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Sarah K Lee,1 Kaushik Mukherjee2 1Department of Plastic Surgery, University of California Irvine Health, Irvine, CA, USA; 2Division of Acute Care Surgery, Loma Linda University Health, Loma Linda, CA, USACorrespondence: Kaushik Mukherjee, Division of Acute Care Surgery, Loma Linda University Health, 11175 Campus Street, CP, 21111, Loma Linda, CA, 92350, USA, Tel +001 909-558-4286, Fax +001 909-558-236, Email kmukherjee@llu.eduAbstract: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has emerged as a promising intervention for hemorrhagic shock and traumatic injury management, offering a minimally invasive means of aortic occlusion compared to resuscitative thoracotomy. While REBOA’s origin dates back to the 1950s, recent advancements have made it more accessible and applicable in various clinical scenarios. REBOA has become increasingly utilized in not only the exsanguinating trauma patient but also in non-traumatic hemorrhage as a bridge to definitive hemostatic control. This article reviews the procedure and mechanism, clinical applications, and challenges associated with the REBOA. There are several challenges to consider when implementing the REBOA, particularly in procedural execution and patient selection. Determining the ideal candidates for REBOA remains inconclusive, with varying outcomes reported in different patient populations. Additionally, the potential for ischemic complications, such as visceral organ injury, end organ damage, and lower extremity ischemia, underscores the critical importance of procedural planning and ongoing monitoring. Partial and intermittent REBOA techniques have been introduced to mitigate ischemic complications associated with complete occlusion, but their efficacy and safety warrant further investigation. Beyond technical considerations, logistical and institutional factors pose as potential barriers to the effective utilization of REBOA, highlighting the importance of standardized training and a multidisciplinary approach when establishing a REBOA program. REBOA offers promising advancements in hemorrhage control, and the technology continues to evolve to address potential challenges and complications. Further research is imperative to delineate its optimal use and potential impact on patient outcomes.Keywords: traumatic hemorrhagic shock, REBOA, postpartum hemorrhage, partial REBOA, aortic occlusion, endovascular

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

The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

Wen Ling Hsieh,1 Shin Ting Yeh,2 Wen I Liu,1 I Hsien Li,1 Shih Kai Lee,3 Wai Tong Chien4 1School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei City, Taiwan; 2Department of Gerontological Health Care, National Taipei University of Nursing and Health Sciences, Taipei City, Taiwan; 3Department of Nursing, Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nan-Tou, Taiwan; 4The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of ChinaCorrespondence: Wen I Liu, School of Nursing, National Taipei University of Nursing and Health Sciences, No. 365, Ming-Te Road, Peitou District, Taipei City, 112303, Taiwan, Tel +886-2-28227101 ext. 3184, Fax +886-2-28213233, Email wenyi@ntunhs.edu.tw Shih Kai Lee, Department of Nursing, Tsaotun Psychiatric Center, Ministry of Health and Welfare, No. 161, Yu-Pin Road, Tsaotun Township, Nan-Tou, 54249, Taiwan, Tel +886-49-2550800 ext. 2100, Email sklee@ttpc.mohw.gov.twBackground: Increased medication adherence improves patient outcomes and lowers the overall cost of care by preventing disease relapse and hospital readmission. Several systematic reviews have identified that insight, therapeutic alliance, and attitude towards medication affect medication adherence in patients with schizophrenia; however, no study has examined all the aforementioned variables together nor has discussed the chains of these mediators.Purpose: To examine the insight–medication adherence relationship among community-dwelling schizophrenia patients through a serial multiple mediation model of therapeutic alliance and medication attitude.Patients and Methods: This study with a cross-sectional correlational design included a convenience sample of community-dwelling schizophrenia patients from Taiwan (n = 229). From January 2017 to January 2018, data were collected by trained nurses using questionnaires. The PROCESS tool was used to analyse fine-grained chains.Results: In serial multiple mediation, the indirect effect of insight on medication adherence through therapeutic alliance and, subsequently, alteration of medication attitude was significant. However, the direct effect changed from significant to non-significant, indicating a complete mediating effect.Conclusion: In community-dwelling schizophrenia patients, the effects of therapeutic alliance and medication attitude on medication adherence are greater than that of insight. We recommend revising the strategy of community home visits by different psychiatrists or nurses in alternating shifts. Therapeutic alliance is the first step required to promote medication adherence. Based on this alliance, altering the patients’ medication attitude may be more effective in improving medication adherence than merely enhancing insight.Keywords: medication adherence, insight, medication attitude, mediating effect, schizophrenia, therapeutic alliance, nursing

