopathic

Sue-Jung Kim,1 Hyo-Jeong Kim,2 Kiho Kim3 1Department of Psychology, Chung-Ang University, Seoul, South Korea; 2Department of Psychology, Seoul National University, Seoul, South Korea; 3Department of Psychology of Counseling, Sejong Cyber University, Seoul, South KoreaCorrespondence: Kiho Kim Department of Psychology of CounselingSejong Cyber University, Cheonho-Daero 680, Gwangjin-Gu, Seoul 04992, South KoreaEmail kihohere@gmail.comPurpose: This study investigated how an individual’s time perspective of the present and the future affects the delay of gratification, using the construal level theory. In addition, the mechanisms that influence the time perspective on the delay of gratification were examined through the mediating roles of the psychological distance and the perceived possibility of getting a future reward.Participants and Methods: One hundred twenty university students completed the Korean version of the Swedish Zimbardo Time Perspective Inventory (S-ZTPI) and performed a Temporal Discounting task to aid in the evaluation of their ability to delay gratification. Their psychological distance to the future and perceived possibility of getting a future reward were measured using the visual analogue scale.Results: The results showed that once the Present-Hedonistic and Future-Negative from among the six-time perspectives increased, and the ability to delayed gratification decreased. On the other hand, once the Future-Positive time perspective increased, the ability to delayed gratification increased. Only the psychological distance for 9 months was associated with time perspective and the mediation effect was not significant. Present-Hedonistic time perspective negatively predicted the perceived possibility of getting a future reward and the delay of gratification. The perceived possibility of getting a future reward fully mediated the relation between the Future-Negative time perspective and the delay of gratification.Conclusion: These findings suggest that problems involved with the delay of gratification (such as smoking, addiction, and binge eating behavior) are more likely to occur in people who have high Present-Hedonistic and Future-Negative time perspectives, because these time perspectives lead to a lower perceived possibility of getting a future.Keywords: time perspective, delay of gratification, construal level theory, psychological distance, perceived possibility of getting a future reward

Hyun Jeong Kim, 1,* Nga Thi Trinh, 1,* Yunjeong Choi, 1 Woorim Kim, 1 Kyung Hyun Min, 1 Sang Oh Kang, 1 Joo Hee Kim, 2 Hyoun-Ah Kim, 3 Ju-Yang Jung, 3 In Ah Choi, 4 Kyung Eun Lee 1 1College of Pharmacy, Chungbuk National University, Cheongju-si, Republic of Korea; 2College of Pharmacy, Ajou University, Suwon, Republic of Korea; 3Department of Rheumatology, Ajou University School of Medicine, Suwon, Republic of Korea; 4Division of Rheumatology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea*These authors contributed equally to this workCorrespondence: Kyung Eun LeeCollege of Pharmacy, Chungbuk National University, 660-1 Yeonje-ri, Osong-eup, Heungdeok-gu, Cheongju-si 28160, Republic of KoreaTel +82 43 261 3590Fax +82 43 268 2732Email kaylee@cbnu.ac.krPurpose: TNF-α is a transmembrane protein which requires cleavage by ADAM17 in order to act systemically. The activation of ADAM17 to generate soluble TNF‑α results in an increased inflammatory activity. We hypothesized that variants spanning the ADAM17 gene contribute towards the observed variation in patient response defined by the number of changes in TNF‑α inhibitors.Patients and Methods: Seven single-nucleotide polymorphisms (SNPs) of ADAM17 in 63 patients with rheumatoid arthritis who received TNF-α inhibitors were analyzed: rs57467365, rs62117540, rs117645314, rs6432013, rs532704607, rs117179141, and rs12692386. Univariate and multivariate regression analysis were employed to investigate the independent predictable factors for changes in TNF-α inhibitors.Results: ADAM17 rs117645314 and rs117179141 showed significant association with the number of changes in TNF-α inhibitors. Patients with GA in rs117645314 and AT in rs117179141 had significantly higher chance of two or more changes of TNF-α inhibitors than those with wild homozygous alleles. Multivariate analysis showed that rs117179141 explained 5.7% of the 23.8% variability in TNF-α inhibitor response.Conclusion: This study showed that the number of changes in TNF-α inhibitor is associated with ADAM17 SNPs.Keywords: rheumatoid arthritis, TNF-α inhibitor, ADAM17, single-nucleotide polymorphism

Seo Eun Hwang,*,1 Hyuktae Kwon,*,1 Su-Min Jeong,1 Hyun-Jin Kim,2 Jin-Ho Park1,31Department of Family Medicine, Seoul National University Hospital, Seoul, South Korea; 2Big Data Center, National Cancer Control Institute, National Cancer Center, Goyang, South Korea; 3Department of Family Medicine, Seoul National University College of Medicine, Seoul, South Korea*These authors contributed equally to this workPurpose: Although some studies have tried to determine the impact of long-term air pollution exposure on obesity, they have mainly focused on body mass index (BMI) and the results are inconsistent. Therefore, we investigated the association of annual ambient air pollution exposure with various obesity traits, including computed tomography-measured abdominal fatness, in a large Korean adult population.Patients and methods: A total of 5,114 participants who underwent routine health check-ups at Seoul National University Hospital were included in the analysis. We calculated the annual average concentrations of ambient air pollutants, such as particulate matter ≤10 μm in diameter (PM10) and nitrogen dioxide (NO2), using the individual’s zip code. Obesity-related indicators included the BMI, waist circumference (WC), percent body fat (PBF), total adipose tissue (TAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT).Results: The mean age of the population was 53.5 and 70.9% were men. The mean annual concentrations of PM10 and NO2 were 49.4 μg/m3 and 30.3 ppb, respectively. In the full covariates model, adjusted for demographic and clinical variables, interquartile range increase in annual average concentration of PM10 and NO2 was not associated with any obesity-related phenotypes including BMI, WC, PBF, TAT, VAT, and SAT (all P>0.05). Likewise, no significant association between air pollutants and obesity-related traits was observed in any subgroups, stratified by sex and age (all P>0.05).Conclusion: Annual exposure to ambient air pollution is not associated with any obesity-related traits in Korean adults.Keywords: air, pollution, particulate, matter, obesity, abdominal adiposity

