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Ho Joong Choi, Dong Goo Kim, Bong Jun Kwak, Jae Hyun Han, Tae Ho Hong, Young Kyoung You Department of Surgery, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Introduction: The purpose of this study was to compare the safety and efficacy of generic tacrolimus (Tacrobell [TCB]) and a reference tacrolimus (Prograf [PGF]) in liver transplant recipients. Patients and methods: We retrospectively analyzed 167 patients who used TCB or PGF between January 2009 and March 2016 for >1 year (TCB group, n=86; PGF group, n=81). To assess the efficacy and safety of TCB, we evaluated the relationship between drug dose and trough level, survival, rejection, infection, kidney function, and side effects. Results: There was no difference in the preoperative demographics between the two groups. Moreover, there was no difference in the drug dose and trough level between the groups at 1 week after surgery. Coefficient of variation (CV) values were obtained at the drug trough level for each patient and no differences in CV values were identified within 1 year (p=0.587) and up to 5 years (p=0.824) in both groups. Rehospitalization (p=0.1) and total rejection (p=0.915) did not differ between the two groups, but the rejection severity, recorded as the rejection activity index value, was worse in the PGF group (p=0.039). No difference was found in the infection rate (p=0.818), and with regard to nephrotoxicity, there was no difference in the rate of patients with chronic kidney disease stage 3 and above during the follow-up period. No differences were found between the two groups in terms of drug side effects and adverse events. Conclusion: The generic tacrolimus, TCB, is a comparable alternative to the original tacrolimus, PGF, as a main immunosuppressive drug for liver transplantation. Keywords: liver transplantation, generic tacrolimus, Tacrobell, Prograf

Seunghoon Han,1,2 Gun Hyung Na,3 Dong-Goo Kim3 1Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul, South Korea; 2Pharmacometrics Institute for Practical Education and Training, The Catholic University of Korea, Seocho-gu, Seoul, South Korea; 3Department of Surgery, Seoul St Mary’s Hospital, The Catholic University of Korea, Seocho-gu, Seoul, South Korea Background: Although individualized dosage regimens for anti-hepatitis B immunoglobulin (HBIG) therapy have been suggested, the pharmacokinetic profile and factors influencing the basis for individualization have not been sufficiently assessed. We sought to evaluate the pharmacokinetic characteristics of anti-HBIG quantitatively during the first 6 months after liver transplantation. Methods: Identical doses of 10,000 IU HBIG were administered to adult liver transplant recipients daily during the first week, weekly thereafter until 28 postoperative days, and monthly thereafter. Blood samples were obtained at days 1, 7, 28, 84, and 168 after transplantation. Plasma HBIG titer was quantified using 4 different immunoassay methods. The titer determined by each analytical method was used for mixed-effect modeling, and the most precise results were chosen. Simulations were performed to predict the plausible immunoglobulin maintenance dose. Results: HBIG was eliminated from the body most rapidly in the immediate post-transplant period, and the elimination rate gradually decreased thereafter. In the early post-transplant period, patients with higher DNA titer tend to have lower plasma HBIG concentrations. The maintenance doses required to attain targets in 90%, 95%, and 99% of patients were ~15.3, 18.2, and 25.1 IU, respectively, multiplied by the target trough level (in IU/L). Conclusion: The variability (explained and unexplained) in HBIG pharmacokinetics was relatively larger in the early post-transplant period. Dose individualization based upon patient characteristics should be adjusted focusing quantitatively on the early post-transplant period. Keywords: population pharmacokinetics, liver transplantation, DNA titer, individualized therapy, dosage regimen

Exercise is vital for maintaining bone strength and architecture. Follistatin-like 3 (FSTL3), a member of follistatin family, is a mechanosensitive protein upregulated in response to exercise and is involved in regulating musculoskeletal health. Here, we investigated the potential role of FSTL3 in exercise-driven bone remodeling. Exercise-dependent regulation of bone structure and functions was compared in mice with global Fstl3 gene deletion (Fstl3-/-) and their age-matched Fstl3+/+ littermates. Mice were exercised by low-intensity treadmill walking. The mechanical properties and mineralization were determined by μCT, three-point bending test and sequential incorporation of calcein and alizarin complexone. ELISA, Western-blot analysis and qRT-PCR were used to analyze the regulation of FSTL3 and associated molecules in the serum specimens and tissues. Daily exercise significantly increased circulating FSTL3 levels in mice, rats and humans. Compared to age-matched littermates, Fstl3-/- mice exhibited significantly lower fracture tolerance, having greater stiffness, but lower strain at fracture and yield energy. Furthermore, increased levels of circulating FSTL3 in young mice paralleled greater strain at fracture compared to the lower levels of FSTL3 in older mice. More significantly, Fstl3-/- mice exhibited loss of mechanosensitivity and irresponsiveness to exercise-dependent bone formation as compared to their Fstl3+/+ littermates. In addition, FSTL3 gene deletion resulted in loss of exercise-dependent sclerostin regulation in osteocytes and osteoblasts, as compared to Fstl3+/+ osteocytes and osteoblasts, in vivo and in vitro. The data identify FSTL3 as a critical mediator of exercise-dependent bone formation and strengthening and point to its potential role in bone health and in musculoskeletal diseases.