Chun-Chang Ho,1 Giha Kim,1 Chin Hee Mun,2 Ju-Won Kim,3 Jieun Han,3 Ji Yoon Park,1 Yong-Beom Park,2– 4 Sang-Kyou Lee1,5 1Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea; 2Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Department of Medical Science, Brain Korea 21 PLUS Project, Yonsei University, Seoul, Republic of Korea; 4Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Good T Cells, Inc., Seoul, Republic of KoreaCorrespondence: Sang-Kyou LeeDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, Republic of KoreaTel +82 2 2123 2889Email sjrlee@yonsei.ac.krPurpose: Th17 cells and their cytokines are implicated in the pathogenesis of various autoimmune diseases. Retinoic acid-related orphan receptor alpha (RORα) is a transcription factor for the differentiation and the inflammatory functions of Th17 cells. In this study, we generated the nucleus-transducible form of transcription modulation domain of RORα (nt-RORα-TMD) to investigate the functional roles of RORα in vitro and in vivo under normal physiological condition without genetic alteration.Methods: The functions of nt-RORα-TMD were analyzed in vitro through flow cytometry, luciferase assay, ELISA, and transcriptome sequencing. Finally, the in vivo therapeutic effects of nt-RORα-TMD were verified in dextran sulfate sodium (DSS)-induced colitis mice.Results: nt-RORα-TMD was effectively delivered into the cell nucleus in a dose- and time-dependent manner without any cellular toxicity. nt-RORα-TMD competitively inhibited the RORα-mediated transcription but not RORγt-mediated transcription. Secretion of IL-17A from the splenocytes was suppressed by nt-RORα-TMD without affecting the secretion of Th1- or Th2-type cytokine and T cell activation events such as induction of CD69 and CD25. The differentiation potential of naïve T cells into Th17 cells, not into Th1, Th2, or Treg cells, was significantly blocked by nt-RORα-TMD. Consistently, mRNA sequencing analysis showed that nt-RORα-TMD treatment down-regulated the expression of the genes related to the differentiation and functions of Th17 cells. Treatment of DSS-induced colitis mice with nt-RORα-TMD improved the overall symptoms of colitis, such as body weight change, colon length, infiltration of inflammatory cells, and the level of inflammatory cytokines in the serum. In the mesenteric lymph node (MLN) of the nt-RORα-TMD-treated mice, the population of CD4+IL-17A+ Th17 cells was reduced, and the population of CD4+Foxp3+ Treg cells increased.Conclusion: nt-RORα-TMD has a potential to be developed as a novel therapeutic reagent for treating various inflammatory diseases in which Th17 cells are the leading pathological player.Keywords: retinoic acid-related orphan receptor, T helper 17, transcriptional modulation, DSS-induced colitis, inflammatory disease