Yoo Jin Shim,1* Hong Jun Kim,2* Sang Cheul Oh,3 Sun Il Lee,4 Seung Wook Choi11Department of Sports and Leisure, Sungshin Women’s University, Seongbuk-gu, Seoul 02844, Republic of Korea; 2Division of Oncology, Department of Internal Medicine, Kyung Hee University School of Medicine, Dong-dae-mun-gu, Seoul 02447, Republic of Korea; 3Division of Oncology, Department of Internal Medicine, Korea University Guro Hospital, Guro-gu, Seoul 08308, Republic of Korea; 4Department of Surgery, Korea University Guro Hospital, Guro-gu, Seoul 08308, Republic of Korea*These authors contributed equally to this work Objectives: The primary aim of this study was to investigate the beneficial effect of exercise on completion rates of adjuvant treatment, which is one of the major prognostic factors among patients with locally advanced colorectal cancer after undergoing curative resection followed by adjuvant treatment.Design: Prospective pilot studyMethods: We assigned patients who were scheduled to undergo adjuvant treatment (N=39) to the exercise group or the control group in a 2:1 ratio in the order of enrollment. Patients completed questionnaires and underwent assessment of the outcome variables at the start of chemotherapy and upon completion of treatment.Results: A fivefold lower possibility of dose adjustment in the exercise group compared to the control group was demonstrated (OR, 0.188; p=0.023; 95% CI, 0.044–0.793). A significantly smaller proportion of the exercise group had grade 3 or 4 nausea (p=0.018) and neurotoxicity (P=0.024) symptoms. Muscle to fat ratios were significantly reduced in the control group (p=0.039), but not in the exercise group (p=0.742). Serum levels of leptin were significantly increased in the control group (p=0.038), but not in the exercise group (p=0.073). Serum levels of adiponectin were significantly increased in the exercise group (p=0.026) but tended to be decreased in the control group with no statistical significance (p=0.418).Conclusions: Exercise training among patients with colorectal cancer was found to have a beneficial impact on adjuvant treatment completion rates and treatment-associated toxicities. This program was also shown to be beneficial to patients’ body compositions and serum levels of adipokines.Keywords: exercise, chemotherapy, adjuvant, chemoradiotherapy, adjuvant, colorectal neoplasms, body composition, adipokines

Hyo-Jung Kim,1 Joo-Young Lee,1 Eun-Song Lee,1 Hyo-Jung Jung,2 Hyung-Joon Ahn,2 Baek-Il Kim11Department of Preventive Dentistry & Public Oral Health, Brain Korea 21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea; 2Department of Orofacial pain & Oral medicine, Yonsei University College of Dentistry, Seoul, Republic of KoreaPurpose: Conventional oral exercises in previous studies are considered impractical for continuous use in the elderly because of the extended duration needed for effective outcomes. Therefore, in the present study, a simple oral exercise (SOE) was developed to reduce performance time, focusing on improvements in mastication, salivation, and swallowing functions. The aim of this study was to determine the short-term effects of the SOE with respect to improving mastication, salivation, and swallowing function in elderly subjects ≥65 years of age.Patients and methods: The study included 84 subjects, all of whom performed the SOE 2 times per day for 1 week. Masticatory performance was assessed using the mixing ability index (MAI). Unstimulated saliva and the degree of moisture of the tongue/buccal mucosa were evaluated, and the repetitive saliva swallowing test was performed. On the basis of each of these four measurements, subjects were dichotomized into two groups with high (good) and low (poor) conditions. The same evaluations were conducted before and immediately after intervention, as well as after 1 week of intervention. A subjective evaluation with questionnaires was performed after 1 week of intervention. The changes were analyzed using repeated-measures ANOVA, Cochran’s Q test, and McNemar’s test.Results: The mean MAI increased by 6% immediately after the intervention, and by 16% in the poor-chewing group. Similarly, the amount of unstimulated saliva increased by 0.1 ml/min immediately after the SOE, and by 29% in the poor-salivation group. The degree of tongue moisture increased by 3% and was maintained. In the poor-swallowing group, 25% and 40% of the subjects were upgraded to the good-swallowing group immediately after intervention, as well as after 1 week of intervention, respectively. The subjects experienced less discomfort as their oral function improved.Conclusion: The SOE was effective in immediately improving oral functions, and improvement was maintained for 1 week.Keywords: deglutition disorders, elderly, mastication, oral exercise, salivation, xerostomia

Hyun Jeong Kim,* Young-Mo Yang,* Eun Joo Choi Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, South Korea *These authors contributed equally to this work Background: A number of symptomatic patients tend to use over-the-counter (OTC) medications and prescription medications. OTC medications can be easily obtained in pharmacies for self-treatment, but using OTC medications is not always safe and beneficial for patients. The aims of this study were to examine the use patterns of OTC medications and assess patients’ perspectives regarding the use of OTC medications in Korean patients with chronic diseases. Patients and methods: A descriptive, cross-sectional survey was carried out with Korean patients who visited the community pharmacy, located at the southern region of South Korea, during September 2015. Results: A total of 345 patients participated in this survey. Approximately 64% of Korean survey respondents reported that they had used OTC drugs. The most commonly used OTC medications were antipyretics, analgesics and anti-inflammatory drugs. The perception level of Korean consumers on adverse drug reactions and drug–drug interactions from OTC medications was relatively low. Although OTC package leaflets are a main source of information about OTC medications, Korean consumers’ level of reading OTC package leaflets was relatively low. Conclusion: Based on these results, this study can serve as a meaningful starting point for interventions of health care professionals regarding OTC medications in South Korea. In particular, pharmacists should inform their consumers of drug-related problems from OTC drugs during consultation with the consumers; however, information about OTC drugs should be tailored to consumer information needs with the consideration of his or her circumstance. It is somewhat difficult to generalize the results from this study to other regions of South Korea since most of the respondents were probably residents of a small rural city located in the southern region of South Korea. Keywords: over-the-counter drugs, chronic disease, community pharmacy, survey, Korea

Woo Youl Kang,1,2,* Sook Jin Seong,1,* Boram Ohk,1,2 Mi-Ri Gwon,1,3 Bo Kyung Kim,1,2 Sookie La,4 Hyun-Ju Kim,3 Seungil Cho,1 Young-Ran Yoon,1,2 Dong Heon Yang,5 Hae Won Lee1 1Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea; 2Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, Daegu, Republic of Korea; 3Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea; 4Analytical Research Division, Biocore Co Ltd, Seoul, Republic of Korea; 5Division of Cardiology, Department of Internal Medicine, Kyungpook National University School of Medicine & Hospital, Daegu, Republic of Korea *These authors contributed equally to this work Purpose: A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance.Methods: The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography–tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period.Results: Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax) and the area under the plasma concentration–time curve from time 0 to the last measurement (AUC0–t) values of telmisartan were 522.29 ng/mL and 2,475.16 ng⋅h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng⋅h/mL for the individual agents concomitantly administered, respectively. The mean Cmax and AUC0–t values of S-amlodipine were 2.71 ng/mL and 130.69 ng⋅h/mL for the FDC, and 2.74 ng/mL and 129.81 ng⋅h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan Cmax and AUC0–t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353–0.9846) and 0.9431 (0.8698–1.0226), respectively. The GMR and 90% CI for the S-amlodipine Cmax and AUC0–t (FDC/concomitant administration) were 0.9829 (0.9143–1.0567) and 0.9632 (0.8798–1.0546), respectively. As the intrasubject variability of the Cmax for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. Conclusion: CKD-828 FDC tablets were shown to be bioequivalent to coadministration of the individual agents with the respective strength, in healthy subjects under fasting conditions. There was no significant difference in safety profile between the two treatments. Keywords: fixed-dose combination, pharmacokinetics, S-amlodipine, telmisartan, safety

