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Background: Differentiation of postoperative neck abscess from non-infected fluid is important because the treatment is different. Purpose: To determine specific CT findings that might help to differentiate abscesses from non-infected fluid collections in the postoperative neck. Material and Methods: We retrospectively reviewed CT scans of 50 patients (43 men and 7 women; mean age, 62.5 ± 8.9 years) who had postoperative fluid collections in the neck (26 abscesses and 24 non-infected fluid collections). Diagnosis of an abscess was determined by a positive bacteria culture from the fluid collection. Diagnoses were correlated with the following CT findings: anatomic spaces involved, the maximum transverse diameter, margin, attenuation, rim enhancement, gas bubbles, and manifestations of soft tissue adjacent to a fluid collection. Results: Rim enhancement pattern and soft tissue manifestations showed significant differences between abscess and non-infected fluid. The reliable CT findings for abscess were: (i) rim enhancement > 50% of the circumference, 54% sensitive, 71% specific, and 62% accurate; and (ii) severe soft tissue manifestations, 39% sensitive, 92% specific, and 64% accurate. There were no significant differences in the anatomic spaces involved, the maximum transverse diameter, margin, attenuation, and gas bubbles between abscess and non-infected fluid. Conclusion: CT findings that may help differentiate postoperative neck abscess from non-infected fluid were rim enhancement > 50% of the circumference and severe soft tissue manifestations. [ABSTRACT FROM AUTHOR]

Objectives: To compare the diagnostic performance of ultrasound, contrast-enhanced computed tomography (CT) and (18)F-FDG positron emission tomography (PET)/CT for detecting recurrent differentiated thyroid cancer in the neck.Methods: Twenty patients who had undergone previous surgery for differentiated thyroid cancer (19 papillary carcinomas; 1 medullary carcinoma) and presented with pathologically proven recurrence in the neck were included. All patients had undergone ultrasound, CT and PET/CT in the 2 months before further surgery. In each patient, ultrasound, CT and PET/CT images were retrospectively reviewed to determine the presence of loco-regional recurrence by level-by-level analysis. Imaging results were correlated with the histological evaluation of the neck dissection as a standard of reference.Results: Recurrences were found at 52 out of 110 cervical nodal levels surgically explored. The sensitivity, specificity and accuracy were 69.2 %, 89.7 % and 80.0 % for ultrasound; 63.5 %, 94.8 % and 80.0 % for CT; and 53.8 %, 79.3 % and 67.3 % for PET/CT, respectively. ROC analysis revealed higher diagnostic performance with ultrasound than with PET/CT for detecting recurrent tumour.Conclusions: Although no significant difference was found among the three techniques, the sensitivity and specificity of ultrasound and CT were higher than those of PET/CT for the evaluation of cervical recurrence in patients with differentiated thyroid cancer.Key Points: • Ultrasound, CT and ( 18 ) F-FDG PET/CT can all detect recurrent thyroid cancer. • Ultrasound and CT have higher sensitivity and specificity. • Ultrasound, CT and ( 18 ) F-FDG PET/CT frequently demonstrated discordant findings. [ABSTRACT FROM AUTHOR]

For advanced stage tonsil cancer, extensive resection of the soft palate is unavoidable. The purpose of this study is to report on the speech outcome according to the various types of defects and reconstruction techniques. This prospective study was performed on 53 patients of tonsil cancer. The postoperative speech function was evaluated for three factors: nasalance, speech intelligibility, and velopharyngeal insufficiency. Four reconstruction methods used for the soft palate defect: local flap, patch method, Gehanno method, and Denude method. Univariate analysis showed that the Denuded reconstruction technique, more than one-half of the soft palate resection, and T stage was significantly associated for nasalance, speech intelligibility, and velopharyngeal insufficiency. Multivariate analysis showed that the Denuded reconstruction technique (for patients with extensive soft palate and posterior pharyngeal wall defect) was the most significant variable. When the defect of tonsil cancer is extensive, especially when it extends to the posterior pharyngeal wall, a reconstruction method that can reduce the velopharyngeal cross-sectional area efficiently, such as the Gehanno method, is preferred. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in Parkinson's disease (PD). However, the therapeutic value and/or the placebo effect of rTMS on PD remain to be elucidated. To investigate the therapeutic value and/or placebo effect of rTMS in PD, we compared the motor section of unified PD rating scale (UPDRS III) and the amount of extracellular dopamine concentration using [(11)C] raclopride PET before and after two sessions of rTMS in 9 PD patients. During a consecutive 2 days while off-medication, two series of 15 trains of 5 Hz-frequency rTMS (intensity, 90% of the resting motor threshold) were applied to the hand area of more severely symptomatic motor cortex (MC). After unilateral rTMS of MC, mean raclopride binding potentials (BPs) were reduced not only in putaminal and caudate areas on the stimulated side (-4.9% and -6.5%, respectively) (P > 0.05) but also in putaminal and caudate areas of nonstimulated hemispheres (-6.6%, P > 0.05 and -12.1%, P = 0.049, respectively). UPDRS III scores were significantly decreased (35.0 +/- 14.1 to 32.0 +/- 13.4, P = 0.049). A reduction of raclopride BP in nonstimulated ventral striatum by unilateral rTMS supports the placebo response during rTMS. [ABSTRACT FROM AUTHOR]