Min-Hee Lee,1 Seung Ku Lee,1 Robert J Thomas,2 Jee-Eun Yoon,3 Chang-Ho Yun,4,&ast; Chol Shin1,5,&ast; 1Institute of Human Genomic Study, College of Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea; 2Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 3Department of Neurology, Uijeongbu Eulji Medical Center, Uijeongbu, Republic of Korea; 4Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 5Department of Pulmonary Sleep and Critical Care Medicine Disorder Center, College of Medicine, Korea University, Ansan, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Chang-Ho YunDepartment of Neurology, Bundang Clinical Neuroscience Institute, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam, 13620, Republic of KoreaTel +82 31 787 7469Fax +82 31 787 4059Email ych333@gmail.comChol ShinDivision of Pulmonary, Sleep, and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital and Institute of Human Genomic Study, Korea University Ansan Hospital, 516, Gojan-1-dong, Danwon-gu, Ansan, Gyeonggi-do, 15355, Republic of KoreaTel +82 31 412 5541Fax +82 31 412 5604Email chol-shin@korea.ac.krPurpose: Obstructive sleep apnea (OSA) is associated with altered pairwise connections between brain regions, which might explain cognitive impairment and daytime sleepiness. By adopting a deep learning method, we investigated brain connectivity related to the severity of OSA and daytime sleepiness.Patients and Methods: A cross-sectional design applied a deep learning model on structural brain networks obtained from 553 subjects (age, 59.2 ± 7.4 years; men, 35.6%). The model performance was evaluated with the Pearson’s correlation coefficient (R) and probability of absolute error less than standard deviation (PAE

A long-standing paradigm in astrophysics is that collisions-or mergers-of two neutron stars form highly relativistic and collimated outflows (jets) that power γ-ray bursts of short (less than two seconds) duration. The observational support for this model, however, is only indirect. A hitherto outstanding prediction is that gravitational-wave events from such mergers should be associated with γ-ray bursts, and that a majority of these bursts should be seen off-axis, that is, they should point away from Earth. Here we report the discovery observations of the X-ray counterpart associated with the gravitational-wave event GW170817. Although the electromagnetic counterpart at optical and infrared frequencies is dominated by the radioactive glow (known as a kilonova') from freshly synthesized rapid neutron capture (r-process) material in the merger ejecta, observations at X-ray and, later, radio frequencies are consistent with a short γ-ray burst viewed off-axis. Our detection of X-ray emission at a location coincident with the kilonova transient provides the missing observational link between short γ-ray bursts and gravitational waves from neutron-star mergers, and gives independent confirmation of the collimated nature of the γ-ray-burst emission.

Jeongmin Lee,1 Jeonghoon Ha,2 Sang-Kuon Lee,3 Hye Lim Park,4 Sung-Hoon Kim,5 Dong-Jun Lim,2 Jung Min Lee,1 Sang-Ah Chang,1 Moo Il Kang,2 Min-Hee Kim1 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pancreatobiliary Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 4Division of Nuclear Medicine, Department of Radiology, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 5Division of Nuclear Medicine, Department of Radiology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Min-Hee KimDivision of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaTel +82-2-2030-4348Fax +82-2-2030-4641Email benedict@catholic.ac.krPurpose: Primary aldosteronism (PA) is mainly comprised of aldosterone-producing adenoma and bilateral idiopathic adrenal hyperplasia. Current guidelines recommend adrenal venous sampling (AVS) as a gold standard method to classify the subtypes. However, because of technical challenges in AVS including invasiveness of AVS and a wide range of success rate for cannulation, it is not uncommon that appropriate decisions could not be made depending on AVS. The aim of this study is to elucidate the proper role of I‑131‑6β‑iodomethyl‑norcholesterol (NP-59) scintigraphy in management of PA.Patients and Methods: Between January 2009 and October 2018, patients with PA were retrospectively reviewed for the study. Five patients were included in the study who had NP-59 scintigraphy with non-conclusive AVS results or without AVS. We described the clinical outcome of patients in whom clinical decisions were made according to NP-59 scintigraphy results.Results: Patients in the presenting cases were diagnosed for PA. AVS, the most reliable test to identify unilateral APA, were not applicable because of hypersensitivity to contrast dye (patient 1), and use of antiplatelet agents after acute cerebral infarction (patient 2). NP-59 scintigraphy was performed in patients 3 and 4 whose result of AVS and CT scan were inconsistent. In patient 5, who had bilateral adrenal adenomas (two in the left and one in the right adrenal gland), both unsuccessful catheterization and coexistence of cortisol overproduction made AVS results unreliable.Conclusion: Based on clinical outcomes of these case series, it is noticeable that NP-59 scintigraphy could play a substantial role in management of PA in selected cases.Keywords: hyperaldosteronism, angiography, aldosterone, radionuclide imaging