Yun Hwan Oh,1,2 Ji Hyun Moon,1,2 Hyeon Ju Kim,1,3 Mi Hee Kong1,3 1Department of Family Medicine, Jeju National University Hospital, 2Department of Medicine, Graduate School of Jeju National University, 3Department of Family Medicine, School of Medicine, Jeju National University, Jeju, Republic of Korea Purpose: Visceral obesity has been recognized as a predictor of metabolic risk factors. However, few studies have evaluated the metabolic risks in subjects with normal waist circumference (WC). We aimed to examine if the visceral-to-subcutaneous fat ratio (VSR) has diagnostic value to identify multiple metabolic risk factors in subjects with normal WC, compared with visceral fat area (VFA) and subcutaneous fat area (SFA).Methods: This is a cross-sectional study in which we have compared mean VFA, SFA, and VSR according to each metabolic risk factor. We performed a receiver operating characteristic (ROC) curve analysis for VFA, SFA, and VSR to assess their accuracy in picking out two or more non-adipose factors for metabolic syndrome.Results: For each metabolic risk factor, mean VSRs were significantly different between groups (risk-absent group vs risk-present group) in men and women, except for men with low high-density lipoprotein. However, mean VFAs and SFAs showed no significant differences between groups. VSR showed superior diagnostic values in predicting at least two non-adipose metabolic risk factors in men and similar diagnostic value in women. Areas under ROC curves for VSR and VFA were 0.705 and 0.649 in men (P=0.028) and 0.798 and 0.785 in women (P=0.321).Conclusion: For men with a normal WC, VSR appeared to effectively predict the presence of multiple metabolic risk factors. Thus, VSR may serve as an indicator for identifying men who have a normal WC and multiple metabolic risk factors. Keywords: visceral fat, subcutaneous fat, metabolic syndrome, visceral-to-subcutaneous fat ratio

Howard Lee,1,2,* Heechan Lee,1,2,* Jungmi Baik,3 Hyunjung Kim,3 Rachel Kim4 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, 3Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea, 4Global Clinical Trial Execution, Pfizer Korea, Seoul, Republic of Korea *These authors contributed equally to this work Background: Failure mode and effects analysis (FMEA) is a risk management tool to proactively identify and assess the causes and effects of potential failures in a system, thereby preventing them from happening. The objective of this study was to evaluate effectiveness of FMEA applied to an academic clinical trial center in a tertiary care setting.Methods: A multidisciplinary FMEA focus group at the Seoul National University Hospital Clinical Trials Center selected 6 core clinical trial processes, for which potential failure modes were identified and their risk priority number (RPN) was assessed. Remedial action plans for high-risk failure modes (RPN >160) were devised and a follow-up RPN scoring was conducted a year later.Results: A total of 114 failure modes were identified with an RPN score ranging 3–378, which was mainly driven by the severity score. Fourteen failure modes were of high risk, 11 of which were addressed by remedial actions. Rescoring showed a dramatic improvement attributed to reduction in the occurrence and detection scores by >3 and >2 points, respectively.Conclusions: FMEA is a powerful tool to improve quality in clinical trials. The Seoul National University Hospital Clinical Trials Center is expanding its FMEA capability to other core clinical trial processes. Keywords: clinical trial, failure modes and effects analysis, quality improvement, quality management, quality risks

Hae Won Lee,1,* Sook Jin Seong,1,* Boram Ohk,1,2 Woo Youl Kang,1,2 Mi-Ri Gwon,1 Bo Kyung Kim,1,2 Hyun-Ju Kim,3 Young-Ran Yoon1,2 1Clinical Trial Center, Kyungpook National University Hospital, 2Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, 3Cell and Matrix Research Institute, Daegu, Republic of Korea *These authors contributed equally to this work Objective: This study evaluated the pharmacokinetics (PKs) and safety of a newly developed β-lapachone (MB12066) tablet, a natural NAD(P)H:quinone oxidoreductase 1 (NQO1) substrate, in healthy male volunteers.Methods: In a randomized, double-blind, multiple-dose, two-treatment study, 100 mg MB12066 or placebo was given twice daily for 8 days to groups of eight or three fasted healthy male subjects, respectively, followed by serial blood sampling. Plasma concentrations for β-lapachone were determined using liquid chromatography–tandem mass spectrometry. PK parameters were obtained with non-compartmental analysis. Tolerability was assessed based on physical examinations, vital signs, clinical laboratory tests, and electrocardiograms.Results: Following a single 100 mg MB12066 oral dose, maximum plasma concentration (Cmax) of β-lapachone was 3.56±1.55 ng/mL, and the median (range) time to reach Cmax was 3 h (2–5 h). After the 8 days of 100 mg twice daily repeated dosing was completed, mean terminal half-life was determined to be 18.16±3.14 h, and the mean area under the plasma concentration vs time curve at steady state was 50.44±29.68 ng·h/mL. Accumulation index was 2.72±0.37. No serious adverse events (AEs) were reported, and all reported intensities of AEs were mild.Conclusion: The results demonstrated that MB12066 was safe and well tolerated in healthy volunteers and that there were no serious AEs. Accumulation in plasma with twice-daily administration was associated with a 2.72 accumulation ratio. Keywords: β-lapachone, healthy volunteers, MB12066, pharmacokinetics, safety

Rafael Taeho Han,1,2 Sewon Kim,3 Kyungmin Choi,1,2 Hyeonseok Jwa,1,2 JaeHee Lee,1,2 Hye Young Kim,1,2 Hee Jin Kim,4 Hang-Rae Kim,5 Seung Keun Back,6 Heung Sik Na1,2 1Neuroscience Research Institute, 2Department of Physiology, 3Department of Microbiology, College of Medicine, Korea University, Seoul, 4Division of Biological Science and Technology, Science and Technology College, Yonsei University Wonju Campus, Wonju, 5Department of Anatomy, College of Medicine, Seoul National University, Seoul, 6Department of Pharmaceutics and Biotechnology, College of Medical Engineering, Konyang University, Chungnam, South Korea Abstract: Recent studies have shown that approximately 70% of patients with severe atopic dermatitis (AD) develop asthma. Development of AD in infancy and subsequent other atopic diseases such as asthma in childhood is referred to as atopic march. However, a causal link between the diseases of atopic march has remained largely unaddressed, possibly due to lack of a proper animal model. Recently, we developed an AD rat model showing chronically relapsing dermatitis and scratching behaviors induced by neonatal capsaicin treatment. Here, we investigated whether our model also showed asthmatic changes, with the aim of expanding our AD model into an atopic march model. First, we confirmed that capsaicin treatment (50 mg/kg within 24 h after birth) induced dermatitis and scratching behaviors until 6 weeks of age. After that, the mRNA expression of Th1 and Th2 cytokines, such as IFN-γ and TNF-α, and IL-4, IL-5, and IL-13, respectively, was quantified with quantitative real-time polymerase chain reaction in the skin and the lungs. The number of total cells and eosinophils was counted in bronchoalveolar lavage (BAL) fluid. The levels of IgE in the serum and BAL fluid were determined with enzyme-linked immunosorbent assay. Paraffin-embedded sections (4 μm) were stained with hematoxylin/eosin to analyze the morphology of the lung and the airway. Airway responsiveness was measured in terms of airway resistance and compliance using the flexiVent system. In the capsaicin-treated rats, persistent dermatitis developed, and scratching behaviors increased over several weeks. The levels of IgE in the serum and BAL fluid as well as the mRNA expression of Th2 cytokines, including IL-4, IL-5, and IL-13, in both the skin and the lungs were elevated, and the number of eosinophils in the BAL fluid was also increased in the capsaicin-treated rats compared to control rats. Morphological analysis of the airway revealed smooth muscle hypertrophy and extensive mucus plug in the capsaicin-treated rats. Functional studies demonstrated an increment of the airway resistance and a decrement of lung compliance in the capsaicin-treated rats compared to control rats. Taken together, our findings suggested that neonatal capsaicin treatment induced asthma-like airway inflammation and responses in juvenile rats. Keywords: atopic march, scratching, cytokines, eosinophils, BAL fluid, pruritus, flexiVent, airway hypertrophy and remodelling