There is evidence that alteration in plasma fatty acid composition may play a role in certain neurological disorders. This case control study was conducted to evaluate the association between plasma fatty acid levels and mental retardation in Korean children. Plasma phospholipid fatty acids, plasma lipids, dietary fatty acids and selected nutrients were measured in 31 mentally retarded boys (mean age 9.93 +/-1.5 yrs) and matched controls. Total plasma omega-3 fatty acids (Sigmaw3), docosahexaenoic acid (DHA) and high density lipoprotein (HDL) concentrations were significantly lower and the Sigmaomega-6/Sigmaomega-3 ratio was significantly higher in cases than in controls. The odds in favor of mental retardation increased by 69% for each unit increase in the Sigmaomega-6/ Sigmaomega-3 ratio (adjusted odds ratio = 1.69, 95% CI = 1.25-2.29). Significant variation in plasma Sigmaomega-3 and the Sigmaomega-6/ Sigmaomega-3 ratio was explained by mental retardation and plasma HDL concentrations (45% and 37% respectively). There was a significant inverse association between plasma DHA and mental retardation. For each unit increase in plasma DHA, odds of mental retardation decreased by 74%. There was no significant difference in either total dietary fat or fatty acids intakes between cases and controls. The energy intake of cases was significantly higher than the controls. These results suggest that proportion of plasma Sigmaomega-3 fatty acids, particularly, DHA, and the Sigmaomega-6/ Sigmaomega-3 ratio are associated with mental retardation in children in this study. [ABSTRACT FROM AUTHOR]

Background: This study evaluates functional larynx preservation in patients with hypopharyngeal cancer (HPC) and laryngeal cancer (LC) who achieved complete remission following radiotherapy (RT) or concurrent chemoradiation (CCRT)., Methods: HPC and LC patients treated with RT/CCRT from 1999 to 2017 were retrospectively analyzed. Severe late dysphagia and tracheostomy cases were assessed to determine laryngeal function. Long-term preservation rate of functional larynx and associated factors were evaluated., Results: Of 152 patients (55 HPC, 97 LC), nine developed severe dysphagia, occurring on average 58.2 months post-treatment. HPC and cervical node metastasis significantly increased the risk of laryngeal function impairment (p < 0.001 and p = 0.014, respectively), presenting a continued decline in functional larynx preservation rate beyond 10 years., Conclusions: Patients with HPC and cervical node metastasis demonstrate an increased risk for long-term laryngeal function impairment despite successful oncologic outcomes. This risk extends beyond 10 years, underscoring the need for prolonged monitoring and comprehensive support., (© 2024 Wiley Periodicals LLC.)

The relinquishment of companion animals to shelters presents significant challenges for animal welfare organizations and has substantial implications for the well-being of both the animals and their owners. This study aims to investigate the reasons for voluntarily relinquishing animals to shelters, to examine species-specific differences (cats and dogs), to compare initial relinquishments to returns (re-relinquishments or readmissions), and to identify potential changes over a 6-year period framing the onset of the COVID-19 pandemic. A retrospective analysis of owner relinquishment records from an open admission shelter in the US was conducted using content analysis, a novel approach in this area of research. A total of 13 relinquishment reason categories were identified, as well as 9 separate categories for specific behavioral issues. Among 2836 randomly selected records, the most frequent reasons cited were Behavior Issues (28%), Housing/Moving (18%), Unable to Care (16%), Too Many Pets (10%), Financial (6%), and Owner Allergies (5%). The most common behavioral reasons reported were Aggression (32% of behavioral surrenders), Social Conflict (28%), and Soiling (13%). However, differences were observed in the pattern of relinquishment reasons based on statistical analyses of species, type of relinquishment, and year. Regarding temporal trends, Housing/Moving and Financial reasons were not found to have changed significantly since the pandemic, but the relative frequency of the category Unable to Care increased significantly in 2022 and 2023. Collectively, these findings partially replicate those from research spanning the past several decades in this area that has employed less systematic methodology and can further be used to help identify and understand the primary drivers of owner relinquishments.

Introduction: In this study, we aimed to analyze the incidence of acute endophthalmitis after secondary intraocular lens (IOL) implantation in South Korea., Methods: This study used information from the National Health Insurance Service (NHIS)-National Health Information Database (NHID). We identified patients who underwent secondary IOL implantation or IOL exchange surgeries during 2002-2021 due to diagnoses of IOL dislocation or mechanical complication of IOL. Postoperative endophthalmitis (POE) was defined as patients having received intravitreal antibiotic injection or vitrectomy for acute endophthalmitis diagnosed within 42 days after the claim for secondary IOL surgeries. All statistical analyses were performed with a significance level p &lt; 0.05, and we used the univariate and multivariate Cox proportional hazard model to identify risk factors., Results: From 2002 to 2021, 39,364 patients received secondary IOL implantation, and acute POE was diagnosed in 62 patients. The overall incidence of acute POE was 0.16% during the 20-year period. More than half of the patients were diagnosed with POE within the first week after surgery. In the univariate analysis, there was a higher incidence of endophthalmitis in the group with pre-existing glaucoma (hazard ratio [HR], 1.945; 95% confidence interval [CI], 1.036-3.652; p=0.0385) and the group undergoing concurrent vitrectomy (hazard ratio [HR], 2.329; 95% confidence interval [CI], 1.003-5.405; p=0.0491)., Conclusions: The incidence of acute endophthalmitis after secondary IOL implantation in South Korea was similar to that of other countries. This is the largest retrospective claims data-based study of acute endophthalmitis after secondary IOL implantation in patients in South Korea., (S. Karger AG, Basel.)