Abstract There is an increasing interest in the potential of exhaled biomarkers, such as volatile organic compounds (VOCs), to improve accurate diagnoses and management decisions in pulmonary diseases. The objective of this manuscript is to systematically review the current knowledge on exhaled VOCs with respect to their potential clinical use in asthma, lung cancer, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and respiratory tract infections. A systematic literature search was performed in PubMed, EMBASE, Cochrane database, and reference lists of retrieved studies. Controlled, clinical, English-language studies exploring the diagnostic and monitoring value of VOCs in asthma, COPD, CF, lung cancer and respiratory tract infections were included. Data on study design, setting, participant characteristics, VOCs techniques, and outcome measures were extracted. Seventy-three studies were included, counting in total 3,952 patients and 2,973 healthy controls. The collection and analysis of exhaled VOCs is non-invasive and could be easily applied in the broad range of patients, including subjects with severe disease and children. Various research groups demonstrated that VOCs profiles could accurately distinguish patients with a pulmonary disease from healthy controls. Pulmonary diseases seem to be characterized by a disease specific breath-print, as distinct profiles were found in patients with dissimilar diseases. The heterogeneity of studies challenged the inter-laboratory comparability. In conclusion, profiles of VOCs are potentially able to accurately diagnose various pulmonary diseases. Despite these promising findings, multiple challenges such as further standardization and validation of the diverse techniques need to be mastered before VOCs can be applied into clinical practice.

Abstract Background Asthma is the most common chronic disease in childhood, characterized by chronic airway inflammation. There are problems with the diagnosis of asthma in young children since the majority of the children with recurrent asthma-like symptoms is symptom free at 6 years, and does not have asthma. With the conventional diagnostic tools it is not possible to differentiate between preschool children with transient symptoms and children with asthma. The analysis of biomarkers of airway inflammation in exhaled breath is a non-invasive and promising technique to diagnose asthma and monitor inflammation in young children. Moreover, relatively new lung function tests (airway resistance using the interrupter technique) have become available for young children. The primary objective of the ADEM study (Asthma DEtection and Monitoring study), is to develop a non-invasive instrument for an early asthma diagnosis in young children, using exhaled inflammatory markers and early lung function measurements. In addition, aetiological factors, including gene polymorphisms and gene expression profiles, in relation to the development of asthma are studied. Methods/design A prospective case-control study is started in 200 children with recurrent respiratory symptoms and 50 control subjects without respiratory symptoms. At 6 years, a definite diagnosis of asthma is made (primary outcome measure) on basis of lung function assessments and current respiratory symptoms ('golden standard'). From inclusion until the definite asthma diagnosis, repeated measurements of lung function tests and inflammatory markers in exhaled breath (condensate), blood and faeces are performed. The study is registered and ethically approved. Discussion This article describes the study protocol of the ADEM study. The new diagnostic techniques applied in this study could make an early diagnosis of asthma possible. An early and reliable asthma diagnosis at 2–3 years will have consequences for the management of the large group of young children with asthma-like symptoms. It will avoid both over-treatment of children with transient wheeze and under-treatment of children with asthma. This might have a beneficial influence on the prognosis of asthma in these young children. Besides, insight into the pathophysiology and aetiology of asthma will be obtained. Trial registration This study is registered by clinicaltrials.gov (NCT00422747).

Objectives: To test the hypothesis that the use of low-level laser therapy (LLLT) reduces elevated pain by controlling the release of neurochemicals during orthodontic tooth movement.Setting and Sample Population: Department of Orthodontics and Dentofacial Orthopedics, Okayama University. Sixty-five Sprague Dawley rats were subjected to tooth movement and LLLT.Materials and Methods: Adult Sprague Dawley rats were used in this study. Groups included day 0 controls, irradiation only controls and with or without irradiation sacrificed at 1, 3, 5, 7 and 14 days after tooth movement (n=5 each, total n=65). Tooth movement was achieved by insertion of an elastic module between molar teeth. Immunohistochemistry for CD-11b, GFAP and c-fos in the brain stem was performed. Stains were quantified by constructing a three-dimensional image using IMARIS, and counted using NEURON TRACER and WinROOF software. Two-way ANOVA followed by a Tukey's post hoc test (P<.05) was used for statistical comparison between groups.Results: C-fos expression was significantly increased at one and three days after tooth movement. LLLT significantly diminished this increase in c-fos expression only at one day after tooth movement CD-b11 and GFAP expression also significantly increased after tooth movement. No significant change was observed for CD-11b and GFAP expression in the central nervous system upon LLLT.Conclusion: Low-level laser therapy may reduce early neurochemical markers but have no effect on delayed pain neurochemical markers after tooth movement. [ABSTRACT FROM AUTHOR]