Min Kwang Byun,1 Eun Na Cho,1 Joon Chang,2 Chul Min Ahn,1 Hyung Jung Kim1 1Division of Pulmonology, Department of Internal Medicine, Gangnam Severance Hospital, 2Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea Background: Muscle wasting and chronic inflammation are predominant features of patients with COPD. Systemic inflammation is associated with an accelerated decline in lung function. In this study, the prevalence of sarcopenia and the relationships between sarcopenia and systemic inflammations in patients with stable COPD were investigated. Materials and methods: In a cross-sectional design, muscle strength and muscle mass were measured by handgrip strength (HGS) and bioelectrical impedance analysis in 80 patients with stable COPD. Patients (≥40 years old) diagnosed with COPD were recruited from outpatient clinics, and then COPD stages were classified. Sarcopenia was defined as the presence of both low muscle strength (by HGS) and low muscle mass (skeletal muscle mass index [SMMI]). Levels of circulating inflammatory biomarkers (IL-6 and high-sensitivity TNFα [hsTNFα]) were measured. Results: Sarcopenia was prevalent in 20 (25%) patients. Patients with sarcopenia were older, had lower body mass index, and a higher percentage of cardiovascular diseases. In addition, they had significantly higher modified Medical Research Council scores and lower 6-minute walk distance than those without sarcopenia. HGS was significantly correlated with age, modified Medical Research Council score, and COPD Assessment Test scores. Both HGS and SMMI had associations with IL-6 and hsTNFα (HGS, r=-0.35, P=0.002; SMMI, r=-0.246, P=0.044) level. In multivariate analysis, old age, lower body mass index, presence of cardiovascular comorbidities, and higher hsTNFα levels were significant determinants for sarcopenia in patients with stable COPD. Conclusion: Sarcopenia is very common in patients with stable COPD, and is associated with more severe dyspnea-scale scores and lower exercise tolerance. Systemic inflammation could be an important contributor to sarcopenia in the stable COPD population. Keywords: sarcopenia, muscle wasting, handgrip strength, systemic inflammation, COPD

Young Hyun Yeo,1 Keon-Hyung Lee,2 Hye Jeong Kim3 1Department of Public Administration, Sunmoon University, Asan, ChungNam, South Korea; 2Askew School of Public Administration and Policy, Florida State University, Tallahassee, FL, USA; 3Department of Public Administration, Sunmoon University, Asan, ChungNam, South Korea Abstract: Just as living organisms have a creation-maintenance-extinction life cycle, organizations also have a life cycle. Private organizations will not survive if they fail to acquire necessary resources through market competition. Public organizations, however, continue to survive because the government has provided financial support in order to enhance public interest. Only a few public organizations in Korea have closed. With the introduction of new public management since the economic crisis in 1997, however, public organizations have had to compete with private organizations. Public hospitals are not free to open or close their business. They are also controlled by the government in terms of their prices, management, budgets, and operations. As they pursue public interest by fulfilling the government’s order such as providing free or lower-priced care to the vulnerable population, they tend to provide a lower quality of care and suffer a financial burden. Employing a case study analysis, this study attempts to understand the external environment that local public hospitals face. The fundamental problem of local public hospitals in Korea is the value conflict between public interest and profitability. Local public hospitals are required to pursue public interest by assignment of a public mission including building a medical safety net for low-income patients and managing nonprofitable medical facilities and emergent health care situations. At the same time, they are required to pursue profitability by achieving high-quality care through competition and the operation of an independent, self-supporting system according to private business logic. Under such paradoxical situations, a political decision may cause an unexpected result. Keywords: local public hospital closure, publicness, organizational life cycle, South Korea

Hye Jung Park,1 Min Kwang Byun,1 Hyung Jung Kim,1 Jae Yeol Kim,2 Yu-Il Kim,3 Kwang-Ha Yoo,4 Eun Mi Chun,5 Ji Ye Jung,6 Sang Haak Lee,7 Chul Min Ahn1 On behalf of the Korean Smoking Cessation Study Group 1Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 2Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, 3Department of Internal Medicine, Chonnam National University Hospital, Gwangju, 4Department of Internal Medicine, Konkuk University School of Medicine, 5Department of Internal Medicine, Ewha Womans University School of Medicine, 6Division of Pulmonology, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, 7Division of Pulmonology, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Background: Vitamin C, as an antioxidant, has recently been suggested to provide protection against COPD; however, only few national cohort studies have investigated these effects. We aimed to confirm the protective effects of vitamin C against COPD in Korean patients. Patients and methods: We analyzed the data of 3,283 adults aged ≥40 years (representing 23,541,704 subjects) who underwent pulmonary function tests and responded to questionnaires on smoking history and vitamin C intake, with stratification variables and sampling weight designated by the Korea 2012 National Health and Nutrition Examination Survey. Results: Among all the subjects, 512 (representing 3,459,679 subjects; 15.6%) were diagnosed as having COPD based on pulmonary function test results. Male gender, old age, residence in suburban/rural regions, low household income, low educational level, an occupation in agriculture or fisheries, and heavy smoking were significantly associated with COPD. Low intake of nutrients, including potassium, vitamin A, carotene, retinol, and vitamin C, was significantly associated with COPD. The prevalence of COPD in heavy smokers with the lowest quartile (Q1, 141.63 mg; 32.6%) of vitamin C intake (P=0.015). In multivariate analysis, male gender, old age, heavy smoking, and a low intake of vitamin C were significant independent risk factors for COPD. A significant reduction of 76.7% in COPD risk was observed with a Q3 vitamin C intake compared to Q1 vitamin C intake (odds ratio, 0.233; 95% confidence interval, 0.094-0.576) in heavy smokers. Conclusion: This large-scale national study suggests that dietary vitamin C provides protection against COPD, independent of smoking history, in the general Korean population. Keywords: chronic obstructive lung disease, vitamin C, nutrition, risk factor, smoking