Introduction: Long COVID can also lead to neurological sequelae that affect existing diseases. This study explored how COVID-19 infection affects neurological patients and the relationship between long COVID and exacerbating factors., Methods: This retrospective study was conducted on 85 patients with neurological diseases after COVID-19 at the Neurology Department, Inje University Busan Paik Hospital, Korea. The data were collected between August and October 2022. The patients had a medical history, including COVID-19 infection, and completed symptom questionnaires. A long COVID questionnaire consisting of 35 inquiries in 10 categories was completed. Anxiety, depression, fatigue, functional difficulties, QOL, and health status changes were assessed., Results: The analysis comprised 85 participants (age: 56.4 ± 15.2 years; 63.5% women). Of the categories, neurological symptoms (68.2%) were the most prevalent, followed by systemic symptoms (64.7%) and cardiopulmonary symptoms (56.5%). Anxiety, depression, and fatigue symptoms were reported by 36.5%, 34.1%, and 42.4% of the participants. Subjective neurological deterioration after COVID-19 was reported in 28 participants (28/81, 34.6%). Anxiety, depression, and fatigue were influenced by long COVID symptoms and the subjective deterioration of neurological conditions., Conclusion: This study analyzed the long COVID symptoms in patients with pre-existing neurological conditions and their impact on mental health and quality of life. One-third of the participants reported a subjective worsening of their preexisting neurological conditions. This study highlights the need for comprehensive follow-ups and a multidisciplinary approach for patients with neurological conditions and prolonged COVID-19 symptoms., (The Author(s). Published by S. Karger AG, Basel.)

Obstructive sleep apnea (OSA) is closely associated with the development and chronicity of temporomandibular disorder (TMD). Given the intricate pathophysiology of both OSA and TMD, comprehensive diagnostic approaches are crucial. This study aimed to develop an automatic prediction model utilizing multimodal data to diagnose OSA among TMD patients. We collected a range of multimodal data, including clinical characteristics, portable polysomnography, X-ray, and MRI data, from 55 TMD patients who reported sleep problems. This data was then analyzed using advanced machine learning techniques. Three-dimensional VGG16 and logistic regression models were used to identify significant predictors. Approximately 53% (29 out of 55) of TMD patients had OSA. Performance accuracy was evaluated using logistic regression, multilayer perceptron, and area under the curve (AUC) scores. OSA prediction accuracy in TMD patients was 80.00-91.43%. When MRI data were added to the algorithm, the AUC score increased to 1.00, indicating excellent capability. Only the obstructive apnea index was statistically significant in predicting OSA in TMD patients, with a threshold of 4.25 events/h. The learned features of the convolutional neural network were visualized as a heatmap using a gradient-weighted class activation mapping algorithm, revealing that it focuses on differential anatomical parameters depending on the absence or presence of OSA. In OSA-positive cases, the nasopharynx, oropharynx, uvula, larynx, epiglottis, and brain region were recognized, whereas in OSA-negative cases, the tongue, nose, nasal turbinate, and hyoid bone were recognized. Prediction accuracy and heat map analyses support the plausibility and usefulness of this artificial intelligence-based OSA diagnosis and prediction model in TMD patients, providing a deeper understanding of regions distinguishing between OSA and non-OSA., (© 2024. The Author(s).)

Purpose: This study aimed to analyze the incidence and characteristics of intraocular lens (IOL) dislocation after cataract surgery in South Korea., Methods: We retrospectively analyzed the incidence of IOL dislocation after cataract surgery in patients diagnosed between 2002 and 2021. Data of all pseudophakic patients who underwent secondary IOL or IOL exchange surgeries due to IOL dislocation were extracted from the Korean National Health Insurance System (KNHIS) database and the Korean Standard Classification of Diseases-7 codes. The incidence per 1,000,000 person-years and corresponding 95% confidence intervals (CIs) were calculated., Results: Between 2002 and 2021, 39,965 (0.82 %) of the 4,848,125 pseudophakic patients were diagnosed with IOL dislocation and surgically treated. The incidence of IOL dislocation requiring surgery in pseudophakic patients was 28,900/1,000,000 person-years (95% CI: 28,431-29,369), comprising 57,800 cases in male and 10,800 in female patients (95% CI: male: 56,730-58,870 vs. 95% CI: female patients: 10,523-11,077), and mean male-to-female ratio was 5.35. The incidence rate peaked in younger age group below 40 years, showing 107,000 per 1,000,000 person-years (95% CI: 102,900-111,100), and the average age of IOL dislocation requiring surgery was 68.1 ± 10.7 years. The average time lapse from cataract surgery to secondary IOL surgery due to IOL dislocation was 4.1±4.7 years (median, 2.2 years), and the number of secondary IOL surgery due to dislocation of artificial lens rapidly occurred 10 years after cataract surgery among all age groups., Conclusions: The incidence of IOL dislocation requiring surgery was higher in younger and male patients. Our findings could be expected to aid establishing future healthcare policies for South Korean populations with an increased risk of IOL dislocation after cataract surgery.

Objectives: Facial nerve sacrifice during radical parotidectomy can impair quality of life. This study assessed the effectiveness of single-stage facial reanimation surgery performed concurrently with radical parotidectomy in restoring facial function., Methods: A retrospective analysis was conducted on patients who underwent single-stage facial reanimation combined with radical parotidectomy. The techniques employed included selective reinnervation and orthodromic temporalis tendon transfer. Outcomes were evaluated using the modified House-Brackmann and Terzis grading systems, Emotrics facial assessment, and the Facial Disability Index (FDI)., Results: Among the 13 patients studied (median age, 54 years; 69% male), 10 underwent selective reinnervation. Of these, nine patients demonstrated improvement, achieving House-Brackmann grade III and Terzis grade 4 or 5. The other three patients underwent tendon transfer and achieved moderate functional outcomes. Emotrics analysis revealed balanced facial symmetry in the selective reinnervation group. Furthermore, FDI scores indicated satisfactory physical and social/well-being functions., Conclusion: Single-stage facial reanimation effectively restores facial function in patients undergoing radical parotidectomy. This approach offers meaningful benefits in the early recovery of facial function.