Yoo-Jeong Jeon,1 Seung Ku Lee,2,3 Chol Shin2– 5 1Department of Sports & Health Science, Hanbat National University, Daejeon, Korea; 2Institute of Human Genomic Study, College of Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea; 3College of Medicine, Korea University, Seoul, Republic of Korea; 4Department of Pulmonary, Sleep and Critical Care Medicine, College of Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea; 5Transdisciplinary Major in Learning Health Systems, Department of Healthcare, Sciences, Graduate School, Korea University, Seoul, Republic of KoreaCorrespondence: Chol ShinDepartment of Pulmonary, Sleep and Critical Care Medicine, College of Medicine, Korea University Ansan Hospital, 123 Jeokgeum-ro, Danwon-gu, Gyeonggi-do, Ansan-si, 15355, Republic of KoreaTel +82-31-412-5603Email chol-shin@hanmail.netPurpose: Muscle strength is associated with type 2 diabetes mellitus (T2DM). However, it is controversial whether muscle strength and normalized muscle strength is a risk factor for T2DM. Moreover, the relationship of back muscle strength (BMS) and incident T2DM has not been reported. In this study, we investigated the relationship between HGS, BMS, normalized HGS and BMS, and incident T2DM.Methods: A total of 2699 non-diabetes subjects aged 40– 69 years (1313 women and 1386 men) in the Korean Genome and Epidemiology Study (KoGES) Ansan cohort were followed for 16 years. At the baseline and biennial follow‐up visits, fasting glucose, postprandial 2-h glucose, clinical examinations, HGS, and BMS were measured by trained interviewers and examiners. HGS and BMS were measured at baseline. The relationships between incident T2DM, HGS, BMS, and normalized HGS and BMS were estimated using Cox proportional hazard regression models after adjusting for the confounding factors.Results: HGS and BMS were not associated with incident T2DM in multivariate analysis. However, the hazard ratio (HR) per one standard deviation (SD) increase in the body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR)-normalized HGS, and BMS was associated with a lower risk for incident T2DM in both women and men after adjusting for the confounding factors (HR = 0.842– 0.880-fold for women, p ≤ 0.015; HR = 0.887– 0.903-fold for men, p ≤ 0.024). In the sub-analysis of menopause status, the HR per one SD increase in BMI, weight2/3, WC, and WHR-normalized HGS was associated with a lower risk for incident T2DM in both pre- and post-menopausal women after adjusting for the confounding factors (HR = 0.860– 0.820-fold for premenopausal, P ≤ 0.006; HR = 0.900– 0.867-fold for postmenopausal, p ≤ 0.024). Additionally, we confirmed that the quartile group with higher muscle strength was associated with a lower risk for incident T2DM.Conclusion: The present study suggested that normalized HGS and BMS were associated with a lower risk for the future development of T2DM. Moreover, weak muscle strength in premenopausal women may be the cause of T2DM. Further research is needed to determine whether efforts to improve muscle strength, such as exercise can reduce the risk of T2DM.Keywords: incident type 2 diabetes mellitus, hand grip strength, back strength