Eva Bagyinszky,1,* Sun Ah Park,2,* Hyung Jun Kim,2 Seong Hye Choi,3 Seong Soo A An,1 SangYun Kim4 1Department of BioNano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Inha University School of Medicine, Incheon, 4Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea *These authors contributed equally to this work Abstract: In this study, we report a first 226leucine (Leu) mutation to phenylalanine (Phe) in (PSEN1, CTC>TTC, L226F) in Asia from a Korean early-onset Alzheimer’s disease (EOAD) patient. Polymerase chain reaction (PCR)–single strand conformation polymorphism, sequencing, and in silico predictions were performed. Previously, L226F was reported in EOAD patients by Zekanowski et al and Gómez-Tortosa et al. Disease phenotypes appeared in their thirties, and family history was positive in both cases. In our patient, age of onset was similar (37 years of age), but the mutation seemed to be de novo, since no affected family member was found. This leucine to phenylalanine substitution may cause additional stresses inside the transmembrane region due to large aromatic side chain and increased hydrophobic interactions with hydrocarbon chains in the membrane and its binding partners. Clinical phenotype of the mutation was aggressive progression into neurodegeneration, resulting in rapid cognitive decline. One of the patients was initially diagnosed with frontotemporal dementia, but the diagnosis was revised to AD upon postmortem studies in which Aβ plaques were seen. A second mutation, L226R, was found for the L226 residue. Similar to L226F, the patient with L226R also developed the first symptoms in his 30s, but EOAD was diagnosed in his 40s. These findings suggested that L226 might be an important residue in PSEN1, since mutations could result in neurodegenerative disease phenotypes at relatively young ages. There are mutations, such as L226F, which may not present clear clinical symptoms for the definitive diagnosis between frontotemporal dementia and AD. In addition, the similarities in the phenotypes could also be possible between AD and frontotemporal dementia, suggesting difficulties in differential diagnosis of various neurodegenerative diseases. Keywords: Alzheimer’s disease, PSEN1 mutation, sequencing, frontotemporal dementia

Sohyun Jeong,1 In-Wha Kim,1 Kook-Hwan Oh,2 Nayoung Han,1 Kwon Wook Joo,2 Hyo Jin Kim,2 Jung Mi Oh1 1College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, 2Department of Internal Medicine, Division of Nephrology, Seoul National University Hospital, Seoul, Korea Background: Secondary hyperparathyroidism (SHPT) is one of the major risk factors of morbidity and mortality in end-stage renal disease. Cinacalcet effectively controls SHPT without causing hypercalcemia and hyperphosphatemia. However, there is significant inter-individual response variance to cinacalcet treatment. Therefore, we aimed to evaluate the genetic effects related with parathyroid hormone regulation as factors for cinacalcet response variance. Methods: Patients with a diagnosis of SHPT based on intact parathyroid hormone (iPTH) >300 pg/mL on dialysis were included in this study. They were over 18 years and have been treated by cinacalcet for more than 3 months. Responders and nonresponders were grouped by the serum iPTH changes. Twenty-four single nucleotide polymorphisms of CASR, VDR, FGFR1, KL, ALPL, RGS14, NR4A2, and PTHLH genes were selected for the pharmacogenetic analysis. Results: After adjusting for age, sex, and calcium level, CASR rs1042636 (odds ratio [OR]: 0.066, P=0.027) and rs1802757 (OR: 10.532, P=0.042) were associated with cinacalcet response. The association of haplotypes of CASR rs1042636, rs10190, and rs1802757; GCC (OR: 0.355, P=0.015); and ATT (OR: 2.769, P=0.014) with cinacalcet response was also significant. Conclusion: We obtained supporting information of the associations between cinacalcet response and CASR polymorphisms. CASR single nucleotide polymorphisms (SNPs) rs1802757, rs1042636, and haplotypes of rs1042636, rs10190, and rs1802757 were significantly associated with cinacalcet response variance. Keywords: CASR, calcium sensing receptor, SHPT, genetic polymorphisms, haplotype, single nucleotide polymorphisms

Hyung-Jun Kim,1,2 Jinwoo Lee,1,2 Young Sik Park,1,2 Chang-Hoon Lee,1,2 Sang-Min Lee,1,2 Jae-Joon Yim,1,2 Chul-Gyu Yoo,1,2 Young Whan Kim,1,2 Sung Koo Han,1,2 Sun Mi Choi1,2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea Purpose: Chronic obstructive pulmonary disease (COPD) is associated with increased postoperative complications. Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classified COPD patients into four groups based on spirometry results and the severity of symptoms. The objective of this study was to evaluate the impact of GOLD groups on postoperative complications. Patients and methods: We reviewed the medical records of COPD patients who underwent preoperative spirometry between April and August 2013 at a tertiary hospital in Korea. We divided the patients into GOLD groups according to the results of spirometry and self-administered questionnaires that assessed the symptom severity and exacerbation history. GOLD groups, demographic characteristics, and operative conditions were analyzed. Results: Among a total of 405 COPD patients, 70 (17.3%) patients experienced various postoperative complications, including infection, wound, or pulmonary complications. Thoracic surgery, upper abdominal surgery, general anesthesia, large estimated blood loss during surgery, and longer anesthesia time were significant risk factors for postoperative complications. Patients in high-risk group (GOLD groups C or D) had an increased risk of postoperative complications compared to those in low-risk group (GOLD groups A or B). Conclusion: COPD patients in GOLD groups representing a high exacerbation risk have an increased risk of postoperative complications compared to those with low risk. Keywords: chronic obstructive pulmonary disease, dyspnea, postoperative complications, risk assessment, spirometry

Min-Sun Kwak,1 Eunyoung Kim,2 Eun Jin Jang,3 Hyun Jung Kim,4 Chang-Hoon Lee5 1Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea; 2Department of Statistics, Kyungpook National University, Daegu, Republic of Korea; 3Department of Information Statistics, Andong National University, Andong, Republic of Korea; 4Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Republic of Korea; 5Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea Purpose: Although tiotropium (TIO) and inhaled corticosteroid (ICS)/long-acting β-agonists are frequently prescribed together, the efficacy of “triple therapy” has not been scientifically demonstrated. We conducted a systematic review and meta-analysis using Bayesian methods to compare triple therapy and TIO monotherapy.Methods: We searched the MEDLINE, EMBASE, and Cochrane Library databases for randomized controlled trials comparing the efficacy and safety of triple therapy and TIO monotherapy in patients with chronic obstructive pulmonary disease (COPD). We conducted a meta-analysis to compare the effectiveness and safety of triple therapy and TIO monotherapy using Bayesian random effects models.Results: Seven trials were included, and the risk of bias in the majority of the studies was acceptable. There were no statistically significant differences in the incidence of death and acute exacerbation of disease in the triple therapy and TIO monotherapy groups. Triple therapy improved the prebronchodilator forced expiratory volume in 1 second (mean difference [MD], 63.68 mL; 95% credible interval [CrI], 45.29–82.73), and patients receiving triple therapy showed more improvement in St George Respiratory Questionnaire scores (MD, -3.11 points; 95% CrI, -6.00 to -0.80) than patients receiving TIO monotherapy. However, both of these differences were lower than the minimal clinically important difference (MCID). No excessive adverse effects were reported in triple therapy group.Conclusion: Triple therapy with TIO and ICSs/long-acting β-agonists was only slightly more efficacious than TIO monotherapy in treating patients with COPD. Further investigations into the efficacy of new inhaled drugs are needed. Keywords: inhaled long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), inhaled long-acting β2-agonists (LABAs), chronic obstructive pulmonary disease (COPD)