Contents Immunocastration is an alternative method to replace surgical castration that is commonly performed in domestic and pet animals. In this study, a new immunocastration vaccine was developed, and its efficacy was evaluated in male rats. Six tandem copies of gonadotrophin-releasing hormone (GnRH) peptide were genetically fused to Salmonella typhimurium flagellin fljB (STF2) that is a ligand of toll-like receptor 5 (TLR5). The recombinant STF2-GnRH protein expressed in Escherichia coli was used as the immunocastration vaccine. Sixteen male rats were equally assigned to four groups. Excluding the control rats, three groups were immunized with 100, 200 and 400 μg of the STF2-GnRH vaccine, respectively. All of the immunized rats developed significantly higher titres of antibodies to GnRH than the control rats. The size and weight of both testes and epididymides from the immunized rats were significantly smaller than those of the control rats. Testicular tissues in the immunized rats demonstrated atrophy of seminiferous tubules and decreased numbers of both spermatogonia and spermatocytes. These data indicate that the newly developed STF2-GnRH vaccine has a potent immunogenicity to GnRH and efficiently suppresses the development of testes in rats. [ABSTRACT FROM AUTHOR]

Objective: To evaluate tumour response after gamma knife (GK) radiosurgery for residual vestibular schwannoma (VS) based on MRI morphological features. Methods: Sixty-one patients with histopathologically confirmed VS underwent GK radiosurgery with marginal tumour doses of 9.0-14.0 Gy (mean, 12.5). Mean tumour volume at GK radiosurgery was 3.65 ml (range, 0.52-15.50). GK radiosurgery was performed 0.3-95.7 months (median, 5.8) after microsurgery. Tumour volumes and half-reduction time were calculated using serial MRI. The morphological features of VS were documented by pre-microsurgical MRI. Histopathological investigation included Antoni-type dominance, the proliferation marker Ki-67 and tumour vascularity. Results: Median duration of radiological follow-up was 53.7 months (range, 24.1-102.2) and the 8-year actuarial tumour control rate was 93.5%. No factor was associated with tumour control, although a cystic VS had borderline significance (p = 0.089). Mean tumour half-reduction time was 8.70 years (range, 0.57-79.89) and tumour half-reduction time in cystic VS proved to be significantly shorter than those in solid VS (p = 0.006). Thrombotic vessels (p = 0.015) and abnormal vessel proliferation (p = 0.003) were significantly more prominent in cystic VS than those in solid VS. Conclusions: GK radiosurgery appeared to be an effective treatment modality for residual tumour control after microsurgery. Owing to having relatively abundant tumour vascularity, residual solid portions of cystic VS resulted in efficient shrinkage after GK radiosurgery. Therefore, GK radiosurgery was found to be a rewarding therapeutic approach to the residual solid portions of cystic VS. [ABSTRACT FROM AUTHOR]

Purpose: Autologous arteriovenous fistulas (AVFs) are considered the gold standard for hemodialysis access, with outcomes largely dependent on the surgeon's experience. Nevertheless, few studies have been conducted on the learning curve of junior vascular surgeons in AVF creation. This study aims to address this by examining the development of surgical skills among junior vascular surgeons., Materials and Methods: A retrospective analysis was conducted on 100 patients who underwent autologous AVF procedures performed by five junior surgeons between January 2018 and December 2023. To establish the cutoff number of cases for the learning curve, we examined the cubic spline curve using the hazard ratio for primary failure., Results: The cutoff number for operation cases was 15.33, and we divided the analysis into a pre-learning curve period (≤15 cases of AVF) and a post-learning curve period (>15 cases of AVF). The 1-year primary patency rate for AVF during the post-learning curve period was 84.0%, which was higher than the 65.5% rate observed during the pre-learning curve period. In a subgroup analysis based on AVF type, the radiocephalic fistula patient group demonstrated a significant increase in 1-year primary patency in the post-learning curve period compared to that in the pre-learning curve period (80.0% vs. 43.0%, log-rank P=0.033). In contrast, there was no significant difference in the primary patency rates between the post- and pre-learning curve periods in the brachiocephalic fistula patient group (90.0% vs. 89.2%, log-rank P=0.930)., Conclusion: Junior vascular surgeons demonstrated improved primary AVF patency beyond the learning curve benchmark in 15 patients, with particularly notable enhancements in radiocephalic fistulas.