The Cancer Genome Atlas (TCGA) network study of 12 cancer types (PanCancer 12) revealed frequent mutation of TP53, and amplification and expression of related TP63 isoform ΔNp63 in squamous cancers. Further, aberrant expression of inflammatory genes and TP53/p63/p73 targets were detected in the PanCancer 12 project, reminiscent of gene programs comodulated by cREL/ΔNp63/TAp73 transcription factors we uncovered in head and neck squamous cell carcinomas (HNSCCs). However, how inflammatory gene signatures and cREL/p63/p73 targets are comodulated genome wide is unclear. Here, we examined how the inflammatory factor tumor necrosis factor-α (TNF-α) broadly modulates redistribution of cREL with ΔNp63α/TAp73 complexes and signatures genome wide in the HNSCC model UM-SCC46 using chromatin immunoprecipitation sequencing (ChIP-seq). TNF-α enhanced genome-wide co-occupancy of cREL with ΔNp63α on TP53/p63 sites, while unexpectedly promoting redistribution of TAp73 from TP53 to activator protein-1 (AP-1) sites. cREL, ΔNp63α and TAp73 binding and oligomerization on NF-κB-, TP53- or AP-1-specific sequences were independently validated by ChIP-qPCR (quantitative PCR), oligonucleotide-binding assays and analytical ultracentrifugation. Function of the binding activity was confirmed using TP53-, AP-1- and NF-κB-specific REs or p21, SERPINE1 and IL-6 promoter luciferase reporter activities. Concurrently, TNF-α regulated a broad gene network with cobinding activities for cREL, ΔNp63α and TAp73 observed upon array profiling and reverse transcription-PCR. Overlapping target gene signatures were observed in squamous cancer subsets and in inflamed skin of transgenic mice overexpressing ΔNp63α. Furthermore, multiple target genes identified in this study were linked to TP63 and TP73 activity and increased gene expression in large squamous cancer samples from PanCancer 12 TCGA by CircleMap. PARADIGM inferred pathway analysis revealed the network connection of TP63 and NF-κB complexes through an AP-1 hub, further supporting our findings. Thus, inflammatory cytokine TNF-α mediates genome-wide redistribution of the cREL/p63/p73, and AP-1 interactome, to diminish TAp73 tumor suppressor function and reciprocally activate NF-κB and AP-1 gene programs implicated in malignancy.

We measure the evolution of the quiescent fraction and quenching efficiency of satellites around star-forming and quiescent central galaxies with stellar mass at . We combine imaging from three deep near-infrared-selected surveys (ZFOURGE/CANDELS, Ultra Deep Survey, and UltraVISTA), which allows us to select a stellar-mass complete sample of satellites with . Satellites for both star-forming and quiescent central galaxies ("centrals") have higher quiescent fractions compared to field galaxies matched in stellar mass at all redshifts. We also observe "galactic conformity": satellites around quiescent centrals are more likely to be quenched compared to the satellites around star-forming centrals. In our sample, this conformity signal is significant at for , whereas it is only weakly significant at and . Therefore, conformity (and thus satellite quenching) has been present for a significant fraction of the age of the universe. The satellite quenching efficiency increases with increasing stellar mass of the central, but does not appear to depend on the stellar mass of the satellite to the mass limit of our sample. When we compare the satellite quenching efficiency of star-forming centrals with stellar masses 0.2 dex higher than quiescent centrals (which should account for any difference in halo mass), the conformity signal decreases, but remains statistically significant at . This is evidence that satellite quenching is connected to the star formation properties of the central galaxy as well as to the mass of the halo. We discuss physical effects that may contribute to galactic conformity, and emphasize that they must allow for continued star formation in the central galaxy even as the satellites are quenched.

Jong Man Kim, Jae-Won Joh, Gyu-Seong Choi, Suk-Koo Lee Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaCorrespondence: Jae-Won JohDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-Ro 81, Gangnam-Gu, Seoul 06351, Republic of KoreaTel +82-2-3410-3466Fax +82-2-3410-0040Email jw.joh@samsung.comBackground: Generic tacrolimus (Tacrobell®) is commonly used in liver transplant patients in Korea. No previous studies have assessed the long-term efficacy and safety of generic tacrolimus for adult deceased donor liver transplantation (DDLT) patients. The aim of the present study was to evaluate the long-term efficacy and safety of generic tacrolimus compared to brand-name tacrolimus (Prograf®) in adult DDLT recipients.Methods: Two hundred sixty-five adult DDLTs were performed in our center between 2003 and 2017. To determine the efficacy and safety of generic tacrolimus, renal function (estimated glomerular filtration rate [eGFR] and creatinine), infectious complications, rejection-free survival rates, and patient survival rates were investigated.Results: Of 265 patients, 193 were selected and divided into a generic tacrolimus group (n=147) and a brand-name group (n=46). Mean follow-up duration was 63.2 ± 44.3 months. The 1-year, 3-year, 5-year, and 10-year patient survival rates were 89.1%, 86.9%, 84.5%, and 75.2%, respectively, in the generic tacrolimus group and 95.7%, 88.9%, 86.3%, and 83.7% in the brand-name tacrolimus group. There were no statistically significant differences in the infectious complications, new-onset diabetes, and renal dysfunction included mean serum creatinine level or eGFR after DDLT between the two groups. Increased recipient age, continuous renal replacement therapy (CRRT) in the pre-transplant phase, and acute rejection were predisposing factors for patient death.Conclusion: The present study shows that generic tacrolimus is an alternative comparable to brand-name tacrolimus in adult DDLT patients.Keywords: liver transplantation, immunosuppression, safety, efficacy