In viral infections, natural killer (NK) cells exhibit anti-viral activity by inducing apoptosis in infected host cells and impeding viral replication through heightened cytokine release. Extracellular vesicles derived from NK cells (NK-EVs) also contain the membrane composition, homing capabilities, and cargo that enable anti-viral activity. These characteristics, and their biocompatibility and low immunogenicity, give NK-EVs the potential to be a viable therapeutic platform. This study characterizes the size, EV-specific protein expression, cell internalization, biocompatibility, and anti-viral miRNA cargo to evaluate the anti-viral properties of NK-EVs. After 48 h of NK-EV incubation in inflamed A549 lung epithelial cells, or conditions that mimic lung viral infections such as during COVID-19, cells treated with NK-EVs exhibit upregulated anti-viral miRNA cargo (miR-27a, miR-27b, miR-369-3p, miR-491-5p) compared to the non-treated controls and cells treated with control EVs derived from lung epithelial cells. Additionally, NK-EVs effectively reduce expression of viral RNA and pro-inflammatory cytokine (TNF-α, IL-8) levels in SARS-CoV-2 infected Vero E6 kidney epithelial cells and in infected mice without causing tissue damage while significantly decreasing pro-inflammatory cytokine compared to non-treated controls. Herein, this work elucidates the potential of NK-EVs as safe, anti-viral nanomaterials, offering a promising alternative to conventional NK cell and anti-viral therapies., (© 2024 Wiley‐VCH GmbH.)

Dermacoccus barathri is the first reported pathogen within the Dermacoccus genus to cause a catheter-related bloodstream infection, which occurred in 2015. In this study, the complete genome assembly of Dermacoccus barathri was constructed, and the complete genome of Dermacoccus barathri FBCC-B549 consists of a single chromosome (3,137,745 bp) without plasmids. The constructed genome of D. barathri was compared with those of two closely related species within the Dermacoccus genus. D. barathri exhibited a pattern similar to Dermacoccus abyssi in terms of gene clusters and synteny analysis. Contrary to previous studies, biosynthetic gene cluster (BGC) analysis for predicting secondary metabolites revealed the presence of the LAP biosynthesis pathway in the complete genome of D. barathri , predicting the potential synthesis of the secondary metabolite plantazolicin. Furthermore, an analysis to investigate the potential pathogenicity of D. barathri did not reveal any antibiotic resistance genes; however, nine virulence factors were identified in the Virulence Factor Database (VFDB). According to these matching results in the VFDB, despite identifying a few factors involved in biofilm formation, further research is required to determine the actual impact of D. barathri on pathogenicity. The complete genome of D. barathri is expected to serve as a valuable resource for future studies on D. barathri , which currently lack sufficient genomic sequence information.

Although cardiovascular diseases (CVD) are the leading cause of global mortality, there is a lack of therapies that target and revert underlying pathological processes. Mitochondrial dysfunction is involved in the pathophysiology of CVD, and thus is a potential target for therapeutic development. To target the mitochondria and improve therapeutic efficacy, nanoparticle-based delivery systems have been proposed as promising strategies for the delivery of therapeutic agents to the mitochondria. This review will first discuss how mitochondrial dysfunction is related to the progression of several CVD and then delineate recent progress in mitochondrial targeting using nanoparticle-based delivery systems including peptide-based nanosystems, polymeric nanoparticles, liposomes, and lipid nanoparticles. In addition, we summarize the advantages of these nanocarriers and remaining challenges in targeting the mitochondria as a therapeutic strategy for CVD treatment., (© 2024 Wiley Periodicals LLC.)

Autosomal dominant polycystic kidney disease (ADPKD) is a complex disorder characterized by uncontrolled renal cyst growth, leading to kidney function decline. The multifaceted nature of ADPKD suggests that single-pathway interventions using individual small molecule drugs may not be optimally effective. As such, a strategy encompassing combination therapy that addresses multiple ADPKD-associated signaling pathways could offer synergistic therapeutic results. However, severe off-targeting side effects of small molecule drugs pose a major hurdle to their clinical transition. To address this, we identified four drug candidates from ADPKD clinical trials, bardoxolone methyl (Bar), octreotide (Oct), salsalate (Sal), and pravastatin (Pra), and incorporated them into peptide amphiphile micelles containing the RGD peptide (GRGDSP), which binds to the basolateral surface of renal tubules via integrin receptors on the extracellular matrix. We hypothesized that encapsulating drug combinations into RGD micelles would enable targeting to the basolateral side of renal tubules, which is the site of disease, via renal secretion, leading to superior therapeutic benefits compared to free drugs. To test this, we first evaluated the synergistic effect of drug combinations using the 20% inhibitory concentration for each drug (IC 20 ) on renal proximal tubule cells derived from Pkd1 flox/- :TSLargeT mice. Next, we synthesized and characterized the RGD micelles encapsulated with drug combinations and measured their in vitro therapeutic effects via a 3D PKD growth model. Upon both IV and IP injections in vivo , RGD micelles showed a significantly higher accumulation in the kidneys compared to NT micelles, and the renal access of RGD micelles was significantly reduced after the inhibition of renal secretion. Specifically, both Bar+Oct and Bar+Sal in the RGD micelle treatment showed enhanced therapeutic efficacy in ADPKD mice ( Pkd1 fl/fl ;Pax8-rtTA;Tet-O-Cre ) with a significantly lower KW/BW ratio and cyst index as compared to PBS and free drug-treated controls, while other combinations did not show a significant difference. Hence, we demonstrate that renal targeting through basolateral targeting micelles enhances the therapeutic potential of combination therapy in genetic kidney disease.