Jung Eun Lee,1,2 In Young Jo,3 Song Mi Lee,3 Woo Jeong Kim,3 Hoon Young Choi,2,4 Sung Kyu Ha,4 Hyung Jong Kim,5 Hyeong Cheon Park2,4 1Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 2Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, 3Department of Nutrition Services, Gangnam Severance Hospital, 4Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 5Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea Background: The number of elderly people on dialysis is increasing rapidly. Fluid overload and malnutrition status are serious problems in elderly dialysis patients. We aimed to compare the hydration and nutritional status through bioimpedance analysis (BIA) between young and elderly hemodialysis (HD) patients and to analyze risk factors related to fluid overload and malnutrition status in these patients.Method: We conducted a cross-sectional study, in which 82 HD (males 42, mean age 58.7±12.9 years) patients were enrolled. We collected different types of data: laboratory data, such as serum creatinine, albumin, total iron-binding capacity, hemoglobin, total cholesterol; anthropometric data, such as hand grip strength (HGS); BIA data, such as intracellular water, skeletal muscle mass, body cell mass, bone mineral content, phase angle (PhA), extra cellular water (ECW)/total body water (TBW) ratio; and malnutrition-inflammation score (MIS), which is a traditional nutritional parameter for dialysis patients. All patients were stratified into two groups according to their age: young (

Hui-Jun Yang,1 Ji Young Yun,2 Young Eun Kim,3 Yong Hoon Lim,4 Han-Joon Kim,5 Sun Ha Paek,4 Beom S Jeon5 1Department of Neurology, Ulsan University Hospital, Ulsan, 2Department of Neurology, Ewha Womans University Mokdong Hospital, Seoul, 3Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, 4Department of Neurosurgery, Seoul National University Hospital, Seoul, 5Department of Neurology and Movement Disorder Center, Parkinson’s Disease Study Group and Neuroscience Research Institute, Seoul National University Hospital, Seoul, South Korea Abstract: The number of deep brain stimulation (DBS) hardware complications has increased during the past decade. In cases of abnormally high lead impedance with no evidence of a macroscopic fracture, optimal treatment options have not yet been established. Here, we present the case of a 49-year-old woman with a 12-year history of Parkinson’s disease who received bilateral subthalamic nucleus DBS in March 2006. The patient showed good control of parkinsonism until December 24, 2010, when she awoke with abrupt worsening of parkinsonian symptoms. At telemetric testing, lead impedances were found at >2,000 Ω in all four leads on the left side. Fracture of a lead or an extension wire was suspected. However, radiological screening and palpation revealed no macroscopic fracture. In June 2011, the implantable pulse generator (IPG) was changed under local anesthesia without any complications. Postoperatively, her parkinsonism immediately improved to the previous level, and the lead impedance readings by telemetry were also normalized. The disconnection of the neurostimulator connector block and the hybrid circuit board of the IPG was confirmed by destructive analysis. The present report illustrates that a staged approach that starts with simple IPG replacement can be an option for some cases of acute DBS effect loss with high impedance, when radiological findings are normal, thereby sparing the intact electrodes and extension wires. Keywords: connector block, hardware complication, implantable neurostimulators, Parkinson’s disease

Tae Won Kwak,1,* Hee Jae Shin,2,* Young-Il Jeong,1 Myoung-Eun Han,3 Sae-Ock Oh,3 Hyun-Jung Kim,4 Do Hyung Kim,5 Dae Hwan Kang1 1Biomedical Research Institute, Pusan National University Hospital, Busan, 2Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 3Department of Anatomy, School of Medicine, Pusan National University, Gyeongnam, 4Genewel Co Ltd. Gyeonggi-do, 5School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea *These authors contributed equally to this work Background: The aim of this study is to investigate the anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma. Methods: The anticancer activity of streptochlorin was evaluated in vitro in various cholangiocarcinoma cell lines for apoptosis, proliferation, invasiveness, and expression of various protein levels. A liver metastasis model was prepared by splenic injection of HuCC-T1 cholangiocarcinoma cells using a BALB/c nude mouse model to study the systemic antimetastatic efficacy of streptochlorin 5 mg/kg at 8 weeks. The antitumor efficacy of subcutaneously injected streptochlorin was also assessed using a solid tumor xenograft model of SNU478 cells for 22 days in the BALB/c nude mouse. Results: Streptochlorin inhibited growth and secretion of vascular endothelial growth factor by cholangiocarcinoma cells in a dose-dependent manner and induced apoptosis in vitro. In addition, streptochlorin effectively inhibited invasion and migration of cholangiocarcinoma cells. Secretion of vascular endothelial growth factor and activity of matrix metalloproteinase-9 in cholangiocarcinoma cells were also suppressed by treatment with streptochlorin. Streptochlorin effectively regulated metastasis of HuCC-T1 cells in a mouse model of liver metastasis. In a tumor xenograft study using SNU478 cells, streptochlorin significantly inhibited tumor growth without changes in body weight when compared with the control. Conclusion: These results reveal that streptochlorin is a promising chemotherapeutic agent to the treatment of cholangiocarcinoma. Keywords: streptochlorin, cholangiocarcinoma, chemotherapeutic agent, invasion, metastasis

Kunwoo Lee,1,2 Pengzhi Yu,3 Nithya Lingampalli,1 Hyun Jin Kim,1 Richard Tang,1 Niren Murthy1,2 1Department of Bioengineering, University of California, Berkeley, CA, USA; 2UC Berkeley and UCSF Joint Graduate Program in Bioengineering, Berkeley/San Francisco, CA, USA; 3Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA Abstract: The treatment of myocardial infarction is a major challenge in medicine due to the inability of heart tissue to regenerate. Direct reprogramming of endogenous cardiac fibroblasts into functional cardiomyocytes via the delivery of transcription factor mRNAs has the potential to regenerate cardiac tissue and to treat heart failure. Even though mRNA delivery to cardiac fibroblasts has the therapeutic potential, mRNA transfection in cardiac fibroblasts has been challenging. Herein, we develop an efficient mRNA transfection in cultured mouse cardiac fibroblasts via a polyarginine-fused heart-targeting peptide and lipofectamine complex, termed C-Lipo and demonstrate the partial direct reprogramming of cardiac fibroblasts towards cardiomyocyte cells. C-Lipo enabled the mRNA-induced direct cardiac reprogramming due to its efficient transfection with low toxicity, which allowed for multiple transfections of Gata4, Mef2c, and Tbx5 (GMT) mRNAs for a period of 2 weeks. The induced cardiomyocyte-like cells had α-MHC promoter-driven GFP expression and striated cardiac muscle structure from a-actinin immunohistochemistry. GMT mRNA transfection of cultured mouse cardiac fibroblasts via C-Lipo significantly increased expression of the cardiomyocyte marker genes, Actc1, Actn2, Gja1, Hand2, and Tnnt2, after 2 weeks of transfection. Moreover, this study provides the first direct evidence that the stoichiometry of the GMT reprogramming factors influence the expression of cardiomyocyte marker genes. Our results demonstrate that mRNA delivery is a potential approach for cardiomyocyte generation. Keywords: direct cardiac reprogramming, cardiac fibroblast transfection, mRNA transfection, cardiac regeneration