Wen Ling Hsieh,1 Shih Kai Lee,2 Wai Tong Chien,3 Wen I Liu,4 Chien Yu Lai,4 Chieh Yu Liu4 1Department of Nursing, Taipei Municipal Wanfang Hospital (Managed by Taipei Medical University), Taipei City, Taiwan; 2Department of Nursing, Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nan-Tou, Taiwan; 3The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong; 4College of Nursing, National Taipei University of Nursing and Health Sciences, Taipei City, TaiwanCorrespondence: Wen I LiuNational Taipei University of Nursing and Health Sciences, No. 365, Ming-Te Road, Peitou District, Taipei City 11219, TaiwanTel +886 2 2822 7101 Ext. 3184Fax +886 2 2821 3233Email wenyi@ntunhs.edu.twBackground: Nearly half of patients with schizophrenia do not adhere to the long-term medical treatment needed to manage their disease. Programs to promote medication adherence include promotion of motivation as a critical element to influence task performance.Purpose: This study investigated the mediating effect of motivation for medication use on disease management and medication adherence in schizophrenia.Methods: This cross-sectional, descriptive correlational study enrolled a convenience sample of 373 community-dwelling patients with schizophrenia in the northern and central regions of Taiwan. Data were collected with questionnaires and a series of validated assessment tools. Hierarchical regression was used to analyze the mediating effect of motivation for medication use on disease management and medication adherence.Results: The medication adherence rate of the patients was 47.2%. The mediating effect of motivation for medication use on therapeutic alliance and medication adherence was 50%, whereas that on insight and medication adherence was 41% and that on medical social support and medication adherence was 72%.Conclusion: Developing a medication motivation care model may be more effective than promoting therapeutic alliance, insight, or medical social support for promoting medication adherence. It also had greater impact on preventing relapses of community-dwelling patients with schizophrenia.Keywords: cross-sectional study, medication adherence, disease management, motivation for medication use, schizophrenia, community-dwelling patients

Young-Hee Nam, Soo-Keol Lee Department of Internal Medicine, College of Medicine, Dong-A University, Busan, Republic of Korea Background: Allergen immunotherapy (AIT) is currently the only immune-modifying treatment for allergic disease. The clinical efficacy of AIT for the treatment of allergic rhinitis and bronchial asthma is well documented. However, many factors including inconvenience, cost, side effects, and adherence influence the initiation and persistence of AIT, and patients lack knowledge and have misconceptions about the treatment. Objective: We evaluated the knowledge, attitude, and satisfaction of patients who received AIT.Methods: We conducted a retrospective analysis of medical records of 167 patients who received AIT, and compared the clinical characteristics between conventional immunotherapy (CIT) and rush immunotherapy (RIT). Ninety-nine patients completed a questionnaire survey.Results: Of the total 167 patients, 65.9% (n=110) were treated with CIT and 34.1% (n=57) with RIT. More than half of the patients (68.7%) initiated AIT according to their physician’s recommendation. Frequent hospital visits were the main barrier for persistence of AIT. RIT patients were younger and started AIT earlier than CIT patients. The majority (77%) of patients who received AIT were satisfied, with no significant difference between CIT and RIT groups. RIT and fewer allergens used in AIT were related with preference for AIT to pharmacotherapy. The longer duration of AIT was associated with higher treatment satisfaction.Conclusion: A majority of patients initiated AIT by the physician’s recommendation and were satisfied with treatment regardless of CIT or RIT schedule. Adequate patient education and a strict patient–physician relationship in early AIT period could improve the effectiveness and compliance of AIT. Keywords: allergen, immunotherapy, compliance