Chronic and genetic kidney diseases such as autosomal dominant polycystic kidney disease (ADPKD) have few therapeutic options, and clinical trials testing small molecule drugs have been unfavorable due to low kidney bioavailability and adverse side effects. Although nanoparticles can be designed to deliver drugs directly to the diseased site, there are no kidney-targeted nanomedicines clinically available, and most FDA-approved nanoparticles are administered intravenously which is not ideal for chronic diseases. To meet these challenges of chronic diseases, we developed a biomaterials-based strategy using chitosan particles (CP) for oral delivery of therapeutic, kidney-targeting peptide amphiphile micelles (KMs). We hypothesized that encapsuling KMs into CP would enhance the bioavailability of KMs upon oral administration given the high stability of chitosan in acidic conditions and mucoadhesive properties enabling absorption within the intestines. To test this, we evaluated the mechanism of KM access to the kidneys via intravital imaging and investigated the KM biodistribution in a porcine model. Next, we loaded KMs carrying the ADPKD drug metformin into CP (KM-CP -met ) and measured in vitro therapeutic effect. Upon oral administration in vivo, KM-CP -met showed significantly greater bioavailability and accumulation in the kidneys as compared to KM only or free drug. As such, KM-CP -met treatment in ADPKD mice ( Pkd1 fl/fl ; Pax8-rtTA ; Tet-O-Cre which develops the disease over 120 days and mimics the slow development of ADPKD) showed enhanced therapeutic efficacy without affecting safety despite repeated treatment. Herein, we demonstrate the potential of KM-CP as a nanomedicine strategy for oral delivery for the long-term treatment of chronic kidney diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Data on the durability of booster dose immunity of COVID-19 vaccines are relatively limited., Methods: Immunogenicity was evaluated for up to 9-12 months after the third dose of vaccination in 94 healthy adults., Results: Following the third dose, the anti-spike immunoglobulin G (IgG) antibody response against the wild-type was boosted markedly, which decreased gradually over time. However, even 9-12 months after the booster dose, both the median and geometric mean of anti-spike IgG antibody levels were higher than those measured 4 weeks after the second dose. Breakthrough infection during the Omicron-dominant period boosted neutralizing antibody titers against Omicron sublineages (BA.1 and BA.5) and the ancestral strain. T-cell immune response was efficiently induced and maintained during the study period., Conclusions: mRNA vaccine booster dose elicited durable humoral immunity for up to 1 year after the third dose and T-cell immunity was sustained during the study period, supporting an annual COVID-19 vaccination strategy., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Joon Young Song reports financial support was provided by Korea Disease Control and Prevention Agency. Joon Young Song reports a relationship with Korea Disease Control and Prevention Agency that includes: board membership., (© 2024 The Authors.)

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target., (© 2024. The Author(s).)

Biopsy is the clinical standard for diagnosing lymph node (LN) metastasis, but it is invasive and poses significant risk to patient health. Magnetic resonance imaging (MRI) has been utilized as a noninvasive alternative but is limited by low sensitivity, with only ∼35% of LN metastases detected, as clinical contrast agents cannot discriminate between healthy and metastatic LNs due to nonspecific accumulation. Nanoparticles targeted to the C-C chemokine receptor 2 (CCR2), a biomarker highly expressed in metastatic LNs, have the potential to guide the delivery of contrast agents, improving the sensitivity of MRI. Additionally, cancer cells in metastatic LNs produce monocyte chemotactic protein 1 (MCP1), which binds to CCR2 + inflammatory monocytes and stimulates their migration. Thus, the molecular targeting of CCR2 may enable nanoparticle hitchhiking onto monocytes, providing an additional mechanism for metastatic LN targeting and early detection. Hence, we developed micelles incorporating gadolinium (Gd) and peptides derived from the CCR2-binding motif of MCP1 (MCP1-Gd) and evaluated the potential of MCP1-Gd to detect LN metastasis. When incubated with migrating monocytes in vitro , MCP1-Gd transport across lymphatic endothelium increased 2-fold relative to nontargeting controls. After administration into mouse models with initial LN metastasis and recurrent LN metastasis, MCP1-Gd detected metastatic LNs by increasing MRI signal by 30-50% relative to healthy LNs. Furthermore, LN targeting was dependent on monocyte hitchhiking, as monocyte depletion decreased accumulation by >70%. Herein, we present a nanoparticle contrast agent for MRI detection of LN metastasis mediated by CCR2-targeting and demonstrate the potential of monocyte hitchhiking for enhanced nanoparticle delivery.