Study Objective: This study aimed to analyze the effects of two volatile anesthetic agents, desflurane and sevoflurane, on graft outcomes in patients undergoing deceased donor liver transplantation (DDLT) for cirrhosis, with a specific focus on fatty grafts., Design: A retrospective observational study., Setting: A tertiary hospital (Severance Hospital, Korea)., Patients: This study included 151 patients with liver cirrhosis who underwent DDLT for cirrhosis between January 2006 and December 2022., Interventions: Patients were grouped according to maintenance anesthesia received (desflurane or sevoflurane), the model for end-stage liver disease (MELD) score, and macrovesicular steatosis (MVS) of the liver graft., Measurements: Survival curves were constructed from the date of surgery to graft failure or death. After propensity score matching (PSM), Cox regression analysis was used to compare hazards ratios (HR) for 5-year graft and overall survival. Subgroup analyses were performed for the MELD score and MVS of the liver graft. Incidences of 1-month acute rejection and early allograft dysfunction (EAD) were also compared between the two groups., Main Results: Among 151 eligible patients, 49 patients remained in each group after PSM, with 14 (28.6 %) graft failures and deaths occurring in each group. In matched analysis, sevoflurane showed poorer 5-year graft and overall survival compared to desflurane in recipients of graft with ≥10 % MVS, and this trend was significant in patients with MELD score of ≥35. In Cox regression model, compared to desflurane sevoflurane showed a propensity score-matched HR of 5.8 (95 % CI, 1.13-30.50 for both 5-year graft and overall survival. Additionally, sevoflurane showed an increased risk of 1-month acute rejection; however, no difference was observed for EAD., Conclusions: Sevoflurane as a maintenance agent during DDLT in recipients with high MELD scores and fatty grafts may be associated with poorer outcomes compared to desflurane., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

BACKGROUND Clavicle fractures are a common injury, and the standard surgical treatment for displaced shaft fractures is plate fixation using a single superiorly-placed plate. However, the use of this technique in dementia patients poses challenges, including increased risk of postoperative complications such as fixation failure, mal-union, and non-union. CASE REPORT This is a case series of 2 patients who had clavicle shaft fracture with dementia. The first was a 90-year-old woman with right clavicle fracture and vascular dementia. She underwent superior locking compression plate fixation, but the plate was pulled out because of her uncooperativeness. Therefore, we performed dual-plate fixation. She did not immobilize her arm after the surgery, but the plate did not pull out and she was doing well without any problems in daily life. The second patient was a 78-year-old man with advanced dementia who had a displaced midshaft clavicle fracture after a fall. Due to his inability to cooperate and follow postoperative instructions, a decision was made to employ a dual plating technique with plates applied anteriorly and superiorly. At 6-month follow-up, he had satisfactory functional outcomes and radiographic evidence of fracture healing. CONCLUSIONS The use of dual-plate fixation in the treatment of clavicle fractures in dementia patients is a viable option that can lead to successful outcomes and no failure-related implants.

Introduction This research aims to validate the proficiency and accuracy of the robotic microsurgery platform using rat femoral vessel model. Materials and Methods Total of 256 rat femoral vessels were performed, half using robotic and the other by manual microanastomosis by 8 microsurgeons with less than 5 years of experience given 8 trials (rats) each. Vessel demographics, proficiency (duration of suture and Structured Assessment of Robotic Microsurgical Skills (SARMS)) and accuracy (patency and Scanning Electron Microscopic (SEM)) was analyzed between the two groups. Results Using the robot, an average of 4 trials was needed to reach a plateau in total anastomosis time and patency. Significant more time was required for each vessel anastomosis (34.33 versus 21.63 minutes on the 8th trial, p<0.001) one factor being higher number of sutures compared to the hand-sewn group (artery: 7.86±0.51 versus 5.86±0.67, p=0.035, vein: 12.63±0.49 versus 9.57±0.99, p=0.055). The SARMS scores became nonsignificant between the two group on the 4th trial. The SEM showed higher tendency of unevenly spaced sutures, infolding, tears in the vessel wall for the hand-sewn group. Conclusion Using the robot, similar patency, accuracy, and proficiency can be reached through fast but steep learning process within 4 trials (anastomosis of 8 vessels) as the hand-sewn group. The robotic anastomosis may take longer time, but this is due to the increased number of sutures reflecting higher precision and accuracy. Further insight of precision and accuracy was found through the SEM demonstrating the possibility of the robot to prevent unexpected and unwanted complications., Competing Interests: This research was funded in part by MMI. Symani robotic platform and necessary robotic instrumentation was provided by MMI as part of the research funding agreement between MMI and Asan Medical Center. The senior author Joon Pio Hong is a consultant for MMI., (Thieme. All rights reserved.)