Chiun-Fang Chiou,1 Bruce CM Wang,2 Ronald Caldwell,3 Wesley Furnback,2 Jung-Sun Lee,4 Nathan Kothandaraman,5 SunKyoung Lee,6 Jin Wang,7 Fan Zhang8 1Regional Market Access, Janssen Asia-Pacific, Singapore; 2Elysia Group, LLC, Taipei, Taiwan; 3Department of Economics, University of Michigan, Ann Arbor, MI, USA; 4Department of Psychiatry, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea; 5Government Affairs, Johnson & Johnson Sdn Bhd, Selangor, Malaysia; 6Market Access, Janssen Korea Ltd, Seoul, Korea; 7Strategy and Development, Xian Janssen Pharmaceutical Co, Ltd, 8Medical Affairs, Xian Janssen Pharmaceutical Co, Ltd, Beijing, People’s Republic of China Background: Schizophrenia results in substantial health care utilization costs. Much of these costs can be attributed to health care use resulting from nonadherence to treatment, relapse, and hospitalization.Aims of the study: The objective of this research is to further estimate the health care resource utilization costs of patients with schizophrenia in the People’s Republic of China, Korea, and Malaysia with a specific focus on the reduction in hospitalization costs associated with the use of long-acting, injectable paliperidone palmitate (PP) relative to alternative treatment medications.Methods: The study focuses exclusively on the estimated reduction in hospitalization days following treatment with PP and the potential associated cost savings. Cost analysis was done using a payer’s perspective and only includes direct health care costs associated with hospitalization. Localized cost data were taken from published sources, and health care utilization was estimated based on a clinical study conducted in countries in the Asia-Pacific region. People’s Republic of China, Korea, and Malaysia had the highest number of patients enrolled in the clinical study, and thus were chosen for this research. Analysis looked at 12-month and 18-month periods following initial treatment with PP relative to a retrospective 12-month period utilizing alternative treatment medications.Results: Results suggest that reductions in hospital utilization cost over 12 months may occur through the use of PP relative to alternatives – ranging from $1,991 for the People’s Republic of China to $6,698 for Korea and $6,716 for Malaysia.Conclusion: Given the substantial costs associated with the treatment of schizophrenia both worldwide and in Asia, it is important to fully understand the costs and outcomes associated with various treatment options. In this research, we have specifically analyzed the direct health care cost savings associated with hospital utilization for patients taking PP relative to alternative treatment methods. The results suggest that reductions in hospital utilization cost were associated with PP treatment, likely largely due to increased adherence to treatment. Keywords: schizophrenia, antipsychotic treatment, health economics, cost savings

KR Jyothi,1 Jagadish Beloor,2 Ara Jo,1 Minh Nam Nguyen,1 Tae Gyu Choi,1 Jin-Hwan Kim,1 Salima Akter,1 Sang-Kyung Lee,2 Chi Hoon Maeng,3 Hyung Hwan Baik,1 Insug Kang,1 Joohun Ha,1 Sung Soo Kim1 1Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 2Department of Bioengineering and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, Republic of Korea; 3Department of Medical Oncology and Hematology, Kyung Hee University Hospital, Seoul, Republic of Korea Abstract: Therapeutic options for hepatitis C virus (HCV) infection have been limited by drug resistance and adverse side effects. Targeting the host factor cyclophilin A (CypA), which is essential for HCV replication, offers a promising strategy for antiviral therapy. However, due to its immunosuppressive activity and severe side effects, clinical application of cyclosporine A (CsA) has been limited as an antiviral agent. To overcome these drawbacks, we have successfully developed a liver-specific, sustained drug delivery system by conjugating the liver-targeting peptide (LTP) to PEGylated CsA-encapsulated poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Furthermore, our delivery system exhibited high specificity to liver, thus contributing to the reduced immunosuppressive effect and toxicity profile of CsA. Finally, targeted nanoparticles were able to effectively inhibit viral replication in vitro and in an HCV mouse model. As a proof of principle, we herein show that our delivery system is able to negate the adverse effects of CsA and produce therapeutic effects in an HCV mouse model.Keywords: HCV, liver-targeting peptide, targeted drug delivery