Cholera is a waterborne disease caused by Vibrio cholerae bacteria generally transmitted through contaminated food or water sources. Although it has been eradicated in most Western countries, cholera continues to be a highly transmitted and lethal disease in several African and Southeast Asian countries. Unfortunately, current diagnostic methods for cholera have challenges including high cost or delayed diagnoses that can lead to increased disease transmission during pandemics, while current treatments such as therapeutic drugs and vaccines have limited efficacy against drug-resistant serogroups of Vibrio cholerae. As such, new solutions that can treat cholera in an efficient manner that avoids Vibrio cholerae's adaptive immunity are needed. Nanoparticles (NPs) are a suitable platform for enhancing current theranostic tools because of their biocompatibility and ability to improve drug circulation and targeting. Nanoparticle surfaces can also be modified with various protein receptors targeting cholera toxins produced by Vibrio cholerae. This review will address recent developments in diagnostics, therapeutics, and prevention against cholera particularly focusing on the use of metal-based nanoparticles and organic nanoparticles. We will then discuss future directions regarding nanoparticle research for cholera., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eun Ji Chung reports financial support was provided by University of Southern California., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: The pathogenesis of isolated rapid eye movement sleep behavior disorders (iRBD) is poorly understood. The severity of RBD may reflect its pathogenesis., Methods: We compared motor function and non-motor symptoms (NMSs) between iRBD patients and healthy volunteers. We correlated motor function, NMSs, and striatal dopaminergic activity with RBD severity using video-polysomnography., Results: Twenty-one iRBD patients and 17 controls participated. The Unified Parkinson's Disease Rating Scale part III scores were higher in patients compared to controls ( p  < 0.001). There was no difference in upper extremity function between patients and controls (right, p  = 0.220; left, p  = 0.209), but gait was slower in iRBD patients (walking time, p  < 0.001; number of steps, p  < 0.001). The mean value of the Korean version of the Mini-Mental State Exam and Clinical Dementia Rating were lower in patients ( p  = 0.006, p  = 0.003, respectively). Patients with were also more depressed ( p  = 0.002), had decreased olfactory function ( p  < 0.001), reported more frequent sleep/fatigue episodes ( p  < 0.001), worse attention/memory capacity ( p  < 0.001), gastrointestinal problems ( p  = 0.009), urinary problems ( p  = 0.007), and pain ( p  = 0.083). Further, iRBD patients reported more frequent sleep-related disturbances ( p  = 0.004), but no difference in daytime sleepiness ( p  = 0.663). Disease severity was correlated with pain ( r  = 0.686, p  = 0.002) and visuospatial function ( r = -0.507, p  = 0.038). There were no correlations between RBD severity and striatal dopaminergic activities ( p  > 0.09)., Conclusions: iRBD is a multisystem neurodegenerative disorder, and gait abnormalities may be a disease characteristic, possibly related to the akinetic-rigid phenotype of Parkinson's disease. The correlation between pain/visuospatial dysfunction and RBD severity may be related to its pathogenesis.

Despite a high vaccination rate, the COVID-19 pandemic continues with immune-evading Omicron variants. The success of additional antigenic stimulation through breakthrough infection (BI) and updated vaccination in overcoming antigenic imprinting needs to be determined. Participants in a long-term follow-up cohort of healthcare worker (HCW) vaccinee were categorized according to their infection/vaccination status. Anti-SARS-CoV-2 spike/nucleocapsid protein antibodies were measured, and plaque reduction neutralization tests (PRNTs) against wild-type (WT), BA.5, BN.1, and XBB.1.5 were conducted. The neutralization activity of intravenous immunoglobulin (IVIG) products was evaluated to assess the immune status of the general population. Ninety-five HCWs were evaluated and categorized into seven groups. The WT PRNT ND 50 value was highest regardless of infection/vaccination status, and groups with recent antigenic stimulation showed high PRNT titers overall. Groups with double Omicron stimulation, either by BI plus BA.4/5 bivalent vaccination or repeated BI, exhibited significantly higher BA.5 and BN.1 PRNT to WT PRNT ratios than those with single Omicron stimulation. Overall group immunity was estimated to be boosted in January 2023, reflecting the effect of the BA.4/5 bivalent booster and additional BIs, but slightly declined in June 2023. A substantial increase in the antibody concentrations of IVIG products was noticed in 2022, and recently produced IVIG products exhibited a substantial level of cross-reactive neutralizing activity against emerging variants. Neutralizing activity against emerging variants could be enhanced by repeated antigenic stimulation via BI and/or updated vaccination. Overall group immunity was elevated accordingly, and IVIG products showed substantial activity against circulating strains., (© 2023 Wiley Periodicals LLC.)

In extrusion-based 3D printing, the use of synthetic polymeric hydrogels can facilitate fabrication of cellularized and implanted scaffolds with sufficient mechanical properties to maintain the structural integrity and physical stress within the in vivo conditions. However, synthetic hydrogels face challenges due to their poor properties of cellular adhesion, bioactivity, and biofunctionality. New compositions of hydrogel inks have been designed to address this limitation. A viscous poly(maleate-propylene oxide)-lipoate-poly(ethylene oxide) (MPLE) hydrogel is recently developed that shows high-resolution printability, drug-controlled release, excellent mechanical properties with adhesiveness, and biocompatibility. In this study, the authors demonstrate that the incorporation of cell-adhesive proteins like gelatin and albumin within the MPLE gel allows printing of biologically functional 3D scaffolds with rapid cell spreading (within 7 days) and high cell proliferation (twofold increase) as compared with MPLE gel only. Addition of proteins (10% w/v) supports the formation of interconnected cell clusters (≈1.6-fold increase in cell areas after 7-day) and spreading of cells in the printed scaffolds without additional growth factors. In in vivo studies, the protein-loaded scaffolds showed excellent biocompatibility and increased angiogenesis without inflammatory response after 4-week implantation in mice, thus demonstrating the promise to contribute to the printable tough hydrogel inks for tissue engineering., (© 2023 Wiley-VCH GmbH.)