Jwa-Kyung Kim,1 Young Rim Song,1 Young-Jun Kwon,2 Hyung Jik Kim,1 Sung Gyun Kim,1 Young-Su Ju21Department of Internal Medicine, Kidney Research Institute, 2Department of Occupational and Environmental Medicine, Hallym University Sacred Heart Hospital, Anyang-si, South KoreaBackground: With increasing age, body fat increases and muscle mass reduces. Even people with a normal weight may have a higher percentage of body fat. The aim of this study is to investigate the association between increased body fat and renal function decline (RFD) in the general elderly population with normal or mildly impaired renal function.Method: We conducted a prospective study of 615 healthy individuals in the general Korean population aged ≥60 years who participated in two health screening check-ups separated by a 4-year period. Obesity was defined as the highest sex-specific tertiles of the percentage body fat (PBF). The main outcome was changes of estimated glomerular filtration rate (eGFR) during the 4 years. Significant RFD was defined as a decrease of eGFR over the upper quartile (≤-2.1% per year). Results: The mean age was 67.2±6.6 years. The median value of the absolute decline in the eGFR and the percent change was -3.0 mL/minute/1.73 m2 and -0.87%/year in men and -3.1 mL/minute/1.73 m2 and -0.89%/year in women, respectively. When stratified by sex-specific PBF tertiles, pronounced differences were observed in both sexes; those at the highest tertile of PBF showed the greatest decline in eGFR. Even after adjustments for traditional risk factors of RFD, PBF was independently associated with eGFR changes (ß=-0.181; P

Hyo Jong Kim, Kyu Yeol Lee, Lih WangDepartment of Orthopaedic Surgery, College of Medicine, Dong-A University, Busan, KoreaBackground: The purpose of this study was to analyze the complications, clinical outcomes, and any correlative risk factors associated with degenerative lumbar deformity surgery in elderly patients.Methods: We reviewed 78 patients who underwent posterior decompression and posterolateral fusion requiring a minimum three-level fusion for degenerative lumbar deformity associated with spinal stenosis between May 2001 and May 2006, with at least a one-year follow-up period. We assessed and compared the postoperative complications and clinical outcomes for patients aged 65 years and over (group A) and patients aged 50–64 years (group B). Risk factors that could influence complications and clinical outcome were evaluated and statistically analyzed.Results: The postoperative complication rate was not significantly different between the two age groups (53% in group A and 40% in group B); however, group A had a significantly higher frequency of minor complications than group B, especially for urinary retention and postoperative delirium. A statistical relationship between diabetes mellitus and deep wound infection, one of the major complications of degenerative lumbar deformity surgery, was observed in both group A and group B. Male sex was a risk factor for urinary retention and long operative time, and abundant blood loss was a significant risk factor for postoperative delirium in group A.Conclusion: There were no significant differences in results for degenerative lumbar deformity surgery between patients older and younger than 65 years. However, diabetes mellitus showed a significant correlation with deep wound infection, which is one of the major complications of degenerative lumbar deformity surgery, and with urinary retention and postoperative delirium, which occurred frequently in patients aged older than 65 years.Keywords: spinal stenosis, lumbar deformity, elderly, risk factor, complication, clinical outcome

Seong-Ho Hong1,*, Ji-Eun Kim1,6,*, You-Kyoung Kim2, Arash Minai-Tehrani1, Ji-Young Shin1, Bitna Kang1, Hye-Joon Kim1, Chong-Su Cho2, Chanhee Chae3, Hu-Lin Jiang1, Myung-Haing Cho1,4–71Laboratory of Toxicology, 2Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, 3Laboratory of Pathology, College of Veterinary Medicine, 4Graduate Group of Tumor Biology, 5Center for Food and Toxicology, Seoul National University, Seoul, Korea; 6Department of Nano Fusion Technology, Graduate School of Convergence Science and Technology, 7Advanced Institute of Convergence Technology, Seoul National University, Suwon, Korea*These authors contributed equally to this workBackground: Polyethylenimine (PEI)-based nonviral gene-delivery systems are commonly employed because of their high transfection efficiency. However, the toxic nature of PEI is a significant obstacle in clinical gene therapy. In this study, we developed biocompatible glycerol triacrylate–spermine (GT–SPE) polyspermine as a nanosized gene carrier for potential lung cancer gene therapy.Methods: The GT–SPE was synthesized using the Michael addition reaction between GT and SPE. The molecular weight was characterized using gel permeability chromatography multiangle laser light scattering and the composition of the polymer was analyzed using proton nuclear magnetic resonance.Results: The GT–SPE successfully protected the DNA from nucleases. The average particle size of the GT–SPE was 121 nm with a zeta potential of +23.45 mV. The GT–SPE was found to be less toxic than PEI for various cell lines, as well as for a murine model. Finally, our results showed that the GT–SPE/small hairpin Akt1 (shAkt1) complex suppressed lung tumorigenesis in a K-rasLA1 lung cancer mice model by inducing apoptosis through the Akt signaling pathway and cell cycle arrest. Aerosol delivered GT–SPE/shAkt1, which reduced matrix metalloproteinase-9 activity and suppressed the expression levels of proliferating cell nuclear antigen, as well as vascular endothelial growth factors and CD31, which are known proliferation and angiogenesis markers, respectively.Conclusion: Our data suggest that GT–SPE may be a candidate for short hairpin-shaped RNA-based aerosol lung cancer gene therapy.Keywords: lung cancer, gene therapy, aerosol delivery, spermine

Abstract Fibrous dysplasia (FD) is a non-malignant condition caused by post-zygotic, activating mutations of the GNAS gene that results in inhibition of the differentiation and proliferation of bone-forming stromal cells and leads to the replacement of normal bone and marrow by fibrous tissue and woven bone. The phenotype is variable and may be isolated to a single skeletal site or multiple sites and sometimes is associated with extraskeletal manifestations in the skin and/or endocrine organs (McCune-Albright syndrome). The clinical behavior and progression of FD may also vary, thereby making the management of this condition difficult with few established clinical guidelines. This paper provides a clinically-focused comprehensive description of craniofacial FD, its natural progression, the components of the diagnostic evaluation and the multi-disciplinary management, and considerations for future research.