Objective: To evaluate the in vivo effect of 14 d repeatedly oral administration of Clinacanthus nutans (C. nutans) methanol leaves extract (250 mg/kg, 500 mg/kg and 1 000 mg/kg bw) on the acetylcholinesterase (AChE) activity in male Balb/C mice. Method: First group was served as control group, orally treated with distilled water as vehicle and group 2-4 were orally treated with a single daily dose of 250 mg/kg, 500 mg/kg and 1 000 mg/kg bw of C. nutans extract, respectively for 14 d. Each group consisted of six animals (n =6). The activity of acetylcholinesterase in brain, liver, kidney and heart of mice was determined according to Ellman method (1961). Results: From the results obtained, the AChE activity was found to be highest in mice liver, followed by brain, kidney and heart. Methanol extract of C. nutans leaves at 250 mg/kg (P

Susannah K Lee,1 Jill Dawson,2 Jack A Lee,3 Gizem Osman,4 Maria O Levitin,5 Refika Mine Guzel,5 Mustafa BA Djamgoz5,61Pomona College, Claremont, CA, USA; 2Healthcare Communications Consultancy, Danville, CA, USA; 3College of Arts and Sciences, Vanderbilt University, Nashville, TN, USA; 4Department of Chemical Engineering, Loughborough University, Loughborough, UK; 5Division of Cell and Molecular Biology, Neuroscience Solutions to Cancer Research Group, South Kensington Campus, Imperial College London, London, UK; 6Cyprus International University, Biotechnology Research Centre, Haspolat, North Cyprus, Mersin, TurkeyAbstract: In this review, the first of two parts, we first provide an overview of the orthodox analgesics used commonly against cancer pain. Then, we examine in more detail the emerging evidence for the potential impact of analgesic use on cancer risk and disease progression. Increasing findings suggest that long-term use of nonsteroidal anti-inflammatory drugs, particularly aspirin, may reduce cancer occurrence. However, acetaminophen may raise the risk of some hematological malignancies. Drugs acting upon receptors of gamma-aminobutyric acid (GABA) and GABA “mimetics” (eg, gabapentin) appear generally safe for cancer patients, but there is some evidence of potential carcinogenicity. Some barbiturates appear to slightly raise cancer risks and can affect cancer cell behavior in vitro. For cannabis, studies suggest an increased risk of squamous cell carcinoma of the tongue, larynx, and possibly lung. Morphine may stimulate human microvascular endothelial cell proliferation and angiogenesis; it is not clear whether this might cause harm or produce benefit. The opioid, fentanyl, may promote growth in some tumor cell lines. Opium itself is an emerging risk factor for gastric adenocarcinoma and possibly cancers of the esophagus, bladder, larynx, and lung. It is concluded that analgesics currently prescribed for cancer pain can significantly affect the cancer process itself. More futuristically, several ion channels are being targeted with novel analgesics, but many of these are also involved in primary and/or secondary tumorigenesis. Further studies are needed to elucidate possible cellular and molecular effects of orthodox analgesics and their possible long-term impact, both positive and negative, and thus enable the best possible clinical gain for cancer patients.Keywords: NSAIDs, cannabinoids, opioids, GABA-ergic drugs, GABA mimetics, ion channels