Objective: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]., Background: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS., Methods: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed., Results: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression., Conclusions: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed., Trial Registration: ClinicalTrials.gov Identifier: NCT02938702., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The coronavirus disease 2019 pandemic persisted for 3 years and is now transitioning to endemicity. We illustrated the change in group immunity induced by vaccination (monovalent vaccines) and breakthrough infections (BIs) in a healthcare worker (HCW) cohort. Five sampling points were analyzed: before the third dose and 1, 3, 5, and 8 months after the vaccination. The last two points corresponded roughly to 1 and 4 months after omicron BA.1/BA.2 BI. A semi-quantitative anti-spike binding antibody (Sab) assay and plaque reduction neutralization test (PRNT) against circulating variants were conducted. A linear regression model was utilized to deduce correlation equations. Baseline characteristics and antibody titers after the third dose were not different between 106 HCWs with or without BI (54/52). One month after the third dose, BA.1 PRNT increased with wild-type (WT), but 3 months after the third dose, it decreased more rapidly than WT PRNT. After BI, BA.1 PRNT increased robustly and waned slower than WT. A linear equation of waning kinetics was deduced between log 10 Sab and months, and the slope became gradual after BI. The estimated BA.5 PRNT titers at the beginning of the BA.5 outbreak were significantly higher than the BA.1 PRNT titers of the initial BA.1/BA.2 wave, which might be associated with the smaller size of the BA.5 wave. BA.1/BA.2 BI after the third dose elicited robust and broad neutralizing activity, preferentially maintaining cross-neutralizing longevity against BA.1 and BA.5. The estimated kinetics provide an overview of group immunity through the third vaccination and BA.1/BA.2 BI, correlating with the actual outbreaks. IMPORTANCE This study analyzed changes in group immunity induced by coronavirus disease 2019 (COVID-19) vaccination and BA.1/BA.2 breakthrough infections (BIs) in a healthcare worker cohort. We investigated the longitudinal kinetics of neutralizing antibodies against circulating variants and confirmed that BA.1/BA.2 BIs enhance the magnitude and durability of cross-neutralization against BA.1 and BA.5. Correlation equations between semi-quantitative anti-spike antibody and plaque reduction neutralization test titers were deduced from the measured values using a linear regression model. Based on the equations, group immunity was estimated to last up to 11 months following the third dose of the COVID-19 vaccine. The estimated group immunity suggests that the augmented immunity and flattened waning slope through BI could correlate with the overall outbreak size. Our findings could provide a better understanding to establish public health strategies against future endemicity.

Background/aims: Vision impairment (VI) increases the risk of various comorbidities, including depression. However, the relationship between depression and VI is unclear, and existing findings are inconsistent. We therefore investigated the risk of depression in adults before and after their registration as visually impaired., Methods: In this longitudinal, nationwide, retrospective cohort study, 131 434 patients (aged ≥18 years) with newly registered VI during 2005-2013 were evaluated using the Korean National Health Insurance Service database. Using 1:1 propensity score matching, randomly selected patients (control group) were compared with patients with VI (patient group) according to age, sex, residential area and household income. Each patient was tracked from 3 years before and 5 years after registration. The risk of depression before and after VI registration was evaluated using a conditional logistic regression model., Results: The risk of depression gradually increased from 3 years before registration (OR, 1.186; 95% CI 1.089 to 1.290), then peaked at the time of registration (OR, 1.925; 95% CI 1.788 to 2.073), and then gradually decreased until 5 years after registration (OR, 1.128; 95% CI 1.046 to 1.216). Male patients, those with severe VI and those aged 18-29 years had a higher risk of depression., Conclusions: Patients with VI had an increased risk of depression from 3 years before to 5 years after registration. Significant risk factors included severity, male sex and younger age. Thus, public mental health services are necessary to provide appropriate support and interventions to people before and after registration as visually impaired., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aimed to assess predictors of the response to varying durations of proton pump inhibitor (PPI) use and lifestyle modification treatment for laryngopharyngeal reflux disease (LPRD)., Methods: Between October 2014 and June 2016, a prospective, multicenter, open-label, single-cohort, intention-to-treat, observational study was conducted at eight referral hospitals across the Republic of Korea to examine predictors of early and late response to treatment in adult patients (age ≥19 years) with LPRD. Participants underwent standard treatment (PPI [Esomezol] and lifestyle modification) for 3 months. Response to treatment was defined as greater than 50% improvement in reflux symptom index score. The primary outcome was potential predictors of treatment response at 1 and 3 months. The secondary outcome was potential predictors distinguishing early from late responders., Results: In total, 394 patients were enrolled. Improved sleep habits was a positive predictor (odds ratio [OR], 1.785; 95% confidence interval [CI], 1.06-3.007; P=0.029), while initial alcohol consumption (OR, 0.587; 95% CI, 0.355-0.969; P=0.037) and past medication history (OR, 0.438; 95% CI, 0.215-0.891; P=0.005) were negative predictors of response after 1 month of treatment. High pre-reflux finding score was a positive predictor (OR, 1.187; 95% CI, 1.049- 1.344; P=0.007), while male sex (OR, 0.516; 95% CI, 0.269-0.987; P=0.046), higher depression score (OR, 0.867; 95% CI, 0.784-0.958; P=0.005), and past thyroid hormone medication history (OR, 0.161; 95% CI, 0.033-0.788; P=0.024) were negative predictors of response after 3 months of treatment. Past medication history (OR, 0.438; 95% CI, 0.215-0.891; P=0.023) was the only negative predictor for early responders compared to late responders., Conclusion: Adult patients with LPRD and a history of prior medication use may require longer treatment durations to achieve a therapeutic response. Future research should explore the incorporation of diverse treatment approaches to improve treatment outcomes for patients exhibiting negative prognostic indicators.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease and is characterized by the formation of renal cysts and the eventual development of end-stage kidney disease. One approach to treating ADPKD is through inhibition of the mammalian target of rapamycin (mTOR) pathway, which has been implicated in cell overproliferation, contributing to renal cyst expansion. However, mTOR inhibitors, including rapamycin, everolimus, and RapaLink-1, have off-target side effects including immunosuppression. Thus, we hypothesized that the encapsulation of mTOR inhibitors in drug delivery carriers that target the kidneys would provide a strategy that would enable therapeutic efficacy while minimizing off-target accumulation and associated toxicity. Toward eventual in vivo application, we synthesized cortical collecting duct (CCD) targeted peptide amphiphile micelle (PAM) nanoparticles and show high drug encapsulation efficiency (>92.6%). In vitro analysis indicated that drug encapsulation into PAMs enhanced the anti-proliferative effect of all three drugs in human CCD cells. Analysis of in vitro biomarkers of the mTOR pathway via western blotting confirmed that PAM encapsulation of mTOR inhibitors did not reduce their efficacy. These results indicate that PAM encapsulation is a promising way to deliver mTOR inhibitors to CCD cells and potentially treat ADPKD. Future studies will evaluate the therapeutic effect of PAM-drug formulations and ability to prevent off-target side effects associated with mTOR inhibitors in mouse models of ADPKD., Competing Interests: Declaration of competing interests The authors declare no financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia., Methods: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology., Results: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended., Conclusion: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