Background: The ataxia telangiectasia mutated (ATM) gene is involved in the repair of double-stranded DNA breaks and a component of the DNA damage repair pathway. Tumors with mutations or low expression of both ARID1A and ATM exhibit increased numbers of tumor-infiltrating lymphocytes and a favorable prognosis. However, the relationship between ATM and ARID1A in gastric carcinoma (GC) is unclear., Methods: We used the mRNA expression data from the Asian Cancer Research Group to construct tissue microarrays (N = 249). Next-generation sequencing (NGS) databases of Samsung Medical Center (SMC) (N = 813) were used to compare genetic alterations. Tissue microarrays were used for ATM and ARID1A immunohistochemistry, and expressions were categorized as "low" and "high." NGS data from TCGA-STAD (N = 431) were used as independent cohorts for genetic alterations validation., Results: In GCs, 32.1 % (80/249) of the cases showed low ATM protein expression (ATM low ) and 20.9 % (52/249) showed low ARID1A expression (ARID1A low ). ATM low was significantly associated with older age (P <.01), gross type of tumor (P =.02), histology (P <. 01), lower incidence of perineural invasion (P =.04), lower disease stage (P <.01), microsatellite instability-high (P <.01), and ARID1A low (P <.01). Furthermore, GCs in the SMC NGS database showed that ATM mutations were significantly correlated with ARID1A mutations (P <.01), and this finding remained significant in TCGA-STAD validation cohort (P <.01)., Conclusion: ATM low in GCs shows a characteristic clinicopathological feature that correlates strongly with ARID1A low . ATM mutation was also associated with ARID1A mutations, highlighting the interactions between ATM and ARID1A in GC and suggesting a potential therapeutic target., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Purpose: The number of patients presenting with vaccination-related cardiovascular symptoms after receiving mRNA vaccines (mRNA-VRCS) is increasing. We investigated the incidence of vaccine-related adverse events (VAEs), including myocarditis and pericarditis, in patients with mRNA-VRCS after receiving BNT162b2-Pfizer-BioNTech and mRNA-1273-Moderna vaccines., Materials and Methods: We retrospectively collected data on patients presenting with mRNA-VRCS who visited the outpatient clinic of two tertiary medical centers. Clinical characteristics, laboratory findings, echocardiographic findings, and electrocardiographic findings were evaluated. VAE was defined as myocarditis or pericarditis in patients after mRNA vaccination. Clinical outcomes during short-term follow-up, including emergency room (ER) visit, hospitalization, or death, were also assessed among the patients., Results: A total of 952 patients presenting with mRNA-VRCS were included in this study, with 89.7% receiving Pfizer-BioNTech and 10.3% receiving Moderna vaccines. The mean duration from vaccination to symptom was 5.6±7.5 days. VAEs, including acute myocarditis and acute pericarditis, were confirmed in 11 (1.2%) and 10 (1.1%) patients, respectively. The VAE group showed higher rates of dyspnea, echocardiography changes, and ST-T segment changes. During the short-term follow-up period of 3 months, the VAE group showed a higher hospitalization rate compared to the control group; there was no significant difference in ER visit ( p =0.320) or mortality rates ( p >0.999)., Conclusion: Amongst the patients who experienced mRNA-VRCS, the total incidence of VAEs, including acute myocarditis and pericarditis, was 2.2%. Patients with VAEs showed higher rates of dyspnea, echocardiographic changes, and ST-T segment changes compared to those without VAEs. With or without the cardiovascular events, the prognosis in patients with mRNA-VRCS was favorable., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Purpose: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV)., Methods: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups., Results: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution., Conclusion: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Although ABO-incompatible liver transplantation (ABOi LT) has undergone remarkable progress, the prognostic factors are poorly understood. This study aimed to elucidate the preoperative factors affecting graft survival after ABOi LT., Methods: Patients who underwent ABOi LT between January 2012 and December 2020 at a single institution in South Korea were retrospectively reviewed. A total of 146 recipients, including 34 patients with graft loss, were analyzed., Results: In the multivariate Cox proportional hazard model, recipient age (≥55 y; hazard ratio, 2.47; 95% confidence interval, 1.18-5.19; P = 0.017) and donor ABO type (donor A, hazard ratio, 3.12; 95% confidence interval, 1.33-7.33; P = 0.009) were significantly associated with an increased risk of graft loss. The most common cause of graft loss was recipient death due to bacterial infection (15/34, 44.1%). Both recipient age and donor ABO type were associated with an increased risk of recipient death due to bacterial infections. The incidence of complications after ABOi LT, including antibody-mediated rejection and diffuse intrahepatic biliary stricture, did not differ according to recipient age or donor ABO type., Conclusions: These findings suggest that recipient age and donor ABO type should be considered when preparing for ABOi LT. Careful monitoring and care after transplantation are required for recipients with preoperative risk factors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Few studies have examined the long-term outcomes of recipients in minimally invasive donor hepatectomies, particularly comparing robotic and laparoscopic donor procedures. Understanding these outcomes is crucial for optimizing surgical approaches and improving the overall success of living donor liver transplantation. This study aimed to compare the feasibility and safety of robotic donor right hepatectomy (RDRH) and laparoscopic donor right hepatectomy (LDRH) by evaluating total follow-up patient outcomes., Methods: This retrospective, single-center study included 117 and 118 donors who underwent RDRH and LDRH between March 2016 and June 2023, respectively. After performing 1:1 propensity score matching, 71 donor-recipient pairs were included in each group. Donor and recipient complications were divided into early (within 90 d) and late (after 90 d) biliary and vascular complications., Results: In the matched cohort, major complication rates of donors were similar in both groups. Bile duct (BD) variation was not significantly different; however, the rates of multiple BD openings (26.8% versus 54.9%; P = 0.001) and major biliary complications in recipients were higher in the LDRH group (22.5% versus 42.3%; P = 0.012). The cumulative biliary complication rate was significantly higher in the LDRH group. Early biliary complications were not significantly different; however, the rate of late biliary complications was higher in the LDRH group (11.3 versus 23.9%; P = 0.047)., Conclusions: RDRH demonstrated comparable postoperative complications to LDRH in donors but showed fewer recipient biliary complications. This could be attributed to the precision of robotic dissection and BD division, resulting in fewer multiple BD openings., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