Hong SH, Kim JE, Kim YK, et al. Suppression of lung cancer progression by biocompatible glycerol triacrylate– spermine-mediated delivery of shAkt1. Int J Nanomedicine. 2012;7:2293–2306.Figure 3 has been corrected.Read the original article.

We present a measurement of the time-dependent CP asymmetry for the neutral B-meson decay B0-->phiK0. We use a sample of approximately 114 x 10(6) B-meson pairs taken at the Upsilon(4S) resonance with the BABAR detector at the PEP-II B-meson factory at SLAC. We reconstruct the CP eigenstates phiK0S and phiK0L, where phi-->K+K-, K0S-->pi+pi-, and K0L is observed via its hadronic interactions. The other B meson in the event is tagged as either a B0 or Bbar0 from its decay products. The values of the CP-violation parameters are SphiK=0.47+/-0.34(stat)+0.08-0.06(syst) and CphiK=0.01+/-0.33(stat)+/-0.10(syst).

AIM:To determine whether repeated gadolinium-based contrast agent administration (GBCA) in children is associated with the development of increased T1-weighted signal intensity within the cerebellar dentate nucleus. MATERIALS AND METHODS:With institutional review board approval for this The Health Insurance Portability and Accountability Act-compliant retrospective study, a cohort of 41 patients under the age of 18 years who underwent at least four contrast-enhanced magnetic resonance imaging (MR) examinations of the brain from 2005 to 2015 were identified. For each examination, both dentate nuclei were manually contoured, and the mean dentate nucleus-to-pons signal intensity (DN-P SI) ratio was calculated. The DN-P SI ratios from the last to first MRI examination were compared, and the correlation between DN-P SI ratio and cumulative gadolinium dose was calculated using a linear mixed effect model to control for potentially confounding variables. RESULTS:For the 41 patients in the cohort, there was a significant increase in the mean DN-P SI ratio from the first MRI to the last MRI examination (1.05 versus 1.11, p=0.004). After controlling for patient diagnosis, history of chemotherapy or radiation, sex, and age, there was a significant positive association between DN-P SI ratio and cumulative gadolinium dose (coefficient=0.401, p=0.032). CONCLUSION:Repeated GBCA administration in children is associated with increased T1-weighted signal intensity within the dentate nucleus.

Background and purposeMenière disease and idiopathic sudden sensorineural hearing loss can have overlapping clinical presentation and may have similar pathophysiology. Prior studies using postcontrast 3D-FLAIR MR imaging suggest abnormal blood-labyrinth barrier permeability in both conditions, but the 2 diseases have not been directly compared by using the same imaging techniques. We hypothesized that delayed postcontrast 3D-FLAIR MR imaging would show differences in blood-labyrinth barrier permeability between Menière disease and idiopathic sudden sensorineural hearing loss.Materials and methodsPatients with unilateral Menière disease (n = 32) and unilateral idiopathic sudden sensorineural hearing loss (n = 11) imaged with delayed postcontrast 3D-FLAIR MR imaging were retrospectively studied. Signal intensities of the medulla and perilymph of the cochlear basal turns of both ears in each patient were measured in a blinded fashion. Cochlea/medulla ratios were calculated for each ear as a surrogate for blood-labyrinth barrier permeability. The ears were segregated by clinical diagnosis.ResultsCochlea/medulla ratio was higher in symptomatic ears of patients with Menière disease (12.6 ± 7.4) than in patients with idiopathic sudden sensorineural hearing loss (5.7 ± 2.0) and asymptomatic ears of patients with Menière disease (8.0 ± 3.1), indicating increased blood-labyrinth barrier permeability in Menière disease ears. The differences in cochlea/medulla ratio between symptomatic and asymptomatic ears were significantly higher in Menière disease than in idiopathic sudden sensorineural hearing loss. Asymptomatic ears in patients with Menière disease showed higher cochlea/medulla ratio than symptomatic and asymptomatic ears in patients with idiopathic sudden sensorineural hearing loss.ConclusionsIncreased cochlea/medulla ratio indicates increased blood-labyrinth barrier permeability in Menière disease compared with idiopathic sudden sensorineural hearing loss. Increased cochlea/medulla ratio in asymptomatic ears of patients with Menière disease also suggests an underlying systemic cause of Menière disease and may provide a pathophysiologic biomarker.

PurposeTo investigate the effects of dose level and reconstruction method on density and texture based features computed from CT lung nodules.MethodsThis study had two major components. In the first component, a uniform water phantom was scanned at three dose levels and images were reconstructed using four conventional filtered backprojection (FBP) and four iterative reconstruction (IR) methods for a total of 24 different combinations of acquisition and reconstruction conditions. In the second component, raw projection (sinogram) data were obtained for 33 lung nodules from patients scanned as a part of their clinical practice, where low dose acquisitions were simulated by adding noise to sinograms acquired at clinical dose levels (a total of four dose levels) and reconstructed using one FBP kernel and two IR kernels for a total of 12 conditions. For the water phantom, spherical regions of interest (ROIs) were created at multiple locations within the water phantom on one reference image obtained at a reference condition. For the lung nodule cases, the ROI of each nodule was contoured semiautomatically (with manual editing) from images obtained at a reference condition. All ROIs were applied to their corresponding images reconstructed at different conditions. For 17 of the nodule cases, repeat contours were performed to assess repeatability. Histogram (eight features) and gray level co-occurrence matrix (GLCM) based texture features (34 features) were computed for all ROIs. For the lung nodule cases, the reference condition was selected to be 100% of clinical dose with FBP reconstruction using the B45f kernel; feature values calculated from other conditions were compared to this reference condition. A measure was introduced, which the authors refer to as Q, to assess the stability of features across different conditions, which is defined as the ratio of reproducibility (across conditions) to repeatability (across repeat contours) of each feature.ResultsThe water phantom results demonstrated substantial variability among feature values calculated across conditions, with the exception of histogram mean. Features calculated from lung nodules demonstrated similar results with histogram mean as the most robust feature (Q ≤ 1), having a mean and standard deviation Q of 0.37 and 0.22, respectively. Surprisingly, histogram standard deviation and variance features were also quite robust. Some GLCM features were also quite robust across conditions, namely, diff. variance, sum variance, sum average, variance, and mean. Except for histogram mean, all features have a Q of larger than one in at least one of the 3% dose level conditions.ConclusionsAs expected, the histogram mean is the most robust feature in their study. The effects of acquisition and reconstruction conditions on GLCM features vary widely, though trending toward features involving summation of product between intensities and probabilities being more robust, barring a few exceptions. Overall, care should be taken into account for variation in density and texture features if a variety of dose and reconstruction conditions are used for the quantification of lung nodules in CT, otherwise changes in quantification results may be more reflective of changes due to acquisition and reconstruction conditions than in the nodule itself.