DNA methylation aberrancies are found in autosomal dominant polycystic kidney disease (ADPKD), which suggests the methylome to be a promising therapeutic target. However, the impact of combining DNA methylation inhibitors (DNMTi) and ADPKD drugs in treating ADPKD and on disease-associated methylation patterns has not been fully explored. To test this, ADPKD drugs, metformin and tolvaptan (MT), were delivered in combination with DNMTi 5-aza-2'-deoxycytidine (Aza) to 2D or 3D cystic Pkd1 heterozygous renal epithelial cells (PKD1-Het cells) as free drugs or within nanoparticles to enable direct delivery for future in vivo applications. We found Aza synergizes with MT to reduce cell viability and cystic growth. Reduced representation bisulfite sequencing (RRBS) was performed across four groups: PBS, Free-Aza (Aza), Free-Aza+MT (F-MTAza), and Nanoparticle-Aza+MT (NP-MTAza). Global methylation patterns showed that while Aza alone induces a unimodal intermediate methylation landscape, Aza+MT recovers the bimodality reminiscent of somatic methylomes. Importantly, site-specific methylation changes associated with F-MTAza and NP-MTAza were largely conserved including hypomethylation at ADPKD-associated genes. Notably, we report hypomethylation of cancer-associated genes implicated in ADPKD pathogenesis as well as new target genes that may provide additional therapeutic effects. Overall, this study motivates future work to further elucidate the regulatory mechanisms of observed drug synergy and apply these combination therapies in vivo ., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

Objective: We evaluated the efficacy and safety of postoperative radiotherapy (PORT) for differentiated thyroid cancer (DTC) with high risk features., Materials and Methods: This retrospective study analyzed 187 patients treated for DTC from 1985 to 2019. DTC referred to nonanaplastic thyroid cancer originating from follicular cells. PORT was defined as the administration of external beam radiation to the thyroid and regional lymph nodes following surgery for initially diagnosed DTC. The patients were included in the analysis if they received PORT or exhibited any of the following features: (a) pT4 or pN1b according to the 8th American Joint Committee on Cancer, (b) poorly differentiated thyroid cancer (PDTC), or (c) unfavourable variants such as anaplastic foci and etc. After 1:1 propensity matching, a total of 108 patients were analyzed according to PORT receipt. The median follow-up duration of the matched group was 10.4 years., Results: After matching, most of the variables became balanced, but the PORT group still had more PDTC and DTC with anaplastic foci. Radioactive iodine (RAI) was less frequently administered in the PORT group. PORT yielded a significantly higher 5-year locoregional recurrence free survival (LRFS) than the No PORT group (5-year LRFS 86.1% vs. 72.7%, p = 0.022), but the 10-year cancer specific survival (CSS) was similar between them (97.8% vs. 85.9%, p = 0.122). The multivariable analysis indicated that PORT was a favourable prognostic factor (Hazard ratio 0.3, 95% Confidence interval 0.1-0.8, p = 0.02) for LRFS, but not for CSS. Among 133 patients without PORT for initial disease, 39 of them received salvage surgery followed by salvage PORT. No severe toxicity after PORT was reported., Conclusion: PORT reduced locoregional recurrence in DTC patients without severe toxicity. PORT can be an effective and safe treatment to improve locoregional control in DTC with high risk features. However, further study is warranted to identify those who can benefit from PORT., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background and Purpose: To determine the role of adjuvant radiotherapy (ART) in parotid gland cancer without nodal metastasis, we evaluated the survival outcomes, prognostic factors, and dose-response relationships in patients with node-negative parotid gland cancer patients., Materials and Methods: Patients who underwent curative parotidectomy and were pathologically diagnosed with parotid gland cancer without regional or distant metastases between 2004 and 2019 were reviewed. The benefit of ART in terms of locoregional control (LRC) and progression-free survival (PFS) were evaluated., Results: In total, 261 patients were included in the analysis. Of them, 45.2 % received ART. The median follow-up period was 66.8 months. Multivariate analysis revealed that histological grade and ART were independent prognostic factors for LRC and PFS (all p <.05). For patients with high-grade histology, ART was associated with a significant improvement in 5-year LRC (p =.005) and PFS (p =.009). Among patients with high-grade histology who completed RT, higher biologic effective dose (≥77 Gy10) significantly increased PFS (adjusted hazard ratio [HR], 0.10 per 1-Gy increase; 95 % confidence interval [CI], 0.02-0.58; p =.010). ART significantly improved LRC (p =.039) in patients with low-to-intermediate histological grade as well per multivariate analysis, and subgroup analyses revealed patients with T3-4 stage and close/positive resection margins (<1 mm) would benefit from ART., Conclusion: ART should be strongly recommended for patients with node-negative parotid gland cancer with high-grade histology in terms of disease control and survival. In patients with low-to-intermediate-grade disease, those with high T stage and incomplete resection margin benefit with ART., 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 © 2023 Elsevier B.V. All rights reserved.)

Objectives: Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model., Methods: We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning technique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold, and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreactor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long resection) in a canine model., Results: Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly and circumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was confirmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed that there were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Significant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin immunostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months., Conclusion: Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach for esophageal tissue engineering.