As actuated devices become smaller and more complex, there is a need for smart materials and structures that directly function as complete mechanical units without an external power supply. The strategy uses light-powered, twisted, and coiled azobenzene-functionalized semicrystalline liquid crystal elastomer (AC-LCE) springs. This twisting and coiling, which has previously been used for only thermally, electrochemically, or absorption-powered muscles, maximizes uniaxial and radial actuation. The specially designed photochemical muscles can undergo about 60% tensile stroke and provide 15 kJ m -3 of work capacity in response to light, thus providing about three times and two times higher performance, respectively, than previous azobenzene actuators. Since this actuation is photochemical, driven by ultraviolet (UV) light and reversed by visible light, isothermal actuation can occur in a range of environmental conditions, including underwater. In addition, photoisomerization of the AC-LCEs enables unique latch-like actuation, eliminating the need for continuous energy application to maintain the stroke. Also, as the light-powered muscles processed to be either homochiral or heterochiral, the direction of actuation can be reversed. The presented approach highlights the novel capabilities of photochemical actuator materials that can be manipulated in untethered, isothermal, and wet environmental conditions, thus suggesting various potential applications, including underwater soft robotics., (© 2024 Wiley‐VCH GmbH.)

Background: Acute-on-chronic liver failure (ACLF) is a syndrome of patients with chronic liver disease presenting with multiple organ failures. Recently, Sundaram-ACLF-LT Mortality (SALT-M) score has been developed to predict 1-year post-liver transplantation mortality. We validated the SALT-M score in a large-volume, Asian single-centre cohort., Aims: We validated the SALT-M score in a large-volume, Asian single-centre cohort., Methods: We analysed 224 patients of ACLF grade 2-3. Area under the receiver operating characteristic curve (AUROC) and concordance index (c-index) were used to assess and compare the predictability of posttransplant mortality of SALT-M and other scores. Moreover, we compared the survivals of patients with high and low SALT-M, in conjunction with MELD score and ACLF grade., Results: The AUROC for prediction of 1-year post-LT survival was higher in SALT-M (0.691) than in MELD, MELD-Na, MELD 3.0 and delta-MELD. Similarly, the c-index of the SALT-M (0.650) was higher than aforementioned MELD systems. When categorised by the cut-off of SALT-M ≥ 20 and MELD ≥ 30, patients with high SALT-M exhibited lower post-LT survival than those with low SALT-M scores regardless of high or low MELD (40.0% for high SALT-M/high MELD vs. 42.9% for high SALT-M/low MELD vs. 73.8% for low SALT-M/high MELD vs. 63.7% for low SALT-M/low MELD, p < 0.001). In patients with ACLF grade 3, SALT-M effectively stratified the posttransplant mortality (39.4% for high SALT-M vs. 63.1% for low SALT-M, p = 0.018)., Conclusions: SALT-M outperformed previous MELD systems for predicting posttransplant mortality in Asian LT cohort with severe ACLF. Transplantability for patients with severe ACLF could be determined based on SALT-M., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Autophagy is essential for cell survival and cellular homeostasis under various stress conditions. Therefore, autophagy dysfunction is associated with the pathogenesis of various human diseases. We explored the regulatory role of RhoBTB3 in autophagy and its interaction with activating molecules in AMBRA1. RhoBTB3 deficiency was found to induce autophagy, while its overexpression inhibited autophagy induction. Through immunoprecipitation and mass spectrometry, AMBRA1 was identified as a substrate of RhoBTB3. The study revealed that RhoBTB3 regulates AMBRA1 stability by influencing its protein levels without affecting its mRNA levels. RhoBTB3 induced the ubiquitination of AMBRA1, leading to proteasome-mediated degradation, with the ubiquitination occurring at K45 on AMBRA1 through a K27-linked ubiquitin chain. The knockdown of AMBRA1 blocked RhoBTB3 knockdown-induced autophagy, indicating the dependency of autophagy on AMBRA1. Thus, RhoBTB3 negatively regulates autophagy by mediating AMBRA1 ubiquitination and degradation, suggesting RhoBTB3 as a potential therapeutic target for autophagy-related diseases.

Background: Extensor tendon injuries require surgical repair, followed by rehabilitation to ensure optimal outcomes. Immobilization has been the cornerstone of postoperative management. However, immobilization after surgery frequently makes the finger stiffness, often resulting in reduced functionality and quality of life for patients. Recent studies indicate that early controlled motion can significantly improve outcomes, but safe early range of motion (ROM) exercise is a significant clinical challenge. This article aims to check the efficacy of the novel designed finger ROM brace for preventing finger stiffness for extensor tendon injuries with case series., Methods: A finger ROM brace was designed based on the natural finger movement. Like a real finger, there are two tiny hinge joints and three round-shape body components. The design aimed to be ergonomic dynamic splint assisting controlled motion to promote early motion, thus reducing tendon tension and preventing stiffness. Elastic resistant ROM exercise could be by inserting a silicone band into the groove on the components and free movement could be achieved by removing a silicone band., Result: Between December 2022 and July 2023, 10 patients who underwent tenorrhaphy because of extensor tendon laceration were involved. Complete extensor tendon laceration was 3 patients, other seven patients had partial laceration of extensor tendons. Surgery was performed within 2 days of injury, and no infection was observed in all patients. After the extensor tendon was confirmed as healed state by ultrasound, the patients were permit the active exercise wearing finger ROM brace with a silicone band. Within 1-2 weeks after elastic resistant exercise, the patients could achieve free full ROM movement without any complication., Conclusion: The novel finger ROM brace combines the advantages of dynamic splinting and under-actuated mechanisms to offer a comprehensive solution for preventing stiffness after extensor tendon suture. Future studies should focus on clinical trials to validate the efficacy and safety of this brace in a larger population., (© 2024. The Author(s).)

In the meat industry, the quality grading system is commonly applied to classify carcasses based on quality and value. Presently, to facilitate consumer convenience, pork bellies are prepared into slices and retailed in supermarkets and butchers. The objective of this study was to assess the effect of quality grade (QG) and retail cutting manner on the quality properties of pork bellies. Thirty-two bellies with different QGs: QG1 + , 1, 2, and off-grade ( n = 8 each) randomly collected from a commercial slaughterhouse were used. Each belly was cut into 3 portions: A (5-10th rib, cranial edge), B (11-15th rib), and C (without rib, caudal edge) according to the commonly used retail cutting manner. Samples were subjected to chemical composition, quality traits, and aroma analysis. Fat content was highest in QG1 + and lowest in off-grade and distributed at a higher level in portions A and B than in portion C in all QGs ( p < 0.05). Off-grade was associated with higher shear force and chewiness values and lower levels of palmitic and stearic acids, regardless of the cutting portion. The bellies used in this study exhibited variations in chemical composition and quality properties not only among the QGs but also across the cutting portions within each QG.

Among the most frequent causes of respiratory infections in humans are influenza A virus H1N1 (H1N1), influenza B virus (IVB), and respiratory syncytial virus (RSV). Echinacea is a perennial wildflower belonging to the Asteraceae family. Echinacea purpurea (L.) Moench is a species belonging to the Echinacea genus. Its characteristic compound, chicoric acid (CA), is known for its physiological activities, including antiviral effects and immune enhancement. Activities of E. purpurea 60% ethanol extract (EPE) and CA in inhibiting infections caused by H1N1, IVB, and RSV subtype A (RSV-A) were evaluated through plaque inhibition tests, quantification of viral gene expression, and analysis of transmission electron microscopy (TEM) images. Additionally, inhibitory activities of EPE and CA for hemagglutination and neuraminidase (NA) of H1N1 and IVB were determined. In the plaque reduction assays, both EPE and CA reduced infectivity against H1N1, IVB, and RSV-A. Furthermore, quantitative real-time polymerase chain reaction analysis revealed that EPE and CA reduced gene expression levels for H1N1, IVB, and RSV-A, whereas TEM image analysis confirmed their inhibitory effects on host cell infection by these viruses. Hemagglutination assays exhibited the ability of EPE and CA to hinder H1N1 and IVB attachment to host cell receptors. Furthermore, EPE and CA displayed inhibition activity against the NA of H1N1 and IVB. These findings suggest that EPE and CA can suppress the infection and propagation of H1N1, IVB, and RSV-A, demonstrating their potential as preventive and therapeutic agents for viral respiratory infections or as ingredients for health functional foods., Competing Interests: AUTHOR DISCLOSURE STATEMENT Author SKL, DRL, DEM, SHP, DGK, EJK, and BKC were employed by the company NUON Co., Ltd. The remaining authors declare no conflict of interest., (© 2024 The Korean Society of Food Science and Nutrition.)

Alzheimer's disease (AD) is a progressive neurological disorder that represents a major cause of dementia worldwide. Its pathogenesis involves multiple pathways, including the amyloid cascade, tau protein, oxidative stress, and metal ion dysregulation. Recent studies have suggested a critical link between changes in gut microbial diversity and the disruption of the gut-brain axis in AD. Previous studies primarily explored the potential benefits of probiotics and prebiotics in managing AD. However, studies have yet to fully describe a novel promising approach involving the use of synbiotics, which include a combination of active probiotics and new-generation prebiotics. Synbiotics show potential for mitigating the onset and progression of AD, thereby offering a holistic approach to address the multifaceted nature of AD. This review article primarily aims to gain further insights into the mechanisms of AD, specifically the intricate interaction between gut bacteria and the brain via the gut-brain axis. By understanding this relationship, we can identify potential targets for intervention and therapeutic strategies to combat AD effectively. This review also discusses substantial evidence supporting the role of synbiotics as a promising AD treatment that surpasses traditional probiotic or prebiotic interventions. We find that synbiotics may be used not only to address cognitive decline but also to reduce AD-related psychological burden, thus enhancing the overall quality of life of patients with AD.

Non-alcoholic fatty acid disease (NAFLD) is caused by a build-up of fat in the liver, inducing local inflammation and fibrosis. We evaluated the effects of probiotic lactic acid-generating bacteria (LAB) derived from a traditional fermented beverage in a mouse model of NAFLD. The LAB isolated from this traditional Korean beverage were screened using the human hepatic cell line HepG2, and Lactocaseibacillus paracasei HY7207 (HY7207), which was the most effective inhibitor of fat accumulation, was selected for further study. HY7207 showed stable productivity in industrial-scale culture. Whole-genome sequencing of HY7207 revealed that the genome was 2.88 Mbp long, with 46.43% GC contents and 2778 predicted protein-coding DNA sequences (CDSs). HY7207 reduced the expression of lipogenesis and hepatic apoptosis-related genes in HepG2 cells treated with palmitic acid. Furthermore, the administration of 10 9 CFU/kg/day of HY7207 for 8 weeks to mice fed an NAFLD-inducing diet improved their physiologic and serum biochemical parameters and ameliorated their hepatic steatosis. In addition, HY7207 reduced the hepatic expression of genes important for lipogenesis ( Srebp1c , Fasn , C / ebpa , Pparg , and Acaca ), inflammation ( Tnf , Il1b , and Ccl2 ), and fibrosis ( Col1a1 , Tgfb1 , and Timp1 ). Finally, HY7207 affected the expression of the apoptosis-related genes Bax (encoding Bcl2 associated X, an apoptosis regulator) and Bcl2 (encoding B-cell lymphoma protein 2) in the liver. These data suggest that HY7207 consumption ameliorates NAFLD in mice through effects on liver steatosis, inflammation, fibrosis, and hepatic apoptosis. Thus, L. paracasei HY7207 may be suitable for use as a functional food supplement for patients with NAFLD.

AIMP2-DX2 (hereafter DX2) is an oncogenic variant of aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) that mediates tumorigenic interactions with various factors involved in cancer. Reducing the levels of DX2 can effectively inhibit tumorigenesis. We previously reported that DX2 can be degraded through Siah1-mediated ubiquitination. In this study, we identified a compound, SDL01, which enhanced the interaction between DX2 and Siah1, thereby facilitating the ubiquitin-dependent degradation of DX2. SDL01 was found to bind to the pocket surrounding the N-terminal flexible region and GST domain of DX2, causing a conformational change that stabilized its interaction with Siah1. Our findings demonstrate that protein-protein interactions (PPIs) can be modulated through chemically induced conformational changes., Competing Interests: Declaration of interests This work has been patented in 2020 under patent number (WO2020204548A1, worldwide applications)., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/aim: TP53 mutation in breast cancer (BC) is associated with chemoresistance, endocrine therapy resistance, and late recurrence, resulting in poor prognosis. Nuclear accumulation of p53 in immunohistochemistry (IHC) is a surrogate marker of TP53 mutation. This study analyzed the frequency, type, and distribution of TP53 mutations in BCs and assessed the efficacy of p53 IHC as a surrogate marker of TP53 mutation., Patients and Methods: We collected data from 112 BC cases, including the results of p53 IHC and next-generation sequencing (NGS)., Results: Over-expression of p53 IHC was observed in 36 patients (32.1%), complete absence in 19 patients (17.0%), aberrant cytoplasmic staining in 1 patient (0.9%), and wild-type in 56 (50.0%) patients. The concordance rate between TP53 mutation and p53 IHC was 88.4% in all BCs, 89.9% in luminal BCs, and 86.0% in triple-negative BCs (TNBC). TNBC, abnormal p53 IHC pattern, p53 IHC over-expression, neoadjuvant chemotherapy (NAC) history, TP53 mutation, and high pre-treatment ki-67 labeling index (≥50%) were significantly associated with worse distant metastasis-free survival (DMFS) and overall survival (OS) (p<0.05). Pre-NAC clinical stage III was associated with worse DMFS but not OS. Multivariate analysis showed that NAC history, TNBC, and p53 IHC over-expression were independent predictors of worse DMFS. An abnormal p53 IHC pattern and NAC history were independent predictors of worse OS., Conclusion: P53 IHC is a valid surrogate marker of TP53 mutation in BC. Accumulation of abnormal p53 alone, regardless of TP53 mutation, was associated with worse DMFS and can be used as an easily accessible biomarker to predict chemoresistance., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)